Immunopharmacology and Immunotoxicology最新文献

{"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}

{"title":"Fumaric acid per se and in combination with methotrexate arrests inflammation via moderating inflammatory and oxidative stress biomarkers in arthritic rats.","authors":"Anne Xaviera, Ammara Saleem, Muhammad Furqan Akhtar, Abdulrahman Alshammari, Norah A Albekairi","doi":"10.1080/08923973.2024.2405171","DOIUrl":"10.1080/08923973.2024.2405171","url":null,"abstract":"<p><p><b>Objective:</b> Fumaric acid is a dicarboxylic acid that belongs to the phenolic class enriched in fruits and vegetables that are traditionally used for the treatment of various ailments. The research was planned to find out the anti-inflammatory and anti-arthritic activities of fumaric acid using <i>in-vitr</i>o and <i>in-vivo</i> assays. Moreover, safety study was also done.</p><p><p><b>Materials and methods:</b> The 0.1 ml complete Freund's adjuvant was injected in left hind paw in all Wistar rats except normal rats at day 1 to induced arthritis. The treatment with fumaric acid at 10, 20, 40, and fumaric acid 40 mg/kg together with methotrexate (MTX) was administered to immunized rats at 8th day <i>via</i> oral gavage and continued till 28th day though, MTX was administered as standard control.</p><p><p><b>Results:</b> The fumaric acid notably (<i>p</i> < 0.0001) lessened the paw edema and arthritic scoring, reinstated body and immune organ weight, and oxidation status in treated rats. Fumaric acid notably restored altered C-reactive protein, rheumatoid factor, liver function tests, ESR, WBCs, RBCs and Hb levels in treated rats. The fumaric acid in combination noticeably (<i>p</i> < 0.01-0.0001) suppressed the expression of TNF- α, IL-6, IL-1β, NF-kβ, and COX-2, and over expressed IL-4, and IL-10 in contrast to other treated groups. Fumaric acid had presented a dose-dependent antioxidant, anti-inflammatory and anti-arthritic activities while notable activity exhibited by fumaric acid in combination with MTX. The fumaric acid exhibited non-significant clinical signs of toxicity and mortality in acute toxicity study. The LD50 was more than 2000 mg/kg.</p><p><p><b>Conclusion:</b> Fumaric acid in combination can be used as disease-modifying anti-rheumatic drug but it will need extensive pre-clinical and clinical studies.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"793-804"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365034","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":"Sirt1/Nrf2/TNFα; TLR4/Myd88/NF-κB signaling pathways are involved in mediating hepatoprotective effect of bupropion in rat model of myocardial infarction.","authors":"Walaa Yehia Abdelzaher, Ayman Geddawy, Mina Ezzat Attya, Abdel Hamid Sayed AboBakr Ali, Doaa Mohamed Elroby Ali, Dania S Waggas, Heba K Alshaeri, Yasmine F Ibrahim","doi":"10.1080/08923973.2024.2415461","DOIUrl":"10.1080/08923973.2024.2415461","url":null,"abstract":"<p><strong>Background: </strong>The aim of the current study is to identify the possible protective effect of bupropion (BUP) on liver injury in rat model of myocardial infarction (MI). BUP was administered in the presence and absence of MI.</p><p><strong>Materials and methods: </strong>Thirty-two Wistar adult male rats were randomly arranged into four groups: control, BUP (30 mg/kg/day, intraperitoneal) for 28 days, isoproterenol (ISO) was injected subcutaneous (85 mg/kg) in the 26th and 27th days and BUP/ISO groups. Cardiac and hepatic enzymes were measured, also Hepatic oxidative stress indicators, as well as inflammatory and apoptotic biomarkers, were evaluated. Cardiac and hepatic histopathological examination and hepatic nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) immunohistochemical study were also detected.</p><p><strong>Results: </strong>ISO significantly increased cardiac and hepatic enzymes, hepatic oxidative stress, inflammatory, apoptotic, with a histopathological picture of cardiac and hepatic damage and high hepatic NF-κB immunoexpression were detected. BUP significantly normalized the upraised oxidative, inflammatory, and apoptotic parameters, with an impressive improvement in the histopathological picture and a reduction in hepatic NF-κB immunoexpression.</p><p><strong>Conclusion: </strong>BUP protects against liver injury on top of MI in rat model <i>via</i> modulation of Sirtuin type 1 (Sirt1)/Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/tumor necrosis factor α (TNFα); Toll-like receptor 4 (TLR4)/Hepatic myeloid differentiation primary response 88(Myd88)/NF-κB signaling pathways.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"872-883"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400151","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":"Clinical features, treatment, and outcome of nivolumab-induced cholangitis.","authors":"Yang He, Zhiqiang Fan, Wei Sun, Linqi Ouyang, Chunjiang Wang","doi":"10.1080/08923973.2024.2402338","DOIUrl":"10.1080/08923973.2024.2402338","url":null,"abstract":"<p><strong>Background: </strong>Cholangitis is an uncommon and severe adverse reaction of nivolumab with unclear clinical features. The purpose of this study was to investigate the clinicopathological features, imaging, and treatment of nivolumab-induced cholangitis.</p><p><strong>Methods: </strong>Case reports, case series, and clinical studies of nivolumab-induced cholangitis were retrospectively analyzed by searching Chinese and English databases from January 1, 2017 to December 31, 2023.</p><p><strong>Results: </strong>Thirty-eight patients entered the study. The median number of cycles of cholangitis onset was seven cycles after administration (range 1, 28) and the median time was 11 days (range 78, 390). Abdominal pain (42.1%) and fever (18.4%) were the most important initial symptoms. Some patients (15.8%) showed elevated liver enzymes without any clinical symptoms. The median alkaline phosphatase level was 1721 IU/L (range 126, 9118), and the median γ-glutamyltranspeptidase level was 829 IU/L (range 104, 3442). Anti-nuclear antibodies, anti-mitochondrial antibodies, and IgG4 typically show negative results. Imaging shows extrahepatic bile duct and intrahepatic bile duct dilation, hypertrophy, and stenosis. Liver biopsy and biliary tract biopsy mainly found CD8 inflammatory cell infiltration. Systemic steroids (84.2%) and ursodeoxycholic acid (UDCA) (34.2%) were administered, and 24 patients (63.2%) had poor to moderate response to steroids. Thirty-one patients (81.6%) improved and seven patients (18.4%) did not improve.</p><p><strong>Conclusions: </strong>Clinicians must remain vigilant for patients experiencing cholestasis while on nivolumab and should assess for cholangitis and carry out appropriate imaging tests. Considering the excellent efficacy of UCDA in cholangitis, steroids combined with UDCA may be a viable treatment option in cases where steroids are ineffective for cholangitis.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"757-762"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153917","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":"Neuroprotection of isoorientin against microglia activation induced by lipopolysaccharide via regulating GSK3β, NF-κb and Nrf2/HO-1 pathways.","authors":"Xiaoqin Tan, Mindie Cao, Yijing Zhao, Lang Yi, Yingui Li, Changhong He, Qing X Li, Yan Dong","doi":"10.1080/08923973.2024.2399249","DOIUrl":"10.1080/08923973.2024.2399249","url":null,"abstract":"<p><p><b>Background:</b> Isoorientin (ISO), a flavone C-glycoside, is a glycogen synthase kinase 3β (GSK3β) substrate-competitive inhibitor. ISO has potential in treatment of Alzheimer's disease (AD). An excessive activation of GSK3β can lead to neuroinflammation causing neuronal damage. Microglia cells, as resident immune cells of the central nervous system, mediate neuroinflammation. Here, we studied the effects of ISO on microglial activation to alleviate neuroinflammation.</p><p><p><b>Methods:</b> Effects of ISO were observed upon the stimulation of mouse microglia BV2 or SIM-A9 cells by lipopolysaccharide (LPS). Lithium chloride (LiCl) was the positive control as a GSK3β inhibitor. The release of TNF-α and NO were analyzed by ELISA and Griess assays, while expressions of COX-2, Iba-1, BDNF, GSK3β, NF-κB p65, IκB, Nrf2 and HO-1 were detected by Western blotting. In the co-culture model of SIM-A9 cells and differentiated SH-SY5Y human neuroblastoma cells, effects of ISO on microglia-mediated neuronal damage were evaluated with the MTS assay.</p><p><p><b>Results:</b> ISO significantly inhibited the production of TNF-α (<i>p</i> < 0.01), NO (<i>p</i> < 0.001) and the expression of COX-2 (<i>p</i> < 0.01) and Iba-1 (<i>p</i> < 0.05) induced by LPS, and increased BDNF. The cell viability of SH-SY5Y was inhibited by LPS in the co-culture, which was prevented by ISO pretreatment. ISO increased the expression of p-GSK3β (Ser9), IκB and HO-1 in the cytoplasm, decreased NF-κB p65 and increased Nrf2 in the nucleus compared with the LPS group.</p><p><p><b>Conclusion:</b> ISO attenuated the activation of microglia through regulating the GSK3β, NF-κB and Nrf2/HO-1 signaling pathways to exert neuroprotection.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"741-750"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153918","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":"BACE1 inhibition via miR-6838-5p overexpression inhibits insulin resistance and the immune response in HFD-induced obesity in mice model.","authors":"Yubo Han, Zhenhua Quan, Miao Tian, Ruinan Wang, Donghao Guo, Dandan Zhang, Li Liu","doi":"10.1080/08923973.2024.2430668","DOIUrl":"https://doi.org/10.1080/08923973.2024.2430668","url":null,"abstract":"<p><strong>Context: </strong>Obesity is a chronic inflammatory disorder, which promotes the progression of metabolic disorders. MicroRNA (miR)-6838-5p is dysregulated and participates in the progression of several disorder models.</p><p><strong>Objective: </strong>To explore the role and mechanism of miR-6838-5p in insulin resistance.</p><p><strong>Methods: </strong>Mice were fed with high-fat diet (HFD) to construct an obesity animal model. The role of miR-6838-5p was evaluated by insulin tolerance test (ITT), glucose tolerance test (GTT), homeostasis model assessment of insulin resistance (HOMA-IR) analysis, enzyme-linked immunosorbent assay (ELISA) and western blot assays. The potential target of miR-6838-5p was screened through the starBase online website and confirmed by the luciferase assay.</p><p><strong>Results: </strong>HFD supply induced a prominent increase in the body weight, white adipose tissue (WAT) weight, the area under the curve (AUC) of GTT and ITT, HOMA-IR, the serum level of insulin and the serum concentrations and relative protein levels of interleukin (IL)-1β, IL-6 and monocyte chemoattractant protein-1 (MCP-1) accompanied with reduced levels of IL-10 in mice. The level of miR-6838-5p was reduced in HFD-fed mice. Upregulation of miR-6838-5p partly reversed the above-mentioned indicators. Moreover, miR-6838-5p directly targeted to β-site amyloid precursor protein cleaving enzyme1 (BACE1) and negatively regulated the BACE1 expression. Downregulation of BACE1 improved insulin sensitivity and inflammatory mediators release involving in AKT/GSK3β signaling pathway in HFD-fed mice. Besides, overexpression of BACE1 counteracted the depressant role of miR-6838-5p overexpression in insulin resistance and inflammatory factors release in HFD-fed mice.</p><p><strong>Conclusion: </strong>MiR-6838-5p/BACE1 axis regulated insulin resistance and inflammatory factors release in HFD-fed mice.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739257","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":"Factors inducing cutaneous adverse reactions in cancer patients treated with PD-1 and PD-L1 inhibitors: a machine-learning algorithm approach.","authors":"Young-Ah Cho, Youngyun Moon, Wooyoung Park, Yerin Lee, Kyung-Eun Lee, Dong-Chul Kim, Woorim Kim","doi":"10.1080/08923973.2024.2430670","DOIUrl":"10.1080/08923973.2024.2430670","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) show promise in cancer treatment but can lead to immune-related adverse events (irAEs), notably affecting the skin. Understanding the factors behind these skin reactions is crucial for effective management during treatment. Hence, the aim of this study was to uncover associations between patient characteristics and cutaneous adverse reactions among cancer patients undergoing ICI treatment.</p><p><strong>Methods: </strong>The study involved 209 cancer patients receiving ICIs. Statistical methods, including the chi-square test, Fisher's exact test, and multivariable logistic regression, were employed to analyze variables such as hypertension, antihistamine use, cancer metastasis, diabetes, and opioid usage. Additionally, machine learning techniques, including logistic regression, elastic net, random forest, and support vector machines (SVM), were utilized to develop predictive models anticipating skin-related adverse events.</p><p><strong>Results: </strong>Results highlighted significant associations between specific patient attributes and the incidence of skin reactions post-ICI treatment. Notably, patients using antihistamines or with cancer metastasis exhibited higher rates of skin adverse reactions, while those with diabetes or using opioids displayed lower incidence rates. Robust performance in forecasting these adverse events was observed, particularly in the predictive models employing logistic regression and elastic net.</p><p><strong>Conclusions: </strong>This pioneering study contributes crucial insights into predictive modeling for ICI-induced skin reactions, emphasizing the importance of personalized treatment strategies. By identifying risk factors and utilizing tailored predictive models, healthcare providers can proactively manage adverse events, optimizing the benefits of ICIs while mitigating potential side effects.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-6"},"PeriodicalIF":2.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619347","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":"Tanshinone IIA inhibits the apoptosis process of nerve cells by upshifting SIRT1 and FOXO3α protein and regulating anti- oxidative stress molecules and inflammatory factors in cerebral infarction model.","authors":"Jiao Xu, Xiufeng Liu, Heng Yu, Zhenyu Wang","doi":"10.1080/08923973.2024.2428662","DOIUrl":"10.1080/08923973.2024.2428662","url":null,"abstract":"<p><strong>Background: </strong>As a prevalent cerebrovascular disorder, cerebral infarction (CI) has garnered extensive attention globally due to its high incidence and substantial fatality rate. Ischemia-reperfusion injury (IRI) exacerbates not only neuronal demise but also amplifies neural functional impairment. Tanshinone IIA (Tan IIA) has been identified to confer protection against IRI, yet the precise underlying mechanisms remain elusive. This work aimed to delve into the mechanistic role of Tan IIA in CI, with the goal of furnishing more distinct theoretical substantiation for its clinical application.</p><p><strong>Methods: </strong>Initially, a middle cerebral artery embolization model group (MCAO) model was established, followed by the categorization of rats into distinct groups based on different administration modes. Therapeutic effects were evaluated through indices including mortality rate, cerebral tissue water content, CI proportion, and neural functional scoring. Meanwhile, cellular apoptosis rates in hippocampal and cortical tissues, as well as levels of oxidative stress molecules (OSM), Sirtuin 1 (SIRT1), Forkhead box O3 (FOXO3α), and inflammatory factors, were examined to explore the mechanism of action.</p><p><strong>Results: </strong>This work revealed that within varying doses of Tan IIA groups, as dosage escalated, mortality rate, cerebral edema severity, CI proportion, and neural functional scoring gradually diminished. Notably, the 35 mg/kg dose group exhibited the most significant reductions, with decreases of 74.9%, 12.7%, 47.5%, and 54%, respectively. Cellular apoptosis rates in hippocampal and cortical tissues displayed a stepwise descending trend, with the 35 mg/kg dose group showcasing the largest reduction. SIRT1 and FOXO3α proteins exhibited a steady increase, with the 35 mg/kg dose group manifesting respective elevations of 87.9% and 65.5%, the highest among all groups. Antioxidant molecules glutathione (GSH) and superoxide dismutase (SOD) contents progressively increased, whereas malondialdehyde (MDA) and nitric oxide (NO) content decreased. The 35 mg/kg dose group recorded the highest increments of 49.1% and 58.1% for GSH and SOD content, while achieving the greatest reductions of 55.6% and 56.2% for MDA and NO content. Expression of inflammatory factors, namely tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and interleukin-6 (IL-6), gradually declined, with reductions of 42.1%, 32.2%, and 29.1%, respectively, in the 35 mg/kg dose group, exhibiting drastic differences (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>In conclusion, this research elucidates that Tan IIA improves cerebral edema and neural function by elevating intracellular expression of SIRT1 and FOXO3α proteins, modulating OSM and inflammatory factors. These findings yielded robust experimental support for the potential use of Tan IIA as a therapeutic agent for CI.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-11"},"PeriodicalIF":2.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619354","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}