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Bone marrow microRNA-34a is a good indicator for response to treatment in acute myeloid leukemia

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Oncology Research 2024年第3期32卷 577-584页

作者： MONA SA BDELLATEIF NAGLAA MHASSAN MAHMOUD MKAMEL YOMNA MEL-MELIGUI department of Cancer Biology Medical Biochemistry and Molecular BiologyNational Cancer InstituteCairo UniversityCairo11976Egypt department of Cinical pathology National Cancer InstituteCairo UniversityCairo11976Egypt

Background:microRNA 34a(miR 34a)had been reported to have a diagnostic role in acute myeloid leukemia(AML).However,its value in the bone marrow(BM)of AML patients,in addition to its role in response to therapy is still *** current study was designed to assess the diagnostic,prognostic,and predictive significance of miR 34a in the BM of AML ***:The miR.34a was assed in BM aspirate of 82 AML patients in relation to 12 normal control subjects using *** data were assessed for correlation with the relevant dinical critenia,response to therapy,disease-free survival(DFS),and overall survival(OS)***:miR.34a was significantly downregulated in AML patients[0.005(3.3×10^(-6)-1.32)],compared to the control subjects[0.108(3.2× 10^(-4)-1.64),p=0.021].*** relative quantification(RQ)of miR-34a was 0.106(range;0-32.12).The specifaity,sensitivity,and area under the curve(AUC)for the diagnosis of AML were(58.3%,69.5%,0.707,respectively,p=0.021).patients with upregulated miR-34a showed decreased platelets count<34.5 × 10^(9)/L,and achieved early complete remission(CR,p=0.031,p=0.044,respectively).Similarly,patients who were refractory to therapy showed decreased miR 34a levels in comparison to those who achieved CR[0.002(0-0.01)and 0.12(0-32.12),respectively,p=0.002].Therefore,miR 34a could significantly identify patients with CR with a specificity of 75%and sensitivity of 100%at a cut-off of 0.014(AUC=0.927,p=0.005).There was no considerable association between miR-34a expression and survival rates of the induded AML ***:miR-34a could be a beneficial diagnostic biomarker for AML *** addition,it serves as a good indicator for response to therapy,which could possibly identify patients who are refractory to treatment with 100%sensitivity and 75%specificity.

关键词： AML miR 34a microRNA Leukemia

Roles and application of exosomes in the development,diagnosis and treatment of gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 630-642页

作者： Xiao-Li Guan Xiao-Ying Guan Zheng-Yi Zhang department of General Medicine The Second Hospital of Lanzhou UniversityLanzhou 730030Gansu ProvinceChina department of pathology The Second Hospital of Lanzhou UniversityLanzhou 730030Gansu ProvinceChina

As important messengers of intercellular communication,exosomes can regulate local and distant cellular communication by transporting specific exosomal con-tents and can also promote or suppress the development and progression of gas-tric cancer(GC)by regulating the growth and proliferation of tumor cells,the tumor-related immune response and tumor *** transport bioactive molecules including DNA,proteins,and RNA(coding and noncoding)from donor cells to recipient cells,causing reprogramming of the target *** this review,we will describe how exosomes regulate the cellular immune respon-se,tumor angiogenesis,proliferation and metastasis of GC cells,and the role and mechanism of exosome-based therapy in human *** will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treat-ment of GC and their relationship with drug resistance.

关键词： Exosomes Gastric cancer Immune regulation Diagnosis Cancer therapy

RLKdb:A comprehensively curated database of plant receptor-like kinase

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Molecular Plant 2024年第4期17卷 513-515页

作者： Zhiyuan Yin Jinding Liu Daolong Dou department of Plant pathology Nanjing Agricultural UniversityNanjing 210095China Academy for Advanced Interdisciplinary Studies Nanjing Agricultural UniversityNanjing 210095China

Dear Editor,Since the first plant receptor-like kinase(RLK)gene ZmPK1 was cloned from Zea mays in 1990(Walker and Zhang,1990),this large gene family has been extensively studied and shown to play crucial roles in growth,development,and immunity(Tang et al.,2017).RLKs are widespread in the plant ***,biological functions of most RLKs remain largely elusive(Dievart et al.,2020).Given RLKs share a conserved monophyletic RLK/Pelle kinase domain,RLKs in several model plants are classified into distinct families by extracellular domains(Shiu and Bleecker,2001).However,independent domain shuffling in specific lineages drives the origin of novel families,which raises a question what is the landscape of RLKs across the entire plant kingdom?Previously,sequence-homology-based methods have been widely used for RLK identification and classification,which might miss distantly related proteins with similar structures and potential novel families not mentioned in the *** academic community urgently requires a dedicated database for a systematic overview of the RLK gene family,providing data support for in-depth research on RLK ***,we used a topology-based method to accurately isolate the RLKomes from *** obtained RLKomes were further classified into(sub)families based on extracellular *** con-structed a comprehensively curated plant RLK database(https://***/rlkdb),which contains valuable re-sources for investigating the origin and evolution of the RLK fam-ily and multiple online tools for personalized analysis.

关键词： database comprehensive origin

Cellular zinc metabolism and zinc signaling:from biological functions to diseases and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 401-441页

作者： Bonan Chen Peiyao Yu Wai Nok Chan Fuda Xie Yigan Zhang Li Liang Kam Tong Leung Kwok Wai Lo Jun Yu Gary M.K.Tse Wei Kang Ka Fai To department of Anatomical and Cellular pathology State Key Laboratory of Translational OncologyPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina State Key Laboratory of Digestive Disease Institute of Digestive DiseaseThe Chinese University of Hong KongHong KongChina CUHK-Shenzhen Research Institute The Chinese University of Hong KongShenzhenChina department of pathology Nanfang Hospital and Basic Medical CollegeSouthern Medical UniversityGuangdong Province Key Laboratory of Molecular Tumor PathologyGuangzhouChina Institute of Biomedical Research Taihe HospitalHubei University of MedicineShiyanChina department of Pediatrics The Chinese University of Hong KongHong KongChina department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

Zinc metabolism at the cellular level is critical for many biological processes in the body.A key observation is the disruption of cellular homeostasis,often coinciding with disease *** an essential factor in maintaining cellular equilibrium,cellular zinc has been increasingly spotlighted in the context of disease *** research suggests zinc’s involvement in promoting malignancy and invasion in cancer cells,despite its low tissue *** has led to a growing body of literature investigating zinc’s cellular metabolism,particularly the functions of zinc transporters and storage mechanisms during cancer *** transportation is under the control of two major transporter families:SLC30(ZnT)for the excretion of zinc and SLC39(ZIP)for the zinc ***,the storage of this essential element is predominantly mediated by metallothioneins(MTs).This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression,with a special focus on *** also compile a summary of clinical trials involving zinc *** the main localization of zinc transporters at the cell membrane,the potential for targeted therapies,including small molecules and monoclonal antibodies,offers promising avenues for future exploration.

关键词： metabolism invasion involvement

Cellular crosstalk of regulatory T cells in pancreatic ductal adenocarcinoma

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胰腺病学杂志(英文) 2024年第2期7卷 131-140页

作者： Shi Xuqing Liu Hangqi Liang Zhiyong department of pathology State Key Laboratory of Complex Severe and Rare Disease Molecular Pathology Research Center Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid tumors and is characterized by dense desmoplasia and immune desert. Regulatory T cells (Tregs) are critical components of the immune tumor microenvironment (TIME) of PDAC. Treg-induced immune evasion presents a significant hurdle in enhancing the efficacy of conventional and emerging therapeutic strategies. Nonetheless, Treg deficiency alone led to inconsistent outcomes. To unveil the underlying potential reasons for these results and to determine the role of Tregs in other therapeutic strategies, in-depth insights into the crosstalk between Tregs and other cells in PDAC are indispensable and currently lacking. Therefore, in this review, we comprehensively delineate the direct and indirect interplay between Tregs and various cellular constituents ranging from cancer cells and immune cells to stromal cells in PDAC in an attempt to uncover potential leads for the development of Treg-associated therapies.

关键词： Cancer-associated fibroblasts Cellular crosstalk Myeloid cells Pancreatic ductal adenocarcinoma Regulatory T cells

Management of Mandibular Fractures in Children in Ivory Coast: Experience of the Stomatology and Maxillofacial Surgery department at the University Hospital of Cocody from 2000 to 2019

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Open Journal of Stomatology 2024年第7期14卷 341-349页

作者： Bakary Ouattara Camille Assouan Laurent Boka Koffi Konan René Kouakou Ake Lucien Jonathan Yapo Annick Zoglo-Bro Ahi Morel Mounin Chapo Affoué Linda Marie Pierre Koffi Kahder Morel Diarra Atse Kobo N’Guessan Konan Marc Koffi department of Stomatology Maxillofacial Surgery University Flix Houphout-Boigny Abidjan Republic of Ivory Coast department of Oral pathology University Flix Houphout-Boigny Abidjan Republic of Ivory Coast

Introduction: Mandibular fractures in children are becoming increasingly common. Treatment of these fractures is difficult due to their anatomical and physiological complexity. Therefore, there is a need for well-codified management. Our main aim was to develop a decision algorithm for the management of mandibular fractures in children based on our experience. Materials and Methods: This was a retrospective descriptive study carried out in the department of Stomatology and Maxillofacial Surgery at the University Hospital of Cocody over a period of 20 years (2000-2019). Results: We enrolled 58 patients. The mean age of the patients was 9.35 ± 2.3 years with a sex ratio of 2.22. Traffic accidents were the main cause of mandibular fractures (60.35%). Condylar fractures were the most common (46.87%). Treatment was orthopedic in 45.76% of cases, mixed (orthopedic and surgical) in 24.14% and surgical in 5.17%. Patients were followed up weekly for 1 month, then monthly for 6 months and annually for 3 years, with panoramic radiographs of the maxilla starting at 21 days. We observed 2 cases of complications: temporomandibular ankylosis and gingival stomatitis. Conclusion: Mandibular fractures are common in children. Management is difficult due to anatomical and physiological peculiarities. The choice of treatment depends on several criteria.

关键词： Fractures Mandible Children Treatment Ivory Coast

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

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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

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