-
12 Posts
-
0 Photos
-
0 Videos
-
Male
-
22/01/1980
-
Followed by 0 people
Recent Updates
-
Background Synovial sarcoma can present morphologically in multiple forms, including biphasic and monophasic subtypes. As a result, the histological diagnosis can sometimes be challenging. Transducin-Like Enhancer 1 (TLE1) is a transcriptional corepressor that normally is involved in embryogenesis and hematopoiesis but is also expressed in certain tumors. This systematic review examines the potential role of TLE1 as a diagnostic biomarker for the synovial sarcoma. Materials and Methods. A literature review and meta-analysis were conducted using the electronic databases Pubmed, the Cochrane Library, and Google Scholar. Thirteen studies met our eligibility criteria and were selected for in-depth analysis. Results The mean sensitivity and specificity of TLE1 in detecting synovial sarcoma were 94% (95% CI 91%-97%) and 81% (95% CI 72%-91%), respectively, when all studies were aggregated together. The mean positive predictive value (PPV) of TLE1 was 75% (95% CI 62%-87%), whereas the negative predictive value (NPV) was 96% (95% CI 93%-98%). Conclusion TLE1 is a sensitive and specific marker for synovial sarcoma that can aid in its diagnosis. Due to its involvement in several relevant signaling pathways, TLE1 might have direct relevance to the pathophysiology of the disease. Copyright © 2020 Marc El Beaino et al.This study sought to gather information through a survey of how newcomer parents' beliefs about technology usage and how they engage with technology as they support their children with twenty-first century literacies. Parent respondents (N = 70) were drawn from two publicly funded schools in the Niagara Region, Ontario, Canada, where the population tends to be immigrant, visible minority, with post-secondary education, but unemployed and low income. Descriptive statistics quantified daily technology activities as being communication-oriented with the majority of parents holding distinct beliefs about the amount and type of their children's technology usage. Chi-square tests indicated significant associations for demographic characteristics such as the gender, age, education, first language, and ethnicity of the parents as determinants of their beliefs about their children's technology usage (e.g., social media, mobile phones, television). As well, levels of access and use varied in terms of the number of new technologies and the types of literacy practices that families engage in. Immigrant parents might hold misconceptions about twenty-first century literacies, therefore there should be an attempt to assist them to provide responsive twenty-first century literacy and technology support for their children. © Springer Science+Business Media, LLC, part of Springer Nature 2020.To study the influence of fireworks in atmospheric aerosols and their effect on health during the extreme firework days, fireworks tracer metals and carbonaceous species in size-distributed aerosols in the lower troposphere at Raipur in eastern central India were investigated during the 2018 Deepawali festival. Aerosol samples were collected, before Deepawali period (BDP, n = 5), during Deepawali period (DDP, n = 5) and after Deepawali period (ADP, n = 5). Bimodal size-distribution with intense fine mode peak was found for Na during DDP. Bimodal distribution with fine mode intense peak was found for K during DDP. The bimodal size distribution of K was found common for other events because of biomass burning emissions, whereas high intense peak during DDP indicated mixed sources from biomass burning and fireworks. During DDP, K and Ca were well correlated (r2 = 0.93) together. Strong metal-metal correlations were found between the following pairs, Zn-Fe, Cu-Fe and Cu-Ca, which indicated the similar firecrackers burning source. The atmospheric aging of aerosols was also found significantly high during fireworks days. Aging of aerosols were higher because of heterogeneous reactions of SO2 and NOx on aerosols directly emitted from fireworks. The observed high values of inhalation dose of elemental carbon during DDP period imposed higher risk of respiratory diseases. This study has provided carbonaceous fractions composition data as a tool to detect the aging processes of fireworks in ultra-fine, fine and coarse mode particles during the extreme firework days. Inhalation doses were calculated to establish potential influence on human health. © 2020 Turkish National Committee for Air Pollution Research and Control. Production and hosting by Elsevier B.V. All rights reserved.Coprecipitation can be an effective treatment method for the removal of environmentally relevant metals from industrial wastewaters such as produced waters from the oil and gas industry. The precipitation of barite, BaSO4, through the addition of sulfate removes barium while coprecipitating strontium and other alkaline earth metals even when these are present at concentrations below their solubility limit. Among other analytical methods, X-ray fluorescence (XRF) nanospectroscopy at the Hard X-ray Nanoprobe (HXN) beamline at the National Synchrotron Light Source II (NSLS-II) was used to quantify Sr incorporation into barite. Thermodynamic modeling of (Ba,Sr)SO4 solid solutions was done using solid solution-aqueous solution (SS-AS) theory. https://www.selleckchem.com/pharmacological_epigenetics.html The quantitative, high-resolution nano-XRF data show clearly that the Sr content in (Ba,Sr)SO4 solid solutions varies widely among particles and even within a single particle. We observed substantial Sr incorporation that is far larger than thermodynamic models predict, likely indicating the formation of metastable solid solutions. We also observed that increasing barite supersaturation of the aqueous phase led to increased Sr incorporation, as predicted by available kinetic models. These results suggest that coprecipitation offers significant potential for designing treatment systems for aqueous metals' removal in desired metastable compositions. Solution conditions may be optimized to enhance the incorporation of Sr by increasing sulfate addition such that the barite saturation index remains above ∼3 or by increasing the aqueous Sr to Ba ratio. © Heather A. Hunter et al. 2020; Published by Mary Ann Liebert, Inc.
Background Synovial sarcoma can present morphologically in multiple forms, including biphasic and monophasic subtypes. As a result, the histological diagnosis can sometimes be challenging. Transducin-Like Enhancer 1 (TLE1) is a transcriptional corepressor that normally is involved in embryogenesis and hematopoiesis but is also expressed in certain tumors. This systematic review examines the potential role of TLE1 as a diagnostic biomarker for the synovial sarcoma. Materials and Methods. A literature review and meta-analysis were conducted using the electronic databases Pubmed, the Cochrane Library, and Google Scholar. Thirteen studies met our eligibility criteria and were selected for in-depth analysis. Results The mean sensitivity and specificity of TLE1 in detecting synovial sarcoma were 94% (95% CI 91%-97%) and 81% (95% CI 72%-91%), respectively, when all studies were aggregated together. The mean positive predictive value (PPV) of TLE1 was 75% (95% CI 62%-87%), whereas the negative predictive value (NPV) was 96% (95% CI 93%-98%). Conclusion TLE1 is a sensitive and specific marker for synovial sarcoma that can aid in its diagnosis. Due to its involvement in several relevant signaling pathways, TLE1 might have direct relevance to the pathophysiology of the disease. Copyright © 2020 Marc El Beaino et al.This study sought to gather information through a survey of how newcomer parents' beliefs about technology usage and how they engage with technology as they support their children with twenty-first century literacies. Parent respondents (N = 70) were drawn from two publicly funded schools in the Niagara Region, Ontario, Canada, where the population tends to be immigrant, visible minority, with post-secondary education, but unemployed and low income. Descriptive statistics quantified daily technology activities as being communication-oriented with the majority of parents holding distinct beliefs about the amount and type of their children's technology usage. Chi-square tests indicated significant associations for demographic characteristics such as the gender, age, education, first language, and ethnicity of the parents as determinants of their beliefs about their children's technology usage (e.g., social media, mobile phones, television). As well, levels of access and use varied in terms of the number of new technologies and the types of literacy practices that families engage in. Immigrant parents might hold misconceptions about twenty-first century literacies, therefore there should be an attempt to assist them to provide responsive twenty-first century literacy and technology support for their children. © Springer Science+Business Media, LLC, part of Springer Nature 2020.To study the influence of fireworks in atmospheric aerosols and their effect on health during the extreme firework days, fireworks tracer metals and carbonaceous species in size-distributed aerosols in the lower troposphere at Raipur in eastern central India were investigated during the 2018 Deepawali festival. Aerosol samples were collected, before Deepawali period (BDP, n = 5), during Deepawali period (DDP, n = 5) and after Deepawali period (ADP, n = 5). Bimodal size-distribution with intense fine mode peak was found for Na during DDP. Bimodal distribution with fine mode intense peak was found for K during DDP. The bimodal size distribution of K was found common for other events because of biomass burning emissions, whereas high intense peak during DDP indicated mixed sources from biomass burning and fireworks. During DDP, K and Ca were well correlated (r2 = 0.93) together. Strong metal-metal correlations were found between the following pairs, Zn-Fe, Cu-Fe and Cu-Ca, which indicated the similar firecrackers burning source. The atmospheric aging of aerosols was also found significantly high during fireworks days. Aging of aerosols were higher because of heterogeneous reactions of SO2 and NOx on aerosols directly emitted from fireworks. The observed high values of inhalation dose of elemental carbon during DDP period imposed higher risk of respiratory diseases. This study has provided carbonaceous fractions composition data as a tool to detect the aging processes of fireworks in ultra-fine, fine and coarse mode particles during the extreme firework days. Inhalation doses were calculated to establish potential influence on human health. © 2020 Turkish National Committee for Air Pollution Research and Control. Production and hosting by Elsevier B.V. All rights reserved.Coprecipitation can be an effective treatment method for the removal of environmentally relevant metals from industrial wastewaters such as produced waters from the oil and gas industry. The precipitation of barite, BaSO4, through the addition of sulfate removes barium while coprecipitating strontium and other alkaline earth metals even when these are present at concentrations below their solubility limit. Among other analytical methods, X-ray fluorescence (XRF) nanospectroscopy at the Hard X-ray Nanoprobe (HXN) beamline at the National Synchrotron Light Source II (NSLS-II) was used to quantify Sr incorporation into barite. Thermodynamic modeling of (Ba,Sr)SO4 solid solutions was done using solid solution-aqueous solution (SS-AS) theory. https://www.selleckchem.com/pharmacological_epigenetics.html The quantitative, high-resolution nano-XRF data show clearly that the Sr content in (Ba,Sr)SO4 solid solutions varies widely among particles and even within a single particle. We observed substantial Sr incorporation that is far larger than thermodynamic models predict, likely indicating the formation of metastable solid solutions. We also observed that increasing barite supersaturation of the aqueous phase led to increased Sr incorporation, as predicted by available kinetic models. These results suggest that coprecipitation offers significant potential for designing treatment systems for aqueous metals' removal in desired metastable compositions. Solution conditions may be optimized to enhance the incorporation of Sr by increasing sulfate addition such that the barite saturation index remains above ∼3 or by increasing the aqueous Sr to Ba ratio. © Heather A. Hunter et al. 2020; Published by Mary Ann Liebert, Inc.0 Comments 0 Shares 253 Views 0 ReviewsPlease log in to like, share and comment! -
Aim To assess the influence of artefacts generated by metal posts on the detection of simulated internal root resorption (IRR) in adjacent teeth using cone-beam computed tomography (CBCT), as well as to verify the impact of metal artefact reduction (MAR) on these cases. Methodology CBCT images of 14 premolar teeth were acquired before and after IRR simulation using chemical and mechanical procedures, in an OP300 Maxio unit, with and without MAR. Each tooth was placed in the socket of a human mandible and scanned under three different conditions 1, without adjacent teeth - control group; 2, distal adjacent tooth restored with metal post; and 3, with both adjacent teeth restored with metal post. Five oral radiologists scored the IRR detection using a 5-point scale. Diagnostic values were obtained for the tested groups and compared using two-way analysis of variance (α=0.05). Results The presence of a single adjacent tooth restored with metal post did not significantly influence the diagnostic values for IRR detection (p>0.05). The presence of both adjacent teeth with metal posts, without MAR application, were associated with a significantly lower area under the ROC curve (Az) compared to the control (p=0.0182). In this case, the application of MAR increased Az, leading to non-significant differences from the control group and the group with one adjacent restored tooth (p>0.05). Sensitivity decreased significantly when two adjacent restored teeth were present, regardless of MAR application (p=0.0379). Specificity was not affected by the conditions tested (p>0.05). Conclusion CBCT detection of internal root resorption was impaired by artefacts only when both adjacent teeth restored with metal posts were present. In such cases, activation of MAR improved the performance on this diagnostic task.Background Endothelin-1 (EDN1) can evoke histamine-independent pruritus in mammals and is upregulated in the lesional epidermis of atopic dermatitis (AD). EDN1 increases the production of interleukin 25 (IL-25) from keratinocytes to accelerate T helper type 2 immune deviation. Plasma EDN1 levels are positively correlated with the clinical severity and itch intensity of AD. Therefore, we hypothesized that the inhibition of EDN1 might be useful for treating atopic inflammation and itch and investigated the effects of the topical application of the EDN1 receptor antagonist bosentan on the skin inflammation and itch in a murine AD model. Methods We analyzed the mite-induced AD-like NC/Nga murine model, which was topically applied with bosentan or ethanol control every day for 3 weeks. We also subjected in vitro primary sensory neuron culture systems to nerve elongation and branching assays after EDN1 stimulation. Results Topical application of bosentan significantly attenuated the development of mite-induced AD-like skin inflammation, dermatitis scores, ear thickness, scratching bouts, and serum level of thymus and activation-regulated chemokine in NC/Nga ****. https://www.selleckchem.com/products/ITF2357(Givinostat).html Bosentan application also significantly reduced the gene expression of Il13, Il17, and Ifng in the treated lesions. Histologically, the number of infiltrated dermal cells, the epidermal EDN1 expression, and the number of intraepidermal nerve fibers were significantly inhibited upon bosentan application. While EDN1 significantly elongated the neurites of dorsal root ganglion cells in a dose- and time-dependent manner, bosentan treatment attenuated this. Conclusions EDN1 plays a significant role in mite-induced inflammation and itch. Topical bosentan is a potential protective candidate for AD.Urinary β2 microglobulin (β2-m) is a marker of renal tubule dysfunction; however, β2-m might become degraded under acidic conditions. To confirm the degradation and consequent deactivation of β2-m under acidic conditions, we used matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) to detect the levels and forms of β2-m in the urine samples of patients with high proteinuria (n = 21) and healthy subjects (n = 6). β2-m was purified in crude form using immunoprecipitation. A signal of 11.74 kDa, corresponding to the molecular weight of β2-m, was detected in all samples. In addition, several high-molecular-weight proteins were detected in a patient as integrals of the intensity at 11.74 kDa. These results indicate that post-translational modifications of β2-m might be involved in the pathological process of proteinuria. Therefore, MS can be used for monitoring proteinuria and predicting the risk of progression.Intrinsically disordered regions (IDR) play an important role in key biological processes and are closely related to human diseases. IDRs have great potential to serve as targets for drug discovery, most notably in disordered binding regions. Accurate prediction of IDRs is challenging because their genome wide occurrence and a low ratio of disordered residues make them difficult targets for traditional classification techniques. Existing computational methods mostly rely on sequence profiles to improve accuracy which is time consuming and computationally expensive. This article describes an ab initio sequence-only prediction method - which tries to overcome the challenge of accurate prediction posed by IDRs - based on reduced amino acid alphabets and convolutional neural networks (CNNs). We experiment with six different 3-letter reduced alphabets. We argue that the dimensional reduction in the input alphabet facilitates the detection of complex patterns within the sequence by the convolutional step. Experimental results show that our proposed IDR predictor performs at the same level or outperforms other state-of-the-art methods in the same class, achieving accuracy levels of 0.76 and AUC of 0.85 on the publicly available Critical Assessment of protein Structure Prediction dataset (CASP10). Therefore, our method is suitable for proteome-wide disorder prediction yielding similar or better accuracy than existing approaches at a faster speed. This article is protected by copyright. All rights reserved.Chemical herbicides, which are commonly used to kill weeds in the field, have been extensively applied and transformed the way of weed management in modern agriculture due to its efficiency, ease of use and relatively low cost. In last decades, a large number of transgenic herbicide-tolerant crops (i.e. corn, soybean, cotton, rice etc.) have been developed and commercialized, reshaping the global seed market (Schutte et al., 2017). However, the use of chemical herbicides (i.e. ALS inhibitors, EPSPS inhibitors, ACCase inhibitors etc.) has also drastically increased, resulting in the occurrence of weed species resistant to these herbicides.
Aim To assess the influence of artefacts generated by metal posts on the detection of simulated internal root resorption (IRR) in adjacent teeth using cone-beam computed tomography (CBCT), as well as to verify the impact of metal artefact reduction (MAR) on these cases. Methodology CBCT images of 14 premolar teeth were acquired before and after IRR simulation using chemical and mechanical procedures, in an OP300 Maxio unit, with and without MAR. Each tooth was placed in the socket of a human mandible and scanned under three different conditions 1, without adjacent teeth - control group; 2, distal adjacent tooth restored with metal post; and 3, with both adjacent teeth restored with metal post. Five oral radiologists scored the IRR detection using a 5-point scale. Diagnostic values were obtained for the tested groups and compared using two-way analysis of variance (α=0.05). Results The presence of a single adjacent tooth restored with metal post did not significantly influence the diagnostic values for IRR detection (p>0.05). The presence of both adjacent teeth with metal posts, without MAR application, were associated with a significantly lower area under the ROC curve (Az) compared to the control (p=0.0182). In this case, the application of MAR increased Az, leading to non-significant differences from the control group and the group with one adjacent restored tooth (p>0.05). Sensitivity decreased significantly when two adjacent restored teeth were present, regardless of MAR application (p=0.0379). Specificity was not affected by the conditions tested (p>0.05). Conclusion CBCT detection of internal root resorption was impaired by artefacts only when both adjacent teeth restored with metal posts were present. In such cases, activation of MAR improved the performance on this diagnostic task.Background Endothelin-1 (EDN1) can evoke histamine-independent pruritus in mammals and is upregulated in the lesional epidermis of atopic dermatitis (AD). EDN1 increases the production of interleukin 25 (IL-25) from keratinocytes to accelerate T helper type 2 immune deviation. Plasma EDN1 levels are positively correlated with the clinical severity and itch intensity of AD. Therefore, we hypothesized that the inhibition of EDN1 might be useful for treating atopic inflammation and itch and investigated the effects of the topical application of the EDN1 receptor antagonist bosentan on the skin inflammation and itch in a murine AD model. Methods We analyzed the mite-induced AD-like NC/Nga murine model, which was topically applied with bosentan or ethanol control every day for 3 weeks. We also subjected in vitro primary sensory neuron culture systems to nerve elongation and branching assays after EDN1 stimulation. Results Topical application of bosentan significantly attenuated the development of mite-induced AD-like skin inflammation, dermatitis scores, ear thickness, scratching bouts, and serum level of thymus and activation-regulated chemokine in NC/Nga mice. https://www.selleckchem.com/products/ITF2357(Givinostat).html Bosentan application also significantly reduced the gene expression of Il13, Il17, and Ifng in the treated lesions. Histologically, the number of infiltrated dermal cells, the epidermal EDN1 expression, and the number of intraepidermal nerve fibers were significantly inhibited upon bosentan application. While EDN1 significantly elongated the neurites of dorsal root ganglion cells in a dose- and time-dependent manner, bosentan treatment attenuated this. Conclusions EDN1 plays a significant role in mite-induced inflammation and itch. Topical bosentan is a potential protective candidate for AD.Urinary β2 microglobulin (β2-m) is a marker of renal tubule dysfunction; however, β2-m might become degraded under acidic conditions. To confirm the degradation and consequent deactivation of β2-m under acidic conditions, we used matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) to detect the levels and forms of β2-m in the urine samples of patients with high proteinuria (n = 21) and healthy subjects (n = 6). β2-m was purified in crude form using immunoprecipitation. A signal of 11.74 kDa, corresponding to the molecular weight of β2-m, was detected in all samples. In addition, several high-molecular-weight proteins were detected in a patient as integrals of the intensity at 11.74 kDa. These results indicate that post-translational modifications of β2-m might be involved in the pathological process of proteinuria. Therefore, MS can be used for monitoring proteinuria and predicting the risk of progression.Intrinsically disordered regions (IDR) play an important role in key biological processes and are closely related to human diseases. IDRs have great potential to serve as targets for drug discovery, most notably in disordered binding regions. Accurate prediction of IDRs is challenging because their genome wide occurrence and a low ratio of disordered residues make them difficult targets for traditional classification techniques. Existing computational methods mostly rely on sequence profiles to improve accuracy which is time consuming and computationally expensive. This article describes an ab initio sequence-only prediction method - which tries to overcome the challenge of accurate prediction posed by IDRs - based on reduced amino acid alphabets and convolutional neural networks (CNNs). We experiment with six different 3-letter reduced alphabets. We argue that the dimensional reduction in the input alphabet facilitates the detection of complex patterns within the sequence by the convolutional step. Experimental results show that our proposed IDR predictor performs at the same level or outperforms other state-of-the-art methods in the same class, achieving accuracy levels of 0.76 and AUC of 0.85 on the publicly available Critical Assessment of protein Structure Prediction dataset (CASP10). Therefore, our method is suitable for proteome-wide disorder prediction yielding similar or better accuracy than existing approaches at a faster speed. This article is protected by copyright. All rights reserved.Chemical herbicides, which are commonly used to kill weeds in the field, have been extensively applied and transformed the way of weed management in modern agriculture due to its efficiency, ease of use and relatively low cost. In last decades, a large number of transgenic herbicide-tolerant crops (i.e. corn, soybean, cotton, rice etc.) have been developed and commercialized, reshaping the global seed market (Schutte et al., 2017). However, the use of chemical herbicides (i.e. ALS inhibitors, EPSPS inhibitors, ACCase inhibitors etc.) has also drastically increased, resulting in the occurrence of weed species resistant to these herbicides.0 Comments 0 Shares 113 Views 0 Reviews -
Cellulose beads were successfully prepared from waste denim using a dissolution-regeneration approach with ionic liquids as the dissolving solvent. Cellulose beads with different morphologies were achieved by altering the dissolving and coagulating solvents. The morphological differences were quantified by N2 physisorption. The impact of morphology on the cellulose beads' potential application was investigated in the context of drug loading and release. https://www.selleckchem.com/products/blu-285.html The results show that the fibrous morphology showed a better loading capacity than the globular analogue due to its higher surface area and pore volume.The decision for dairy farmers to invest in automated oestrus detection (AOD) technologies involves the weighing up of the costs and benefits of implementation. In this paper, through a review of the existing literature, we examine the impacts of investment in AOD technologies in relation to the profitability and technical performance of dairy farms. Peer-reviewed articles published between 1970 and 2019 on the investment viability of AOD technologies were collated and analysed. We capture the different measures used in assessing the economic performance of investment in AOD technologies over time which include net present value (NPV), milk production, Benefit-Cost Ratio (BCR), internal rate of return (IRR) and payback period (PBP). The study concludes that investment in AOD technologies is not only worthwhile but also contributes to farm profitability.
This cross-sectional study aimed to explore the microbial composition of the gut and its possible association with the Mediterranean diet (MD) after adjusting for demographic and anthropometric characteristics in a sample of healthy young Italian adults.
Gut microbiota, demographic information, and data on adherence to MD and physical activity (PA) habits were collected in a sample of 140 university students (48.6% males, mean age 22.5 ± 2.9) with a mean body mass index (BMI) of 22.4 ± 2.8 kg/m
(15.2-33.8) and a mean PA level of 3006.2 ± 2973.6 metabolic equivalent (MET)-minutes/week (148-21,090).
A high prevalence of
and
was found in all the fecal samples. Significant dissimilarities in the microbiota composition were found on the basis of MD adherence and PA levels (
= 0.001). At the genus level,
and
were highly abundant in overweight/obese individuals,
and
in participants with lower adherence to MD, and
in subjects with low levels of PA (
= 0.001). A significantly higher abundance of
was shown by individuals with lower BMI, lower MD adherence, and lower PA levels (
= 0.001).
This study contributes to the characterization of the gut microbiome of healthy humans. The findings suggest the role of diet and PA in determining gut microbiota variability.
This study contributes to the characterization of the gut microbiome of healthy humans. The findings suggest the role of diet and PA in determining gut microbiota variability.Alternative splicing is a highly sophisticated process, playing a significant role in posttranscriptional gene expression and underlying the diversity and complexity of organisms. Its regulation is multilayered, including an intrinsic role of RNA structural arrangement which undergoes time- and tissue-specific alterations. In this review, we describe the principles of RNA structural arrangement and briefly decipher its cis- and trans-acting cellular modulators which serve as crucial determinants of biological functionality of the RNA structure. Subsequently, we engage in a discussion about the RNA structure-mediated mechanisms of alternative splicing regulation. On one hand, the impairment of formation of optimal RNA structures may have critical consequences for the splicing outcome and further contribute to understanding the pathomechanism of severe disorders. On the other hand, the structural aspects of RNA became significant features taken into consideration in the endeavor of finding potential therapeutic treatments. Both aspects have been addressed by us emphasizing the importance of ongoing studies in both fields.Laminates with unidirectionally arrayed chopped strands (UACS) are one of the advanced short fiber reinforced polymer composites (SFRP) with significant application prospect, which greatly improves mechanical properties compared to the traditional SFRP, meanwhile ensuring excellent flowability. In practice, composite laminate with an open hole is one of the typical connective components, and it is necessary to clarify the allowable load and damage tolerance performance of notched structures. In the present study, UACS laminates were fabricated using the continuous carbon fiber reinforced polymer (CFRP) prepreg, on which regularly arrayed bi-angled slits were introduced by a commercial numerical control cutter. The tensile strength and strain distribution around the open hole of the notched UACS laminate were experimentally investigated, while the damage progression near the open hole of the notched UACS laminate was analyzed by the finite element method (FEM). The tensile strength of the notched UACS laminate was measured at 298 MPa, which is about 60% of the strength of the unnotched UACS laminate. The simulation results match well with the experimental results, although there is a little overestimate on strength, by about 5% and 7%, for unnotched and notched UACS laminates, respectively. The final critical failure mode for the notched UACS laminate is mainly dominated by the delamination instead of the fiber breakage in the unnotched UACS laminate.Microalgal biomass is a sustainable and valuable source of lipids with omega-3 fatty acids. The efficient extraction of lipids from microalgae requires fast and alternative extraction methods, frequently combined with biomass pre-treatment by different procedures. In this work, Pressurized liquid extraction (PLE) was optimized and compared with traditional lipid extraction methods, Folch and Bligh and Dyer, and with a new Ultrasound Assisted Extraction (UAE) method for lipids from microalgae Isochrysis galbana. To further optimize PLE and UAE, enzymatic pre-treatment of microalga Isochrysis galbana was studied with commercial enzymes Viscozyme and Celluclast. No significant differences were found for lipid yields among different extraction techniques used. However, advanced extraction techniques with or without pre-treatment are a green, fast, and toxic solvent free alternative to traditional techniques. Lipid composition of Isochrysis was determined by HPLC-ELSD and included neutral and polar lipids, showing that each fraction comprised different contents in omega-3 polyunsaturated fatty acids (PUFA).
Cellulose beads were successfully prepared from waste denim using a dissolution-regeneration approach with ionic liquids as the dissolving solvent. Cellulose beads with different morphologies were achieved by altering the dissolving and coagulating solvents. The morphological differences were quantified by N2 physisorption. The impact of morphology on the cellulose beads' potential application was investigated in the context of drug loading and release. https://www.selleckchem.com/products/blu-285.html The results show that the fibrous morphology showed a better loading capacity than the globular analogue due to its higher surface area and pore volume.The decision for dairy farmers to invest in automated oestrus detection (AOD) technologies involves the weighing up of the costs and benefits of implementation. In this paper, through a review of the existing literature, we examine the impacts of investment in AOD technologies in relation to the profitability and technical performance of dairy farms. Peer-reviewed articles published between 1970 and 2019 on the investment viability of AOD technologies were collated and analysed. We capture the different measures used in assessing the economic performance of investment in AOD technologies over time which include net present value (NPV), milk production, Benefit-Cost Ratio (BCR), internal rate of return (IRR) and payback period (PBP). The study concludes that investment in AOD technologies is not only worthwhile but also contributes to farm profitability. This cross-sectional study aimed to explore the microbial composition of the gut and its possible association with the Mediterranean diet (MD) after adjusting for demographic and anthropometric characteristics in a sample of healthy young Italian adults. Gut microbiota, demographic information, and data on adherence to MD and physical activity (PA) habits were collected in a sample of 140 university students (48.6% males, mean age 22.5 ± 2.9) with a mean body mass index (BMI) of 22.4 ± 2.8 kg/m (15.2-33.8) and a mean PA level of 3006.2 ± 2973.6 metabolic equivalent (MET)-minutes/week (148-21,090). A high prevalence of and was found in all the fecal samples. Significant dissimilarities in the microbiota composition were found on the basis of MD adherence and PA levels ( = 0.001). At the genus level, and were highly abundant in overweight/obese individuals, and in participants with lower adherence to MD, and in subjects with low levels of PA ( = 0.001). A significantly higher abundance of was shown by individuals with lower BMI, lower MD adherence, and lower PA levels ( = 0.001). This study contributes to the characterization of the gut microbiome of healthy humans. The findings suggest the role of diet and PA in determining gut microbiota variability. This study contributes to the characterization of the gut microbiome of healthy humans. The findings suggest the role of diet and PA in determining gut microbiota variability.Alternative splicing is a highly sophisticated process, playing a significant role in posttranscriptional gene expression and underlying the diversity and complexity of organisms. Its regulation is multilayered, including an intrinsic role of RNA structural arrangement which undergoes time- and tissue-specific alterations. In this review, we describe the principles of RNA structural arrangement and briefly decipher its cis- and trans-acting cellular modulators which serve as crucial determinants of biological functionality of the RNA structure. Subsequently, we engage in a discussion about the RNA structure-mediated mechanisms of alternative splicing regulation. On one hand, the impairment of formation of optimal RNA structures may have critical consequences for the splicing outcome and further contribute to understanding the pathomechanism of severe disorders. On the other hand, the structural aspects of RNA became significant features taken into consideration in the endeavor of finding potential therapeutic treatments. Both aspects have been addressed by us emphasizing the importance of ongoing studies in both fields.Laminates with unidirectionally arrayed chopped strands (UACS) are one of the advanced short fiber reinforced polymer composites (SFRP) with significant application prospect, which greatly improves mechanical properties compared to the traditional SFRP, meanwhile ensuring excellent flowability. In practice, composite laminate with an open hole is one of the typical connective components, and it is necessary to clarify the allowable load and damage tolerance performance of notched structures. In the present study, UACS laminates were fabricated using the continuous carbon fiber reinforced polymer (CFRP) prepreg, on which regularly arrayed bi-angled slits were introduced by a commercial numerical control cutter. The tensile strength and strain distribution around the open hole of the notched UACS laminate were experimentally investigated, while the damage progression near the open hole of the notched UACS laminate was analyzed by the finite element method (FEM). The tensile strength of the notched UACS laminate was measured at 298 MPa, which is about 60% of the strength of the unnotched UACS laminate. The simulation results match well with the experimental results, although there is a little overestimate on strength, by about 5% and 7%, for unnotched and notched UACS laminates, respectively. The final critical failure mode for the notched UACS laminate is mainly dominated by the delamination instead of the fiber breakage in the unnotched UACS laminate.Microalgal biomass is a sustainable and valuable source of lipids with omega-3 fatty acids. The efficient extraction of lipids from microalgae requires fast and alternative extraction methods, frequently combined with biomass pre-treatment by different procedures. In this work, Pressurized liquid extraction (PLE) was optimized and compared with traditional lipid extraction methods, Folch and Bligh and Dyer, and with a new Ultrasound Assisted Extraction (UAE) method for lipids from microalgae Isochrysis galbana. To further optimize PLE and UAE, enzymatic pre-treatment of microalga Isochrysis galbana was studied with commercial enzymes Viscozyme and Celluclast. No significant differences were found for lipid yields among different extraction techniques used. However, advanced extraction techniques with or without pre-treatment are a green, fast, and toxic solvent free alternative to traditional techniques. Lipid composition of Isochrysis was determined by HPLC-ELSD and included neutral and polar lipids, showing that each fraction comprised different contents in omega-3 polyunsaturated fatty acids (PUFA).0 Comments 0 Shares 92 Views 0 Reviews -
RNA-Seq and immunoblotting analyses showed that the MEOX1 knockdown decreases expression of tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 5B (STAT5B), and STAT6 in P53- and PTEN-deficient TNBC cells. These results reveal the effects of combined P53/PTEN deficiency on MEOX1 expression and TNBC cell proliferation, suggesting that MEOX1 may serve as a potential therapeutic target for managing P53- and PTEN-deficient TNBC.The accumulation of amyloid Tau aggregates is implicated in Alzheimer's disease (AD) and other tauopathies. Molecular chaperones are known to maintain protein homeostasis. Here we show that an ATP-dependent human chaperone system disassembles Tau fibrils in vitro We found that this function is mediated by the core chaperone HSC70, assisted by specific co-chaperones, in particular class B J‑domain proteins and a heat shock protein 110 (Hsp110)-type nucleotide exchange factor (NEF). The Hsp70 disaggregation machinery processed recombinant fibrils assembled from all six Tau isoforms as well as sarkosyl-resistant Tau aggregates extracted from cell cultures and human AD brain tissues, demonstrating the ability of the Hsp70 machinery to recognize a broad range of Tau aggregates. However, the chaperone activity released monomeric and small oligomeric Tau species, which induced the aggregation of self-propagating Tau conformers in a Tau cell culture model. We conclude that the activity of the Hsp70 disaggregation machinery is a double-sided sword, as it eliminates Tau amyloids at the cost of generating new seeds.Graded transcription factors are pivotal regulators of embryonic patterning, but whether their role changes over time is unclear. A light-regulated protein degradation system was used to assay temporal dependence of the transcription factor Dorsal in dorsal-ventral axis patterning of Drosophila embryos. Surprisingly, the high-threshold target gene snail only requires Dorsal input early but not late when Dorsal levels peak. Instead, late snail expression can be supported by action of the Twist transcription factor, specifically, through one enhancer, sna.distal This study demonstrates that continuous input is not required for some Dorsal targets and downstream responses, such as twist, function as molecular ratchets.Chromatin modifiers play critical roles in epidermal development, but the functions of histone deacetylases in this context are poorly understood. The class I HDAC, HDAC3, is of particular interest because it plays divergent roles in different tissues by partnering with tissue-specific transcription factors. We found that HDAC3 is expressed broadly in embryonic epidermis and is required for its orderly stepwise stratification. HDAC3 protein stability in vivo relies on NCoR and SMRT, which function redundantly in epidermal development. However, point mutations in the NCoR and SMRT deacetylase-activating domains, which are required for HDAC3's enzymatic function, permit normal stratification, indicating that HDAC3's roles in this context are largely independent of its histone deacetylase activity. HDAC3-bound sites are significantly enriched for predicted binding motifs for critical epidermal transcription factors including AP1, GRHL, and KLF family members. Our results suggest that among these, HDAC3 operates in conjunction with KLF4 to repress inappropriate expression of Tgm1, Krt16, and Aqp3 In parallel, HDAC3 suppresses expression of inflammatory cytokines through a Rela-dependent mechanism. These data identify HDAC3 as a hub coordinating multiple aspects of epidermal barrier acquisition.Introduction Microangiopathic and macroangiopathic complications are the main cause of morbidity and mortality in the diabetic population. Numerous publications have highlighted the role of glycation in the onset of complications of diabetes. In this context, the detection of fructosamine-3-kinase (FN3K)-an enzyme capable of counteracting the effect of hyperglycemia by intervening in protein glycation-has attracted great interest. Several studies have linked FN3K genetic variability to its enzymatic activity and glycated hemoglobin (HbA1c) levels. Here, we investigated the role of FN3K polymorphisms in the development of microvascular and macrovascular complications of diabetes. Research design and methods The anthropometric and biochemical parameters, and any medical history of microangiopathic and macroangiopathic complications, were documented in a sample of 80 subjects with type 2 diabetes. All subjects were screened for FN3K gene and analyzed for the combination of three polymorphisms known to be associated with its enzymatic activity (rs3859206 and rs2256339 in the promoter region and rs1056534 in exon 6). Results The combination of allelic variants of FN3K polymorphisms resulted in 13 distinct genotypic variants within the cohort. Comparison between genotypes showed no significant differences in terms of demographic, anthropometric and biochemical parameters, risk markers and long-term complications, except for a higher age and vitamin E levels associated with the genotype presenting GG at position -385, TT at position -232, and CC at c.900 A. Evaluating the microangiopathic and macroangiopathic complications as a whole, we found that they appeared significantly less present in this genotype compared with all other genotypes (p=0.0306). Conclusions The group of patients carrying the favorable allele for the three polymorphisms of the FN3K gene revealed less severe microangiopathy and macroangiopathy, suggesting a protective role of this genotype against the onset of the complications of diabetes.Mouse models are frequently used to study diabetes-associated ulcers, however, whether these models accurately simulate impaired wound healing has not been thoroughly investigated. This systematic review aimed to determine whether wound healing is impaired in mouse models of diabetes and assess the quality of the past research. A systematic literature search was performed of publicly available databases to identify original articles examining wound healing in mouse models of diabetes. A meta-analysis was performed to examine the effect of diabetes on wound healing rate using random effect models. https://www.selleckchem.com/products/rin1.html A meta-regression was performed to examine the effect of diabetes duration on wound healing impairment. The quality of the included studies was also assessed using two newly developed tools. 77 studies using eight different models of diabetes within 678 non-diabetic and 720 diabetic **** were included. Meta-analysis showed that wound healing was impaired in all eight models. Meta-regression suggested that longer duration of diabetes prior to wound induction was correlated with greater degree of wound healing impairment.
RNA-Seq and immunoblotting analyses showed that the MEOX1 knockdown decreases expression of tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 5B (STAT5B), and STAT6 in P53- and PTEN-deficient TNBC cells. These results reveal the effects of combined P53/PTEN deficiency on MEOX1 expression and TNBC cell proliferation, suggesting that MEOX1 may serve as a potential therapeutic target for managing P53- and PTEN-deficient TNBC.The accumulation of amyloid Tau aggregates is implicated in Alzheimer's disease (AD) and other tauopathies. Molecular chaperones are known to maintain protein homeostasis. Here we show that an ATP-dependent human chaperone system disassembles Tau fibrils in vitro We found that this function is mediated by the core chaperone HSC70, assisted by specific co-chaperones, in particular class B J‑domain proteins and a heat shock protein 110 (Hsp110)-type nucleotide exchange factor (NEF). The Hsp70 disaggregation machinery processed recombinant fibrils assembled from all six Tau isoforms as well as sarkosyl-resistant Tau aggregates extracted from cell cultures and human AD brain tissues, demonstrating the ability of the Hsp70 machinery to recognize a broad range of Tau aggregates. However, the chaperone activity released monomeric and small oligomeric Tau species, which induced the aggregation of self-propagating Tau conformers in a Tau cell culture model. We conclude that the activity of the Hsp70 disaggregation machinery is a double-sided sword, as it eliminates Tau amyloids at the cost of generating new seeds.Graded transcription factors are pivotal regulators of embryonic patterning, but whether their role changes over time is unclear. A light-regulated protein degradation system was used to assay temporal dependence of the transcription factor Dorsal in dorsal-ventral axis patterning of Drosophila embryos. Surprisingly, the high-threshold target gene snail only requires Dorsal input early but not late when Dorsal levels peak. Instead, late snail expression can be supported by action of the Twist transcription factor, specifically, through one enhancer, sna.distal This study demonstrates that continuous input is not required for some Dorsal targets and downstream responses, such as twist, function as molecular ratchets.Chromatin modifiers play critical roles in epidermal development, but the functions of histone deacetylases in this context are poorly understood. The class I HDAC, HDAC3, is of particular interest because it plays divergent roles in different tissues by partnering with tissue-specific transcription factors. We found that HDAC3 is expressed broadly in embryonic epidermis and is required for its orderly stepwise stratification. HDAC3 protein stability in vivo relies on NCoR and SMRT, which function redundantly in epidermal development. However, point mutations in the NCoR and SMRT deacetylase-activating domains, which are required for HDAC3's enzymatic function, permit normal stratification, indicating that HDAC3's roles in this context are largely independent of its histone deacetylase activity. HDAC3-bound sites are significantly enriched for predicted binding motifs for critical epidermal transcription factors including AP1, GRHL, and KLF family members. Our results suggest that among these, HDAC3 operates in conjunction with KLF4 to repress inappropriate expression of Tgm1, Krt16, and Aqp3 In parallel, HDAC3 suppresses expression of inflammatory cytokines through a Rela-dependent mechanism. These data identify HDAC3 as a hub coordinating multiple aspects of epidermal barrier acquisition.Introduction Microangiopathic and macroangiopathic complications are the main cause of morbidity and mortality in the diabetic population. Numerous publications have highlighted the role of glycation in the onset of complications of diabetes. In this context, the detection of fructosamine-3-kinase (FN3K)-an enzyme capable of counteracting the effect of hyperglycemia by intervening in protein glycation-has attracted great interest. Several studies have linked FN3K genetic variability to its enzymatic activity and glycated hemoglobin (HbA1c) levels. Here, we investigated the role of FN3K polymorphisms in the development of microvascular and macrovascular complications of diabetes. Research design and methods The anthropometric and biochemical parameters, and any medical history of microangiopathic and macroangiopathic complications, were documented in a sample of 80 subjects with type 2 diabetes. All subjects were screened for FN3K gene and analyzed for the combination of three polymorphisms known to be associated with its enzymatic activity (rs3859206 and rs2256339 in the promoter region and rs1056534 in exon 6). Results The combination of allelic variants of FN3K polymorphisms resulted in 13 distinct genotypic variants within the cohort. Comparison between genotypes showed no significant differences in terms of demographic, anthropometric and biochemical parameters, risk markers and long-term complications, except for a higher age and vitamin E levels associated with the genotype presenting GG at position -385, TT at position -232, and CC at c.900 A. Evaluating the microangiopathic and macroangiopathic complications as a whole, we found that they appeared significantly less present in this genotype compared with all other genotypes (p=0.0306). Conclusions The group of patients carrying the favorable allele for the three polymorphisms of the FN3K gene revealed less severe microangiopathy and macroangiopathy, suggesting a protective role of this genotype against the onset of the complications of diabetes.Mouse models are frequently used to study diabetes-associated ulcers, however, whether these models accurately simulate impaired wound healing has not been thoroughly investigated. This systematic review aimed to determine whether wound healing is impaired in mouse models of diabetes and assess the quality of the past research. A systematic literature search was performed of publicly available databases to identify original articles examining wound healing in mouse models of diabetes. A meta-analysis was performed to examine the effect of diabetes on wound healing rate using random effect models. https://www.selleckchem.com/products/rin1.html A meta-regression was performed to examine the effect of diabetes duration on wound healing impairment. The quality of the included studies was also assessed using two newly developed tools. 77 studies using eight different models of diabetes within 678 non-diabetic and 720 diabetic mice were included. Meta-analysis showed that wound healing was impaired in all eight models. Meta-regression suggested that longer duration of diabetes prior to wound induction was correlated with greater degree of wound healing impairment.0 Comments 0 Shares 90 Views 0 Reviews -
The frequency of disruptive TP53-mutations was not significantly different between groups. Compared with nonsmoking, heavy smoking of 20 pack-years or more was significantly associated with decreased hmMGMT (adjusted odds ratio, 0.08; 95% CI, 0.01 to 0.56; P = 0.01). Patients who had both hmMGMT and disruptive TP53-mutations showed a significantly higher relapse rate than all other patients (subdistribution hazard ratio, 1.77; 95% CI, 1.07 to 2.92; P = 0.026). CONCLUSIONS It was found that hmMGMT was suppressed by heavy smoking, and hmMGMT combined with disruptive TP53-mutations may indicate a poor prognosis in patients with HNSCC.Stored muscle carbohydrate supply and energetic efficiency constrain muscle functional capacity during exercise and are influenced by common physiological variables (e.g. age, diet, and physical activity level). Whether these constraints affect overall functional capacity or the timing of muscle energetic failure during acute hypoxia is not known. We interrogated skeletal muscle contractile properties in two anatomically distinct rodent hindlimb muscles that have well characterized differences in energetic efficiency (locomotory- extensor digitorum longus (EDL) and postural- soleus muscles) following a 24 hour fasting period that resulted in substantially reduced muscle carbohydrate supply. 180 mins of acute hypoxia resulted in complete energetic failure in all muscles tested, indicated by loss of force production, substantial reductions in total adenosine nucleotide pool intermediates, and increased adenosine nucleotide degradation product-inosine monophosphate (IMP). These changes occurred in the absence of apparent myofiber structural damage assessed histologically by both transverse section and whole mount. Fasting and the associated reduction of the available intracellular carbohydrate pool (~50% decrease in skeletal muscle) did not significantly alter the timing to muscle functional impairment or affect the overall force/work capacities of either muscle type. Fasting resulted in greater passive tension development in both muscle types, which may have implications for the design of pre-clinical studies involving optimal timing of reperfusion or administration of precision therapeutics.BACKGROUND Next-generation sequencing (NGS) has enabled efficient high-resolution typing of human leukocyte antigen (HLA) genes with minimal ambiguity. Most commercially available assays amplify individual or subgroup of HLA genes by long-range PCR followed by library preparation and sequencing. The AllType assay simplifies the workflow by amplifying 11 transplant-relevant HLA genes in one PCR reaction. Here, we report the performance of this unique workflow evaluated using 218 genetically diverse samples. METHODS Five whole genes (HLA-A/****DQA1/DPA1) and six near-whole genes (HLA-DRB1/DRB345/DQB1/DPB1; excluding exon 1 and part of intron 1) were amplified in a multiplexed, long-range PCR. Manual library preparation was performed per manufacturer's protocol, followed by template preparation and chip loading on the Ion Chef, and sequencing on the Ion S5 sequencer. Pre-specified rules for quality control and repeat testing were followed; technologists were blinded to the reference results. The concordance betwclinical HLA typing at the 2-field resolution. The multiplex PCR strategy simplifies the laboratory procedure without compromising the typing accuracy.PURPOSE The purpose of this study was to compare early and late rapid torque parameters of the plantar flexors (PFs) in middle-aged (MM) and older (OM) males, and determine the effect of normalization to peak torque (PT) and muscle cross-sectional area (CSA). METHODS Twenty-nine healthy, MM (n = 14; 45 ± 2 yrs) and OM (n = 15; 65 ± 3 yrs) performed rapid, maximal isometric contractions of the PFs. PT, as well as rate of torque development and impulse during the early (0-50 ms; RTD0-50, IMP0-50) and late (100-200 ms; RTD100-200, IMP100-200) contraction phases were calculated. Torque at 50 (TQ50), 100 (TQ100), and 200 (TQ200) ms was also obtained. CSA and echo-intensity (EI) of the gastrocnemii were acquired via ultrasonography. Torque variables were normalized to PT and CSA. Rate of EMG rise (RER) for the medial gastrocnemius was calculated at 30, 50 and 75 ms. RESULTS TQ100 (MM = 69.71 ± 16.85 vs. https://www.selleckchem.com/products/Thiazovivin.html OM = 55.99 ± 18.54 Nm; p = 0.046), TQ200 (MM = 114.76 ± 26.79 vs. OM = 91.56 ± 28.10 Nm; p = 0.031), and IMP100-200 (MM = 4.79 ± 1.11 vs. OM = 3.83 ± 1.17 Nm·s; p = 0.032) were lower in OM. PT, TQ50, RTD0-50, IMP0-50, RTD100-200, RER, CSA, and EI were similar between groups (p > 0.05). No differences were found for normalized torque variables (p > 0.05). EI was moderately associated with normalized torque parameters only (r = -0.38 --0.45). RER, at 75 ms, was moderately correlated with early, absolute torque measures and rapid torque variables made relative to PT and CSA (r = 0.41 --0.64). CONCLUSION Late rapid torque parameters of the PFs were preferentially impaired in OM compared to MM, and PT as well as CSA appeared to mediate this result.BACKGROUND Poor diet is a risk factor for anemia, overweight, and obesity among adolescent girls. However, comprehensive assessment on dietary quality and habits in this population is limited. We assessed the association of meal patterning, dietary quality, and dietary diversity with both anemia and overweight-obesity. METHODS We conducted a cross-sectional survey in 335 school-going adolescent girls aged 12-19 years from three districts in West Java using multi-stage cluster sampling. Meal patterning, Dietary Quality Index for Adolescents (DQI-A), and Dietary Diversity Score (DDS) were determined using 2-day 24-h recall. RESULTS Of the girls, 45% were anemic and 17% overweight or obese. Eating occasions of 3-4 times (AOR 2.68, 95% CI 1.21-5.98) and >4 times (AOR 2.43, 95% CI 1.01-5.83) were associated with greater odds of developing anemia compared to eating occasions of less then 3 times. Adolescent girls who skipped dinner had greater odds of being overweight or obese (AOR 2.13, 95% CI 1.10-4.10) and werety among adolescent girls.
The frequency of disruptive TP53-mutations was not significantly different between groups. Compared with nonsmoking, heavy smoking of 20 pack-years or more was significantly associated with decreased hmMGMT (adjusted odds ratio, 0.08; 95% CI, 0.01 to 0.56; P = 0.01). Patients who had both hmMGMT and disruptive TP53-mutations showed a significantly higher relapse rate than all other patients (subdistribution hazard ratio, 1.77; 95% CI, 1.07 to 2.92; P = 0.026). CONCLUSIONS It was found that hmMGMT was suppressed by heavy smoking, and hmMGMT combined with disruptive TP53-mutations may indicate a poor prognosis in patients with HNSCC.Stored muscle carbohydrate supply and energetic efficiency constrain muscle functional capacity during exercise and are influenced by common physiological variables (e.g. age, diet, and physical activity level). Whether these constraints affect overall functional capacity or the timing of muscle energetic failure during acute hypoxia is not known. We interrogated skeletal muscle contractile properties in two anatomically distinct rodent hindlimb muscles that have well characterized differences in energetic efficiency (locomotory- extensor digitorum longus (EDL) and postural- soleus muscles) following a 24 hour fasting period that resulted in substantially reduced muscle carbohydrate supply. 180 mins of acute hypoxia resulted in complete energetic failure in all muscles tested, indicated by loss of force production, substantial reductions in total adenosine nucleotide pool intermediates, and increased adenosine nucleotide degradation product-inosine monophosphate (IMP). These changes occurred in the absence of apparent myofiber structural damage assessed histologically by both transverse section and whole mount. Fasting and the associated reduction of the available intracellular carbohydrate pool (~50% decrease in skeletal muscle) did not significantly alter the timing to muscle functional impairment or affect the overall force/work capacities of either muscle type. Fasting resulted in greater passive tension development in both muscle types, which may have implications for the design of pre-clinical studies involving optimal timing of reperfusion or administration of precision therapeutics.BACKGROUND Next-generation sequencing (NGS) has enabled efficient high-resolution typing of human leukocyte antigen (HLA) genes with minimal ambiguity. Most commercially available assays amplify individual or subgroup of HLA genes by long-range PCR followed by library preparation and sequencing. The AllType assay simplifies the workflow by amplifying 11 transplant-relevant HLA genes in one PCR reaction. Here, we report the performance of this unique workflow evaluated using 218 genetically diverse samples. METHODS Five whole genes (HLA-A/B/C/DQA1/DPA1) and six near-whole genes (HLA-DRB1/DRB345/DQB1/DPB1; excluding exon 1 and part of intron 1) were amplified in a multiplexed, long-range PCR. Manual library preparation was performed per manufacturer's protocol, followed by template preparation and chip loading on the Ion Chef, and sequencing on the Ion S5 sequencer. Pre-specified rules for quality control and repeat testing were followed; technologists were blinded to the reference results. The concordance betwclinical HLA typing at the 2-field resolution. The multiplex PCR strategy simplifies the laboratory procedure without compromising the typing accuracy.PURPOSE The purpose of this study was to compare early and late rapid torque parameters of the plantar flexors (PFs) in middle-aged (MM) and older (OM) males, and determine the effect of normalization to peak torque (PT) and muscle cross-sectional area (CSA). METHODS Twenty-nine healthy, MM (n = 14; 45 ± 2 yrs) and OM (n = 15; 65 ± 3 yrs) performed rapid, maximal isometric contractions of the PFs. PT, as well as rate of torque development and impulse during the early (0-50 ms; RTD0-50, IMP0-50) and late (100-200 ms; RTD100-200, IMP100-200) contraction phases were calculated. Torque at 50 (TQ50), 100 (TQ100), and 200 (TQ200) ms was also obtained. CSA and echo-intensity (EI) of the gastrocnemii were acquired via ultrasonography. Torque variables were normalized to PT and CSA. Rate of EMG rise (RER) for the medial gastrocnemius was calculated at 30, 50 and 75 ms. RESULTS TQ100 (MM = 69.71 ± 16.85 vs. https://www.selleckchem.com/products/Thiazovivin.html OM = 55.99 ± 18.54 Nm; p = 0.046), TQ200 (MM = 114.76 ± 26.79 vs. OM = 91.56 ± 28.10 Nm; p = 0.031), and IMP100-200 (MM = 4.79 ± 1.11 vs. OM = 3.83 ± 1.17 Nm·s; p = 0.032) were lower in OM. PT, TQ50, RTD0-50, IMP0-50, RTD100-200, RER, CSA, and EI were similar between groups (p > 0.05). No differences were found for normalized torque variables (p > 0.05). EI was moderately associated with normalized torque parameters only (r = -0.38 --0.45). RER, at 75 ms, was moderately correlated with early, absolute torque measures and rapid torque variables made relative to PT and CSA (r = 0.41 --0.64). CONCLUSION Late rapid torque parameters of the PFs were preferentially impaired in OM compared to MM, and PT as well as CSA appeared to mediate this result.BACKGROUND Poor diet is a risk factor for anemia, overweight, and obesity among adolescent girls. However, comprehensive assessment on dietary quality and habits in this population is limited. We assessed the association of meal patterning, dietary quality, and dietary diversity with both anemia and overweight-obesity. METHODS We conducted a cross-sectional survey in 335 school-going adolescent girls aged 12-19 years from three districts in West Java using multi-stage cluster sampling. Meal patterning, Dietary Quality Index for Adolescents (DQI-A), and Dietary Diversity Score (DDS) were determined using 2-day 24-h recall. RESULTS Of the girls, 45% were anemic and 17% overweight or obese. Eating occasions of 3-4 times (AOR 2.68, 95% CI 1.21-5.98) and >4 times (AOR 2.43, 95% CI 1.01-5.83) were associated with greater odds of developing anemia compared to eating occasions of less then 3 times. Adolescent girls who skipped dinner had greater odds of being overweight or obese (AOR 2.13, 95% CI 1.10-4.10) and werety among adolescent girls.0 Comments 0 Shares 92 Views 0 Reviews -
Background The most dangerous atherosclerotic plaques, referred to as "vulnerable," are most likely to trigger acute atherothrombotic events such as myocardial infarction (heart attack) and stroke. Our goal was to uncover the molecular drivers of vulnerable plaque formation. Methods To elucidate the functional gene modules that drive vulnerable plaque formation, we performed a weighted gene coexpression network analysis integrated with a protein-protein interaction network analysis in human atherosclerotic carotid samples, which identified the candidate gene granulocyte-macrophage colony-stimulating factor 2 (GM-CSF) receptor alpha subunit (CSF2RA). Follow-up in vitro experiments were performed to elucidate the regulatory relationship between CSF2RA and the microRNA miR-532-3p as well as modifiers of macrophagic miR-532-3p-CSF2RA axis expression. Microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) studies elucidated the effect of statins on carotid miR-532-3p-CSF2RA axis exprs dysregulation is a key driver in vulnerable plaque formation.Patients with advanced HIV disease have a high risk of mortality, mainly from tuberculosis and cryptococcal meningitis. The advanced HIV disease management package recommended by WHO, which includes diagnostics, therapeutics, and patient psychosocial support, is barely implemented in many different countries. Here, we present a framework for the implementation of advanced HIV disease diagnostics. Laboratory and point-of-care-based reflex testing, coupled with provider-initiated requested testing, for cryptococcal antigen and urinary Mycobacterium tuberculosis lipoarabinomannan antigen, should be done for all patients with CD4+ cell counts of 200 cells per μL or less. Implementation of the advanced HIV disease package should be encouraged within primary health-care facilities and task shifting of testing to lay cadres could facilitate access to rapid results. Implementation of differentiated antiretroviral therapy delivery models can allow clinicians enough time to focus on the management of patients with advanced HIV disease. Efficient up-referral and post-discharge systems, including the development of patient-centric advanced HIV disease literacy, are also crucial. Implementation of the advanced HIV disease package is feasible at all health-care levels, and it should be part of the core of the global response towards ending AIDS as a public health threat.Mother-infant bonding develops rapidly following parturition and is accompanied by changes in sensory perception and behavior. Here, we study how ultrasonic vocalizations (USVs) are represented in the brain of mothers. Using a mouse line that allows temporally controlled genetic access to active neurons, we find that the temporal association cortex (TeA) in mothers exhibits robust USV responses. Rabies tracing from USV-responsive neurons reveals extensive subcortical and cortical inputs into TeA. A particularly dominant cortical source of inputs is the primary auditory cortex (A1), suggesting strong A1-to-TeA connectivity. Chemogenetic silencing of USV-responsive neurons in TeA impairs auditory-driven maternal preference in a pup-retrieval assay. Furthermore, dense extracellular recordings from awake **** reveal changes of both single-neuron and population responses to USVs in TeA, improving discriminability of pup calls in mothers compared with naive females. These data indicate that TeA plays a key role in encoding and perceiving pup cries during motherhood.In the eye, the function of same-type photoreceptors must be regionally adjusted to process a highly asymmetrical natural visual world. Here, we show that UV cones in the larval zebrafish area temporalis are specifically tuned for UV-bright prey capture in their upper frontal visual field, which may use the signal from a single cone at a time. For this, UV-photon detection probability is regionally boosted more than 10-fold. Next, in vivo two-photon imaging, transcriptomics, and computational modeling reveal that these cones use an elevated baseline of synaptic calcium to facilitate the encoding of bright objects, which in turn results from expressional tuning of phototransduction genes. Moreover, the light-driven synaptic calcium signal is regionally slowed by interactions with horizontal cells and later accentuated at the level of glutamate release driving retinal networks. These regional differences tally with variations between peripheral and foveal cones in primates and hint at a common mechanistic origin.Autophagy is activated by prolonged fasting but cannot overcome the ensuing hepatic lipid overload, resulting in fatty liver. Here, we describe a peroxisome-lysosome metabolic link that restricts autophagic degradation of lipids. Acyl-CoA oxidase 1 (Acox1), the enzyme that catalyzes the first step in peroxisomal β-oxidation, is enriched in liver and further increases with fasting or high-fat diet (HFD). Liver-specific Acox1 knockout (Acox1-LKO) protected **** against hepatic steatosis caused by starvation or HFD due to induction of autophagic degradation of lipid droplets. https://www.selleckchem.com/products/azd3229.html Hepatic Acox1 deficiency markedly lowered total cytosolic acetyl-CoA levels, which led to decreased Raptor acetylation and reduced lysosomal localization of mTOR, resulting in impaired activation of mTORC1, a central regulator of autophagy. Dichloroacetic acid treatment elevated acetyl-CoA levels, restored mTORC1 activation, inhibited autophagy, and increased hepatic triglycerides in Acox1-LKO ****. These results identify peroxisome-derived acetyl-CoA as a key metabolic regulator of autophagy that controls hepatic lipid homeostasis.Normal oocyte meiosis is a prerequisite for successful human reproduction, and abnormalities in the process will result in infertility. In 2016, we identified mutations in TUBB8 as responsible for human oocyte meiotic arrest. However, the underlying genetic factors for most affected individuals remain unknown. TRIP13, encoding an AAA-ATPase, is a key component of the spindle assembly checkpoint, and recurrent homozygous nonsense variants and a splicing variant in TRIP13 are reported to cause Wilms tumors in children. In this study, we identified homozygous and compound heterozygous missense pathogenic variants in TRIP13 responsible for female infertility mainly characterized by oocyte meiotic arrest in five individuals from four independent families. Individuals from three families suffered from oocyte maturation arrest, whereas the individual from the fourth family had abnormal zygote cleavage. All displayed only the infertility phenotype without Wilms tumors or any other abnormalities. In vitro and in vivo studies showed that the identified variants reduced the protein abundance of TRIP13 and caused its downstream molecule, HORMAD2, to accumulate in HeLa cells and in proband-derived lymphoblastoid cells.
Background The most dangerous atherosclerotic plaques, referred to as "vulnerable," are most likely to trigger acute atherothrombotic events such as myocardial infarction (heart attack) and stroke. Our goal was to uncover the molecular drivers of vulnerable plaque formation. Methods To elucidate the functional gene modules that drive vulnerable plaque formation, we performed a weighted gene coexpression network analysis integrated with a protein-protein interaction network analysis in human atherosclerotic carotid samples, which identified the candidate gene granulocyte-macrophage colony-stimulating factor 2 (GM-CSF) receptor alpha subunit (CSF2RA). Follow-up in vitro experiments were performed to elucidate the regulatory relationship between CSF2RA and the microRNA miR-532-3p as well as modifiers of macrophagic miR-532-3p-CSF2RA axis expression. Microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) studies elucidated the effect of statins on carotid miR-532-3p-CSF2RA axis exprs dysregulation is a key driver in vulnerable plaque formation.Patients with advanced HIV disease have a high risk of mortality, mainly from tuberculosis and cryptococcal meningitis. The advanced HIV disease management package recommended by WHO, which includes diagnostics, therapeutics, and patient psychosocial support, is barely implemented in many different countries. Here, we present a framework for the implementation of advanced HIV disease diagnostics. Laboratory and point-of-care-based reflex testing, coupled with provider-initiated requested testing, for cryptococcal antigen and urinary Mycobacterium tuberculosis lipoarabinomannan antigen, should be done for all patients with CD4+ cell counts of 200 cells per μL or less. Implementation of the advanced HIV disease package should be encouraged within primary health-care facilities and task shifting of testing to lay cadres could facilitate access to rapid results. Implementation of differentiated antiretroviral therapy delivery models can allow clinicians enough time to focus on the management of patients with advanced HIV disease. Efficient up-referral and post-discharge systems, including the development of patient-centric advanced HIV disease literacy, are also crucial. Implementation of the advanced HIV disease package is feasible at all health-care levels, and it should be part of the core of the global response towards ending AIDS as a public health threat.Mother-infant bonding develops rapidly following parturition and is accompanied by changes in sensory perception and behavior. Here, we study how ultrasonic vocalizations (USVs) are represented in the brain of mothers. Using a mouse line that allows temporally controlled genetic access to active neurons, we find that the temporal association cortex (TeA) in mothers exhibits robust USV responses. Rabies tracing from USV-responsive neurons reveals extensive subcortical and cortical inputs into TeA. A particularly dominant cortical source of inputs is the primary auditory cortex (A1), suggesting strong A1-to-TeA connectivity. Chemogenetic silencing of USV-responsive neurons in TeA impairs auditory-driven maternal preference in a pup-retrieval assay. Furthermore, dense extracellular recordings from awake mice reveal changes of both single-neuron and population responses to USVs in TeA, improving discriminability of pup calls in mothers compared with naive females. These data indicate that TeA plays a key role in encoding and perceiving pup cries during motherhood.In the eye, the function of same-type photoreceptors must be regionally adjusted to process a highly asymmetrical natural visual world. Here, we show that UV cones in the larval zebrafish area temporalis are specifically tuned for UV-bright prey capture in their upper frontal visual field, which may use the signal from a single cone at a time. For this, UV-photon detection probability is regionally boosted more than 10-fold. Next, in vivo two-photon imaging, transcriptomics, and computational modeling reveal that these cones use an elevated baseline of synaptic calcium to facilitate the encoding of bright objects, which in turn results from expressional tuning of phototransduction genes. Moreover, the light-driven synaptic calcium signal is regionally slowed by interactions with horizontal cells and later accentuated at the level of glutamate release driving retinal networks. These regional differences tally with variations between peripheral and foveal cones in primates and hint at a common mechanistic origin.Autophagy is activated by prolonged fasting but cannot overcome the ensuing hepatic lipid overload, resulting in fatty liver. Here, we describe a peroxisome-lysosome metabolic link that restricts autophagic degradation of lipids. Acyl-CoA oxidase 1 (Acox1), the enzyme that catalyzes the first step in peroxisomal β-oxidation, is enriched in liver and further increases with fasting or high-fat diet (HFD). Liver-specific Acox1 knockout (Acox1-LKO) protected mice against hepatic steatosis caused by starvation or HFD due to induction of autophagic degradation of lipid droplets. https://www.selleckchem.com/products/azd3229.html Hepatic Acox1 deficiency markedly lowered total cytosolic acetyl-CoA levels, which led to decreased Raptor acetylation and reduced lysosomal localization of mTOR, resulting in impaired activation of mTORC1, a central regulator of autophagy. Dichloroacetic acid treatment elevated acetyl-CoA levels, restored mTORC1 activation, inhibited autophagy, and increased hepatic triglycerides in Acox1-LKO mice. These results identify peroxisome-derived acetyl-CoA as a key metabolic regulator of autophagy that controls hepatic lipid homeostasis.Normal oocyte meiosis is a prerequisite for successful human reproduction, and abnormalities in the process will result in infertility. In 2016, we identified mutations in TUBB8 as responsible for human oocyte meiotic arrest. However, the underlying genetic factors for most affected individuals remain unknown. TRIP13, encoding an AAA-ATPase, is a key component of the spindle assembly checkpoint, and recurrent homozygous nonsense variants and a splicing variant in TRIP13 are reported to cause Wilms tumors in children. In this study, we identified homozygous and compound heterozygous missense pathogenic variants in TRIP13 responsible for female infertility mainly characterized by oocyte meiotic arrest in five individuals from four independent families. Individuals from three families suffered from oocyte maturation arrest, whereas the individual from the fourth family had abnormal zygote cleavage. All displayed only the infertility phenotype without Wilms tumors or any other abnormalities. In vitro and in vivo studies showed that the identified variants reduced the protein abundance of TRIP13 and caused its downstream molecule, HORMAD2, to accumulate in HeLa cells and in proband-derived lymphoblastoid cells.0 Comments 0 Shares 85 Views 0 Reviews -
Recently, the purine nucleoside inosine has been demonstrated to have several neuroprotective effects. Similarly, exercise training has well-known beneficial effects on mental health and cognitive function. Neuronal nitric oxide synthase (nNOS) is a key neuronal messenger in several brain regions, and the downregulation of nNOS has been shown to improve brain function. However, whether inosine and exercise training have combined effects on nNOS pathway-related proteins in the brain remains unknown. We found, for the first time, that inosine monophosphate (IMP), which is a precursor of inosine, decreases nNOS levels in the ventral hippocampus (vHp) and the cerebellum (Ce), but not in the dorsal hippocampus (dHp). In the vHp, the phosphorylation of cAMP response element-binding protein (CREB) was also upregulated, which negatively correlated with nNOS protein levels. In the cerebral cortex (Cx), no significant activation of the nNOS pathway was observed. In the dHp, vHp, Cx, and Ce, no interactions between the effects of IMP and exercise on nNOS protein and CREB phosphorylation levels were observed. The phosphorylation of nNOS was regulated by the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. Although IMP induced minor changes in Akt phosphorylation, nNOS phosphorylation was unchanged by either IMP or exercise. In conclusion, in the vHp, which is associated with emotional behavior, IMP decreased nNOS levels and activated CREB, suggesting that IMP can elicit anxiolytic effects.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new viral disease that has gained global attention owing to its ability to provoke community and health-care-associated outbreaks of severe infections in human populations. The virus poses serious challenges to clinical management because there are still no approved anti- SARS-CoV-2 drugs available. In this mini-review, we summarize the **** updated published reports that demonstrate the mechanism of SARS-CoV-2 entry into host cells, and discuss the availability and development of attractive host-based therapeutic options for SARS-CoV-2 infections.Dopamine (DA) in medial prefrontal cortex is crucial in extinction of aversive or appetitive experiences. Although attention has been mostly focused on the infralimbic area of prefrontal cortex, a role of the prelimbic (PL) area has been envisaged pointing to DA transmission in the extinction of drug conditioned behavior. Evidence shows that DA exerts its action also via both D1 and D2 receptor subtypes. Here we investigated the effects of D1 and D2 receptor agonist microinfusion in the PL cortex of C57BL/6J **** on expression and extinction of amphetamine-induced conditioned place preference (CPP), in order to ascertain the effects of selective vs concomitant receptor subtypes stimulation. SKF38393 and Quinpirole were used at doses not impairing expression of amphetamine-induced CPP on the day of infusion. Acute infusion of each agonist alone did not affect extinction in subsequent days in comparison with Vehicle-treated ****, while concomitant infusion of both agonists produced a clear-cut advance of extinction of preference for the compartment previously paired with amphetamine. These results show that concomitant stimulation of D1 and D2 receptors in PL is required to foster extinction suggesting a synergic action between receptors or a heteromeric receptor involvement.Objective The effects of aminoguanidine (AG) were investigated in a rat model of lipopolysaccharide (LPS)-induced anxiety- and depression-like behaviors. Materials and methods The animals were allocated to five groups (n = 10 in each) and treated by (1) saline as a control group, (2) LPS 1 mg/kg injected two hours before behavioral tests, (3-5) AG 50, 100 or 150 mg/kg before LPS. The open-field test (OFT), elevated plus maze test (EPT), and forced swimming (FS) tests were performed. The brains and blood were then collected to examine oxidative stress and inflammation criteria. Results LPS increased the immobility while decreased the active time in the FS test. In EPT, LPS decreased the time spent in the open arms, whereas it increased the time spent in the closed arms. https://www.selleckchem.com/products/bms-927711.html In OFT, LPS decreased the time spent in the central zone compared with the controls. A higher dose of selenium improved the performances of the rats in behavioral tests. LPS injection also increased malondialdehyde (MDA) while it decreased thiol, superoxide dismutase (***), and catalase. LPS also increased interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), but decreased IL-10 in the LPS group. AG protected the brain from inflammation and oxidative damage. Conclusion It was demonstrated that AG improves the behaviors of depression and anxiety in a rat model of LPS-induced anxiety- and depression-like behaviors. Moreover, the effects of AG were accompanied by improved inflammation and oxidative damage biomarkers in brain tissues.The Prefrontal cortex (PFC) has been highly related to executive functions such as working memory (WM). This study assesses the activity of the PFC in performing the Sternberg WM task (ST) with three levels of difficulty (easy, medium and hard) using the near-infrared spectroscopy (fNIRS) technique. Participants were 43 young and healthy right-handed women. Nine WM task blocks were pseudo randomly presented, three for each difficulty task. The results showed that the participant's performance was better in the easy trials than in the medium and hard trials. Performance in the medium trials was also better than in the hard ones. Bonferroni-corrected paired post-hoc t-tests indicated higher oxygenation in medium and hard tasks than in the easy ones for times between 13 and 42 s in the left lateral PFC and in both, medial and lateral, right PFC. Significant differences in Oxygenated hemoglobin (HbO), Total hemoglobin (HbT) and oxygenation (Oxy) changes depending on the Sternberg WM task were found. Unlike previous studies with fNIRS and WM, the current study uses a highly controlled WM task that differentiates between encoding, retention and retrieval phases, comparing different levels of task load.
Recently, the purine nucleoside inosine has been demonstrated to have several neuroprotective effects. Similarly, exercise training has well-known beneficial effects on mental health and cognitive function. Neuronal nitric oxide synthase (nNOS) is a key neuronal messenger in several brain regions, and the downregulation of nNOS has been shown to improve brain function. However, whether inosine and exercise training have combined effects on nNOS pathway-related proteins in the brain remains unknown. We found, for the first time, that inosine monophosphate (IMP), which is a precursor of inosine, decreases nNOS levels in the ventral hippocampus (vHp) and the cerebellum (Ce), but not in the dorsal hippocampus (dHp). In the vHp, the phosphorylation of cAMP response element-binding protein (CREB) was also upregulated, which negatively correlated with nNOS protein levels. In the cerebral cortex (Cx), no significant activation of the nNOS pathway was observed. In the dHp, vHp, Cx, and Ce, no interactions between the effects of IMP and exercise on nNOS protein and CREB phosphorylation levels were observed. The phosphorylation of nNOS was regulated by the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. Although IMP induced minor changes in Akt phosphorylation, nNOS phosphorylation was unchanged by either IMP or exercise. In conclusion, in the vHp, which is associated with emotional behavior, IMP decreased nNOS levels and activated CREB, suggesting that IMP can elicit anxiolytic effects.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new viral disease that has gained global attention owing to its ability to provoke community and health-care-associated outbreaks of severe infections in human populations. The virus poses serious challenges to clinical management because there are still no approved anti- SARS-CoV-2 drugs available. In this mini-review, we summarize the much updated published reports that demonstrate the mechanism of SARS-CoV-2 entry into host cells, and discuss the availability and development of attractive host-based therapeutic options for SARS-CoV-2 infections.Dopamine (DA) in medial prefrontal cortex is crucial in extinction of aversive or appetitive experiences. Although attention has been mostly focused on the infralimbic area of prefrontal cortex, a role of the prelimbic (PL) area has been envisaged pointing to DA transmission in the extinction of drug conditioned behavior. Evidence shows that DA exerts its action also via both D1 and D2 receptor subtypes. Here we investigated the effects of D1 and D2 receptor agonist microinfusion in the PL cortex of C57BL/6J mice on expression and extinction of amphetamine-induced conditioned place preference (CPP), in order to ascertain the effects of selective vs concomitant receptor subtypes stimulation. SKF38393 and Quinpirole were used at doses not impairing expression of amphetamine-induced CPP on the day of infusion. Acute infusion of each agonist alone did not affect extinction in subsequent days in comparison with Vehicle-treated mice, while concomitant infusion of both agonists produced a clear-cut advance of extinction of preference for the compartment previously paired with amphetamine. These results show that concomitant stimulation of D1 and D2 receptors in PL is required to foster extinction suggesting a synergic action between receptors or a heteromeric receptor involvement.Objective The effects of aminoguanidine (AG) were investigated in a rat model of lipopolysaccharide (LPS)-induced anxiety- and depression-like behaviors. Materials and methods The animals were allocated to five groups (n = 10 in each) and treated by (1) saline as a control group, (2) LPS 1 mg/kg injected two hours before behavioral tests, (3-5) AG 50, 100 or 150 mg/kg before LPS. The open-field test (OFT), elevated plus maze test (EPT), and forced swimming (FS) tests were performed. The brains and blood were then collected to examine oxidative stress and inflammation criteria. Results LPS increased the immobility while decreased the active time in the FS test. In EPT, LPS decreased the time spent in the open arms, whereas it increased the time spent in the closed arms. https://www.selleckchem.com/products/bms-927711.html In OFT, LPS decreased the time spent in the central zone compared with the controls. A higher dose of selenium improved the performances of the rats in behavioral tests. LPS injection also increased malondialdehyde (MDA) while it decreased thiol, superoxide dismutase (SOD), and catalase. LPS also increased interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), but decreased IL-10 in the LPS group. AG protected the brain from inflammation and oxidative damage. Conclusion It was demonstrated that AG improves the behaviors of depression and anxiety in a rat model of LPS-induced anxiety- and depression-like behaviors. Moreover, the effects of AG were accompanied by improved inflammation and oxidative damage biomarkers in brain tissues.The Prefrontal cortex (PFC) has been highly related to executive functions such as working memory (WM). This study assesses the activity of the PFC in performing the Sternberg WM task (ST) with three levels of difficulty (easy, medium and hard) using the near-infrared spectroscopy (fNIRS) technique. Participants were 43 young and healthy right-handed women. Nine WM task blocks were pseudo randomly presented, three for each difficulty task. The results showed that the participant's performance was better in the easy trials than in the medium and hard trials. Performance in the medium trials was also better than in the hard ones. Bonferroni-corrected paired post-hoc t-tests indicated higher oxygenation in medium and hard tasks than in the easy ones for times between 13 and 42 s in the left lateral PFC and in both, medial and lateral, right PFC. Significant differences in Oxygenated hemoglobin (HbO), Total hemoglobin (HbT) and oxygenation (Oxy) changes depending on the Sternberg WM task were found. Unlike previous studies with fNIRS and WM, the current study uses a highly controlled WM task that differentiates between encoding, retention and retrieval phases, comparing different levels of task load.0 Comments 0 Shares 88 Views 0 Reviews -
Neonatal rhinovirus impairs the immune response of alveolar macrophages to facilitate Streptococcus pneumonia infection via TLR3 signaling. © FEMS 2020.A total of 594 Vibrio parahaemolyticus isolates from cultivated oysters (n = 361) and estuarine water (n = 233) were examined for antimicrobial resistance (AMR) phenotype and genotype and virulence genes. Four hundred and forty isolates (74.1%) exhibited resistance to at least one antimicrobial agent and 13.5% of the isolates were multidrug-resistant strains. Most of the V. parahaemolyticus isolates were resistant to erythromycin (54.2%), followed by sulfamethoxazole (34.7%), and trimethoprim (27.9%). The most common resistance genes were qnr (77.8%), strB (27.4%), and tet(A) (22.1%), whereas blaTEM (0.8%) was rarely found. Four isolates (0.7%) from oysters (n = 2) and estuarine water (n = 2) were positive to tdh, whereas no trh-positive isolates were observed. Significantly positive associations among AMR genes were observed. The SXT elements and classes 1, 2, and 3 integrons were absent in all isolates. The results indicated that V. parahaemolyticus isolated from oysters and estuarine water were potential reservoirs of resistance determinants in the environment. This increasing threat of resistant bacteria in the environment potentially affects human health. A 'one health' approach involved in multidisciplinary collaborations must be implemented to effectively manage antimicrobial resistance. © FEMS 2020.BACKGROUND Mechanically isolated stromal vascular fraction (tSVF, tissue SVF) is a potent regenerative solution, increasingly used as a therapeutic modality for a variety of pathologies. With recent evidence conclusively favoring mechanical isolation over enzymatic alternatives, the therapeutic share and indications of tSVF are expected to grow even further. OBJECTIVES To provide a systematic review of all studies reporting on the use of tSVF. METHODS A systematic search was undertaken using the Embase, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials databases. Outcome measures included clinical indications including recipient area, adverse events, clinical results recipient area, method of application, follow-up duration and evaluation methods. RESULTS Of the total 4505 articles, 186 full-texts were screened. Thirty-five studies, reporting on 1458 patients were included. Mechanically isolated SVF-based therapy was observed for 11 different pathologies, including aged skin (8 studies), scars (5), wounds (6), osteoarthritis (6), tendinopathy (2), temporomandibular joint disorders (1), androgenic alopecia (1), perianal fistula (3), vasculopathy (1), migraine (1), and vocal fold scarring (1). Across all studies, tSVF-based therapy resulted in favorable clinical results. Overall, 50 (3.43%) minor and one (0.07%) major adverse events were observed, mainly related to the liposuction procedure. CONCLUSIONS Mechanically isolated SVF offers a safe, easy and legal treatment modality for a range of indications. Future research is indicated to identify the optimal isolation protocol, dose and timing. In addition, basic research remains crucial to identify the mechanism of action of SVF within different pathologies. © 2020 The Aesthetic Society. Reprints and permission journals.permissions@oup.com.BACKGROUND A novel coronavirus, SARS-CoV-2, has recently emerged and caused the rapid spread of COVID-19 worldwide. METHODS We did a retrospective study and included COVID-19 patients admitted to Renmin Hospital of Wuhan University between February 1 and February 29, 2020. Antibody assay was conducted to detect COVID-19 envelope protein E and nucleocapsid protein N antigen. RESULTS 112 patients were recruited with symptoms of fever, cough, fatigue, myalgia, and diarrhoea. All patients underwent antibody tests. Fifty-eight (51.79%) were positive for both IgM and IgG, 7 (6.25%) were negative for both antibodies, 1 (0.89%) was positive for only IgM, and 46 (41.07%) were positive for only IgG. IgM antibody appeared within a week post disease onset, and lasted for one month and gradually decreased, while IgG antibody was produced 10 days after infection, and lasted for a longer time. However, no significant difference in level of IgM and IgG antibody between positive and negative patients of nucleic acid test after treatment was found. CONCLUSIONS Our results indicate that serological tests could be powerful approach for the early diagnosis of COVID-19. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.BACKGROUND To explore and describe the current literature surrounding bacterial/fungal co-infection in patients with coronavirus infection. METHODS MEDLINE, EMBASE, and Web of Science were searched using broad based search criteria relating to coronavirus and bacterial co-infection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-COV-2, and other coronavirus) and bacterial/fungal co-infection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal co-infections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-COV-2 even in the absence of co-infection was performed. RESULTS 1007 abstracts were identified. Eighteen full texts reported bacterial/fungal co-infection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140;61%). https://www.selleckchem.com/products/rin1.html 9/18 (50%) studies reported on COVID-19, 5/18 (28%) SARS-1, 1/18 (6%) MERS, and 3/18 (17%) other xford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.BACKGROUND Despite recent advancements in surgical techniques, chemotherapy, and radiotherapy, the 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) remains an unsatisfactory ~8%. MATERIAL AND METHODS Data were extracted to identify patients with non-metastatic pancreatic adenocarcinoma diagnosed in the periods 1988-1996 and 2010-2014 in the Surveillance, Epidemiology, and End Results (SEER) database. The statistical analyses were performed with the log-rank test, Pearson's chi-square test, propensity score matching, and Cox regression model. RESULTS The hazard ratio (HR) of surgery was reduced from 0.454 to 0.302 in Cox regression modeling, and there was no overlapping about the 95% confidence intervals (CI) of surgery between the 2 periods. The HR values of radiotherapy, which were new prognostic factor for resectable PDAC in 2010-2014, were reduced in both the resectable and unresectable groups. The upgraded chemotherapy regimen reduced the HR values from 0.738 to 0.689 in all PADC patients, and from 0.
Neonatal rhinovirus impairs the immune response of alveolar macrophages to facilitate Streptococcus pneumonia infection via TLR3 signaling. © FEMS 2020.A total of 594 Vibrio parahaemolyticus isolates from cultivated oysters (n = 361) and estuarine water (n = 233) were examined for antimicrobial resistance (AMR) phenotype and genotype and virulence genes. Four hundred and forty isolates (74.1%) exhibited resistance to at least one antimicrobial agent and 13.5% of the isolates were multidrug-resistant strains. Most of the V. parahaemolyticus isolates were resistant to erythromycin (54.2%), followed by sulfamethoxazole (34.7%), and trimethoprim (27.9%). The most common resistance genes were qnr (77.8%), strB (27.4%), and tet(A) (22.1%), whereas blaTEM (0.8%) was rarely found. Four isolates (0.7%) from oysters (n = 2) and estuarine water (n = 2) were positive to tdh, whereas no trh-positive isolates were observed. Significantly positive associations among AMR genes were observed. The SXT elements and classes 1, 2, and 3 integrons were absent in all isolates. The results indicated that V. parahaemolyticus isolated from oysters and estuarine water were potential reservoirs of resistance determinants in the environment. This increasing threat of resistant bacteria in the environment potentially affects human health. A 'one health' approach involved in multidisciplinary collaborations must be implemented to effectively manage antimicrobial resistance. © FEMS 2020.BACKGROUND Mechanically isolated stromal vascular fraction (tSVF, tissue SVF) is a potent regenerative solution, increasingly used as a therapeutic modality for a variety of pathologies. With recent evidence conclusively favoring mechanical isolation over enzymatic alternatives, the therapeutic share and indications of tSVF are expected to grow even further. OBJECTIVES To provide a systematic review of all studies reporting on the use of tSVF. METHODS A systematic search was undertaken using the Embase, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials databases. Outcome measures included clinical indications including recipient area, adverse events, clinical results recipient area, method of application, follow-up duration and evaluation methods. RESULTS Of the total 4505 articles, 186 full-texts were screened. Thirty-five studies, reporting on 1458 patients were included. Mechanically isolated SVF-based therapy was observed for 11 different pathologies, including aged skin (8 studies), scars (5), wounds (6), osteoarthritis (6), tendinopathy (2), temporomandibular joint disorders (1), androgenic alopecia (1), perianal fistula (3), vasculopathy (1), migraine (1), and vocal fold scarring (1). Across all studies, tSVF-based therapy resulted in favorable clinical results. Overall, 50 (3.43%) minor and one (0.07%) major adverse events were observed, mainly related to the liposuction procedure. CONCLUSIONS Mechanically isolated SVF offers a safe, easy and legal treatment modality for a range of indications. Future research is indicated to identify the optimal isolation protocol, dose and timing. In addition, basic research remains crucial to identify the mechanism of action of SVF within different pathologies. © 2020 The Aesthetic Society. Reprints and permission journals.permissions@oup.com.BACKGROUND A novel coronavirus, SARS-CoV-2, has recently emerged and caused the rapid spread of COVID-19 worldwide. METHODS We did a retrospective study and included COVID-19 patients admitted to Renmin Hospital of Wuhan University between February 1 and February 29, 2020. Antibody assay was conducted to detect COVID-19 envelope protein E and nucleocapsid protein N antigen. RESULTS 112 patients were recruited with symptoms of fever, cough, fatigue, myalgia, and diarrhoea. All patients underwent antibody tests. Fifty-eight (51.79%) were positive for both IgM and IgG, 7 (6.25%) were negative for both antibodies, 1 (0.89%) was positive for only IgM, and 46 (41.07%) were positive for only IgG. IgM antibody appeared within a week post disease onset, and lasted for one month and gradually decreased, while IgG antibody was produced 10 days after infection, and lasted for a longer time. However, no significant difference in level of IgM and IgG antibody between positive and negative patients of nucleic acid test after treatment was found. CONCLUSIONS Our results indicate that serological tests could be powerful approach for the early diagnosis of COVID-19. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.BACKGROUND To explore and describe the current literature surrounding bacterial/fungal co-infection in patients with coronavirus infection. METHODS MEDLINE, EMBASE, and Web of Science were searched using broad based search criteria relating to coronavirus and bacterial co-infection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-COV-2, and other coronavirus) and bacterial/fungal co-infection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal co-infections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-COV-2 even in the absence of co-infection was performed. RESULTS 1007 abstracts were identified. Eighteen full texts reported bacterial/fungal co-infection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140;61%). https://www.selleckchem.com/products/rin1.html 9/18 (50%) studies reported on COVID-19, 5/18 (28%) SARS-1, 1/18 (6%) MERS, and 3/18 (17%) other xford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.BACKGROUND Despite recent advancements in surgical techniques, chemotherapy, and radiotherapy, the 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) remains an unsatisfactory ~8%. MATERIAL AND METHODS Data were extracted to identify patients with non-metastatic pancreatic adenocarcinoma diagnosed in the periods 1988-1996 and 2010-2014 in the Surveillance, Epidemiology, and End Results (SEER) database. The statistical analyses were performed with the log-rank test, Pearson's chi-square test, propensity score matching, and Cox regression model. RESULTS The hazard ratio (HR) of surgery was reduced from 0.454 to 0.302 in Cox regression modeling, and there was no overlapping about the 95% confidence intervals (CI) of surgery between the 2 periods. The HR values of radiotherapy, which were new prognostic factor for resectable PDAC in 2010-2014, were reduced in both the resectable and unresectable groups. The upgraded chemotherapy regimen reduced the HR values from 0.738 to 0.689 in all PADC patients, and from 0.0 Comments 0 Shares 83 Views 0 Reviews -
vely maintain the expansion effect. The new bone formation rate was accelerated during the expansion process and decreased to normal levels during the retention period. INTRODUCTION The quantity of remaining periodontal ligament (PDL) on the root surface of donor teeth is essential for the success of tooth autotransplantation. Preapplication of orthodontic loading increases this quantity on rat tooth root surfaces. However, little is known about the effects of preloading on human PDL or the ease of tooth extraction. This study aimed to determine the optimal duration of preloading for enhanced PDL on the root surface of extracted human premolars and for facilitating extraction. METHODS Sixty patients received orthodontic preloading with a bracket connected to an archwire on one of their maxillary first premolars for 2, 4, 6, or 8 weeks, whereas the contralateral premolar was not loaded as a control. https://www.selleckchem.com/products/zanubrutini-bgb-3111.html Premolar extractions were performed with a record of the duration and difficulty of extraction. The extracted premolars were fixed and stained with toluidine blue. Digitized images were recorded under a stereomicroscope, and the percentage of stained PDL was analyzed. RESULTS Orthodontic preloading for 4, 6, and 8 weeks significantly increased the percentage of stained PDL on the root surface compared with the control (P less then 0.05). The duration and difficulty of extraction were significantly less in preloaded than that of unloaded teeth after 4, 6, and 8 weeks (P less then 0.05). CONCLUSIONS A 4-week duration of orthodontic preloading is suggested as the shortest duration to adequately enhance PDL and ease tooth extraction; both outcomes may be beneficial for tooth autotransplantation. INTRODUCTION Anchorage, which is defined as resistance against undesired tooth movements, is one of the most important factors in success of orthodontic treatment. In recent years, mini-implants have been used instead of uncomfortable headgears and Nance appliances. The pullout test is the most common method for measuring the anchorage capacity of mini-implants. The aim of this study was to investigate the effects of cortical bone thickness and cortical layer bone density on pullout strength of mini-implants. METHODS Mini-implants were placed in polyurethane foam blocks representing 3 different cortical thicknesses (1 mm, 2 mm, and 3 mm) and 3 different cortical bone densities (grade 40, grade 45, and grade 50). Pullout tests were performed with 5 mm/min loading rate. Load vs displacement values were recorded during the tests. RESULTS Comparing cortical thicknesses on the same bone densities, statistically significant differences were found between 1 mm, 2 mm, and 3 mm thicknesses. Likewise, comparing bone densities on the same cortical thicknesses, statistically significant differences were found among all groups. Spearman rank tests showed that both cortical thickness and cortical bone density are correlated with pullout strength (rs, 0.548; P less then 0.001 and rs, 0.691; P less then 0.001, respectively). CONCLUSIONS Although both factors are positively correlated with pullout strength, the effect of cortical bone density was the dominant factor affecting primary stability. INTRODUCTION The aim of this study was to evaluate the impact of being overweight or obese while wearing orthodontic fixed appliances on the prevalence of gingivitis in adolescents. METHODS A total of 334 adolescents, aged between 12 and 18 years, were recruited from 3 public schools in Cuiabá, Brazil. Participants were divided in dichotomized categories of body mass index (BMI) (under and normal weight or overweight and obesity) and fixed orthodontic appliance usage (yes or no). Gingival inflammation was evaluated by Löe & Silness index. Socioeconomic status was determined by the criteria of the Brazilian Association of Research Companies, and sugar consumption was assessed by a questionnaire of dietary habits. The statistical analysis was performed with P less then 0.05 considered significant. RESULTS In a multivariate linear regression model, gingivitis was directly related to BMI (%) variation and orthodontic appliance use. In addition, excess weight seemed to be 2 times more relevant in predicting gingivitis than orthodontic fixed appliance usage. A strong positive correlation was observed between BMI (%) variation and gingival index (ρ = 0.97, P less then 0.001). CONCLUSIONS Orthodontic fixed appliance usage and excess weight were associated with increased gingivitis in adolescents; BMI (%) variation was the most significant predictor of gingival inflammation. INTRODUCTION The initial stability of orthodontic mini-implants is well investigated over a period of 6 weeks. There is no clinical data available dealing with the long-term stability. The aim of this study was the assessment of long-term stability of paramedian palatal mini-implants in humans. METHODS Stability of 20 implants was measured after removal of the orthodontic appliance (sliding mechanics for sagittal molar movement 200 cN each side) before explantation (T4) using resonance frequency analysis (RFA). Data were compared with a matched group of 21 mini-implants assessing the stability immediately after insertion, and after 2, 4, and 6 weeks (T0-T3). The mini-implants used in this study were machined self-drilling titanium implants (2.0 × 9.0 mm). Gingival thickness at the insertion site was 1-2 mm. RESULTS The implant stability quotient (ISQ) values before removal of the implant at T4 were 25.2 ± 2.9 after 1.7 ± 0.2 years and did not show a statistically significant change over time compared with the initial healing group (T0-T3). CONCLUSIONS Comparing the stability of mini-implants just after completion of the healing period and at the end of their respective usage period revealed no significant difference. An increase of secondary stability could not be detected. The level of stability seemed to be appropriate for orthodontic anchorage. INTRODUCTION The objective of this systematic review was to assess the available evidence in the literature for the effects of fixed orthodontic retainers on periodontal health. METHODS The following databases were searched up to August 31, 2019 Medline, EMBASE, the Cochrane Oral Health Group's Trials Register, CENTRAL, ClinicalTrials.gov, the National Research Register, and Pro-Quest Dissertation Abstracts and Thesis database. Randomized controlled trials (RCTs), controlled clinical trials, cohort studies of prospective and retrospective design, and cross-sectional studies reporting on periodontal measurements of patients who received fixed retention after orthodontic treatment were eligible for inclusion. The quality of the included RCTs was assessed per the revised Cochrane risk of bias tool for randomized trials (RoB 2.0), whereas the risk of bias of the included cohort studies was assessed using the Risk Of Bias In Nonrandomized Studies of Interventions tool. A modified version of the Newcastle-Ottawa scale was used for cross-sectional studies.
vely maintain the expansion effect. The new bone formation rate was accelerated during the expansion process and decreased to normal levels during the retention period. INTRODUCTION The quantity of remaining periodontal ligament (PDL) on the root surface of donor teeth is essential for the success of tooth autotransplantation. Preapplication of orthodontic loading increases this quantity on rat tooth root surfaces. However, little is known about the effects of preloading on human PDL or the ease of tooth extraction. This study aimed to determine the optimal duration of preloading for enhanced PDL on the root surface of extracted human premolars and for facilitating extraction. METHODS Sixty patients received orthodontic preloading with a bracket connected to an archwire on one of their maxillary first premolars for 2, 4, 6, or 8 weeks, whereas the contralateral premolar was not loaded as a control. https://www.selleckchem.com/products/zanubrutini-bgb-3111.html Premolar extractions were performed with a record of the duration and difficulty of extraction. The extracted premolars were fixed and stained with toluidine blue. Digitized images were recorded under a stereomicroscope, and the percentage of stained PDL was analyzed. RESULTS Orthodontic preloading for 4, 6, and 8 weeks significantly increased the percentage of stained PDL on the root surface compared with the control (P less then 0.05). The duration and difficulty of extraction were significantly less in preloaded than that of unloaded teeth after 4, 6, and 8 weeks (P less then 0.05). CONCLUSIONS A 4-week duration of orthodontic preloading is suggested as the shortest duration to adequately enhance PDL and ease tooth extraction; both outcomes may be beneficial for tooth autotransplantation. INTRODUCTION Anchorage, which is defined as resistance against undesired tooth movements, is one of the most important factors in success of orthodontic treatment. In recent years, mini-implants have been used instead of uncomfortable headgears and Nance appliances. The pullout test is the most common method for measuring the anchorage capacity of mini-implants. The aim of this study was to investigate the effects of cortical bone thickness and cortical layer bone density on pullout strength of mini-implants. METHODS Mini-implants were placed in polyurethane foam blocks representing 3 different cortical thicknesses (1 mm, 2 mm, and 3 mm) and 3 different cortical bone densities (grade 40, grade 45, and grade 50). Pullout tests were performed with 5 mm/min loading rate. Load vs displacement values were recorded during the tests. RESULTS Comparing cortical thicknesses on the same bone densities, statistically significant differences were found between 1 mm, 2 mm, and 3 mm thicknesses. Likewise, comparing bone densities on the same cortical thicknesses, statistically significant differences were found among all groups. Spearman rank tests showed that both cortical thickness and cortical bone density are correlated with pullout strength (rs, 0.548; P less then 0.001 and rs, 0.691; P less then 0.001, respectively). CONCLUSIONS Although both factors are positively correlated with pullout strength, the effect of cortical bone density was the dominant factor affecting primary stability. INTRODUCTION The aim of this study was to evaluate the impact of being overweight or obese while wearing orthodontic fixed appliances on the prevalence of gingivitis in adolescents. METHODS A total of 334 adolescents, aged between 12 and 18 years, were recruited from 3 public schools in Cuiabá, Brazil. Participants were divided in dichotomized categories of body mass index (BMI) (under and normal weight or overweight and obesity) and fixed orthodontic appliance usage (yes or no). Gingival inflammation was evaluated by Löe & Silness index. Socioeconomic status was determined by the criteria of the Brazilian Association of Research Companies, and sugar consumption was assessed by a questionnaire of dietary habits. The statistical analysis was performed with P less then 0.05 considered significant. RESULTS In a multivariate linear regression model, gingivitis was directly related to BMI (%) variation and orthodontic appliance use. In addition, excess weight seemed to be 2 times more relevant in predicting gingivitis than orthodontic fixed appliance usage. A strong positive correlation was observed between BMI (%) variation and gingival index (ρ = 0.97, P less then 0.001). CONCLUSIONS Orthodontic fixed appliance usage and excess weight were associated with increased gingivitis in adolescents; BMI (%) variation was the most significant predictor of gingival inflammation. INTRODUCTION The initial stability of orthodontic mini-implants is well investigated over a period of 6 weeks. There is no clinical data available dealing with the long-term stability. The aim of this study was the assessment of long-term stability of paramedian palatal mini-implants in humans. METHODS Stability of 20 implants was measured after removal of the orthodontic appliance (sliding mechanics for sagittal molar movement 200 cN each side) before explantation (T4) using resonance frequency analysis (RFA). Data were compared with a matched group of 21 mini-implants assessing the stability immediately after insertion, and after 2, 4, and 6 weeks (T0-T3). The mini-implants used in this study were machined self-drilling titanium implants (2.0 × 9.0 mm). Gingival thickness at the insertion site was 1-2 mm. RESULTS The implant stability quotient (ISQ) values before removal of the implant at T4 were 25.2 ± 2.9 after 1.7 ± 0.2 years and did not show a statistically significant change over time compared with the initial healing group (T0-T3). CONCLUSIONS Comparing the stability of mini-implants just after completion of the healing period and at the end of their respective usage period revealed no significant difference. An increase of secondary stability could not be detected. The level of stability seemed to be appropriate for orthodontic anchorage. INTRODUCTION The objective of this systematic review was to assess the available evidence in the literature for the effects of fixed orthodontic retainers on periodontal health. METHODS The following databases were searched up to August 31, 2019 Medline, EMBASE, the Cochrane Oral Health Group's Trials Register, CENTRAL, ClinicalTrials.gov, the National Research Register, and Pro-Quest Dissertation Abstracts and Thesis database. Randomized controlled trials (RCTs), controlled clinical trials, cohort studies of prospective and retrospective design, and cross-sectional studies reporting on periodontal measurements of patients who received fixed retention after orthodontic treatment were eligible for inclusion. The quality of the included RCTs was assessed per the revised Cochrane risk of bias tool for randomized trials (RoB 2.0), whereas the risk of bias of the included cohort studies was assessed using the Risk Of Bias In Nonrandomized Studies of Interventions tool. A modified version of the Newcastle-Ottawa scale was used for cross-sectional studies.0 Comments 0 Shares 0 Views 0 Reviews -
Dysfunction of apoptosis and DNA damage response pathways often drive cancer, and so a better understanding of these pathways can contribute to new cancer therapeutic strategies. Diverse discovery approaches have identified many apoptosis regulators, DNA damage response, and DNA damage repair proteins; however, many of these approaches rely on indirect detection of DNA damage. Here, we describe a novel discovery platform based on the comet assay that leverages previous technical advances in assay precision by incorporating high-throughput robotics. The high-throughput screening (HTS) CometChip is the first high-throughput-compatible assay that can directly detect physical damage in DNA. We focused on DNA double-strand breaks (DSBs) and utilized our HTS CometChip technology to perform a first-of-its-kind screen using an shRNA library targeting 2564 cancer-relevant genes. Conditions of the assay enable detection of DNA fragmentation from both exogenous (ionizing radiation) and endogenous (apoptosis) sources. Using this approach, we identified LATS2 as a novel DNA repair factor as well as a modulator of apoptosis. We conclude that the HTS CometChip is an effective assay for HTS to identify modulators of physical DNA damage and repair.The Nursing Working Group of the International Society of Pediatric Oncology developed baseline standards for pediatric oncology nursing care in low- and middle-income countries. The standards represent the foundational support required to provide quality nursing care and address barriers such as inadequate staffing, lack of support, limited access to education, and unsafe nursing environments. The purpose of the current study was to develop and validate an instrument to accurately measure the standards. Content validity was assessed by a panel of expert pediatric oncology nurses from all geographical regions of the World Health Organization. The experts were informed about the study's purpose and provided the publications used to develop the instrument. The experts rated how well each criterion measured the corresponding standard by using a 4-point scale. A content validity index (CVI) was computed by using the percentage of total standards given a score of 3 or 4 by the experts. A CVI of .98 was obtained from the panel's evaluation. A CVI of more than .80 is recommended for a newly developed instrument. On the basis of the panel's recommendations, minor modifications were made to the instrument. We developed and validated the content of an instrument to accurately measure baseline standards for pediatric oncology nursing care. This instrument will aid future research on the effect of nursing standards on clinical outcomes, including mortality and abandonment of treatment, with the potential to influence health policy decisions and improve nursing support in low- and middle-income countries.Background Bacillary dysentery (BD) remains a significant public health issue, especially in developing countries. Evidence assessing the risk of BD from temperature is limited, particularly from national studies including multiple locations with different climatic characteristics. Objectives We estimated the effect of temperature on BD across China, assessed heterogeneity and attributable risks across cities and regions, and projected the future risk of BD under climate change. Methods Daily BD surveillance and meteorological data over 2014-2016 were collected from the Chinese Center for Disease Control and Prevention and the China Meteorology Administration, respectively. A two-stage statistical model was used to estimate city-specific temperature-BD relationships that were pooled to derive regional and national estimates. The risk of BD attributable to temperature was estimated, and the future burden of BD attributable to temperature was projected under different climate change scenarios. Results A positivd the projection for increased risk due to climate change, support efforts to mitigate future risks. https//doi.org/10.1289/EHP5779.Background The purpose of our research was to recommend the initial tacrolimus dosage for Chinese pediatric patients undergoing kidney transplantation based on population pharmacokinetics and pharmacogenetics. Methods Demographic data, laboratory results, drug combinations, and pharmacogenetics from Chinese pediatric patients undergoing kidney transplantation were analyzed using non-linear mixed-effects modeling. A Monte Carlo simulation was performed to evaluate the optimal initial dose of tacrolimus. Results Body weight and post-transplant days, combined with wuzhi-capsule (WZ, extracted from schisandra sphenanthera, whose primary efficient constituents are schisantherin A, schisandrol B, schisandrin, etc., and often used to treat drug-induced hepatitis in Chinese organ transplant patients) and CYP3A5 polymorphisms, influenced the clearance of tacrolimus in these patients. With same weight and post-transplant days, tacrolimus clearance rates from patients carrying CYP3A5*3/*3 and without WZ, carrying CYP3A5*1 allele and without WZ, carrying CYP3A5*3/*3 and with WZ, carrying CYP3A5*1 allele and with WZ were 1, 1.6, 0.72, and 1.152, respectively. In addition, the initial dose for each condition is recommended. Conclusions The initial dosage recommendations in the tacrolimus instructions were not individualized, and we have developed more accurate initial doses based on weight and the CYP3A5 genotype. In addition, lower initial doses are recommended with concurrent use of WZ.People with a mental illness may be exposed to stigma which, when internalised, negatively influences self-esteem, personal goal attainment and quality of life. Avoiding the use of stigmatising language and using terminology that does not exclude the positive characteristics of the individual may play an important role in challenging stigma. This study involved a mixed method approach to identify the terminology preferences of people with a mental illness in Australia. N = 173 participants were recruited via convenience sampling. The humanistic terms 'individual' and 'person with lived experience' were identified as the preferred terms. https://www.selleckchem.com/products/PD-98059.html Qualitatively there was a wide variation in how the terms made the respondents think or feel, with only one of the terms - 'survivor,' having solely negative themes. When contrasting the two most commonly used clinical terms, 'client' was significantly preferred to 'patient'. The term 'consumer' was one of the least preferred terms. This suggests that the use of this term, which is in regular use in Australia, should be reconsidered.
Dysfunction of apoptosis and DNA damage response pathways often drive cancer, and so a better understanding of these pathways can contribute to new cancer therapeutic strategies. Diverse discovery approaches have identified many apoptosis regulators, DNA damage response, and DNA damage repair proteins; however, many of these approaches rely on indirect detection of DNA damage. Here, we describe a novel discovery platform based on the comet assay that leverages previous technical advances in assay precision by incorporating high-throughput robotics. The high-throughput screening (HTS) CometChip is the first high-throughput-compatible assay that can directly detect physical damage in DNA. We focused on DNA double-strand breaks (DSBs) and utilized our HTS CometChip technology to perform a first-of-its-kind screen using an shRNA library targeting 2564 cancer-relevant genes. Conditions of the assay enable detection of DNA fragmentation from both exogenous (ionizing radiation) and endogenous (apoptosis) sources. Using this approach, we identified LATS2 as a novel DNA repair factor as well as a modulator of apoptosis. We conclude that the HTS CometChip is an effective assay for HTS to identify modulators of physical DNA damage and repair.The Nursing Working Group of the International Society of Pediatric Oncology developed baseline standards for pediatric oncology nursing care in low- and middle-income countries. The standards represent the foundational support required to provide quality nursing care and address barriers such as inadequate staffing, lack of support, limited access to education, and unsafe nursing environments. The purpose of the current study was to develop and validate an instrument to accurately measure the standards. Content validity was assessed by a panel of expert pediatric oncology nurses from all geographical regions of the World Health Organization. The experts were informed about the study's purpose and provided the publications used to develop the instrument. The experts rated how well each criterion measured the corresponding standard by using a 4-point scale. A content validity index (CVI) was computed by using the percentage of total standards given a score of 3 or 4 by the experts. A CVI of .98 was obtained from the panel's evaluation. A CVI of more than .80 is recommended for a newly developed instrument. On the basis of the panel's recommendations, minor modifications were made to the instrument. We developed and validated the content of an instrument to accurately measure baseline standards for pediatric oncology nursing care. This instrument will aid future research on the effect of nursing standards on clinical outcomes, including mortality and abandonment of treatment, with the potential to influence health policy decisions and improve nursing support in low- and middle-income countries.Background Bacillary dysentery (BD) remains a significant public health issue, especially in developing countries. Evidence assessing the risk of BD from temperature is limited, particularly from national studies including multiple locations with different climatic characteristics. Objectives We estimated the effect of temperature on BD across China, assessed heterogeneity and attributable risks across cities and regions, and projected the future risk of BD under climate change. Methods Daily BD surveillance and meteorological data over 2014-2016 were collected from the Chinese Center for Disease Control and Prevention and the China Meteorology Administration, respectively. A two-stage statistical model was used to estimate city-specific temperature-BD relationships that were pooled to derive regional and national estimates. The risk of BD attributable to temperature was estimated, and the future burden of BD attributable to temperature was projected under different climate change scenarios. Results A positivd the projection for increased risk due to climate change, support efforts to mitigate future risks. https//doi.org/10.1289/EHP5779.Background The purpose of our research was to recommend the initial tacrolimus dosage for Chinese pediatric patients undergoing kidney transplantation based on population pharmacokinetics and pharmacogenetics. Methods Demographic data, laboratory results, drug combinations, and pharmacogenetics from Chinese pediatric patients undergoing kidney transplantation were analyzed using non-linear mixed-effects modeling. A Monte Carlo simulation was performed to evaluate the optimal initial dose of tacrolimus. Results Body weight and post-transplant days, combined with wuzhi-capsule (WZ, extracted from schisandra sphenanthera, whose primary efficient constituents are schisantherin A, schisandrol B, schisandrin, etc., and often used to treat drug-induced hepatitis in Chinese organ transplant patients) and CYP3A5 polymorphisms, influenced the clearance of tacrolimus in these patients. With same weight and post-transplant days, tacrolimus clearance rates from patients carrying CYP3A5*3/*3 and without WZ, carrying CYP3A5*1 allele and without WZ, carrying CYP3A5*3/*3 and with WZ, carrying CYP3A5*1 allele and with WZ were 1, 1.6, 0.72, and 1.152, respectively. In addition, the initial dose for each condition is recommended. Conclusions The initial dosage recommendations in the tacrolimus instructions were not individualized, and we have developed more accurate initial doses based on weight and the CYP3A5 genotype. In addition, lower initial doses are recommended with concurrent use of WZ.People with a mental illness may be exposed to stigma which, when internalised, negatively influences self-esteem, personal goal attainment and quality of life. Avoiding the use of stigmatising language and using terminology that does not exclude the positive characteristics of the individual may play an important role in challenging stigma. This study involved a mixed method approach to identify the terminology preferences of people with a mental illness in Australia. N = 173 participants were recruited via convenience sampling. The humanistic terms 'individual' and 'person with lived experience' were identified as the preferred terms. https://www.selleckchem.com/products/PD-98059.html Qualitatively there was a wide variation in how the terms made the respondents think or feel, with only one of the terms - 'survivor,' having solely negative themes. When contrasting the two most commonly used clinical terms, 'client' was significantly preferred to 'patient'. The term 'consumer' was one of the least preferred terms. This suggests that the use of this term, which is in regular use in Australia, should be reconsidered.0 Comments 0 Shares 0 Views 0 Reviews -
According to the high IC50 of saffron extracts in normal cells, its toxicity against non-cancerous cells is low and its use is safe. Besides, the studies suggested the cytotoxic effects of saffron on some of the more cancers, including nervous system cancer and common cancers. Further studies are required to determine the effective dose and influence of mechanism of saffron in various animal type of cancers.
Considering the observed effects of saffron on the removal of cancer cells, saffron extract can be used in the treatment and prevention of cancer after confirmation in human clinical trials. According to the high IC50 of saffron extracts in normal cells, its toxicity against non-cancerous cells is low and its use is safe. Besides, the studies suggested the cytotoxic effects of saffron on some of the more cancers, including nervous system cancer and common cancers. Further studies are required to determine the effective dose and influence of mechanism of saffron in various animal type of cancers.
Evidence-based protocols of topical therapy for oral mucositis (OM) induced by chemoradiotherapy (CRT) are continuously established and updated. Thus, the present systematic review aims to evaluate the scientific literature in terms of effectiveness of topical treatment of OM in cancer patients undergoing CRT. Materials and Methods This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist. Randomized clinical trials were identified through electronic database searches on CINAHL, Cochrane Library, LILACS, Livivo, PubMed, SCOPUS, and Web of Science. Grey literature was also assessed on Google Scholar, Open Grey, and ProQuest. The risk of bias in the included studies was assessed by the Cochrane Collaboration Risk of Bias Tool.
Twenty-three randomized clinical trials (n=1169 patients) met the inclusion criteria. Twenty-three different topical agents were examined and categorized into five groups analgesics (30.4%), natural agents (21.7%), other topical agents (21.7%), antimicrobial agents (17.4%), and growth factors (8.8%). Of the included studies, 50% presented a resolution of OM within 14 days. Topical natural agents yielded good results with average resolution time of 3-7 days. The included studies generally demonstrated that patients treated with mouthwashes presented superior benefits compared to the control, depending on OM severity.
Topical agents effectively reduced the severity of OM lesions and pain intensity in patients receiving chemoradiotherapy, although the effects varied by agent type. However, the heterogeneity in the results of these topical intervention studies underscores the need for standardized clinical trial methodologies.
Topical agents were effective in patients with severe OM lesions receiving chemoradiotherapy and are a good alternative of home care in relation to pain control, reduction of inflammation and consequent improvement in quality of life.<br />.
.The aim of this study was to investigate the protective effect of rosmarinic acid (RA) in a premature ovarian failure (POF) mouse model and the potential mechanisms. The POF model was induced by a single intraperitoneal injection of 120 mg/kg cyclophosphamide (CP). Additionally, 40 mg/kg RA was administered for 7 days before CP injection. The concentration of sex hormones was determined by fluorescence immunohistochemistry. Histological analysis was performed after ovarian tissue sections were stained with hematoxylin and eosin. The expression of the NLRP3 inflammasome was examined by western blot analysis and polymerase chain reaction. The expression of apoptosis markers of cytochrome c and caspase-3 was also detected by western blot analysis and immunohistochemistry. The results showed that RA not only decreased the ovarian index in POF **** but also improved the abnormal secretion of reproductive hormones associated with POF. Treatment with RA suppressed the ovarian expression of the NLRP3 inflammasome and regulated the ovarian expression of apoptosis-related proteins. The results suggested that RA exhibited a protective effect against CP-induced POF potentially by suppressing apoptosis and the NLRP3 inflammasome.Apoptosis is an important process of cell death that controls the intrinsic and extrinsic pathways. Syringic acid (SRA)-a phenolic compound well-known in traditional Indian Ayurvedic medicine-has been reported to suppress cell proliferation of various cancer cells. https://www.selleckchem.com/products/apx-115-free-base.html Therefore, the current study aimed to investigate the inhibitory role of SRA on the proliferation of oral squamous cell carcinoma cells (SCC131) via reactive oxygen species (ROS) and induced mitochondria-mediated apoptosis. The study results showed that SRA (IC50 ) was able to induce apoptosis in SCC131 cells via increased ROS generation, alteration of mitochondrial membrane potential, nuclear fragmentation, apoptotic morphological differences, and DNA injury. Moreover, SRA inhibited proliferative markers such as proliferating cell nuclear antigen and cyclin D1 protein expression in SCC131 cells. A diminished level of B-cell lymphoma 2 (Bcl-2) and augmented level of Bcl-2-associated X protein (Bax) were considered as markers of apoptotic cell death. In addition, SRA was able to decrease Bcl-2 and increase mutant p53, caspase-9, Bax, and caspase-3 expression in SCC131 cells. Taken together, SRA succeeded in inhibiting SCC131 cell growth through the ROS and mitochondria-mediated apoptosis in oral cancer cells.
The main purpose of this study was to compare the postoperative complications caused by surgical reconstruction via either retrosternal (RS) or prevertebral (PV) routes in thoracoscopic and laparoscopic esophagectomy patients.
We retrospectively screened the perioperative data in total 59 patients who underwent minimally invasive esophagectomy in time period from January 2016 to January 2018. All the patients were subgrouped into two cohorts according to the surgical routes being taken the RS route group (28 patients) and the PV route group (31 patients). The perioperative data including operation and hospitalization time and surgical complications were comparatively analyzed.
The surgical procedure in all patients was successful and no case of death occurred during perioperative stage in both groups. Notably, patients in the RS group had significantly lower propensity of pneumonia than patients in the PV group (
< 0.05). However, comparative analysis revealed almost an identical time for both operative process and postoperative hospitalization.
According to the high IC50 of saffron extracts in normal cells, its toxicity against non-cancerous cells is low and its use is safe. Besides, the studies suggested the cytotoxic effects of saffron on some of the more cancers, including nervous system cancer and common cancers. Further studies are required to determine the effective dose and influence of mechanism of saffron in various animal type of cancers. Considering the observed effects of saffron on the removal of cancer cells, saffron extract can be used in the treatment and prevention of cancer after confirmation in human clinical trials. According to the high IC50 of saffron extracts in normal cells, its toxicity against non-cancerous cells is low and its use is safe. Besides, the studies suggested the cytotoxic effects of saffron on some of the more cancers, including nervous system cancer and common cancers. Further studies are required to determine the effective dose and influence of mechanism of saffron in various animal type of cancers. Evidence-based protocols of topical therapy for oral mucositis (OM) induced by chemoradiotherapy (CRT) are continuously established and updated. Thus, the present systematic review aims to evaluate the scientific literature in terms of effectiveness of topical treatment of OM in cancer patients undergoing CRT. Materials and Methods This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist. Randomized clinical trials were identified through electronic database searches on CINAHL, Cochrane Library, LILACS, Livivo, PubMed, SCOPUS, and Web of Science. Grey literature was also assessed on Google Scholar, Open Grey, and ProQuest. The risk of bias in the included studies was assessed by the Cochrane Collaboration Risk of Bias Tool. Twenty-three randomized clinical trials (n=1169 patients) met the inclusion criteria. Twenty-three different topical agents were examined and categorized into five groups analgesics (30.4%), natural agents (21.7%), other topical agents (21.7%), antimicrobial agents (17.4%), and growth factors (8.8%). Of the included studies, 50% presented a resolution of OM within 14 days. Topical natural agents yielded good results with average resolution time of 3-7 days. The included studies generally demonstrated that patients treated with mouthwashes presented superior benefits compared to the control, depending on OM severity. Topical agents effectively reduced the severity of OM lesions and pain intensity in patients receiving chemoradiotherapy, although the effects varied by agent type. However, the heterogeneity in the results of these topical intervention studies underscores the need for standardized clinical trial methodologies. Topical agents were effective in patients with severe OM lesions receiving chemoradiotherapy and are a good alternative of home care in relation to pain control, reduction of inflammation and consequent improvement in quality of life.<br />. .The aim of this study was to investigate the protective effect of rosmarinic acid (RA) in a premature ovarian failure (POF) mouse model and the potential mechanisms. The POF model was induced by a single intraperitoneal injection of 120 mg/kg cyclophosphamide (CP). Additionally, 40 mg/kg RA was administered for 7 days before CP injection. The concentration of sex hormones was determined by fluorescence immunohistochemistry. Histological analysis was performed after ovarian tissue sections were stained with hematoxylin and eosin. The expression of the NLRP3 inflammasome was examined by western blot analysis and polymerase chain reaction. The expression of apoptosis markers of cytochrome c and caspase-3 was also detected by western blot analysis and immunohistochemistry. The results showed that RA not only decreased the ovarian index in POF mice but also improved the abnormal secretion of reproductive hormones associated with POF. Treatment with RA suppressed the ovarian expression of the NLRP3 inflammasome and regulated the ovarian expression of apoptosis-related proteins. The results suggested that RA exhibited a protective effect against CP-induced POF potentially by suppressing apoptosis and the NLRP3 inflammasome.Apoptosis is an important process of cell death that controls the intrinsic and extrinsic pathways. Syringic acid (SRA)-a phenolic compound well-known in traditional Indian Ayurvedic medicine-has been reported to suppress cell proliferation of various cancer cells. https://www.selleckchem.com/products/apx-115-free-base.html Therefore, the current study aimed to investigate the inhibitory role of SRA on the proliferation of oral squamous cell carcinoma cells (SCC131) via reactive oxygen species (ROS) and induced mitochondria-mediated apoptosis. The study results showed that SRA (IC50 ) was able to induce apoptosis in SCC131 cells via increased ROS generation, alteration of mitochondrial membrane potential, nuclear fragmentation, apoptotic morphological differences, and DNA injury. Moreover, SRA inhibited proliferative markers such as proliferating cell nuclear antigen and cyclin D1 protein expression in SCC131 cells. A diminished level of B-cell lymphoma 2 (Bcl-2) and augmented level of Bcl-2-associated X protein (Bax) were considered as markers of apoptotic cell death. In addition, SRA was able to decrease Bcl-2 and increase mutant p53, caspase-9, Bax, and caspase-3 expression in SCC131 cells. Taken together, SRA succeeded in inhibiting SCC131 cell growth through the ROS and mitochondria-mediated apoptosis in oral cancer cells. The main purpose of this study was to compare the postoperative complications caused by surgical reconstruction via either retrosternal (RS) or prevertebral (PV) routes in thoracoscopic and laparoscopic esophagectomy patients. We retrospectively screened the perioperative data in total 59 patients who underwent minimally invasive esophagectomy in time period from January 2016 to January 2018. All the patients were subgrouped into two cohorts according to the surgical routes being taken the RS route group (28 patients) and the PV route group (31 patients). The perioperative data including operation and hospitalization time and surgical complications were comparatively analyzed. The surgical procedure in all patients was successful and no case of death occurred during perioperative stage in both groups. Notably, patients in the RS group had significantly lower propensity of pneumonia than patients in the PV group ( < 0.05). However, comparative analysis revealed almost an identical time for both operative process and postoperative hospitalization.0 Comments 0 Shares 0 Views 0 Reviews -
Autophagy refers to a set of catabolic pathways that together facilitate degradation of superfluous, damaged and toxic cellular components. The most studied type of autophagy, called macroautophagy, involves membrane mobilisation, cargo engulfment and trafficking of the newly formed autophagic vesicle to the recycling organelle, the lysosome. Macroautophagy responds to a variety of intra- and extra-cellular stress conditions including, but not limited to, pathogen intrusion, oxygen or nutrient starvation, proteotoxic and organelle stress, and elevation of reactive oxygen species (ROS). ROS are highly reactive oxygen molecules that can interact with cellular macromolecules (proteins, lipids, nucleic acids) to either modify their activity or, when released in excess, inflict irreversible damage. Although increased ROS release has long been recognised for its involvement in macroautophagy activation, the underlying mechanisms and the wider impact of ROS-mediated macroautophagy stimulation remain incompletely understood. We therefore discuss the growing body of evidence that describes the variety of mechanisms modulated by ROS that trigger cytoprotective detoxification via macroautophagy. We outline the role of ROS in signalling upstream of autophagy initiation, by increased gene expression and post-translational modifications of transcription factors, and in the formation and nucleation of autophagic vesicles by cysteine modification of conserved autophagy proteins including ATG4B, ATG7 and ATG3. Furthermore, we review the effect of ROS on selective forms of macroautophagy, specifically on cargo recognition by autophagy receptor proteins p62 and NBR1 (neighbour of BRCA1) and the recycling of mitochondria (mitophagy), and peroxisomes (pexophagy). Finally, we highlight both, the standalone and mutual contributions of abnormal ROS signalling and macroautophagy to the development and progression of neurodegenerative diseases. Alzheimer's disease (AD) is the most common form of neurodegenerative disorder with dementia, accounting for approximately 70% of the all cases. Currently, 5.8 million people in the U.S. are living with AD and by 2050 this number is expected to double resulting in a significant socio-economic burden. https://www.selleckchem.com/products/bpv-hopic.html Despite intensive research, the exact mechanisms that trigger AD are still not known and at the present there is no cure for it. In recent years, many signaling pathways associated with AD neuropathology have been explored as possible candidate targets for the treatment of this condition including glycogen synthase kinase-3β (GSK3-β). GSK3-β is considered a key player in AD pathophysiology since dysregulation of this kinase influences all the major hallmarks of the disease including tau phosphorylation, amyloid-β production, memory, neurogenesis and synaptic function. The present review summarizes the current understanding of the GSK3-β neurobiology with particular emphasis on its effects on specific signaling pathways associated with AD pathophysiology. Moreover, it discusses the feasibility of targeting GSK3-β for AD treatment and provides a summary of the current research effort to develop GSK3-β inhibitors in preclinical and clinical studies. The pleiotropic peptide insulin-like growth factor 1 (IGF-I) regulates human body homeostasis and cell growth. IGF-I activates two major signaling pathways, namely phosphoinositide-3-kinase (PI3K)/protein kinase B (PKB/Akt) and Ras/extracellular signal-regulated kinase (ERK), which contribute to brain development, metabolism and function as well as to neuronal maintenance and survival. In this review, we discuss the general and tissue-specific effects of the IGF-I pathways. In addition, we present a comprehensive overview examining the role of IGF-I in neurodegenerative diseases, such as spinal and muscular atrophy, amyotrophic lateral sclerosis, and polyglutamine diseases. In each disease, we analyze the disturbances of the IGF-I pathway, the modification of the disease protein by IGF-I signaling, and the therapeutic strategies based on the use of IGF-I developed to date. Lastly, we highlight present and future considerations in the use of IGF-I for the treatment of these disorders. Hypertension is an independent risk factor for atrial fibrillation (AF), although its specific mechanisms remain unclear. Previous research has been focused on cyclic stretch, ignoring the role of high hydrostatic pressure. The present study aimed to explore the effect of high hydrostatic pressure stimulation on electrical remodeling in atrial myocytes and its potential signaling pathways. Experiments were performed on left atrial appendages from patients with chronic AF or sinus rhythm, spontaneously hypertensive rats (SHRs) treated with or without valsartan (10 mg/kg/day) and HL-1 cells were exposed to high hydrostatic pressure using a self-developed device. Whole-cell patch-clamp recordings and western blots demonstrated that the amplitudes of ICa,L, Ito, and IKur were reduced in AF patients with corresponding changes in protein expression. Angiotensin protein levels increased and Ang1-7 decreased, while focal adhesion kinase (FAK) and Src kinase were enhanced in atrial tissue from AF patients and SHRs. After rapid atrial pacing, AF inducibility in SHR was significantly higher, accompanied by a decrease in ICa,L, upregulation of Ito and IKur, and a shortened action potential duration. Angiotensin upregulation and FAK/Src activation in SHR were inhibited by angiotensin type 1 receptor inhibitor valsartan, thus, preventing electrical remodeling and reducing AF susceptibility. These results were verified in HL-1 cells treated with high hydrostatic pressure, and demonstrated that electrical remodeling regulated by the FAK-Src pathway could be modulated by valsartan. The present study indicated that high hydrostatic pressure stimulation increases AF susceptibility by activating the renin-angiotensin system and FAK-Src pathway in atrial myocytes. Measures of well-being have proliferated over the past decades. Very little guidance has been available as to which measures to use in what contexts. This paper provides a series of recommendations, based on the present state of knowledge and the existing measures available, of what measures might be preferred in which contexts. The recommendations came out of an interdisciplinary workshop on the measurement of well-being. The recommendations are shaped around the number of items that can be included in a survey, and also based on the differing potential contexts and purposes of data collection such as, for example, government surveys, or multi-use cohort studies, or studies specifically about psychological well-being. The recommendations are not intended to be definitive, but to stimulate discussion and refinement, and to provide guidance to those relatively new to the study of well-being.
Autophagy refers to a set of catabolic pathways that together facilitate degradation of superfluous, damaged and toxic cellular components. The most studied type of autophagy, called macroautophagy, involves membrane mobilisation, cargo engulfment and trafficking of the newly formed autophagic vesicle to the recycling organelle, the lysosome. Macroautophagy responds to a variety of intra- and extra-cellular stress conditions including, but not limited to, pathogen intrusion, oxygen or nutrient starvation, proteotoxic and organelle stress, and elevation of reactive oxygen species (ROS). ROS are highly reactive oxygen molecules that can interact with cellular macromolecules (proteins, lipids, nucleic acids) to either modify their activity or, when released in excess, inflict irreversible damage. Although increased ROS release has long been recognised for its involvement in macroautophagy activation, the underlying mechanisms and the wider impact of ROS-mediated macroautophagy stimulation remain incompletely understood. We therefore discuss the growing body of evidence that describes the variety of mechanisms modulated by ROS that trigger cytoprotective detoxification via macroautophagy. We outline the role of ROS in signalling upstream of autophagy initiation, by increased gene expression and post-translational modifications of transcription factors, and in the formation and nucleation of autophagic vesicles by cysteine modification of conserved autophagy proteins including ATG4B, ATG7 and ATG3. Furthermore, we review the effect of ROS on selective forms of macroautophagy, specifically on cargo recognition by autophagy receptor proteins p62 and NBR1 (neighbour of BRCA1) and the recycling of mitochondria (mitophagy), and peroxisomes (pexophagy). Finally, we highlight both, the standalone and mutual contributions of abnormal ROS signalling and macroautophagy to the development and progression of neurodegenerative diseases. Alzheimer's disease (AD) is the most common form of neurodegenerative disorder with dementia, accounting for approximately 70% of the all cases. Currently, 5.8 million people in the U.S. are living with AD and by 2050 this number is expected to double resulting in a significant socio-economic burden. https://www.selleckchem.com/products/bpv-hopic.html Despite intensive research, the exact mechanisms that trigger AD are still not known and at the present there is no cure for it. In recent years, many signaling pathways associated with AD neuropathology have been explored as possible candidate targets for the treatment of this condition including glycogen synthase kinase-3β (GSK3-β). GSK3-β is considered a key player in AD pathophysiology since dysregulation of this kinase influences all the major hallmarks of the disease including tau phosphorylation, amyloid-β production, memory, neurogenesis and synaptic function. The present review summarizes the current understanding of the GSK3-β neurobiology with particular emphasis on its effects on specific signaling pathways associated with AD pathophysiology. Moreover, it discusses the feasibility of targeting GSK3-β for AD treatment and provides a summary of the current research effort to develop GSK3-β inhibitors in preclinical and clinical studies. The pleiotropic peptide insulin-like growth factor 1 (IGF-I) regulates human body homeostasis and cell growth. IGF-I activates two major signaling pathways, namely phosphoinositide-3-kinase (PI3K)/protein kinase B (PKB/Akt) and Ras/extracellular signal-regulated kinase (ERK), which contribute to brain development, metabolism and function as well as to neuronal maintenance and survival. In this review, we discuss the general and tissue-specific effects of the IGF-I pathways. In addition, we present a comprehensive overview examining the role of IGF-I in neurodegenerative diseases, such as spinal and muscular atrophy, amyotrophic lateral sclerosis, and polyglutamine diseases. In each disease, we analyze the disturbances of the IGF-I pathway, the modification of the disease protein by IGF-I signaling, and the therapeutic strategies based on the use of IGF-I developed to date. Lastly, we highlight present and future considerations in the use of IGF-I for the treatment of these disorders. Hypertension is an independent risk factor for atrial fibrillation (AF), although its specific mechanisms remain unclear. Previous research has been focused on cyclic stretch, ignoring the role of high hydrostatic pressure. The present study aimed to explore the effect of high hydrostatic pressure stimulation on electrical remodeling in atrial myocytes and its potential signaling pathways. Experiments were performed on left atrial appendages from patients with chronic AF or sinus rhythm, spontaneously hypertensive rats (SHRs) treated with or without valsartan (10 mg/kg/day) and HL-1 cells were exposed to high hydrostatic pressure using a self-developed device. Whole-cell patch-clamp recordings and western blots demonstrated that the amplitudes of ICa,L, Ito, and IKur were reduced in AF patients with corresponding changes in protein expression. Angiotensin protein levels increased and Ang1-7 decreased, while focal adhesion kinase (FAK) and Src kinase were enhanced in atrial tissue from AF patients and SHRs. After rapid atrial pacing, AF inducibility in SHR was significantly higher, accompanied by a decrease in ICa,L, upregulation of Ito and IKur, and a shortened action potential duration. Angiotensin upregulation and FAK/Src activation in SHR were inhibited by angiotensin type 1 receptor inhibitor valsartan, thus, preventing electrical remodeling and reducing AF susceptibility. These results were verified in HL-1 cells treated with high hydrostatic pressure, and demonstrated that electrical remodeling regulated by the FAK-Src pathway could be modulated by valsartan. The present study indicated that high hydrostatic pressure stimulation increases AF susceptibility by activating the renin-angiotensin system and FAK-Src pathway in atrial myocytes. Measures of well-being have proliferated over the past decades. Very little guidance has been available as to which measures to use in what contexts. This paper provides a series of recommendations, based on the present state of knowledge and the existing measures available, of what measures might be preferred in which contexts. The recommendations came out of an interdisciplinary workshop on the measurement of well-being. The recommendations are shaped around the number of items that can be included in a survey, and also based on the differing potential contexts and purposes of data collection such as, for example, government surveys, or multi-use cohort studies, or studies specifically about psychological well-being. The recommendations are not intended to be definitive, but to stimulate discussion and refinement, and to provide guidance to those relatively new to the study of well-being.0 Comments 0 Shares 0 Views 0 Reviews
More Stories