Critical Reviews in Immunology最新文献

{"title":"Study of Therapeutic Mechanisms of Puerarin against Sepsis-Induced Myocardial Injury by Integrating Network Pharmacology, Bioinformatics Analysis, and Experimental Validation.","authors":"Yin Li,&nbsp;Lei Feng,&nbsp;Lin Bai,&nbsp;Hao Jiang","doi":"10.1615/CritRevImmunol.2023050050","DOIUrl":"10.1615/CritRevImmunol.2023050050","url":null,"abstract":"<p><p>Myocardial injury is the most prevalent and serious complication of sepsis. The potential of puerarin (Pue) to treat sepsis-induced myocardial injury (SIMI) has been recently reported. Nevertheless, the specific anti-SIMI mechanisms of Pue remain largely unclear. Integrating network pharmacology, bioinformatics analysis, and experimental validation, we aimed to clarify the anti-SIMI mechanisms of Pue, thereby furnishing novel therapeutic targets. Pue-associated targets were collected from HIT, GeneCards, SwissTargetPrediction, SuperPred, and CTD databases. SIMI-associated targets were acquired from GeneCards and DisGeNET. Differentially expressed genes (DEGs) were identified from GEO database. Potential anti-SIMI targets of Pue were determined using VennDiagram. ClusterProfiler was employed for GO and KEGG analyses. STRING database and Cytoscape were used for protein-protein interaction (PPI) network construction, and cytoHubba was used for hub target screening. PyMOL and AutoDock were utilized for molecular docking. An in vitro SIMI model was built to further verify the therapeutic mechanisms of Pue. Seventy-three Pue-SIMI-DEG intersecting target genes were obtained. GO and KEGG analyses revealed that the targets were principally concentrated in cellular response to chemical stress, response to oxidative stress (OS), and insulin and neurotrophin signaling pathways. Through PPI analysis and molecular docking, AKT1, CASP3, TP53, and MAPK3 were identified as the pivotal targets. In vivo experiments indicated that Pue promoted cell proliferation, downregulated AKT1, CASP3, TP53, and MAPK3, and inhibited inflammation, myocardial injury, OS, and apoptosis in the cell model. Pue might inhibit inflammation, myocardial injury, OS, and apoptosis to treat SIMI by reducing AKT1, CASP3, TP53, and MAPK3.</p>","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology to Reveal the Molecular Mechanisms of Rutaceous Plant-derived Limonin Ameliorating Non-alcoholic Steatohepatitis.","authors":"Wei Wang,&nbsp;Li Yang,&nbsp;Minjie Hu,&nbsp;Yonglin Yang,&nbsp;Qiang Ma,&nbsp;Jiayu Chen","doi":"10.1615/CritRevImmunol.2023050080","DOIUrl":"10.1615/CritRevImmunol.2023050080","url":null,"abstract":"<p><strong>Background: </strong>Limonin shows promise in alleviating non-alcoholic fatty liver disease. We investigated the mechanisms of limonin against non-alcoholic steatohepatitis (NASH) using network pharmacology and molecular docking.</p><p><strong>Methods: </strong>Public databases provided NASH- and limonin-associated targets. VennDiagram identified potential limonin targets for NASH. Enrichment analysis explored the limonin-NASH relationship. PPI network analysis, CytoHubba models, and bioinformatics identified hub genes for NASH treatment. Molecular docking assessed limonin's binding ability to hub targets.</p><p><strong>Results: </strong>We found 37 potential limonin targets in NASH, involved in oxidative stress, inflammation, and signaling pathways. PPI network analysis revealed seven hub genes (STAT3, NFKBIA, MTOR, TLR4, CASP8, PTGS2, NFKB1) as NASH treatment targets. Molecular docking confirmed limonin's binding to STAT3, CASP8, and PTGS2. Animal experiments on high-fat diet mice showed limonin reduced hepatic steatosis, lipid accumulation, and expression of p-STAT3/STAT3, CASP8, and PTGS2.</p><p><strong>Conclusion: </strong>Limonin's therapeutic effects in NASH may stem from its antioxidant and anti-inflammatory properties. STAT3, CASP8, and PTGS2 are potential key targets for NASH treatment, warranting further investigation.</p>","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Cytotoxic Immune Effector Function by AJ3 Probiotic Bacteria in Amyotrophic Lateral Sclerosis (ALS).","authors":"Po-Chun Chen,&nbsp;Kawaljit Kaur,&nbsp;Meng-Wei Ko,&nbsp;Sara Huerta-Yepez,&nbsp;Yash Jain,&nbsp;Anahid Jewett","doi":"10.1615/CritRevImmunol.2023047231","DOIUrl":"10.1615/CritRevImmunol.2023047231","url":null,"abstract":"<p><p>Our recent studies indicated that amyotrophic lateral sclerosis (ALS) patients suffer from significantly elevated levels of interferon-gamma (IFN-γ) secretion by natural killer (NK) and CD8+ T cells, which may be responsible for the immune-pathologies seen in central nervous system and in peripheral organs of the patients. In order to counter such elevated induction of IFN-γ in patients we designed a treatment strategy to increase anti-inflammatory cytokine interleukin-10 (IL-10) by the use of probiotic strains which significantly increase the levels of IL-10. Therefore, in this paper we demonstrate disease specific functions of Al-Pro (AJ3) formulated for the adjunct treatment of auto-immune diseases including ALS, and compared the function with CA/I-Pro (AJ4) for the treatment of cancer and viral diseases, and NK-CLK (AJ2) for maintenance of immune balance and promotion of disease prevention. The three different formulations of probiotic bacteria have distinct profiles of activation of peripheral blood mononuclear cells (PBMCs), NK, and CD8+ T cells, and their induced activation is different from those mediated by either IL-2 or IL-2 + anti-CD16 monoclonal antibodies (mAbs) or IL-2 + anti-CD3/CD28 mAbs. IL-2 + anti-CD16 mAb activation of PBMCs and NK cells had the highest IFN-γ/IL-10 ratio, whereas IL-2 combination with sAJ4 had the next highest followed by IL-2 + sAJ2 and the lowest was seen with IL-2 + sAJ3. Accordingly, the highest secretion of IFN-γ was seen when the PBMCs and NK cells were treated with IL-2 + sAJ4, intermediate for IL-2 + sAJ2 and the lowest with IL-2 + sAJ3. The levels of IFN-γ induction and the ratio of IFN-γ to IL-10 induced by different probiotic bacteria formulation in the absence of IL-2 treatment remained much lower when compared to those treated in the presence of IL-2. Of note is the difference between NK cells and CD8+ T cells in which synergistic induction of IFN-y by IL-2 + sAJ4 was significantly higher in NK cells than those seen by CD8+ T cells. Based on these results, sAJ3 should be effective in alleviating auto-immunity seen in ALS since it will greatly regulate the levels and function of IFN-γ negatively, decreasing overactivation of cytotoxic immune effectors and prevention of death in motor neurons.</p>","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9889278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZC3H13 Enhances the Malignancy of Cervical Cancer by Regulating m6A Modification of CKAP2.","authors":"Yuan Zhang, Xiaoqing Chen, Huiqun Chen, Ying Zhang","doi":"10.1615/CritRevImmunol.2023049342","DOIUrl":"10.1615/CritRevImmunol.2023049342","url":null,"abstract":"<p><p>Sustained expression of zinc finger CCCH-type containing 13 (ZC3H13) in tumors is essential for cancer cell malignancy; however, our understanding of its clinical effects and mechanisms in cervical cancer (CC) is limited. In this study, we aimed to reveal the effect on CC progression of ZC3H13-mediated N6-methyladenosine (m6A) modification to stabilize cytoskeleton-associated protein 2 (CKAP2) expression. CC tissues and paired adjacent normal tissues were collected from 50 patients. qRT-PCR was used to clarify ZC3H13 and CKAP2 expression levels in the CC tissues. The functional roles of ZC3H13 and CKAP2 in CC were analyzed by detecting the changes in CC cell proliferation, migration, invasion, and tumor growth in vivo. The regulatory relationship between ZC3H13 and CKAP2 was investigated by confirming m6A modification levels and their expression correlation. ZC3H13 and CKAP2 were highly expressed in CC and linked with poor prognosis. We observed that ZC3H13 inhibition decreased CC cell proliferation, invasion, and migration, while its facilitation promoted CC cell malignancy. ZC3H13 mediated m6A modification of CKAP2 to enhance CKAP2 expression in CC cells. Furthermore, CKAP2 overexpression partially restored the malignant phenotypic promotion induced by ZC3H13 overexpression in CC cells. In summary, this study revealed that ZC3H13-mediating m6A modification of CKAP2 promotes CC development. This finding should be conducive to an understanding of the role of ZC3H13-m6A-CKAP2 in CC and should provide an effective therapeutic target for this cancer.</p>","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67425701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Index, Volume 43, 2023","authors":"","doi":"10.1615/critrevimmunol.v43.i6.40","DOIUrl":"https://doi.org/10.1615/critrevimmunol.v43.i6.40","url":null,"abstract":"","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135319366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"microRNA-99b regulates Bacillus Calmette-Guerin-infected immature dendritic cell-induced CD4 T cell differentiation by targeting mTOR signaling","authors":"Libo Zhen, Yuanyuan Chen, Juwei Gao, Boying Li, Yangmin Jia","doi":"10.1615/critrevimmunol.2023050312","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023050312","url":null,"abstract":"Objective: This study aimed to elucidate the mechanisms by which microRNA-99b (miR-99b) regulates CD4 T cell differentiation induced by Bacillus Calmette-Guerin (BCG)-infected immature dendritic cells (imDCs). Methods: BCG-infected imDCs were employed to induce CD4 T cell differentiation. Levels of miR-99b, interferon-gamma (IFN-γ), Foxp3, interleukin (IL)-10, IL-17, IL-23, and ROR-γt were assessed. Effects of miR-99b inhibition and mechanistic target of rapamycin (mTOR) agonist on Th17/Treg cell ratio and cytokine levels (IL-6, IL-17, IL-23) were studied. Expression of mTOR, S6K1, and 4E-BP1 related to miR-99b was analyzed. Results: BCG-infected imDCs led to CD4 T cell differentiation and altered levels of IFN-γ, Foxp3, IL-10, miR-99b, IL-17, IL-23, and ROR-γt. Inhibition of miR-99b increased the Th17/Treg cell ratio in CD4 T cells co-cultured with BCG-infected imDCs, and this effect was further enhanced by the mTOR agonist. Additionally, the miR-99b inhibitor elevated the levels of IL-6, IL-17, and IL-23 when CD4 T cells were co-cultured with BCG-infected imDCs, and the mTOR agonist further amplified this increase. Notably, miR-99b negatively regulated mTOR signaling, as the miR-99b inhibitor upregulated the expression levels of mTOR, S6K1, and 4E-BP1 while decreasing miR-99b. Conclusion: miR-99b modulates CD4 T cell differentiation via mTOR pathway in response to BCG-infected imDCs. Inhibiting miR-99b affects Th17/Treg ratio and pro-inflammatory cytokines, potentially impacting tuberculosis immunotherapies.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135267404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin 34 in Disease Progressions: A Comprehensive Review.","authors":"Prerona Boruah, Nikhita Deka","doi":"10.1615/CritRevImmunol.2023050326","DOIUrl":"10.1615/CritRevImmunol.2023050326","url":null,"abstract":"<p><p>IL-34, a cytokine, discovered a decade before and is known to be a colony stimulating factor CSF-1 receptor (CSF-1R) ligand. Along with CSF-1R, it also interacts with syndecan-1 receptors and protein-tyrosine phosphatase (PTP-ζ). Hence, IL-34 takes part in a number of biological activities owing to its involvement in different signaling pathways. This review was done to analyze the recent studies on the functions of IL-34 in progression of diseases. The role of IL-34 under the physiological and pathological settings is studied by reviewing current data. In the last ten years, studies suggested that the IL-34 was involved in the regulation of morbid states such as inflammatory diseases, infections, transplant rejection, autoimmune diseases, neurologic diseases, and cancer. In general, the involvement of IL-34 is observed in many serious health ailments like metabolic diseases, heart diseases, infections and even cancer. As such, IL-34 can be regarded as a therapeutic target, potential biomarker or as a therapeutic tool, which ought to be assessed in future research activities.</p>","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71523361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advancement and Novel Application of Natural Polyphenols for the Treatment of Allergy Asthma: From Phytochemistry to Biological Implications.","authors":"Meera Kumari,&nbsp;Mohd Aftab Siddiqui,&nbsp;Amresh Gupta","doi":"10.1615/CritRevImmunol.2023050289","DOIUrl":"10.1615/CritRevImmunol.2023050289","url":null,"abstract":"<p><p>Allergic diseases, primarily IgE-mediated, exert a substantial global health burden. A pivotal role in allergic reactions is played by mast cells, with histamine serving as a central mediator. Within this context, plant-based polyphenols, abundantly present in vegetables and fruits, show promising potential for allergy prevention. These natural compounds, particularly flavonoids, possess anti-inflammatory and anti-allergic properties, influencing dendritic cells, modulating macrophages, and fostering the proliferation of B cells and T cells. The potent anti-allergic effects of flavonoids are attributed to their ability to reduce the production of signaling factors, suppress cytokine production, and regulate signal transduction and gene expression in mast cells, basophils, and T cells. Notably, their benefits extend beyond allergy prevention, as they hold promise in the prevention and treatment of autoimmune illnesses such as diabetes, rheumatoid arthritis, and multiple sclerosis. In the context of allergic reactions and autoimmune diseases, polyphenols exhibit immunomodulatory effects by inhibiting autoimmune T cell proliferation and downregulating pro-inflammatory cytokines. In recent times, flavonoids, being the most prevalent polyphenols in food, have garnered significant attention from researchers due to their potential health advantages. This review compiles the latest scientific research to highlight the impact of flavonoids on allergic illnesses and their potential as a beneficial dietary component.</p>","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical Activity Increases Immunity to COVID-19 Infection.","authors":"Kiran Dudhat","doi":"10.1615/CritRevImmunol.2023049460","DOIUrl":"10.1615/CritRevImmunol.2023049460","url":null,"abstract":"<p><p>Coronavirus are truly one of the maximum critical fantastic-stranded non-segmented RNA viruses, named after the approximately 126-nm-diameter envelope around the nucleic acid-protein complicated. The virus causes significant harm to human fitness, including direct injury to the respiratory system, immune system compromise, worsening of the underlying clinical conditions, and eventually systemic failure and death. Exercise affects the immune system's antiviral mechanisms. Modest exercise, done before or after infection, improves morbidity and mortality to the contamination, according to animal investigations using influenza and simplex virus in the respiratory tract. Moreover, preclinical research has demonstrated that overtraining has a negative impact on the body's response to viral infections. Follow-up research has shed some light on the mechanisms underlying these discoveries. Through the activation of muscle protein synthesis, physical activity (PA) and exercise are essential for maintaining muscle mass. On the other hand, a lack of muscle contractile activity throughout the country of no exercise, particularly in elderly people, is a major contributor to anabolic rigidity and muscle atrophy.</p>","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Th17 Cells: Orchestrators of Mucosal Inflammation and Potential Therapeutic Targets.","authors":"Dorsa Iraji,&nbsp;Bergithe E Oftedal,&nbsp;Anette S B Wolff","doi":"10.1615/CritRevImmunol.2023050360","DOIUrl":"10.1615/CritRevImmunol.2023050360","url":null,"abstract":"<p><p>T helper 17 (Th17) cells represent a specialized subgroup of effector CD4+ T cells known for their role in provoking neutrophil-driven tissue inflammation, particularly within mucosal tissues. Although they are pivotal for defending the host against extracellular bacteria and fungi, they have also been associated with development of various T cell-mediated inflammatory conditions, autoimmune diseases, and even cancer. Notably, Th17 cells exhibit a dual nature, with different Th17 cell subtypes showcasing distinct effector functions and varying capacities to incite autoimmune tissue inflammation. Furthermore, Th17 cells exhibit significant plasticity, which carries important functional implications, both in terms of their expression of cytokines typically associated with other effector T cell subsets and in their interactions with regulatory CD4+ T cells. The intricate balance of Th17 cytokines can also be a double-edged sword in inflammation, autoimmunity, and cancer. Within this article, we delve into the mechanisms that govern the differentiation, function, and adaptability of Th17 cells. We culminate with an exploration of therapeutic potentials in harnessing the power of Th17 cells and their cytokines. Targeted interventions to modulate Th17 responses are emerging as promising strategies for autoimmunity, inflammation, and cancer treatment. By precisely fine-tuning Th17-related pathways, we may unlock new avenues for personalized therapeutic approaches, aiming to restore immune balance, alleviate the challenges of these disorders, and ultimately enhance the quality of life for individuals affected by them.</p>","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41220753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}