Objective: The detailed knowledge about protective effects of capsaicin(cap) and involved mechanisms against testicular torsion(TT) is still not available completely.Methods: Male Wistar rats were assigned into four m...Objective: The detailed knowledge about protective effects of capsaicin(cap) and involved mechanisms against testicular torsion(TT) is still not available completely.Methods: Male Wistar rats were assigned into four major cohorts:(i) sham,(ii) TT,(iii) three subgroups subjected to TT and different doses of cap(100, 500, and 1000 μg/mL), and(iv) three subgroups of healthy animals subjected to various concentrations of cap. The animals were decapitated at 24 h after reperfusion, and the evaluation of protein expression was performed by Western blotting assay. At 72 h after reperfusion, apoptotic cell death and tissue injury were evaluated by TUNEL nuclear and H&E staining,respectively.Results: The results showed that cap administration following TT significantly increased the expression of tuberous sclerosis proteins 1 and 2(Tsc1/Tsc2) in a dose-dependent manner(P < 0.05). Cap decreased cell apoptosis at highest dose. Likewise, cap contributed to the preservation of tubular morphology and decreased tissue injury at the highest tested concentration(1000 μg/m L).Conclusion: Collectively, our findings demonstrate the validity of cap as a therapeutic agent against TT through targeting Tsc1/Tsc2 in a dose-dependent manner.展开更多
Background Tuberous sclerosis complex(TSC),an inherited neurocutaneous disorder,is caused by variants in the TSC1 or TSC2 genes.The mosaic variants of TSC1 and TSC2 are scarcely detectable using the conventional nextg...Background Tuberous sclerosis complex(TSC),an inherited neurocutaneous disorder,is caused by variants in the TSC1 or TSC2 genes.The mosaic variants of TSC1 and TSC2 are scarcely detectable using the conventional nextgeneration sequencing(NGS).Therefore,this study aims to explore the detection and distribution of mosaic variants within affected families.Methods Through whole-exome sequencing(WES)or the TSC1/TSC2 panel to detect the variants of the TSC1 and TSC2 genes,the reaction system of droplet digital PCR(ddPCR)was designed to detect the mosaicism of these variants in affected families.Results Genetic testing was carried out on 29 TSC patients via WES or the TSC1/TSC2 panel.The results showed that 27 patients had positive results in the TSC gene variant tests.Fourteen cases were confirmed as de novo variants,and the asymptomatic fathers or mothers of 4 patients were identified as somatic mosaics by ddPCR,with mosaic proportions of 0.8%,24.18%,8.02%,and 0.33%respectively.Conclusions The ddPCR holds the potential to improve diagnostic accuracy,genetic risk assessment,and clinical diagnosis rates.Consequently,it could potentially be adopted as one of the modalities for prompt clinical diagnosis.展开更多
Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and af...Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
基金support by Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Grant No. 66005282
文摘Objective: The detailed knowledge about protective effects of capsaicin(cap) and involved mechanisms against testicular torsion(TT) is still not available completely.Methods: Male Wistar rats were assigned into four major cohorts:(i) sham,(ii) TT,(iii) three subgroups subjected to TT and different doses of cap(100, 500, and 1000 μg/mL), and(iv) three subgroups of healthy animals subjected to various concentrations of cap. The animals were decapitated at 24 h after reperfusion, and the evaluation of protein expression was performed by Western blotting assay. At 72 h after reperfusion, apoptotic cell death and tissue injury were evaluated by TUNEL nuclear and H&E staining,respectively.Results: The results showed that cap administration following TT significantly increased the expression of tuberous sclerosis proteins 1 and 2(Tsc1/Tsc2) in a dose-dependent manner(P < 0.05). Cap decreased cell apoptosis at highest dose. Likewise, cap contributed to the preservation of tubular morphology and decreased tissue injury at the highest tested concentration(1000 μg/m L).Conclusion: Collectively, our findings demonstrate the validity of cap as a therapeutic agent against TT through targeting Tsc1/Tsc2 in a dose-dependent manner.
基金supported by Wuhan Knowledge innovation special project(2023020201020554)the Key research and development program of Hubei Province(2023BCB136)+3 种基金the Construction of the Clinical Research Laboratory of Wuhan Children’s Hospital(2022 FEYJS001)Construction Project of Hubei Provincial Clinical Medical Research Center for Childhood Neurodevelopmental Disorders(No.HST2020-19)Nature Science Foundation of Hubei Province(2023 AFB360)Research Project Grant of Wuhan Children’s Hospital(2023 FEBSJJ002).
文摘Background Tuberous sclerosis complex(TSC),an inherited neurocutaneous disorder,is caused by variants in the TSC1 or TSC2 genes.The mosaic variants of TSC1 and TSC2 are scarcely detectable using the conventional nextgeneration sequencing(NGS).Therefore,this study aims to explore the detection and distribution of mosaic variants within affected families.Methods Through whole-exome sequencing(WES)or the TSC1/TSC2 panel to detect the variants of the TSC1 and TSC2 genes,the reaction system of droplet digital PCR(ddPCR)was designed to detect the mosaicism of these variants in affected families.Results Genetic testing was carried out on 29 TSC patients via WES or the TSC1/TSC2 panel.The results showed that 27 patients had positive results in the TSC gene variant tests.Fourteen cases were confirmed as de novo variants,and the asymptomatic fathers or mothers of 4 patients were identified as somatic mosaics by ddPCR,with mosaic proportions of 0.8%,24.18%,8.02%,and 0.33%respectively.Conclusions The ddPCR holds the potential to improve diagnostic accuracy,genetic risk assessment,and clinical diagnosis rates.Consequently,it could potentially be adopted as one of the modalities for prompt clinical diagnosis.
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
