Aim: To evaluate chronic exposure of carmoisine at ADI doses on some hepatocellular and renal parameters of male and female albino rats as well as to determine sex-dependent toxicity. Study Design: The study involves ...Aim: To evaluate chronic exposure of carmoisine at ADI doses on some hepatocellular and renal parameters of male and female albino rats as well as to determine sex-dependent toxicity. Study Design: The study involves treatment for 30, 60, and 90 days. Each phase consists of 40 rats, divided into treatment and control groups. The treated groups were orally administered with 4.0 mg/kg of carmoisine daily for the periods of 30, 60, and 90 days. Methodology: At the end of the treatment, the rats were allowed to fast for 18 hours followed by the collection of 5 ml of whole blood specimens by means of cardiac puncture into Lithium Heparin bottles and fluoride oxalate bottles (for glucose only). Plasma obtained was analyzed for glucose (GLU), AST, ALT, ALP, creatinine (CRT), and urea. Hepatic and Renal tissues collected were fixed in 10% formol saline and later examined histologically using H&E stain. Statistical data analysis was done using GraphPad Prism version 9.02. Results: Glucose indicated significant increases after 30, 60, and 90 days of chronic treatment at ADI doses. Urea, Creatinine, AST, ALT and ALP showed significantly higher values after 60 and 90 days of treatment (except creatinine in male rats and ALP in female rats after 60 and 90 days respectively). Hepatic distortions, vacuolation, compression of central vein were seen in the liver section while distortion of proximal and distal tubules, and inflammation of the glomerulus were observed in the renal tissue of the treated rats. Conclusion: The administration of camoisine over a period of 30 days at ADI dose did not indicate hepatocellullar and renal derangements as well histological distortions in liver, and kidneys. However, after 60 and 90 days, mild hepatocellular, and renal derangements were seen. No sex-dependent toxicity was observed.展开更多
Type 2 diabetes(T2D)is characterized by the malfunction of pancreaticβcells.Susceptibility and pathogenesis of T2D can be affected by multiple factors,including sex differences.However,the mechanisms underlying sex d...Type 2 diabetes(T2D)is characterized by the malfunction of pancreaticβcells.Susceptibility and pathogenesis of T2D can be affected by multiple factors,including sex differences.However,the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear.Using single-cell RNA sequencing(scRNA-seq),we demonstrate the presence of sexually dimorphic transcriptomes in mouseβcells.Using a high-fat diet-induced T2D mouse model,we identified sex-dependent T2D altered genes,suggesting sex-based differences in the pathological mechanisms of T2D.Furthermore,based on islet transplantation experiments,we found that compared to mice with sexmatched islet transplants,sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway ofβcells.Moreover,the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance.These data suggest sexual dimorphism in T2D pathogenicity,indicating that sex should be considered when treating T2D.We hope that our findings could provide new insights for the development of precision medicine in T2D.展开更多
The prevalence of residual antibiotics is a global threat to human health.Less is known about the potential health effects of residual antibiotics in freshwater systems.Here,zebrafish were used to explore chronic effe...The prevalence of residual antibiotics is a global threat to human health.Less is known about the potential health effects of residual antibiotics in freshwater systems.Here,zebrafish were used to explore chronic effects of environmentally relevant concentrations(ERCs)of tetracycline(TC).Although chronic exposure to TC did not significantly alter the body weight of adult zebrafish,the exposed zebrafish parents exhibited substantial changes in gut microbiota composition and a reduced gut-weight ratio.Notably,male fish exposed to TC showed a significant decline of critical intestinal function-related metabolites(i.e.,triglycerides,glucose,and free fat acid),while this was not observed in females,resulting in sex-dependency.The gut microbial composition of chronically exposed zebrafish parents changed substantially,but the disruption was not transferred to their respective offspring without exposure.However,the perturbation of insulinrelated signaling pathways caused by TC exposure was not attenuated in the zebrafish offspring after removal of TC exposure.Taken together,our findings suggest that chronic exposure to TC disturbs gut microbial communities and metabolism and exerts chronic effects on the insulin/IGF-1 mediated signaling cascades,implying that exposure to antibiotics not only leads to the selection of resistant microbes but also poses long-term deleterious health risks for the next generation.展开更多
文摘Aim: To evaluate chronic exposure of carmoisine at ADI doses on some hepatocellular and renal parameters of male and female albino rats as well as to determine sex-dependent toxicity. Study Design: The study involves treatment for 30, 60, and 90 days. Each phase consists of 40 rats, divided into treatment and control groups. The treated groups were orally administered with 4.0 mg/kg of carmoisine daily for the periods of 30, 60, and 90 days. Methodology: At the end of the treatment, the rats were allowed to fast for 18 hours followed by the collection of 5 ml of whole blood specimens by means of cardiac puncture into Lithium Heparin bottles and fluoride oxalate bottles (for glucose only). Plasma obtained was analyzed for glucose (GLU), AST, ALT, ALP, creatinine (CRT), and urea. Hepatic and Renal tissues collected were fixed in 10% formol saline and later examined histologically using H&E stain. Statistical data analysis was done using GraphPad Prism version 9.02. Results: Glucose indicated significant increases after 30, 60, and 90 days of chronic treatment at ADI doses. Urea, Creatinine, AST, ALT and ALP showed significantly higher values after 60 and 90 days of treatment (except creatinine in male rats and ALP in female rats after 60 and 90 days respectively). Hepatic distortions, vacuolation, compression of central vein were seen in the liver section while distortion of proximal and distal tubules, and inflammation of the glomerulus were observed in the renal tissue of the treated rats. Conclusion: The administration of camoisine over a period of 30 days at ADI dose did not indicate hepatocellullar and renal derangements as well histological distortions in liver, and kidneys. However, after 60 and 90 days, mild hepatocellular, and renal derangements were seen. No sex-dependent toxicity was observed.
基金This work was supported by the National Key R&D Program of China(Grant Nos.2016YFA0102200,2017YFA0106500,2018YFA0107102,and 2020YFA0112500 awarded to WL,Grant No.2018YFA0107602 awarded to ZS)Key Project of the Science and Technology Commission of Shanghai Municipality,China(Grant No.19JC1415300 awarded to WL)+2 种基金the National Key R&D Program of China(Grant No.2018YFD0900604 awarded to WS)the National Natural Science Foundation of China(Grant Nos.41676119 and 41476120 awarded to WS)the start-up fund from Ocean University of China(awarded to WS).
文摘Type 2 diabetes(T2D)is characterized by the malfunction of pancreaticβcells.Susceptibility and pathogenesis of T2D can be affected by multiple factors,including sex differences.However,the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear.Using single-cell RNA sequencing(scRNA-seq),we demonstrate the presence of sexually dimorphic transcriptomes in mouseβcells.Using a high-fat diet-induced T2D mouse model,we identified sex-dependent T2D altered genes,suggesting sex-based differences in the pathological mechanisms of T2D.Furthermore,based on islet transplantation experiments,we found that compared to mice with sexmatched islet transplants,sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway ofβcells.Moreover,the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance.These data suggest sexual dimorphism in T2D pathogenicity,indicating that sex should be considered when treating T2D.We hope that our findings could provide new insights for the development of precision medicine in T2D.
基金thank the High-level Talents Project of Chongqing Medical University(R4014 and R4020)Research Program of Chongqing Science and Technology Commission(cstc2019jcyj-zdxmX0035 and CSTCCXLJRC201714)+2 种基金National Natural Science Foundation of China(No.51878642 to L.Y.S.and No.32200386 to P.P.J.)Chongqing Postdoctoral Innovation Mentor Studio(X7928 D.S.P.)Program of China−Sri Lanka Joint Research and Demonstration Center for Water Technology and China−Sri Lanka Joint Center for Education and Research by Chinese Academy of Sciences,China for their financial support.
文摘The prevalence of residual antibiotics is a global threat to human health.Less is known about the potential health effects of residual antibiotics in freshwater systems.Here,zebrafish were used to explore chronic effects of environmentally relevant concentrations(ERCs)of tetracycline(TC).Although chronic exposure to TC did not significantly alter the body weight of adult zebrafish,the exposed zebrafish parents exhibited substantial changes in gut microbiota composition and a reduced gut-weight ratio.Notably,male fish exposed to TC showed a significant decline of critical intestinal function-related metabolites(i.e.,triglycerides,glucose,and free fat acid),while this was not observed in females,resulting in sex-dependency.The gut microbial composition of chronically exposed zebrafish parents changed substantially,but the disruption was not transferred to their respective offspring without exposure.However,the perturbation of insulinrelated signaling pathways caused by TC exposure was not attenuated in the zebrafish offspring after removal of TC exposure.Taken together,our findings suggest that chronic exposure to TC disturbs gut microbial communities and metabolism and exerts chronic effects on the insulin/IGF-1 mediated signaling cascades,implying that exposure to antibiotics not only leads to the selection of resistant microbes but also poses long-term deleterious health risks for the next generation.
