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Albeit the encouraging results that emerge from both experimental and clinical evidence, further studies are needed to confirm and better understand the mental-health promoting, and specifically, the antidepressant effects of these herbs.Extracellular vesicles (EVs) are known for their important role in cancer progression and hold considerable potential as a source for tumor biomarkers. However, purification of tumor-specific EVs from patient plasma is still an urgent unmet need due to contamination by normal host cell-derived EVs, that results in compromised analytical sensitivity. Here we identified fatty acid synthase (FASN), a key lipogenic enzyme which is highly expressed in malignant glioma cells, to be elevated in CD63- and CD81-positive EVs in glioma patient plasma samples, opening vital opportunities to sort brain tumor-specific EVs.The genus Dionysia, belonging to the Primulaceae family, encompasses more than 50 species worldwide with a center of diversity located in the arid Irano-Turanian mountains. In this study, a phytochemical investigation of the aerial parts of D. diapensifolia Bioss. led to the isolation of 24 phenolic compounds 1-7 and 9-25, and one sesquiterpenoid 8. Compound 1 was identified as new natural product, while isolation of 2 and 3, already known as synthetic products, from a natural source is reported for the first time in the present study. Isolation of compound 8 from a Dionysia species and indeed the whole Primulaceae family is reported for the first time too. Structure elucidation was performed by extensive spectroscopic analyses (1D-, 2D-NMR, and MS), and by comparison with reported literature data. Furthermore, DP4+ chemical shift probability calculations were performed to establish the relative configuration of compound 1. Additionally, subfractions obtained by liquid-liquid extraction of the methanolic extract of the plant, and subsequently the isolated new and selected known compounds 1-4, 6, 8-11 obtained from the diethyl ether subfraction were investigated for their inhibitory effect on NO release and iNOS and COX-2 expression in J774A.1 murine macrophages. The results showed a potential anti-inflammatory activity of the obtained subfractions, of which the diethyl ether subfraction was the most active one in inhibiting NO release and COX-2 expression (p less then 0.001). Among the investigated isolated compounds, compound 4 significantly (p less then 0.001) inhibited NO release and iNOS and COX-2 expression in a comparable manner like the used positive controls (L-NAME and indomethacin, respectively). Moreover, other isolated substances displayed moderate to high inhibitory activities, illustrating the potential anti-inflammatory activity of Dionysia diapensifolia.Talk of mechanisms is ubiquitous in the natural sciences. Interdisciplinary fields such as biochemistry and pharmacy frequently discuss mechanisms with the assistance of diagrams. Such diagrams usually depict entities as structures or boxes and activities or interactions as arrows. While some of these arrows may indicate causal or componential relations, others may represent temporal or operational orders. Importantly, what kind of relation an arrow represents may not only vary with context but also be underdetermined by empirical data. In this manuscript, we investigate how an analysis of pharmacological mechanisms in terms of producing and underlying mechanisms-as discussed in the contemporary philosophy of science-may shed light on these issues. Specifically, we shall argue that while pharmacokinetic mechanisms usually describe causal chains of production, pharmacodynamics tends to focus on mechanisms of action underlying the in vivo effects of a drug. Considering the action of thyroid gland hormones in the human body as a case study, we further demonstrate that pharmacodynamic schemes tend to incorporate entities and interactions on multiple levels. Yet, traditional pharmacodynamic schemes are sketched "flat", i.e., non-hierarchically. We suggest that transforming flat pharmacodynamic schemes into mechanistic multi-level representations may assist in disentangling the different kinds of mechanisms and relations depicted by arrows in flat schemes. The resulting Baumkuchen model provides a powerful and practical alternative to traditional flat schemes, as it explicates the relevant mechanisms and relations more clearly. On a more general note, our discussion demonstrates how pharmacology and related disciplines may benefit from applying concepts from the new mechanist philosophy to guide the interpretation of scientific diagrams.Shiga toxin-producing Escherichia coli O157H7 is a food-borne pathogen and the major cause of hemorrhagic colitis. Pseudomonas is the genus most frequent psychrotrophic spoilage microorganisms present in milk. Two-species bacterial systems with E. coli O157H7, non-pathogenic E. coli, and P. fluorescens in skimmed milk at 7, 13, 19, or 25 °C were studied. Bacterial interactions were modelled after applying a Bayesian approach. https://www.selleckchem.com/products/ndi-091143.html No direct correlation between P. fluorescens's growth rate and its effect on the maximum population densities of E. coli species was found. The results show the complexity of the interactions between two species in a food model. The use of natural microbiota members to control foodborne pathogens could be useful to improve food safety during the processing and storage of refrigerated foods.Glioblastoma (GBM) is a particularly devastating tumor with a median survival of about 16 months. Recent research has revealed novel insights into the outstanding heterogeneity of this type of brain cancer. However, all GBM subtypes share the hallmark feature of aggressive invasion into the surrounding tissue. Invasive glioblastoma cells escape surgery and focal therapies and thus represent a major obstacle for curative therapy. This review aims to provide a comprehensive understanding of glioma invasion mechanisms with respect to tumor-cell-intrinsic properties as well as cues provided by the microenvironment. We discuss genetic programs that may influence the dissemination and plasticity of GBM cells as well as their different invasion patterns. We also review how tumor cells shape their microenvironment and how, vice versa, components of the extracellular matrix and factors from non-neoplastic cells influence tumor cell motility. We further discuss different research platforms for modeling invasion. Finally, we highlight the importance of accounting for the complex interplay between tumor cell invasion and treatment resistance in glioblastoma when considering new therapeutic approaches.
Albeit the encouraging results that emerge from both experimental and clinical evidence, further studies are needed to confirm and better understand the mental-health promoting, and specifically, the antidepressant effects of these herbs.Extracellular vesicles (EVs) are known for their important role in cancer progression and hold considerable potential as a source for tumor biomarkers. However, purification of tumor-specific EVs from patient plasma is still an urgent unmet need due to contamination by normal host cell-derived EVs, that results in compromised analytical sensitivity. Here we identified fatty acid synthase (FASN), a key lipogenic enzyme which is highly expressed in malignant glioma cells, to be elevated in CD63- and CD81-positive EVs in glioma patient plasma samples, opening vital opportunities to sort brain tumor-specific EVs.The genus Dionysia, belonging to the Primulaceae family, encompasses more than 50 species worldwide with a center of diversity located in the arid Irano-Turanian mountains. In this study, a phytochemical investigation of the aerial parts of D. diapensifolia Bioss. led to the isolation of 24 phenolic compounds 1-7 and 9-25, and one sesquiterpenoid 8. Compound 1 was identified as new natural product, while isolation of 2 and 3, already known as synthetic products, from a natural source is reported for the first time in the present study. Isolation of compound 8 from a Dionysia species and indeed the whole Primulaceae family is reported for the first time too. Structure elucidation was performed by extensive spectroscopic analyses (1D-, 2D-NMR, and MS), and by comparison with reported literature data. Furthermore, DP4+ chemical shift probability calculations were performed to establish the relative configuration of compound 1. Additionally, subfractions obtained by liquid-liquid extraction of the methanolic extract of the plant, and subsequently the isolated new and selected known compounds 1-4, 6, 8-11 obtained from the diethyl ether subfraction were investigated for their inhibitory effect on NO release and iNOS and COX-2 expression in J774A.1 murine macrophages. The results showed a potential anti-inflammatory activity of the obtained subfractions, of which the diethyl ether subfraction was the most active one in inhibiting NO release and COX-2 expression (p less then 0.001). Among the investigated isolated compounds, compound 4 significantly (p less then 0.001) inhibited NO release and iNOS and COX-2 expression in a comparable manner like the used positive controls (L-NAME and indomethacin, respectively). Moreover, other isolated substances displayed moderate to high inhibitory activities, illustrating the potential anti-inflammatory activity of Dionysia diapensifolia.Talk of mechanisms is ubiquitous in the natural sciences. Interdisciplinary fields such as biochemistry and pharmacy frequently discuss mechanisms with the assistance of diagrams. Such diagrams usually depict entities as structures or boxes and activities or interactions as arrows. While some of these arrows may indicate causal or componential relations, others may represent temporal or operational orders. Importantly, what kind of relation an arrow represents may not only vary with context but also be underdetermined by empirical data. In this manuscript, we investigate how an analysis of pharmacological mechanisms in terms of producing and underlying mechanisms-as discussed in the contemporary philosophy of science-may shed light on these issues. Specifically, we shall argue that while pharmacokinetic mechanisms usually describe causal chains of production, pharmacodynamics tends to focus on mechanisms of action underlying the in vivo effects of a drug. Considering the action of thyroid gland hormones in the human body as a case study, we further demonstrate that pharmacodynamic schemes tend to incorporate entities and interactions on multiple levels. Yet, traditional pharmacodynamic schemes are sketched "flat", i.e., non-hierarchically. We suggest that transforming flat pharmacodynamic schemes into mechanistic multi-level representations may assist in disentangling the different kinds of mechanisms and relations depicted by arrows in flat schemes. The resulting Baumkuchen model provides a powerful and practical alternative to traditional flat schemes, as it explicates the relevant mechanisms and relations more clearly. On a more general note, our discussion demonstrates how pharmacology and related disciplines may benefit from applying concepts from the new mechanist philosophy to guide the interpretation of scientific diagrams.Shiga toxin-producing Escherichia coli O157H7 is a food-borne pathogen and the major cause of hemorrhagic colitis. Pseudomonas is the genus most frequent psychrotrophic spoilage microorganisms present in milk. Two-species bacterial systems with E. coli O157H7, non-pathogenic E. coli, and P. fluorescens in skimmed milk at 7, 13, 19, or 25 °C were studied. Bacterial interactions were modelled after applying a Bayesian approach. https://www.selleckchem.com/products/ndi-091143.html No direct correlation between P. fluorescens's growth rate and its effect on the maximum population densities of E. coli species was found. The results show the complexity of the interactions between two species in a food model. The use of natural microbiota members to control foodborne pathogens could be useful to improve food safety during the processing and storage of refrigerated foods.Glioblastoma (GBM) is a particularly devastating tumor with a median survival of about 16 months. Recent research has revealed novel insights into the outstanding heterogeneity of this type of brain cancer. However, all GBM subtypes share the hallmark feature of aggressive invasion into the surrounding tissue. Invasive glioblastoma cells escape surgery and focal therapies and thus represent a major obstacle for curative therapy. This review aims to provide a comprehensive understanding of glioma invasion mechanisms with respect to tumor-cell-intrinsic properties as well as cues provided by the microenvironment. We discuss genetic programs that may influence the dissemination and plasticity of GBM cells as well as their different invasion patterns. We also review how tumor cells shape their microenvironment and how, vice versa, components of the extracellular matrix and factors from non-neoplastic cells influence tumor cell motility. We further discuss different research platforms for modeling invasion. Finally, we highlight the importance of accounting for the complex interplay between tumor cell invasion and treatment resistance in glioblastoma when considering new therapeutic approaches.0 Commenti 0 condivisioni 3 Views 0 AnteprimaEffettua l'accesso per mettere mi piace, condividere e commentare! -
Copyright © 2020, The Korean Society for Vascular Surgery.Purpose It is well known that congenital diaphragmatic hernia (CDH) in infants impacts pulmonary function rehabilitation after surgery. However, the risk factors of postoperative pulmonary function are still unclear. In this research, we analyzed the potential risk factors of postoperative pulmonary function in CDH patients in order to improve the clinical management of CDH patients. Methods Thirty-three cases CDH infants followed were enrolled from November 2016 to September 2018. Clinical data were reviewed. Tidal breathing pulmonary function testing was performed after surgery. Correlation between pulmonary function and clinical characteristics was evaluated using multivariate analysis of variance. Results Pulmonary dysfunction was detected in 87.9% patients (29 of 33). The defect size was found to be significantly larger in patients with obstructed and mixed ventilatory disorders (P = 0.001). Diagnosis of gestational age (GA) was also significantly earlier compared to restrictive ventilatory disorders (P = 0.001). Larger defect size, and earlier prenatal diagnosis of GA were detected in severe obstructive ventilatory disorders (P = 0.007, P = 0.001, retrospectively). Conclusion Most patients had various degrees of pulmonary dysfunction after surgery. Patients with larger defect size and earlier diagnosis time might be vulnerable to severe obstructive and mixed ventilatory disorders. Copyright © 2020, the Korean Surgical Society.Purpose Minute T1 colorectal cancer (CRC) lesions (≤5 mm) are rare; however, little is known about their characteristics and aggressiveness. In this study, we evaluated the characteristics of minute T1 CRC in relevance to pathology and treatment. Methods This retrospective study included 849 patients with T1 CRC endoscopically or surgically treated between January 2001 and December 2016. The patients were stratified into 4 groups according to tumor size; minute group (≤5 mm), small group (6-10 mm), medium group (11-20 mm), and large group (≥21 mm). Clinicopathological variables were evaluated with respect to tumor size. Results The incidence of the minute T1 CRC was 2.4% (20 of 849). Minute T1 CRC was significantly associated with flat type (minute, 25%; small, 12.6%; medium, 8.8%; large, 12.6%; P = 0.016), right-sided cancer (30%, 15.4%, 15.4%, 15.1%, P = 0.002) and the absence of background adenoma (BGA) (50%, 40.7%, 32.8%, 18.1%, P less then 0.001). https://www.selleckchem.com/products/trastuzumab-emtansine-t-dm1-.html In patients who underwent surgery, lymph node metastasis (LNM) was significantly higher in the minute group (36.4%, 15.9%, 15.7%, 9.2%, P = 0.029). Conclusion Minute T1 CRC is significantly associated with flat type, right-sided cancers, as well as with the absence of BGA and LNM. These results suggested the minute T1 CRC lesions are often aggressive and are likely to be missed during colonoscopy. Copyright © 2020, the Korean Surgical Society.Purpose Pancreatic duct decompression relieves pancreatic duct stone (PDS)-associated abdominal pain, though a consensus indication for the drainage procedure of the main pancreatic duct (MPD) is lacking. Moreover, major prognostic factors for postsurgical long-term pain relief and recurrence are largely unknown. Methods The clinical outcomes of 65 consecutive PDS patients undergoing surgery from 2008-2012 with 3+ years of follow-up were assessed. Results At postsurgical follow-up (median, 4.5 years; range, 3-7 years; procedure Partington, n = 32; Frey, n = 27; pancreatoduodenectomy, n = 3; distal pancreatectomy, n = 3), the early complication and complete stone clearance rates were 29.2% and 97%, respectively. Long-term, complete and partial pain relief were 93.9%, 83.1%, and 10.8%, respectively. The risk of pancreatic fistula was higher in the 8 mm group (P less then 0.05), and 80% of the pancreatic fistula cases occurred in the less then 8 mm group. A shorter pain duration (P = 0.007), smaller MPD diameter (P = 0.04), and lower Izbicki pain score (P less then 0.001) predicted long-term pain relief. Pain recurrence after initial remission occurred in 5 patients and was only related to pain duration (P = 0.02). Stone recurrence and pancreatic exocrine functional and endocrine functional deterioration occurred in 2, 5, and 11 patients, respectively. Conclusion Surgery provides excellent stone clearance, long-term pain relief, and acceptable postoperative morbidity. Using 8 mm as the criterion for drainage surgery can minimize the postoperative pancreatic fistula risk. Individualized and timely surgical treatment may improve the effect of surgery. Copyright © 2020, the Korean Surgical Society.Purpose Since the treatment strategy for benign and malignant pancreatic lesions differ, we aimed to evaluate the clinical value of PET/CT in the diagnosis and management of pancreatic lesions. Methods Ninety patients who had a histologically confirmed pancreatic lesion were studied. Receiver operating characteristic (ROC) curve analysis was used to investigate the ability of PET/CT to differentiate malignant lesions from benign tumors. Results The malignant and benign groups comprised 64 and 26 patients, respectively. Despite the similarity in the size of primary tumors (P = 0.588), the mean maximum standardized uptake values (SUVmax) obtained from PET/CT imaging were significantly higher in malignant lesions (9.36 ± 5.9) than those of benign tumors (1.04 ± 2.6, P less then 0.001). ROC analysis showed that the optimal SUVmax cutoff value for differentiating malignant lesions (to an accuracy of 91%; 95% confidence interval, 83%-98%) from benign tumors was 3.9 (sensitivity, 92.2%; specificity, 84.6%). Conclusion PET/CT evaluation of pancreatic lesions confers advantages including fine assessment of malignant potential with high sensitivity and accuracy using a threshold SUVmax value of 3.9. Copyright © 2020, the Korean Surgical Society.Purpose Although pancreatoduodenectomy (PD) in patients who have previously undergone gastrectomy is challenging, little is known about the clinical outcomes and the differences compared to those with conventional PD. We collected cases and conducted studies in retrospective review. Methods Of the 1,722 patients who underwent PD at Seoul National University Hospital between 2000 and 2014, 49 (2.8%) underwent previous gastrectomy. Clinical outcomes including operation-related factors and postoperative morbidities were analyzed. Results Among the 49 patients with curative surgery, 25 patients were male (51.0%) and the mean age was 64.7 years. Gastric cancer was the most frequent cause of previous gastrectomy (93.8%). With one-to-one propensity score matching analysis, lower preoperative body mass index (22.6 kg/m2 vs. 20.8 kg/m2, P = 0.002), higher EBL (390.0 mL vs. 729.5 mL, P = 0.027), and higher transfusion rates (10.2% vs. 36.7%, P = 0.002) were shown in the gastrectomy group. Operation time, postoperative hospital stay, and rate of clinically relevant pancreatic fistula were comparable.
Copyright © 2020, The Korean Society for Vascular Surgery.Purpose It is well known that congenital diaphragmatic hernia (CDH) in infants impacts pulmonary function rehabilitation after surgery. However, the risk factors of postoperative pulmonary function are still unclear. In this research, we analyzed the potential risk factors of postoperative pulmonary function in CDH patients in order to improve the clinical management of CDH patients. Methods Thirty-three cases CDH infants followed were enrolled from November 2016 to September 2018. Clinical data were reviewed. Tidal breathing pulmonary function testing was performed after surgery. Correlation between pulmonary function and clinical characteristics was evaluated using multivariate analysis of variance. Results Pulmonary dysfunction was detected in 87.9% patients (29 of 33). The defect size was found to be significantly larger in patients with obstructed and mixed ventilatory disorders (P = 0.001). Diagnosis of gestational age (GA) was also significantly earlier compared to restrictive ventilatory disorders (P = 0.001). Larger defect size, and earlier prenatal diagnosis of GA were detected in severe obstructive ventilatory disorders (P = 0.007, P = 0.001, retrospectively). Conclusion Most patients had various degrees of pulmonary dysfunction after surgery. Patients with larger defect size and earlier diagnosis time might be vulnerable to severe obstructive and mixed ventilatory disorders. Copyright © 2020, the Korean Surgical Society.Purpose Minute T1 colorectal cancer (CRC) lesions (≤5 mm) are rare; however, little is known about their characteristics and aggressiveness. In this study, we evaluated the characteristics of minute T1 CRC in relevance to pathology and treatment. Methods This retrospective study included 849 patients with T1 CRC endoscopically or surgically treated between January 2001 and December 2016. The patients were stratified into 4 groups according to tumor size; minute group (≤5 mm), small group (6-10 mm), medium group (11-20 mm), and large group (≥21 mm). Clinicopathological variables were evaluated with respect to tumor size. Results The incidence of the minute T1 CRC was 2.4% (20 of 849). Minute T1 CRC was significantly associated with flat type (minute, 25%; small, 12.6%; medium, 8.8%; large, 12.6%; P = 0.016), right-sided cancer (30%, 15.4%, 15.4%, 15.1%, P = 0.002) and the absence of background adenoma (BGA) (50%, 40.7%, 32.8%, 18.1%, P less then 0.001). https://www.selleckchem.com/products/trastuzumab-emtansine-t-dm1-.html In patients who underwent surgery, lymph node metastasis (LNM) was significantly higher in the minute group (36.4%, 15.9%, 15.7%, 9.2%, P = 0.029). Conclusion Minute T1 CRC is significantly associated with flat type, right-sided cancers, as well as with the absence of BGA and LNM. These results suggested the minute T1 CRC lesions are often aggressive and are likely to be missed during colonoscopy. Copyright © 2020, the Korean Surgical Society.Purpose Pancreatic duct decompression relieves pancreatic duct stone (PDS)-associated abdominal pain, though a consensus indication for the drainage procedure of the main pancreatic duct (MPD) is lacking. Moreover, major prognostic factors for postsurgical long-term pain relief and recurrence are largely unknown. Methods The clinical outcomes of 65 consecutive PDS patients undergoing surgery from 2008-2012 with 3+ years of follow-up were assessed. Results At postsurgical follow-up (median, 4.5 years; range, 3-7 years; procedure Partington, n = 32; Frey, n = 27; pancreatoduodenectomy, n = 3; distal pancreatectomy, n = 3), the early complication and complete stone clearance rates were 29.2% and 97%, respectively. Long-term, complete and partial pain relief were 93.9%, 83.1%, and 10.8%, respectively. The risk of pancreatic fistula was higher in the 8 mm group (P less then 0.05), and 80% of the pancreatic fistula cases occurred in the less then 8 mm group. A shorter pain duration (P = 0.007), smaller MPD diameter (P = 0.04), and lower Izbicki pain score (P less then 0.001) predicted long-term pain relief. Pain recurrence after initial remission occurred in 5 patients and was only related to pain duration (P = 0.02). Stone recurrence and pancreatic exocrine functional and endocrine functional deterioration occurred in 2, 5, and 11 patients, respectively. Conclusion Surgery provides excellent stone clearance, long-term pain relief, and acceptable postoperative morbidity. Using 8 mm as the criterion for drainage surgery can minimize the postoperative pancreatic fistula risk. Individualized and timely surgical treatment may improve the effect of surgery. Copyright © 2020, the Korean Surgical Society.Purpose Since the treatment strategy for benign and malignant pancreatic lesions differ, we aimed to evaluate the clinical value of PET/CT in the diagnosis and management of pancreatic lesions. Methods Ninety patients who had a histologically confirmed pancreatic lesion were studied. Receiver operating characteristic (ROC) curve analysis was used to investigate the ability of PET/CT to differentiate malignant lesions from benign tumors. Results The malignant and benign groups comprised 64 and 26 patients, respectively. Despite the similarity in the size of primary tumors (P = 0.588), the mean maximum standardized uptake values (SUVmax) obtained from PET/CT imaging were significantly higher in malignant lesions (9.36 ± 5.9) than those of benign tumors (1.04 ± 2.6, P less then 0.001). ROC analysis showed that the optimal SUVmax cutoff value for differentiating malignant lesions (to an accuracy of 91%; 95% confidence interval, 83%-98%) from benign tumors was 3.9 (sensitivity, 92.2%; specificity, 84.6%). Conclusion PET/CT evaluation of pancreatic lesions confers advantages including fine assessment of malignant potential with high sensitivity and accuracy using a threshold SUVmax value of 3.9. Copyright © 2020, the Korean Surgical Society.Purpose Although pancreatoduodenectomy (PD) in patients who have previously undergone gastrectomy is challenging, little is known about the clinical outcomes and the differences compared to those with conventional PD. We collected cases and conducted studies in retrospective review. Methods Of the 1,722 patients who underwent PD at Seoul National University Hospital between 2000 and 2014, 49 (2.8%) underwent previous gastrectomy. Clinical outcomes including operation-related factors and postoperative morbidities were analyzed. Results Among the 49 patients with curative surgery, 25 patients were male (51.0%) and the mean age was 64.7 years. Gastric cancer was the most frequent cause of previous gastrectomy (93.8%). With one-to-one propensity score matching analysis, lower preoperative body mass index (22.6 kg/m2 vs. 20.8 kg/m2, P = 0.002), higher EBL (390.0 mL vs. 729.5 mL, P = 0.027), and higher transfusion rates (10.2% vs. 36.7%, P = 0.002) were shown in the gastrectomy group. Operation time, postoperative hospital stay, and rate of clinically relevant pancreatic fistula were comparable.0 Commenti 0 condivisioni 14 Views 0 Anteprima
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