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Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

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World Journal of Gastroenterology 2024年第5期30卷 471-484页

作者： Hui Hua Qian-Qian Zhao Miriam Nkesichi Kalagbor Guo-Zhi Yu Man Liu Zheng-Rui Bian Bei-Bei Zhang Qian Yu Yin-Hai Xu Ren-Xian Tang Kui-Yang Zheng Chao Yan Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Demonstration Center for Experimental Basic Medical Science EducationLaboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina department of Laboratory Medicine The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221002Jiangsu ProvinceChina

BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment *** adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been *** To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing *** A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC *** sacrifice,the liver and the serum were collected from each *** hepatobiliary injuries,hepatic inflammation and fibrosis were *** targets of let-7a-5p and downstream molecule NF-κB were detected using Western *** rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 *** reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary ***,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic *** Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.

关键词： Primary sclerosing cholangitis Recombinant adeno-associated virus 8 Let-7a-5p Therapeutic effects Inflammation

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Virus-like nanoparticle vaccines for inducing long-lasting immunity against infectious diseases

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National Science Review 2024年第4期11卷 13-15页

作者： Yi-Nan Zhang Sarah Auclair Jiang Zhu department of Integrative Structural and Computational biology The Scripps Research Institute department of immunology and Microbiology The Scripps Research Institute

Prophylactic vaccines that can generate long-lasting protective immune responses are needed for many infectious diseases. Efficient vaccination requires vaccine antigens to be retained and presented to B cells in lymp...

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Identification of gene classifier and modules associated with SARS-CoV-2 ARI in nasal swab

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Genes & Diseases 2024年第1期11卷 38-41页

作者： Pandikannan Krishnamoorthy Athira S.Raj Himanshu Kumar department of Biological Sciences Laboratory of Immunology and Infectious Disease BiologyIndian Institute of Science Education and Research(llSER)BhopalBhopalMP 462066India Laboratory of Host Defense WPl ImmunologyFrontier ResearchCentreOsakaUniversityOsaka 5650871Japan

During a sudden viral pandemic,where the pathogenesis and nature of the infection are unclear,early and accurate identification of the patients infected with the pandemiccausing pathogen is crucial to prevent excess *** the coronavirus disease 2019(COvID-19)pandemic,early diagnosis of severe acute respiratory syndrome virus-2(SARS-CoV-2)is limited by the incidence of the symptoms that are shared with acute respiratory illnesses(ARl)caused by other pathogens.

关键词： acute diagnosis respiratory

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Long-COVID-19: the persisting imprint of SARS-CoV-2 infections on the innate immune system

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Signal Transduction and Targeted Therapy 2024年第1期9卷 12-13页

作者： Marianne Boes Pascal Falter-Braun Center for Translational immunology and department of Pediatric immunology University Medical Center UtrechtUtrecht UniversityUtrechtThe Netherlands Institute of Network biology(INET) Molecular Targets and Therapeutics Center(MTTC)Helmholtz MunichNeuherbergGermany Microbe-Host Interactions Faculty of BiologyLudwig-Maximilians-Universität MünchenPlanegg-MartinsriedGermany

In a recent Cell publication,Cheong et *** how COVID-19 causes IL-6 induced epigenetic reprogramming of human immune stem cells,which causes lasting alterations in the composition and response characteristics of circulating immune cells.1 The study provides important insights into the mechanisms by which SARSCoV-2 infections impact the human immune system and is an important hook into unraveling the mechanisms of post-acute sequelae of COVID-19(PASC)commonly referred to as longCOVID.

关键词： system COV programming

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Cmtm4 deficiency exacerbates colitis by inducing gut dysbiosis and S100a8/9 expression

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Journal of Genetics and Genomics 2024年第8期51卷 811-823页

作者： Qiao Meng Jing Ning Jingjing Lu Jing Zhang Ming Zu Jing Zhang Xiurui Han Huiling Zheng Yueqing Gong Xinyu Hao Ying Xiong Fang Gu Wenling Han Weiwei Fu Jun Wang Shigang Ding department of Gastroenterology Peking University Third HospitalBeijing 100191China Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases(BZ0371) Beijing 100191China CAS Key Laboratory of pathogenic Microbiology and immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100101China department of immunology School of Basic Medical SciencesPeking University Health Science CenterNHC Key Laboratory of Medical Immunology(Peking University)Beijing 100191China Peking University Center for Human Disease Genomics Beijing 100191China

The dysfunction of innate immunity components is one of the major drivers for ulcerative colitis(UC),and increasing reports indicate that the gut microbiome serves as an intermediate between genetic mutations and UC ***,we find that the IL-17 receptor subunit,CMTM4,is reduced in UC patients and dextran sulfate sodium(DSS)-induced *** deletion of CMTM4(Cmtm4^(-/-))in mice leads to a higher susceptibility to DSS-induced colitis than in wild-type,and the gut microbiome significantly changes in *** causal role of the gut microbiome is confirmed with a cohousing *** further identify that S100a8/9 is significantly up-regulated in Cmtm4^(-/-)colitis,with the block of its receptor RAGE that reverses the phenotype associated with the CMTM4 ***4 deficiency rather suppresses S100a8/9 expression in vitro via the IL17 pathway,further supporting that the elevation of S100a8/9 in vivo is most likely a result of microbial *** together,the results suggest that CMTM4 is involved in the maintenance of intestinal homeostasis,suppression of S100a8/9,and prevention of colitis *** study further shows CMTM4 as a crucial innate immunity component,confirming its important role in UC development and providing insights into potential targets for the development of future therapies.

关键词： Ulcerative colitis CMTM4 Gut microbiota IL-17 receptor C(IL-17RC) S100a8/9

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Immune checkpoint inhibitors:breakthroughs in cancer treatment

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Cancer biology & Medicine 2024年第6期21卷 451-472页

作者： Xueqing Kong Jinyi Zhang Shuwei Chen Xianyang Wang Qing Xi Han Shen Rongxin Zhang Laboratory of immunology and Inflammation School of Life Sciences and BiopharmaceuticsGuangdong Pharmaceutical UniversityGuangzhou 510006China department of biology School of Life Sciences and BiopharmaceuticsGuangdong Pharmaceutical UniversityGuangzhou 510006China

Over the past two decades,immunotherapies have increasingly been considered as first-line treatments for most *** such treatment is immune checkpoint blockade(ICB),which has demonstrated promising results against various solid tumors in clinical *** antibodies(mAbs)are currently available as immune checkpoint inhibitors(ICIs).These ICIs target specific immune checkpoints,including cytotoxic T-lymphocyte-associated antigen-4(CTLA-4)and programmed cell death protein 1(PD-1).Clinical trial results strongly support the feasibility of this immunotherapeutic ***,a substantial proportion of patients with cancer develop resistance or tolerance to treatment,owing to tumor immune evasion mechanisms that counteract the host immune ***,substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1,anti-programmed cell death ligand 1(anti-PD-L1),and anti-CTLA-4 ***,several immune checkpoint molecular targets have been identified,such as T cell immunoreceptor with Ig and ITIM domains(TIGIT),mucin domain containing-3(TIM-3),lymphocyte activation gene-3(LAG-3),V-domain immunoglobulin suppressor of T cell activation(VISTA),B and T lymphocyte attenuator(BTLA),and signal-regulatory proteinα(SIRPα).Functional m Abs targeting these molecules are under ***-4,PD-1/PD-L1,and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of *** review discusses these structures,as well as clinical progress in m Abs targeting these immune checkpoint molecules and their potential applications.

关键词： Immunotherapy cancer ICIs PD-1 CTLA-4

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Role of ACLY in the development of gastric cancer under hyperglycemic conditions

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Quantitative biology 2024年第1期12卷 100-116页

作者： Keran Sun Jingyuan Ning Keqi Jia Xiaoqing Fan Hongru Li Jize Ma Meiqi Meng Cuiqing Ma Lin Wei department of immunology Immunology Department of Hebei Medical UniversityShijiazhuangChina department of Pathology Pathology Department of the Fourth Hospital of Hebei Medical UniversityShijiazhuangChina

To investigate the impact of hyperglycemia on the prognosis of patients with gastric cancer and identify key molecules associated with high glucose levels in gastric cancer development,RNA sequencing data and clinical features of gastric cancer patients were obtained from The Cancer Genome Atlas(TCGA)*** glucose-related genes strongly associated with gastric cancer were identified using weighted gene co-expression network and differential analyses.A gastric cancer prognosis signature was constructed based on these genes and patients were categorized into high-and low-risk *** immune statuses of the two patient groups were *** citrate lyase(ACLY),a gene significantly related to the prognosis,was found to be upregulated upon high-glucose *** and molecular analyses confirmed high ACLY expression in gastric cancer tissues and *** Set Enrichment Analysis(GSEA)revealed the involvement of ACLY in cell cycle and DNA replication *** of ACLY affected the proliferation and migration of gastric cancer cells induced by high glucose *** findings suggest that ACLY,as a high glucose-related gene,plays a critical role in gastric cancer progression.

关键词： ACLY gastric cancer high glucose immune microenvironment

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Artificial light at night(ALAN) pollution alters bat lunar chronobiology:insights from broad-scale long-term acoustic monitoring

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Ecological Processes 2024年第01期13卷 176-187页

作者： Han Li Pauline Allen Saige Boris Samantha Lagrama Jade Lyons Christina Mills Pauline Moussi Casey Nichols Carter Tacosik Mc Kenzie Tsaousis Nyzaya Livingston Wilson John F.Grider Kevin A.Parker Matina C.Kalcounis-Rueppell department of biology University of Nebraska Omaha department of biology University of North Carolina Greensboro Colorado Parks and Wild-life Parker Ecology LLC department of Biological Sciences University of Alberta

Background The timing of behavior and habitat use of nocturnal animals can be influenced by the lunar cycle in nature. The prevalence of artificial light at night(ALAN) has been recognized as a source of environmental pol-lution. The interaction between ALAN and the lunar cycle on bat behavior is important for understanding anthro-pogenic effects on bats. We utilized a decade(2012–2022) of acoustic monitoring data collected in North Carolina, United States, to investigate the relationship between bat activity, lunar cycle, and light pollution. We examined whether the amount of lunar illumination affected species-specific nightly activity and whether hourly bat activity patterns varied between nights with different moon phases. We further investigated if the relationship between bat activity and the lunar cycle might be altered by light *** We found that seven bat species showed activity variation across nights in relation to the amount of moon illumination when ALAN was absent. In general, bats were less active on full moon nights compared to new moon nights. Light pollution interacted with the bat–lunar relationship in five of the seven species, masking the effect of the lunar cycle. We identified delayed bat activity patterns on nights with a full or waxing moon in seven species, and light pollution altered that pattern in four species. Overall, ALAN was associated with decreased bat activity inde-pendent of lunar cycle *** Our study demonstrated that at a broad spatial scale, ALAN negatively affected many North American temperate bat species and altered their lunar chronobiology. As light pollution is spreading to historically dark areas and habitats, ALAN might couple with other threats, such as the white-nose syndrome or climate change, to cause cascading damage in the environment that depends on ecosystem services such as pest control provided by bats. We argue that further research and conservation actions are needed to mitigate

关键词： Artificial light at night ALAN Bats Chiroptera Chronobiology Light pollution Lunar cycle Moonlight

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Brain Transcriptome Analysis Reveals Metabolic Changes Adapting to Hyperhaline or Hypohaline Environments in Spotted Scat(Scatophagus argus)

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Journal of Ocean University of China 2024年第3期23卷 755-765页

作者： LIN Ting ZHAI Yi TIAN Changxu JIANG Dongneng SHI Hongjuan JIANG Mouyan LI Guangli DENG Siping Fisheries College Guangdong Ocean UniversityZhanjiang 524088China Guangdong Research Center on Reproductive Control and Breeding Technology of Indigenous Valuable Fish Species Zhanjiang 524088China Guangdong Provincial Key Laboratory of pathogenic biology and Epidemiology for Aquatic Economic Animals Zhanjiang 524088China

The fish brain is crucial for adjusting to environmental *** changes play a vital role in the adaptation to salinity change in aquatic ***,few studies have evaluated the responses of the fish brain to salinity *** evaluate the response to various salinities,spotted scat(Scatophagus argus)was cultured in water with salinity levels of 5(low salinity:LS),25(control group:Ctrl),and 35(high salinity group:HS)for 22 *** brain transcriptome was *** total,1698 differentially expressed genes(DEGs)were identified between the HS and Ctrl groups,and 841 DEGs were identified between the LS and Ctrl *** analysis showed that the DEGs in the HS *** comparison were involved in steroid biosynthesis,terpenoid backbone biosynthesis,fatty acid biosynthesis,ascorbate and aldarate metabolism,other types of O-glycan biosynthesis,and fatty acid *** and dicarboxylate metabolism,one carbon pool by folate,steroid biosynthesis,and cysteine and methionine metabolism were significantly enriched in the LS *** ***,the genes related to metabolism(acc,fas,hmgcr,hmgcs1,mvd,soat1,nsdhl,sqle,cel,fdft1,dnmt3a and mtr)were significantly up-regulated in the HS *** *** genes related to metabolism(lipa,sqle,acc,fas,bhmt,mpst,dnmt3a,mtr,hao2,LOC111225351 and hmgcs1)were significantly up-regulated,while hmgcr and soat1 were significantly down-regulated in the LS *** *** results suggest that salinity stress affects signaling pathways and genes’expressions involved in metabolic processes in the brain,and the differences in metabolism play an important role in adaptation to hyperhaline or hypohaline environments in spotted *** research provides a comprehensive overview of transcriptional changes in the brain under hyperhaline or hypohaline conditions,which is helpful to understand the mechanisms underlying salinity adaptation in euryhaline fishes.

关键词： Scatophagus argus brain salinity transcriptome analysis

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Attenuation of the Activation of NLRP3 Inflammasome in Fibroblast Like Synoviocytes of Rheumatoid Arthritis by Baicalin through Regulating the Let-7i-3p/PI3K/Akt/NF-κB Signaling Axis

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Medicinal Plant 2024年第2期15卷 69-73,76页

作者： Wei ZHANG Li WANG Yuxin YANG Rui MA Li WANG Ling HUANG Qiaofeng WAN department of pathogenic biology and immunology School of Basic MedicineNingxia Medical UniversityYinchuan 750004China department of Rheumatology Ningxia Medical University General HospitalYinchuan 750003China School of Clinical Medicine Ningxia Medical UniversityYinchuan 750004China

[Objectives]To study the effect and mechanism of baicalin on the activation of NLRP3 inflammasome in human fibroblast like synoviocytes of rheumatoid arthritis(HFLS-RA).[Methods]To confirm that baicalin alleviated the activation of NLRP3 inflammasome in HFLS-RA,the expression of NLRP3 before and after baicalin treatment was observed by *** blot was used to detect the protein expression of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1 after baicalin treatment for 48 h,and the contents of IL-1 and IL-18 in the supernatents were detected by *** order to explore the mechanism of baicalin alleviating the activation of NLRP3 inflammasome,the corresponding relationship between let-7i-3p and PIK3CA was verified by double luciferin and Westen blot *** expression of let-7i-3p and PI3K before and after baicalin intervention was detected by ***-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasome.[Results]Baicalin(50 and 100 mg/L)significantly reduced the activation of NLRP3 inflammasome,inhibited the protein expressions of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1,and the secretion of IL-1 and ***-7i-3p and PIK3CA had a targeted correspondence,and baicalin up-regulated the expression of let-7i-3p and down-regulated the expression of *** attenuated the activation of NLRP3 inflammasome enhanced by let-7i-3p interference.[Conclusions]Baicalin can up-regulate let-7i-3p expression,inhibit PI3K/Akt/NF-κB signal transduction,and thus reduce the activation of NLRP3 inflammasome in HFLS-RA.

关键词： Baicalin Rheumatoid arthritis Human fibroblast like synoviocytes of rheumatoid arthritis NLRP3 inflammasome miRNA Dual-luciferase

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