Cognitive decline in Alzheimer’s disease correlates with the extent of tau pathology,in particular tau hyperphosphorylation that initially appears in the transentorhinal and related regions of the brain including the...Cognitive decline in Alzheimer’s disease correlates with the extent of tau pathology,in particular tau hyperphosphorylation that initially appears in the transentorhinal and related regions of the brain including the hippocampus.Recent evidence indicates that tau hyperphosphorylation caused by either amyloid-βor long-term depression,a form of synaptic weakening involved in learning and memory,share similar mechanisms.Studies from our group and others demonstrate that long-term depression-inducing low-frequency stimulation triggers tau phosphorylation at different residues in the hippocampus under different experimental conditions including aging.Conversely,certain forms of long-term depression at hippocampal glutamatergic synapses require endogenous tau,in particular,phosphorylation at residue Ser396.Elucidating the exact mechanisms of interaction between tau and long-term depression may help our understanding of the physiological and pathological functions of tau/tau(hyper)phosphorylation.We first summarize experimental evidence regarding tau-long-term depression interactions,followed by a discussion of possible mechanisms by which this interplay may influence the pathogenesis of Alzheimer’s disease.Finally,we conclude with some thoughts and perspectives on future research about these interactions.展开更多
Objective:To investigate the modulatory effects of bitter gourd extract on the insulin signaling pathway in the liver and skeletal muscle tissues of diabetic rats.Methods:The ethanolic extract of bitter gourd was prep...Objective:To investigate the modulatory effects of bitter gourd extract on the insulin signaling pathway in the liver and skeletal muscle tissues of diabetic rats.Methods:The ethanolic extract of bitter gourd was prepared and its contents of total polyphenols and flavonoids were assayed.A neonatal streptozotocin-induced diabetic rat model was established and the diabetic rats were assigned into different groups and were treated with different doses of bitter gourd extract(100,200,400,or 600 mg/kg)or with glibenclamide(0.1 mg/kg)for 30 d.Fasting blood glucose,insulin,and lipid profile were evaluated and the insulin signaling pathway in the liver and skeletal muscle of rats was investigated.The correlations between homeostasis model assessment(HOMA)and the components of insulin signaling pathway were also evaluated.Results:Different doses of bitter gourd extract significantly ameliorated fasting blood glucose level and HOMA index for insulin resistance.Moreover,bitter gourd extract increased serum insulin and improved disrupted serum lipid profile.The levels of insulin receptor substrate-1(IRS-1),p-insulin receptorβ(p-IR-β),protein kinase C(PKC),GLUT2,and GLUT4 were improved by treatment with bitter gourd extract.The best results were obtained with 400 mg/kg dose of the extract,the effect of which was equivalent to that of glibenclamide.HOMA in the bitter gourd treated rats was negatively correlated with p-IR-β,IRS-1 and PKC in hepatic and skeletal muscle.HOMA was also negatively correlated with skeletal muscle GLUT4.Conclusions:Bitter gourd extract improves glucose homeostasis and lipid profile in diabetic rats via enhancement of insulin secretion and sensitivity.Therefore,bitter gourd can be used as a potential pharmacological agent for the treatment of type 2 diabetes mellitus.展开更多
Our recent breakthrough discovery demonstrated that the anticancer drug FL118 tightly binds to and then dephosphorylates and degrades the oncogenic protein DEAD-box helicase 5(DDX5),leading to the inhibition of DDX5 d...Our recent breakthrough discovery demonstrated that the anticancer drug FL118 tightly binds to and then dephosphorylates and degrades the oncogenic protein DEAD-box helicase 5(DDX5),leading to the inhibition of DDX5 downstream targets(e.g.,survivin,myeloid cell leukemia 1(Mcl-1),X-linked inhibitor of apoptosis(XIAP),c-Myc,mutant Kras,etc.)[1].FL118 is a molecular glue(MG)that can alter the interactomes of two or more non-interacting proteins[2].Thus,FL118 exhibits high efficacy against colorectal and pancreatic cancer xenograft tumors[1,3].However,moving FL118 into clinical trials requires a clinically compatible FL118 drug product(DP)that possesses high antitumor efficacy and low toxicity via oral(ideal)or intravenous(iv)administration.Here,we report the development and characterization of a clinically and orally compatible FL118 DP.We show that(1)FL118 drug substances(DS)exhibit high chemical stability under various test conditions;(2)a clinically and orally compatible FL118 DP can be manufactured through the formulation of FL118 DS with 2-hydroxypropyl-bcyclodextrin(HPbCD)using mixed solvents of glacial acetic acid(GAA)with ethanol through microfluidizer-mediated spray dried dispersion(M-SDD).展开更多
The paracrine and immunomodulatory cytokines secreted by mesenchymal stem cells(MSCs),generally referred to as the MSCs derived secretome,has substantial potential for the treatment of many chronic and degenerative di...The paracrine and immunomodulatory cytokines secreted by mesenchymal stem cells(MSCs),generally referred to as the MSCs derived secretome,has substantial potential for the treatment of many chronic and degenerative diseases.MSCs secretome contains both common and disease specific cytokines and modulators that can be beneficial against a wide range of chronic diseases.Herein,we discuss the MSCs secretome composition profile and its translational applicability and the challenges surrounding its use in clinical settings.展开更多
Background:Prenatal iron and folic acid supplementation is an economical strategy for reducing iron and folic acid deficiency anemia among expectant mothers in resource-limited countries like Uganda.This study aimed t...Background:Prenatal iron and folic acid supplementation is an economical strategy for reducing iron and folic acid deficiency anemia among expectant mothers in resource-limited countries like Uganda.This study aimed to assess the level of compliance with iron and folic acid supplementation(IFAS)and identify associated factors among mothers receiving prenatal services in Lira district,Uganda.Methods:A cross-sectional study was conducted at the antenatal clinic of Lira Regional Referral Hospital,involving 252 pregnant mothers.Adherence levels to IFAS were evaluated using a visual analogue scale,and associated factors were collected through an interviewer-administered questionnaire.The data were analyzed using SPSS software,and the results were presented in tables.Results:Only 46%of the mothers attending the antenatal clinic adhered to IFAS during the 30 days preceding the study.Participants who had good knowledge of IFAS before recruitment(odds ratio(OR)1.49,95%confidence interval(CI)1.12–1.97),utilized reminder techniques(OR 1.05,95%CI 1.02–1.09),and received support from their partners or relatives(OR 1.56,95%CI 1.07–2.29)were more likely to have good adherence.The main reasons for missing IFAS were forgetfulness and fear of taking too many tablets.Conclusions:There was a low adherence rate to IFAS among mothers attending antenatal clinics in Lira district.Further investigations are recommended to identify barriers to adherence,and comprehensive health education programs should be provided to pregnant mothers.展开更多
基金supported by the National Natural Science Foundation of China (U2004134)Zhengzhou University (140/32310295) to NWH+2 种基金by Science Foundation Ireland(19/FFP/6437 and 14/IA/2571) to MJRa scholarship granted by the China Scholarship Council (CSC20200704504 7) to YY
文摘Cognitive decline in Alzheimer’s disease correlates with the extent of tau pathology,in particular tau hyperphosphorylation that initially appears in the transentorhinal and related regions of the brain including the hippocampus.Recent evidence indicates that tau hyperphosphorylation caused by either amyloid-βor long-term depression,a form of synaptic weakening involved in learning and memory,share similar mechanisms.Studies from our group and others demonstrate that long-term depression-inducing low-frequency stimulation triggers tau phosphorylation at different residues in the hippocampus under different experimental conditions including aging.Conversely,certain forms of long-term depression at hippocampal glutamatergic synapses require endogenous tau,in particular,phosphorylation at residue Ser396.Elucidating the exact mechanisms of interaction between tau and long-term depression may help our understanding of the physiological and pathological functions of tau/tau(hyper)phosphorylation.We first summarize experimental evidence regarding tau-long-term depression interactions,followed by a discussion of possible mechanisms by which this interplay may influence the pathogenesis of Alzheimer’s disease.Finally,we conclude with some thoughts and perspectives on future research about these interactions.
文摘Objective:To investigate the modulatory effects of bitter gourd extract on the insulin signaling pathway in the liver and skeletal muscle tissues of diabetic rats.Methods:The ethanolic extract of bitter gourd was prepared and its contents of total polyphenols and flavonoids were assayed.A neonatal streptozotocin-induced diabetic rat model was established and the diabetic rats were assigned into different groups and were treated with different doses of bitter gourd extract(100,200,400,or 600 mg/kg)or with glibenclamide(0.1 mg/kg)for 30 d.Fasting blood glucose,insulin,and lipid profile were evaluated and the insulin signaling pathway in the liver and skeletal muscle of rats was investigated.The correlations between homeostasis model assessment(HOMA)and the components of insulin signaling pathway were also evaluated.Results:Different doses of bitter gourd extract significantly ameliorated fasting blood glucose level and HOMA index for insulin resistance.Moreover,bitter gourd extract increased serum insulin and improved disrupted serum lipid profile.The levels of insulin receptor substrate-1(IRS-1),p-insulin receptorβ(p-IR-β),protein kinase C(PKC),GLUT2,and GLUT4 were improved by treatment with bitter gourd extract.The best results were obtained with 400 mg/kg dose of the extract,the effect of which was equivalent to that of glibenclamide.HOMA in the bitter gourd treated rats was negatively correlated with p-IR-β,IRS-1 and PKC in hepatic and skeletal muscle.HOMA was also negatively correlated with skeletal muscle GLUT4.Conclusions:Bitter gourd extract improves glucose homeostasis and lipid profile in diabetic rats via enhancement of insulin secretion and sensitivity.Therefore,bitter gourd can be used as a potential pharmacological agent for the treatment of type 2 diabetes mellitus.
文摘Our recent breakthrough discovery demonstrated that the anticancer drug FL118 tightly binds to and then dephosphorylates and degrades the oncogenic protein DEAD-box helicase 5(DDX5),leading to the inhibition of DDX5 downstream targets(e.g.,survivin,myeloid cell leukemia 1(Mcl-1),X-linked inhibitor of apoptosis(XIAP),c-Myc,mutant Kras,etc.)[1].FL118 is a molecular glue(MG)that can alter the interactomes of two or more non-interacting proteins[2].Thus,FL118 exhibits high efficacy against colorectal and pancreatic cancer xenograft tumors[1,3].However,moving FL118 into clinical trials requires a clinically compatible FL118 drug product(DP)that possesses high antitumor efficacy and low toxicity via oral(ideal)or intravenous(iv)administration.Here,we report the development and characterization of a clinically and orally compatible FL118 DP.We show that(1)FL118 drug substances(DS)exhibit high chemical stability under various test conditions;(2)a clinically and orally compatible FL118 DP can be manufactured through the formulation of FL118 DS with 2-hydroxypropyl-bcyclodextrin(HPbCD)using mixed solvents of glacial acetic acid(GAA)with ethanol through microfluidizer-mediated spray dried dispersion(M-SDD).
文摘The paracrine and immunomodulatory cytokines secreted by mesenchymal stem cells(MSCs),generally referred to as the MSCs derived secretome,has substantial potential for the treatment of many chronic and degenerative diseases.MSCs secretome contains both common and disease specific cytokines and modulators that can be beneficial against a wide range of chronic diseases.Herein,we discuss the MSCs secretome composition profile and its translational applicability and the challenges surrounding its use in clinical settings.
文摘Background:Prenatal iron and folic acid supplementation is an economical strategy for reducing iron and folic acid deficiency anemia among expectant mothers in resource-limited countries like Uganda.This study aimed to assess the level of compliance with iron and folic acid supplementation(IFAS)and identify associated factors among mothers receiving prenatal services in Lira district,Uganda.Methods:A cross-sectional study was conducted at the antenatal clinic of Lira Regional Referral Hospital,involving 252 pregnant mothers.Adherence levels to IFAS were evaluated using a visual analogue scale,and associated factors were collected through an interviewer-administered questionnaire.The data were analyzed using SPSS software,and the results were presented in tables.Results:Only 46%of the mothers attending the antenatal clinic adhered to IFAS during the 30 days preceding the study.Participants who had good knowledge of IFAS before recruitment(odds ratio(OR)1.49,95%confidence interval(CI)1.12–1.97),utilized reminder techniques(OR 1.05,95%CI 1.02–1.09),and received support from their partners or relatives(OR 1.56,95%CI 1.07–2.29)were more likely to have good adherence.The main reasons for missing IFAS were forgetfulness and fear of taking too many tablets.Conclusions:There was a low adherence rate to IFAS among mothers attending antenatal clinics in Lira district.Further investigations are recommended to identify barriers to adherence,and comprehensive health education programs should be provided to pregnant mothers.
