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World Journal of Diabetes 2024年第2期15卷 133-136页

作者： Mahmoud Nassar Ajay Chaudhuri Husam Ghanim Paresh Dandona Department of Internal medicine Division of EndocrinologyDiabetes and MetabolismJacobs School of Medicine and Biomedical SciencesUniversity of BuffaloBuffaloNY 14221United States

Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and *** management of T1D primarily focuses on exogenous insulin replacement to control blood glucose ***,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta *** research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of ***-1RAs are medications initially developed for treating type 2 *** exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric *** evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with *** article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of *** article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.

关键词： Type 1 diabetes Semaglutide Glucagon-like peptide-1 receptor agonists Insulin therapy Autoimmune response Blood glucose monitoring Β-cell preservation Early screening Teplizumab Randomized controlled trials

Digesting gluten with oral endopeptidases to improve the management of celiac disease

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World Journal of Gastroenterology 2024年第26期30卷 3201-3205页

作者： Katelin Durham Mirac Nedim Ince Department of Internal medicine Division of Gastroenterology and HepatologyUniversity of IowaCarver College of Medicineand the Iowa City Veterans Affairs Medical CenterIowa CityIA 52242United States

In our editorial,we want to comment on the article by Stefanolo et al titled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”.Celiac disease is an immune-mediated disorder triggered by dietary gluten in genetically predisposed *** avoiding gluten can permit patients to live symptom-free,ongoing voluntary or involuntary exposure to gluten is common and associated with persistent villous atrophy in small bowel *** villous atrophy predisposes patients to life threatening complications,such as osteoporotic fractures or malignancies,therapeutic adjuncts to gluten-free diet become important to improve patients’quality of life and,if these adjuncts can be shown to improve villous atrophy,avoid *** administration of enzyme preparations,such as endopeptidases that digest gluten and mitigate its antigenicity to trigger inflam-mation,is one clinical strategy under *** article is about the utility of one endopeptidase isolated from Aspergillus *** critique findings of this clinical trial and also summarize endopeptidase-based as well as other strategies and how they can complement gluten-free diet in the management of celiac disease.

关键词： Celiac disease Gluten-free diet Endopeptidase Villous atrophy Aspergillus niger Adjunct therapy

Echocardiographic predictors and associated outcomes of multiple vegetations in infective endocarditis:A pilot study

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World Journal of Cardiology 2024年第6期16卷 318-328页

作者： Ajay Kumar Mishra Kannu Bansal Ibragim Al-Seykal Pradnya B Bhattad Anu Anna George Anil Jha Nitish Sharma Jennifer Sargent Mark J Kranis division of Cardiology Saint Vincent HospitalWorcesterMA 01608United States Department of Internal medicine Saint Vincent HospitalWorcesterMA 01608United States Department of medicine Division of CardiologySaint Vincent HospitalWorcesterMA 01608United States division of Cardiovascular medicine Saint Vincent HospitalWorcesterMA 01608United States

BACKGROUND Infective endocarditis(IE)is a life-threatening infection with an annual mortality of 40%.Embolic events reported in up to 80%of *** of>10 mm size are associated with increased embolic events and poor *** is a paucity of literature on the association of multiple vegetations with *** To study the echocardiographic(ECHO)features and outcomes associated with the presence of multiple *** In this retrospective,single-center,cohort study patients diagnosed with IE were recruited from June 2017 to June 2019.A total of 84 patients were diagnosed to have IE,of whom 67 with vegetation were *** demographic,clinical,laboratory,and ECHO parameters were *** that were studied included recurrent admission,embolic phenomenon,and *** Twenty-three(34%)patients were noted to have multiple vegetations,13(56.5%)were male and 10(43.5%)were *** mean age of these patients was ***(35%)had a prior episode of *** features of moderate to severe valvular regurgitation[odds ratio(OR)=4],presence of pacemaker lead(OR=4.8),impaired left ventricle(LV)relaxation(OR=4),and elevated pulmonary artery systolic pressure(PASP)(OR=2.2)are associated with higher odds of multiple *** these moderate to severe valvular regurgitation(P=0.028),pacemaker lead(P=0.039)and impaired relaxation(P=0.028)were statistically *** patients were noted to have an increased association of recurrent admissions(OR=3.6),recurrent bacteremia(OR=2.4),embolic phenomenon(OR=2.5),intensive care unit stay(OR=2.8),hypotension(OR=2.1),surgical intervention(OR=2.8)and device removal(OR=4.8).Of this device removal(P=0.039)and recurrent admissions(P=0.017)were statistically *** This study highlights the associations of ECHO predictors and outcomes in patients with IE having multiple *** features of moderate to severe regurgitation,presence of pacemaker lead,impai

关键词： Endocarditis Echocardiography Vegetations Predictors Outcome

Melanocortin 3,5 receptors immunohistochemical expression in colonic mucosa of inflammatory bowel disease patients:A matter of disease activity?

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World Journal of Gastroenterology 2024年第9期30卷 1132-1142页

作者： Antonietta Gerarda Gravina Iacopo Panarese Maria Consiglia Trotta Michele D'Amico Raffaele Pellegrino Franca Ferraraccio Marilena Galdiero Roberto Alfano Paolo Grieco Alessandro Federico Hepatogastroenterology division Department of Precision MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy Pathology division Department of Mental and Physical Health and Preventive MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of Experimental medicine Division of PharmacologyUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of Advanced Medical and Surgical Sciences(DAMSS) University of Campania Luigi VanvitelliNaples 80138Italy Department of Pharmacy University of Naples Federico IINaples 80131Italy

BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin ***,data regarding their role in inflammatory bowel diseases(IBD)are currently *** This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic *** Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and *** sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal *** MC3R and MC5R are expressed in the colon of IBD ***,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology.

关键词： Melanocortin 3 receptor Melanocortin 5 receptor Ulcerative colitis Crohn's disease Inflammatory bowel disease

Exploiting open source omics data to advance pancreas research

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Journal of Pancreatology 2024年第1期7卷 21-27页

作者： Gayathri Swaminathan Toshie Saito Sohail Z.Husain division of Gastroenterology Hepatology and NutritionDepartment of PediatricsStanford University School of MedicineStanfordCA

The"omics"revolution has transformed the biomedical research landscape by equipping scientists with the ability to interrogate complex biological phenomenon and disease processes at an unprecedented *** volume of"big"data generated by the different omics studies such as genomics,transcriptomics,proteomics,and metabolomics has led to the concurrent development of computational tools to enable in silico analysis and aid data *** the intensive resources and high costs required to generate and analyze big data,there has been centralized,collaborative efforts to make the data and analysis tools freely available as"Open Source,"to benefit the wider research *** research studies have contributed to this"big data rush"and have additionally benefitted from utilizing the open source data as evidenced by the increasing number of new research findings and publications that stem from such *** this review,we briefly introduce the evolution of open source omics data,data types,the"FAIR"guiding principles for data management and reuse,and centralized platforms that enable free and fair data accessibility,availability,and provide tools for omics data *** illustrate,through the case study of our own experience in mining pancreatitis omics data,the power of repurposing open source data to answer translationally relevant questions in pancreas research.

关键词： Gene expression Omics Open source data Pancreatitis

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

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World Journal of Gastroenterology 2024年第13期30卷 1815-1835页

作者： Samantha Sharma Naresh Singh Anita Ahmed Turk Isabella Wan Akshay Guttikonda Julia Lily Dong Xinna Zhang Mateusz Opyrchal Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202United States division of Hematology/Oncology Department of MedicineIndiana University School of MedicineIndianapolisIN 46202United States Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202United States

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical *** considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely *** the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint *** aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor *** therapies thus have shown promising results in many clinical trials alone or in *** efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical *** trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair ***,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC *** this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the *** review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in *** underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

关键词： Colorectal cancer Immune checkpoint inhibitors Clinical trials Immunotherapy Microsatellite instability Microsatellite stability DNA mismatch repair

Disease clearance in ulcerative colitis:A new therapeutic target for the future

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World Journal of Gastroenterology 2024年第13期30卷 1801-1809页

作者： Syed Adeel Hassan Neeraj Kapur Fahad Sheikh Anam Fahad Somia Jamal division of Digestive Disease and Nutrition University of KentuckyLexingtonKY 40536United States Department of Pathology and Laboratory medicine Montefiore Medical CenterAlbert Einstein College of MedicineNew YorkNY 10461United States division of Primary Care Essen HealthcareNew YorkNY 10457United States Department of Internal medicine Karachi Medical and Dental CollegeKarachi 74700SindhPakistan

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and *** has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic ***,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal *** the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic *** recommendations lack consideration of histological *** simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully *** has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.

关键词： Inflammatory bowel disease Ulcerative colitis Clinical remission Endoscopic remission Histological remission Mucosal healing Disease clearance

METTL9-catalyzed histidine methylation of S100A9 suppresses the anti-Staphylococcus aureus activity of neutrophils

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Protein & Cell 2024年第3期15卷 223-229页

作者： Dan Cao Mengyue Lv Chi Hu Shukai Li Siwen Wang Chao Xu Wen Pan Department of Digestive Disease The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technologyof ChinaHefei230001China division of Life Sciences and medicine The CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesInstitute of ImmunologyUniversity of Science and Technology of ChinaHefei 230027China division of Life Sciences and medicine MOE Key Laboratory for Cellular DynamicsHefei National Center for Cross-Disciplinary SciencesUniversity of Science and Technology of ChinaHefei 230027China

Dear Editor,Protein histidine methylation has been found to be a widespread post-translational modification(PTM)in mammalian cells and represents more than 13%of all protein methylation events in the human methylome(Ning et al.,2016;Kapell and Jakobsson,2021).Recently,we and other groups independently identified METTL9 as the first broad-specificity histidine N1 methyltransferase in mammals(Davydova et al.,2021;Lv et al.,2021).METTL9 methylates a variety of substrates with a common x-His-x-His motif(His is for histidine;the second x is preferably small amino acids:A/C/G/S)and catalyzes methyl transfer to the last histidine.

关键词： S100A9 specificity

Sleep quality and characteristics of older adults with acute cardiovascular disease

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Journal of Geriatric Cardiology 2024年第3期21卷 369-373页

作者： Haroon Munir Michael Goldfarb Faculty of medicine and Health Sciences McGill UniversityMontrealCanada division of Cardiology Jewish General HospitalMcGill UniversityMontrealCanada

Sleep plays a vital role in restoring the physical and mental health of people with cardiovascular ***,the hospital setting is not a conducive environment for *** interruptions by members of the care team,including vital sign checks,medication delivery,and blood draws for laboratory investigations,are routinely done in many *** interruptions by staff and noise by other patients have been cited as barriers to restorative sleep in the hospital.

关键词： Sleep routine characteristics

New evidence for the epigenetic regulation of skeletal stem cells

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Science Bulletin 2024年第13期69卷 2004-2006页

作者： Liming Zhao Jun Xiao Charles K.F.Chan Institute for Stem Cell Biology and Regenerative medicine Stanford University School of MedicineStanford CA 94305USA Department of Surgery Division of Plastic and Reconstructive SurgeryStanford University School of MedicineStanford CA 94305USA Department of Orthopaedic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Skeletal stem cells(SSCs)are crucial for skeletal development and regeneration,yet the epigenetic regulation of these cells remains poorly *** studies have delineated the epigenetic landscape across the developmental trajectory of SSCs,highlighting the involvement of Ptip in regulating SSC *** skeletal system undergoes dynamic remodeling throughout *** stem cells(SSCs),residing within the skeleton and lineage-restricted,serve as a cellular reserve to foster development and maintain skeletal *** categorized within the broader mesenchymal stromal/stem cells(MSCs).

关键词： skeletal involvement maintain