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Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

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Neural Regeneration Research 2025年第9期20卷 2633-2644页

作者： Zhimin Long Chuanhua Ge Yueyang Zhao Yuanjie Liu Qinghua Zeng Qing Tang Zhifang Dong Guiqiong He Institute of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqingChina Department of Anatomy Chongqing Medical UniversityChongqingChina Department of Physiology Chongqing Medical UniversityChongqingChina Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqingChina Ministry of Education Key Laboratory of Child Development and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina National Clinical Research Center for Child Health and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque ***,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's *** acetylation/deacetylation plays a central role in lysosomal ***,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's *** rthermore,we found that treatment with valproic acid markedly enhanced *** clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's *** findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

关键词： Alzheimer's disease amyloid-β APP/PS1 mice autophagy cognitive impairment histone deacetylase 6 lysosomal acidification microtubule acetylation valproic acid V-ATPase

Characteristics of fecal microbiota in non-alcoholic fatty liver disease patients

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Science China(Life Sciences) 2018年第7期61卷 770-778页

作者： Fan Li Gang Sun Zikai Wang Wenming Wu He Guo Lihua Peng Lili Wu Xu Guo Yunsheng Yang Department of Gastroenterology and Hepatology Chinese PLA General Hospital Department of Liver Disease PLA Army General Hospital Department of Gastroenterology General Hospital of Jinan Military Region

This study was designed to investigate the gut microbiota of patients with non-alcoholic fatty liver disease. The inclusive and exclusive criteria for NAFLD patients and healthy subjects were formulated, and detailed clinical data were collected. The genomic DNA of stool samples were extracted for 16 S r DNA sequencing, and the amplified V4-region was sequenced on the Illumina Miseq platform. Metastats analysis was performed to identify the differential taxa between the groups. Redundancy analysis was used to evaluate the association between gut microbial structure and clinical variables. Thirty NAFLD patients and37 healthy controls were involved. The 16 S r DNA sequencing showed that there was a dramatic variability of the fecal microbiota among all the individuals. Metastats analysis identified eight families and 12 genera with significant differences between the two groups. When some clinical parameters, such as waist-to-hip ratio(WHR) and homeostasis model assessment of insulin resistance(HOMA-IR), were enrolled in Redundancy analysis, the distribution of the two group of samples was obviously changed. The compositional shifts in fecal bacterial communities of NAFLD patients from the healthy controls were mainly at family or genus levels. According to our Redundancy analysis, insulin resistance and obesity might be closely related to both NAFLD phenotype and intestinal microecology.

关键词： non-alcoholic fatty liver disease bacterial microbiota 16S rDNA

Recurrent orbital space-occupying lesions:a clinicopathologic study of 253 cases

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Chinese Journal of Cancer Research 2013年第4期25卷 423-429页

作者： Weiqiang Tang Yan Hei Lihua Xiao Department of Ophthalmology the First Hospital Affiliated to PLA General Hospital Institute of Orbital Diseases the General Hospital of the Armed Police Force

Objective：To analyze the clinical features,histopathologic classification and frequencies of various types of recurrent orbital space-occupying ***：A retrospective study was carried out in 253 consecutive patients with recurrent orbital spaceoccupying lesions treated by surgical excision in the Institute of Orbital Diseases,the general hospital of the Armed Police Force from January 2009 to December ***：The patients included 123 males and 130 females aged 2 to 78 years（mean,36.2 years）,and the last recurrence interval after operation ranged from 1 month to 40 years（median,4.75 years）.Of all the cases,159（62.8%）,65（25.7%）,20（7.9%）,8（3.2%） and 1（0.4%） had previously experienced once,twice,three,four and six times of surgeries,*** them,29（11.5%） cases had recurred 3 times or over,and 37（14.6%） cases got recurrence in 10 or more years *** of the patients with local recurrence presented with various clinical manifestations,while 31（12.3%） cases were *** hundred and thirty-one（91.3%） cases underwent surgical removal of the recurrent orbital lesions,and another 22（8.7%） cases had to receive the exenteration of *** of these recurrent orbital lesions after operation were as follows：lacrimal gland tumors,65（25.7%） cases;vasogenic diseases,54（21.3%） cases;neurogenic tumors,42（16.6%） cases;secondary tumors,24（9.5%） cases;orbital inflammation,21（8.3%） cases;myogenic tumors,14（5.5%） cases;fibrous and adipose tumors,12（4.7%） cases;lympho-hematopoietic tumors,7（2.8%） cases;bone or cartilage tumors,7（2.8%） cases;orbital cysts,6（2.4%） cases;and indefinitely differentiated tumor,1（0.4%） *** 10 top histopathologic diagnoses were lacrimal gland pleomorphic adenoma,hemangiolymphangioma,lacrimal gland adenoid cystic carcinoma,meningioma,inflammatory pseudotumor,neurofibroma,sebaceous gland carcinoma,vascular malformation,rhabdomyosarcoma and ***：The variety of recurrent orbital lesions a

关键词： Orbital space-occupying lesions recurrence lacrimal gland epithelial tumor vascular malformation orbital inflammatory lesions

Expression of Wnt and NCX1 and its correlation with cardiomyocyte apoptosis in mouse with myocardial hypertrophy

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Asian Pacific Journal of Tropical Medicine 2015年第11期8卷 909-914页

作者： Jing He Yi Cai Leiming Luo Rong Wang Department of general Surgery PLA General Hospital

Objective:To study the correlation between expression of Wnt and NCXl and cardiomyocyte apoptosis in mouse with myocardial ***:C57B/16 male mice were given the subcutaneous injection of 1 mg/kg isoprenaline to build the myocardial hypertrophy *** 14 d of model building,mice were executed by cervical vertebra *** ratio of heart weight/body weight(HW/BW) and heart weight/tibia length(HW/TL) was observed and proved using HE staining mat detected the size of eaidiomyocytes.40 male C57B/16 mice were randomly divided into the sham group(normal saline) and model group(isoprenaline),with 20 mice in each *** terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was applied to detect the cardiomyocyte apoptosis;while Western blot and immunohistochemistry were employed to detect the expression of Wnt and ***,the correlation between these two proteins and cardiomyocyte apoptosis was ***:Compared with the sham group,the ratio of HW/BW and HW/TL was increased in the model group,as well as the bigger and hypertrophied cardiomyocytes,decreased number and increased apoptosis of eaidiomyocytes,and increased positive expression of Wnt3 a,WntSa and NCXl in the cardiac muscle ***,there was positive correlation between the expression of Wnt and NCXl and the cardiomyocyte ***:The expression of Wnt3 a,Wnt5a and NCXl in mouse with myocardial hypertrophy is increased and positively correlated with the cardiomyocyte apoptosis.

关键词： Myocardial hypertrophy Wnt NCX1 Cardiomyocyte apop

Irreversible electroporation for metastatic pancreatic carcinoma with liver metastasis:What does the evidence say

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World Journal of Clinical Cases 2025年第3期13卷 30-34页

作者： Ranit Seal Akash Bararia Bitan Kumar Chattopadhyay Nilabja Sikdar Department of general Surgery IPGME&R and SSKM HospitalKolkata 700020West BengalIndia Human Genetics Unit Indian Statistical InstituteKolkata 700108West BengalIndia Estaurine and Coastal Studies Foundation Howrah 711101India

Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some ***,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy *** studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.

关键词： Irreversible electroporation Locally advanced pancreatic carcinoma Metastatic pancreatic carcinoma Advanced pancreatic carcinoma Chemotherapy

Human umbilical cord Wharton's jelly-derived oligodendrocyte precursor-like cells for axon and myelin sheath regeneration

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Neural Regeneration Research 2013年第10期8卷 890-899页

作者： Hong Chen Yan Zhang Zhijun Yang Hongtian Zhang Department of Anesthesiology Military General Hospital of Beijing PLA Affiliated Bayi Brain hospital Military General Hospital of Beijing PLA

Human umbilical mesenchymal stem cells from Wharton＇s jelly of the umbilical cord were induced to differentiate into oligodendrocyte precursor-like cells in vitro. Oligodendrocyte precursor cells were transplanted into contused rat spinal cords. Immunofluorescence double staining indicated that transplanted cells survived in injured spinal cord, and differentiated into mature and immature oligodendrocyte precursor cells. Biotinylated dextran amine tracing results showed that cell transplantation promoted a higher density of the corticospinal tract in the central and caudal parts of the injured spinal cord. Luxol fast blue and toluidine blue staining showed that the volume of residual myelin was significantly increased at 1 and 2 mm rostral and caudal to the lesion epicenter after cell transplantation. Furthermore, immunofluorescence staining verified that the newly regenerated myelin sheath was derived from the central nervous system. Basso, Beattie and Bresnahan testing showed an evident behavioral recovery. These results suggest that human umbilical mesenchymal stem cell-derived oligodendrocyte precursor cells promote the regeneration of spinal axons and myelin sheaths.

关键词： neural regeneration stem cells spinal cord injury Wharton's jelly human umbilical mesenchymalstem cells oligodendrocyte precursor-like cells axon myelin sheath nerve repair grants-supportedpaper neuroregeneration

Protective effects of ginsenoside Rg1 against hydrogen peroxide-induced injury in human neuroblastoma cells

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Neural Regeneration Research 2016年第7期11卷 1159-1164页

作者： Zhi-gao Sun Li-ping Chen Fa-wei Wang Cheng-yong Xu Miao Geng Department of Traditional Chinese Medicine Hainan Branch Hospital of Chinese PLA General Hospital Department of Traditional Chinese Medicine Chinese PLA General Hospital Institute of Gerontology Chinese PLA General Hospital

The active ingredient of ginseng,ginsenosides Rg1,has been shown to scavenge free radicals and improve antioxidant *** study hypothesized that ginsenosides Rg1 has a protective role in human neuroblastoma cells injured by *** Rg1 at different concentrations（50 and 100 μM） was used to treat H2O2（150 μM）-injured SH-SY5 Y *** demonstrated that ginsenoside Rg1 elevated the survival rate of SH-SY5 Y cells injured by H2O2,diminished the amount of leaked lactate dehydrogenase,and increased superoxide dismutase *** Rg1 effectively suppressed caspase-3 immunoreactivity,and contributed to heat shock protein 70 gene expression,in a dose-dependent *** results indicate that ginsenoside Rg1 has protective effects on SH-SY5 Y cells injured by H2O2 and that its mechanism of action is associated with anti-oxidation and the inhibition of apoptosis.

关键词： ginsenoside neuroblastoma peroxide injured protective caspase dehydrogenase suppressed manner antioxidant

Fecal microbiota in pouchitis and ulcerative colitis

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World Journal of Gastroenterology 2016年第40期22卷 8929-8939页

作者： Kai-Yu Li Jian-Lin Wang Jiang-Peng Wei Sen-Yang Gao Ying-Ying Zhang Li-Tian Wang Gang Liu Department of general Surgery Tianjin Medical University General Hospital Department of general Surgery Tianjin NanKai Hospital

AIM To investigate the changes in microbiota in feces of patients with ulcerative colitis(UC) and pouchitis using genomic *** Fecal samples were obtained from UC patients with or without an ileal pouch-anal anastomosis(IPAA) procedure, as well as healthy controls. The touchdown polymerase chain reaction technique was used to amplify the whole V3 region of the 16 S r RNA gene, which was transcribed from DNA extracted from fecal samples. Denaturing gradient gel electrophoresis was used to separate the amplicons. The band profiles and similarity indices were analyzed digitally. The predominant microbiota in different groups was confirmed by sequencing the 16 S rR NA gene. RESULTS Microbial biodiversity in the healthy controls was significantly higher compared with the UC groups(P < 0.001) and IPAA groups(P < 0.001). Compared with healthy controls, the UC patients in remission and those in the mildly active stage, the predominant species in patients with moderately and severely active UC changed obviously. In addition, the proportion of the dominant microbiota, which was negatively correlated with the disease activity of UC(r =-6.591, P < 0.01),was decreased in pouchitis patients. The numbers of two types of bacteria, Faecalibacterium prausnitzii and Eubacterium rectale, were reduced in UC. Patients with pouchitis had an altered microbiota composition compared with UC patients. The microbiota from pouchitis patients was less diverse than that from severely active UC patients. Sequencing results showed that similar microbiota, such as Clostridium perfringens, were shared in both UC and *** Less diverse fecal microbiota was present in patients with UC and pouchitis. Increased C. perfringens in feces suggest its role in the exacerbation of UC and pouchitis.

关键词： Pouchitis Intestinal flora Ulcerative colitis Disease activity index Ileal pouch-anal anastomosis

Effect of toll-like receptor 3 agonist poly I:C on intestinal mucosa and epithelial barrier function in mouse models of acute colitis

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World Journal of Gastroenterology 2017年第6期23卷 999-1009页

作者： Hong-Wei Zhao Yue-Hong Yue Hua Han Xiu-Li Chen Yong-Gang Lu Ji-Min Zheng Hong-Tao Hou Xiao-Meng Lang Li-Li He Qi-Lu Hu Zi-Qian Dun Department of Gastroenterology Hebei General Hospital Department of Neurology Hebei General Hospital Department of Obstetrics and Gynecology Hebei General Hospital Research Center The Fifth Hospital of Shijiazhuang Department of Clinical Laboratory Hebei General Hospital Department of Spleen and Stomach Hebei Province Hospital of Traditional Chinese Medicine Department of Gerontology Hebei General Hospital Department of Oncology Hebei General Hospital Department of general Internal Medicine The Fifth Hospital of Shijiazhuang

AIM To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis. METHODS Thirty C57BL/6 mice were given either regular drinking water (control group) or 2% (w/v) DSS drinking water (model and poly I:C groups) ad libitum for 7 d. Poly I:C was administrated subcutaneously (20 mu g/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-a (TNF-alpha), interleukin 17 (IL-17) and interferon-. (IFN-gamma). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeled-dextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction (TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The mRNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-qPCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-alpha, IL-17 and I

关键词： Dextran sulfate sodium-induced acute colitis Mucosal injury Epithelial barrier disruption Tight junction Poly I:C