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Upregulation of α-ENaC induces pancreatic β-cell dysfunction,ER stress,and SIRT2 degradation

Journal of Biomedical Research 2024年第3期38卷 241-255页

作者： Xue Zhang Dan Zhang Lei Huo Xin Zhou Jia Zhang Min Li Dongming Su Peng Sun Fang Chen Xiubin Liang department of Pathophysiology Nanjing Medical UniversityNanjingJiangsu 211166China department of pathology Nanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjingJiangsu 210009China Key Laboratory of Human Functional Genomics of Jiangsu Province Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjingJiangsu 211166China department of pathology Nanjing Medical UniversityNanjingJiangsu 211166China

Islet beta cells(β-cells)produce insulin in response to high blood glucose levels,which is essential for preserving glucose ***-gated ion channels inβ-cells,including Na+,K+,and Ca2+channels,aid in the release of *** epithelial sodium channel alpha subunit(α-ENaC),a voltage-independent sodium ion channel,is also expressed in human pancreatic endocrine ***,there is no reported study on the function of ENaC in theβ-*** the current study,we found thatα-ENaC was expressed in human pancreatic glandule and pancreatic isletβ-*** the pancreas of db/db mice and high-fat diet-induced mice,and in mouse isletβ-cells(MIN6 cells)treated with palmitate,α-ENaC expression was ***α-ENaC was overexpressed in MIN6 cells,insulin content and glucose-induced insulin secretion were significantly *** the other hand,palmitate injured isletβ-cells and suppressed insulin synthesis and secretion,but increasedα-ENaC expression in MIN6 ***,α-ENaC knockout(Scnn1a−/−)in MIN6 cells attenuatedβ-cell disorder induced by ***,α-ENaC regulated the ubiquitylation and degradation of sirtuin 2 inβ-cells.α-ENaC also modulatedβ-cell function in correlation with the inositol-requiring enzyme 1 alpha/X-box binding protein 1(IRE1α/XBP1)and protein kinase RNA-like endoplasmic reticulum kinase/C/EBP homologous protein(PERK/CHOP)endoplasmic reticulum stress *** results suggest thatα-ENaC may play a novel role in insulin synthesis and secretion in theβ-cells,and the upregulation ofα-ENaC promotes isletβ-cell *** conclusion,α-ENaC may be a key regulator involved in isletβ-cell damage and a potential therapeutic target for type 2 diabetes mellitus.

关键词： α-ENaC pancreaticβ-cells type 2 diabetes mellitus endoplasmic reticulum stress sirtuin 2

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ATM Activation is Key in Vasculogenic Mimicry Formation by Glioma Stem-like Cells

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Biomedical and Environmental Sciences 2024年第8期37卷 834-849页

作者： Jing Xie Jiaxin Tang Yuan Li Xue Kong Wei Wang Haibo Wu department of pathology the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036AnhuiChina Intelligent pathology Institute Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036AnhuiChina

Objective Vasculogenic mimicry(VM)is a novel vasculogenic process integral to glioma stem cells(GSCs)in glioblastoma(GBM).However,the relationship between VM and ataxia-telangiectasia mutated(ATM)serine/threonine kinase activation,which confers chemoradiotherapy resistance,remains *** We investigated VM formation and phosphorylated ATM(pATM)levels by CD31/GFAPperiodic acid-Schiff dual staining and immunohistochemical staining in 145 GBM *** stem-like cells(GSLCs)derived from the formatted spheres of U87 and U251 cell lines and their pATM level and VM formation ability were examined using western blot and three-dimensional *** the examination of the function of pATM in VM formation by GSLCs,ATM knockdown by shRNAs and deactivated via ATM phosphorylation inhibitor KU55933 were *** VM and high pATM expression occurred in 38.5% and 41.8% of tumors,respectively,and were significantly associated with reduced progression-free and overall *** with VM-positive GBMs exhibited higher pATM levels(r_(s)=0.425,P=0.01).The multivariate analysis established VM as an independent negative prognostic factor(P=0.002).Furthermore,GSLCs expressed high levels of pATM and formed vascular-like networks in *** inactivation or knockdown hindered VM-like network formation concomitant with the downregulation of pVEGFR-2,VE-cadherin,and laminin *** VM may predict a poor GBM prognosis and is associated with pATM *** propose that pATM promotes VM through extracellular matrix modulation and VE-Cadherin/pVEGFR-2 activation,thereby highlighting ATM activation as a potential target for enhancing anti-angiogenesis therapies for GBM.

关键词： Glioblastoma Vasculogenic mimicry Ataxia-telangiectasia mutated(ATM) Glioma stem-like cell

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World Journal of Clinical Cases 2024年第1期12卷 176-179页

作者： Hsin-Chia Angela Lin Kam-Fai Lee Tzu Hao Huang Division of General Surgery Department of SurgeryChang Gung Memorial HospitalChiayi 613Taiwan department of Anatomic pathology Chang Gung Memorial HospitalChiayi 613Taiwan

BACKGROUND Gastric IgG4-related disease(IgG4-RD)is rarely encountered in clinical practice,and especially more so among pediatric *** our knowledge,this is the first report of IgG4-RD presenting as a calcifying gastric mass in a *** describe how this entity was difficult to differentiate from a gastrointestinal stromal tumor(GIST)imaging-based ***,this case highlights the importance of considering IgG4-RD in the differential diagnosis of gastric tumor before performing surgical resection,especially to distinguish it from malignancy to avoid unnecessary *** SUMMARY The patient suffered from epigastric pain for several *** and computed tomography scan revealed a submucosal *** diagnoses included GIST,leiomyoma,teratoma,and mucinous ***,laparoscopic proximal gastrectomy allowed for the definitive diagnosis of IgG4-related stomach *** We emphasize the importance of considering IgG4-RD in the differential diagnosis of gastric submucosal tumors before performing surgical resection.

关键词： IgG4-related disease Gastrointestinal stromal tumor Child Pediatric Case report

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Novel insights into autophagy in gastrointestinal pathologies,mechanisms in metabolic dysfunction-associated fatty liver disease and acute liver failure

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World Journal of Gastroenterology 2024年第27期30卷 3273-3277页

作者： Tsvetelina Velikova Milena Gulinac Medical Faculty Sofia University St Kliment OhridskiSofia 1407Bulgaria department of General and Clinical pathology Medical University of PlovdivPlovdiv 4002Bulgaria

In this editorial,we comment on three articles published in a recent issue of World Journal of *** is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains ***,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further ***,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly *** studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.

关键词： Gastrointestinal diseases Autophagy Metabolic dysfunction-associated fatty liver disease High-normal alanine aminotransferase level Silent information regulator sirtuin 1 Acute liver failure

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Epithelioid malignant peripheral nerve sheath tumor of the bladder and concomitant urothelial carcinoma: A case report

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World Journal of Clinical Cases 2024年第3期12卷 551-559页

作者： Sami Berk Ozden Muhammed Fatih Simsekoglu Ipek Sertbudak Cetin Demirdag Iclal Gurses Istanbul University-Cerrahpasa Cerrahpasa School of Medicine Department of UrologyIstanbul 34100FatihTurkey Istanbul University-Cerrahpasa Cerrahpasa School of Medicine Department of PathologyIstanbul 34100FatihTurkey

BACKGROUND Epithelioid malignant peripheral nerve sheath tumor(EMPNST)of the bladder is a rare entity with devastating *** tumors are thought to originate from malignant transformation of pre-existing schwannomas of pelvic autonomic nerve plexuses,and unlike the conventional malignant peripheral nerve sheath tumor(MPNST),are not associated with *** tumor has dis-tinctive morphological,immunohistochemical and molecular ***-tionally,it tends to be more aggressive and have a higher *** is the first case that presents with a synchronous urothelial carcinoma of the bladder and the epithelioid variant of MPNST in the ***’s also the second re-ported case of EMPNST originating from the bladder *** SUMMARY In this case report,we present the detailed clinical course of a 71-year-old patient with EMPNST of the bladder alongside a literature *** During the management of EMPNST cases,offering aggressive treatment moda-lities to the patient,such as radical cystectomy,is appropriate for the best chance to contain the disease,regardless of the tumor stage and the extent of local disease at initial diagnosis.

关键词： Epithelioid Peripheral nerve sheath tumor Bladder Case report Urothelial Cystoprostatectomy

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Black radish root extract alleviates sodium valproate-induced liver damage via inhibiting mitochondrial membrane potential collapse and oxidative stress in mice

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Asian Pacific Journal of Tropical Biomedicine 2024年第7期14卷 298-306页

作者： Mohammad Hadi Zarei Sami Akbulut Maryam Zafari Elham Saghaei Zahra Lorigooini Hossein AminiKhoei Somaye Khosravi Elham Bijad Medical Plants Research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran department of Liver Transplant Institute and Biostatistics Inonu University Faculty of Medicine44280MalatyaTurkey Student Research Committee Shahrekord University of Medical SciencesShahrekordIran Physiology and Pharmacology department School of MedicineShahrekord University of Medical SciencesShahrekordIran department of anatomical Sciences School of MedicineShahrekord University of Medical SciencesShahrekordIran

Objective:To explore the effect of black radish(Raphanus sativus *** niger)root extract on liver enzymes,oxidative stress,and histopathological alterations in mice with sodium valproate-induced ***:Thirty-two mice were divided into four groups:the control group received drinking water by gavage,the second group was administered with 100 mg/kg of sodium valproate,the third group received 300 mg/kg of black radish root extract,and the fourth group was given both sodium valproate(100 mg/kg)and black radish root extract(300 mg/kg).After 28 days,the mice were euthanized,and serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),and alkaline phosphatase(ALP),along with liver malondialdehyde(MDA),reactive oxygen species(ROS),mitochondrial parameters,tumor necrosis factor-alpha(TNF-α)gene expression,and histopathological changes were ***:Sodium valproate caused hepatic damage in mice,characterized by elevated serum levels of liver enzymes,increased MDA and ROS levels and TNF-αgene expression,as well as histopathological *** black radish root extract significantly alleviated sodium valproate-caused hepatic injury by decreasing the serum levels of ALT and AST,MDA,ROS,TNF-αgene expression,as well as mitochondrial impairment,but did not have a significant effect on sodium valproate-induced histopathological ***:The black radish root extract demonstrates protective effects against sodium valproate-induced liver injury,possibly through mitigating oxidative stress,mitochondrial impairment,and inflammatory mediator expression.

关键词： Black radish Raphanus sativus Sodium valproate Hepatotoxicity Oxidative stress Anti-inflammation

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Stable diffusion gradients in microfluidic conduits bounded by fluid walls

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Microsystems & Nanoengineering 2024年第3期10卷 357-367页

作者： Federico Nebuloni Cyril Deroy Peter R.Cook Edmond J.Walsh department of Engineering Science Osney Thermo-Fluids InstituteUniversity of OxfordOxford OX20ESUK Sir William Dunn School of pathology University of OxfordOxford OX13REUK

Assays mimicking in vitro the concentration gradients triggering biological responses like those involved in fighting infections and blood clotting are essential for biomedical *** assays prove especially attractive as they allow precise control of gradient shape allied to a reduction in *** microfluidic devices are fabricated using solid plastics that prevent direct access to responding ***-walled microfluidics allows the manufacture of circuits on standard Petri dishes in seconds,coupled to simple operating methods;cell-culture medium sitting in a standard dish is confined to circuits by fluid walls made of an immiscible *** develop and experimentally validate an analytical model of diffusion between two or more aqueous streams flowing at different rates into a fluid-walled conduit with the cross-section of a circular *** solid walls,fluid walls morph during flows as pressures fall,with wall shape changing down the *** model is validated experimentally for Fourier numbers<0.1 using fluorescein diffusing between laminar *** enables a priori prediction of concentration gradients throughout a conduit,so allowing rapid circuit design as well as providing bioscientists with an accurate way of predicting local concentrations of bioactive molecules around responsive and nonresponsive cells.

关键词： walls diffusion attractive

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miR-125b reverses cisplatin resistance by regulating autophagy via targeting RORA/BNIP3L axis in lung adenocarcinoma

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Oncology Research 2024年第4期32卷 643-658页

作者： LEI LIU NA GUO XIANGLING LI QIAN XU RUILONG HE LIMIN CHENG CHUNYAN DANG XINYU BAI YIYING BAI XIN WANG QIANHUI CHEN LI ZHANG department of Immunology Chengde Medical UniversityChengde067000China department of pathology Chengde Medical UniversityChengde067000China department of Oncology The Affiliated Hospital of Chengde Medical UniversityChengde067000China department of Hepatobiliary Surgery The Affiliated Hospital of Chengde Medical UniversityChengde067000China

The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the *** has been shown that microRNAs(miRNAs)play a significant role in tumor *** this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR *** decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival ***-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of *** addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in *** mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed *** on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.

关键词： Lung adenocarcinoma miRNAs Cisplatin Resistance Autophagy

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Clinical manifestations,diagnosis and long-term prognosis of adult autoimmune enteropathy:Experience from Peking Union Medical College Hospital

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World Journal of Gastroenterology 2024年第19期30卷 2523-2537页

作者： Mu-Han Li Ge-Chong Ruan Wei-Xun Zhou Xiao-Qing Li Sheng-Yu Zhang Yang Chen Xiao-Yin Bai Hong Yang Yu-Jie Zhang Peng-Yu Zhao Ji Li Jing-Nan Li department of Gastroenterology Chinese Academy of Medical Sciences&Peking Union Medical College HospitalBeijing 100730China department of pathology Chinese Academy of Medical Scinences&Peking Union Medical College HospitalBeijing 100730China department of pathology Tianjin First Central HospitalNankai UniversityTianjin 300192China Affairs Office Chinese Academy of Medical Sciences&Peking Union Medical College Hospital(West campus)Beijing 100032China

BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE *** To improve overall understanding of this disease’s diagnosis and *** We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic *** Diarrhea in AIE patients was characterized by secretory *** common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and *** blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal ***,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte *** patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)*** were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s *** cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,*** Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult *** long-term prognosis is still unsatisfac

关键词： Autoimmune enteropathy Clinical manifestations Diagnostic criteria Pathological features Long-term prognosis

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Mitochondrial DNA methylation and mitochondria-related epigenetics in neurodegeneration

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Neural Regeneration Research 2024年第2期19卷 405-406页

作者： Fabio Coppedè department of Translational Research and of New Surgical and Medical Technologies Laboratory of Medical GeneticsUniversity of PisaPisaItaly、Interdepartmental Research Center of Biology and Pathology of AgingUniversity of PisaPisaItaly

Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy *** are particularly abundant in tissues with high energy demands,including muscle,liver,and brain,and mitochondrial dysfunction,oxidative mitochondrial DNA(mtDNA)damage,and impaired mitochondrial dynamics have often been associated with neurodegeneration.

关键词： impaired neurodegeneration oxidative

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