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World Journal of Clinical Cases 2019年第6期7卷 691-704页

作者： Shao-Jie Hu Sha-Sha Jiang Jin Zhang Dan Luo Bo Yu Liang-Yan Yang Hua-Hua Zhong Mei-Wen Yang Li-Yu Liu Fen-Fang Hong Shu-Long Yang Department of Physiology College of MedicineNanchang University Department of Nurse Nanchang University Hospital experimental teaching center Nanchang University

As an irreversible and perennial process,aging is accompanied by functional and morphological declines in organs. Generally,aging liver exhibits a decline in volume and hepatic blood flow. Even with a preeminent regenerative capacity to restore its functions after liver cell loss,its biosynthesis and metabolism abilities decline,and these are difficult to restore to previous standards. Apoptosis is a programmed death process via intrinsic and extrinsic pathways,in which Bcl-2 family proteins and apoptosis-related genes,such as p21 and p53,are involved.Apoptosis inflicts both favorable and adverse influences on liver aging.Apoptosis eliminates transformed abnormal cells but promotes age-related liver diseases,such as nonalcoholic fatty liver disease,liver fibrosis,cirrhosis,and liver cancer. We summarize the roles of apoptosis in liver aging and age-related liver diseases.

关键词： Apoptosis Liver aging Oxidative stress Caloric restriction Cirrhosis

Molecular chaperones in stroke-induced immunosuppression

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Neural Regeneration Research 2023年第12期18卷 2638-2644页

作者： Haoduo Qiao Qing Xu Yunfei Xu Yao Zhao Nina He Jie Tang Jie Zhao Ying Liu Department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Pathophysiology Xiangya School of MedicineCentral South UniversityChangshaHunan ProvinceChina Sepsis Translational medicine Key Laboratory of Hunan Province ChangshaHunan ProvinceChina National Medicine Functional Experimental Teaching Center ChangshaHunan ProvinceChina Department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Stroke-induced immunosuppression is a process that leads to peripheral suppression of the immune system after a stroke and belongs to the central nervous system injury-induced immunosuppressive syndrome.Stroke-induced immunosuppression leads to increased susceptibility to post-stroke infections,such as urinary tract infections and stroke-associated pneumonia,worsening prognosis.Molecular chaperones are a large class of proteins that are able to maintain proteostasis by directing the folding of nascent polypeptide chains,refolding misfolded proteins,and targeting misfolded proteins for degradation.Various molecular chaperones have been shown to play roles in stroke-induced immunosuppression by modulating the activity of other molecular chaperones,cochaperones,and their associated pathways.This review summarizes the role of molecular chaperones in stroke-induced immunosuppression and discusses new approaches to restore host immune defense after stroke.

关键词： Hsp70 Hsp72 Hsp90 HspB5 hypothalamic-pituitary-adrenal axis molecular chaperones neuroprotection stroke stroke-induced immunosuppression sympathetic nervous system

Responsive changes of rumen microbiome and metabolome in dairy cows with different susceptibility to subacute ruminal acidosis

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Animal Nutrition 2022年第1期8卷 331-340页

作者： Tao Zhang Yingyu Mu Ruiyang Zhang Yanfeng Xue Changzheng Guo Wangpan Qi Jiyou Zhang Shengyong Mao national center for International Research on Animal Gut Nutrition National Experimental Teaching Demonstration Center of Animal ScienceCentre for Ruminant Nutrition and Feed Technology ResearchCollege of Animal Science and TechnologyNanjing Agricultural UniversityNanjing210095China College of Animal Science and Veterinary medicine Shenyang Agricultural UniversityShenyang110866China College of Animal Science and Technology Shihezi UniversityShihezi832000China

Subacute ruminal acidosis(SARA)represents one of the most important digestive disorders in intensive dairy farms,and dairy cows are individually different in the severity of SARA risk.The objectives of the current study were to investigate differences in the ruminal bacterial community and metabolome in dairy cattle with different susceptibility to SARA.In the present study,12 cows were initially enrolled in the experiment.Based on average ruminal pH,4 cows with the lowest ruminal pH were assigned to the susceptible group(SUS,pH=5.76,n=4)and 4 cows with the highest ruminal pH assigned to the tolerant group(TOL,pH=6.10,n=4).Rumen contents from susceptible(SUS,n=4)and tolerant(TOL,n=4)dairy cows were collected through rumen fistula to systematically reveal the rumen microbial and metabolic alterations of dairy cows with different susceptibility to SARA using multi-omics approaches(16S and 18S rRNA gene sequencing and metabolome).The results showed that despite being fed the same diet,SUS cows had lower ruminal pH and higher concentrations of total volatile fatty acids(VFA)and propionate than TOL cows(P0.05).The principal coordinates analysis based on the analysis of molecular variance indicated a significant difference in bacterial composition between the two groups(P=0.01).More specifically,the relative abundance of starch-degrading bacteria(Prevotella spp.)was greater(P0.05).Metabolomics analysis revealed that the concentrations of organic acids(such as lactic acid),biogenic amines(such as histamine),and bacterial degradation prod

关键词： Subacute ruminal acidosis Microbiome Metabolome Dairy cows

Jianpi Qingchang decoction regulates intestinal motility of dextran sulfate sodium-induced colitis through reducing autophagy of interstitial cells of Cajal

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World Journal of Gastroenterology 2017年第26期23卷 4724-4734页

作者： Yan-Cheng Dai Lie Zheng Ya-Li Zhang Xuan Chen De-Liang Chen Li-Juan Wang Zhi-Peng Tang Department of Gastroenterology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Institute of Digestive Diseases Shanghai University of Traditional Chinese Medicine experimental teaching center Shanghai University of Traditional Chinese Medicine

AIM To investigate the underlying effect of Jianpi Qingchang decoction(JQD) regulating intestinal motility of dextran sulfate sodium(DSS)-induced colitis in mice. METHODS C57BL/6 mice were randomly divided into four groups: the control group, the DSS group, the JQD group, and the 5-aminosalicylic acid group. Except for the control group, colitis was induced in other groups by giving distilled water containing 5% DSS. Seven days after modeling, the mice were administered corresponding drugs intragastrically. The mice were sacrificed on the 15^(th) day. The disease activity index, macroscopic and histopathologic lesions, and ultrastructure of colon interstitial cells of Cajal(ICC) were observed. The levels of tumor necrosis factor-alpha(TNF-α), interleukin(IL)-1β, IL-10 and interferon gamma(IFN-γ), the expression of nuclear factor-kappa B(NF-κB) p65, c-kit, microtubule-associated protein 1 light chain 3(LC3-Ⅱ) and Beclin-l m RNA, and the colonic smooth muscle tension were assessed. RESULTS Acute inflammation occurred in the mice administered DSS. Compared with the control group, the levels of IL-1β, TNF-α, IL-10 and IFN-γ, the expression of LC3-Ⅱ, Beclin-1 and NF-κB p65 m RNA, and the contractile frequency increased(P < 0.05), the expression of c-kit m RNA and the colonic smooth muscle contractile amplitude decreased in the DSS group(P < 0.05). Compared with the DSS group, the levels of IL-10 and IFN-γ, the expression of c-kit m RNA, and the colonic smooth muscle contractile amplitude increased(P < 0.05), the levels of TNF-α and IL-1β, the expression of LC3-Ⅱ, Beclin-1 and NF-κB p65 m RNA, and the contractile frequency decreased in the JQD group(P < 0.05).CONCLUSION JQD can regulate the intestinal motility of DSS-induced colitis in mice through suppressing intestinal inflammatory cascade reaction, reducing autophagy of ICC, and regulating the network path of ICC/smooth muscle cells.

关键词： Intestinal motility Interstitial cells of Cajal Autophagy ulcerative colitis Jianpi Qingchang decoction

Regulation of serotonin production by specific microbes from piglet gut

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Journal of Animal Science and Biotechnology 2023年第6期14卷 2539-2553页

作者： Ziyu Liu Yidan Ling Yu Peng Shuibing Han Yuting Ren Yujia Jing Wenlu Fan Yong Su Chunlong Mu Weiyun Zhu Laboratory of Gastrointestinal Microbiology College of Animal Science and TechnologyNanjing Agricultural UniversityNanjingChina. national center for International Research on Animal Gut Nutrition National Experimental Teaching Demonstration Center of Animal ScienceNanjing Agricultural UniversityNanjingChina. Hubei CAT Biological Technology Co. Ltd.WuhanChina. Department of Biochemistry and Molecular Biology Cumming School of MedicineUniversity of CalgaryCalgaryCanada

Background Serotonin is an important signaling molecule that regulates secretory and sensory functions in the gut.Gut microbiota has been demonstrated to affect serotonin synthesis in rodent models.However,how gut microbes regulate intestinal serotonin production in piglets remains vague.To investigate the relationship between microbiota and serotonin specifically in the colon,microbial composition and serotonin concentration were analyzed in ileum-cannulated piglets subjected to antibiotic infusion from the ileum when comparing with saline infusion.Microbes that correlated positively with serotonin production were isolated from piglet colon and were further used to investi-gate the regulation mechanisms on serotonin production in IPEC-J2 and a putative enterochromaffin cell line RIN-14B cells.Results Antibiotic infusion increased quantities of Lactobacillus amylovorus(LA)that positively correlated with increased serotonin concentrations in the colon,while no effects observed for Limosilactobacillus reuteri(LR).To understand how microbes regulate serotonin,representative strains of LA,LR,and Streptococcus alactolyticus(SA,enriched in feces from prior observation)were selected for cell culture studies.Compared to the control group,LA,LR and SA supernatants significantly up-regulated tryptophan hydroxylase 1(TPH1)expression and promoted serotonin production in IPEC-J2 cells,while in RIN-14B cells only LA exerted similar action.To investigate potential mechanisms mediated by microbe-derived molecules,microbial metabolites including lactate,acetate,glutamine,andγ-aminobutyric acid were selected for cell treatment based on computational and metabolite profiling in bacte-rial supernatant.Among these metabolites,acetate upregulated the expression of free fatty acid receptor 3 and TPH1 while downregulated indoleamine 2,3-dioxygenase 1.Similar effects were also recapitulated when treating the cells with AR420626,an agonist targeting free fatty acid receptor 3.Conclusions Overall,these results suggest that Lactobacillus am

关键词： Colon Lactobacillus Microbial metabolites Serotonin

Key questions about the checkpoint blockade-are microRNAs an answer?

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Cancer Biology & medicine 2018年第2期15卷 103-115页

作者： Mihnea Dragomir Baoqing Chen Xiao Fu George A.Calin Department of experimental Therapeutics The University of Texas MD Anderson Cancer Center Research center for functional Genomics Biomedicine and Translational MedicineIuliu Hatieganu University of Medicine and Pharmacy Department of Surgery Fundeni Clinical HospitalCarol Davila University of Medicine and Pharmacy center for RNA Interference and Non-coding RNAs The University of Texas MD Anderson Cancer Center

The introduction of immune-checkpoint blockade in the cancer therapy led to a paradigm change of the management of late stage cancers. There are already multiple FDA approved checkpoint inhibitors and many other agents are undergoing phase 2 and early phase 3 clinical trials. The therapeutic indication of immune checkpoint inhibitors expanded in the last years, but still remains unclear who can benefit. Micro RNAs are small RNAs with no coding potential. By complementary pairing to the 3' untranslated region of messenger RNA, microRNAs exert posttranscriptional control of protein expression. A network of microRNAs directly and indirectly controls the expression of checkpoint receptors and several microRNAs can target multiple checkpoint molecules,mimicking the therapeutic effect of a combined immune checkpoint blockade. In this review, we will describe the microRNAs that control the expression of immune checkpoints and we will present four specific issues of the immune checkpoint therapy in cancer:(1) imprecise therapeutic indication,(2) difficult response evaluation,(3) numerous immunologic adverse-events, and(4)the absence of response to immune therapy. Finally, we propose microRNAs as possible solutions for these pitfalls. We consider that in the near future microRNAs could become important therapeutic partners of the immune checkpoint therapy.

关键词：检查点封锁癌症治疗询问免疫力治疗学 RNA 管理局

Rapid detection of pesticide residues in Chinese herbal medicines by molecularly imprinted membrane electrospray ionization mass spectrometry

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Chinese Chemical Letters 2021年第7期32卷 2174-2178页

作者： Chunmei Wu Tianyi Li Dongju Li Shanshan Jia Jianmei Huang Haimin Lei Mei Zhang School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 102488China national Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China experimental teaching center School of Basic Medical SciencesFudan UniversityShanghai 200032China

Chinese herbal medicines(CHMs)play an increasingly important role in the field of medicine and affects public health in the world.Although more and more strict has been employed to ensure the quality and safety of CHMs,pesticide residues in CHMs remain a serious issue and are the bottleneck for the global development of CHMs.In this work,we applied molecularly imprinted membrane electrospray mass spectrometry(MIM-ESI MS)for rapid detecting 4 classes of pesticide residues in CHMs,including organophosphorus(OPP),carbamates,pyrethroids and neonicotinoids in CHMs.Compared with our previous ambient ionization method MESI,MIM-ESI is capable of achieving a~50-fold increase in the detection limit of conventional analytical methods owing to the specificity recognition and unique enrichment of MIM.The optimal experimental conditions were determined,and the method was further validated for its sensitivity and specificity.Our data showed that MIM-ESI MS is applicable for the direct quantitation of pesticide residues in CHMs.This detection technology may help to ensure the quality of CHMs in the future.

关键词： Pesticides residue Chinese herbal medicines(CHMs) Rapid detection Molecularly imprinted membrane Ambient ionization Mass spectrometry

Progress in active compounds effective on ulcerative colitis from Chinese medicines

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Chinese Journal of Natural medicines 2019年第2期17卷 81-102页

作者： CAO Si-Yu YE Sheng-Jie WANG Wei-Wei WANG Bing ZHANG Tong PU Yi-Qiong School of Pharmacy Shanghai University of Traditional Chinese Medicine Experiment center for teaching and Learning Shanghai University of Traditional Chinese Medicine

Ulcerative colitis(UC), a chronic inflammatory disease affecting the colon, has a rising incidence worldwide. The known pathogenesis is multifactorial and involves genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. Nowadays, the drugs for UC include 5-aminosalicylic acid, steroids, and immunosuppressants. Long-term use of these drugs, however, may cause several side effects, such as hepatic and renal toxicity, drug resistance and allergic reactions. Moreover, the use of traditional Chinese medicine(TCM) in the treatment of UC shows significantly positive effects, low recurrence rate, few side effects and other obvious advantages. This paper summarizes several kinds of active compounds used in the experimental research of anti-UC effects extracted from TCM, mainly including flavonoids, acids, terpenoids, phenols, alkaloids, quinones, and bile acids from some animal medicines. It is found that the anti-UC activities are mainly focused on targeting inflammation or oxidative stress, which is associated with increasing the levels of anti-inflammatory cytokine(IL-4, IL-10, SOD), suppressing the levels of pro-inflammatory cytokines(TNF-α, IL-1β, IL-6, IL-8, IL-23, NF-κB, NO), reducing the activity of MPO, MDA, IFN-γ, and iNOS. This review may offer valuable reference for UC-related studies on the compounds from natural medicines.

关键词： Ulcerative colitis Chinese medicine Flavonoids Terpenoids Alkaloids

Sleep disorders in Alzheimer’s disease:the predictive roles and potential mechanisms

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Neural Regeneration Research 2021年第10期16卷 1965-1972页

作者： Huang Kuang Yu-Ge Zhu Zhi-Feng Zhou Mei-Wen Yang Fen-Fang Hong Shu-Long Yang Department of Physiology College of MedicineNanchang UniversityNanchangJiangxi ProvinceChina Department of Nurse Nanchang University HospitalNanchangJiangxi ProvinceChina Department of experimental teaching center Nanchang UniversityNanchangJiangxi ProvinceChina

Sleep disorders are common in patients with Alzheimer’s disease,and can even occur in patients with amnestic mild cognitive impairment,which appears before Alzheimer’s disease.Sleep disorders further impair cognitive function and accelerate the accumulation of amyloid-βand tau in patients with Alzheimer’s disease.At present,sleep disorders are considered as a risk factor for,and may be a predictor of,Alzheimer’s disease development.Given that sleep disorders are encountered in other types of dementia and psychiatric conditions,sleep-related biomarkers to predict Alzheimer’s disease need to have high specificity and sensitivity.Here,we summarize the major Alzheimer’s disease-specific sleep changes,including abnormal non-rapid eye movement sleep,sleep fragmentation,and sleep-disordered breathing,and describe their ability to predict the onset of Alzheimer’s disease at its earliest stages.Understanding the mechanisms underlying these sleep changes is also crucial if we are to clarify the role of sleep in Alzheimer’s disease.This paper therefore explores some potential mechanisms that may contribute to sleep disorders,including dysregulation of the orexinergic,glutamatergic,andγ-aminobutyric acid systems and the circadian rhythm,together with amyloid-βaccumulation.This review could provide a theoretical basis for the development of drugs to treat Alzheimer’s disease based on sleep disorders in future work.

关键词： Alzheimer’s disease amyloid-βaccumulation circadian rhythm GABAergic system glutamatergic system non-rapid eye movement sleep orexinergic system sleep disorders sleep fragmentation sleep-disordered breathing