Mediators of Inflammation最新文献

{"title":"The Association Study Between Cytokines and the Risk for Cerebral Palsy.","authors":"Baotian Wang, Fan Wang, Li Yang, Junhong Jiang, Jiulai Tang, De Wu","doi":"10.1155/mi/3742331","DOIUrl":"10.1155/mi/3742331","url":null,"abstract":"<p><p><b>Background:</b> Cerebral palsy (CP) is a debilitating condition characterized by abnormal movement or posture beginning early in development. Recent evidence has shown that immunological abnormalities are associated with an increased risk of CP. However, there are no valuable biomarkers for CP diagnosis. <b>Methods:</b> In this case-control study, we recruited 108 children with CP and 52 healthy children as controls. The white blood cell (WBC) counts and the levels of inflammatory markers (interleukin-1<i>β</i> (IL-1<i>β</i>), sIL-2R, interleukin-6 (IL-6), IL-8, IL-10, and tumor necrosis factor-<i>α</i> (TNF-<i>α</i>)), neuron-specific enolase (NSE), immunoglobulin E (IgE), and C3/C4 in the blood were measured and the results were statistically analyzed. Subgroup analyzes based on age, complications, and clinical subtypes were also carried out. <b>Results:</b> Compared with the controls, CP patients had elevated levels of NSE, sIL-2R, and TNF-<i>α</i>. There were no differences in WBC count, IL-1<i>β</i>, IL-6, IL-8, IL-10, IgE, C3, or C4. Subgroup analysis revealed significant differences in the personal-social developmental quotient (DQ) among the different CP subtypes. We found that TNF-<i>α</i>, sIL-2R, gross motor DQ, and adaptive DQ were greater in children with CP without epilepsy (EP) than in those with EP. Correlation analysis revealed positive correlations between TNF-<i>α</i> and sIL-2R, gross motor DQ, fine motor DQ, adaptive DQ, and personal-social DQ; moreover, sIL-2R was positively correlated with TNF-<i>α</i>, gross motor DQ, adaptive DQ, personal-social DQ, and eosinophil (EO) count and negatively correlated with age. NSE and TNF-<i>α</i> were associated with a 1.64-fold and 1.66-fold increased risk of CP, respectively. The peripheral blood NSE and TNF-<i>α</i> levels exhibited good diagnostic value for CP. Moreover, receiver operating characteristic (ROC) curve analysis revealed a significant increase in the area under the curve (AUC) when these indicators were combined. <b>Conclusions:</b> This study revealed significant associations between NSE and TNF-<i>α</i> and CP risk, suggesting that NSE and TNF-<i>α</i> might be useful blood biomarkers for identifying patients at high risk of CP.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"3742331"},"PeriodicalIF":4.4,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691816","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":"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}

{"title":"Systematic Review of Interleukin-35 in Endothelial Dysfunction: A New Target for Therapeutic Intervention.","authors":"Kai Li, Jie Feng, Meng Li, Leilei Han, Yanqing Wu","doi":"10.1155/mi/2003124","DOIUrl":"10.1155/mi/2003124","url":null,"abstract":"<p><p>Endothelial dysfunction is a significant factor in the pathogenesis of various diseases. In pathological states, endothelial cells (ECs) undergo activation, resulting in dysfunction characterized by the stimulation of inflammatory responses, oxidative stress, cell proliferation, blood coagulation, and vascular adhesions. Interleukin-35 (IL-35), a novel member of the IL-12 family, is primarily secreted by regulatory T cells (Tregs) and regulatory B cells (Bregs). The role of IL-35 in immunomodulation, antioxidative stress, resistance to apoptosis, control of EC activation, adhesion, and angiogenesis in ECs remains incompletely understood, as the specific mechanisms of IL-35 action and its regulation have yet to be fully elucidated. Therefore, this systematic review aims to comprehensively investigate the impact of IL-35 on ECs and their physiological roles in a range of conditions, including cardiovascular diseases, tumors, sepsis, and rheumatoid arthritis (RA), with the objective of elucidating the potential of IL-35 as a therapeutic target for these ailments.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"2003124"},"PeriodicalIF":4.4,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458661","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":"Inhibition of SIK1 Alleviates the Pathologies of Psoriasis by Disrupting IL-17 Signaling.","authors":"Dongxuan Huang, Huimin Sun, Lianhui Su, Fan Yang, Dongsheng Huang, Hanchao Gao, Mengtao Cao","doi":"10.1155/mi/3540219","DOIUrl":"10.1155/mi/3540219","url":null,"abstract":"<p><p>Psoriasis is an inflammatory skin disease mediated by multiple immune cells, including T cells, macrophages, and dendritic cells, which exhibit complex pathologies and limited clinical treatment. Here, we found that salt-inducible kinase 1 (SIK1) was upregulated in the imiquimod (IMQ)-induced psoriasis mouse model. This increment may be due to a higher level of interleukin-17, which promoted the expression of SIK1 in keratinocytes. Inhibition of SIK1 kinase activity using a small molecular inhibitor (HG-9-91-01 or YKL-06-062) dramatically alleviated IMQ-induced psoriasis, showing reduced epidermal thickness, inflammation, and hyperproliferative epidermal keratinocytes. Our data demonstrated that SIK1 inhibitors HG-9-91-01 or YKL-06-062 blocked the expression of IL-17-induced proinflammatory cytokines and chemokines, including <i>Il6</i>, <i>Kc</i>, and <i>Ccl20</i>. Mechanistically, we found that SIK1 inhibitor HG-9-91-01 or YKL-06-062 suppressed the phosphorylation of I<i>κ</i>b<i>α</i> and P38. Consistently, SIK1 overexpression in keratinocytes promoted the activation of I<i>κ</i>b<i>α</i> and P38. Collectively, our results reveal that SIK1 participates to promote IL17-induced signaling through enhancing activation of NF-<i>κ</i>B and MAPKs and exacerbates psoriasis-like skin inflammation. Thus, inhibition of SIK1 presents a potential new therapeutic target for psoriasis.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"3540219"},"PeriodicalIF":4.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433475","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":"NLRP3 Inflammasome Activation Is Involved in Geniposide-Induced Hepatotoxicity.","authors":"Yixuan Liu, Baoyue Liu, Mingzhu Shi, Tianxiang Ye, Huifang Li","doi":"10.1155/mi/4112856","DOIUrl":"10.1155/mi/4112856","url":null,"abstract":"<p><p><b>Background:</b> Geniposide, a prominent iridoid glycoside derived from <i>Gardenia jasminoides J</i>. Ellis, has garnered attention due to its association with hepatotoxicity despite its well-documented pharmacological efficacy in preclinical and clinical contexts. The NOD-like receptor protein 3 (NLRP3) inflammasome is implicated in numerous pathological conditions, including drug-induced liver injury. This study aims to explore the involvement of the NLRP3 inflammasome in geniposide-induced liver toxicity. <b>Methods:</b> Rats were administered geniposide for 5 days, concurrently treated with or without glibenclamide (GLY), an in vivo inhibitor of NLRP3. In vitro, HL-7702 cells were exposed to genipin (a metabolite of geniposide via hepatointestinal circulation), with or without GLY supplement. Liver tissue was examined through pathological sections. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), and total bilirubin (T-Bil) levels were determined using the enzyme plate method. IL-1<i>β</i> and IL-18 levels in the supernatant and serum were quantified through ELISA. Apoptosis-associated speck-like protein (ASC), NLRP3, caspase-1, pro-IL-1<i>β</i>, and pro-IL-18 mRNA levels in cells or the liver were assessed by RT-PCR. Protein levels of ASC, NLRP3, caspase-1, pro-IL-1<i>β</i>, and pro-IL-18 in cells or the liver were analyzed by Western blot. <b>Results:</b> Rats treated with geniposide displayed notable liver damage characterized by inflammatory infiltration, elevated serum transaminases, and heightened levels of inflammatory factors IL-1<i>β</i> and IL-18. This liver damage was concomitant with NLRP3 inflammasome activation within the liver. Furthermore, genipin induction led to reduced cell viability, increased transaminases in the cell supernatant, and an upsurge in inflammatory factors, resulting in heightened NLRP3 inflammasome expression within the cells. However, GLY effectively curtailed excessive NLRP3 activation, dampened the production of inflammatory factors IL-1<i>β</i> and IL-18, and ameliorated liver damage caused by geniposide. <b>Conclusions:</b> Our findings collectively elucidate that geniposide induces hepatotoxicity by triggering NLRP3 inflammasome signaling. Inhibition of the inflammasome presents a promising novel therapeutic target for mitigating geniposide-induced hepatotoxicity.</p>","PeriodicalId":18371,"journal":{"name":"Mediators of Inflammation","volume":"2025 ","pages":"4112856"},"PeriodicalIF":4.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11824841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414698","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}