Mediators of Inflammation最新文献

{"title":"Deciphering the Interplay Among Inflammatory Bowel Disease, Gut Microbiota, and Inflammatory Biomarkers in the Risk of Colorectal Cancer.","authors":"Chenyu Luo, Bowen Tian, Yueyang Zhou, Jiahui Luo, Qing Shang, Si Yu, Min Dai, Yue Li, Hongda Chen","doi":"10.1155/mi/4967641","DOIUrl":"https://doi.org/10.1155/mi/4967641","url":null,"abstract":"<p><p><b>Background:</b> Patients with inflammatory bowel disease (IBD) have an elevated colorectal cancer (CRC) risk, though the etiology remains unclear. This study aimed to elucidate the interplay among IBD, gut microbiota (GM), inflammatory biomarkers, and CRC risk. <b>Methods:</b> First, we employed cohort analysis using the UK Biobank (UKB), linkage disequilibrium score regression (LDSC), and Mendelian randomization (MR) analyses to investigate the association between IBD and CRC. Second, inflammatory biomarkers' indirect effect was assessed using mediation analysis. Third, the causal effects of IBD on GM and GM on inflammatory biomarkers were evaluated using MR. Finally, we constructed a disease severity biomarker score and evaluated its CRC risk stratification performance. <b>Results:</b> Among 441,321 participants, IBD was associated with a 1.78-fold (95% confidence interval (CI): 1.45-2.18) increased risk of CRC. While LDSC and MR analyses showed no genetic correlation between IBD and CRC, mediation analyses revealed that C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) significantly mediated 10.41% and 9.97% of the IBD-CRC association, respectively. IBD increased the GM abundance of <i>Rikenellaceae RC9 gut group</i>, and decreased <i>Lactobacillaceae</i> and <i>Ruminococcus 2</i>, which in turn affected CRP, neutrophils, and lymphocytes. Notably, IBD decreased the abundance of <i>Ruminococcus 2</i> after Bonferroni correction (<i>β</i> = -9.463, <i>p</i>=0.0002). A disease severity biomarker score comprising of CRP, platelets, platelet-to-lymphocyte ratio (PLR), NLR, hemoglobin (Hgb), and albumin was constructed. IBD patients with the highest scores had a 3.07-fold (95% CI: 1.35-7.00) higher CRC risk compared to those with the lowest scores. <b>Conclusions:</b> IBD alters the microbial abundance of <i>Rikenellaceae RC9 gut group</i>, <i>Lactobacillaceae</i>, and <i>Ruminococcus 2</i>, thereby, influencing inflammatory biomarkers including CRP, neutrophils, and lymphocytes, which mediate the increased risk of CRC in IBD patients. The constructed biomarker score enables individualized CRC risk stratification in IBD patients.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4967641"},"PeriodicalIF":4.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1,25-D3 Protects Diabetic Brain Injury Through GLP-1R/PI3K/Akt Pathway by Experimental and Molecular Docking Studies.","authors":"Ting Song, Bin Wang, Yutian Li, Yingzhe Zhao, Jian Li, Yanqiang Wang, Xiangling Li","doi":"10.1155/mi/8217035","DOIUrl":"https://doi.org/10.1155/mi/8217035","url":null,"abstract":"<p><p><b>Background:</b> Diabetes can cause an increase in intracellular glucose, leading to neuronal damage and microvascular dysfunction. Neuroprotective agents 1<i>α</i>,25-dihydroxyvitamin D3 (1,25-D3) can reduce neurological complications. The main purpose of this study is to evaluate the levels of inflammatory factors and vascular protective factors in streptozotocin (STZ)-induced diabetic rats and determine whether 1,25-D3 can protect the rat brains from hyperglycemia through the glucagon-like peptide-1 (GLP-1)R/PI3K/AKT signal pathway. <b>Methods:</b> We first evaluated whether the relevant target could effectively bind to 1,25-D3 through molecular docking. Next, we established STZ-induced diabetic rat models for in vivo experiments to verify the targets in molecular docking that have good binding effects on 1,25-D3. After 8 weeks of a high-fat diet (HFD) and an intraperitoneal injection of STZ (35 mg/kg body weight), the experimental type 2 diabetic rat model was created, and the morphological changes of the cerebral cortex were measured by performing hematoxylin and eosin (H&E) staining. Western blotting (WB) was used to detect the proteins' expression of relevant targets, and the RT-qPCR was used to analyze the mRNA levels of relevant targets in the cerebral cortex. We also utilized the enzyme-linked immunosorbent assay (ELISA) kit for detecting the protein content of relevant targets. <b>Results:</b> Molecular docking showed that 1,25-D3 had good binding ability with related targets, such as GLP-1R, PI3K, AKT1, vascular endothelial growth factor-<i>α</i> (VEGF-<i>α</i>), endothelial nitric oxide (NO) synthase (e-NOS), intercellular adhesion molecule-1 (ICAM-1), and vascular intercellular adhesion molecule-1 (VCAM-1). Experimental verification results found that 1,25-D3 partially prevented abnormalities in brain function and structure caused by diabetes. Meanwhile, the ICAM-1 and VCAM-1 levels were increased in the high-glucose group, e-NOS levels were decreased, and the relative expression of GLP-1R, VEGF-<i>α</i>, p-PI3K/PI3K, and p-AKT/AKT was reduced. 1,25-D3 abolished these changes, and these effects were suppressed by specific inhibitors. <b>Conclusions:</b> 1,25-D3 alleviates neuroinflammation and improves vascular endothelial dysfunction through multitarget and multipathway by upregulating the GLP-1R/PI3K/AKT signaling axis to improve diabetes-induced brain injury.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8217035"},"PeriodicalIF":4.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Role of GRK2: From Immune Regulation to Cancer Therapeutics.","authors":"Xizhuang Gao, Dehuai Jing, Yaowen Zhang, Fengqin Zhu, Yonghong Yang, Guangxi Zhou","doi":"10.1155/mi/8837640","DOIUrl":"https://doi.org/10.1155/mi/8837640","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) represent humans' most prominent family of membrane proteins. In contrast, G protein-coupled receptor kinases (GRKs) play a pivotal role in the rapid desensitization of GPCRs. GRK2 is a particularly significant member of the GRK family. Recent studies have demonstrated that GRK2 primarily regulates immune cell function and homeostasis through receptor desensitization. Over the past decade, substantial progress has been made in elucidating the role of GRK2 in various human diseases. Notably, GRK2 is implicated in a range of autoimmune disorders, including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), Sjögren's syndrome (SS), autoimmune myocarditis, hepatitis, and Graves' disease. Furthermore, emerging research has expanded our understanding of GRK2's involvement in cancer biology. Comprehensive investigations into the biological and pathological functions of GRK2 have facilitated the development of therapeutic strategies aimed at targeting the GRK2 signaling pathway in cancer, inflammation, and autoimmune diseases. Promising results have been observed with targeted biologics in preclinical and clinical trials. This review aims to elucidate the multifaceted role of GRK2 in immune function, autoimmune diseases, and cancer to uncover the remaining complexities associated with this kinase. A thorough understanding of GRK2 may position it as a potent therapeutic target in treating inflammation and cancer.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"8837640"},"PeriodicalIF":4.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukins-27 Aggravates Liver Injury by Impairing the Antimicrobial Response of Macrophages via the Promotion of Mitochondrial Dysfunction in the Context of Sepsis.","authors":"Yuehua You, Yuyan Li, Lin Ye, Fang Xu, Jing Fan","doi":"10.1155/mi/6608718","DOIUrl":"10.1155/mi/6608718","url":null,"abstract":"<p><p><b>Background and Aims:</b> Plasma interleukin (IL)-27 is an important mediator of acute hepatic injury (AHI) associated with sepsis. Mitochondria contribute to the proper regulation of macrophage phagocytosis. In this study, we investigated the effect of IL-27 on mitochondrial function and the antimicrobial response of macrophages in sepsis-associated AHI. <b>Methods:</b> Wild-type (WT) and IL-27 receptor WSX-1 deficient (IL-27R^-/-) mice underwent cecal ligation and puncture (CLP). The severity of hepatic injury, inflammatory cytokine levels, hepatic pyroptosis, and bacterial load in the liver and blood were assessed 24 h after CLP. In vitro, RAW264.7 cells and peritoneal macrophages were treated with lipopolysaccharide (LPS) and/or IL-27. The phagocytosis and killing functions of macrophages were detected. Mitochondrial function and mitophagy were detected using western blot, glutathione (GSH)/malondialdehyde (MDA) content measurement, fluorescence staining, and JC-1 staining in vivo and in vitro. After treatment with nicotinamide mononucleotide (NMN, NAD + precursor), a pharmacologic agent that improves mitochondrial function, the inflammatory response, hepatic injury, and hepatic pyroptosis were assessed. <b>Results:</b> IL-27R^-/- mice exhibited a marked reduction in hepatic injury, pyroptosis (based on cleaved GSDMD and cleaved Caspases 1 protein levels), and systemic inflammation (based on serum IL-6, IL-10, and TNF-<i>α</i> levels) compared to WT mice following CLP. After CLP, mice lacking IL-27R displayed significantly higher bacterial clearance and greater local infection control. Subsequent studies demonstrated that IL-27 directly impaired the LPS-induced bacterial phagocytosis, killing capacity, and mitochondrial function of macrophages. Finally, enhanced mitochondrial function using NMN in vivo significantly alleviated pathological liver injury and inflammation. <b>Conclusions:</b> These findings indicated that IL-27 impairs the bacterial phagocytosis capacity of macrophages by aggravating mitochondrial dysfunction to aggravate AHI during sepsis.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"6608718"},"PeriodicalIF":4.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress of ADAM17 in Fibrosis-Related Diseases.","authors":"Suyan Yan, Yaqi Zhao, Yuyu Yang, Baocheng Liu, Wei Xu, Zhenzhen Ma, Qingrui Yang","doi":"10.1155/mi/9999723","DOIUrl":"https://doi.org/10.1155/mi/9999723","url":null,"abstract":"<p><p>Fibrosis leads to structural damage and functional decline and is characterized by an accumulation of fibrous connective tissue and a reduction in parenchymal cells. Because of its extremely poor prognosis, organ fibrosis poses a significant economic burden. In order to prevent and treat fibrosis more effectively, potential mechanisms need to be investigated. A disintegrin and metalloprotease 17 (ADAM17) is a membrane-bound protein. It regulates intracellular signaling and membrane protein degradation. Fibrosis mediated by ADAM17 has been identified as an important contributor, although the specific relationship between its multiple regulatory functions and the pathogenesis is unclear. This article describes ADAM17 activation, function, and regulation, as well as the role of ADAM17 mediated fibrosis injury in kidney, liver, heart, lung, skin, endometrium, and retina. To develop new therapeutic approaches based on ADAM17 related signal pathways.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9999723"},"PeriodicalIF":4.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aeroallergen Sensitization Patterns and Related Factors in Children With Allergic Rhinitis in Guangzhou.","authors":"Qingxiang Zeng, Chao Yang, Jinyuan Li, Xiangqian Qiu, Wenlong Liu","doi":"10.1155/mi/5887915","DOIUrl":"10.1155/mi/5887915","url":null,"abstract":"<p><p><b>Background:</b> Certain patterns of children's serum immunoglobulin E (IgE) sensitivity to aeroallergens may offer useful clinical insight into forecasting the course and prognosis of allergic rhinitis (AR). The study aimed to investigate the changes in aeroallergen sensitization patterns in children with AR during the last decade and compare the sensitization pre- and post-coronavirus disease 2019 (COVID-19) pandemic in Children who visited our center. <b>Methods:</b> This is a retrospective study, examining the serum IgE of nine aeroallergens from 21,362 children (1-12 years old) from AR who visited Guangzhou Women and Children's Medical Center from June 2013 to June 2023. <b>Result:</b> The dust mites were the most prevalent aeroallergen in Guangzhou, with positive sensitization rates of 74.30% for <i>Dermatophagoides farinae</i> (<i>D. farinae</i>), 73.30% for <i>Dermatophagoides pteronyssinus</i> (<i>D. pteronyssinus</i>), and common ragweed (1.6%) was the lowest. After the COVID-19 pandemic, the sensitization rates to <i>D. farinae</i> were consistent and <i>D. pteronyssinus</i> was slightly decreased while German cockroach, cat, and dog dander were increased. Most of the aeroallergens other than common ragweed were increased in school-age children than preschool stage. Boys have a higher positive rate than girls for <i>D. farinae</i> and <i>D. pteronyssinus</i>. <b>Conclusions:</b> With the unraveling of allergens' sensitization rates in various conditions, avoidance from <i>D. farinae</i> and <i>D. pteronyssinus</i> should still be the most important objectives to maintain in reducing AR episodes.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"5887915"},"PeriodicalIF":4.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taohong Siwu Decoction Combined With the LncRNA H19/miR-675-5p Axis Repairs Limb Ischemia-Reperfusion Injury Through the Regulation of the Wnt3a/Ca²⁺ Signaling Pathway.","authors":"Fuping Zhu, Hui Liu, Yinsheng Cao, Bing Dai, Hang Wu, Yutong Zhu, Wuping Li","doi":"10.1155/mi/3096848","DOIUrl":"10.1155/mi/3096848","url":null,"abstract":"<p><p><b>Background:</b> Taohong Siwu decoction (THSWT) has shown therapeutic effects on ischemia/reperfusion injury (IRI). This study tended to investigate the role of THSWT combined with the long non-coding RNA (LncRNA) H19 (H19)/miR-675-5p axis in improving limb IRI (LIRI). <b>Methods:</b> Hind LIRI rats and simulated IRI skeletal myoblasts models were constructed to evaluate the therapeutic effects of THSWT. The mechanism of THSWT treatment on LIRI was investigated by the regulation of the H19/miR-675-5p axis and the wingless/integrated (Wnt)/Ca²⁺ signaling pathway. Various assessments, such as H&E staining, TUNEL staining, flow cytometry, cell counting kit-8 (CCK-8) assay, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC) staining, enzyme-linked immunosorbent assay (ELISA), biochemical assay, and calcium fluorescence imaging, were conducted to observe skeletal muscle injury, cell apoptosis, skeletal myoblast proliferation, gene and protein expressions, cytokine levels, glucose (Glu) uptake, and Ca²⁺ concentration. <b>Results:</b> THSWT intervention effectively improved skeletal muscle injury in LIRI rats, as evidenced by reduced muscle fiber damage and decreased cell apoptosis, accompanied by downregulation of H19, miR-675-5p, cleaved-Caspase3, Bax, PLC, and PKC expressions and upregulation of Bcl2 expression. Furthermore, silencing of H19 inhibited cell apoptosis of skeletal muscle and reduced IL-1<i>β</i>, IL-6, and TNF-<i>α</i> levels in LIRI rats. Notably, THSWT intervention combined with the silencing of H19 synergistically promoted the repair of skeletal muscle injury in LIRI rats. Mechanistically, THSWT intervention combined with regulation of the H19/miR-675-5p axis promoted the proliferation of skeletal myoblasts damaged by IRI through the Wnt3a/Ca²⁺ signaling pathway, increasing the levels of intracellular Bcl2, while decreasing the levels of Ca²⁺, CaMKⅡ, PLC, PKC, cleaved-Caspase3, Bax, TNF-<i>α</i>, IL-1<i>β</i>, IL-6, Wnt3a, and <i>β</i>-catenin. <b>Conclusions:</b> THSWT combined with the regulation of the H19/miR-675-5p axis effectively improved LIRI by modulating the Wnt3a/Ca²⁺ signaling pathway, providing insights for potential therapeutic strategies for LIRI.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"3096848"},"PeriodicalIF":4.4,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro, In Vivo, and In Silico Investigation of Synbiotic-Mediated Activation of PPAR-<i>α</i> Curtails Nonalcoholic Steatohepatitis (NASH) in Wistar Rats by Inhibiting PNPLA3/SREBP1-c Lead Inflammatory Injury of Hepatic Cells.","authors":"Dixa Sharma, Dhara Patel, Palash Mandal","doi":"10.1155/mi/9948679","DOIUrl":"10.1155/mi/9948679","url":null,"abstract":"<p><p>Nonalcoholic steatohepatitis (NASH) is an inflammation of the liver and a menace to human health. To treat NASH various pharmaceutical products have been used, but their prohibitive side effects limit their effectiveness. NASH, a multihit hypothesis involves high-fat diet and signals from the gut to the liver. <i>Lactobacillus plantarum</i> (probiotic) and aged garlic extract (AGE, a prebiotic) are antioxidative and anti-inflammatory and may be a latent combination therapy for NASH. The NASH model was developed using Wistar rats and treatments were administered to understand the mechanism. Initially, in the in vitro models, transepithelial electrical resistance (TEER) 2'-7'-dichlorodihydrofluorescein diacetate (DCFDA), 4-6-diamidino-2-phenylindole (DAPI) labeling and Oil Red O (ORO) conducted on HepG2 and Caco2 cells. Afterwards, in in vivo studies rat liver tissues were examined through confocal microscopy using the ORO staining and hematoxylin and eosin (H/E) stain, malondialdehyde (MDA), and biochemical indices were recorded. The levels of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and sterol regulatory element binding protein-1c (SREBP-1c), peroxisome proliferators activated receptors (PPARs)-<i>α</i>, inflammatory, and apoptotic biomarkers were quantified by qRT-PCR. Synbiotic reduced the hepatic inflammation and apoptosis examined through the levels of PNPLA3, SREBP-1c, IL-6, TGF-<i>β</i>, Bcl-2, and caspase-3 in NASH models. In turn, the gram-negative species and bacterial translocation associated were reduced. Consequently, the Insilco analysis supports the theory that each (eight) bioactive compound of AGE targets PNPLA3 and enhances the PPAR-<i>α</i> activity. Additionally, PPAR-<i>α</i> inhibitors upregulated the PNPLA3 and SREBP-1C expression. As a result, the synbiotic may inhibit NASH progression by affecting PNPLA3/SREBP1-c through PPAR-<i>α</i>.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"9948679"},"PeriodicalIF":4.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11865469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selenium Nanoparticles Decorated With Stevioside Potentially Attenuate Fructose Palmitate Induced Lipid Accumulation in HepG2 Cells.","authors":"Shuai Li, Hui Yang, Wenjun Zhou, Ruoting Wang, Likang Li, Changfa Zhang, Jingyi Zhang, Yingxin Liu, Zhi Huang, Guowei Li","doi":"10.1155/mi/7942947","DOIUrl":"10.1155/mi/7942947","url":null,"abstract":"<p><p>The excessive accumulation of lipid droplets within hepatocytes stands as a hallmark characteristic of metabolic-associated fatty liver disease (MAFLD). Selenium (Se) nanoparticles (NPs) have garnered considerable attention for their notable bioavailability, minimal toxicity, and exceptional antioxidant properties. However, a critical limitation lies in the propensity of SeNPs to aggregate into the biologically inactive elemental Se, thereby constraining their utility. Here, we utilized <i>Stevioside</i> (<i>SV</i>), a natural sweetener, to modify SeNPs and obtained the SV-SeNPs with a size of about 187 ± 7 nm. We aimed to investigate the effect of SV-SeNPs on high fructose-palmitate (HFP) induced lipid accumulation in HepG2 cells. Noteworthy is the absence of overt cytotoxicity attributed to SV-SeNPs on normal HepG2 cells. Of significance, our findings delineate the profound inhibitory effects of SV-SeNPs on the expression of key genes implicated in de novo lipogenesis, such as fatty-acid synthase (FASN), acetyl-CoA-carboxylase 1 (ACC1), and stearoyl-CoA desaturase-1 (SCD1) within HFP-induced HepG2 cells. Furthermore, our investigation reveals that SV-SeNPs mediate a significant reduction in lipid accumulation by activating the PI3K/AKT/Nrf2 signaling cascades. Additionally, the antioxidative properties of SV-SeNPs are underscored by their ability to counteract oxidative stress via the upregulation of two pivotal antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx). In conclusion, our study unveils the potential beneficial effects of SV-SeNPs on the prevention and treatment of MAFLD by effectively suppressing lipid accumulation and ameliorating oxidative stress.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"7942947"},"PeriodicalIF":4.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Herbal Medicine Extracts Improve Motor Function by Anti-Inflammatory Activity in hSOD1^G93A Animal Model.","authors":"Eun Jin Yang, Sun Hwa Lee","doi":"10.1155/mi/1999953","DOIUrl":"10.1155/mi/1999953","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a multicomplex neurodegenerative disorder characterized by motor neuron death, muscle atrophy, and respiratory failure. Owing to its multicomplex mechanisms and multifactorial nature in the skeletal muscle and spinal cord (SC), no effective therapy has been developed. However, herbal medicines, known for their multitarget properties, have demonstrated promising efficacy with limited side effects in treating various diseases. Specifically, <i>Paeonia lactiflora</i> Pallas has been demonstrated to exhibit analgesic, antidepressant, anti-inflammatory, and neuroprotective effects. However, the pharmacological mechanisms underlying the beneficial effects of <i>P. lactiflora</i> in hSOD1^G93A animal models remain unexplored. Therefore, this study was conducted to investigate the multitarget effects of <i>P. lactiflora</i> in hSOD1^G93A transgenic mice, an ALS model. Footprint tests, western blot assays, and immunohistochemical analysis were used to assess the effect of <i>P. lactiflora</i> on the tibia anterior (TA), gastrocnemius (GC), and SC. The results revealed that <i>P. lactiflora</i> augmented motor function and decreased motor neuron loss in hSOD1^G93A mice. Furthermore, <i>P. lactiflora</i> significantly lowered the expression of proteins associated with inflammation and oxidative stress in the skeletal muscle (TA and GC) and SC. <i>P. lactiflora</i> also regulated autophagy function by reducing the levels of key markers, such as P62/sequestosome 1 (SQSTM1), microtubule-associated proteins 1A/1B light chain 3B, and SMAD family member 2, in the muscle and SC. Overall, <i>P. lactiflora</i> treatment improved motor function, prevented motor neuron death, and exhibited anti-inflammatory and antioxidative effects in the skeletal muscle and SC of ALS mouse models. These results suggest that <i>P. lactiflora</i> could serve as a promising multitarget therapeutic agent for systemic and multipathological diseases.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"1999953"},"PeriodicalIF":4.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}