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Protein lipidation in health and disease:molecular basis,physiological function and pathological implication

Signal Transduction and Targeted Therapy 2024年第4期9卷 1423-1465页

作者： Yuan Yuan Peiyuan Li jianghui Li Qiu Zhao Ying Chang Xingxing He department of gastroenterology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina department of gastroenterology Zhongnan Hospital of Wuhan UniversityWuhanChina Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases WuhanChina

Posttranslational modifications increase the complexity and functional diversity of proteins in response to complex external stimuli and internal changes.Among these,protein lipidations which refer to lipid attachment to proteins are prominent,which primarily encompassing five types including S-palmitoylation,N-myristoylation,S-prenylation,glycosylphosphatidylinositol(GPl)anchor and cholesterylation.Lipid attachment to proteins plays an essential role in the regulation of protein trafficking,localisation,stability,conformation,interactions and signal transduction by enhancing hydrophobicity.Accumulating evidence from genetic,structural,and biomedical studies has consistently shown that protein lipidation is pivotal in the regulation of broad physiological functions and is inextricably linked to a variety of diseases.Decades of dedicated research have driven the development of a wide range of drugs targeting protein lipidation,and several agents have been developed and tested in preclinical and clinical studies,some of which,such as asciminib and lonafarnib are FDA-approved for therapeutic use,indicating that targeting protein lipidations represents a promising therapeutic strategy.Here,we comprehensively review the known regulatory enzymes and catalytic mechanisms of various protein lipidation types,outline the impact of protein lipidations on physiology and disease,and highlight potential therapeutic targets and clinical research progress,aiming to provide a comprehensive reference for future protein lipidation research.

关键词： Lipid ation primarily

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Success rate of current human-derived gastric cancer organoids establishment and influencing factors:A systematic review and meta-analysis

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1626-1646页

作者： Kai-Lin Jiang Xiang-Xiang Wang Xue-Jiao Liu Li-Kun Guo Yong-Qi Chen Qing-Ling Jia Ke-Ming Yang Jiang-Hong Ling department of gastroenterology Shuguang HospitalShanghai 200021China department of Pathology Shuguang HospitalShanghai 200021China

BACKGROUND Human-derived gastric cancer organoids(GCOs)are widely used in gastric cancer research;however,the culture success rate is generally low.AIM To explore the potential influencing factors,and the literature on successful culture rates of GCOs was reviewed using meta-analysis.METHODS PubMed,Web of Science,and EMBASE were searched for studies.Two trained researchers selected the studies and extracted data.STATA 17.0 software was used for meta-analysis of the incidence of each outcome event.The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies.Funnel plots and Egger’s test were used to detect publication bias.Subgroup analyses were conducted for sex,tissue source,histo-logical classification,and the pathological tumor-node-metastasis(pTNM)cancer staging system.RESULTS Eight studies with a pooled success rate of 66.6%were included.GCOs derived from women and men had success rates of 67%and 46.7%,respectively.GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9%and 53.7%,respectively.GCOs of poorly-differentiated,moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%,31%,and 32.7%,respectively.GCOs with pTNM stages I-II and III-IV showed success rates of 38.3%and 65.2%,respectively.Y-27632 and non-Y-27632 use showed success rates of 58.2%and 70%,respectively.GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE(72.1%vs 71%,respectively).EDTA digestion showed a 50%lower success rate than other methods(P=0.04).CONCLUSION GCO establishment rate is low and varies by sex,tissue source,histological type,and pTNM stage.Omitting Y-27632,and using Liberase TH,TrypLE,or collagenase yields greater success than EDTA.

关键词： Gastric cancer organoids Human-derived organoids Gastric cancer Cell lines In vitro research models

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Double-nylon purse-string suture in closing postoperative wounds following endoscopic resection of large(≥3 cm)gastric submucosal tumors

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World Journal of gastroenterology 2024年第9期30卷 1143-1153页

作者： Shan-Shan Wang Meng-Yao Ji Xu Huang Yan-Xia Li Shi-Jie Yu Yu Zhao Lei Shen department of gastroenterology Renmin Hospital of Wuhan UniversityWuhan 430000Hubei provinceChina

BACKGROUND Endoscopic full-thickness resection(EFTR)of gastric submucosal tumors(SMTs)is safe and effective;however,postoperative wound management is equally important.Literature on suturing following EFTR for large(≥3 cm)SMTs is scarce and limited.AIM To evaluate the efficacy and clinical value of double-nylon purse-string suture in closing postoperative wounds following EFTR of large(≥3 cm)SMTs.METHODS We retrospectively analyzed the data of 85 patients with gastric SMTs in the fundus of the stomach or in the lesser curvature of the gastric body whose wounds were treated with double-nylon purse-string sutures after successful tumor resection at the Endoscopy Center of Renmin Hospital of Wuhan University.The operative,postoperative,and follow-up conditions of the patients were evaluated.RESULTS All tumors were completely resected using EFTR.36(42.35%)patients had tumors located in the fundus of the stomach,and 49(57.65%)had tumors located in the body of the stomach.All patients underwent suturing with double-nylon sutures after EFTR without laparoscopic assistance or further surgical treatment.Postoperative fever and stomach pain were reported in 13(15.29%)and 14(16.47%)patients,respectively.No serious adverse events occurred during the intraoperative or postoperative periods.A postoperative review of all patients revealed no residual or recurrent lesions.CONCLUSION Double-nylon purse-string sutures can be used to successfully close wounds that cannot be completely closed with a single nylon suture,especially for large(≥3 cm)EFTR wounds in SMTs.

关键词： Endoscopic full-thickness resection Purse-string suture Postoperative wounds Submucosal tumors

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Use of curcumin and its nanopreparations in the treatment of inflammatory bowel disease

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World Journal of gastroenterology 2024年第3期30卷 280-282页

作者： Zi-Wen Meng Bing Chang Li-Xuan Sang department of gastroenterology Shengjing Hospital of China Medical UniversityShenyang 110022Liaoning ProvinceChina department of gastroenterology the First Affiliated Hospital of China Medical UniversityShenyang 110001Liaoning ProvinceChina

Inflammatory bowel disease(IBD)is a nonspecific inflammatory disease of the intestine that includes Crohn’s disease and ulcerative colitis.Because IBD is difficult to heal and easily relapses,it could worsen patient quality of life and increase economic burdens.Curcumin(CUR)is a bioactive component derived from the rhizome of turmeric(Curcuma longa).Many basic and clinical studies have shown that CUR can efficiently treat IBD by decreasing the activity of proinflammatory cytokines by communicating with transcription factors and signaling molecules.However,due to the limitations of being almost insoluble in aqueous solutions and having low oral bioavailability,it is important to select appropriate pharmaceutical preparations.

关键词： Curcumin Inflammatory bowel disease Bioavailability Nanotherapeutics

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A BBS4 mutation causes autosomal dominant polycystic liver disease

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Genes & Diseases 2024年第1期11卷 72-75页

作者： Yalu Cui Wenping Xu Jinpei Liu Shuqing Liu Wei Huang Yihai Shi Xin Zhang Cuihua Lu Weifen Xie department of gastroenterology Changzheng HospitalNaval Medical UniversityShanghai 200003China department of gastroenterology Gongli Hospital of Shanghai Pudong New AreaShanghai 200135China department of gastroenterology Affiliated Hospital of Nantong UniversityNantong UniversityNantongJiangsu 226001China

Autosomal dominant polycystic liver disease(ADPLD)refers to a condition characterized by the presence of numerous cholangiocytes-lined and fluid-filled cysts in the liver and the absence of polycystic kidney disease.1 Although patients with ADPLD may be asymptomatic,some patients suffer from abdominal pain,gastroesophageal reflux,and nausea,because of hepatomegaly.

关键词： liver polycystic patients

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Characteristics of early gastric tumors with different differentiation and predictors of long-term outcomes after endoscopic submucosal dissection

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World Journal of gastroenterology 2024年第14期30卷 1990-2005页

作者： Hong-Yi Zhu Jie Wu Yuan-Miao Zhang Fang-Lan Li Jin Yang Bin Qin Jiong Jiang Ning Zhu Meng-Yao Chen Bai-Cang Zou department of gastroenterology The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710004Shaanxi ProvinceChina department of Pathology The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710004Shaanxi ProvinceChina department of gastroenterology Xianyang Hospital of Yan'an UniversityXianyang 712000Shaanxi ProvinceChina department of gastroenterology The First Hospital of Xi'anXi'an 710000Shaanxi ProvinceChina

BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract,and endosco-pic submucosal dissection(ESD)is the preferred treatment for early-stage gastric cancer.The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD.AIM To analyze the features of gastric mucosal tumors at different differentiation levels,and to explore the prognostic factors of ESD.METHODS We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021,according to the latest Japanese guidelines(sixth edition),and divided them into low-grade intrae-pithelial neoplasia(LGIN),high-grade intraepithelial neoplasia(HGIN),and computed tomography at 3,6 and 12 months after ESD.We compared clinicopathologic characteristics,ESD efficacy,and complications with different degrees of differentiation,and analyzed the related factors associated with ESD.RESULTS HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients(P<0.001)and accounted for more 0-IIc(P<0.001),atrophic gastritis was common(P<0.001),and irregular microvascular patterns(IMVPs)and demarcation lines(DLs)were more obvious(P<0.001).There was more infiltration in the undifferentiated carcinoma tissue(P<0.001),more abnormal folds and poorer mucosal peristalsis(P<0.001),and more obvious IMVPs,irregular microsurface patterns and DLs(P<0.05)than in the LGIN and HGIN tissues.The disease-free survival rates at 2,5,and 8 years after ESD were 95.0%,90.1%,and 86.9%,respectively.Undifferen-tiated lesions(HR 5.066),white moss(HR 7.187),incomplete resection(HR 3.658),and multiple primary cancers(HR 2.462)were significantly associated with poor prognosis.CONCLUSION Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics,which are closely rel

关键词： Gastric mucosal epithelial neoplasia Differentiated early gastric cancer Undifferentiated early gastric cancer Endoscopic submucosal dissection Long-term outcomes

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Assessment of the triglyceride glucose index in adult patients with chronic diarrhea and constipation

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World Journal of Clinical Cases 2024年第6期12卷 1094-1103页

作者： Jing-Yi Zhu Mu-Yun Liu Chang Sun department of gastroenterology The First Affiliated Hospital of Naval Medical UniversityShanghai 200433China department of gastroenterology Navy No.905 HospitalNaval Medical UniversityShanghai 200433China

BACKGROUND Accumulating evidence suggests that the gut microbiome is involved in the pathogenesis of insulin resistance(IR).However,the link between two of the most prevalent bowel disorders,chronic diarrhea and constipation,and the triglyceride glucose(TyG)index,a marker of IR,has not yet been investigated.AIM To investigate the potential association between TyG and the incidence of chronic diarrhea and constipation.METHODS This cross-sectional study enrolled 2400 participants from the National Health and Nutrition Examination Survey database from 2009-2010.TyG was used as an exposure variable,with chronic diarrhea and constipation as determined by the Bristol Stool Form Scale used as the outcome variables.A demographic investigation based on TyG quartile subgroups was performed.The application of multivariate logistic regression models and weighted generalized additive models revealed potential correlations between TyG,chronic diarrhea,and constipation.Subgroup analyses were performed to examine the stability of any potential associations.RESULTS In the chosen sample,chronic diarrhea had a prevalence of 8.00%,while chronic constipation had a prevalence of 8.04%.In multiple logistic regression,a more prominent positive association was found between TyG and chronic diarrhea,particularly in model 1(OR=1.45;95%CI:1.17-1.79,P=0.0007)and model 2(OR=1.40;95%CI:1.12-1.76,P=0.0033).No definite association was observed between the TyG levels and chronic constipation.The weighted generalized additive model findings suggested a more substantial positive association with chronic diarrhea when TyG was less than 9.63(OR=1.89;95%CI:1.05-3.41,P=0.0344),and another positive association with chronic constipation when it was greater than 8.2(OR=1.74;95%CI:1.02-2.95,P=0.0415).The results of the subgroup analyses further strengthen the extrapolation of these results to a wide range of populations.CONCLUSION Higher TyG levels were positively associated with abnormal bowel health.

关键词： Triglyceride glucose index National Health and Nutrition Examination Survey Chronic diarrhea Chronic constipation Cross-sectional study Bowel health

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Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

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World Journal of gastroenterology 2024年第7期30卷 759-769页

作者： Maja Cigrovski Berkovic Alessandro Coppola Vibor Sesa Anna Mrzljak Quirino Lai department for Sport and Exercise Medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia department of Surgery Sapienza University of RomeRome 00185Italy department of gastroenterology and hepatology Liver Transplant CenterUniversity Hospital Centre ZagrebZagreb 10000Croatia department of Medicine School of MedicineZagreb 10000Croatia General Surgery and Organ Transplantation Unit Department of SurgerySapienza University of RomeRome 00018Italy

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies wi

关键词： Pancreatic neuroendocrine tumors Type 2 diabetes mellitus Prognosis Treatment Metformin

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Fatal intratumoral hemorrhage in a patient with hepatocellular carcinoma following successful treatment with atezolizumab/bevacizumab:A case report

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World Journal of Clinical Cases 2024年第22期12卷 5177-5183页

作者： Kyeong-Hoon Park Jeong-Ju Yoo Sang Gyune Kim Young Seok Kim department of gastroenterology and hepatology Soonchunhyang University School of MedicineBucheon 14584South Korea

BACKGROUND Atezolizumab/bevacizumab is emerging as the new standard for advanced hepatocellular carcinoma(HCC),with ongoing real-world implementation to study its effectiveness.As the use of atezolizumab/bevacizumab increases,various side effects have been reported in clinical practice,most notably increased bleeding caused by bevacizumab.CASE SUMMARY In this case report,we present a rare and fatal case of intratumoral hemorrhage in a patient with advanced HCC following successful treatment with atezolizumab/bevacizumab.A 63-year-old male diagnosed with HCC initially underwent four cycles of intra-arterial chemotherapy.However,follow-up abdominal computed tomography(CT)revealed disease progression.Subsequently,the treatment plan was modified to atezolizumab/bevacizumab.After the fifth cycle of atezolizumab/bevacizumab,CT showed partial regression of HCC.One week later,he visited the emergency room due to severe abrupt abdominal pain.Abdominal CT revealed focal rupture of HCC in the medial segment inferior portion with active bleeding and a large amount of hemoperitoneum.Angiography was performed on the same day,and embolization of A4 and A8 branches using lipiodol and gelfoam was implemented.Despite successful hemostasis,the patient subsequently developed liver failure and died.CONCLUSION Atezolizumab/bevacizumab for advanced HCC suggests that intratumoral hemorrhage may be crucial despite good tumor response after immunotherapy,emphasizing the continuous monitoring of this side effect.

关键词： Adverse events Atezolizumab Bevacizumab Complication Hemorrhage Bleeding Hepatocellular carcinoma Case report

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Clinical application of COVID-19 vaccine in liver transplant recipients

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 339-343页

作者： Feng-Chao Liu Man Xie Wei Rao Division of hepatology Liver Disease CenterThe Affiliated Hospital of Qingdao UniversityQingdao 266000China Organ Transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266000China Institute of Organ Donation and Transplantation of Qingdao University Qingdao 266000China department of gastroenterology The Affiliated Hospital of Qingdao UniversityQingdao 266000China

Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related complications.Therefore,COVID-19 vaccination has been recommended to be administered as early as possible in LTRs.Data sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in PubMed.Results:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination.Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained unresponsive.Furthermore,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver injury.Conclusions:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.

关键词： Liver transplant COVID-19 SARS-CoV-2 Vaccine Antibody response

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