{"title":"The role of cellular lipid metabolism and lipid-lowering drugs in periodontitis","authors":"Mohammad Kiarashi , Saman Yasamineh","doi":"10.1016/j.intimp.2025.114434","DOIUrl":"10.1016/j.intimp.2025.114434","url":null,"abstract":"<div><div>Initiated by bacteria, periodontitis (PD) is a complex, chronic inflammatory disease of the supporting tissue of the gums and teeth. Also linked to PD include human papillomavirus (HPV), hepatitis B virus (HBV), Epstein–Barr virus (EBV), human cytomegalovirus (CMV), and Herpes Simplex Virus (HSV). PD also raises the risk of cardiovascular disease (CVD) because it triggers inflammatory reactions throughout the body. CVD and chronic PD were linked to significantly elevated levels of C-reactive protein and blood lipids. Furthermore, elevated lipid peroxidation (LPO) levels may influence PD-related inflammation and periodontium degradation. In addition, there was a correlation between a reduction in oxidized low-density lipoprotein (LDL) levels and a reduction in circulating oxidative stress (OS); this was shown to be achieved by improved dental hygiene and non-surgical periodontal treatment. Consequently, this research set out to examine the connections between lipid metabolism and PD, as well as the effects of PD on the efficacy of statins and other medications that decrease cholesterol, as well as inhibitors and other lipid-lowering agents. Additionally, it's worth mentioning that statins and other cholesterol-lowering drugs may affect gum and tooth health. We found that higher blood levels of bad cholesterol exacerbate PD. Furthermore, PD makes CVD worse. The involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) in bacterial infections and the development of PD is inversely proportional to the increase in LDL levels. The treatment of this disease could, therefore, benefit greatly by inhibiting this chemical. Medications that lower cholesterol levels may potentially help treat this problem. The possible side effects of this medication on PD patients need more investigation. We have reviewed the literature on PD and its relationship to lipid metabolism, LDL receptors, and lipid rafts. Afterward, we investigated the role of lipid metabolism in the local viral infection that causes PD. Lastly, we examined how statins and other lipid-lowering medications impact PD.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114434"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiahong Li , Peicen Zou , Ruiqi Xiao , Yajuan Wang
{"title":"Indole-3-propionic acid alleviates DSS-induced colitis in mice through macrophage glycolipid metabolism","authors":"Jiahong Li , Peicen Zou , Ruiqi Xiao , Yajuan Wang","doi":"10.1016/j.intimp.2025.114388","DOIUrl":"10.1016/j.intimp.2025.114388","url":null,"abstract":"<div><div>Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease for which current therapeutic approaches still face many dilemmas, and targeting macrophage polarization and metabolism for the treatment of this disease is a potentially effective strategy. The gut microbial metabolite indole-3-propionic acid (IPA) has favorable anti-inflammatory and antioxidant effects and plays a role in a variety of disease models. IPA is effective in the treatment of UC, but the underlying mechanisms have not been well explored. In the present study, we investigated the mechanisms by which IPA ameliorates colitis in mice from the perspective of macrophage polarization and metabolism. In this study, mice colitis was induced by sodium dextran sulfate and treated with oral IPA. RAW264.7 cells were induced by LPS to polarize into M1 macrophages and treated with IPA. The results showed that IPA could improve colitis by inhibiting M1 polarization of colonic macrophages and promoting M2 polarization. The inhibition of IPA on M1 macrophages was verified in vitro through JNK/MAPK pathway, which inhibited the glycolysis of macrophages. IPA promotes macrophage M2 polarization and enhances fatty acid oxidation through upregulating of CPT1A and ACSL1, which may be related to the activation of PPAR-γ. In summary, IPA can improve colitis by regulating macrophage glucose and lipid metabolism, and targeting intestinal macrophage metabolism may be an effective target for the treatment of UC.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114388"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanlan Wu , Hao Ge , Haoran Zhao , Kaiping Zou , Pei Wang , Yi Wang , Yang Zhang
{"title":"The active ingredient β-sitosterol in the anti-inflammatory agents alleviates perianal inflammation in rats by inhibiting the expression of Srebf2, activating the PPAR signaling pathway, and altering the composition of gut microbiota","authors":"Yanlan Wu , Hao Ge , Haoran Zhao , Kaiping Zou , Pei Wang , Yi Wang , Yang Zhang","doi":"10.1016/j.intimp.2025.114470","DOIUrl":"10.1016/j.intimp.2025.114470","url":null,"abstract":"<div><h3>Background</h3><div>Anti-inflammatory herbal formulations are common in traditional Chinese medicine for clearing heat and detoxifying; however, the specific active components and their mechanisms remain unclear.</div></div><div><h3>Objective</h3><div>This study investigates the role of Sitosterol in alleviating perianal inflammation and its underlying mechanisms.</div></div><div><h3>Methods</h3><div>Sitosterol was identified as a key active ingredient through the TCMSP database. Its structure was analyzed using PubChem, target genes were explored with STITCH, and KEGG pathways related to Srebf2 were revealed by STRING. An animal model of perianal inflammation was induced with 75 % acetic acid and treated with Sitosterol, water, normal saline, or antibiotics. The effects on gut microbiota were assessed using 16S rRNA sequencing, and inflammation was evaluated through HE stains, IHC, and TUNEL assays. In vitro, LPS-treated Caco-2 cells were used to measure proliferation, apoptosis, and cytokine levels, with PPAR pathway involvement examined using GW6471.</div></div><div><h3>Results</h3><div>Sitosterol emerged as the primary active ingredient targeting Srebf2, with KEGG analysis highlighting the PPAR signaling pathway. In rats, Sitosterol reduced weight loss, inflammatory cell infiltration, edema, and vasodilation in perianal tissue. Additionally, it decreased PCNA levels, increased apoptosis, and elevated serum levels of IL-1β, IL-6, and TNF-α, particularly at high doses compared to antibiotics. Sitosterol also restored gut microbiota. Srebf2 knockdown improved tissue conditions and modulated cytokine levels, effects that were countered by GW6471. In LPS-treated Caco-2 cells, Sitosterol reversed reductions in cell viability and proliferation and modulated the expression of proteins and cytokines.</div></div><div><h3>Conclusion</h3><div>Sitosterol restores gut microbiota composition and further alleviates perianal inflammation in rats by inhibiting Srebf2 expression and activating the PPAR signaling pathway.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114470"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yun Zhang, Shuhan Shi, Changda Lin, Quanzuan Zeng, Lishuang Che, Yuangen Li, Weiyuan Lin
{"title":"Thiolutin, a novel NLRP3 inflammasome inhibitor, mitigates IgA nephropathy in mice","authors":"Yun Zhang, Shuhan Shi, Changda Lin, Quanzuan Zeng, Lishuang Che, Yuangen Li, Weiyuan Lin","doi":"10.1016/j.intimp.2025.114440","DOIUrl":"10.1016/j.intimp.2025.114440","url":null,"abstract":"<div><div>NLRP3 inflammasome plays a key role in IgA Nephropathy (IgAN) pathogenesis. Thiolutin (THL) is an NLRP3 inflammasome inhibitor with anti-inflammatory effects, but its role in IgAN is unclear. This study aimed to evaluate the protective efficacy of THL in IgAN mice, alongside assessing its inhibitory mechanisms. IgAN was induced by administration of bovine serum albumin combined with Staphylococcal Enterotoxin B in mice, followed by THL treatment. Kidney injury biomarkers, inflammatory cytokines, histological changes and the NLRP3 inflammasome pathway were assessed. The effect of THL on pyroptosis and action site on inflammasome was examined in J774A.1 cells, and co-immunoprecipitation was used to study specific protein interactions. In IgAN mice, THL treatment significantly reduced renal dysfunctional markers and histological injury without affecting hepatic function, accompanied by decreased serum IgA levels, renal IgA deposition and pro-inflammatory cytokine accumulation via regulating the mRNA and protein expression of key inflammasome components. It also attenuated pyroptosis and NLRP3 inflammasome activation instead of priming in macrophages, via disturbing the combination of NLRP3 with apoptosis-associated speck-like protein and NIMA-Related Kinase 7. THL has significant anti-inflammatory and renal protective effects in IgAN via inhibiting the NLRP3 inflammasome pathway. Its selective impact on the activation and assembly of the inflammasome, without affecting priming, highlights its potential as a targeted therapeutic agent in IgAN management.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114440"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jinzhong Guo , Zaixing Jia , Yourong Yang , Nan Wang , Yong Xue , Li Xiao , Fenghua Wang , Lan Wang , Xiaoou Wang , Yinping Liu , Jie Wang , Wenping Gong , Haimei Zhao , Yan Liang , Xueqiong Wu
{"title":"Bioinformatics analysis, immunogenicity, and therapeutic efficacy evaluation of a novel multi-stage, multi-epitope DNA vaccine for tuberculosis","authors":"Jinzhong Guo , Zaixing Jia , Yourong Yang , Nan Wang , Yong Xue , Li Xiao , Fenghua Wang , Lan Wang , Xiaoou Wang , Yinping Liu , Jie Wang , Wenping Gong , Haimei Zhao , Yan Liang , Xueqiong Wu","doi":"10.1016/j.intimp.2025.114415","DOIUrl":"10.1016/j.intimp.2025.114415","url":null,"abstract":"<div><h3>Background</h3><div>The global tuberculosis (TB) epidemic remains severe. We aimed to develop a therapeutic DNA vaccine as an adjunct to TB treatment to improve efficacy.</div></div><div><h3>Methods</h3><div>The W545 DNA vaccine was constructed using the <em>M. tuberculosis</em> (MTB) antigens Ag85A and Rv1419, integrated with epitopes from the Ag85B, Rv3407, and Rv2628. Bioinformatics tools were used to predict and analyze the physicochemical properties, structure modelling and molecular docking, epitopes (HTL, CTL, and B-cell), safety, population coverage, and simulated immunization of the W545 vaccine protein. Animal studies were then performed to evaluate the vaccine's immunogenicity by measuring Th1-type immune responses (IFN-γ, IL-2) and IgG antibody levels, as well as its therapeutic efficacy in reducing lung inflammation and pathological damage in a murine TB model.</div></div><div><h3>Results</h3><div>The vaccine protein is a 70 kDa hydrophilic protein with a half-life of 30 h, an instability index of 43.33, and strong affinity to Toll-like receptor (TLR) 2 and TLR4. It contains 397 helper T cell (HTL) epitopes, 248 cytotoxic T cell (CTL) epitopes, and 27 B cell epitopes, with broad population coverage (global: 99.7 %, Chinese: 97.6 %). The W545 vaccine significantly induced a Th1-type immune response, producing high levels of IFN-γ (5.38 pg/ml ± 0.89 pg/ml) and IgG antibodies (OD450: 0.13 ± 0.06). It also reduced the lung weight index, tissue lesions, and severity in the murine TB model.</div></div><div><h3>Conclusion</h3><div>The W545 DNA vaccine effectively induces a Th1-type immune response, alleviates pathological damage, and demonstrates potential as an immunotherapeutic agent. Bioinformatics analysis provides valuable guidance for vaccine design and optimization.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114415"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhengcai Ma , Juan Li , Jianyu Zhu , Zhipeng Yang , Xiaoduo Li , Hongmei Wang , Qin Tang , Yuan Zhou , Rakia Manzoor , Xiantao Chen , Hang Ma , Xiaoli Ye
{"title":"Jatrorrhizine retard obesity by modulating transcription factor c-Jun/c-Fos to downregulate Mmp12-mediated inflammation","authors":"Zhengcai Ma , Juan Li , Jianyu Zhu , Zhipeng Yang , Xiaoduo Li , Hongmei Wang , Qin Tang , Yuan Zhou , Rakia Manzoor , Xiantao Chen , Hang Ma , Xiaoli Ye","doi":"10.1016/j.intimp.2025.114405","DOIUrl":"10.1016/j.intimp.2025.114405","url":null,"abstract":"<div><div>Obesity is a systemic, chronic, low-grade inflammatory disease. Nutritional obesity, in particular, is also accompanied by inflammation and metabolic disorders, which are the primary causes of malignant metabolic diseases. <em>Rhizoma Coptidis</em> (<em>Coptis Chinensis Franch</em>) (RC), a traditional Chinese medicine, is primarily used for its anti-inflammatory and anti-diarrheal properties. Our previous studies have shown that RC can reduce body weight and lower fat levels, demonstrating its potential to improve nutritional obesity.However, the effects and mechanisms of the active small molecules in RC extracts in treating obesity-induced chronic inflammation need to be further investigated. In this study, we investigated the ameliorative effect and mechanism study of the monomeric jatrorrhizine (JAT) extracted from RC on high-fat diet-induced obese mice. First, JAT could dose-dependently reduce body weight and decrease the expression of inflammatory factors such as IL6, IL1β, and TNFα in the tissues of obese mice.Secondly, transcriptomics and bioinformatics studies of epididymal white adipose tissue (eWAT) identified Mmp12 as a key target through which JAT may alleviate obesity. Next, the effect of JAT on c-Jun/c-Fos promoter activity, which in turn down-regulates the transcript and protein levels of Mmp12, was analyzed and determined by qPCR, transcription factor prediction, single fluorescent promoter activity assay, Cell thermodynamic stability analysis (CETSA), molecular dynamics simulation mimicry, circular dichroism (CD) and Co-Immunoprecipitation (Co-IP). In conclusion, JAT may ameliorate high-fat diet-induced obesity and its associated inflammation through the c-Jun/c-Fos-Mmp12 axis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114405"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiandeng Li , Shuyan Zhao , Mi Li , Xiaodong Xing , Jing Xie , Mo Wang , Ajing Xu , Qinjian Zhao , Jian Zhang
{"title":"Wogonoside ameliorates oxidative damage in tubular epithelial cells of diabetic nephropathy by modulating the HNF4A-NRF2 axis","authors":"Xiandeng Li , Shuyan Zhao , Mi Li , Xiaodong Xing , Jing Xie , Mo Wang , Ajing Xu , Qinjian Zhao , Jian Zhang","doi":"10.1016/j.intimp.2025.114481","DOIUrl":"10.1016/j.intimp.2025.114481","url":null,"abstract":"<div><div>Diabetic nephropathy (DN), a leading cause of end-stage renal disease, presents significant challenges due to its complex pathophysiology and limited effective treatment options. Increasing evidence suggests that tubular injury is an early event preceding glomerular damage in DN. Wogonoside, a natural flavonoid derived from <em>Scutellaria baicalensis</em>, has not been previously reported for DN treatment. This study aims to investigate the protective effects and underlying mechanisms of wogonoside on renal tubular epithelial cells (TECs) in DN. The results showed that wogonoside mitigates high glucose (HG)-induced oxidative stress in TCMK-1 cells. Additionally, wogonoside protects renal function, reduces renal tubular damage, and modulates the oxidative stress response in HFD/STZ-induced DN mouse model. Importantly, our results indicated that hepatocyte nuclear factor 4 alpha (HNF4A) expression is downregulated in the kidneys of DN mice and HG-induced TCMK-1 cells. Wogonoside can bind to HNF4A, upregulate its expression, and promote nuclear translocation. Bioinformatic analysis suggested that NRF2 might be a downstream signaling of HNF4A. This was confirmed by Co-IP and experiments involving HNF4A overexpression and NRF2 knockdown, which demonstrated that wogonoside regulates the HNF4A-NRF2 axis to alleviate oxidative stress in TECs. Collectively, these findings identify wogonoside as a possible therapeutic agent for DN, highlighting HNF4A as a promising target for intervention.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114481"},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qian Liu , Guohao Deng , Xian Jiang , Yanpeng Fu , Jian Zhang , Xue Wu , Xinlong Li , Jingang Ai , Honghui Liu , Guolin Tan
{"title":"Macrophage-mediated activation of the IL4I1/AhR axis is a key player in allergic rhinitis","authors":"Qian Liu , Guohao Deng , Xian Jiang , Yanpeng Fu , Jian Zhang , Xue Wu , Xinlong Li , Jingang Ai , Honghui Liu , Guolin Tan","doi":"10.1016/j.intimp.2025.114439","DOIUrl":"10.1016/j.intimp.2025.114439","url":null,"abstract":"<div><h3>Background</h3><div>Epidemiological evidence suggests that environmental pollutants precipitate the occurrence of allergic rhinitis (AR). The aryl hydrocarbon receptor (AhR), a receptor or sensor for various contaminants, is closely related to immunomodulation and the polarization of M2 macrophages. However, the mechanisms involving AhR and M2 macrophages in AR remain unclear.</div></div><div><h3>Methods</h3><div>Bioinformatics analysis of GEO datasets (GSE180697 and GSE180697) assessed AhR and IL4I1 expression levels, which were then verified in the nasal mucosa, monocytes and serum of patients with AR using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). Primary human mononuclear cells were isolated from peripheral blood using a magnetic separation technique, and THP-1 cell lines with IL4I1 overexpression or downexpression were established through lentiviral constructs. M2 macrophages were induced with the cytokines CSF, IL4 and IL13 and then treated with the AhR agonist FICZ or inhibitor CH223191. The polarization of M2 macrophages was measured by flow cytometry and western blotting. Furthermore, primary nasal epithelial cells and macrophages were co-cultured to assess the epithelial-mesenchymal transition (EMT) in epithelial cells. The AR murine model was established using ovalbumin (OVA). Inflammation within the nasal mucosa and lung tissue was examined after CH223191 or IL4I1 treatment.</div></div><div><h3>Results</h3><div>Nuclear translocation of AhR and upregulation of IL4I1 was observed in peripheral mononuclear cells and nasal mucosal tissue of patients with AR. Through the activation of AhR, IL4I1 promoted M2 macrophage polarization. Furthermore, modulation of the IL4I1/AhR axis regulated the migratory impact of OVA on T-M2 cells. The IL4I1/AhR axis was involved in the regulation of M2 macrophage-associated EMT and contributed to the expression of IL-33 and STAT6 phosphorylation in epithelial cells. In AR mice, increased AhR nuclear translocation and higher expression of IL4I1 and the M2 macrophage marker CD206 in the lungs was observed. The IL4I1/AhR axis exacerbated allergic symptoms in AR mice, fostering allergic inflammation within the nasal mucosa and lungs.</div></div><div><h3>Conclusions</h3><div>The IL4I1/AhR axis is activated within the mononuclear phagocyte system of patients with AR. This activation facilitates the polarization of mononuclear cells into M2 macrophages, which further aggravates EMT in epithelial cells and exacerbates inflammation in AR. This study may provide novel strategies for the precise treatment of AR.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114439"},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tong-Tong Pan , Jia-Yin Huang , Xiao-Dong Wang , Da-Zhi Chen , Yong-Ping Chen
{"title":"Copper's dual role: Reviewing its impact on liver health and disease","authors":"Tong-Tong Pan , Jia-Yin Huang , Xiao-Dong Wang , Da-Zhi Chen , Yong-Ping Chen","doi":"10.1016/j.intimp.2025.114391","DOIUrl":"10.1016/j.intimp.2025.114391","url":null,"abstract":"<div><div>As an essential trace element in the human body, Cu exists in the oxidation states of Cu(II) and Cu(I). The interconversion between these states is closely associated with various redox reactions and plays a pivotal role in cellular respiration regulation, energy metabolism, cell growth regulation, and angiogenesis promotion among other biological processes. As the primary metabolic organ, the liver synthesises and secretes Cu-binding proteins to maintain Cu homeostasis and regulate its metabolism. Studies have increasingly demonstrated that abnormally high or low levels of Cu can negatively affect the immune and metabolic microenvironment within the liver. In this review, we summarise the mechanisms underlying Cu metabolism and its dysregulation and highlight the potential involvement of disrupted Cu metabolism in several liver diseases. Our review provides insights that will help in the future development of novel therapeutic targets focusing on Cu metabolism.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114391"},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuyao Yang , Xinnan Zhang , Yao Wang , Jie Liu , Lu Wang , Yi Liao , Yanwen Yang , Tao Dai , Xuemei Yin , Shanshan Li , Lu Han , Jiangjiang Zhu , Haibo Feng
{"title":"Mannose-modified erythrocyte membrane-coated Chuanmingshen violaceum polysaccharide PLGA nanoparticles to improve immune responses in mice","authors":"Shuyao Yang , Xinnan Zhang , Yao Wang , Jie Liu , Lu Wang , Yi Liao , Yanwen Yang , Tao Dai , Xuemei Yin , Shanshan Li , Lu Han , Jiangjiang Zhu , Haibo Feng","doi":"10.1016/j.intimp.2025.114450","DOIUrl":"10.1016/j.intimp.2025.114450","url":null,"abstract":"<div><div>This study developed a poly(lactic-<em>co</em>-glycolic acid) (PLGA) biomimetic nanoparticle (Man-RBC-CVPP) containing <em>Chuanmingshen violaceum</em> polysaccharide (CVP) and coated with a macrophage-targeting mannose receptor (DSPE-PEG-Man) modified RBCM. <em>In vitro</em> experiments demonstrated that Man-RBC-CVPP enhances antigen uptake and immune responses in RAW264.7 cells and can induce an immune response in mouse macrophages by activating the TLR4-mediated NF-κB signaling pathway. <em>In vivo</em> experiments showed that Man-RBC-CVPP promotes the activation of splenic dendritic cells (DCs) by increasing the expression of major histocompatibility complex class II (MHCII), CD80<sup>+</sup>, and CD86<sup>+</sup>. Further, it improves the maturation of splenic lymphocytes, increasing the expression of CD4<sup>+</sup> and CD8<sup>+</sup>. It also upregulates the secretion of cytokines, raises serum levels of the specific antibody IgG, and slows the release of OVA at the injection site. In summary, Man-RBC-CVPP can effectively enhance both cellular and humoral immune responses and provide controlled, long-term antigen release.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"152 ","pages":"Article 114450"},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}