Dental implant biomaterials are expected to be in contact with living tissues, therefore their toxicity and osseointegration ability must be carefully assessed. In the current study, the wettability, cytotoxicity, and genotoxicity of different alumina-zirconia-titania composites were evaluated. The surface wettability determines the biological event cascade in the bioceramic/human living tissues interface. The measured water contact angle indicated that the wettability strongly depends on the ceramic composition. Notwithstanding the contact angle variability, the ceramic surfaces are hydrophilic. The cytotoxicity of human gingival fibroblast cells with materials, evaluated by an (3-(4,5 methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) test, revealed an absence of any cytotoxic effect. A relationship was found between the cell viability and the wettability. It was subsequently deduced that the cell viability increases when the wettability increases. This effect is more pronounced when the titania content is higher. Finally, a comet test was applied as complementary biocompatibility test to detect any changes in fibroblast cell DNA. The results showed that the DNA damage is intimately related to the TiO2 content. Genotoxicity was mainly attributed to ceramic composites containing 10 wt.% TiO2. Our research revealed that the newly developed high performance alumina-zirconia-titania ceramic composites contain less than 10 wt.% TiO2, and display promising surface properties, making them suitable for dental implantology applications.BACKGROUND Prostate cancer (PCa) dissemination shows a tendency to develop in the bone, where heme oxygenase 1 (HO-1) plays a critical role in bone remodeling. https://www.selleckchem.com/products/gkt137831.html Previously by LC/ESI-MSMS, we screened for HO-1 interacting proteins and identified annexin 2 (ANXA2). The aim of this study was to analyze the relevance of ANXA2/HO-1 in PCa and bone metastasis. METHODS We assessed ANXA2 levels using a co-culture transwell system of PC3 cells (pre-treated or not with hemin, an HO-1 specific inducer) and the pre-osteoclastic Raw264.7 cell line. RESULTS Under co-culture conditions, ANXA2 mRNA levels were significantly modulated in both cell lines. Immunofluorescence analysis unveiled a clear ANXA2 reduction in cell membrane immunostaining for Raw264.7 under the same conditions. This effect was supported by the detection of a decrease in Ca2+ concentration in the conditioned medium. HO-1 induction in tumor cells prevented both, the ANXA2 intracellular relocation and the decrease in Ca2+ concentration. Further, secretome analysis revealed urokinase (uPA) as a key player in the communication between osteoclast progenitors and PC3 cells. To assess the clinical significance of ANXA2/HO-1, we performed a bioinformatics analysis and identified that low expression of each gene strongly associated with poor prognosis in PCa regardless of the clinico-pathological parameters assessed. Further, these genes appear to behave in a dependent manner. CONCLUSIONS ANXA2/HO-1 rises as a critical axis in PCa.Extraocular muscles (EOMs) show resistance to muscle dystrophies and sarcopenia. It has been recently demonstrated that they are endowed with different types of myogenic cells, all of which present an outstanding regenerative potential. Neurotrophins are important modulators of myogenic regeneration and act promoting myoblast proliferation, enhancing myogenic fusion rates and protecting myotubes from inflammatory stimuli. Here, we adapted the pre-plate cell isolation technique to obtain myogenic progenitors from the rat EOMs, and quantified their in vitro expression of neurotrophins and their receptors by RT-qPCR and immunohistochemistry, respectively. The results were compared with the expression on progenitors isolated from buccinator, tongue and limb muscles. Our quantitative analysis of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3) transcripts showed, for the first time, that EOMs-derived cells express more of these factors and that they expressed TrkA, but not TrkB and TrkC receptors. On the contrary, the immunofluorescence analysis demonstrated high expression of p75NTR on all myogenic progenitors, with the EOMs-derived cells showing higher expression. Taken together, these results suggest that the intrinsic trophic differences between EOMs-derived myogenic progenitors and their counterparts from other muscles could explain why those cells show higher proliferative and fusion rates, as well as better regenerative properties.Dendritic cells (DCs) play a critical role in the immune system which sense pathogens and present their antigens to prime the adaptive immune responses. As the progression of sepsis occurs, DCs are capable of orchestrating the aberrant innate immune response by sustaining the Th1/Th2 responses that are essential for host survival. Hence, an in-depth understanding of the characteristics of DCs would have a beneficial effect in overcoming the obstacle occurring in sepsis. This paper focuses on the role of DCs in the progression of sepsis and we also discuss the reverse sepsis-induced immunosuppression through manipulating the DC function. In addition, we highlight some potent immunotherapies that could be used as a novel strategy in the early treatment of sepsis.One of the most challenging goals in modern pharmaceutical research is to develop models that can predict drugs' behavior, particularly permeability in human tissues. Since the permeability is closely related to the molecular properties, numerous characteristics are necessary in order to develop a reliable predictive tool. The present study attempts to decode the permeability by correlating the apparent permeability coefficient (Papp) of 33 steroids with their properties (physicochemical and structural). The Papp of the molecules was determined by in vitro experiments and the results were plotted as Y variable on a Partial Least Squares (PLS) model, while 37 pharmacokinetic and structural properties were used as X descriptors. The developed model was subjected to internal validation and it tends to be robust with good predictive potential (R2Y = 0.902, RMSEE = 0.00265379, Q2Y = 0.722, RMSEP = 0.0077). Based on the results specific properties (logS, logP, logD, PSA and VDss) were proved to be more important than others in terms of drugs Papp.
Dental implant biomaterials are expected to be in contact with living tissues, therefore their toxicity and osseointegration ability must be carefully assessed. In the current study, the wettability, cytotoxicity, and genotoxicity of different alumina-zirconia-titania composites were evaluated. The surface wettability determines the biological event cascade in the bioceramic/human living tissues interface. The measured water contact angle indicated that the wettability strongly depends on the ceramic composition. Notwithstanding the contact angle variability, the ceramic surfaces are hydrophilic. The cytotoxicity of human gingival fibroblast cells with materials, evaluated by an (3-(4,5 methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) test, revealed an absence of any cytotoxic effect. A relationship was found between the cell viability and the wettability. It was subsequently deduced that the cell viability increases when the wettability increases. This effect is more pronounced when the titania content is higher. Finally, a comet test was applied as complementary biocompatibility test to detect any changes in fibroblast cell DNA. The results showed that the DNA damage is intimately related to the TiO2 content. Genotoxicity was mainly attributed to ceramic composites containing 10 wt.% TiO2. Our research revealed that the newly developed high performance alumina-zirconia-titania ceramic composites contain less than 10 wt.% TiO2, and display promising surface properties, making them suitable for dental implantology applications.BACKGROUND Prostate cancer (PCa) dissemination shows a tendency to develop in the bone, where heme oxygenase 1 (HO-1) plays a critical role in bone remodeling. https://www.selleckchem.com/products/gkt137831.html Previously by LC/ESI-MSMS, we screened for HO-1 interacting proteins and identified annexin 2 (ANXA2). The aim of this study was to analyze the relevance of ANXA2/HO-1 in PCa and bone metastasis. METHODS We assessed ANXA2 levels using a co-culture transwell system of PC3 cells (pre-treated or not with hemin, an HO-1 specific inducer) and the pre-osteoclastic Raw264.7 cell line. RESULTS Under co-culture conditions, ANXA2 mRNA levels were significantly modulated in both cell lines. Immunofluorescence analysis unveiled a clear ANXA2 reduction in cell membrane immunostaining for Raw264.7 under the same conditions. This effect was supported by the detection of a decrease in Ca2+ concentration in the conditioned medium. HO-1 induction in tumor cells prevented both, the ANXA2 intracellular relocation and the decrease in Ca2+ concentration. Further, secretome analysis revealed urokinase (uPA) as a key player in the communication between osteoclast progenitors and PC3 cells. To assess the clinical significance of ANXA2/HO-1, we performed a bioinformatics analysis and identified that low expression of each gene strongly associated with poor prognosis in PCa regardless of the clinico-pathological parameters assessed. Further, these genes appear to behave in a dependent manner. CONCLUSIONS ANXA2/HO-1 rises as a critical axis in PCa.Extraocular muscles (EOMs) show resistance to muscle dystrophies and sarcopenia. It has been recently demonstrated that they are endowed with different types of myogenic cells, all of which present an outstanding regenerative potential. Neurotrophins are important modulators of myogenic regeneration and act promoting myoblast proliferation, enhancing myogenic fusion rates and protecting myotubes from inflammatory stimuli. Here, we adapted the pre-plate cell isolation technique to obtain myogenic progenitors from the rat EOMs, and quantified their in vitro expression of neurotrophins and their receptors by RT-qPCR and immunohistochemistry, respectively. The results were compared with the expression on progenitors isolated from buccinator, tongue and limb muscles. Our quantitative analysis of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3) transcripts showed, for the first time, that EOMs-derived cells express more of these factors and that they expressed TrkA, but not TrkB and TrkC receptors. On the contrary, the immunofluorescence analysis demonstrated high expression of p75NTR on all myogenic progenitors, with the EOMs-derived cells showing higher expression. Taken together, these results suggest that the intrinsic trophic differences between EOMs-derived myogenic progenitors and their counterparts from other muscles could explain why those cells show higher proliferative and fusion rates, as well as better regenerative properties.Dendritic cells (DCs) play a critical role in the immune system which sense pathogens and present their antigens to prime the adaptive immune responses. As the progression of sepsis occurs, DCs are capable of orchestrating the aberrant innate immune response by sustaining the Th1/Th2 responses that are essential for host survival. Hence, an in-depth understanding of the characteristics of DCs would have a beneficial effect in overcoming the obstacle occurring in sepsis. This paper focuses on the role of DCs in the progression of sepsis and we also discuss the reverse sepsis-induced immunosuppression through manipulating the DC function. In addition, we highlight some potent immunotherapies that could be used as a novel strategy in the early treatment of sepsis.One of the most challenging goals in modern pharmaceutical research is to develop models that can predict drugs' behavior, particularly permeability in human tissues. Since the permeability is closely related to the molecular properties, numerous characteristics are necessary in order to develop a reliable predictive tool. The present study attempts to decode the permeability by correlating the apparent permeability coefficient (Papp) of 33 steroids with their properties (physicochemical and structural). The Papp of the molecules was determined by in vitro experiments and the results were plotted as Y variable on a Partial Least Squares (PLS) model, while 37 pharmacokinetic and structural properties were used as X descriptors. The developed model was subjected to internal validation and it tends to be robust with good predictive potential (R2Y = 0.902, RMSEE = 0.00265379, Q2Y = 0.722, RMSEP = 0.0077). Based on the results specific properties (logS, logP, logD, PSA and VDss) were proved to be more important than others in terms of drugs Papp.
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