International immunopharmacology最新文献

{"title":"The use of ozone in the anti-aging and wellbeing proposals. A proof of concern.","authors":"Salvatore Chirumbolo, Marianno Franzini, Umberto Tirelli, Luigi Valdenassi","doi":"10.1016/j.intimp.2024.113609","DOIUrl":"https://doi.org/10.1016/j.intimp.2024.113609","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":" ","pages":"113609"},"PeriodicalIF":4.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin inhibits the progression of hyperlipidemia via OGT mediated O-GlcNAcylation modulation of APOC3","authors":"Guotong Sun ,&nbsp;Yaowen Xu ,&nbsp;Xiuwen Liang ,&nbsp;Lei Wang ,&nbsp;Yu Liu","doi":"10.1016/j.intimp.2024.113647","DOIUrl":"10.1016/j.intimp.2024.113647","url":null,"abstract":"<div><div>The etiology of hyperlipidemia is complex, and our understanding of its underlying mechanisms is limited. Effective therapeutic strategies for hyperlipidemia remain elusive. This study aimed to confirm the effect of curcumin on hyperlipidemia treatment and elucidate the precise mechanism. A high-fat diet-induced hyperlipidemia model using C57BL/6J mice and HaCaT cells was established. Co-immunoprecipitation and immunofluorescence were performed to detect protein interactions, and immunoprecipitation coupled with Western blotting was used to assess protein succinylation. 40 μM of curcumin administration promoted cell viability, increased the levels of glutathione peroxidase, glutathione, catalase, and superoxide dismutase, while reducing reactive oxygen species activity and the levels of triglycerides and malondialdehyde. Additionally, curcumin attenuated the development of hyperlipidemia in vivo. Mechanistically, 100 mg/kg of curcumin promoted O-GlcNAcylation and increased the expression of O-linked N-acetylglucosamine transferase in HaCaT cells. Furthermore, apolipoprotein C3 was identified as a substrate of O-linked N-acetylglucosamine transferase, and O-GlcNAcylation of apolipoprotein C3 enhanced its stability. Rescue experiments further verified that curcumin exerts its effects by regulating apolipoprotein C3 expression. In conclusion, these findings provide novel insights into the treatment of hyperlipidemia.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113647"},"PeriodicalIF":4.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luteolin ameliorates periodontitis by modulating mitochondrial dynamics and macrophage polarization via the JAK2/STAT3 pathway","authors":"SiJia Ma ,&nbsp;Hongbing He ,&nbsp;Xiaobin Ren ,&nbsp;Rongkun Chen ,&nbsp;Ruoyu Zhao ,&nbsp;Keyu Dong ,&nbsp;Chenxi Wei","doi":"10.1016/j.intimp.2024.113612","DOIUrl":"10.1016/j.intimp.2024.113612","url":null,"abstract":"<div><h3>Background</h3><div>Periodontal disease (PD) is a chronic inflammatory condition affecting oral and systemic health. Luteolin (LUT), a natural flavonoid, has shown anti-inflammatory effects, but its therapeutic potential and mechanisms in PD remain unclear.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the effects of LUT on PD, focusing on its impact on mitochondrial dynamics, macrophage polarization, and the JAK2/STAT3 signaling pathway.</div></div><div><h3>Methods</h3><div>A combination of network pharmacology analysis and in vivo and in vitro experiments was employed. The efficacy of LUT was evaluated using a ligature-induced rat PD model and LPS-stimulated THP-1-derived macrophages. Key assessments included micro-CT for bone loss, flow cytometry for macrophage polarization, and Western blot for pathway analysis.</div></div><div><h3>Results</h3><div>LUT significantly reduced alveolar bone loss and enhanced M2 macrophage polarization, as indicated by increased CD206 and Arg1 expression. Additionally, it improved mitochondrial function by reducing ROS and restoring membrane potential, decreasing mitochondrial fission, and promoting mitochondrial fusion. Mechanistically, LUT inhibited JAK2/STAT3 phosphorylation, promoting anti-inflammatory effects.</div></div><div><h3>Conclusion</h3><div>These findings suggest that LUT ameliorates periodontal inflammation and bone loss by modulating mitochondrial dynamics, promoting M2 macrophage polarization, and suppressing the JAK2/STAT3 signaling pathway. This highlights LUT as a promising multitarget candidate for PD treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113612"},"PeriodicalIF":4.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The gut-reproductive axis: Bridging microbiota balances to reproductive health and fetal development","authors":"Bohao Li ,&nbsp;Yan Xiong ,&nbsp;Dong Guo ,&nbsp;Guohong Deng ,&nbsp;Haibo Wu","doi":"10.1016/j.intimp.2024.113627","DOIUrl":"10.1016/j.intimp.2024.113627","url":null,"abstract":"<div><div>The gut microbiota is a highly complex microbial community residing in the digestive tract of humans and animals, closely linked to host health. Dysbiosis within the gut microbiota has been associated with various diseases. Moreover, it interacts with the female reproductive system’s microbiota, influencing maternal reproductive homeostasis. Although the gut microbiota holds potential for treating reproductive system diseases and modulating offspring fertility, research in this domain remains limited. This review examines the relationship between both balanced and imbalanced gut microbiota and reproductive system diseases, as well as their effects on fetal development. It is highlighted that dysbiosis in the gut microbiota may contribute to several reproductive conditions, including polycystic ovary syndrome (PCOS), preeclampsia (PE), endometriosis, gestational diabetes, and reproductive cancers. The abundance of specific gut microbial species or interactions among various species can influence the reproductive system through hormonal pathways and other mechanisms, ultimately affecting pregnancy outcomes and fetal health. Therefore, the concept of the gut-reproductive axis is proposed, emphasizing the significant role of maternal gut microbiota in shaping fetal development, metabolic capacity, and immunity.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113627"},"PeriodicalIF":4.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal effects of circulating inflammatory proteins on oral phenotypes: Deciphering immune-mediated profiles in the host-oral axis","authors":"Xinjian Ye ,&nbsp;Tan Chen ,&nbsp;Jiuhao Cheng,&nbsp;Yue Song,&nbsp;Peihui Ding,&nbsp;Zhiyong Wang,&nbsp;Qianming Chen","doi":"10.1016/j.intimp.2024.113642","DOIUrl":"10.1016/j.intimp.2024.113642","url":null,"abstract":"<div><h3>Background</h3><div>Oral manifestations function as precursors to potential systemic pathologies, signaling early indicators of underlying health complications or immunological dysfunctions. Within these dynamics, circulating inflammatory proteins are recognized as critical mediators in immunopharmacology, bridging holistic health, immune response, and oral health.</div></div><div><h3>Methods</h3><div>We employed genetic data from genome-wide association studies to perform comprehensive Mendelian randomization (MR) analyses on 91 circulating inflammatory proteins and 17 oral phenotypes. Six MR algorithms and five auxiliary control measures were utilized to estimate the causal effects. Subsequently, the MR-Bayesian model averaging (MR-BMA) approach was conducted to elucidate the priorities in host-oral communication, followed by network analyses to explore the interactions among phenotypes.</div></div><div><h3>Results</h3><div>After multiple corrections, MR identified five genetically predicted proteins associated with oral phenotypes. Specifically, FGF21 was correlated with Nteeth and DMFS; hGDNF with gingival pain; CCL4 with stomatitis; and S100A12 with denture use. The causal associations remained robust in sensitivity analyses. Nine protein-phenotype clusters were prioritized using MR-BMA. Among these, S100A12, FGF19, FGF21, and CCL4 exhibited extensive correlations with various oral phenotypes.</div></div><div><h3>Conclusions</h3><div>Our study offers novel genetic insights into the causal relationships, prioritizations, and connections between circulating inflammatory proteins and oral phenotypes. These findings comprehensively depict immune-mediated proteomic profiles underlying the host-oral axis, providing significant implications for clinical practice, public health, and immunopharmacology.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113642"},"PeriodicalIF":4.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testosterone deficiency aggravates diet-induced non-alcoholic fatty liver disease by inducing hepatocyte ferroptosis via targeting BMAL1 in mice","authors":"Yingying Fan ,&nbsp;Yujie Ren ,&nbsp;Liqun Deng ,&nbsp;Dongying Lv ,&nbsp;Jiayan Chen ,&nbsp;Yun Ling ,&nbsp;Jue Tu ,&nbsp;Xiaoping Xu ,&nbsp;Dejun Wang ,&nbsp;Zhaowei Cai","doi":"10.1016/j.intimp.2024.113641","DOIUrl":"10.1016/j.intimp.2024.113641","url":null,"abstract":"<div><h3>Background</h3><div>Testosterone deficiency is linked to an increased prevalence of non-alcoholic fatty liver disease (NAFLD), although the mechanisms underlying this association are not fully understood. Ferroptosis, a regulated cell death pathway driven by iron-dependent lipid peroxidation, has been suggested to play a role in NAFLD pathogenesis. Since testosterone deficiency is associated with lipid disorders and iron deposition, we hepothesize that ferroptosis may be involved in the pathogenesis of diet-induced NAFLD exacerbated by testosterone deficiency.</div></div><div><h3>Methods</h3><div>Apolipoprotein E (APOE^−/−) mice were subjected to sham surgery or bilateral castration and subsequently fed a high-fat diet for 16 weeks. Liver gene expression was analyzed using RNA sequencing. Additional assessments included blood analysis, histological staining, measurement of iron and antioxidant enzyme levels, quantitative real-time PCR, Western blotting, and electron microscopy. The effects of testosterone on ferroptosis induced by free fatty acids (FFAs) and Erastin were further investigated in HepG2 cells in vitro.</div></div><div><h3>Results</h3><div>Testosterone deficiency resulted in increased hepatic lipid accumulation and macrovesicular steatosis in high-fat diet-fed APOE^−/− mice, accompanied by hepatic inflammation, fibrosis, and elevated liver enzyme levels. Transcriptomic analysis revealed that testosterone deficiency affects ferroptosis and circadian rhythm-related signaling pathways. Castrated APOE^−/− mice exhibited significantly higher hepatic iron deposition, lipid peroxidation, and expression of key ferroptosis-related proteins, along with decreased Brain and muscle ARNT-like gene 1 (BMAL1) protein expression. In vitro, testosterone treatment reduced lipid and iron accumulation and lipid peroxidation in HepG2 cells subjected to FFAs and Erastin. Moreover, BMAL1 knockdown negated the protective effects of testosterone against ferroptosis in hepatocytes.</div></div><div><h3>Conclusion</h3><div>Our study demonstrated that testosterone deficiency exacerbates NAFLD induced by a high-fat diet by promoting hepatocyte ferroptosis through modulation of the circadian protein BMAL1.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113641"},"PeriodicalIF":4.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kanglaite alleviates lung squamous cell carcinoma through ferroptosis","authors":"Mei-Ling Jiang ,&nbsp;Li Liu ,&nbsp;Zilin Wang ,&nbsp;Xue Yang ,&nbsp;Zhiyong Lin ,&nbsp;Runqiu Jiang ,&nbsp;Cun-Jin Zhang ,&nbsp;Weiyan Wang","doi":"10.1016/j.intimp.2024.113616","DOIUrl":"10.1016/j.intimp.2024.113616","url":null,"abstract":"<div><div>Kanglaite, a compound predominantly composed of polyunsaturated fatty acids (PUFAs), has been employed in the clinical treatment of adenocarcinoma non-small cell lung cancer (NSCLC) in China for decades. However, its therapeutic efficacy and specific mechanism in the treatment of squamous NSCLC remains unexplored. In this study, we demonstrate that the co-treatment with ferric ion significantly enhances the cytotoxic effects of kanglaite by inducing ferroptosis in NCL-H1703, a cell line of human lung squamous cell carcinoma. Mechanistic investigations reveal that kanglaite induces mitochondrial dysfunction resulting in reactive oxygen species (ROS) excessive production, which is critical for the induction of ferroptosis. Further analysis shows that kanglaite suppresses the PI3K/AKT signaling pathway, leading to increased IP3 generation. IP3 subsequently binds to and activates IP3R, an endoplasmic reticulum (ER) calcium channel, exacerbating the excessive calcium transfer from the ER to mitochondria. The overloaded mitochondrial calcium contributes to its dysfunction and elevates ROS production. To optimize the synergistic effects of ferric ion and kanglaite, we develop a mesoporous silica-based nanodrug delivery system co-loaded with Kanglaite and Fe₃O₄, which offers several notable advantages, including reduced drug dosage and a faster therapeutic onset. Finally, in an NCL-H1703 xenograft model, the DMSN/Fe₃O₄-Kanglaite nanodrug significantly inhibited tumor growth. In conclusion, we identified the function and mechanism of kanglaite in treatment of squamous NSCLC and have developed a DMSN/Fe₃O₄-Kanglaite nanodrug, providing a superior therapeutic approach for the treatment of squamous NSCLC.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113616"},"PeriodicalIF":4.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ITGB4/GNB5 axis promotes M2 macrophage reprogramming in NSCLC metastasis","authors":"Xiaofeng Huang ,&nbsp;Guiping Yu ,&nbsp;Xuewei Jiang,&nbsp;Fei Shen,&nbsp;Dengshu Wang,&nbsp;Song Wu,&nbsp;Yedong Mi","doi":"10.1016/j.intimp.2024.113564","DOIUrl":"10.1016/j.intimp.2024.113564","url":null,"abstract":"<div><h3>Objective</h3><div>Metastasis of non-small cell lung cancer (NSCLC) is a leading cause of high mortality. In recent years, the role of M2 macrophages in promoting tumor metastasis within the tumor microenvironment has garnered increasing attention. This study aims to investigate the role and potential mechanisms of the ITGB4/GNB5 axis in regulating M2 macrophage reprogramming and influencing NSCLC metastasis.</div></div><div><h3>Methods</h3><div>This study first used single-cell sequencing technology to reveal the diverse subpopulation structure of NSCLC tumor tissues. Data analysis then identified the correlation between M2 macrophages and the malignant phenotype of NSCLC. Flow cytometry and immunohistochemistry were used to detect changes in M2 macrophages in NSCLC tissues. The impact of the ITGB4/GNB5 axis on M2 macrophage function was assessed through RNA sequencing and proteomic analysis. Finally, <em>in vitro</em> cell experiments and <em>in vivo</em> mouse models were used to validate the function and regulatory mechanisms of this axis.</div></div><div><h3>Results</h3><div>Our study found diverse cellular subpopulations in NSCLC tumor tissues, with M2 macrophages closely associated with the malignant phenotype of NSCLC. We identified ITGB4 as a characteristic gene of NSCLC and predicted GNB5 as an interacting gene through database analysis. Activation of the ITGB4/GNB5 axis was shown to enhance M2 macrophage polarization, promoting their accumulation in the tumor microenvironment. This change further facilitated NSCLC invasion and metastasis by modulating related cytokines and signaling pathways. Animal experiments demonstrated that inhibition of the ITGB4/GNB5 axis significantly reduced tumor growth and metastasis.</div></div><div><h3>Conclusion</h3><div>The ITGB4/GNB5 axis reshapes the TME by promoting M2 macrophage polarization and functional enhancement, thereby facilitating tumor invasion and metastasis in NSCLC. This research provides new insights into the molecular mechanisms of NSCLC and offers potential molecular targets for future targeted therapies.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113564"},"PeriodicalIF":4.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXO3a overexpression ameliorates intervertebral disc degeneration by decreasing NLRP3-mediated pyroptosis","authors":"Qi Min ,&nbsp;Xu Chen ,&nbsp;Gu Yifei ,&nbsp;Sun Baifeng,&nbsp;Wu Zichuan,&nbsp;Shen Xiaolong,&nbsp;Chen Huajiang,&nbsp;Yuan Wen,&nbsp;Liu Yang","doi":"10.1016/j.intimp.2024.113596","DOIUrl":"10.1016/j.intimp.2024.113596","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113596"},"PeriodicalIF":4.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron chelation therapy and chondrocyte health in osteoarthritis management in patients with beta thalassaemia major","authors":"Alper Uysal","doi":"10.1016/j.intimp.2024.113601","DOIUrl":"10.1016/j.intimp.2024.113601","url":null,"abstract":"","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113601"},"PeriodicalIF":4.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}