Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primar...Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.展开更多
Hearing loss is one of the most frequent health issues in industrialized countries. The pathogenesis and molecular mechanisms of hearing loss are still unclear. Histone deacetylases(HDACs) are emerging as key enzymes ...Hearing loss is one of the most frequent health issues in industrialized countries. The pathogenesis and molecular mechanisms of hearing loss are still unclear. Histone deacetylases(HDACs) are emerging as key enzymes in many physiological processes, including chromatin remodeling,regulation of transcription, DNA repair, metabolism, genome stability and protein secretion. Recent studies indicated that HDACs are associated with the development and progression of hearing loss. Dysfunction of HDACs could promote the oxidative stress and aging in the inner ear. In light of considering the current stagnation in the development of therapeutic options, the need for new strategies in the treatment of hearing loss has never been so pressing. In this review, we will summarize the reported literatures for HDACs in hearing loss and discuss how HDAC family members show different performances for the possibility of process of diseases development. The possibility of pharmacological intervention on hearing loss opens a novel path in the treatment of hearing loss.展开更多
Non-pharmaceutical interventions(NPIs)have been proven effective in reducing the spread of the coronavirus disease 2019(COVID-19),but their broader impact on gastrointestinal disorders remains poorly studied.Here,we r...Non-pharmaceutical interventions(NPIs)have been proven effective in reducing the spread of the coronavirus disease 2019(COVID-19),but their broader impact on gastrointestinal disorders remains poorly studied.Here,we report an observational analysis and retrospective study that compares the incidence of acute diarrheal diseases in Hangzhou,Zhejiang,China,between 2019 and 2020,with an examination of the antimicrobial resistance and genetic spectrum of non-typhoidal Salmonella(NTS)from 2015 to 2022,before and during the COVID-19 pandemic.Our findings underscore that NPIs related to COVID-19 effectively reduced the incidence of acute diarrhea,with a substantial decrease in most enteric pathogens.Notably,NTS exhibited an unexpected surge.Further genomic investigations of NTS isolates revealed an overall reduction in antimicrobial-resistant(AMR),disinfection-tolerant,and virulent capabilities,but with marked variations detected between human and animal isolates.Additional genome-based analysis confirmed a decrease in the scale of zoonotic transmission in response to NPIs,suggesting particular NTS types may contribute to human infections via alternative pathways.The collective findings manifested that COVID-19-related NPIs had a mixed impact on NTS infections,which may inform AMR NTS mitigation policy.展开更多
基金financially supported by the Science and Technology Innovation Program of Hunan Province,No.2022RC1220(to WP)China Postdoctoral Science Foundation,No.2022M711733(to ZZ)+2 种基金the National Natural Science Foundation of China,No.82160920(to ZZ)Hebei Postdoctoral Scientific Research Project,No.B2022003040(to ZZ)Hunan Flagship Department of Integrated Traditional Chinese and Western Medicine(to WP)。
文摘Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.
基金supported by Zhejiang Provincial Medical Technology Fund, China (No. 2015KYB340)Ningbo Municipal Natural Science Grant (No. 2016A610130)
文摘Hearing loss is one of the most frequent health issues in industrialized countries. The pathogenesis and molecular mechanisms of hearing loss are still unclear. Histone deacetylases(HDACs) are emerging as key enzymes in many physiological processes, including chromatin remodeling,regulation of transcription, DNA repair, metabolism, genome stability and protein secretion. Recent studies indicated that HDACs are associated with the development and progression of hearing loss. Dysfunction of HDACs could promote the oxidative stress and aging in the inner ear. In light of considering the current stagnation in the development of therapeutic options, the need for new strategies in the treatment of hearing loss has never been so pressing. In this review, we will summarize the reported literatures for HDACs in hearing loss and discuss how HDAC family members show different performances for the possibility of process of diseases development. The possibility of pharmacological intervention on hearing loss opens a novel path in the treatment of hearing loss.
基金We would like to thank Annemieke van den Dool(Duke Kunshan University)for the critical reading of the manuscriptThis study was supported by the National Program on the Key Research Project of China(2022YFC2604201)+4 种基金the European Union’s Horizon 2020 Research and Innovation Programme(861917-SAFFI)Zhejiang Provincial Key R&D Program of China(2023C030452022C02024)Zhejiang Provincial Naturaal Science Foundation of China(LZ24C180002)Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Techonology City(2021JJLH0083).
文摘Non-pharmaceutical interventions(NPIs)have been proven effective in reducing the spread of the coronavirus disease 2019(COVID-19),but their broader impact on gastrointestinal disorders remains poorly studied.Here,we report an observational analysis and retrospective study that compares the incidence of acute diarrheal diseases in Hangzhou,Zhejiang,China,between 2019 and 2020,with an examination of the antimicrobial resistance and genetic spectrum of non-typhoidal Salmonella(NTS)from 2015 to 2022,before and during the COVID-19 pandemic.Our findings underscore that NPIs related to COVID-19 effectively reduced the incidence of acute diarrhea,with a substantial decrease in most enteric pathogens.Notably,NTS exhibited an unexpected surge.Further genomic investigations of NTS isolates revealed an overall reduction in antimicrobial-resistant(AMR),disinfection-tolerant,and virulent capabilities,but with marked variations detected between human and animal isolates.Additional genome-based analysis confirmed a decrease in the scale of zoonotic transmission in response to NPIs,suggesting particular NTS types may contribute to human infections via alternative pathways.The collective findings manifested that COVID-19-related NPIs had a mixed impact on NTS infections,which may inform AMR NTS mitigation policy.
