International immunopharmacology最新文献

{"title":"Circulating mitochondria carrying cGAS promote endothelial Secreted group IIA phospholipase A2-mediated neuroinflammation through activating astroglial/microglial Integrin-alphavbeta3 in subfornical organ to augment central sympathetic overdrive in heart failure rats","authors":"Shutian Zhang , Yijun Huang , Chengzhi Han , Maoxiang Chen , Zhaohua Yang , Chunsheng Wang","doi":"10.1016/j.intimp.2024.113649","DOIUrl":"10.1016/j.intimp.2024.113649","url":null,"abstract":"<div><h3>Background</h3><div>Sympathoexcitation, a manifestation of heart–brain axis dysregulation, contributes to the progression of heart failure (HF). Our recent study revealed that circulating mitochondria (C-Mito), a newly identified mediator of multi-organ communication, promote sympathoexcitation in HF by aggravating endothelial cell (EC)-derived neuroinflammation in the subfornical organ (SFO), the cardiovascular autonomic neural center. The precise molecular mechanism by which C-Mito promotes SFO-induced endothelial neuroinflammation has not been fully elucidated.</div></div><div><h3>Objective</h3><div>C-Mito carrying cGAS promote sympathoexcitation by targeting PLA2G2A in ECs of the SFO in HF rats.</div></div><div><h3>Methods</h3><div>Male Sprague–Dawley (SD) rats received a subcutaneous injection of isoprenaline (ISO) at a dosage of 5 mg/kg/day for seven consecutive days to establish a HF model. C-Mito were isolated from HF rats and evaluated. The level of cGAS, a dsDNA sensor recently discovered to be directly localized on the outer membrane of mitochondria, was detected in C-Mito. C-Mito from HF rats (C-Mito<sup>HF</sup>) or control rats (C-Mito<sup>Ctrl</sup>) were intravenously infused into HF rats. The accumulation of C-Mito in the ECs in the SFO was detected via double immunofluorescence staining. The SFO was processed for RNA sequencing (RNA-Seq) analysis. Secreted group IIA phospholipase A2 (PLA2G2A), the key gene involved in C-Mito<sup>HF</sup>-associated SFO dysfunction, was identified via bioinformatics analysis. Upregulation of PLA2G2A in the SFO ECs was assessed via immunofluorescence staining and immunoblotting, and PLA2G2A activity was evaluated. The interaction between cGAS and PLA2G2A was detected via co-immunoprecipitation. The dowstream molecular mechanisms of which PLA2G2A induced astroglial/microglial activation were also investigated. AAV9-TIE-shRNA (PLA2G2A) was introduced into the SFO to specifically knockdown endothelial PLA2G2A. Neuronal activation and glial proinflammatory polarization in the SFO were also evaluated. Renal sympathetic nerve activity (RSNA) was measured to evaluate central sympathetic output. Cardiac sympathetic hyperinnervation, myocardial remodeling, and left ventricular systolic function were assessed in C-Mito-treated HF rats.</div></div><div><h3>Results</h3><div>Respiratory functional incompetence and oxidative damage were observed in C-Mito<sup>HF</sup> compared with C-Mito<sup>Ctrl</sup>. Surprisingly, cGAS protein levels in C-Mito<sup>HF</sup> were significantly higher than those in C-Mito<sup>Ctrl</sup>, while blocking cGAS with its specific inhibitor, RU.521, mitigated respiratory dysfunction and oxidative injury in C-Mito<sup>HF</sup>. C-Mito entered the ECs of the SFO in HF rats. RNA sequencing revealed that PLA2G2A is a key molecule for the induction of SFO dysfunction by C-Mito<sup>HF</sup>. The immunoblotting and immunofluorescence results confirmed that, compared with C-Mito<su","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113649"},"PeriodicalIF":4.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716167","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":"Exercise-induced upregulation of TRIM9 attenuates neuroinflammation in Alzheimer’s disease-like rat","authors":"Xin-Yang Zhang ,&nbsp;Jia-Hao Zhang ,&nbsp;Xiao-Chuan Li ,&nbsp;Hui Lu ,&nbsp;Timon Cheng-Yi Liu","doi":"10.1016/j.intimp.2024.113676","DOIUrl":"10.1016/j.intimp.2024.113676","url":null,"abstract":"<div><h3>Objective</h3><div>Exercise exerts protective effects against Alzheimer’s disease (AD). However, the factors and mechanisms underlying these effects remain largely unknown. This study aims to elucidate the molecular mechanisms by which exercise exerts its protective effects against AD.</div></div><div><h3>Methods</h3><div>Male 7-week-old Sprague-Dawley rats were randomly allocated to four groups (n = 10 per group): control (CON), exercise control (EXE), sedentary AD model induced by intracerebroventricular streptozotocin (STZ) injection, and AD model with treadmill exercise (EXE + STZ). The exercise groups underwent a 13-week treadmill exercise. An intracerebroventricular injection of STZ was used to induce a rat model of AD. The Barnes maze task was employed as an assessment of spatial learning and memory. Hippocampal tissues from three rats per group was collected for proteomic analysis. Immunofluorescence staining, western blot analysis and polymerase chain reaction were performed for the evaluation of Aβ production, tau hyperphosphorylation, differential protein and corresponding signaling pathway.</div></div><div><h3>Results</h3><div>Treadmill exercise could significantly improve STZ-induced cognitive dysfunction and provide neuroprotection by reducing Aβ deposition and tau hyperphosphorylation. Proteomic analysis and further studies demonstrated that treadmill training could significantly increase the expression of tripartite motif-containing 9 (TRIM9). Subsequent research indicated that the upregulation of TRIM9 may<!--> <!-->be due, in part,<!--> <!-->to the inhibition of the NF-κB pathway, thereby reducing the pro-inflammatory factor, and exerting an anti-inflammatory effect.</div></div><div><h3>Conclusions</h3><div>Treadmill exercise attenuates cognitive decline in AD models by upregulating TRIM9 expression, which in turn inhibits NF-κB-mediated neuroinflammation. These findings suggest that TRIM9 may serve as a potential therapeutic target for immunomodulatory strategies against AD.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113676"},"PeriodicalIF":4.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709449","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":"Natural product extract fractions as potential arthritis treatments: A detailed analysis using in-silico, in-vivo, and in-vitro methods","authors":"Bharathiraja Anthony Samy ,&nbsp;Kannan Raman ,&nbsp;Suresh Velayutham ,&nbsp;Nangan Senthilkumar ,&nbsp;Natesan Thirumalaivasan ,&nbsp;Kuppusamy Kanagaraj ,&nbsp;Ramyakrishna Pothu ,&nbsp;Rajender Boddula ,&nbsp;Ahmed Bahgat Radwan ,&nbsp;Noora Al-Qahtani","doi":"10.1016/j.intimp.2024.113595","DOIUrl":"10.1016/j.intimp.2024.113595","url":null,"abstract":"<div><div>Two characteristics of the systemic autoimmune disease rheumatoid arthritis (<strong>RA</strong>) include extra-articular involvement and inflammatory arthritis. It is a long-term inflammatory condition that mostly affects the synovial joints and is often triggered by a confluence of environmental factors, including tobacco use, and genetics. The review investigates natural products’ role in arthritis through three key approaches. <em>In-silico</em> analysis identifies molecular mechanisms and targets of these products, revealing their potential for therapeutic use. <em>In-vivo</em> studies evaluate how well these products work and their safety in reducing joint inflammation. <em>In-vitro</em> studies focus on how these compounds interact at the cellular level and their effects on signaling pathways. Together, these approaches offer a comprehensive understanding of how natural products could benefit arthritis management. This review focuses on translational studies and highlights the possible role of natural compounds as adjunctive therapies to conventional arthritis treatments. In conclusion, this study indicates that natural products have potential advantages in treating osteoarthritis and rheumatoid arthritis based on <em>in-silico</em> analysis which shows anti-inflammatory effects, <em>in-vivo</em> studies that reduce joint inflammation, and <em>in-vitro</em> studies that amplify arthritis management. To improve the therapeutic advantages of natural products utilized for treating arthritis, an all-inclusive examination has been done to give direction for the following research efforts.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113595"},"PeriodicalIF":4.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709966","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":"Inhibition of CRLF1 expression by miR-8485 alleviates IL-1β-induced chondrocyte inflammation, apoptosis, and extracellular matrix degradation","authors":"Guang Yang ,&nbsp;Bingzhou Ji ,&nbsp;Hengzhen Li ,&nbsp;Xiu liu ,&nbsp;Gaoming Liu ,&nbsp;Jianfeng Sun ,&nbsp;Yuming Yao ,&nbsp;Yusheng Li ,&nbsp;Shuguang Liu ,&nbsp;Wenfeng Xiao","doi":"10.1016/j.intimp.2024.113643","DOIUrl":"10.1016/j.intimp.2024.113643","url":null,"abstract":"<div><div>The aim of this study was to investigate the impact of differentially expressed miR-8485 on chondrocyte inflammation in osteoarthritis (OA) and its underlying pathological mechanisms. MiR-8485, which was downregulated in OA, was identified by microarray analysis, and was also found to be decreased in IL-1β-induced C28/I2 cells. miR-8485 down-regulation or IL-1β treated of C28/I2 cells induces a decrease in cellular activity, an increase in apoptosis, an elevation in Cleaved caspase-3, MMP13, and ADAMTS5 protein levels, a decrease in Collagen II and Aggrecan levels, and an increase in the levels of pro-inflammatory factors TNF-α and IL-6. CRLF1 was identified to be a downstream target gene of miR-8485 using bioinformatics prediction and dual luciferase reporter gene assays. CRLF1 was shown to be increased in IL-1β-treated C28/I2 cells, and CRLF1 overexpression partially abrogated the suppressive effect of upregulated miR-8485 on chondrocyte inflammation. In addition, miR-8485 was able to inhibit MAPK/ERK and PI3K/AKT signaling activation by inhibiting CRLF1. In conclusion, miR-8485 was able to inhibit CRLF1 expression and thus inhibit IL-1β-triggered inflammation in chondrocytes, potentially through the inhibition of MAPK/ERK and PI3K/AKT signaling pathways.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113643"},"PeriodicalIF":4.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710038","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":"Research progress on anti-inflammatory drugs for preventing colitis-associated colorectal cancer","authors":"Tong Wang ,&nbsp;Yaojing Huang ,&nbsp;Peng Jiang ,&nbsp;Xin Yuan ,&nbsp;Qian Long ,&nbsp;Xiaochen Yan ,&nbsp;Yuwei Huang ,&nbsp;Zongkui Wang ,&nbsp;Changqing Li","doi":"10.1016/j.intimp.2024.113583","DOIUrl":"10.1016/j.intimp.2024.113583","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is the third most prevalent malignancy worldwide. Inflammatory bowel diseases (IBD) encompass a group of chronic intestinal inflammatory disorders, including ulcerative colitis (UC) and Crohn’s disease (CD). As a chronic inflammatory bowel disease, UC may persist and elevate the risk of malignancy, thereby contributing to the development of colorectal cancer, known as colitis-associated colorectal cancer (CAC). Chronic intestinal inflammation is a significant risk factor for colorectal cancer, and the incidence of colitis-associated colorectal cancer continues to rise. Current studies indicate that therapeutic agents targeting inflammation and key molecules or signaling pathways involved in the inflammatory process may effectively prevent and treat CAC. Mechanistically, drugs with anti-inflammatory or modulatory effects on inflammation-related pathways may exert preventive or therapeutic roles in CAC through multiple molecules or signaling pathways implicated in tumor development. Moreover, the development or discovery of novel drugs with anti-inflammatory properties to prevent or delay CAC progression is becoming an emerging field in fighting against CRC. Therefore, this review aims to summarize drugs that prevent or delay CAC through modulating anti-inflammatory pathways. First, we categorize the published studies exploring the role of anti-inflammatory in CAC prevention. Second, we highlight the specific molecular mechanisms underlying the anti-inflammatory effect of the above-mentioned drugs. Finally, we discuss the potential and challenges associated with clinical application of these drugs. It is hoped that this review offers new insights for further drug development and mechanism exploration.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113583"},"PeriodicalIF":4.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710044","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":"Identification of prognostic tumor microenvironment in patients with advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors","authors":"Song Chen ,&nbsp;Lihua Zhao ,&nbsp;Zhiqiang Wu ,&nbsp;Hongjie Cai ,&nbsp;Fan Wang ,&nbsp;Lijia Wu ,&nbsp;Huaibo Sun ,&nbsp;Wenbo Guo","doi":"10.1016/j.intimp.2024.113662","DOIUrl":"10.1016/j.intimp.2024.113662","url":null,"abstract":"<div><h3>Background</h3><div>In advanced hepatocellular carcinoma (HCC), the triple combination therapy of hepatic arterial infusion chemotherapy (HAIC) with lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has shown promise as a front-line treatment. This study aimed to explore the tumor microenvironment (TME) characteristics of the population benefiting most from this treatment.</div></div><div><h3>Methods</h3><div>The study included 44 patients, with 38 ultimately receiving the HAIC + FOLFOX + lenvatinib + PD-1 inhibitor treatment. Tumor response was evaluated using modified RECIST criteria, classifying patients as responders (complete or partial response) or non-responders (stable or progressive disease). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were assessed. Additionally, genetic sequencing and RNA analysis were conducted on biopsy samples to identify TME differences between the two groups.</div></div><div><h3>Results</h3><div>Among the 38 patients, 22 responded favorably, showing significantly longer median OS (not-reached <em>vs</em>. 8.6 months) and median PFS (15.3 months <em>vs</em>. 2.0 months) compared to non-responders. Common AEs included AST elevation, stomachache, nausea, and hypertension, with limited severe AEs. Genetic analysis revealed no significant differences in DNA features between the groups. However, RNA analysis indicated that responders had a more robust immune status, better drug sensitivity, and increased immune cell infiltration. Notably, higher levels of tumor-infiltrating T lymphocytes were linked to better responses, longer PFS, and OS.</div></div><div><h3>Conclusion</h3><div>The differences in the initial TME of patients, especially in tumor-infiltrating T lymphocytes, may be potential biomarkers for predicting response and prognosis. This finding provides clues to search for biomarkers for this triple combination therapy in advanced HCC.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113662"},"PeriodicalIF":4.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709537","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":"In silicon desinging of RANKL-targeting vaccine for protection of osteoporosis based on the epitope of Denosumab","authors":"Tailin Wu ,&nbsp;Bin Guan ,&nbsp;Jianzhou Luo ,&nbsp;Lin Li ,&nbsp;Bobo Zhang ,&nbsp;Zili Yang ,&nbsp;Lei Tan ,&nbsp;Huiren Tao","doi":"10.1016/j.intimp.2024.113610","DOIUrl":"10.1016/j.intimp.2024.113610","url":null,"abstract":"<div><h3>Background</h3><div>Life quality of osteoporosis patients is affected significantly due to the severely complications of fracture and pain. RANKL, indicated as the key mediator of osteoporosis, plays a pathogenic role of osteoclasts induction. To target this program, two medications, bisphosphonate and Denosumab, were developed and achieved remarkable advantages in clinics. Unfortunately, fracture-related side-effects always emerge unavoidably, after either long-term administration of bisphosphonates or Denosumab withdrawing. To address these challenges, vaccine-based approach has been adopted to achieve sustainable protection through induction and maintenance of effective antibodies in mild level over decades.</div></div><div><h3>Methods</h3><div>A Denosumab binding peptide was firstly identified as the basic component of vaccine. This peptide was then fused with diphtheria toxin T domain, a widely used adjuvant protein. Its capabilities to penetrate the autologous tolerance and induce the immune responses was then demonstrated with in-silicon evaluation. Finally, the efficacy of the DR3 vaccine was assessed through immunization on the human RANKL transgenic mice model of osteoporosis.</div></div><div><h3>Results</h3><div>The DTT-RANKL_(220–245)3 vaccine, termed as DR3, were predicted as highly antigenic and non-allergenicity. This molecule was comprised of 46.5 % of helix, 8.5 % strand and 45.1 % coil, the optimized Z-value of the tertiary structure was 6.39, and the favored area in the Ramachandran plot was 96.1 % after refinement. Molecular docking showed a tight binding of DR3 vaccine to TLR2 (−9.2 kcal/mol) and TLR4 (−9.5 kcal/mol). In addition, the immune stimulation indicated robust responses post administration of DR3 vaccine, including high level production of of antibodies and cytokines, activated T and B lymphocytes, and the long-last immune memory. In agree with the simulation, vaccinated mice generated high titers anti-hRANKL antibodies and elevated levels of IL-4 and IL-10 at 7th week post immunization.</div></div><div><h3>Conclusion</h3><div>DR3 vaccine was aroused to benefit the prevention and treatment of osteoporosis, and other bone-resorptive diseases potentially.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113610"},"PeriodicalIF":4.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709635","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":"Inflammatory microenvironment promotes extracellular matrix degradation of chondrocytes through ALKBH5-dependent Runx2 m6A modification in the pathogenesis of osteoarthritis","authors":"Guanghua Nie,&nbsp;Yi Li,&nbsp;Hongmou Zhao,&nbsp;Chengyi Liu,&nbsp;Yan Zhang,&nbsp;Xinquan Yang,&nbsp;Feng Tian,&nbsp;Xiaodong Wen","doi":"10.1016/j.intimp.2024.113638","DOIUrl":"10.1016/j.intimp.2024.113638","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the breakdown of cartilage and extracellular matrix (ECM). The degradation of ECM in chondrocytes plays a crucial role in OA pathogenesis, but the underlying molecular mechanisms remain largely unclear.</div></div><div><h3>Methods</h3><div>A sodium monoiodoacetate (MIA) mouse model was used to mimic OA. ECM integrity was accessed by Hematoxylin and Eosin (H&amp;E) staining, Safranin O/fast green staining, and microcomputerized tomography. Enzyme-linked immunosorbent assay measured circulating proinflammatory cytokines. Reverse transcription-quantitative polymerase chain reaction and western blotting analyzed mRNA and protein expression levels. RNA and chromatin immunoprecipitation evaluated RNA-protein and DNA-protein interactions.</div></div><div><h3>Results</h3><div>MIA mice showed significant upregulation of the RNA m⁶A demethylase ALKBH5 (alkylated DNA repair protein AlkB homolog 5), the transcription factor Runx2 (runt-related transcription factor 2), and matrix-degrading enzymes Mmps (matrix metallopeptidase) and Adamts(s) (a disintegrin and metalloproteinase with thrombospondin motifs). In vitro, proinflammatory cytokines induced these proteins in chondrocytes. Mechanically, Alkbh5 cooperated with Ythdf1 (YTH N6-methyladenosine RNA binding protein 1) in the inflammatory microenvironment to regulate the expression and stability of <em>RUNX2</em> mRNA. Runx2, in turn, activated the expression of <em>MMPs</em> and <em>ADAMTSs</em>, promoting ECM degradation in chondrocytes, thereby contributing to OA progression. Notably, inhibition of Alkbh5 and Runx2 in MIA-treated mice significantly alleviated the pathological progression of OA.</div></div><div><h3>Conclusion</h3><div>Our results reveal a novel mechanism of OA pathogenesis and suggest that targeting Alkbh5 and Runx2 may represent a new therapeutic strategy for OA treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113638"},"PeriodicalIF":4.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709728","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":"Plasma extracellular vesicles regulate the Functions of Th2 and ILC2 cells via miRNA-150-5p in patients with allergic rhinitis","authors":"Shu-Bin Fang ,&nbsp;Zhi-Rou Zhou ,&nbsp;Qi Sun ,&nbsp;Xiao-Qing Liu ,&nbsp;Chan-Gu Li ,&nbsp;Ying-Chun Xie ,&nbsp;Bi-Xin He ,&nbsp;Tian Tian ,&nbsp;Xiao-Hui Deng ,&nbsp;Qing-Ling Fu","doi":"10.1016/j.intimp.2024.113644","DOIUrl":"10.1016/j.intimp.2024.113644","url":null,"abstract":"<div><div>Allergic rhinitis (AR), a chronic airway inflammation, has witnessed a rising prevalence in recent decades. Recent research indicates that various EVs are released into plasma in allergic airway inflammation, correlating with impaired airway function and severe inflammation. However, the contribution of plasma EVs to AR pathogenesis remains incompletely understood. We isolated plasma EVs using differential ultracentrifugation or size exclusion chromatography (SEC) and obtained differential microRNA (miRNA) expression profiles through miRNA sequencing. Peripheral blood mononuclear cells (PBMCs) were exposed to plasma EVs and miRNA mimics and inhibitors to assess the effect of plasma EVs and the underlying mechanisms. We found that EVs from HC and AR patients exhibited comparable characteristics in terms of concentration, structure, and EV marker expression. AR-EVs significantly enhanced Th2 cell levels and promoted ILC2 differentiation and IL-13⁺ ILC2 levels compared to HC-EVs. Both HC-EVs and AR-EVs were efficiently internalized by CD4⁺ T cells and ILCs. miRNA sequencing of AR-EVs revealed unique miRNA signatures implicated in diverse biological processes, among which miR-150-5p, miR-144-3p, miR-10a-5p, and miR-10b-5p were identified as pivotal contributors to AR-EVs’ effects on CD4⁺ T cells and ILC2s. MiR-150-5p exhibited the most pronounced impact on cell differentiation and was confirmed to be upregulated in AR-EVs by PCR. In total, our study demonstrated that plasma EVs from patients with AR exhibited a pronounced capacity to significantly enhance the differentiation of Th2 cells and ILC2, which was correlated with an elevated expression of miR-150-5p within AR-EVs. These findings contribute to the advancement of our comprehension of EVs in the pathogenesis of AR and hold the potential to unveil novel therapeutic targets for the treatment of AR.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113644"},"PeriodicalIF":4.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710008","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":"Protective effects of phosphocreatine against Doxorubicin-Induced cardiotoxicity through mitochondrial function enhancement and apoptosis suppression via AMPK/PGC-1α signaling pathway","authors":"Eskandar Qaed ,&nbsp;Marwan almoiliqy ,&nbsp;Wu Liu ,&nbsp;Haitham Saad Al-mashriqi ,&nbsp;Eman Alyafeai ,&nbsp;Waleed Aldahmash ,&nbsp;Mueataz A. Mahyoub ,&nbsp;Zeyao Tang","doi":"10.1016/j.intimp.2024.113677","DOIUrl":"10.1016/j.intimp.2024.113677","url":null,"abstract":"<div><div>Doxorubicin (DOX), a potent chemotherapy drug, is limited by its cardiotoxic effects, which can lead to heart damage. This study explores the cardioprotective potential of Phosphocreatine (PCr) in vitro and in vivo models, focusing on its impact on the AMPK and PGC-1α pathways, apoptosis reduction, and mitochondrial function preservation. Advanced methodologies, including high-resolution respirometry (HRR), were employed to assess mitochondrial bioenergetics, AMPK activity, and apoptotic rates in cardiomyocytes. Electrocardiography (ECG) and echocardiography (echo) were used to monitor cardiac function in vivo. Results showed that PCr significantly activated the AMPK and PGC-1α pathways, reduced apoptosis, and stabilized mitochondrial function in cardiomyocytes exposed to DOX. There was an upregulation of AMPK and PGC-1α target genes, stabilization of mitochondrial membranes, and improvements in cellular energy production and antioxidant defenses. PCr also markedly reduced apoptotic markers, enhancing cardiomyocyte viability. ECG and echocardiography revealed that PCr preserved cardiac function, indicated by improved heart rate variability, reduced QT interval prolongation, and enhanced ejection fraction. These findings highlight PCr’s potential in mitigating DOX-induced cardiotoxicity by enhancing mitochondrial function and reducing apoptosis. The study underscores the promise of PCr as an agent to reduce chemotherapy-related cardiac injuries, paving the way for further research to improve patient outcomes in cancer treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"144 ","pages":"Article 113677"},"PeriodicalIF":4.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710014","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}