Hereditas最新文献

{"title":"Clinical relevance and mechanistic investigation of miR-1908-5p as a prognostic biomarker in colorectal cancer.","authors":"Chenchen Yuan, Shaofei Chen, Qianli Liu, Riwei Wang","doi":"10.1186/s41065-026-00645-2","DOIUrl":"10.1186/s41065-026-00645-2","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is characterized by a complex pathogenesis and substantial heterogeneity in prognosis.</p><p><strong>Objective: </strong>This study aims to elucidate the clinical significance of miR-1908-5p in CRC, as well as its association with clinicopathological parameters and patient prognosis.</p><p><strong>Method: </strong>miR-1908-5p expression in tumor tissues was quantified by RT-qPCR. Survival outcomes were assessed using the Kaplan-Meier method. The chi-square (χ²) test and Cox regression analysis were employed to evaluate clinicopathological correlations and prognostic value.miR-1908-5p was compared between NCM460 and CRC lines (HT-29, HCT116), overexpressed, and functionally tested by CCK-8 and Transwell assays. TargetScan and luciferase assay verified the targeting of SCAMP4 3'-UTR. qPCR and Pearson analysis defined their correlation in CRC.</p><p><strong>Results: </strong>miR-1908-5p is downregulated in CRC tumors versus adjacent normal mucosal tissues. Low expression predicts poor prognosis and is associated with reduced survival rates in colorectal cancer, correlating with advanced TNM stage and elevated serum CA19-9 levels. CRC lines (HT-29 and HCT116) show reduced miR-1908-5p compared to NCM460. miR-1908-5p mimic suppresses proliferation, migration, and invasion. TargetScan-predicted binding to SCAMP4 3'-UTR was validated by dual-luciferase reporter assay. miR-1908-5p overexpression lowers SCAMP4, which is overexpressed in tumor tissues and exhibits an inverse correlation with miR-1908-5p.</p><p><strong>Conclusion: </strong>miR-1908-5p is downregulated in CRC, correlates with TNM stage, nodal metastasis, elevated CA19-9 levels, and poor survival, and suppresses CRC cell proliferation, migration, and invasion by directly targeting SCAMP4, thereby qualifying as a potential prognostic biomarker for CRC.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":"32"},"PeriodicalIF":2.6,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12918142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146062503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis-dependent small extracellular vesicles ULK1 enhances mitophagy and suppresses breast cancer migration.","authors":"Anan Wang, Min Chen, Yonghui Luo, Li Li, Jiahao Rong, Lei Liu, Chenghao Yi","doi":"10.1186/s41065-025-00621-2","DOIUrl":"10.1186/s41065-025-00621-2","url":null,"abstract":"<p><p>BACKGROUND: Breast cancer progression is closely influenced by the tumor microenvironment, including macrophage polarization. Small extracellular vesicles (sEVs) derived from tumor cells serve as key mediators of intercellular communication that regulate immune responses. Ferroptosis, characterized by iron-dependent lipid peroxidation, plays a role in tumor progression. However, whether ferroptosis alters the cargo of breast cancer cell-derived sEVs and affects macrophage function remains largely unknown. RESULTS: In this study, we identify that sEVs derived from ferroptotic breast cancer cells (Fer-sEVs) are enriched in ULK1 and functionally suppress macrophage M2 polarization. Mechanistically, Fer-sEVs-delivered ULK1 promotes mitophagy in macrophages, thereby inhibiting M2-associated pro-tumoral phenotypes. Knockdown of ULK1 in donor cells abrogated this effect, while autophagy induction by rapamycin reversed consequences of ULK1 depletion. Co-culture experiments revealed that Fer-sEVs-educated macrophages significantly suppressed breast cancer cell migration, whereas ULK1-deficient Fer-sEVs restored migratory capacity. Furthermore, hnRNPA2B1 was identified as the key RNA-binding protein that recognizes EXO-motifs within the ULK1 3’ UTR and mediates its selective packaging into sEVs during ferroptosis. Silencing hnRNPA2B1 reduced ULK1 expression in sEVs. CONCLUSION: Together, our findings reveal a novel ferroptosis-sEVs-mitophagy axis, in which hnRNPA2B1-mediated sEVs ULK1 delivery enhances mitophagy and reprograms macrophage polarization, ultimately restraining breast cancer migration. This mechanism providing new insights into ferroptosis-based intercellular communication and identifying potential therapeutic targets for breast cancer metastasis. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":"30"},"PeriodicalIF":2.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12918416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linc01748 regulates the prognosis and related mechanisms of gastric cancer by targeting miR-130a-5p.","authors":"Hui Li, Zhiling Zhong, Yuhan Li, Meini Cen","doi":"10.1186/s41065-026-00634-5","DOIUrl":"10.1186/s41065-026-00634-5","url":null,"abstract":"<p><p>OBJECTIVE: The purpose of this study is to investigate the expression of linc01748 in gastric cancer (GC) tissues and cell lines, and to reveal the influence and potential mechanism of linc01748 on the biological behavior of GC cells. METHODS: Linc01748 levels in GC were predicted through bioinformatics software. The proliferation, migration and invasion abilities of GC cells were respectively estimated by cell function tests. The RT-qPCR experiment was implemented to measure the levels of key proteins in epithelial-mesenchymal transition (EMT). The miRNAs regulated downstream of linc01748 were preliminarily screened through literature review and bioinformatics prediction. The relationship of miR-130a-5p to linc01748 was validated by dual-luciferase assay. The effect of the linc01748/miR-130a-5p axis on the expression of EMT-related genes was detected via in vitro cell experiments. MiR-130a-5p target genes were predicted using bioinformatics databases and verified by luciferase reporter gene experiments. RESULTS: Linc01748 expression in GC tissues and cell lines is significantly upregulated and is associated with prognosis. Linc01748 promotes the proliferation, migration and invasion of GC and regulates the expression of key proteins in EMT. miR-130a-5p is lowly expressed in GC and can mediate the cancer-promoting effect of linc01748. POU2F1 is the target gene of the linc01748/miR-130a-5p axis, and its expression is negatively correlated with miR-130a-5p. CONCLUSION: Linc01748 is highly expressed in GC tissues and cell lines and is closely related to the prognosis. The linc01748/miR-130a-5p axis regulates POU2F1 expression, thereby facilitating the progression of GC and EMT. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":"29"},"PeriodicalIF":2.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12910955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-596 as a novel prognostic biomarker and tumor suppressor in breast cancer through targeting EIF5AL1.","authors":"Rui Huang, Yan Jiang, Yan Bian, Dengyuan Zhong, Baoyong Lv","doi":"10.1186/s41065-026-00641-6","DOIUrl":"10.1186/s41065-026-00641-6","url":null,"abstract":"<p><strong>Background: </strong>In terms of global incidence and mortality, breast cancer continues to surpass all other cancers affecting women.</p><p><strong>Methods: </strong>To explore the role of miR-596, qRT-PCR was applied to measure its expression in tissue and cell samples from 137 enrolled subjects. The regulatory interaction between miR-596 and EIF5AL1 was verified by dual-luciferase reporter assays. CCK-8 and Transwell assays were utilized to respectively measure the proliferation, migration, and invasion capabilities of the two breast cancer cell lines, MCF-7 and MDA-MB-231.</p><p><strong>Results: </strong>A significant downregulation of miR-596 was observed in breast cancer tissues and cell lines (all P < 0.001). Clinically, reduced miR-596 expression was associated with advanced TNM stage, lymph node metastasis, and inferior overall survival (P < 0.05). EIF5AL1 was validated as a direct target gene of miR-596, and their expression levels were inversely correlated in clinical samples (r = -0.801, P < 0.001). Reintroduction of miR-596 markedly suppressed the proliferation, migration, and invasion of cancer cells, effects that were largely reversed by overexpressing EIF5AL1 (all P < 0.001).</p><p><strong>Conclusion: </strong>In breast cancer, miR-596 suppresses malignancy and predicts prognosis by targeting EIF5AL1. Thus, therapeutic modulation of this axis offers novel avenues for treatment and risk assessment.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":"28"},"PeriodicalIF":2.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12911248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic polymorphism of long non-coding RNA TUG1 and susceptibility to polycystic ovary syndrome: a case-control study.","authors":"Hua Zhang, Wei Liu, Xueqian Liu, Jingjing Ren, Yijiao Cheng, Yanjiao Liu, Yanjun Wu","doi":"10.1186/s41065-026-00638-1","DOIUrl":"10.1186/s41065-026-00638-1","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated expression of long non-coding RNA (lncRNA) TUG1 participates in the etiopathogenesis of polycystic ovary syndrome (PCOS). This study analyzed the genetic association of the TUG1 rs5749201 polymorphism in PCOS patients.</p><p><strong>Methods: </strong>Genotype and allele distributions of rs5749201 were analyzed in 210 PCOS patients and 230 healthy volunteers. Serum TUG1 levels were detected via qRT-PCR. The relationship between gene polymorphism and PCOS risk was analyzed via multivariate logistic regression.</p><p><strong>Results: </strong>Compared with the control group, the PCOS group had a significantly higher proportion of carriers with TUG1 rs5749201 AA genotype and a lower proportion of TT genotype carriers. Rs5749201 TT genotype carriers had notably reduced PCOS risk. This genetic association was also found in dominant and recessive models, with the locus independently linked to PCOS (OR = 0.427, 95%CI: 0.242-0.753; P = 0.003). AA genotype carriers had higher LDL, TG and FBS than AT/TT genotype carriers. PCOS patients had elevated TUG1 levels, with AA genotype carriers showing the highest.</p><p><strong>Conclusion: </strong>TUG1 rs5749201 was linked to PCOS susceptibility, which is correlated with its regulatory role in TUG1 expression.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":"27"},"PeriodicalIF":2.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12911283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRV130 inhibits colon cancer progression via suppressing the Hedgehog signaling pathway: in vitro and in vivo evidence.","authors":"Yuanzhao Zhuang, Changcheng Jiang, Yuqing Guo, Jiaxiao Sun","doi":"10.1186/s41065-026-00633-6","DOIUrl":"10.1186/s41065-026-00633-6","url":null,"abstract":"&lt;p&gt;&lt;p&gt;BACKGROUND: Colon cancer, characterized by high incidence and mortality, faces clinical challenges due to high recurrence rates and drug resistance. Aberrant activation of Hedgehog (Hh) signaling pathway is a key driver of colon cancer progression, making it a promising therapeutic target; however, current Hh inhibitors are limited by resistance and adverse effects. Drug repurposing offers a strategic alternative to accelerate oncology drug development. Oliceridine (TRV130) is a clinically approved, selective µ-opioid receptor agonist with a well-established safety profile for pain management. Notably, its potential anti-tumor activity and impact on oncogenic pathways like Hh signaling remain entirely unexplored. This study aims to investigate the anti-colon cancer efficacy of TRV130 and its underlying mechanisms, focusing on the Hh pathway, thereby evaluating its repurposing potential. METHODS: To establish the rationale for targeting the Hh pathway and the novelty of investigating TRV130, a focused literature review was conducted using PubMed and Web of Science databases (search period: 2000–2023), employing keywords including “colon cancer,” “Hedgehog pathway,” “drug repurposing,” and “TRV130/Oliceridine.” Based on this foundational evidence, the anti-tumor effects of TRV130 were systematically evaluated. Cell proliferation was assessed via MTT, EdU, and colony formation assays. Apoptosis was evaluated by flow cytometry and TUNEL assays. Migration and invasion were analyzed by Transwell and wound healing assays. The expressions of Cyclin D1, Bcl-2, Caspase 3, and Hh pathway proteins (PTCH1, GLI1) were detected by Western blot. A subcutaneous xenograft model was established in nude mice using HCT116 cells to validate in vivo efficacy, with tumor tissues analyzed by immunohistochemistry (IHC) and Western blot. RESULTS: TRV130 exhibited potent, dose-dependent inhibition of colon cancer cell proliferation, migration, and invasion. It induced apoptosis through both intrinsic and extrinsic pathways, as evidenced by the downregulation of Cyclin D1 and Bcl-2, and the upregulation of cleaved caspase 3. Mechanistically, TRV130 significantly suppressed the Hh signaling pathway, reducing the expression of its key effectors (GLI1 and PTCH1) to an extent comparable to cyclopamine (Cyc), a canonical Hh inhibitor. In vivo, TRV130 administration dose-dependently inhibited tumor growth in xenograft models, reducing both tumor volume and weight. IHC and Western blot analyses of tumor tissues confirmed the downregulation of Hh pathway proteins and pro-proliferative markers, alongside upregulation of apoptotic markers. CONCLUSION: This study identifies TRV130 as a novel inhibitor of the Hh pathway, demonstrating its significant anti-colon cancer effects in vitro and in vivo. These findings reveal a previously unexplored, oncological mechanism for this clinically safe drug and support its repurposing as a promising therapeutic candidate, potentially offering ","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":"26"},"PeriodicalIF":2.6,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12911246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NSUN2 restrains gastric cancer cell apoptosis and ferroptosis by promoting the m5C modification of EPYC.","authors":"Lei Wu, Boxuan Chen, Si Cheng, Xiaofeng Fang, Fen Zhou","doi":"10.1186/s41065-025-00626-x","DOIUrl":"10.1186/s41065-025-00626-x","url":null,"abstract":"<p><strong>Background: </strong>Epiphycan (EPYC) has been confirmed to play an oncogenic role in many cancers. However, its role and mechanism in gastric cancer (GC) progression has not been explored.</p><p><strong>Methods: </strong>The levels of EPYC and NOP2/Sun domain 2 (NSUN2) were detected by qRT-PCR and western blot. Cell proliferation, apoptosis, migration and invasion were determined by cell counting kit 8 assay, colony formation assay, flow cytometry, wound healing assay and transwell assay. Fe²⁺ and iron levels were examined to assess cell ferroptosis. Actinomycin D assay was used to detect the effect of NSUN2 knockdown on EPYC mRNA stability, and methylated RNA immunoprecipitation (MeRIP) assay was performed to determine the effect of NSUN2 silencing on 5-methylcytosine (m5C) level of EPYC. Xenograft tumors were constructed to explore the regulation of NSUN2 knockdown on GC tumorigenesis in vivo.</p><p><strong>Results: </strong>EPYC was abnormally higher expressed in GC tissues and cells. Knockdown of EPYC restrained GC cell proliferation, migration and invasion, while enhanced apoptosis and ferroptosis. NSUN2 had elevated expression in GC, which could increase the mRNA stability and expression of EPYC through m5C modification. NSUN2 silencing inhibited GC cell proliferation, metastasis, promoted apoptosis and ferroptosis, while these effects were reversed by EPYC overexpression. In vivo experiments revealed that NSUN2 downregulation reduced GC tumorigenesis by decreasing EPYC level in vivo.</p><p><strong>Conclusion: </strong>NSUN2-mediated m5C modification of EPYC contributed to GC cell growth and metastasis, which provided a novel regulatory axis for understanding the pathogenesis of GC.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":"23"},"PeriodicalIF":2.6,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12895582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Luoshi Neiyi prescription (LSNYP) in endometriosis: a network pharmacology and experimental study.","authors":"Lizheng Wu, Rui Su, Jinjin Jia, Zijun Kuang, Cheng Zeng, Fangli Pei","doi":"10.1186/s41065-026-00637-2","DOIUrl":"10.1186/s41065-026-00637-2","url":null,"abstract":"<p><strong>Background: </strong>Luoshi Neiyi prescription (LSNYP) is a traditional Chinese medicine that has a clinical effect on endometriosis (EMs). This study combined network pharmacology with experimental validation to explore its potential molecular mechanisms.</p><p><strong>Methods: </strong>The primary components of LSNYP were identified based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and a Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). The possible target proteins were predicted using the SwissTargetPrediction online tool. The GeneCards and DisGeNET databases were used to identify targets associated with EMs. The protein-protein interaction (PPI) network, herb-component-target network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Molecular docking, molecular dynamics (MD) simulation and experimental verification were carried out.</p><p><strong>Results: </strong>217 potential therapeutic targets were identified. Enrichment analyses revealed involvement in key biological processes and pathways, including cell migration, inflammatory response, focal adhesion, and the VEGF signaling pathway, which are closely related to the adhesion-invasion-angiogenesis progression in EMs pathogenesis. Molecular docking and MD simulation results showed stable binding between corresponding components and typical targets (ICAM1, MMP9 and VEGFA) involved in the progression. Experimental results demonstrated that LSNYP could decrease typical targets of the progression in rats and inhibit the invasion, migration and adhesion capabilities of human endometriotic stromal cells (ESCs).</p><p><strong>Conclusion: </strong>These findings suggest LSNYP may be a promising candidate for EMs, potentially through inhibiting the adhesion-invasion-angiogenesis progression.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":"24"},"PeriodicalIF":2.6,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12903665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of nano-silver small intestine submucosa repair of osteochondral defect in rabbit model by the AMPK-mTOR-ULK1 pathway.","authors":"Heng-Shu Wang, Chong Zhang","doi":"10.1186/s41065-026-00635-4","DOIUrl":"10.1186/s41065-026-00635-4","url":null,"abstract":"<p><p>OBJECTIVE: This study evaluated the regenerative potential of nano-silver small intestine submucosa (NSSIS) scaffolds with a 4-D porous structure for repairing osteochondral defects in rabbit knee joints. METHODS: NSSIS scaffolds were prepared using nanosilver, fresh pig-derived small intestinal submucosa, and chondrocytes. Biocompatibility was assessed by methyl thiazolyl tetrazolium (MTT) assays measuring bone marrow stromal cell (BMSC) proliferation at 24, 48, and 72 h. A rabbit model of intercondylar groove cartilage defects was established and randomized into three groups (n = 12 each): NSSIS, NSSIS + BMSCs, and a control group. Scaffold morphology and cell growth were evaluated in vitro using H&E staining after 24 h. Following implantation, cartilage repair was assessed at 24, 48, and 72 h using ICRS macroscopic scoring and histological staining (H&E, Safranin O-fast green, toluidine blue). After 12 weeks, ELISA measured growth factor expression (PDGF, VEGF, TGF-β, IGF-1, FGF, EGF), and qRT-PCR and Western blotting assessed autophagy-related gene and protein expression (AMPK, ULK1, mTOR, and Beclin-1). RESULTS: Both NSSIS groups demonstrated significantly greater BMSC ingrowth compared with controls, with the NSSIS + BMSCs group exhibiting the most robust repair. This group showed significantly elevated growth factor expression at 12 weeks (p < 0.05), downregulation of AMPK, ULK1, and Beclin-1, and upregulation of mTOR (p < 0.01). Histological analysis revealed enhanced chondrocyte formation, thicker cartilage layers, increased chondroblast proliferation, and abundant extracellular matrix deposition in the NSSIS + BMSCs group, whereas the NSSIS-only group showed less cellular and collagen development. CONCLUSIONS: NSSIS scaffolds demonstrate good biocompatibility and promote BMSC ingrowth, chondrocyte development, and osteochondral repair. The addition of BMSCs further enhances these effects by facilitating in situ chondrogenic differentiation, stimulating BMSC and chondrocyte migration, and initiating tissue regeneration. These findings highlight the potential of NSSIS, particularly when combined with BMSCs, as a promising biomaterial for cartilage and subchondral bone repair, with potential clinical applications in regenerative medicine. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":"25"},"PeriodicalIF":2.6,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12908320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the biological mechanism of Gurigumu-13 in the treatment of non-alcoholic fatty liver disease based on network pharmacology.","authors":"Jie Zhang, Ying Wei, Xuan Li, Liya Su, Haifeng Zhang","doi":"10.1186/s41065-026-00640-7","DOIUrl":"10.1186/s41065-026-00640-7","url":null,"abstract":"&lt;p&gt;&lt;p&gt;CONTEXT: Gurigumu-13 (GR) was a classical Mongolian medicinal compound widely used in clinical practice for the treatment of non-alcoholic fatty liver disease (NAFLD). OBJECTIVES: This study aimed to investigate the underlying mechanism by which GR exerted its therapeutic effects against NAFLD. MATERIALS AND METHODS: The main active components of GR were identified using high-resolution mass spectrometry. Using network pharmacology approaches, key targets and potential pathways of GR against NAFLD were predicted and preliminarily validated through molecular docking. Furthermore, transcriptomic sequencing analysis, combined with in vivo and in vitro experiments was performed to elucidate the efficacy and mechanism of GR in alleviating NAFLD. In vivo, a rat model of NAFLD was established by feeding Wistar rats a methionine-choline deficient (MCD) diet. Serum levels of AST, ALT, TC, TG, MDA, GSH, SOD, HDL-C, and LDL-C were measured. Liver tissues were collected for histopathological examination via H&E staining. In vitro, HepG2 cells were treated with oleic acid and palmitic acid to induce lipid accumulation. Intracellular TG content, as well as MDA and SOD levels, were assessed. Lipid deposition was visualized by Oil Red O staining. The expression of relevant genes and proteins was further analyzed by Western blotting and quantitative real-time PCR (qRT-PCR). RESULTS: Mass spectrometry analysis identified a total of 151 major bioactive compounds in GR. Through network pharmacology, 406 effective active ingredients and 1,012 potential targets of GR were screened. After intersecting with NAFLD-related genes (1,929 genes collected from Genecards and OMIM databases), 329 common targets were obtained. Protein-protein interaction network analysis indicated that STAT3, AKT, and others served as core targets. GO and KEGG enrichment analyses revealed that these genes are primarily involved in biological processes such as oxidative stress and lipid metabolism, as well as signaling pathways including PI3K/AKT and insulin resistance. In vivo, after 8 weeks of MCD diet feeding, rats in the model group exhibited significant hepatocellular fat accumulation, along with increases in body weight (1.82 times of the control group) and liver index (p &lt; 0.05). GR intervention ameliorated these pathological changes, reduced serum levels of AST, ALT, TC, TG, MDA, and LDL-C (p &lt; 0.05), and elevated levels of GSH, SOD, and HDL-C (p &lt; 0.05). In vitro, GR significantly decreased triglyceride content in lipid-loaded HepG2 cells, alleviated intracellular lipid deposition (p &lt; 0.05), and reduced the elevated glucose concentration in the culture medium of the model group. Additionally, GR reversed the increase in ROS and MDA contents and the decrease in SOD activity induced by the lipid-accumulation model. Western blotting results demonstrated that GR upregulated the phosphorylation levels of PI3K, AKT, and mTOR, and reduced STAT3 protein expression (p &lt; 0.05). These change","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12958684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}