Immunopharmacology and Immunotoxicology最新文献

{"title":"Combined Bisoprolol and Trimetazidine ameliorate Arsenic trioxide -Induced Acute Myocardial Injury in Rats: Targeting PI3K/GSK-3β/Nrf2/HO-1 and NF-κB/iNOS Signaling Pathways, Inflammatory Mediators and Apoptosis.","authors":"Yasmin M Ahmed, Ehab A M El-Shoura, Magy R Kozman, Basel A Abdel-Wahab, Asmaa Ramadan Abdel-Sattar","doi":"10.1080/08923973.2024.2435323","DOIUrl":"https://doi.org/10.1080/08923973.2024.2435323","url":null,"abstract":"<p><strong>Background: </strong>Arsenic-trioxide (ATO) is an effective therapy for acute promyelocytic leukemia. Unfortunately, its utility is hindered by the risk of myocardial injury. Both bisoprolol (BIS) and trimetazidine (TMZ) have various pharmacological features, including anti-oxidant, anti-inflammatory, and anti-apoptotic properties.</p><p><strong>Aim: </strong>The cardioprotective effects of BIS and TMZ were studied, and their mechanistic role in ameliorating ATO-induced myocardial injury.</p><p><strong>Materials and methods: </strong>Forty male Wistar rats were randomly allotted into five groups as follows: normal control group (received normal saline, orally), ATO group (7.5 mg/kg, orally), BIS (8 mg/kg, orally), TMZ (60 mg/kg, orally), and finally combination group (BIS + TMZ + ATO). Following 21 days, samples of serum and cardiac tissues were obtained to perform biochemical, molecular, and histopathological investigations.</p><p><strong>Results: </strong>The present study showed that ATO caused myocardial injury evidenced by changes in serum biomarkers (Aspatate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase-MB, and cardiac troponin-1), electrolyte imbalance, and lipid profiles alongside histopathologic changes. In addition, ATO administration significantly elevated malondialdehyde, nicotinamide adenine dinucleotide phosphate hydrogen oxidase, myloperoxidase, total nitrite, inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin-1β, interleukin-6, 8-Hydroxy-2'-deoxyguanosine, nuclear factor NF-kappa-B p65 subunit, glycogen synthase kinase-3 beta, and caspase-3 expression contemporaneously with down-regulation of reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, heme oxygenase 1, nuclear factor erythroid 2-related factor 2, phosphatidylinositol-3 kinase, p-PI3K, and Bcl-2 expression. Interestingly, pre-treatment with BIS and TMZ significantly reversed the detrimental effects of ATO-induced myocardial injury at both cellular and molecular levels. Otherwise, combining the two drugs displayed more enhancement than each drug alone.</p><p><strong>Conclusion: </strong>The present research depicted that BIS and TMZ have the potential to protect the heart and provide therapeutic benefits by preventing acute heart injury induced by ATO. This is achieved by reversing the redox-sensitive pathway, reducing inflammation, and inhibiting apoptosis.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-22"},"PeriodicalIF":2.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739259","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":"OCCUPATIONAL EXPOSURE TO PESTICIDES AFFECTS SYSTEMIC CYTOKINE PROFILE AND CORRELATES WITH POOR CLINICAL PROGNOSIS IN YOUNG WOMEN WITH BREAST CANCER.","authors":"Rafael Cardoso Maciel Costa Silva, Tatiane Renata Fagundes, Carolina Coradi, Bruno Ricardo Barreto Pires, Maria Paula Berne, Lucca L Smaniotto, Rafaela Frederico de Almeida, Daniel Rech, Carolina Panis","doi":"10.1080/08923973.2024.2430665","DOIUrl":"https://doi.org/10.1080/08923973.2024.2430665","url":null,"abstract":"<p><p>Aging is one of the main risk factors for breast cancer. However, the impact of environmental risk factors, such as pesticide exposure, on the clinical outcomes of patients with breast cancer, depending on disease onset, remains unclear. This study analyzed clinicopathological data from 188 women with breast cancer, who were either occupationally or domestically exposed to pesticides, or not exposed, according to their age at disease onset (early onset ≤ 50 years and late onset > 50 years). Additionally, interleukin 4 (IL-4), interleukin 17A (IL-17A), and interleukin 12 (IL-12) levels were measured in plasma samples, and clinicopathological data were assessed. In the late-onset group, a greater frequency of low-grade tumors was detected in the exposed patients compared to the unexposed group (23.14% vs. 45.45%, p = 0.0181). A higher frequency of high-risk stratification for recurrence and death was found in early-onset patients when comparing exposed and unexposed groups (10.0% vs. 30.0%, p = 0.0488). Regarding the molecular subtypes of breast cancer, patients in the late-onset group showed a higher frequency of triple-negative tumors than unexposed women with the same disease onset (20.0% vs. 40.63%, p < 0.0001). IL-12 levels were significantly lower in exposed patients in the early-onset group compared to unexposed patients in the same group. Early-onset patients showed a principal component that positively correlated with pesticide exposure, IL-1β, IL-17A, and IL-4, while late-onset patients showed negative correlations between pesticide exposure and IL-12, IL-4, and IL-17A. These findings suggest that pesticide exposure induces an inflammaging-like state in younger women, contributing to an increased risk of developing more severe disease.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-13"},"PeriodicalIF":2.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716282","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}

{"title":"Safety observation of COVID-19 inactivated vaccine in immature mice.","authors":"Jingxuan Zhou, Yingyan Han, Xiaoyuan Huang, Zhegang Zhang, Jiayou Zhang, Teng Ji","doi":"10.1080/08923973.2024.2421524","DOIUrl":"https://doi.org/10.1080/08923973.2024.2421524","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the safety of COVID-19 inactivated vaccine in immature mice.</p><p><strong>Methods: </strong>We selected 3-week-old immature BALB/c mice, continuously observed until 7 weeks old after continuous immunization with fully inactivated vaccine (initial strengthening), and sacrificed BALB/c mice at 7 weeks old, and used H&E, Masson, mast cells and Ki-67 staining to analyze the changes of heart, liver, spleen, kidney, lung and brain. In addition, RNA was extracted from important organs such as the heart, liver, spleen, kidney, lung, and brain, and to evaluate whether there was any effect after vaccination through bulk-RNA sequencing.</p><p><strong>Results: </strong>After H&E, Masson, mast cells and Ki-67 staining analyses, there are no significant differences between tissues and organs in the vaccine group and the PBS group, and RNA-Seq did not show that the vaccine had any effect on immature mice.</p><p><strong>Conclusion: </strong>COVID-19 inactivated vaccine is safe in immature mice.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-7"},"PeriodicalIF":2.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619349","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":"Ezetimibe protects against Gentamycin-induced ototoxicity in rats by antioxidants, anti-inflammatory mechanisms, and BDNF upregulation.","authors":"Huda I Abd-Elhafiz, Manar A Faried, Suzan A Khodir, Asmaa Salah Moaty, Eman M Sweed","doi":"10.1080/08923973.2024.2390463","DOIUrl":"10.1080/08923973.2024.2390463","url":null,"abstract":"<p><strong>Objective: </strong>The threat of hearing loss has become a universal reality. Gentamycin (GM) can lead to ototoxicity and may result in permanent hearing loss. This study aimed to elucidate whether the hypolipidemic drug Ezetimibe (EZE) has a possible underlying mechanism for protecting rats from GM-induced ototoxicity.</p><p><strong>Methods and results: </strong>30 male Wister albino rats were separated into three groups, ten in each group: control, GM, and GM + EZE. At the end of the experiment, rats underwent hearing threshold evaluation <i>via</i> auditory brainstem response (ABR), carotid artery blood flow velocity (CBV), and resistance (CVR) measurement, in addition to a biochemical assessment of serum malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), hemeOxygenase-1 (HO-1), and tumor necrosis factor-α (TNF-α). Also, real-time PCR was employed to quantify the levels of brain-derived neurotrophic factor (BDNF). Cochlea was also studied <i>via</i> histological and immunohistochemical methods. GM revealed a significant increase in CVR, MDA, NO, and TNF-α and a significant decrease in ABR, CBV, CAT, HO-1, and cochlear BDNF expression. EZE supplementation revealed a significant rise in ARB in addition to CBV and a decline in CVR and protected cochlear tissues <i>via</i> antioxidant, anti-inflammatory, and antiapoptotic mechanisms <i>via</i> downregulating Caspase-3 immunoreaction, upregulating proliferating cellular nuclear antigen (PCNA) immunoreaction, and upregulating of the cochlear BDNF expression. Correlations were significantly negative between BDNF and MDA, NO, TNF-α, COX 2, and caspase-3 immunoreaction and significantly positive with CAT, HO-1, and PCNA immunoreaction.</p><p><strong>Discussion: </strong>EZE can safeguard inner ear tissues from GM <i>via</i> antioxidant, anti-inflammatory, and antiapoptotic mechanisms, as well as upregulation of BDNF mechanisms.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"635-650"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975618","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":"Ginseng polysaccharide promotes the apoptosis of colon cancer cells via activating the NLRP3 inflammasome.","authors":"Xiaoyan Tian, Chuanqiang Zhang, Daojuan Wang, Xiaowei Li, Qiang Wang","doi":"10.1080/08923973.2024.2398472","DOIUrl":"10.1080/08923973.2024.2398472","url":null,"abstract":"<p><strong>Background: </strong>Ginseng polysaccharide (GPS) is an ingredient of ginseng with documented anti-tumor properties. However, its effect on colon cancer and the underlying molecular mechanisms have not been investigated clearly.</p><p><strong>Methods: </strong>Cell viability of HT29 and CT26 cells treated with different concentrations of GPS was assessed using the Cell Counting Kit-8 (CCK-8) assay. Western blot assay was used to detect the expression of apoptotic proteins, while the mRNA levels were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Transwell migration assays were used to examine the migration and invasion of cells.</p><p><strong>Results: </strong>The results revealed that GPS effectively suppressed the proliferation of HT29 and CT26 cells. We demonstrated an upregulation of apoptotic proteins in GPS-treated cells, including Bax, cleaved Caspase-3, and p-p53. GPS treatment also increased the mRNA levels of cytochrome C and Bax. Furthermore, the results showed that GPS treatment concurrently promoted the activation of nucleotide-binding domain leucine-rich family pyrin-containing 3 (NLRP3) inflammasome. Transwell migration assays showed that GPS inhibited the migratory and invasive abilities of colon cancer cells. As expected, inhibition of NLRP3 expression using INF39 attenuated the inhibitory effect of GPS on migration and invasion. Upon NLRP3 inhibition, GPS-induced apoptosis was dramatically alleviated, accompanied by a reduction in the expression of apoptotic proteins.</p><p><strong>Conclusion: </strong>In conclusion, this research provides compelling evidence that the GPS-induced NLRP3 signaling pathway plays a pivotal role in apoptosis of colon cells, suggesting potential clinical implications for the therapeutic intervention of colon cancer. Thus, GPS might be a promising anti-tumor drug for the treatment of colorectal cancer.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"715-726"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107019","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":"Targeting <i>8-oxoguanine DNA glycosylase-1 (OGG1</i>) as a therapeutic strategy in inflammatory-related diseases.","authors":"Abdullahi Samaila, Rusliza Basir, Mukhtar Gambo Lawal, Razif Abas, Maizaton Atmadini Abdullah, Roslaini Abd Majid, Norshariza Nordin, Mohd Khairi Hussain, Nur Izah Ab Razak, Yong Yoke Keong, Basiru Aliyu","doi":"10.1080/08923973.2024.2391471","DOIUrl":"10.1080/08923973.2024.2391471","url":null,"abstract":"<p><strong>Objective: </strong>Inflammatory diseases are influenced by oxidative stress. Oxidatively damaged 8-oxoG in DNA is linked to inflammation. The enzyme OGG1 is responsible for repairing the damaged base in the DNA which is linked to pro-inflammatory signaling and severe inflammation. This study aims to explore the potential of targeting OGG1 as a therapeutic strategy in inflammatory disease conditions.</p><p><strong>Methods: </strong>A comprehensive search and review of literature were conducted using appropriate scientific databases such as Google Scholar, Scopus, PubMed, Web of Science, and other references to obtain relevant information that suited the title and content of this article.</p><p><strong>Results: </strong>Compelling pieces of evidence from many previous studies have shown the crucial role of the OGG1/8oxoG pathway in inflammatory disease conditions, leading to severe inflammatory response and death. Therefore, based on these pieces of evidence, targeting this enzyme (OGG1) using specific pharmacological inhibitors or interventions might lead to downregulation and amelioration of severe inflammation to reduce the morbimortality related to several disease conditions.</p><p><strong>Conclusion: </strong>This review highlighted the molecular mechanism of OGG1 activity <i>via</i> the 8-oxo/OGG1 pathway and its role in inflammation and inflammatory disease conditions. Due to the paucity of studies involving OGG1in inflammatory infectious diseases, further research projects are needed to explore the therapeutic potential of various OGG1 inhibitors to serve as novel therapeutic strategies in infectious inflammatory diseases of medical importance in developing countries such as malaria, meningitis, tuberculosis among others.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"685-694"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008761","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":"The natural sesquiterpene lactone inulicin suppresses the production of pro-inflammatory mediators via inhibiting NF-κB and AP-1 pathways in LPS-activated macrophages.","authors":"Jingjing Yan, Min Cai, Chenchen Zang, Wenjing Li, Zhuangzhuang Liu, Ximeng Li, Yuan Gao, Yun Qi","doi":"10.1080/08923973.2024.2384899","DOIUrl":"10.1080/08923973.2024.2384899","url":null,"abstract":"<p><strong>Objective: </strong>Inulicin is a sesquiterpene lactone in Inulae Flos which is clinically used for the treatment of inflammatory diseases, such as cough, sputum production, and vomiting. This study aimed to demonstrate the anti-inflammatory activity and the underlying mechanism of inulicin by using lipopolysaccharide (LPS)-induced <i>in vitro</i> and <i>in vivo</i> models.</p><p><strong>Methods: </strong>LPS-stimulated RAW264.7 macrophages and mouse peritoneal macrophages (MPMs) were used for evaluating the <i>in vitro</i> anti-inflammatory activity of inulicin, while endotoxemia mice were used for evaluating its <i>in vivo</i> action. Cytokines' levels were determined by ELISA. RT-qPCR and western blot were used for assaying the mRNA and protein levels of target genes. RAW264.7 macrophages transfected with reporter plasmid pNFκB-TA-luc or pAP1-TA-luc were used for assaying the activation of NF-κB or AP-1 signaling.</p><p><strong>Results: </strong>Inulicin significantly inhibited LPS-induced production of NO, IL-6, c-c motif chemokine ligand 2 (CCL2), and IL-1β in both RAW264.7 cells and MPMs. Mechanism study indicated that it could suppress inducible nitric oxide synthase, IL-6, CCL2, and IL-1β mRNA levels in LPS-stimulated RAW264.7 cells. Moreover, inulicin inhibited IκBα phosphorylation and prevented the nuclear translocation of p65, thereby inactivating NF-κB signaling. Concurrently, it also inhibited AP-1 signaling by reducing the phosphorylation of C-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). In endotoxemia mice, a single intraperitoneal administration of inulicin could decrease the production of pro-inflammatory cytokines in serum and peritoneal lavage fluid.</p><p><strong>Conclusions: </strong>The present study demonstrates that inulicin possesses anti-inflammatory effects <i>in vitro</i> and <i>in vivo</i>, which suggests that inulicin might be a promising candidate for the treatment of inflammatory diseases.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"583-593"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758479","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}