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Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis

Cellular & Molecular Immunology 2024年第3期21卷 227-244页

作者： Kang-Gu Lee Bong-Ki Hong Saseong Lee Naeun Lee Seung-Whan Kim Donghyun Kim Wan-Uk Kim Center for Integrative Rheumatoid Transcriptomics and Dynamics The Catholic University of KoreaSeoul 06591Republic of Korea Department of Biomedicine&Health Sciences The Catholic University of KoreaSeoul 06591Republic of Korea Department of pharmacology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Bio-Medical institute of Technology University of UlsanSeoul 05505Republic of Korea Department of Microbiology and Immunology Seoul National University College of MedicineSeoul 03080Republic of Korea institute of Infectious Diseases Seoul National University College of MedicineSeoul 03080Republic of Korea Division of Rheumatology Department of Internal MedicineThe Catholic University of KoreaSeoul 06591Republic of Korea

Transcriptional coactivators regulate the rate of gene expression in the nucleus.Nuclear receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains unclear.Here,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory conditions.Unexpectedly,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic specks.Mechanistically,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active caspase-1.Of note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in macrophages.Genetic ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in mice.Consistent with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling results.Conclusively,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.

关键词： Nuclear receptor coactivator 6 Nuclear-to-cytoplasmic translocation NLRP3 inflammasome NACHT domain Gouty arthritis

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Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair

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Frontiers of Medicine 2024年第2期18卷 258-284页

作者： Tianjing Sun Mo Li Qi Liu Anyong Yu Kun Cheng Jianxing Ma Sean Murphy Patrick Michael McNutt Yuanyuan Zhang Department of Emergency Affiliated Hospital of Zunyi Medical UniversityZunyi563003China Department of Nephrology Affiliated Hospital of Zunyi Medical UniversityZunyi563003China Division of pharmacology and Pharmaceutical Sciences School of PharmacyUniversity of Missouri-Kansas CityKansas CityMO64108USA Department of Biochemistry Wake Forest University School of MedicineWinston-SalemNC27157USA Wake Forest institute of Regenerative Medicine Wake Forest School of MedicineWinston-SalemNC27109USA

Exosome therapy holds great promise as a novel approach to improve acute skin wound healing.This review provides a comprehensive overview of the current understanding of exosome biology and its potential applications in acute skin wound healing and beyond.Exosomes,small extracellular vesicles secreted by various stem cells,have emerged as potent mediators of intercellular communication and tissue repair.One advantage of exosome therapy is its ability to avoid potential risks associated with stem cell therapy,such as immune rejection or stem cells differentiating into unwanted cell types.However,further research is necessary to optimize exosome therapy,not only in the areas of exosome isolation,characterization,and engineering,but also in determining the optimal dose,timing,administration,and frequency of exosome therapy.Thus,optimization of exosome therapy is critical for the development of more effective and safer exosome-based therapies for acute skin wound healing and other diseases induced by cancer,ischemia,or inflammation.This review provides valuable insights into the potential of exosome therapy and highlights the need for further research to optimize exosome therapy for clinical use.

关键词： exosomes stem cells therapeutic impact skin wound healing

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Fundamentals and application in phytoremediation of an efficient arsenate reducing bacterium Pseudomonas putida ARS1

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Journal of Environmental Sciences 2024年第3期137卷 237-244页

作者： Ze-Wen Wang Guang Yang Jian Chen Yaoyu Zhou Avelino Nunez Delgado Hui-Ling Cui Gui-Lan Duan Barry P.Rosen Yong-Guan Zhu Henan institute of Advanced Technology Zhengzhou UniversityZhengzhou 450052China State Key Lab of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Department of Cellular Biology and pharmacology Florida International UniversityHerbert Wertheim College of MedicineMiamiFL33199USA University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Urban Environment and Health Institute of Urban EnvironmentChinese Academy of SciencesXiamen 361021China College of Resources and Environment Hunan Agricultural UniversityChangsha 410128China Department of Soil Science and Agricultura Chemistry Engineering Polytechnic SchoolUniversity of Santiago de CompostelaCampus Univ.s/n27002LugoSpain

Arsenic is a ubiquitous environmental pollutant.Microbe-mediated arsenic biotransformations significantly infuence arsenic mobility and toxicity.Arsenic transformations by soil and aquatic organisms have been well documented,while little is known regarding effects due to endophytic bacteria.An endophyte Pseudomonas putida ARS1 was isolated from rice grown in arsenic contaminated soil.P.putida ARS1 shows high tolerance to arsenite(As(Ⅲ))and arsenate(As(V)),and exhibits efficient As(V)reduction and As(Ⅲ)effux activities.When exposed to 0.6 mg/L As(V),As(V)in the medium was completely converted to As(Ⅲ)by P.putida ARS1 within 4 hr.Genome sequencing showed that P.putida ARS1 has two chromosomal arsenic resistance gene clusters(arsRCBH)that contribute to efficient As(V)reduction and As(Ⅲ)effux,and result in high resistance to arsenicals.Wolffia globosa is a strong arsenic accumulator with high potential for arsenic phytoremediation,which takes up As(Ⅲ)more efficiently than As(V).Co-culture of P.putida ARS1 and W.globosa enhanced arsenic accumulation in W.globosa by 69%,and resulted in 91%removal of arsenic(at initial concentration of 0.6 mg/L As(V))from water within 3 days.This study provides a promising strategy for in situ arsenic phytoremediation through the cooperation of plant and endophytic bacterium.

关键词： Arsenic Pseudomonas putida Arsenate reduction Endophyte Wolffia globosa Phytoremediation

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An Autopsy and Histopathology-based Study to Ascertain the Cause of Death of Brought Dead Cases

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Journal of Forensic Science and Medicine 2024年第1期10卷 28-33页

作者： Chandan Bandyopadhyay Prabir Chandra Paul Prabhas Chandra Chakraborty Department of Forensic and State Medicine Medical CollegeKolkataWest BengalIndia Department of Pathology Jagannath Gupta Institute of Medical Science and HospitalKolkataWest BengalIndia Department of Forensic Medicine and toxicology NRS Medical College and HospitalKolkataand M.G.M Medical College and L S.K HospitalKishanganjBiharIndia

Background and Objectives:The cases of apparent natural deaths are encountered in the hospital casualties who are noted dead at the time of the first medical attention and as such are labeled as“Brought Dead.”These include the cases of sudden death,unexplained death,and unattended death.The cause of such deaths is reported in the literature to emanate principally from the cardiovascular system,though there are some documented geographical,racial,and other variations.In the present study,we endeavored to detect the cause of such natural deaths in terms of the disease and the organ system involved,in the deceased individuals of the contemporary Bengali population,with cases due to obvious unnatural causes being excluded.Materials and Methods:An observational,cross-sectional study with 105(n=105,male:89,female:16)study subjects of age group of 20-80 years,selected by systemic random sampling,from the brought dead subjects coming to the mortuary of the NRS Medical College and Hospital for medicolegal autopsy from April 2011 to March 2012,excluding cases having a history of the obvious unnatural event.Organ system-wise gross examination was done,followed by tissue sampling for histopathological examination.The case-wise findings were tabulated and analyzed for descriptive statistics using SPSS software.Results:In the present study,89 cases were male(84.8%)and 16 cases were female(15.2%),which reflects a male:female ratio of 5.56:1.The dead bodies are mostly recovered from the footpaths(47 cases,44%).Sixty-four(61%)cases are of known identity.In 54 cases out of 105(51.4%),morbid pathology is detected in the respiratory system(RS),lobar pneumonia,and cavitary pulmonary tuberculosis being the most frequent disease entity,in both genders.Fifty-one years-sixty-five years is found to be the most commonly affected age group,in both genders.Interpretation and Conclusions:The present study shows that the most common organ system involved in brought dead cases is the RS,which is supported by a few Indian studies.

关键词： Autopsy brought dead cause of death histopathology

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Estimating the Scarlet Fever Epidemics Using a Seasonal Autoregressive Fractionally Integrated Moving Average Model

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Biomedical and Environmental Sciences 2024年第3期37卷 336-340页

作者： WANG Yong Bin XUE Chen Lu ZHOU Pei Ping ZHANG Bing Jie XU Chun Jie Department of Epidemiology and Health Statistics School of Public HealthThe First Affiliated Hospital of Xinxiang Medical UniversityXinxiang 453003HenanChina Beijing Key Laboratory of Antimicrobial Agents/Laboratory of pharmacology Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Scarlet fever(SF)is a common infectious disease caused by group A streptococcus(GAS)[1].During the 18th and 19th centuries,SF was a significant cause of mortality in children aged 5-15 years worldwide[2].The incidence and fatality rates of SF have decreased remarkably due to the widespread use of effective antibiotics and improvements in diet and sanitation[3].However,the recent resurgence of SF has sparked significant interest in infectious diseases[1,3].Given the insufficient understanding of the triggers that cause SF outbreaks and the absence of available vaccines to prevent GAS infection to date[1],effective prevention and control programs are needed to manage the ongoing spread of SF.

关键词： prevention mortality let

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Causal genetic regulation of DNA replication on immune microenvironment in colorectal tumorigenesis: Evidenced by an integrated approach of trans-omics and GWAS

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The Journal of Biomedical Research 2024年第1期38卷 37-50页

作者： Sumeng Wang Silu Chen Huiqin Li Shuai Ben Tingyu Zhao Rui Zheng Meilin Wang Dongying Gu Lingxiang Liu Department of Oncology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Environmental Genomics Jiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingJiangsu 211166China Department of Genetic toxicology the Key Laboratory of Modern Toxicology of Ministry of EducationCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Department of Biostatistics Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China Department of Oncology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China.

The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.

关键词： trans-omics DNA replication tumor immune microenvironment causal mediation colorectal tumorigenesis

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Emerging and multifaceted potential contributions of polyphenols in the management of type 2 diabetes mellitus

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World Journal of Diabetes 2024年第2期15卷 154-169页

作者： Ileana González Cristian Lindner Ivan Schneider Erik Diaz Miguel Angel Morales Armando Rojas Biomedical Research Laboratories Faculty of MedicineCatholic University of MauleTalca 34600000Chile Department of Radiology Faculty of MedicineUniversity of ConcepciónConcepción 4030000Chile Centre of Primary Attention South Metropolitan Health ServiceSantiago 3830000Chile Faculty of Medicine Catholic University of MauleTalca 3460000Chile Molecular and Clinical pharmacology Program Institute of Biomedical SciencesUniversity of ChileSantiago 8320000Chile

Type 2 diabetes mellitus(T2DM)is recognized as a serious public health concern with a considerable impact on human life,long-term health expenditures,and substantial health losses.In this context,the use of dietary polyphenols to prevent and manage T2DM is widely documented.These dietary compounds exert their beneficial effects through several actions,including the protection of pancreatic islet β-cell,the antioxidant capacities of these molecules,their effects on insulin secretion and actions,the regulation of intestinal microbiota,and their contribution to ameliorate diabetic complications,particularly those of vascular origin.In the present review,we intend to highlight these multifaceted actions and the molecular mechanisms by which these plant-derived secondary metabolites exert their beneficial effects on type 2 diabetes patients.

关键词： Polyphenols Antioxidants Oxidative stress Type 2 diabetes mellitus Health benefits

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Dcalycinumines A-E,Alkaloids with Cytotoxic Activities of Nasopharyngeal Carcinoma Cells from Daphniphyllum calycinum

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Chinese Journal of Chemistry 2024年第1期42卷 35-42页

作者： Qing Tang Xiao-Yong Dai Qiang Lin Zhi-Peng Ling Yi-Kun Hao Tian-Xi Zhu Ji-Hui Zhang Yi-Bo Hou Yao-Lan Li Lai-Qiang Huang Jing-Hao Wang Guo-Cai Wang Yu-Bo Zhang Guangdong Clinical Translational Centerfor Targeted Drug Department of PharmacologySchoolof MedicineJinan University GuangzhouGuangdong 510632China institute of Traditional Chinese Medicine&Natural Products Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchCollegeof PharmacyJinan UniversityGuangzhouGuangdong511443China institute of Biopharmaceutical and Health Engineering Shenzhen Key Laboratory of Gene and Antibody TherapyState Key Laboratory of Chemical OncogenomicsShenzhen International Graduate SchoolTsinghua UniversityShenzhenGuangdong 518055China The Guangzhou Key Laboratoryof Basic and Translational Research on Chronic Disease Department of PharmacyThe First Affiliated HospitalJinan UniversityGuangzhouGuangdong 510630China

Fivenovel Daphniphyllum alkaloids,named dcalycinumines A-E(1-4,6),andeight previously described Daphniphyllum alkaloids(5,7-13)were isolated from Daphniphyllum calycinum.Compound 1 is the first Daphniphyllum alkaloid possessing a highly rearranged 6/6/6/7/5/6 hexacyclic architecture with a unique 3-methyl-1-azabicyclo[4,4,0]decane ring system.Compound 2 represents a rare diamino Daphniphyllum alkaloid with an unprecedented 6/5/5/6/6/5 carbon skeleton featuring a unique 1-aza-6-azaspiro[4,5]decane unit,whereas 3 also represents a rare diamino Daphniphyllum alkaloid as a possible precursor of 2.Compound 4 is the second example of c-22-nor yuzurimine-type alkaloids.Their structures and absolute configurations were elucidated by HRESIMS,NMR spectroscopic analyses,EcD calculations,and single-crystal X-ray diffraction.Moreover,compound 1 showed remarkable antitumor activities,which could inhibit the proliferation,migration and invasion of nasopharyngeal carcinoma cells,and promoted nasopharyngeal carcinoma cells apoptosis.

关键词： Daphniphyllum calycinum Natural products Daphniphyllum alkaloid Structural elucidation Biological activity Apoptosis Nasopharyngealcarcinoma

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Restoration of GABA_(B) receptor expression in cerebral ischemia:a promising novel neuroprotective strategy

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Neural Regeneration Research 2023年第12期18卷 2659-2660页

作者： Musadiq A.Bhat Mohammad Hleihil Dietmar Benke institute of pharmacology and toxicology University of ZurichZurichSwitzerland

Although stroke is a major global health problem, a pharmacological treatment to inhibit ongoing neuronal death in patients is still lacking. In cerebral ischemia, the prevailing form of stroke, severely reduced blood supply by obstruction of blood vessels deprives neurons from oxygen and glucose, eventually leading to metabolic derailment and death of neurons in the affected brain area.

关键词： cerebral ischemia death

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Spectrum of COVID-19 induced liver injury:A review report

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World Journal of Hepatology 2024年第4期16卷 517-536页

作者： Lokjan Singh Anil Kumar Maya Rai Bibek Basnet Nishant Rai Pukar Khanal Kok-Song Lai Wan-Hee Cheng Ahmed Morad Asaad Shamshul Ansari Department of Microbiology Karnali Academy of Health ScienceTeaching HospitalJumla 21200KarnaliNepal Health Sciences Asian College of Advance StudiesPurbanchal UniversitySatdobato 24122LalitpurNepal Department of Biotechnology Graphic Era(Deemed to be University)Dehradun 248002UttarakhandIndia Department of pharmacology&toxicology KLE College of PharmacyBelagaviKLE Academy of Higher Education and ResearchBelagavi 590010KarnatakaIndia Division of Health Sciences Abu Dhabi Women's CollegeHigher Colleges of TechnologyAbu Dhabi 41012United Arab Emirates Health and Life Sciences INTI International UniversityNilai 71800Malaysia Department of Microbiology College of MedicineZagazig UniversityZagazig 44519Egypt

The coronavirus disease 2019(COVID-19)pandemic has caused changes in the global health system,causing significant setbacks in healthcare systems worldwide.This pandemic has also shown resilience,flexibility,and creativity in reacting to the tragedy.The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection targets most of the respiratory tract,resulting in a severe sickness called acute respiratory distress syndrome that may be fatal in some individuals.Although the lung is the primary organ targeted by COVID-19 viruses,the clinical aspect of the disease is varied and ranges from asymptomatic to respiratory failure.However,due to an unorganized immune response and several affected mechanisms,the liver may also experience liver cell injury,ischemic liver dysfunction,and drug-induced liver injury,which can result in respiratory failure because of the immune system’s disordered response and other compromised processes that can end in multisystem organ failure.Patients with liver cirrhosis or those who have impaired immune systems may be more likely than other groups to experience worse results from the SARS-CoV-2 infection.We thus intend to examine the pathogenesis,current therapy,and consequences of liver damage concerning COVID-19.

关键词： Autoimmune liver disease COVID-19 Clinical manifestation of liver Drug-induced liver injury SARS-CoV-2

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