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Metadherin-driven promotion of cancer stem cell phenotypes and its effect on immunity in hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第20期30卷 2624-2628页

作者： Nevena Todorović Amedeo Amedei Department of Experimental and Clinical Medicine University of FlorenceFlorence 50134Italy Clinic for infectious and Tropical diseases University Clinical Centre of SerbiaBelgrade 11000Serbia

In this editorial we provide commentary on the article published by Wang et al,featured in the recent issue of the World Journal of Gastroenterology in *** focus on the metadherin(MTDH),also known as astrocyte elevated gene-1 or lysine rich CEACAM1,and its effects on cancer stem cells(CSCs)and immunity in hepatocellular carcinoma(HCC).HCC is the most common primary liver cancer and one of the leading causes of cancer-related deaths *** HCC cases develop in the context of liver *** the pivotal mechanisms of carcinogenesis are gene mutations,dysregulation of diverse signaling pathways,epigenetic alterations,hepatitis B virus-induced hepatocarcinogenesis,chronic inflammation,impact of tumor microenvironment,oxidative *** the years,extensive research has been conducted on the MTDH role in various tumor pathologies,such as lung,breast,ovarian,gastric,hepatocellular,colorectal,renal carcinoma,neuroblastoma,melanoma,and ***,its involvement in tumor development processes including transformation,apoptosis evasion,angiogenesis,invasion,and metastasis via multiple signaling *** has been demonstrated that knockdown or knockout of MTDH disrupt tumor development and *** addition,numerous reports have been carried out regarding the MTDH influence on HCC,demonstrating its role as a predictor of poor prognosis,aggressive tumor phenotypes prone to metastasis and recurrence,and exhibiting significant potential for therapy ***,more studies finely investigated the influence of MTDH on *** CSCs are a small subpopulation of tumor cells that sharing traits with normal stem cells like self-renewal and differentiation abilities,alongside a high plasticity that alters their *** their presumed role in tumor initiation,they can drive also disease relapse,metastasis,and resistance to chemo and radiotherapy.

关键词： Hepatocellular carcinoma Metadherin Astrocyte elevated gene-1 Lysine rich

Endogenous retrovirus activation: potential for immunology and clinical applications

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National Science Review 2024年第4期11卷 21-23页

作者： Jundan Yu Peishan Qiu Jingwen Ai Bo Liu Guan-Zhu Han Fan Zhu Wenhong Zhang Jie Cui Department of infectious diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response National Medical Center for Infectious Diseases Huashan Hospital Shanghai Medical College Fudan University CAS Key Laboratory of Molecular Virology &Immunology Shanghai Institute of Immunity and Infection Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai Huashen Institute of Microbes and Infections College of Life Sciences Nanjing Normal University State Key Laboratory of Virology and Department of Medical Microbiology School of Basic Medical SciencesWuhan University The Institute of Infection and Health Research Fudan University Key Laboratory of Medical Molecular Virology(MOE/MOH) Shanghai Medical CollegeFudan University Laboratory for Marine Biology and Biotechnology Qingdao Marine Science and Technology Center

Endogenous retroviruses (ERVs), the remnants of ancient retrovirus infections, constitute approximately 8% of the human genome and play important roles in human evolution, development,and diseases. Multiple drugs, such as DNA methyltransferase inhibitors and lysine-specific histone demethylase 1inhibitors, reactivate ERVs, induce viral mimicry and trigger innate immune responses to enhance tumor immunogenicity.

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The interplay of drug therapeutics and immune responses to SARS-CoV-2

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Cellular & Molecular Immunology 2024年第2期21卷 197-200页

作者： Valeria Fumagalli Matteo Iannacone Division of Immunology Transplantationand Infectious DiseasesIRCCS San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly Experimental Imaging centre IRCCS San Raffaele Scientific InstituteMilanItaly

The SARS-CoV-2 pandemic has necessitated rapid therapeutic and preventative *** vaccines form the frontline of defense,antiviral treatments such as nirmatrelvir have emerged as vital adjunctive measures,particularly for those unable or unwilling to be *** review delves into the potential influence of nirmatrelvir on enduring *** parallel,the potential of drug repurposing is explored,with bisphosphonates being examined for their possible effects against COVID-19 due to their immunomodulatory *** importance of rigorous clinical trials and careful interpretation of preliminary data is emphasized.

关键词： SARS-CoV-2 Nirmatrelvir Bisphosphonates Adaptive immunity Drug repurposing

sTREM-1 as promising prognostic biomarker for acute-on-chronic liver failure and mortality in patients with acute decompensation of cirrhosis

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World Journal of Gastroenterology 2024年第9期30卷 1177-1188页

作者： Song-Man Yu Hai Li Guo-Hong Deng Xian-Bo Wang Xin Zheng Jin-Jun Chen Zhong-Ji Meng Yu-Bao Zheng Yan-Hang Gao Zhi-Ping Qian Feng Liu Xiao-Bo Lu Yu Shi Jia Shang Ruo-Chan Chen Yan Huang Department of infectious diseases Xiangya HospitalCentral South UniversityChangsha 410000Hunan ProvinceChina Department of Gastroenterology Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of infectious diseases Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Center of Integrative Medicine Beijing Ditan HospitalCapital Medical UniversityBeijing 100020China Department of infectious diseases Institute of Infection and ImmunologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430020Hubei ProvinceChina Department of infectious diseases Nanfang HospitalSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of infectious Disease Taihe HospitalHubei University of MedicineShiyan 442009Hubei ProvinceChina Department of infectious diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina Department of Hepatology The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina Department of Liver Intensive Care Unit Shanghai Public Health Clinical CentreFudan UniversityShanghai 200093China Tianjin Institute of Hepatology Nankai University Second People's HospitalTianjin 300192China infectious Disease Center The First Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830054Xinjiang Uygur Autonomous RegionChina The State Key Laboratory for Diagnosis and Treatment of infectious diseases The First Affiliated Hospital of School of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvineChina Department of infectious diseases Henan Provincial People's HospitalZhengzhou 463599Henan ProvineChina Department of infectious diseases Hunan Key Laboratory of Viral HepatitisXiangya HospitalCentral South UniversityChangsha 110051Hunan ProvineChina

BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and *** triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory *** To explore the prognostic value of sTREM-1 in patients with AD of *** A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at *** enrolled patients were followed-up for at least 1 *** In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD ***,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d *** ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF *** Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.

关键词： Soluble triggering receptor expressed on myeloid cell-1 Acute decompensation Cirrhosis Acute-on-chronic liver failure Prognostic biomarker

Nonconserved epitopes dominate reverse preexisting T cell immunity in COVID-19 convalescents

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2984-2998页

作者： Xin Wang Jie Zhang Maoshun Liu Yuanyuan Guo Peipei Guo Xiaonan Yang Bingli Shang Min Li Jinmin Tian Ting Zhang Xi Wang Ronghua Jin Jikun Zhou George F.Gao Jun Liu Department of Epidemiology School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China NHC Key Laboratory of Biosafety Research Unit of Adaptive Evolution and Control of Emerging VirusesChinese Academy of Medical SciencesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention(China CDC)Beijing 102206China Beijing Key Laboratory of Emerging infectious diseases Institute of Infectious DiseasesBeijing Ditan HospitalCapital Medical UniversityBeijing 100015China Beijing Institute of infectious diseases Beijing 100015China National Center for infectious diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015P.R.China School of Laboratory Medicine and Life Sciences Wenzhou Medical UniversityWenzhou 325035China School of Ophthalmology&Optometry Wenzhou Medical UniversityWenzhou 325027China Collaborative Innovation centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanningGuangxi 530021China Shijiazhuang Fifth Hospital Shijiazhuang 050011China CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences(CAS)Beijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China

The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing ***,the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well *** our research,we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV,identifying cross-reactive CD8^(+)T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining ***,in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide ***,single-cell T cell receptor reservoir was analyzed based on tetramer ***,we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19,and identified SARS-CoV-2 CD8^(+)T cell epitopes spanning the major structural antigens.T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 ***-T cell reactivity was also observed within the identified series of CD8^(+)T cell *** representative immunodominant peptide pairs,although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar,the TCR repertoires recognizing these peptides were *** results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.

关键词： immunity conserved assessed

Clash of the Cytokine Titans： counter-regulation of interleukin-1 and type I interferon-mediated inflammatory responses

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Cellular & Molecular Immunology 2017年第1期14卷 22-35页

作者： Katrin D Mayer-Barber Bo Yan Inflammation and innate immunity Unit Laboratory of Clinical Infectious Diseases National Institute of Allergy and Infectious Diseases National Institutes of Health. Bethesda. MD 20892. USA

Over the past decades the notion of ＇inflammation＇ has been extended beyond the original hallmarks of rubor （redness）, calor （heat）, tumor （swelling） and dolor （pain） described by Celsus. We have gained a more detailed understanding of the cellular players and molecular mediators of inflammation which is now being applied and extended to areas of biomedical research such as cancer, obesity, heart disease, metabolism, auto-inflammatory disorders, autoimmunity and infectious diseases. innate cytokines are often central components of inflammatory responses. Here, we discuss how the type I interferon and interleukin-1 cytokine pathways represent distinct and specialized categories of inflammatory responses and how these key mediators of inflammation counter-regulate each other.

关键词： cytokines infection inflammation interleukin-1 tuberculosis type-1 interferons

Ets-2 deletion in myeloid cells attenuates IL-1α-mediated inflammatory disease caused by a Ptpn6 point mutation

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Cellular & Molecular Immunology 2021年第7期18卷 1798-1808页

作者： Sarang Tartey Prajwal Gurung Rajendra Karki Amanda Burton Paul Hertzog Thirumala-Devi Kanneganti Department of Immunology St.Jude Children’s Research HospitalMemphisTN38105USA Inflammation Program University of IowaIowa CityIA52241USA centre for innate immunity&infectious diseases Hudson Institute of Medical ResearchDepartment of Molecular and Translational SciencesMonash UniversityClaytonVictoria3168Australia

The SHP-1 protein encoded by the Ptpn6 gene has been extensively studied in hematopoietic cells in the context of inflammation.A point mutation in this gene(Ptpn6spin)causes spontaneous inflammation in mice,which has a striking similarity to neutrophilic dermatoses in *** findings highlighted the role of signaling adapters and kinases in promoting inflammation in Ptpn6spin mice;however,the underlying transcriptional regulation is poorly ***,we report that SYK is important for driving neutrophil infiltration and initiating wound healing responses in Ptpn6spin ***,we found that deletion of the transcription factor Ets2 in myeloid cells ameliorates cutaneous inflammatory disease in Ptpn6spin mice through transcriptional regulation of its target inflammatory ***,Ets-2 drives IL-1α-mediated inflammatory signaling in neutrophils of Ptpn6spin ***,in addition to its well-known role in driving inflammation in cancer,Ets-2 plays a major role in regulating IL-1α-driven Ptpn6spin-mediated neutrophilic dermatoses.

关键词： Autoinflammation ETS-2 IL-1α Neutrophilic dermatoses PTPN6 SHP-1

Necroptosis, pyroptosis and apoptosis: an intricate game of cell death

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Cellular & Molecular Immunology 2021年第5期18卷 1106-1121页

作者： Damien Bertheloot Eicke Latz Bernardo S.Franklin Institute of innate immunity University Hospitals BonnUniversity of BonnBonnNRWGermany Department of infectious diseases and Immunology University of Massachusetts Medical SchoolWorcesterMAUSA German Center for Neurodegenerative diseases BonnNRWGermany

Cell death is a fundamental physiological process in all living *** roles extend from embryonic development,organ maintenance,and aging to the coordination of immune responses and *** recent years,our understanding of the mechanisms orchestrating cellular death and its consequences on immunity and homeostasis has increased *** modalities of what has become known as‘programmed cell death’have been described,and some key players in these processes have been *** have learned more about the intricacies that fine tune the activity of common players and ultimately shape the different types of cell *** studies have highlighted the complex mechanisms tipping the balance between different cell ***,we summarize the latest discoveries in the three most well understood modalities of cell death,namely,apoptosis,necroptosis,and pyroptosis,highlighting common and unique pathways and their effect on the surrounding cells and the organism as a whole.

关键词： Apoptosis Necroptosis Pyroptosis Inflammation Survival

Automated robot and artificial intelligence-powered wastewater surveillance for proactive mpox outbreak prediction

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Biosafety and Health 2024年第4期6卷 225-234页

作者： Guanyong Ou Yuxuan Tang Jiexiang Liu Yabin Hao Zhi Chen Ting Huang Shaxi Li a Shiyu Niu Yun Peng Jiaqi Feng Hongwei Tu Yang Yang Han Zhang Yingxia Liu Shenzhen Key Laboratory of Pathogen and immunity National Clinical Research Center for Infectious DiseaseState Key Discipline of Infectious Diseasethe Third People’s Hospital of ShenzhenSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of EducationInstitute of Microscale OptoelectronicsCollege of Physics and Optoelectronic EngineeringShenzhen UniversityShenzhen 518060China Shenzhen Clinical Medical College Guangzhou University of Chinese MedicineShenzhen 518116China Shenzhen Metasensing Tech Limited Company Shenzhen 518000China Guangdong Provincial centre for diseases Control and Prevention Guangzhou 511430China

In the wake of the largest‐ever recorded outbreak of mpox in terms of magnitude and geographical spread in human history since May 2022,we innovatively developed an automated online sewage virus enrichment and concentration robot for disease *** with an artificial intelligence(AI)model,our research aims to estimate mpox cases based on the concentration of the monkeypox virus(MPXV)in *** research has revealed a compelling link between the levels of MPXV in wastewater and the number of clinically confirmed mpox infections,a finding that is reinforced by the ability of our AI prediction model to forecast cases with remarkable precision,capturing 87%of the data’s ***,it is worth noting that this high precision in predictions may be related to the relatively high frequency of data acquisition and the relatively non‐mobile isolated environment of the hospital *** conclusion,this study represents a significant step forward in our ability to track and respond to mpox *** has the potential to revolutionize public health surveillance by utilizing innovative technologies for disease surveillance and prediction。

关键词： Automated online sewage virus enrichment robot Artificial intelligence(AI)model Early warning system Mpox Monkeypox virus(MPXV)