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

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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Should we perform sigmoidoscopy for colorectal cancer screening in people under 45 years?

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1248-1255页

作者： Waiian Leong Jia-Qi Guo Chun Ning Fei-Fei Luo Rui Jiao Dong-Ye Yang division of Gastroenterology&Hepatology The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina Department of Accident&Emergency The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina Department of anatomical pathology The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina Endoscopy Center The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChin

BACKGROUND The strategy for preventing colorectal cancer is screening by colonoscopy,which offers a direct way for detection and removal of adenomatous polyps(APs).American College of Gastroenterology guidelines recommend that people aged≥45 years should undergo colonoscopy;however,how to deal with people aged≤45 years is still *** To compare the prevalence of APs and high-grade neoplasia between the left and right colon in patients≤45 *** A retrospective observational study was conducted at a single tertiary III hospital in *** study included patients aged 18-45 years with undergoing initial colonoscopy dissection and pathological diagnosis AP or high-grade neoplasia between February 2014 and January *** number of APs in the entire colon while screening and post-polypectomy surveillance in following 1-3 years were *** A total of 3053 cases were *** prevalence of APs in the left and right colon was 55.0%and 41.6%,respectively(OR 1.7,95%CI 1.6-2.4;P3 polyps(14.1%;OR 0.3,95%CI 0.1-0.6;P<0.05).CONCLUSION This study suggests that flexible sigmoidoscopy would be an optimal approach for initial screening in people aged≤45 years and would be a more cost-effective and safe strategy.

关键词： Adenomatous polyps High-grade neoplasia Colonoscopy Flexible sigmoidoscopy

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Liver Characterization of a Cohort of Alpha-1 Antitrypsin Deficiency Patients with and without Lung Disease

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Journal of Clinical and Translational Hepatology 2024年第10期12卷 845-856页

作者： Naweed Mohammad Regina Oshins Tongjun Gu Virginia Clark Jorge Lascano Naziheh Assarzadegan George Marek Mark Brantly Nazli Khodayari division of Pulmonary Critical Care and Sleep MedicineCollege of MedicineUniversity of FloridaGainesvilleFLUSA Interdisciplinary Center for Biotechnology Research Bioinformatics CoreUniversity of FloridaGainesvilleFLUSA division of Gastroenterology Hepatology and NutritionCollege of MedicineUniversity of FloridaGainesvilleFLUSA division of pathology Immunologyand Laboratory MedicineCollege of MedicineUniversity of FloridaGainesvilleFLUSA division of Gastroenterology and Hepatology Mayo ClinicRochesterMNUSA

Background and Aims:Alpha-1 antitrypsin deficiency(AATD)is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin(AAT)within hepatocytes,which limits its access to the circulation and exposes the lungs to protease-mediated tissue *** results in progressive liver disease secondary to AAT polymerization and accumulation,and chronic obstructive pulmonary disease(COPD)due to deficient levels of AAT within the *** goal was to characterize the unique effects of COPD secondary to AATD on liver disease and gene ***:A subcohort of AATD individuals with COPD(n=33)and AATD individuals without COPD(n=14)were evaluated in this study from our previously reported cross-sectional *** used immunohistochemistry to assess the AATD liver phenotype,and RNA sequencing to explore liver *** observed a distinct transcriptomic profile in liver tissues from AATD individuals with COPD compared to those ***:A total of 339 genes were differentially *** pathways related to fibrosis,extracellular matrix remodeling,collagen deposition,hepatocellular damage,and inflammation were significantly upregulated in the livers of AATD individuals with *** analysis also revealed higher levels of fibrosis and hepatocellular damage in these ***:Our data supports a relationship between the development of COPD and liver disease in AATD and introduces genes and pathways that may play a role in AATD liver disease when COPD is *** believe addressing lung impairment and airway inflammation may be an approach to managing AATD-related liver disease.

关键词： Alpha-1 antitrypsin deficiency Chronic obstructive pulmonary disease Liver fibrosis Liver biopsy Liver histology Transcriptomics

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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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Sporophytic control of tapetal development and pollen fertility by a mitogen-activated protein kinase cascade in rice

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Journal of Integrative Plant Biology 2024年第7期66卷 1500-1516页

作者： Jianguo Zeng Manman Duan Yiqing Wang Guangtao Li Yujing You Jie Shi Changhao Liu Jinyang Zhang Juan Xu Shuqun Zhang Jing Zhao Department of Plant pathology Nanjing Agricultural UniversityNanjing 210095China State Key Laboratory of Plant Physiology and Biochemistry College of Life SciencesZhejiang UniversityHangzhou 310058China division of Biochemistry University of MissouriColumbia65211MOUSA

Tapetum,the innermost layer of the anther wall,provides essential nutrients and materials for pollen *** degradation of anther tapetal cells is a prerequisite for normal pollen development in flowering *** cells facilitate male gametogenesis by providing cellular contents after highly coordinated programmed cell death(PCD).Tapetal development is regulated by a transcriptional ***,the signaling pathway(s)involved in this process are poorly *** this study,we report that a mitogen-activated protein kinase(MAPK)cascade composed of OsYDA1/OsYDA2-OsMKK4-OsMPK6 plays an important role in tapetal development and male gametophyte *** of function of this MAPK cascade leads to anther indehiscence,enlarged tapetum,and aborted pollen *** cells in osmkk4 and osmpk6 mutants exhibit an increased presence of lipid body-like structures within the cytoplasm,which is accompanied by a delayed occurrence of *** of a constitutively active version of OsMPK6(CA-OsMPK6)can rescue the pollen defects in osmkk4 mutants,confirming that OsMPK6 functions downstream of OsMKK4 in this *** crosses also demonstrated that the MAPK cascade sporophyticly regulates pollen *** study reveals a novel function of rice MAPK cascade in plant male reproductive biology.

关键词： degradation MAPK cascade pollen fertility rice tapetum

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Unique presentation of neonatal liver failure:A case report

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World Journal of Clinical Pediatrics 2024年第2期13卷 221-226页

作者： Eman Al Atrash Amer Azaz Samar Said Mohammad Miqdady Department of Pediatrics Division of Pediatric GastroenterologySheikh Khalifa Medical CityAbu Dhabi 971United Arab Emirates Department of pathology Mayo ClinicRochesterMN 55905United States

BACKGROUND Acute fulminant liver failure rarely occurs in the neonatal *** etiologies include viral infection(15%),metabolic/genetic disease(10%),hematologic disorders(15%),and ischemic injury(5%).Gestational alloimmune liver disease usually manifests as severe neonatal liver failure,with extensive hepatic and extrahepatic iron overload,sparing the reticuloendothelial *** liver failure is a rare cause of liver failure where a patient presents with liver failure in the neonatal period with no hepatocytes in liver *** SUMMARY A 5-week-old male presented with *** examination revealed an alert but deeply icteric *** data demonstrated direct hyperbilirubinemia,a severely deranged coagulation profile,normal transaminase,and normal *** resonance imaging of the abdomen was suggestive of perinatal *** biopsy showed histiocytic infiltration with an absence of *** hemosiderin deposition was identified in a buccal mucosa *** Neonatal liver failure in the absence of hepatocellular regeneration potentially reflects an acquired or inborn defect in the regulation of hepatic regeneration.

关键词： Liver Hyperbilirubinemia Le foie vide Neonatal hemochromatosis Case report

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Autoimmune pancreatitis:Cornerstones and future perspectives

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World Journal of Gastroenterology 2024年第8期30卷 817-832页

作者： Camilla Gallo Giulia Dispinzieri Nicola Zucchini Pietro Invernizzi Sara Massironi division of Gastroenterology and Center for Autoimmune Liver Diseases Department of Medicine and SurgeryFondazione IRCCS San Gerardo dei TintoriUniversity of Milano-BicoccaMonza 20900Italy Department of pathology Fondazione IRCCS San Gerardo dei TintoriMonza 20900Italy

Autoimmune pancreatitis(AIP)is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas,leading to inflammation and *** AIP is rare,its incidence is increasing and is often misdiagnosed as other pancreatic *** is commonly classified into two *** 1 AIP(AIP-1)is typically associated with elevated serum immunoglobulin G4(IgG4)levels and systemic manifestations,while type 2 AIP is typically a more localized form of the disease,and may coexist with other autoimmune disorders,especially inflammatory bowel ***,there is emerging recognition of a third type(type 3 AIP),which refers to immunotherapy-triggered AIP,although this classification is still gaining acceptance in medical *** clinical manifestations of AIP mainly include painless jaundice and weight *** serum IgG4 levels are particularly characteristic of *** relies on a combination of clinical,laboratory,radiological,and histological findings,given the similarity of AIP symptoms to other pancreatic *** mainstay of treatment for AIP is steroid therapy,which is effective in most *** cases might require additional imm-unosuppressive *** review aims to summarize the current knowledge of AIP,encompassing its epidemiology,etiology,clinical presentation,diagnosis,and treatment *** also address the challenges and controversies in diagnosing and treating AIP,such as distinguishing it from pancreatic cancer and managing long-term treatment,highlighting the need for increased awareness and knowledge of this complex disease.

关键词： Autoimmunity Pancreatitis Autoimmune pancreatitis Immunoglobulin G4 Steroids Relapse

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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

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Multidisciplinary management of ulcerative colitis complicated by immune checkpoint inhibitor-associated colitis with life-threatening gastrointestinal hemorrhage:A case report

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2329-2336页

作者： Na Hong Bo Wang Hang-Cheng Zhou Zheng-Xiang Wu Hua-Ying Fang Geng-Qing Song Yue Yu Department of Gastroenterology The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Department of pathology The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036Anhui ProvinceChina Intelligent pathology Institute Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036Anhui ProvinceChina Department of Gastroenterology and Hepatology Metro Health Medical CenterCase Western Reserve UniversityClevelandOH 44109United States

BACKGROUND Programmed cell death 1(PD-1)inhibitors are immune checkpoint inhibitors(ICI)that have demonstrated significant efficacy in treating various advanced malignant *** most patients tolerate treatment well,several adverse drug reactions,such as fatigue,myelosuppression,and ICI-associated colitis,have been *** SUMMARY This case involved a 57-year-old male patient with ulcerative colitis complicated by hepatocarcinoma who underwent treatment with tirelizumab(a PD-1 inhibitor)for six *** treatment led to repeated life-threatening lower gastrointestinal *** patient received infliximab,vedolizumab,and other salvage procedures but ultimately required subtotal colectomy due to uncontrollable massive lower gastrointestinal ***,postoperative gastrointestinal bleeding has stopped,the patient’s stool has turned yellow,and his full blood cell count has returned to *** This case highlights the necessity of early identification,timely and adequate treatment of ICI-related colitis,and rapid escalation to achieve the goal of improving prognosis.

关键词： Ulcerative colitis Hepatocarcinoma Immune checkpoint inhibitor-associated colitis Colectomy Case report

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The immune response to SARS-CoV-2 in people with HIV

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Cellular & Molecular Immunology 2024年第2期21卷 184-196页

作者： Maxine A.Höft Wendy A.Burgers Catherine Riou Institute of Infectious Disease and Molecular Medicine University of Cape TownCape TownSouth Africa division of Medical Virology Department of PathologyUniversity of Cape TownCape TownSouth Africa Wellcome Centre for Infectious Diseases Research in Africa University of Cape TownCape TownSouth Africa

This review examines the intersection of the HIV and SARS-CoV-2 *** with HIV(PWH)are a heterogeneous group that differ in their degree of immune suppression,immune reconstitution,and viral *** COVID-19 in those with wellcontrolled HIV infection poses no greater risk than that for HIV-uninfected individuals,people with advanced HIV disease are more vulnerable to poor COVID-19 ***-19 vaccines are effective and well tolerated in the majority of PWH,though reduced vaccine efficacy,breakthrough infections and faster waning of vaccine effectiveness have been demonstrated in *** is likely a result of suboptimal humoral and cellular immune responses after *** with advanced HIV may also experience prolonged infection that may give rise to new epidemiologically significant variants,but initiation or resumption of antiretroviral therapy(ART)can effectively clear persistent ***-19 vaccine guidelines reflect these increased risks and recommend prioritization for vaccination and additional booster doses for PWH who are moderately to severely *** recommend continued research and monitoring of PWH with SARS-CoV-2 infection,especially in areas with a high HIV burden.

关键词： SARS-CoV-2 HIV Immune dysfunction Vaccine efficacy Prolonged infection Immunogenicity

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