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Insights into the role of RNA m^(6)A modification in the metabolic process and related diseases

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Genes & Diseases 2024年第4期11卷 270-295页

作者： Haiming Hu Zhibin Li Xia Xie Qiushi Liao Yiyang Hu Chunli Gong Nannan Gao Huan Yang Yufeng Xiao Yang Chen department of gastroenterology Xinqiao HospitalArmy Medical UniversityChongqing 400037China

According to the latest consensus,many traditional diseases are considered meta-bolic diseases,such as cancer,type 2 diabetes,obesity,and cardiovascular ***,metabolic diseases are increasingly prevalent because of the ever-improving living standards and have become the leading threat to human *** therapy methods have been applied to treat these diseases,which improves the quality of life of many patients,but the overall effect is still ***,intensive research on the metabolic process and the pathogenesis of metabolic diseases is imperative.N6-methyladenosine(m^(6)A)is an important modification of eukaryotic *** is a critical regulator of gene expression that is involved in different cellular functions and physiological *** studies have indi-cated that m^(6)A modification regulates the development of many metabolic processes and metabolic *** this review,we summarized recent studies on the role of m^(6)A modifica-tion in different metabolic processes and metabolic ***,we highlighted the potential m^(6)A-targeted therapy for metabolic diseases,expecting to facilitate m^(6)A-targeted strategies in the treatment of metabolic diseases.

关键词： Cancer mm^(6)A-targeted therapy Metabolic disease Metabolism N6-methyladenosine

Nonsteroidal anti-inflammatory drugs before endoscopic ultrasound guided tissue acquisition to reduce the incidence of post procedural pancreatitis

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World Journal of gastroenterology 2024年第8期30卷 811-816页

作者： Mike de Jong Foke van Delft Christine Roozen Erwin-Jan van Geenen Tanya Bisseling Peter Siersema Marco Bruno department of gastroenterology and Hepatology Radboud University Medical CenterNijmegen 6525 GANetherlands department of gastroenterology and Hepatology Erasmus University Medical CenterRotterdam 3015 GDNetherlands

Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst *** most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy *** it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to *** will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.

关键词： Pancreatitis Endoscopic ultrasound Tissue acquisition Nonsteroidal antiinflammatory drugs Pancreatic cancer

Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

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World Journal of gastroenterology 2024年第28期30卷 3428-3446页

作者： Aritoshi Koizumi Kosuke Kaji Norihisa Nishimura Shohei Asada Takuya Matsuda Misako Tanaka Nobuyuki Yorioka Yuki Tsuji Koh Kitagawa Shinya Sato Tadashi Namisaki Takemi Akahane Hitoshi Yoshiji department of gastroenterology Nara Medical UniversityKashihara 634-8521Japan

BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver *** proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ***,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary ***,the benefits of EFN for ALD treatment is *** To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse *** ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 ***(3 and 10 mg/kg/day)was orally administered during the experimental *** and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier *** EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based *** The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN *** promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARα***,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)*** improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory *** protective effect on intestinal bar

关键词： Liver fibrosis Ethanol Gut barrier function Apoptosis Autophagy Peroxisome proliferator activated receptor

Intestinal microecological transplantation for a patient with chronic radiation enteritis:A case report

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World Journal of gastroenterology 2024年第19期30卷 2603-2611页

作者： Lin Wang Yan Li Yu-Jing Zhang Li-Hua Peng department of gastroenterology and Hepatology The First Medical CenterChinese PLA General HospitalBeijing 100853China department of gastroenterology and Hepatology Chinese PLA Medical SchoolBeijing 100853China

BACKGROUND The gut microbiota is strongly associated with radiation-induced gut *** study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with chronic radiation *** SUMMARY A 64-year-old female with cervical cancer developed abdominal pain,diarrhea,and blood in the stool 1 year after *** electronic colonoscopy was performed to diagnose chronic radiation *** courses of intestinal microecological transplantation and full-length 16S rRNA microbiological analysis were *** patient experienced short-and long-term relief from symptoms without adverse *** 16S rRNA sequencing revealed significant differences in the intestinal flora’s composition between patient and healthy *** bacteria,such as Escherichia fergusonii and Romboutsia timonensis,were more in the *** bacteria such as Faecalibacterium prausnitzii,Fusicatenibacter saccharivorans,Ruminococcus bromii,and Bifidobacterium longum were more in the healthy *** microbiota transplantation resulted in a significant change in the patient's intestinal flora *** composition converged with the donor's flora,with an increase in core beneficial intestinal bacteria,such as Eubacterium rectale,and a decrease in pathogenic *** in the intestinal flora corresponded with the patients'alleviating clinical *** Intestinal microecological transplantation is an effective treatment for relieving the clinical symptoms of chronic radiation enteritis by altering the composition of the intestinal *** study provides a new approach for treating patients with chronic radiation enteritis.

关键词： Chronic radiation enteritis Gut microbial transplantation Intestinal microecology Cancer Quality of life Case report

Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

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World Journal of gastroenterology 2024年第8期30卷 901-918页

作者： Yi-Ying Wang Mei-Mei Shen Jian Gao department of gastroenterology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China department of gastroenterology and Hepatology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of *** To explore the role of MTDH on stemness and immune infiltration in *** MTDH expression in HCC tissues was detected using TCGA and GEO *** was used to analyze the tissue *** was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell *** invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing ***,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free *** expression was determined by western blotting and quantitative reverse transcri-ption *** cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like *** effects of MTDH inhibition on tumor growth were evaluated in *** correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB *** HCC tissues expressed higher levels of MTDH than normal liver *** MTDH expression was associated with a poor *** cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these *** inhibition suppressed HCC progression and CD133 expression in *** was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T *** was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 a

关键词： Metadherin Hepatocellular carcinoma Cancer stem cells Immune infiltration

Protective and Adverse Roles of DDX3X in Different Cell Types in Nonalcoholic Steatohepatitis Progression

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Research 2024年第3期6卷 561-574页

作者： Suzhen Yang Lin Zhou Tianming Zhao Hanlong Zhu Tingting Luo Kang Jiang Xiaoxiao Shi Chunyan Chen Han Zhang Si Zhao Xiaoping Zou Yuzheng Zhuge Fangyu Wang Lei Wang Mingzuo Jiang Bing Xu department of gastroenterology the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolJiangsuNanjing210002China. department of gastroenterology and Hepatology the Affiliated Jinling Hospital of Nanjing University Medical SchoolJiangsuNanjing210002China School of Medicine Northwest UniversityShaanxiXi’an710069China. department of gastroenterology Nanjing Drum Tower HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeJiangsuNanjing210008China.

Persistent hepatic cellular metabolic stress and liver inflammatory stimuli are key signatures of nonalcoholic steatohepatitis(NASH).DDX3X is a vital molecule involved in cell fate decisions in both pro-survival stress granule(SG)and pro-death NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome assembly in response to stress ***,the role of DDX3X in NASH remains *** characterized the cell type-specific roles of DDX3X in *** liver tissues from NASH patients and normal control subjects were collected to assess DDX3X expression and *** steatohepatitis models were constructed by feeding macrophage-specific DDX3X knockout(DDX3^(XΔMφ)),hepatocyte-specific DDX3X knockout(DDX3X^(Δhep)),and wild-type control(DDX3X^(fl/fl))mice a high-fat and high-cholesterol(HFHC)diet,a methionine-and choline-deficient(MCD)diet,and a high-fat/high-iron/high-fructose/high-cholesterol,low-methionine,and choline-deficient(HFHIHFHC-MCD)*** study demonstrated that DDX3X was predominantly expressed in macrophages and hepatocytes in control liver tissues,and its expression was down-regulated in patients or mice with *** to DDX3X^(fl/fl) littermates,DDX3^(XΔMφ)mice showed improved liver histology in nutritional steatohepatitis *** of macrophage DDX3X inhibited NLRP3 inflammasome-mediated pyroptosis,causing anti-inflammatory M2 polarization and alleviating hepatocyte steatohepatitic ***3X^(Δhep) mice developed marked steatohepatitis in multiple nutritional steatohepatitis models compared to DDX3X^(fl/fl) ***3X-deleted hepatocytes showed impaired SG assembly,leading to increased sensitivity and intolerance to metabolic stimulation and resultant *** conclusion,DDX3X plays opposite roles in different cell types during the progression of NASH.A better understanding of the cell-specific differences in the crosstalk between SG formation and NLRP3 activation is crucial for developing pr

关键词： NLRP3 impaired inhibited

Knockdown of RCN1 contributes to the apoptosis of colorectal cancer via regulating IP3R1

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BIOCELL 2024年第5期48卷 835-845页

作者： XUAN SHI YUFEN WANG CHENYU LI WANGSHU FU XINYUE ZHANG AIXIA GONG department of gastroenterology The First Affiliated Hospital of Dalian Medical UniversityDalianChina department of gastroenterology The First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina The First Clinical College Dalian Medical UniversityDalianChina

Background:The incidence of colorectal cancer(CRC)has been increasing in recent ***,the discovery of factors that can assist in alleviating CRC is urgently ***:To identify a potential factor involved in the development of CRC,we screened the upregulated genes in tumor tissues through four datasets from an online *** expression of reticulocalbin 1(RCN1),a Ca2+-binding protein,was upregulated in the four *** on loss-offunction experiments,the effect of RCN1 on cell viability was assessed by Cell Counting Kit-8(CCK-8)*** regulatory effect of RCN1 on apoptosis was evaluated through Annexin V-fluorescein 5-isothiocyanate(FITC)/propidium iodide(PI)staining assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)assay in RKO and SW480 *** of endoplasmic reticulum(ER)stress signaling pathways was confirmed by estimating the phosphorylation and expression of PRKR-like ER kinase(PERK),inositol-requiring kinase-1(IRE1),transcription factor 6(ACT6),and CCAAT/enhancer-binding protein-homologous protein(CHOP).The intracellular Ca2+homeostasis regulated by RCN1 was determined through the detection of Ca2+concentration and mitochondrial membrane potential(MMP)***,whether inositol 1,4,5-trisphosphate receptor type 1(IP3R1)was involved in the regulation of RCN1 in CRC was verified through the depletion of IP3R1 in RKO ***:Knockdown of RCN1 reduced cell viability and facilitated apoptosis in RKO and SW480 *** of PERK and IRE1,activation of ATF6,and upregulation of CHOP were induced by the absence of RCN1,suggesting that the unfolded protein response(UPR)was activated in CRC *** concentration of Ca2+in mitochondria was increased after RCN1 depletion,followed by reduction in the MMP and release of cytochrome c from mitochondria to the cytoplasm in RKO and SW480 ***,it was demonstrated that IP3R1 mediates the effect of RCN1 on apoptosis i

关键词： Reticulocalbin 1 Unfolded protein response IP3R1 Colorectal cancer

Standard-definition White-light,High-definition White-light versus Narrow-band Imaging Endoscopy for Detecting Colorectal Adenomas:A Multicenter Randomized Controlled Trial

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Current medical Science 2024年第3期44卷 554-560页

作者： Chang-wei DUAN Hui-hong ZHAI Hui XIE Xian-zong MA Dong-liang YU Lang YANG Xin WANG Yu-fen TANG Jie ZHANG Hui SU Jian-qiu SHENG Jun-feng XU Peng JIN Chinese PLA General Hospital and medical School Beijing100853China department of gastroenterology Xuanwu HospitalCapital Medical UniversityBeijing100053China department of gastroenterology The Seventh Medical Center of Chinese PLA General HospitalBeijing100700China Senior department of gastroenterology The First Medical Center of Chinese PLA General HospitalBeijing100853China

Objective This study aimed to compare the performance of standard-definition white-light endoscopy(SD-WL),high-definition white-light endoscopy(HD-WL),and high-definition narrow-band imaging(HD-NBI)in detecting colorectal lesions in the Chinese *** This was a multicenter,single-blind,randomized,controlled trial with a non-inferiority *** undergoing endoscopy for physical examination,screening,and surveillance were enrolled from July 2017 to December *** primary outcome measure was the adenoma detection rate(ADR),defined as the proportion of patients with at least one adenoma *** associated factors for detecting adenomas were assessed using univariate and multivariate logistic *** Out of 653 eligible patients enrolled,data from 596 patients were *** ADRs were 34.5%in the SD-WL group,33.5%in the HD-WL group,and 37.5%in the HD-NBI group(P=0.72).The advanced neoplasm detection rates(ANDRs)in the three arms were 17.1%,15.5%,and 10.4%(P=0.17).No significant differences were found between the SD group and HD group regarding ADR or ANDR(ADR:34.5%vs.35.6%,P=0.79;ANDR:17.1%vs.13.0%,P=0.16,respectively).Similar results were observed between the HD-WL group and HD-NBI group(ADR:33.5%vs.37.7%,P=0.45;ANDR:15.5%vs.10.4%,P=0.18,respectively).In the univariate and multivariate logistic regression analyses,neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL(HD-WL:OR 0.91,P=0.69;HD-NBI:OR 1.15,P=0.80).Conclusion HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese *** can be concluded that HD-NBI or HD-WL is not superior to SD-WL,but more effective instruction may be needed to guide the selection of different endoscopic methods in the *** study’s conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources,especially advanced imaging technologies.

关键词： standard-definition white-light endoscopy high-definition white-light endoscopy narrow-band imaging colonoscopy colorectal cancer screening adenoma detection rate

TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-β1/Smad3 Signaling Pathway

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Current medical Science 2024年第3期44卷 519-528页

作者： Jia SONG Dong-lei SUN Chen-yang LI Yu-xin LUO Qian LIU Yue YAO Hong ZHANG Ting-ting YANG Mei SONG Xin-li BAI Xiao-lan ZHANG department of gastroenterology The Second Hospital of Hebei Medical UniversityHebei Key Laboratory of GastroenterologyHebei Institute of GastroenterologyHebei Clinical Research Center for Digestive DiseasesShijiazhuang050000China department of Pediatrics The Second Hospital of Hebei Medical UniversityShijiazhuang050000China

Objective Intestinal fibrosis is a refractory complication of inflammatory bowel disease(IBD).Tumor necrosis factor ligand-related molecule-1A(TL1A)is important for IBD-related intestinal fibrosis in a dextran sodium sulfate(DSS)-induced experimental colitis *** study aimed to explore the effects of TL1A on human colonic *** A trinitrobenzene sulfonic acid(TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic(Tg)or wild-type(WT)mice was established to determine the effect and mechanism of TL1A on intestinal *** human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell(PBMC)*** proliferation and activation of CCD-18Co cells were detected by BrdU assays,flow cytometry,immunocytochemistry and Western *** metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction(RT-qPCR).Results The level of collagen metabolism in the TNBS+ethyl alcohol(EtOH)/Tg group was greater than that in the TNBS+EtOH/WT *** growth factor-β1(TGF-β1)and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT *** proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A,and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4%at 24 ***1A promoted cell activation and increased the levels of COL1A2,COL3A1,and TIMP-1 in CCD-18Co *** of CCD-18Co cells with TL1A increased the expression of TGF-β1 and *** TL1A promotes TGF-β1-mediated intestinal fibroblast activation,proliferation,and collagen deposition and is likely related to an increase in the TGF-β1/Smad3 signaling pathway.

关键词： tumor necrosis factor ligand-related molecule-1A fibrosis inflammatory bowel disease myofibroblasts transforming growth factor-β1