Immunopharmacology and Immunotoxicology最新文献

{"title":"Inhibition of Slit3/Robo1 signaling alleviates osteoarthritis in mice by reducing abnormal H-type vessel formation in subchondral bone.","authors":"Peng Li, Kai Feng, Xuehua Zhan","doi":"10.1080/08923973.2024.2424297","DOIUrl":"10.1080/08923973.2024.2424297","url":null,"abstract":"<p><strong>Background: </strong>The aberrant H-type vessel formation was found to be intimately linked to subchondral bone remodeling during osteoarthritis (OA) development. Herein, we investigated the role and mechanism of osteoblast-secreted slit guidance ligand 3 (Slit3) in H-type vessel formation during OA progression.</p><p><strong>Methods: </strong>Slit3 protein levels in subchondral bone samples of OA patients were detected. The isolated osteoblasts were transfected with Slit3 overexpression or knockdown plasmids, and their conditioned medium was cultured with endothelial progenitor cells (EPCs). The migration, tube formation, VEGF, and H-type vessel marker protein CD31 and endomucin (EMCN) levels in EPCs were accessed. The interactions between Slit3 and roundabout (Robo) family members were validated by Co-IP assay. Besides, whether the Slit3/Robo signaling affects the transforming growth factor β1 (TGF-β1)/SMADs pathway was determined. Additionally, sh-Slit3 was injected into OA mice, followed by the detection of articular cartilage degradation, subchondral bone remodeling, and H-type vessel formation.</p><p><strong>Results: </strong>Slit3 was upregulated in subchondral bone tissues of OA patients. Slit3 overexpression in osteoblasts intensified the migration and H-type vessel formation of EPCs, while Slit3 knockdown showed the opposite results. Slit3 overexpression enhanced Robo1 protein level. Robo1 knockdown abrogated Slit3-mediated migration and H-type vessel formation in EPCs. Slit3 activated the TGF-β1/SMADs pathway in EPCs, which might be associated with H-type vessel formation in EPCs. Additionally, Slit3 silencing restrained articular cartilage degradation, aberrant subchondral bone formation, and H-type vessel formation in OA mice.</p><p><strong>Conclusion: </strong>Inhibition of Slit3/Robo1 signaling alleviates osteoarthritis in mice by reducing abnormal H-type vessel formation in the subchondral bone.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"935-946"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604338","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":"Intervention of inflammation associated with ankylosing spondylitis by triptolide promotes histone H3 Iys-27 trimethylation.","authors":"Xiao-Han Xu, Jin-Xu Zhang, Hong-Xiao Liu, Zhe Zhao, Jun-Yi Jiang","doi":"10.1080/08923973.2024.2402911","DOIUrl":"10.1080/08923973.2024.2402911","url":null,"abstract":"<p><p><b>Objective:</b> This study aims to explore the effects of Triptolide (TP) on the differentiation of Th17 cells in ankylosing spondylitis (AS).</p><p><p><b>Methods:</b> Peripheral blood mononuclear cells (PBMCs) collected from 10 patients with active AS patients were exposed to TP, GSK-J4 or vehicle. T lymphocyte subsets were analyzed using flow cytometry. ELISA was used to assess the level of IL-17. Western blot analysis and quantitative RT-PCR were used to measure the mRNA and protein levels of RORγt, JMJD3, EZH2, JAK2 and STAT3 in the JAK2/STAT3 signaling pathway.</p><p><p><b>Results:</b> We observed a tendency toward a greater percentage of IL-17-positive CD4+ T cells in peripheral blood mononuclear cells (PBMCs) from patients with active AS than in those from healthy controls. Triptolide (TP) and GSK-J4 significantly reduced IL-17 expression. In cultured PBMCs from patients with active AS, 24 h of treatment with TP or GSK-J4 decreased the expression of RORγt (<i>p</i> < 0.05), JAK2 and STAT3 (JAK2: <i>p</i> < 0.05; STAT3: <i>p</i> < 0.05). Furthermore, both triptolide and GSK-J4 increased the level of histone 3 with Lys 27 trimethylation (H3K27me3) in patient-derived PBMCs. H3K27me3 enrichment was detected at the promoters of the RORc, STAT3 and IL-17 genes. Consistent with this finding, triptolide upregulated the EZH2 gene and downregulated the JMJD3 gene.</p><p><p><b>Conclusion:</b> Triptolide inhibits Th17 cell differentiation via H3K27me3 upregulation and orchestrates changes in histone-modifying enzymes, including JMJD3 and EZH2. These findings support the clinical efficacy of triptolide for AS and may provide clues for identifying molecular targets for the development of novel treatments.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"785-792"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286187","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":"Azithromycin induces liver injury in mice by targeting the AMPK/Nrf2 pathway.","authors":"Qixiang Xu, Cuifeng Zhang, Jingwen Lu, Haiyi Qian, Xiaodong Wang, Wenjun Guo, Huixian Cheng","doi":"10.1080/08923973.2024.2415115","DOIUrl":"10.1080/08923973.2024.2415115","url":null,"abstract":"<p><strong>Background: </strong>Azithromycin is an antibacterial and anti-inflammatory drug widely used for the treatment of various diseases, including those caused by atypical pathogens, bacterial or viral infections, chronic sinusitis, and bronchial asthma, particularly in pediatric patients. However, concerns have emerged regarding its hepatotoxicity and its precise mechanism of action remains unclear.</p><p><strong>Objective: </strong>To investigate the molecular mechanisms responsible for azithromycin-induced acute liver injury to advance our understanding of the progression and pathogenesis of antibiotic-induced liver damage, and to improve prevention and treatment strategies.</p><p><strong>Materials and methods: </strong>C57BL/6 mice, Nrf2^-/- mice, and primary hepatocytes were used. Primary hepatocytes from mice were isolated using a two-step perfusion method and cultured <i>in vitro via</i> the 'sandwich' culture model.</p><p><strong>Results: </strong>The exposure to azithromycin resulted in increased apoptosis and reactive oxygen species (ROS) levels. In mouse models, intraperitoneal administration of azithromycin at varying concentrations and time points substantially induced hepatic disarray, swelling, and dysfunction. Azithromycin markedly upregulated the mRNA and protein levels of phosphorylated adenosine-activated protein kinase (AMPK) while downregulating nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and NADPH: quinone oxidoreductase 1 (NQO-1). Moreover, HO-1 and NQO-1 protein levels remained largely unaffected in primary hepatocytes co-cultured with azithromycin in Nrf2^-/- mice.</p><p><strong>Conclusions: </strong>Our findings suggest that azithromycin-induced acute liver injury is mediated by suppression of Nrf2 activation and ROS production. This sheds light on the potential mechanisms involved in azithromycin-induced liver damage, underscoring the importance of exploring targeted interventions to mitigate the hepatotoxic effects.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"850-860"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464267","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":"An integrative lipidomics and transcriptomics study revealing Bavachin and Icariin synergistically induce idiosyncratic liver injury.","authors":"Yingying Li, Bo Cao, Mengmeng Lin, Jing Xu, Shuya Qi, Jiabo Wang, Xiaohe Xiao, Guohui Li, Chunyu Li","doi":"10.1080/08923973.2024.2424293","DOIUrl":"10.1080/08923973.2024.2424293","url":null,"abstract":"<p><p><b>Objectives:</b> Reports of traditional Chinese medicine (TCM)-related liver injury have increased over recent years; however, identifying susceptibility-related components and biomarkers remains challenging due to the heterogeneous nature of TCM and idiosyncratic drug-induced liver injury (IDILI). <i>Psoraleae Fructus</i> (PF) and <i>Epimedii Folium</i> (EF), commonly found in TCM prescriptions, have been implicated in IDILI, but their constituents and underlying mechanisms are poorly understood.</p><p><p><b>Methods:</b> In this study, we identified bavachin (Bav) and icariin (Ica) as susceptibility components for IDILI in PF and EF using a TNF-α-mediated mouse model. Lipidomics and transcriptomics were used to investigate their related mechanism.</p><p><p><b>Results:</b> Liver biochemistry and histopathology analyses revealed that co-exposure to Bav, Ica, and a non-toxic dose of TNF-α prestimulation induced significant liver injury, while Bav and Ica alone did not. Lipidomics identified seven differentially abundant metabolites in the Bav/Ica/TNF-α group compared to the Ica/TNF-α or Bav/TNF-α groups, mainly enriched in alpha-linolenic acid (ALA), arachidonic acid (AA), and linoleic acid (LA) metabolic pathways. Additionally, transcriptomics revealed 49 differentially expressed genes (DEGs) in the Bav/TNF-α vs Bav/Ica/TNF-α and Ica/TNF-α vs Bav/Ica/TNF-α groups, primarily associated with the PI3K/AKT/mTOR signaling pathway and sphingolipid metabolism. Integrative lipidomics and transcriptomics analyses identified significant positive correlations between five differential metabolites (DMs) - PC (O-16:0_14:1), PG (22:1_20:3), PI (16:0_14:1), PS (18:0_19:2), and TG (17:0_18:2_22:5) - and ten DEGs - <i>Nr0b2, Btbd19, Btg2, Fam222a, Fam83f, Gtse1, Anln, Gja4, Srrm4, and Zfp13</i>.</p><p><p><b>Conslusions:</b> Collectively, these results suggest that alterations in intracellular metabolism and gene expression levels may contribute to the synergistic induction of IDILI by the incompatible pair Bav and Ica in the presence of TNF-α.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"924-934"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590791","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":"Mannose targeting of poly(lactic-co-glycolic acid): a promising approach for improving sublingual allergen-specific immunotherapy.","authors":"Navideh Haghnavaz, Mohammad Ali Rezaee, Safoora Pordel, Saeideh Sadat Shobeiri, Mohammad Reza Dashti, Bahareh Ansari, Motahare Khorrami, Malihe Moghadam, Mojtaba Sankian","doi":"10.1080/08923973.2024.2410291","DOIUrl":"10.1080/08923973.2024.2410291","url":null,"abstract":"<p><strong>Objective: </strong>One of the most effective treatments for allergic respiratory diseases is allergen-specific sublingual immunotherapy (SLIT). While, mannose targeting has been applied in various immunostimulatory approaches, but it has not been investigated in sublingual allergen-specific immunosuppressive treatment. This study assesses mannose targeting for the ovalbumin (Ova) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles(NPs).</p><p><strong>Methods: </strong>The emulsion-solvent evaporation method was employed for the synthesis of PLGA NPs containing Ova, and subsequently they attached to D-mannose. Ova-sensitized mice underwent treatment in different ways: subcutaneous administration of 10 µg Ova, sublingual administration of 5 and 10 µg Ova loaded in PLGA NPs, 5 and 10 µg Ova loaded in mannose-targeted PLGA NPs, 10 µg Ova, and 10 µg Ova loaded in dendritic cell-specific aptamer-attached PLGA NPs. Serum Ova-specific IgE and IgG2a levels, as well as IFN-γ, IL-4, IL-10, and IL-17a levels in the supernatant of Ova-stimulated splenocytes were measured. Splenocyte proliferation was assessed using an MTT assay, and also lung histological examinations, and nasal lavage fluid cell counting were performed.</p><p><strong>Results: </strong>Ova-specific IgE, IL-4, IL-17a levels, eosinophil cell count, and splenocyte proliferation were remarkably reduced in the mice treated with mannose or aptamer targeted NPs compared to other groups. Also, IL-10 and IFN-γ levels were remarkably increased in the targeted NPs groups.</p><p><strong>Conclusion: </strong>Our findings indicated that mannose targeting of PLGA NPs could decrease allergen dose and improve immunomodulatory effects of SLIT. However, this approach suggests an effective formulation for SLIT in the mice model, further studies with common allergens are needed for application in humans.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"815-828"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390317","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":"Cardioprotective effect of tofisopam against isoprenaline-induced myocardial infarction in rats via modulation of NLRP3IL-1βcaspase-1 pathway.","authors":"Alyaa Abdelfattah Abdelmonaem, Asmaa Mohamed Abdel-Aziz, Yasmine F Ibrahim, Walaa Yehia Abdelzaher, Nada Amgad Mohammed, Heba Marey, Asmaa S Taghian, Amr Setouhi, Ashraf Radi, Sara M Ahmed","doi":"10.1080/08923973.2024.2421528","DOIUrl":"10.1080/08923973.2024.2421528","url":null,"abstract":"<p><strong>Purpose: </strong>Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide. Ischemic heart diseases, particularly acute myocardial infarction (MI), represent the most common cause of death. MI is influenced by multiple factors, including the release of inflammatory mediators. A significant percentage of individuals with CVD experience psychological effects, such as anxiety and depression, which are linked to an increased risk of coronary heart disease. Certain anti-anxiety medications have demonstrated immunomodulatory and anti-inflammatory effects. Tofisopam, a 2,3-benzodiazepine with anxiolytic properties, has been shown to exert <i>in vitro</i> anti-inflammatory and immunomodulatory effects. The present study investigates the potential of tofisopam as a protective adjuvant against isoprenaline-induced MI in rats and explores the possible underlying mechanisms.</p><p><strong>Methods: </strong>The study included four groups: a control group, a group pretreated with tofisopam, an isoprenaline toxic group, and an isoprenaline toxic group pretreated with tofisopam.</p><p><strong>Results: </strong>The findings demonstrated that isoprenaline significantly increased cardiac enzyme levels, as well as elevated oxidative and inflammatory stress parameters, along with evident apoptosis in cardiac cells. In contrast, the tofisopam-pretreated group showed a significant reversal of the cardiac damage induced by isoprenaline.</p><p><strong>Conclusions: </strong>Tofisopam protects against isoprenaline-induced MI through its antioxidant, anti-inflammatory, and anti-apoptotic properties.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"902-911"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499553","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":"Sirtinol, a SIRT1 inhibitor, inhibits the EMT and metastasis of 4T1 breast cancer cells and impacts the tumor microenvironment.","authors":"Sharvari Satam, Nitya Palekar, Kavitha Premkumar, Bhavani S Shankar","doi":"10.1080/08923973.2024.2412110","DOIUrl":"10.1080/08923973.2024.2412110","url":null,"abstract":"<p><strong>Introduction: </strong>The impact of epigenetic drugs on metastasis and the immunological microenvironment is poorly understood. In this study, we looked at how sirtinol, a SIRT1 inhibitor, affected epithelial-mesenchymal transition (EMT), metastasis, and the immune cells.</p><p><strong>Materials and methods: </strong><i>In vitro</i> experiments were carried out using tumor conditioned medium (TCM). For <i>in vivo</i> experiments, sirtinol was administered i.p. in tumor bearing BALB/c mice at a dose of 2 mg/kg body weight either alone or in combination with cisplatin. Estimation of cytokines was carried out using ELISA or ELIspot. Estimation of different markers was done using flow cytometry or western blot.</p><p><strong>Results: </strong>Sirtinol, a SIRT1 inhibitor, was found to be cytotoxic to 4T1 breast cancer cells with no synergistic effects with cisplatin, both under <i>in vitro</i> and <i>in vivo</i> conditions (<i>p</i> < 0.05). Sirtinol significantly reduced cancer cell metastasis to the spleen which was supported by <i>in vitro</i> findings such as decreased vimentin expression and cell mobility in migration and wound healing assays (<i>p</i> < 0.01). Studies on the effects of 4T1 tumor-conditioned medium on spleen cells indicated changes in T cell proliferation as well as differentiation (<i>p</i> < 0.01). In tumor bearing mice, spleen cells showed elevated IFN-γ secretion, increased CD11b⁺ cells, and decreased T cells (<i>p</i> < 0.01). This was reversed by sirtinol as well as the combination treatment, which may also have contributed to metastasis inhibition (<i>p</i> < 0.01).</p><p><strong>Conclusion: </strong>Sirtinol, a SIRT1 inhibitor inhibits EMT and metastasis of 4T1 breast cancer cells and also has an impact on the immune microenvironment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"829-842"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380750","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":"Therapeutic role of physalin A in the pathogenesis of Graves' orbitopathy.","authors":"Eunjin Kim, Ji-Young Kim, Soo Hyun Choi, Hyun Young Park, JaeSang Ko, Jin Sook Yoon","doi":"10.1080/08923973.2024.2422079","DOIUrl":"10.1080/08923973.2024.2422079","url":null,"abstract":"<p><strong>Background: </strong>Graves' orbitopathy (GO) is an autoimmune condition that causes serious ocular symptoms; its treatment strategies are limited. Physalin A is a phytosterol that has shown various therapeutic properties, including anti-inflammatory and anti-fibrotic effects. In this study, we investigated whether physalin A could inhibit inflammation, fibrosis, hyaluronan (hyaluronic acid) production, and adipogenesis, which are crucial to the pathogenesis of GO.</p><p><strong>Methods: </strong>Orbital tissue explants were obtained from patients with GO during orbital decompression surgery and healthy controls. Orbital fibroblasts (OFs) were isolated and treated with different concentrations of physalin A. Using western blot and ELISA analyses, we determined the effects of physalin A on OFs.</p><p><strong>Results: </strong>Physalin A treatment suppressed the production of interleukin (IL)-1β-induced prostaglandin E2 (PGE2) and pro-inflammatory molecules, including cyclooxygenase (COX)-2, IL-6, IL-8, and intercellular adhesion molecule (ICAM)-1. We discovered that physalin A attenuated hyaluronan production induced by IL-1β or insulin-like growth factor (IGF)-1. Moreover, physalin A reduced lipid droplet formation and production of peroxisome proliferator activator (PPAR) γ, CCAAT-enhancer-binding protein (C/EBP) α, C/EBP β, sterol regulatory element binding protein (SREBP)-1, leptin, and adiponectin proteins. Physalin A suppressed the phosphorylation of extracellular signal-related kinase (ERK), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and suppressor of mothers against decapentaplegic (SMAD) 2 signaling protein.</p><p><strong>Conclusions: </strong>Our study suggests that the major mechanisms by which physalin A suppresses GO include reducing inflammation, fibrosis, hyaluronan production, and adipogenesis in OFs. The findings of this study provide evidence of the therapeutic effect of physalin A in GO.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"912-923"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568285","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":"Monotropein alleviates acute pulmonary embolism in rats by inhibiting the NF-κB pathway.","authors":"Peng Xu, Lu Huang, Weizhong Feng, Junqing Zhou, Zhixiang Guo, Jianfeng Xu, Haixia Xu","doi":"10.1080/08923973.2024.2412113","DOIUrl":"10.1080/08923973.2024.2412113","url":null,"abstract":"<p><strong>Objective: </strong>This study examines the therapeutic potential of monotropein (Mon) in a rat model of acute pulmonary embolism (APE), aiming to elucidate its mechanistic role and provide new insights for APE treatment.</p><p><strong>Methods: </strong>Thirty Sprague Dawley (SD) rats were randomly assigned to five groups (<i>n</i> = 6 per group): sham, Mon (40 mg/kg), APE, APE + 20 mg/kg Mon, and APE + 40 mg/kg Mon. APE was induced <i>via</i> autologous thrombus infusion in all groups except sham and Mon-only groups. We assessed blood gas parameters, lung wet/dry weight (W/D) ratio, and oxidative stress markers. Additionally, excised lung tissues underwent evaluation for serum inflammatory factors <i>via</i> ELISA, apoptotic cells <i>via</i> TUNEL assay, and protein expression <i>via</i> Western blot.</p><p><strong>Results: </strong>Compared to the sham group, APE-induced rats exhibited significantly elevated blood oxygen levels and increased pro-inflammatory factors, including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-8. Mon treatment effectively mitigated these APE-induced changes, reducing blood oxygen concentration and downregulating IL-1β and TNF-α levels. Furthermore, Mon demonstrated anti-apoptotic effects by decreasing cleaved caspase-3 and Bax protein levels while upregulating Bcl-2 expression. Mon also suppressed nuclear factor-κB (NF-κB) activation by inhibiting the phosphorylation levels of p65/RelA and IκBα proteins, while the total protein level of IκBα was increased with Mon treatment.</p><p><strong>Conclusion: </strong>Mon effectively ameliorated lung tissue injury in APE rats by inhibiting apoptosis, attenuating inflammatory responses, and alleviating oxidative stress. These beneficial effects appear to be mediated through modulation of the NF-κB pathway, suggesting Mon as a promising therapeutic candidate for APE treatment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"893-901"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365035","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":"Emulsified isoflurane pretreatment attenuates myocardial ischemia-reperfusion injuries by suppressing toll-like Receptor-4.","authors":"Zujin Xu, Zhen Li, Shuxian Chen, Yali Zhu, Yanlin Wang, Jia Zhan, Yun Wu","doi":"10.1080/08923973.2024.2399266","DOIUrl":"10.1080/08923973.2024.2399266","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the mechanism of emulsified isoflurane in reducing myocardial ischemia-reperfusion injury (MIRI).</p><p><strong>Materials and methods: </strong>Forty-eight healthy male Sprague-Dawley rats were randomly divided into four groups (<i>n</i> = 12). In the sham group (group S) and ischemia-reperfusion group (group I/R), saline (4 ml/kg/h) was administered intravenously for 30 min. In intralipid group (group L), intralipid (4 ml/kg/h) was administered intravenously. In the emulsified isoflurane group (group EI), emulsified isoflurane (4 ml/kg/h) was administered intravenously. The infusion was then discontinued for 15 min during the washout period. Apart from group S, ischemia was produced by occlusion of the left anterior descending artery (LADA) for 30 min. After 30 min of occlusion, all groups received reperfusion for two hours.</p><p><strong>Results: </strong>Creatine kinase MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Myocardial infarct size was measured using triphenyl tetrazolium chloride staining. According to the result, pretreatment with emulsified isoflurane attenuated CK-MB and cTnI concentrations (<i>p</i> < 0.05). And serum TNF-α and IL-6 levels and infarct size in the emulsified isoflurane group obviously decreased. An obvious decrease in the expression of the toll-like receptor-4 (TLR-4) mRNA in group EI was observed compared with group I/R.</p><p><strong>Discussion and conclusion: </strong>Emulsified isoflurane precondition had a potent cardioprotective effect against myocardial ischemia-reperfusion injury. The mechanisms involved may be related to the decrease in the expression of TLR-4 and the reduced inflammatory response.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"751-756"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132617","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}