Open Life SciencesPub Date : 2026-06-08eCollection Date: 2026-01-01DOI: 10.1515/biol-2025-1290
Xuekang Pan, Zeyuan Jin, Jiaqi Bi, Huigen Lu, Gang Chen
{"title":"Triptolide alleviates rheumatoid arthritis via modulating gut microbiota - intestinal barrier - TLR4/NF-κB axis.","authors":"Xuekang Pan, Zeyuan Jin, Jiaqi Bi, Huigen Lu, Gang Chen","doi":"10.1515/biol-2025-1290","DOIUrl":"10.1515/biol-2025-1290","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by dysregulated inflammation and intestinal microbiota-gut-joint axis dysfunction. While triptolide, a natural immunosuppressive compound, exhibits anti-RA activity, its mechanism linking gut microbiota modulation, intestinal barrier repair, and inflammatory signaling remains unclear. This study aimed to investigate whether triptolide alleviates adjuvant-induced arthritis (AIA) in mice by regulating the gut microbiota-intestinal barrier-toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) axis. The anti-inflammatory effect of triptolide was assessed using lipopolysaccharide (LPS)-induced RAW 264.7 cells and primary peritoneal macrophages. The anti-RA efficacy was investigated in AIA mice through detecting inflammatory factors, intestinal barrier integrity and gut microbiota. The results showed that triptolide decreased inflammatory factors in both RAW 264.7 cells and primary peritoneal macrophages. Meanwhile, triptolide dose-dependently reduced AI scores and paw swelling in AIA mice (<i>p</i> < 0.05 vs. AIA group), along with restored intestinal barrier integrity by upregulating ZO-1 and Occludin (<i>p</i> < 0.05 vs. AIA group) and modulated gut microbiota. Mechanistically, triptolide inhibited TLR4/NF-κB activation, reducing downstream pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor <i>α</i> (TNF-α)). In sum, these findings reveal that triptolide alleviates AIA by modulating the gut microbiota, repairing the intestinal barrier, and suppressing TLR4/NF-κB signaling. This highlights a novel \"microbiota-gut-joint\" regulatory mechanism of triptolide, supporting its potential as a therapeutic agent targeting RA's multifactorial pathogenesis.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"21 1","pages":"20251290"},"PeriodicalIF":2.3,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13241201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Open Life SciencesPub Date : 2026-06-05eCollection Date: 2026-01-01DOI: 10.1515/biol-2025-1337
Liuying Nong, Ling Shi, Lihong Pang
{"title":"Unveiling molecular mechanisms and therapeutic targets in HbH-CS disease: a focus on oxidative stress and mitochondrial dysfunction.","authors":"Liuying Nong, Ling Shi, Lihong Pang","doi":"10.1515/biol-2025-1337","DOIUrl":"10.1515/biol-2025-1337","url":null,"abstract":"<p><p>This study aimed to investigate the molecular mechanisms and therapeutic targets related to oxidative stress and mitochondrial dysfunction in Hemoglobin H-Constant Spring (HbH-CS) disease. HbH-CS differentially expressed genes (DEGs) were selected from a microarray dataset. Oxidative stress-related genes (OSGs) and mitochondrial function-related genes (MiRGs) were retrieved from public databases. Oxidative stress and mitochondrial function-related genes (OMRGs) were defined as the intersection of HbH-CS DEGs, OSGs, and MiRGs. Programmed cell death (PCD) mechanisms and functional enrichment analyses were subsequently investigated. A protein-protein interaction (PPI) network was constructed to identify hub genes, and potential regulatory mechanisms and expression levels of candidate genes were further explored. A total of 98 OMRGs were identified, which were associated with cellular respiration, oxidative stress response, mitochondrial membrane, and apoptotic signaling. Apoptosis was determined to be the primary PCD mechanism. Three hub genes were identified: AKT serine/threonine kinase 1 (AKT1), B cell lymphoma/leukemia-2 (BCL2), and cytochrome <i>c</i>, somatic (CYCS). Additionally, RNA-binding motif protein 15B (RBM15B) was recognized as a shared N6-methyladenosine (m<sup>6</sup>A) regulator. The mRNA expression levels of these four genes were significantly downregulated in HbH-CS patients. These findings provide novel insights into the molecular mechanisms and identify potential therapeutic targets for clinical intervention.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"21 1","pages":"20251337"},"PeriodicalIF":2.3,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Calcium-dependent regulation of antioxidant metabolism in maize seedlings under cadmium stress.","authors":"Xian Shi, Xun Li, Tiantao Wang, Qiong Kong, Yanhua Tang, Hengling Meng","doi":"10.1515/biol-2025-1313","DOIUrl":"10.1515/biol-2025-1313","url":null,"abstract":"<p><p>Calcium (Ca<sup>2+</sup>) is an essential nutrient for plants, contributing to their improved tolerance against heavy metal stress. This study aimed to investigate how varying Ca<sup>2+</sup> concentrations (0, 0.5, 2, and 5 mM) regulate maize seedling growth, physiological and biochemical traits, and cellular antioxidant defense systems under cadmium (Cd) stress, using hydroponic experiments to elucidate the mechanisms underlying Cd toxicity alleviation. The results revealed that Ca<sup>2+</sup> supplementation mitigated the inhibitory effects of Cd stress on root length, dry weight, and photosynthetic pigment contents. Also, Ca<sup>2+</sup> application increased the activities of superoxide dismutase and catalase, as well as the contents of glutathione and ascorbic acid in leaves, with maximum increases of 14.9 %, 65.39 %, 146 %, and 135 %, respectively, compared with the control (CK) treatment. Peroxidase activity significantly decreased under Ca<sup>2+</sup> treatment, with a maximum reduction of 34.38 % compared with that under CK treatment, whereas malondialdehyde content markedly increased, reaching 19.84 % higher than that under CK treatment. Meanwhile, principal component analysis revealed that the 5 mM Ca<sup>2+</sup> treatment achieved the highest composite score, indicating optimal antioxidant capacity in maize seedlings and reduced membrane lipid peroxidation caused by excessive Cd accumulation. This study enhances the understanding of the role of Ca in plant stress responses and provides insights for safe maize production in Cd-contaminated environments. However, given Cd accumulation in plants, whether the maize used in this study is suitable for animal and human consumption requires further investigation.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"21 1","pages":"20251313"},"PeriodicalIF":2.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13221269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Open Life SciencesPub Date : 2026-05-29eCollection Date: 2026-01-01DOI: 10.1515/biol-2025-1318
Ahlam Mohamed Yusuf, Xiehui Chen, Minmin Weng, Zhenzhen Su, Wei Hu, Nan Wu, Jing Xu, Binsheng Chen, Lishan Wu, Wei Sun, Xiaomin Chen, Zhanke Wang
{"title":"Sodium pyruvate attenuates oxidative stress, lowers ox-LDL and ox-LDL/LDL-P, and mitigates inflammation in diabetic atherosclerotic rats.","authors":"Ahlam Mohamed Yusuf, Xiehui Chen, Minmin Weng, Zhenzhen Su, Wei Hu, Nan Wu, Jing Xu, Binsheng Chen, Lishan Wu, Wei Sun, Xiaomin Chen, Zhanke Wang","doi":"10.1515/biol-2025-1318","DOIUrl":"10.1515/biol-2025-1318","url":null,"abstract":"<p><p>This study aimed to investigate the protective effects of sodium pyruvate against diabetic atherosclerosis in rats by reducing oxidative stress, ox-LDL levels, and inflammatory responses. Wistar rats were randomly divided into four groups: normal control (NC), diabetes mellitus (DM), diabetic atherosclerosis (DA), and diabetic atherosclerosis treated with sodium pyruvate (DA + SP). Serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), remnant-like particle cholesterol (RLP-C), ox-LDL, low-density lipoprotein particle (LDL-P), the ox-LDL/LDL-P ratio, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were measured. Compared with NC and DM groups, DA rats exhibited increased oxidative stress, lipoprotein abnormalities, and inflammation, evidenced by elevated MDA, RLP-C, ox-LDL, LDL-P, ox-LDL/LDL-P ratio, hs-CRP, and IL-6, along with reduced SOD levels. Sodium pyruvate treatment significantly decreased MDA, ox-LDL, ox-LDL/LDL-P ratio, hs-CRP, and IL-6, while increasing SOD activity compared with the DA group. No significant differences in RLP-C and LDL-P were observed between DA and DA + SP groups. Sodium pyruvate alleviates oxidative stress and inflammation and reduces ox-LDL-related indices, suggesting a protective role in diabetic atherosclerosis.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"21 1","pages":"20251318"},"PeriodicalIF":2.3,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13218308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Eruptive xanthomas: a case report with literature review focusing on pathogenesis and clinical management.","authors":"Xianhua Qiao, Xinglong Yu, Juanjuan Gao, Linfang Yang, Fang Cheng","doi":"10.1515/biol-2025-1327","DOIUrl":"10.1515/biol-2025-1327","url":null,"abstract":"<p><p>A typical case of eruptive xanthomas secondary to untreated type 2 diabetes mellitus complicated with severe hyperlipidemia was reported. The patient had a history of acute pancreatitis one month before the onset of xanthomas. Laboratory tests revealed high levels of triglycerides, cholesterol, blood glucose, and acute inflammatory markers. Histopathological examination showed the foam cells in the dermis. After interventions, including a low-fat and low-carbohydrate diet, anti-diabetic therapy and lipid-lowering therapy, the patient's skin lesions partially resolved within two months. At the same time, all laboratory indicators improved. In addition, a comprehensive literature review was conducted on the pathophysiological mechanisms, key clinical diagnostic points, triglyceride level thresholds, and main treatment strategies of eruptive xanthomas. This study emphasizes that eruptive xanthomas and acute pancreatitis are clinical manifestations induced by severe hypertriglyceridemia. For dermatologists, the occurrence of eruptive xanthomas should be used as a trigger to screen for dyslipidemia to effectively prevent life-threatening severe complications.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"21 1","pages":"20251327"},"PeriodicalIF":2.3,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13235822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Open Life SciencesPub Date : 2026-05-25eCollection Date: 2026-01-01DOI: 10.1515/biol-2025-1299
Hong Liang, Yuwen Chen
{"title":"Heterozygous pathogenic variants in <i>SERPINB7</i> potentially associated with Nagashima-type palmoplantar keratoderma and Hashimoto's thyroiditis: a case report.","authors":"Hong Liang, Yuwen Chen","doi":"10.1515/biol-2025-1299","DOIUrl":"10.1515/biol-2025-1299","url":null,"abstract":"<p><p>Nagashima-type palmoplantar keratoderma (NPPK) is an autosomal recessive disorder caused by biallelic loss-of-function variants in the <i>SERPINB7</i> gene, whereas Hashimoto's thyroiditis (HT) is a common autoimmune endocrine disease. The co-occurrence of NPPK and HT has not been previously reported. This study aims to present this novel association and investigate a potential underlying immunogenetic mechanism. We describe a 10-year-old boy presenting with fever, seizures and a long-standing history of palmoplantar erythema and hyperkeratosis. Diagnostic work-up included neurological evaluation, thyroid function tests, cytokine profiling and whole exome sequencing (WES). Laboratory findings during the acute phase revealed elevated anti-thyroid antibodies (anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies) and pro-inflammatory cytokines (interleukin [IL]-6, IL-10, interferon-γ). Skin examination confirmed NPPK, and WES identified compound heterozygous pathogenic <i>SERPINB7</i> mutations (c.522dupT; p.V175Cfs*46). The patient was diagnosed with NPPK, HT and Hashimoto's encephalopathy. Treatment with levothyroxine and levetiracetam led to the resolution of neurological symptoms and normalisation of thyroid function. This first report of coexisting NPPK and HT suggests a potential novel role for <i>SERPINB7</i> in immune dysregulation beyond its known cutaneous functions. The findings advocate considering thyroid screening in patients with NPPK and expand the phenotypic spectrum of <i>SERPINB7</i>-related disorders, warranting further research into its extracutaneous immunological roles.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"21 1","pages":"20251299"},"PeriodicalIF":2.3,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13201084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Research progress on the discovery and mechanism of nutritional intervention substances for pulmonary fibrosis: a focus on astragalus and its bioactive components.","authors":"Yueying Jiang, Hongfei Xing, Ling Li, Wenhua Jin, Hejing Tang, Senyang Hu, Zihao Wang, Yongting Luo, Yinhua Zhu, Qingchang Xing","doi":"10.1515/biol-2025-1330","DOIUrl":"10.1515/biol-2025-1330","url":null,"abstract":"<p><p>Pulmonary fibrosis (PF) is a chronic, progressive, and fatal fibrotic pulmonary interstitial lung disease characterized by excessive fibrosis. Its incidence is increasing globally, and the challenges associated with treatment and poor prognosis make it a significant public health burden, underscoring the urgent need for effective interventions. Nutritional interventions have garnered considerable attention for their potential to ameliorate PF. Notably, certain natural plant-derived bioactive compounds, exemplified by <i>Astragalus</i> and its constituents, demonstrate multifaceted benefits in combating PF. These include attenuating inflammatory responses, modulating immunity, exerting antioxidant effects, and promoting metabolic regulation. Through a comprehensive analysis of the existing literature, this review explores how nutritional interventions may improve the prognosis and quality of life for PF patients. It specifically focuses on discovering and summarizing the therapeutic effects of <i>Astragalus</i> and its active ingredients on PF, aiming to provide a theoretical foundation and reference for developing more effective therapeutic and management strategies for this disease.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"21 1","pages":"20251330"},"PeriodicalIF":2.3,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13201073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Differentiation of rat bone marrow mesenchymal stem cell into uterine smooth muscle cell <i>in vitro</i> study on the mechanism.","authors":"ZhengYong Chen, Yuan Liao, Jing Yang, XiaoLing Zeng","doi":"10.1515/biol-2025-1312","DOIUrl":"10.1515/biol-2025-1312","url":null,"abstract":"<p><p>Although bone marrow mesenchymal stem cells (BMSCs) are an important resource for tissue engineering and have been shown capable of differentiating into uterine smooth muscle cells (USMCs) to aid uterine regeneration, the precise conditions and mechanisms that control this process require further investigation. This study employed a Transwell co-culture system of rat BMSCs and USMCs to investigate both the differentiation of BMSCs into USMCs and the involvement of protein acetylation and microRNA (miR)-214 in this transition. Our results showed that co-cultured BMSCs exhibited upregulated expression of smooth muscle markers (Calponin, alpha-smooth muscle actin, and smooth muscle myosin heavy chain), enhanced contractility, and decreased CD44 levels. Furthermore, we observed increased protein acetylation and a time-dependent upregulation of miR-214 during differentiation. Enhancement of either protein acetylation or miR-214 expression promoted BMSCs differentiation toward a USMC lineage, with miR-214 overexpression also elevating overall protein acetylation levels. These findings demonstrate that BMSCs can be directed to differentiate into USMC-like cells under defined <i>in vitro</i> conditions, a process likely mediated by miR-214 through promotion of protein acetylation, thereby providing mechanistic insights and experimental support for stem cell-based therapies in uterine regeneration.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"21 1","pages":"20251312"},"PeriodicalIF":2.3,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13201085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Relationship between gestational diabetes mellitus and anxiety symptoms and gut microbiome composition in pregnant women.","authors":"Jing Xu, Lina Cai, Sushuang Lu, Lina Chen, Tiantian Zhang, Jing Wang","doi":"10.1515/biol-2025-1317","DOIUrl":"10.1515/biol-2025-1317","url":null,"abstract":"<p><p>Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy associated with poor outcomes for both mother and baby. An expanding body of research highlights the gut microbiota's influence on host metabolism and neurobehavioral processes, yet how gestational diabetes mellitus, anxiety symptoms, and microbial communities interact is still unclear. To address this gap, we profiled gut-microbiome changes in pregnant women presenting with both GDM and clinically significant anxiety. A total of 120 participants were categorized into four groups: GDM with anxiety (G + A), GDM without anxiety (G + NAF), non-GDM with anxiety (NG + A), and non-GDM without anxiety (NG + NA). Stool specimens were obtained and subjected to 16S rRNA gene profiling of the V3-V4 hypervariable region using Illumina MiSeq sequencing. Results showed significant differences in fasting blood glucose between GDM and non-GDM groups. GDM groups exhibited enrichment of Enterobacteriaceae and reduction of Faecalibacterium, while anxiety groups showed increased Lactococcus and Streptococcus. The dual-exposure group (G + A) demonstrated unique enrichment of oral-derived genera (e.g., Fusobacterium and Actinomyces). Among 963 OTUs identified, 681 were core OTUs shared across groups. GDM and anxiety groups possessed 42 and 32 unique OTUs, respectively, with 26 OTUs specific to the G + A group. LEfSe analysis revealed 16 phylogenetically conserved taxa distinguishing GDM and non-GDM groups, while anxiety-positive groups were characterized by Bacilli and Negativicutes. These findings suggest that GDM and anxiety are associated with distinct gut microbiota profiles, highlighting potential microbial biomarkers for early diagnosis and intervention.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"21 1","pages":"20251317"},"PeriodicalIF":2.3,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13201086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Open Life SciencesPub Date : 2026-05-20eCollection Date: 2026-01-01DOI: 10.1515/biol-2025-1319
Xiaoyan Huang, Cuijuan Zhang, Ming Yang, Xiaoshu Dong, Hui Zhang, Xingjiao Liu, Yi Jiang, Yongfei Wang, Yushuang Wei, Bing Yuan, Meiying Wang
{"title":"Alpha-1-antichymotrypsin: a potential inducer for epithelial-mesenchymal transition in lupus nephritis.","authors":"Xiaoyan Huang, Cuijuan Zhang, Ming Yang, Xiaoshu Dong, Hui Zhang, Xingjiao Liu, Yi Jiang, Yongfei Wang, Yushuang Wei, Bing Yuan, Meiying Wang","doi":"10.1515/biol-2025-1319","DOIUrl":"10.1515/biol-2025-1319","url":null,"abstract":"<p><p>Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus and represents a major risk factor for mortality. The critical pathological process affecting the renal parenchyma is fibrosis, which ultimately progresses to end-stage kidney disease. Identifying the molecular mediators of fibrosis is crucial for developing novel therapeutic strategies for lupus patients. Herein, we demonstrate that alpha-1-antichymotrypsin (AACT) is a critical inducer of the epithelial-mesenchymal transition (EMT) in HK-2 cells. Immunohistochemical analysis reveal that AACT expression progressively increases with advancing LN class. We next generate AACT knockout (AACT<sup>KO</sup>) and overexpressing (AACT<sup>OE</sup>) HK-2 cell lines. Our results indicate that AACT levels are positively correlated with cellular migration, the expression of migration-associated proteases, and collagen secretion in HK-2 cells. Notably, AACT inhibits the expression of the epithelial marker E-cadherin while promoting that of the mesenchymal marker α-SMA. Therefore, these findings suggest that AACT may contribute to renal fibrosis via triggering EMT, thereby promoting cell migration and collagen accumulation within renal tissues. Our study identifies AACT as a potential therapeutic target to counteract LN-associated renal fibrosis.</p>","PeriodicalId":19605,"journal":{"name":"Open Life Sciences","volume":"21 1","pages":"20251319"},"PeriodicalIF":2.3,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13211319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}