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Calcium/calcimimetic via calcium-sensing receptor ameliorates cholera toxin-induced secretory diarrhea in mice

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World Journal of gastroenterology 2024年第3期30卷 268-279页

作者： Lie-Qi Tang Johnathan Fraebel Shi Jin Steven P Winesett Jane Harrell Wen-Han Chang Sam Xianjun Cheng department of Pediatrics University of FloridaGainesvilleFL 32610United States College of Medicine University of FloridaGainesvilleFL 32610United States applied physiology and kinesiology University of FloridaGainesvilleFL 32610United States brain rehabilitation research Center Malcom Randall VA Medical CenterGainesvilleFL 32610United States department of Medicine Endocrine Research UnitVeterans Affairs Medical CenterUniversity of CaliforniaSan FranciscoSan FranciscoCA 94121United States department of Pediatric gastroenterology Hepatologyand NutritionUniversity of Florida Shands Children’s HospitalGainesvilleFL 32608United States

bACKgrOUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous ***-sensing receptor(CaSr)inhibits both *** latter has been well documented in vitro but not in *** hypothesis to be tested was that activating CaSr inhibits diarrhea in *** To determine whether CaSr agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in *** CTX was given orally to C57bL/6 mice to induce *** and calci-mimetic r568 were used to activate *** maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(OrS),whereas r568 was applied serosally using an intraperitoneal *** verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSr *** outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight *** CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSr,neither in content nor in ***,calcium and r568 were each able to ameliorate diarrhea when applied to diseased *** CaSr involvement is suggested by gene knockout experiments where the anti-diarrheal actions of r568 were lost in intestinal epithelial CaSr knockouts(villinCre/Casrflox/flox)and neuronal CaSr knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global *** advances in diarrhea research,few have been made in the realm of diarrhea *** therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by *** is no cost-effective therapeutic for *** and other studies suggest that adding calcium to OrS or using calcimimetics to activate intestinal CaSr might

关键词： Cholera Enteric nervous system Secretory diarrhea Oral rehydration solution Calcium-sensing receptor gene knockout

Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques,levels of LDL,and cardiorespiratory fitness in the elderly

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Journal of Sport and Health Science 2024年第3期13卷 288-296,I0002页

作者： Tim böttrich Pascal bauer Vincent gröβer Magdalena Huber Hartmann raifer Torsten Frech Svenja Nolte Theresa Dombrowski Franz Cemic Natascha Sommer robert ringseis Klaus Eder Karsten Krüger Christopher Weyh department of Exercise physiology and Sports Therapy Institute of Sports ScienceJustus-Liebig-UniversityGiessen 35394Germany department of Cardiology and Angiology Justus-Liebig-University GiessenGiessen 35392Germany Institute for Systems Immunology Center for Tumor und ImmunologyMarburg 35032Germany TH Mittelhessen Department of Computer ScienceUniversity of Applied Sciences GiessenGiessen 35390Germany department of Internal Medicine Universities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Giessen 35394Germany Excellence Cluster Cardio-Pulmonary Institute(CPI) Justus-Liebig UniversityGiessen 35394Germany Institute of Animal Nutrition and Nutrition physiology Justus-Liebig-University GiessenGiessen 35390Germany

background:Atherosclerosis forms the pathological basis for the development of cardiovascular *** pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early *** is evidence that regulatory T cells(Tregs)are involved in the development of ***,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated ***:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking *** of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were ***,tests were conducted to assess blood lipids and determine glucose *** of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow *** were categorized according to atherosclerotic plaque *** and logistic regression models were used to analyze associations between ***:SAP was detected in a total of 29 *** participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(Or)=1.20(95%confidence interval(95%CI):1.011.42))and

关键词： Cardiorespiratory fitness Elderly regulatory T cells Subclinical atherosclerosis

Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging

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Science China(Life Sciences) 2024年第4期67卷 745-764页

作者： Shujie Chen Liujing Huang bingdong Liu Huimin Duan Ze Li Yifan Liu Hu Li Xiang Fu Jingchao Lin Yinlan Xu Li Liu Dan Wan Yulong Yin Liwei Xie department of Endocrinology and Metabolism Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China State Key Laboratory of applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and ApplicationGuangdong Open Laboratory of Applied MicrobiologyInstitute of MicrobiologyGuangdong Academy of SciencesGuangzhou 510070China School of Public Health Xinxiang Medical UniversityXinxiang 453003China department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Metabo-Profile biotechnology(Shanghai)Co.Ltd. Shanghai 201315China Institute of Aging research Guangdong Provincial Key Laboratory of Medical Molecular DiagnosticsSchool of Medical TechnologyGuangdong Medical UniversityDongguan 524023China department of rehabilitation Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510000China Laboratory of Animal Nutritional physiology and Metabolic Process Key Laboratory of Agro-ecological Processes in Subtropical RegionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China bioland Laboratory Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhou 510005China

The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle ***,the interplay between gut microbiota/metabolites and the regulation of satellite cell(SC)homeostasis,particularly during aging,remains *** propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development,regeneration,and aging *** investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice,leads to the activation of SCs or a significant reduction in the total ***,employing multi-omics(e.g.,rNA-seq,16S r rNA gene sequencing,and metabolomics)and bioinformatic analysis,we demonstrate that the reduced butyrate levels,alongside the gut microbial dysbiosis,could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle ***,butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota,potentially by inhibiting the proliferation and differentiation of SCs/*** butyrate effect is likely facilitated through the monocarboxylate transporter 1(Mct1),a lactate transporter enriched on membranes of SCs and *** a result,butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle *** findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.

关键词： gut microbiota aging satellite cells butyrate Slc16a1(Mct1)

Chronic training status affects muscle excitation of the vastus lateralis during repeated contractions

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运动医学与健康科学(英文) 2023年第1期5卷 42-49页

作者： Sunggun Jeon Stephanie A.Sontag Trent J.Herda Michael A.Trevino applied Neuromuscular physiology Laboratory Department of KinesiologyApplied Healthand RecreationOklahoma State UniversityStillwaterOKUSA Neuromechanics Laboratory Department of HealthSportand Exercise SciencesThe University of KansasLawrenceKSUSA

This study examined electromyographic amplitude(EMgrMS)-force relationships during repeated submaximal knee extensor muscle actions among chronic aerobically-(AT),resistance-trained(rT),and sedentary(SED)*** adults(5/group)attempted 20 isometric trapezoidal muscle actions at 50%of maximal *** electromyography(EMg)was recorded from vastus lateralis(VL)during the muscle *** the first and last successfully completed contractions,linear regression models were fit to the log-transformed EMgrMS-force relationships during the linearly increasing and decreasing segments,and the b terms(slope)and a terms(antilog of y-intercept)were *** was averaged during steady *** the AT completed all 20 muscle *** the first contraction,the b terms for rT(1.3010.197)were greater than AT(0.9100.123;p?0.008)and SED(0.9120.162;p?0.008)during the linearly increasing segment,and in comparison to the linearly decreasing segment(1.0180.139;p?0.014),*** the last contraction,the b terms for rT were greater than AT during the linearly increasing(rT?1.3730.353;AT?0.8830.129;p?0.018)and decreasing(rT?1.5260.328;AT?0.9700.223;p?0.010)*** addition,the b terms for SED increased from the linearly increasing(0.9680.144)to decreasing segment(1.2680.126;p?0.015).There were no training,segment,or contraction differences for the a *** during steady force increased from the first-([64.0851.68]μV)to last-contraction([86.7349.55]μV;p?0.001)collapsed across training *** b terms differentiated the rate of change for EMgrMS with increments in force among training groups,indicating greater muscle excitation to the motoneuron pool was necessary for the rT than AT during the linearly increasing and decreasing segments of a repetitive task.

关键词： Electromyography Fatigue Isometric trapezoidal muscle action Motor unit control properties Natural log-transformed model Vastus lateralis

Mechanical regulation of lipid and sugar absorption by Piezo1 in enterocytes

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Acta Pharmaceutica Sinica b 2024年第8期14卷 3576-3590页

作者： Tian Tao Qing Shu Yawen Zhao Wenying guo Jinting Wang Yuhao Shi Shiqi Jia Hening Zhai Hui Chen Cunchuan Wang geyang Xu department of physiology School of MedicineJinan UniversityGuangzhou 510632China department of Metabolic and bariatric Surgery the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Endoscopy Center the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China biotherapy Center Cell-gene Therapy Translational Medicine Research Centerthe Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Key Laboratory of Viral Pathogenesis&Infection Prevention and Control(Jinan University) Ministry of EducationGuangzhou 510632China

Obesity is primarily caused by excessive intake as well as absorption of sugar and *** surge in distention pressure and intestinal motility accelerates the absorption of *** response of intestinal epithelial cells to mechanical stimulation is not fully ***1,a mechanosensitive ion channel,is widely expressed throughout the digestive ***,its function in intestinal nutrient absorption is not yet *** our study,excessive lipid deposition was observed in the duodenum of obese patients,while duodenal Piezo1-CaMKK2-AMPKa was decreased when compared to normal-weight *** high-fat diet condition,the Piezo1iKO mice exhibited abnormally elevated sugar and lipid absorption as well as severe lipid deposition in the duodenum and *** phenotypes were mainly caused by the inhibition of duodenal CaMKK2-AMPKa and the upregulation of SgLT1 and *** contrast,Yoda1,a Piezo1 agonist,was found to reduce intestinal lipid absorption in diet induced obese *** of Piezo1,stretch and Yoda1 inhibited lipid accumulation and the expression of DgAT2 and SgLT1,whereas knockdown of Piezo1 stimulated lipid accumulation and DgAT2 in Caco-2 *** study reveals a previously unexplored mechanical regulation of nutrient absorption in intestinal epithelial cells,which may shed new light on the therapy of obesity.

关键词： Piezo1 DgAT2 SgLT1 Lipid metabolism Obesity Mechanical sensing Intestinal lipid absorption Intestinal glucose absorption

Circulating biomarker-and magnetic resonance-based nomogram predicting long-term outcomes in dilated cardiomyopathy

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Chinese Medical Journal 2024年第1期137卷 73-81页

作者： Yupeng Liu Wenyao Wang Jingjing Song Jiancheng Wang Yi Fu Yida Tang department of Cardiology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China guangdong Cardiovascular Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China department of Cardiology Institute of Vascular MedicinePeking University Third HospitalBeijing 100191China department of Cardiology State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100083China department of physiology and Pathophysiology School of Basic Medical SciencesPeking University Health Science CenterBeijing 100083China Key Laboratory of Molecular Cardiovascular Science Ministry of EducationBeijing 100191China

background:Dilated cardiomyopathy(DCM)has a high mortality rate and is the most common indication for heart *** study sought to develop a multiparametric nomogram to assess individualized all-cause mortality or heart transplantation(ACM/HTx)risk in DCM ***:The present study is a retrospective cohort *** demographic,clinical,blood test,and cardiac magnetic resonance imaging(CMrI)data of DCM patients in the tertiary center(Fuwai Hospital)were *** primary endpoint was ACM/*** least absolute shrinkage and selection operator(LASSO)Cox regression model was applied for variable *** Cox regression was used to develop a *** concordance index(C-index),area under the receiver operating characteristic curve(AUC),calibration curve,and decision curve analysis(DCA)were used to evaluate the performance of the ***:A total of 218 patients were included in the present *** were randomly divided into a training cohort and a validation *** nomogram was established based on eight variables,including mid-wall late gadolinium enhancement,systolic blood pressure,diastolic blood pressure,left ventricular ejection fraction,left ventricular end-diastolic diameter,left ventricular end-diastolic volume index,free triiodothyronine,and N-terminal pro-b type natriuretic *** AUCs regarding 1-year,3-year,and 5-year ACM/HTx events were 0.859,0.831,and 0.840 in the training cohort and 0.770,0.789,and 0.819 in the validation cohort,*** calibration curve and DCA showed good accuracy and clinical utility of the ***:We established and validated a circulating biomarker-and CMrI-based nomogram that could provide a personalized prediction of ACM/HTx for DCM patients,which might help risk stratification and decision-making in clinical practice.

关键词： Cardiomyopathy,dilated Heart transplantation Mortality Nomograms Least absolute shrinkage and selection operator Decision curve analysis

Hepatic Zbtb18 (Zinc Finger and bTb Domain Containing 18) alleviates hepatic steatohepatitis via FXr (Farnesoid X receptor)

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Signal Transduction and Targeted Therapy 2024年第2期9卷 766-781页

作者： Lei Zhang Jiabing Chen Xiaoying Yang Chuangpeng Shen Jiawen Huang Dong Zhang Naihua Liu Chaonan Liu Yadi Zhong Yingjian Chen Kaijia Tang Jingyi guo Tianqi Cui Siwei Duan Jiayu Li Shangyi Huang Huafeng Pan Huabing Zhang Xiaoqiang Tang Yongsheng Chang Yong gao State Key Laboratory of Traditional Chinese Medicine Syndrome Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouChina Key Laboratory of Immune Microenvironment and Disease(Ministry of Education) Tianjin Key Laboratory of Cellular Homeostasis and DiseaseDepartment of Physiology and PathophysiologyTianjin Medical UniversityTianjinChina Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhouChina department of Endocrinology The First Clinical CollegeGuangzhou University of Chinese MedicineGuangdongChina The Fourth Clinical Medical College of guangzhou University of Chinese Medicine ShenzhenChina Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor Nanjing University of Chinese MedicineNanjingChina department of biochemistry and Molecular biology Metabolic Disease Research CenterSchool of Basic MedicineAnhui Medical UniversityHefeiChina Key Laboratory of birth Defects and related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengduChina

A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease(NAFLD),coupled with hepatitis and insulin *** the details of the underlying mechanisms are not fully ***,we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of *** Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation(FAO),and induced insulin ***,hepatic Zbtb18 overexpression alleviated hepato-steatosis,insulin resistance,and hyperglycemia in mice fed on a high-fat diet(HFD)or in diabetic ***,in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor(FXr)mediated FAO and Clathrin Heavy Chain(CLTC)protein hinders NLrP3 inflammasome *** key mechanism by which hepatocyte’s Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXr’s deletion and forced expression in mice and cultured mouse primary hepatocytes(MPHs).Moreover,CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLrP3 inflammasome activity in ***,Zbtb18 transcriptionally activates the FXr-mediated FAO and CLTC expression,which inhibits NLrP3 inflammasome’s activity alleviating inflammatory stress and insulin resistance,representing an attractive remedy for hepatic steatosis and fibrosis.

关键词： hepatic Hepatic impaired

Concussion research: Moving beyond the natural history

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Journal of Sport and Health Science 2021年第2期10卷 111-112页

作者： Thomas A.buckley kinesiology and applied physiology University of DelawareNewarkDE 19713USA

The topic of sports-related concussion has been,and will likely continue to be,one of the most challenging topics in sports *** last 2 decades of research has fundamentally altered clinician’s and the public’s view of concussions from a relatively minor“ding”to be shaken off with rapid return to play to the current realization that concussions are brain injuries with potential lifelong *** National Collegiate Athletic Association(NCAA)and the department of Defense(DoD)Concussion Assessment,research and Education(CArE)Consortium Study1 currently elucidating the natural history of concussion will provide clinicians critical recommendations on the diagnosis and management;however,many neuropsychosocial questions remain ***,this special topic on Emerging Concussion research of the Journal of Sport and Health Science(JSHS)is dedicated to addressing key concussion related questions that extend beyond typical clinical concussion management to include broad public health-related concerns.

关键词： injuries beyond return

Systemic epigallocatechin gallate protects against retinal degeneration and hepatic oxidative stress in the P23H-1 rat

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Neural regeneration research 2022年第3期17卷 625-631页

作者： Lorena Perdices Lorena Fuentes-broto Francisco Segura Ana Cavero Elvira Orduna-Hospital gema Insa-Sánchez Ana Isabel Sánchez-Cano Laura Fernández-Sánchez Nicolás Cuenca Isabel Pinilla Aragón Institute for Health research(IIS Aragón) ZaragozaSpain Pharmacology Physiology&Legal and Forensic MedicineUniversity of ZaragozaZaragozaSpain department of applied Physics University of ZaragozaZaragozaSpain Health Sciences Faculty San Jorge UniversityVillanueva de GállegoSpain department of Ophthalmology Miguel Servet University HospitalZaragozaSpain department of physiology Genetics and MicrobiologyUniversity of AlicanteAlicanteSpain department of Surgery Gynecology and ObstetricsUniversity of ZaragozaZaragozaSpain/Department of OphthalmologyLozano Blesa University HospitalZaragozaSpain

retinitis pigmentosa(rP) is a group of inherited retinal disorders that lead to photoreceptor *** has been reported to be related to oxidative stress,autophagy,and inflammation.(-)-Epigallocatechin gallate(EgCg),the most abundant catechin-based flavonoid in green tea leaves,has significant antioxidant,anti-carcinogenic,antimicrobial,and neuroprotective ***,given its low molecular weight and hydrophilic properties,can cross the blood-retinal barrier and is able to reach different ocular tissues such as the lens,cornea,and *** has been shown to provide retinal protection against ischemia;sodium nitroprusside-,N-methyl-D-aspartate-,lipopolysaccharide-,light-,sodium iodate-,or H2 O2-induced damage and diabetic *** suggests that systemic EgCg administration has the potential to protect against retinal degenerative or neurodegenerative diseases such as *** aim of this work was to investigate whether EgCg can protect against rP progression in the animal P23 H line 1,the model of *** P23 H rats were crossed with pigmented Long Evans rats to produce offspring exhibiting the clinical features of *** P23 H rats were treated via intraperitoneal injection with saline or EgCg at a dose of 25 mg/kg every week from P100 to P160 and then compared to wild-type Long Evans *** treated with EgCg showed better visual and retinal electrical function with increased contrast sensitivity and b-wave values compared with those observed in P23 H rats treated with *** reduced lipid peroxidation and increased total antioxidant capacity and catalase and superoxide dismutase *** differences were observed in visual acuity,nitrate levels,nitrite levels or glutathione S-transferase *** conclusion,EgCg not only reduced the loss of visual function in P23 H rats but also improved the levels of antioxidant enzymes and reduced oxidative *** study was approved by the Institutional Animal Care and Use Committee(CE

关键词： antioxidants contrast sensitivity electroretinogram green tea neurodegeneration oxidative stress retinal degeneration retinitis pigmentosa systemic visual acuity