Background. Peritoneal dialysis (PD) can induce fibrosis and functional alterations in PD patients' peritoneal membranes, due to long-term unphysiological dialysate exposure, partially occurring via triggering of epithelial-to-mesenchymal transition (EMT) in peritoneal mesothelial cells (MCs). Vitamin D can ameliorate these negative effects; however, the mechanism remains unexplored. Therefore, we investigated its possible links to MCs EMT inhibition. Methods. Peritoneal fibrosis was established in Sprague-Dawley rats by chlorhexidine gluconate (CG) intraperitoneal injection for 21 days, with and without 1α,25(OH)2D3 treatment. Morphological and functional evaluation and western blot analysis of EMT marker were performed upon peritoneum tissue. In vitro study was also performed in a primary human peritoneal MC culture system; MCs were incubated with transforming growth factor-β1 (TGF-β1) in the absence or presence of 1α,25(OH)2D3. EMT marker expression, migration activities, and cytoskeleton redistribution of MCs were determined. Results. 1α,25(OH)2D3 ameliorated CG-induced morphological and functional deterioration in animal model, along with CG-induced upregulation of α-SMA and downregulation of E-cadherin expression. Meanwhile, 1α,25(OH)2D3 also ameliorated TGF-β1-induced decrease in E-cadherin expression, increase in Snai1 and α-SMA expression, intracellular F-actin redistribution, and migration activity in vitro. Conclusion. 1α,25(OH)2D3 can ameliorate CG-induced peritoneal fibrosis and attenuate functional deterioration through inhibiting MC EMT.
Phthalates are widely used as plasticizers. Humans can be exposed to phthalates through ingestion, inhalation, or treatments that release di(2-ethylhexyl) phthalate (DEHP) and its metabolite, mono(2-ehylhexyl) phthalate (MEHP), into the body from polyvinyl chloride-based medical devices. Phthalate exposure may induce reproductive toxicity, liver damage, and carcinogenesis in humans. This study found that colon cancer cells exposed to DEHP or MEHP exhibited increased cell viability and increased levels of P-glycoprotein, CD133, Bcl-2, Akt, ERK, GSK3β, and β-catenin when treated with oxaliplatin or irinotecan, as compared to control. The P-glycoprotein inhibitor, tariquidar, which blocks drug efflux, reduced the viability of DEHP- or MEHP-treated, anti-cancer drug-challenged cells. DEHP or MEHP treatment also induced colon cancer cell migration and epithelial-mesenchymal transformation. Elevated stemness-related protein levels (β-catenin, Oct4, Sox2, and Nanog) and increased cell sphere sizes indicated that DEHP- or MEHP-treated cells were capable of self-renewal. We also found that serum DEHP concentrations were positively correlated with cancer recurrence. These results suggest phthalate exposure enhances colon cancer cell metastasis and chemotherapeutic drug resistance by increasing cancer cell stemness, and that P-glycoprotein inhibitors might improve outcomes for advanced or drug-resistant colon cancer patients.
BackgroundPeritoneal dialysis (PD) therapy is known to induce morphological and functional changes in the peritoneal membrane. Long-term exposure to conventional bio-incompatible dialysate and peritonitis is the main etiology of inflammation. Consequently, the peritoneal membrane undergoes structural changes, including angiogenesis, fibrosis, and hyalinizing vasculopathy, which ultimately results in technique failure. The epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs) plays an important role during the above process; however, the clinical parameters associated with the EMT process of MCs remain to be explored.MethodsTo investigate the parameters impacting EMT during PD therapy, 53 clinical stable PD patients were enrolled. EMT assessments were conducted through human peritoneal MCs cultured from dialysate effluent with one consistent standard criterion (MC morphology and the expression of an epithelial marker, cytokeratin 18). The factors potentially associated with EMT were analyzed using logistic regression analysis. Primary MCs derived from the omentum were isolated for the in vitro study.ResultsForty-seven percent of the patients presented with EMT, 28% with non-EMT, and 15% with a mixed presentation. Logistic regression analysis showed that patients who received persistent PD therapy (dwelling time of 24 h/day) had significantly higher EMT tendency. These results were consistent in vitro.ConclusionsDwelling time had a significant effect on the occurrence of EMT on MCs.
A design procedure for increasing the indexing accuracy of intermittent grooved globoidal cam mechanisms is presented. It is based on the synthesis of asymmetrical dwell-rise-dwell (D-R-D) roller-follower turret motions to improve the kinematic and dynamic performance of the globoidal cam-turret devices for high-speed applications. Such asymmetrical turret motion curves are defined and tuned by nonparametric rational B-splines. Favorable results of kinematic characteristics, geometric properties including pressure angles and curvatures of cam surfaces, torques, and residual vibrations are revealed and compared to those obtained by traditional methods. Together with experimental results, a practical application example is given to demonstrate the usefulness and effectiveness.
Indium, a rare earth metal characterized by high plasticity, corrosion resistance, and a low melting point, is widely used in the electronics industry, but has been reported to be an environmental pollutant and a health hazard. We designed a study to investigate the effects of subacute exposure of indium compounds on male reproductive function. Twelve-week old male Sprague-Dawley rats were randomly divided into test and control groups, and received weekly intraperitoneal injections of indium acetate (1.5 mg/kg body weight) and normal saline, respectively, for 8 weeks. Serum indium levels, cauda epididymal sperm count, motility, morphology, chromatin DNA structure, mitochondrial membrane potential, oxidative stress, and testis DNA content were investigated. The indium acetate-treated group showed significant reproductive toxicity, as well as an increased percentage of sperm morphology abnormality, chromatin integrity damage, and superoxide anion generation. Furthermore, positive correlations among sperm morphology abnormalities, chromatin DNA damage, and superoxide anion generation were also noted. The results of this study demonstrated the toxic effect of subacute low-dose indium exposure during the period of sexual maturation on male reproductive function in adulthood, through an increase in oxidative stress and sperm chromatin DNA damage during spermiogenesis, in a rodent model.
Indium, a Group IIIA element of the periodic chart and a rare earth metal characterized by high plasticity, corrosion resistance, and a low melting point, is widely used in the electronics industry where released streams can contaminate the environment. Consequently, indium can reach humans mainly by natural ways, which could result in a health hazard. Although reproductive toxicities have been surveyed in some studies in animal models, the infertility effects of sperm function induced by indium compounds have not been greatly investigated. We designed a study to investigate the toxicities of subacute exposure to indium compounds on male sperm function and the process of spermatogenesis in a rodent model. Fourteen Sprague-Dawley rats on postnatal Day (PND) 84 were randomly divided into exposure and control groups, and weekly received intraperitoneal injections of indium chloride (1.5 mg/kg body weight) and normal saline, respectively, for 8 weeks. Cauda epididymal sperm count, motility, morphology, chromatin DNA integrity, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, and testis DNA content were investigated. The indium chloride exposed group showed significant toxicity to sperm function, as well as an increased percentage of sperm morphological abnormality and chromatin DNA damage. Furthermore, positive correlations between abnormal sperm morphology, chromatin DNA damage, and superoxide anion generation were also noted. The results of this study demonstrated the toxic effect of subacute low dose indium exposure during sexual maturation on sperm function, resulting in sperm chromatin DNA damage through an increase in sperm ROS generation in a rodent model.
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