Wen-Chien Cheng, Pei Ying Chen, Xiang Zhang, Yu-Kang Chang, Kok-Tong Tan, Tim C C Lin
{"title":"5,7,3',4'-Tetramethoxyflavone suppresses TGF-β1-induced activation of murine fibroblasts in vitro and ameliorates bleomycin-induced pulmonary fibrosis in mice.","authors":"Wen-Chien Cheng, Pei Ying Chen, Xiang Zhang, Yu-Kang Chang, Kok-Tong Tan, Tim C C Lin","doi":"10.1080/08923973.2024.2371150","DOIUrl":"10.1080/08923973.2024.2371150","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the use of 5,7,3',4'-tetramethoxyflavone (TMF) to treat pulmonary fibrosis (PF), a chronic and fatal lung disease. <i>In vitro</i> and <i>in vivo</i> models were used to examine the impact of TMF on PF.</p><p><strong>Methods: </strong>NIH-3T3 (Mouse Embryonic Fibroblast) were exposed to transforming growth factor‑β1 (TGF-β1) and treated with or without TMF. Cell growth was assessed using the MTT method, and cell migration was evaluated with the scratch wound assay. Protein and messenger ribonucleic acid (mRNA) levels of extracellular matrix (ECM) genes were analyzed by western blotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively. Downstream molecules affected by TGF-β1 were examined by western blotting. <i>In vivo</i>, mice with bleomycin-induced PF were treated with TMF, and lung tissues were analyzed with staining techniques.</p><p><strong>Results: </strong>The <i>in vitro</i> results showed that TMF had no significant impact on cell growth or migration. However, it effectively inhibited myofibroblast activation and ECM production induced by TGF-β1 in NIH-3T3 cells. This inhibition was achieved by suppressing various signaling pathways, including Smad, mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/AKT (PI3K/AKT), and WNT/β-catenin. The <i>in vivo</i> experiments demonstrated the therapeutic potential of TMF in reducing PF induced by bleomycin in mice, and there was no significant liver or kidney toxicity observed.</p><p><strong>Conclusion: </strong>These findings suggest that TMF has the potential to effectively inhibit myofibroblast activation and could be a promising treatment for PF. TMF achieves this inhibitory effect by targeting TGF-β1/Smad and non-Smad pathways.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"496-508"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476504","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":"Prospective therapeutic targets and recent advancements in the treatment of inflammatory bowel disease.","authors":"Akshit Sinha, Supriya Roy","doi":"10.1080/08923973.2024.2381756","DOIUrl":"10.1080/08923973.2024.2381756","url":null,"abstract":"<p><strong>Objective: </strong>Inflammatory Bowel Disease (IBD) poses a persistent challenge in the realm of gastroenterology, necessitating continual exploration of innovative treatment strategies. The limited efficacy and potential side effects associated with existing therapeutic modalities underscore the urgent need for novel approaches in IBD management. This study aims to examine potential therapeutic targets and recent advancements in understanding the disease's intricate pathogenesis, with a spotlight on the gut microbiome, immune dysregulation, and genetic predispositions.</p><p><strong>Methods: </strong>A comprehensive review was conducted to delve into the pressing demand for new avenues in IBD treatment. The study examined potential therapeutic targets such as phosphodiesterase 4 (PDE4) inhibitors, immune system modulators, Tyrosine kinase receptors (TYK), Toll-like receptors (TLRs), modulation of the gut microbiota, stem cell therapy, fibrosis management, interleukins (ILs) regulation, and oxidative stress mitigation. Additionally, advances in precision medicine, biologics, small molecule inhibitors, and microbiome modulation techniques were explored.</p><p><strong>Results: </strong>The investigation unveiled promising therapeutic targets and provided insights into recent breakthroughs that herald a transformative era in the therapeutic landscape for IBD. Advances in precision medicine, biologics, small molecule inhibitors, and the exploration of microbiome modulation techniques stood out as pivotal milestones in the field of gastroenterology.</p><p><strong>Conclusions: </strong>The findings offer renewed hope for enhanced efficacy, reduced side effects, and improved patient outcomes in the treatment of IBD. These innovative approaches necessitate continual exploration and underscore the urgent need for novel strategies in IBD management, potentially revolutionizing the realm of gastroenterology.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"550-563"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626666","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":"Sirtuins: exploring next-gen therapeutics in the pathogenesis osteoporosis and associated diseases.","authors":"Tejal R Waykar, Satish K Mandlik, Deepa S Mandlik","doi":"10.1080/08923973.2024.2315418","DOIUrl":"10.1080/08923973.2024.2315418","url":null,"abstract":"<p><strong>Objective: </strong>Osteoporosis poses a substantial public health challenge due to an ageing population and the lack of adequate treatment options. The condition is marked by a reduction in bone mineral density, resulting in an elevated risk of fractures. The reduction in bone density and strength, as well as musculoskeletal issues that come with aging, present a significant challenge for individuals impacted by these conditions, as well as the healthcare system worldwide.</p><p><strong>Methods: </strong>Literature survey was conducted until May 2023 using databases such as Web of Science, PubMed, Scopus, and Google Scholar.</p><p><strong>Result: </strong>Sirtuins 1-7 (SIRT1-SIRT7), which are a group of Nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, possess remarkable capabilities to increase lifespan and combat diseases related to aging. Research has demonstrated that these proteins play an important role in regular skeletal development and maintenance by directly impacting bone cells. Their dysfunction could be a factor in various bone conditions. Studies conducted on animals before clinical trials have shown that administering Sirtuins agonists to mice provides a safeguard against osteoporosis resulting from aging, menopause, and immobilization. These findings imply that Sirtuins may be a viable target for addressing the irregularity in bone remodeling and treating osteoporosis and other skeletal ailments.</p><p><strong>Conclusion: </strong>The purpose of this review was to present a thorough and current evaluation of the existing knowledge on Sirtuins biology, with a particular emphasis on their involvement in maintaining bone homeostasis and contributing to osteoporosis. Additionally, the review examines potential pharmacological interventions targeting Sirtuins for the treatment of osteoporosis.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"277-301"},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691703","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":"Immunosuppressants against acute kidney injury: what to prefer or to avoid?","authors":"Swati Mishra, Vishwadeep Shelke, Neha Dagar, Maciej Lech, Anil Bhanudas Gaikwad","doi":"10.1080/08923973.2024.2330641","DOIUrl":"10.1080/08923973.2024.2330641","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) is a critical global health issue associated with high mortality rates, particularly in patients undergoing renal transplants and major surgeries. These individuals often receive immunosuppressants to dampen immune responses, but the impact of these drugs on AKI remains unclear.</p><p><strong>Objective: </strong>This review aims to provide a detailed understanding of the effects of different classes of immunosuppressants against AKI, elucidating their role in either exacerbating or mitigating the occurrence or progression of AKI.</p><p><strong>Methods: </strong>Several preclinical and clinical reports were analyzed to evaluate the impact of various immunosuppressants on AKI. Relevant preclinical and clinical studies were reviewed through different databases such as Scopus, PubMed, Google Scholar, and ScienceDirect, and official websites like https://clinicaltrials.gov to understand the mechanisms underlying the effects of immunosuppressants on kidney function.</p><p><strong>Results and discussion: </strong>Specific immunosuppressants have been linked to the progression of AKI, while others demonstrate renoprotective effects. However, there is no consensus on the preferred or avoided immunosuppressants for AKI patients. This review outlines the classes of immunosuppressants commonly used and their impact on AKI, providing guidance for physicians in selecting appropriate drugs to prevent or ameliorate AKI.</p><p><strong>Conclusion: </strong>Understanding the effects of immunosuppressants on AKI is crucial for optimizing patient care. This review highlights the need for further research to determine the most suitable immunosuppressants for AKI patients, considering both their efficacy and potential side effects.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"341-354"},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109953","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":"Tumor cells inhibit the activation of ILC2s through up-regulating PD-1 expression.","authors":"Chaoyun Yin, Yani Pa, Guangyu Li, Qiang Chen, Xizu Wang, Xijun He, Huangao Zhou","doi":"10.1080/08923973.2024.2347315","DOIUrl":"10.1080/08923973.2024.2347315","url":null,"abstract":"<p><strong>Objective: </strong>Up-regulating programmed cell death ligand-1(PD-L1) expressed on tumor cells and tumor-infiltrating myeloid cells interacting with up-regulated programmed cell death-1 (PD-1) expressed on tumor-infiltrating lymphoid cells greatly hinder their tumor-inhibiting effect. It is necessary to explore the deep mechanism of this negative effect, so as to find the potential methods to improve the immunotherapy efficiency.</p><p><strong>Methods and results: </strong>In this study, we found that the PD-1 expression in lung cancer-infiltrating type II innate lymphoid cells (ILC2s) was highly up-regulated, which greatly restrained the activation and function of ILC2s. Furthermore, anti-PD-1 could restore the inhibition and effective cytokine secretion of ILC2s when co-cultured with tumor cells. <i>In vivo</i> studies proved that anti-PD-1 treatment promoted the activation of tumor-infiltrating ILC2s and inhibited the tumor growth of LLC-bearing nude mice.</p><p><strong>Discussion: </strong>Our studies demonstrate a new PD-1/PD-L1 axis regulating mechanism on innate immune cells, which provide a useful direction to ILC2s-based immunotherapy to cancer diseases.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"417-423"},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860644","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}
Jia Jian, Li Yu-Qing, Han Rang-Yue, Zhong Xia, Xie Ke-Huan, Yan Ying, Wang Li, Tan Rui-Zhi
{"title":"Isorhamnetin ameliorates cisplatin-induced acute kidney injury in mice by activating SLPI-mediated anti-inflammatory effect in macrophage.","authors":"Jia Jian, Li Yu-Qing, Han Rang-Yue, Zhong Xia, Xie Ke-Huan, Yan Ying, Wang Li, Tan Rui-Zhi","doi":"10.1080/08923973.2024.2329621","DOIUrl":"10.1080/08923973.2024.2329621","url":null,"abstract":"<p><strong>Objective: </strong>Isorhamnetin (IH) has been reported to have significant anti-inflammatory effects in various diseases, but its role and mechanism in AKI remain unclear. This study aimed to explore the potential role and mechanism of isorhamnetin in inhibiting macrophage related inflammation and improving AKI injury.</p><p><strong>Methods: </strong>We established an AKI mouse model by intraperitoneal injection of cisplatin <i>in vivo</i>, and constructed an inflammatory cell model by stimulating RAW264.7 cells with LPS. Creatinine and urea nitrogen were measured to evaluate the changes of renal function in AKI mice. The changes of renal pathological structure were observed by H&E staining. The inflammatory factor-related proteins and RNA expression levels were detected by Western blot and real time PCR.</p><p><strong>Results: </strong>Isorhamnetin protected the kidney from cisplatin induced AKI and significantly inhibited the mRNA and protein levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) both in AKI kidney and LPS-stimulated RAW264.7 cells. Interestingly, the data also demonstrated that isorhamnetin significantly upregulated the expression of secretory leukocyte peptidase inhibitor (SLPI), an anti-inflammatory factor, in AKI kidney and LPS-stimulated macrophages, as well as inhibited the M1 macrophage and activated M2 macrophage <i>in vitro</i>. Blocking of SLPI by siRNA activated Mincle-associated inflammatory signaling in macrophages, and the inhibitory effect of isorhamnetin on inflammation was significantly attenuated.</p><p><strong>Conclusion: </strong>Isorhamnetin inhibits macrophage inflammation and protects kidney in AKI may be related to downregulating Mincle/Syk/NF-κB-maintained macrophage phenotype by activating SLPI.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"319-329"},"PeriodicalIF":2.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093814","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":"What factors may affect the effect of ICI-combined therapy in patients with metastatic renal cell carcinoma? A meta-analysis.","authors":"Haiyang Yan, Zhaohui Xing, Shuai Liu, Peng Gao, Guiying Guo","doi":"10.1080/08923973.2024.2315462","DOIUrl":"10.1080/08923973.2024.2315462","url":null,"abstract":"<p><strong>Objective: </strong>The prognostic factors of ICI-including combined therapy in patients with metastatic renal cell carcinoma were analyzed by systematic review.</p><p><strong>Method: </strong>We searched Web of Science, Cochrane, PubMed, CNKI, Wanfang and other databases for randomized controlled trials and clinical trials of combination therapy including ICIs in the treatment of metastatic renal cell carcinoma. The search time was from the establishment of the database to September 2023. Data were extracted and evaluated with RevMan 5.4 software.</p><p><strong>Results: </strong>Six studies were included, including 4723 patients. The results showed that ① in terms of progression-free survival, the factors of age < 65 years old, male sex, Canada and Western Europe, nephrectomy, different IMDC class, number of organs with metastases and PD-L1 expression ≥ 1% significantly prolonged PFS in patients with metastatic cancer treated by combination therapy including ICIs; ② in terms of overall survival rate, the factors of age < 65 years old, female sex, nephrectomy, different IMDC class and PD-L1 expression ≥ 1% significantly prolonged the OS of patients with metastatic cancer treated by combination therapy including ICIs.</p><p><strong>Conclusions: </strong>Age, sex, region, nephrectomy, different IMDC class, number of organs with metastases and PD-L1 expression are independent factors influencing the efficacy of combination therapy including ICIs in the treatment of metastatic renal cell carcinoma. Systematic evaluation of baseline indicators of patients with metastatic renal cell carcinoma to predict clinical benefits can effectively improve the benefit rate of patients.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"302-318"},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691704","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":"Comparative analysis of immunological changes following realgar and arsenic trioxide treatments in a murine model of myelodysplastic syndrome.","authors":"Yuchen Tao, Tingting Xue, Xiaodong Li, Runjie Guo, Yanlu Wang, Hao Xu, Kexin Hu, Xiaojie Dong, Dongqin Wang, Jianye Ren, Yu Guan, Jiahui Lu","doi":"10.1080/08923973.2024.2344158","DOIUrl":"https://doi.org/10.1080/08923973.2024.2344158","url":null,"abstract":"<p><strong>Background: </strong>Myelodysplastic syndrome (MDS) is a prevalent hematological neoplastic disorder in clinics and its immunopathogenesis has garnered growing interest. Oral and intravenous arsenic agents have long been used to treat hematological malignancies. The main component of oral arsenic is realgar (arsenic disulfide), while arsenic trioxide is the main component of intravenous arsenic.</p><p><strong>Methods: </strong>This study aimed to assess the effects of ATO and Realgar on the enhancement of peripheral blood, drug safety, and T cell immune status in the NUP98-HOXD13 (NHD13) mice model of MDS, specifically in the peripheral blood, spleen, and liver.</p><p><strong>Results: </strong>The study findings indicate that realgar and arsenic trioxide (ATO) can improve peripheral hemogram in mice, whereas realgar promotes higher peripheral blood cell production than ATO. Furthermore, the clinical administration method and dose did not cause significant toxicity or side effects and thus can be considered safe. Coexistence and interconversion of hyperimmune function and immunosuppression in mice were also observed in this study. In addition, there were interactions between immune cells in the peripheral blood, spleen, and liver to regulate the immune balance of the body and activate immunity <i>via</i> T-cell activation.</p><p><strong>Conclusion: </strong>In summary, oral and intravenous arsenic agents are beneficial in improving peripheral hemogram and immunity in mice.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":"46 3","pages":"408-416"},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179345","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":"Immuno-metabolic reprogramming of T cell: a new frontier for pharmacotherapy of Rheumatoid arthritis.","authors":"Sourav Mondal, Sarthak Saha, Debjeet Sur","doi":"10.1080/08923973.2024.2330636","DOIUrl":"10.1080/08923973.2024.2330636","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a persistent autoimmune condition characterized by ongoing inflammation primarily affecting the synovial joint. This inflammation typically arises from an increase in immune cells such as neutrophils, macrophages, and T cells (TC). TC is recognized as a major player in RA pathogenesis. The involvement of HLA-DRB1 and PTPN-2 among RA patients confirms the TC involvement in RA. Metabolism of TC is maintained by various other factors like cytokines, mitochondrial proteins & other metabolites. Different TC subtypes utilize different metabolic pathways like glycolysis, oxidative phosphorylation and fatty acid oxidation for their activation from naive TC (T<sub>0</sub>). Although all subsets of TC are not deleterious for synovium, some subsets of TC are involved in joint repair using their anti-inflammatory properties. Hence artificially reprogramming of TC subset by interfering with their metabolic status poised a hope in future to design new molecules against RA.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"330-340"},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119374","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}
Mansur Aliyu, Fatema Tuz Zohora, Ayca Ceylan, Fariha Hossain, Reza Yazdani, Gholamreza Azizi
{"title":"Immunopathogenesis of multiple sclerosis: molecular and cellular mechanisms and new immunotherapeutic approaches","authors":"Mansur Aliyu, Fatema Tuz Zohora, Ayca Ceylan, Fariha Hossain, Reza Yazdani, Gholamreza Azizi","doi":"10.1080/08923973.2024.2330642","DOIUrl":"https://doi.org/10.1080/08923973.2024.2330642","url":null,"abstract":"Background: Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating autoimmune disease with increasing global prevalence. It predominantly affects females, especially those of Europ...","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":"65 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609518","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}