Hereditas最新文献

{"title":"Exosomal lncRNA DLEU2 aggravates inflammatory injury and apoptosis in pediatric viral pneumonia via the miR-330-5p.","authors":"Xinxing Su, Haobin Wang, Jianzhu He, Huagui Bai","doi":"10.1186/s41065-026-00665-y","DOIUrl":"10.1186/s41065-026-00665-y","url":null,"abstract":"<p><p>BACKGROUND: Viral pneumonia (VP) is a major cause of severe respiratory illness in children. lncRNAs are involved in disease progression by regulating immune regulation. This study investigates the clinical value and regulatory function of exosomal DLEU2 in pediatric VP. MATERIALS: Include 247 pediatric VP cases, divided into 120 mild and 127 severe groups, and collected plasma exosomes samples. The abundance of DLEU2, miR-330-5p, and CEBPD were quantified using qRT-PCR. ROC curves and logistic regression were performed to determine the diagnostic and prognostic utility. The correlation was assessed between DLEU2 level and clinical indicators. A VP cell model was established by stimulating BEAS-2B with Poly(I: C). Cell transfection, ELISA, flow cytometry and dual-luciferase reporter assays were conducted to detect cytokines, apoptosis level and target gene regulation. RESULTS: Exosomal DLEU2 was elevated in severe VP and showed good diagnostic performance in distinguishing severe from mild disease. High DLEU2 was independently associated with increased disease severity and correlated with adverse status, including tachypnea, respiratory retractions, reduced SpO2, and elevated inflammatory markers. Poly(I: C) stimulation upregulated DLEU2 and promoted cytokine IL-6 and IL-8 secretion and apoptosis in BEAS-2B. Silencing DLEU2 markedly attenuated these effects. DLEU2 functioned as a ceRNA by sponging miR-330-5p, thereby relieving its inhibitory effect on CEBPD. Restoration of miR-330-5p reversed DLEU2-mediated inflammatory and apoptotic responses. CONCLUSION: DLEU2 is upregulated in pediatric VP and is associated with disease severity. Functional assays suggest that DLEU2 may aggravate inflammatory injury in bronchial epithelial cells via miR-330-5p. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511564","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":"Folate-driven changes in snoRNA function: a novel epigenetic-ribosomal axis in hepatocellular carcinoma.","authors":"Xinxin Song, Deyu Kong, Yongjiao Zi, Xu Wang, Juan Ni","doi":"10.1186/s41065-026-00666-x","DOIUrl":"10.1186/s41065-026-00666-x","url":null,"abstract":"<p><p>Folate (FA), essential for DNA synthesis, repair and methylation, is predominantly stored and metabolized in the liver. Dysregulation of folate intake and metabolism is strongly implicated in the pathogenesis of hepatocellular carcinoma (HCC). Although small nucleolar RNAs (snoRNAs) have shown promise as diagnostic and prognostic biomarkers in HCC, the impact of folate deficiency on their expression landscape remains uncharacterized. Here, by performing snoRNA-seq in folate-deficient HepG2 cells, we systematically identified 26 differentially expressed snoRNAs for the first time. Functional enrichment analysis indicated that downregulated snoRNAs were closely associated with cell proliferation pathways. From these, we selected SNORD1B, highly expressed in HCC tissues, correlated with poor prognosis, and significantly suppressed upon 28-day FA deprivation for mechanistic investigation. We demonstrated that FA deficiency coordinately downregulated SNORD1B and its host gene SNHG16 (P < 0.05), with strong positive correlation (R2 = 0.5104, P = 0.0465). This downregulation led to markedly reduced 2′-O-methylation at the G4362 site of 28S rRNA (P < 0.01) and impaired ribosomal activity. Expression of snoRNA-binding proteins (FBL, NOP58, NOP56) as well as IL-6 and CDK1 were significantly suppressed (P < 0.05), alongside decreased TP53 protein levels (P < 0.001). Functional assays confirmed that FA deficiency potently inhibited HepG2 proliferation and migration (P < 0.01). Our findings reveal a previously unrecognized mechanism: folate deficiency attenuates SNORD1B-dependent 2′-O-methylation of 28S rRNA, resulting in ribosomal dysfunction and suppression of global protein synthesis, thereby inhibiting HCC cell proliferation and migration. This study provides novel insight into the epigenetic-ribosomal axis of FA-mediated tumor suppression and highlights snoRNAs as potential therapeutic targets in HCC.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147498634","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":"Enhancer-based gene therapy: a new path for precision medicine.","authors":"Hany E Marei","doi":"10.1186/s41065-026-00655-0","DOIUrl":"10.1186/s41065-026-00655-0","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Enhancers are critical cis-regulatory elements that regulate gene expression in a context-dependent manner by integrating transcription factor binding, chromatin state, and the three-dimensional organization of the genome. Recent advances in functional genomics and synthetic biology have increased interest in harnessing enhancer activity to regulate the expression of therapeutic genes. Unlike traditional approaches that rely on promoter-driven gene regulation, enhancer-based approaches can bias transgene expression toward specific cellular states or disease contexts; however, this control remains probabilistic and highly dependent on the chromatin environment. This review summarizes current knowledge of enhancer biology, discusses new strategies for utilizing enhancer function directly, and examines the potential benefits and drawbacks of using enhancer-based strategies for gene therapy applications. Often delivered using adeno-associated virus (AAV) vectors with tailored capsids, enhancers in gene therapy can be included into expression cassettes. Astrocyte- or microglia-specific enhancers in the brain enable enriched or preferential distribution of neuroprotective or immunomodulatory genes, hence lowering unintentional expression in non-target cell types. It is important to control gene expression for specific cell types for the treatment of neurodegenerative conditions such as Alzheimer’s or Parkinson’s disease, were unintentional gene expression results in negative consequences. However, the uses of enhancer-guided gene therapy go beyond the central nervous system. In cancer, therapeutic constructs are designed to inhibit oncogenic expression or induce tumor suppression pathways, using enhancers in either malignant or immune cells as a target. Similarly, through the use of tissue-specific enhancers in cardiovascular and regenerative medicine, lineage-enriched genes can be used to promote repair of damaged tissues and enhance functional recovery. Enhancer-based systems that modulate the levels of gene expression (enhancer systems that adjust gene expression to levels that are physiologically appropriate for a given cell type) may also be useful in diseases caused by imbalances of gene dosage (e.g., haploinsufficiency and copy number variations). However, despite the potential promise of enhancer-driven gene therapy, many technical and translational hurdles remain. Mapping and validating the function of cell-type-specific enhancers is hampered by the dynamic, context-dependent regulation of chromatin. The identification of enhancers across a variety of developmental stages and clinical states is being accelerated through the combination of recent advances in single-cell epigenomic techniques (e.g., ATAC-seq, ChIP-seq, and multi-omic integration). Recent advances in non-viral delivery methods and AAV capsid engineering are improving the safety, efficacy, and scalability of enhancer-driven gene therapies. However, there must be careful regu","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491121","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":"Identification and external validation of a prognostic signature based on myeloid-derived suppressor cell-related lncRNAs for hepatocellular carcinoma.","authors":"Tong Mu, Shunyao Zhang, Yun Zhong, Zijian Zhou, Lei Xie, Yajie Zhou, Wenxiong Zhang, Liang Zhai","doi":"10.1186/s41065-026-00664-z","DOIUrl":"10.1186/s41065-026-00664-z","url":null,"abstract":"<p><p>BACKGROUND: Hepatocellular carcinoma (HCC) outcomes remain suboptimal. Myeloid-derived suppressor cells (MDSCs) exhibit notable immunosuppressive and pro-tumorigenic properties. However, the relationship with HCC remains insufficiently explored. METHODS: Using TCGA data, we developed an MDSC-associated lncRNA prognostic model and a clinical nomogram. To explore the model’s mechanistic basis and clinical significance, enrichment analysis, tumor mutation burden (TMB) analysis, tumor microenvironment (TME) evaluation, immunotherapy response prediction, and drug sensitivity assessment were performed. RT-qPCR was utilized to confirm lncRNA expression. RESULTS: A 7-lncRNA prognostic signature was established. High-risk patients exhibited significantly worse survival (p < 0.001). The nomogram demonstrated superior accuracy over models excluding the risk evaluation. Enrichment analysis exposed that metabolic and immune-associated pathways were predominant within low-risk cohort, while cell proliferation and gene expression regulation dominant across the high-risk population. Meanwhile, an increased TMB and a degraded TME appeared in the high-risk population. The drug responsiveness evaluation revealed that sorafenib, axitinib, and others exhibited enhanced effectiveness among the low-risk population. High-risk individuals displayed enhanced reactions to medications like staurosporine, savolitinib, and others. CONCLUSIONS: The prognostic model constructed based on the seven MDSCs-associated lncRNAs showed good application value in assessing prognosis and guiding clinical therapy. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485745","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":"Cuproptosis of endothelial cells in a hypoxic environment: from molecular classification to PMAIP1-targeted intervention.","authors":"Jie Wang, Xueying Chen, Huabin Wang, Wenjing Feng, Nan Lin, Xueyun Ren, Manman Wang, Lijun Gan","doi":"10.1186/s41065-026-00667-w","DOIUrl":"10.1186/s41065-026-00667-w","url":null,"abstract":"<p><p>BACKGROUND: Acute myocardial infarction (AMI) is a critical and fatal cardiovascular condition. The role of cuproptosis as an emerging mechanism in the pathogenesis of AMI remains to be fully elucidated. METHODS: Patient data were acquired from the Gene Expression Omnibus database. Differential expression analysis was performed on cuproptosis-related genes (CRGs). LASSO regression was employed to identify key CRGs and develop a diagnostic classification model for AMI. Weighted gene co-expression network analysis was performed to investigate key modules associated with the disease and its molecular classification. Subsequently, machine learning techniques were used to identify critical genes within these modules. The diagnostic efficacy of these genes for AMI was assessed using receiver operating characteristic analysis. The functions of the identified key genes were ultimately validated at the cellular level. RESULTS: Six characteristic CRGs were selected via LASSO regression. The AMI diagnostic classification model based on these CRGs demonstrated superior performance. Patients were classified into two subtypes related to cuproptosis, revealing significant differences in enrichment pathways between these subtypes. SYTL3, SCML1, and PMAIP1 were identified as key genes for AMI, with area under the curves of 0.813, 0.795, and 0.873, respectively. Knocking down PMAIP1 expression reduced intracellular copper levels in hypoxia-induced HUVECs. CONCLUSIONS: This study clarifies the role of cuproptosis in AMI and highlights the potential involvement of PMAIP1, providing a theoretical basis for further investigation into cuproptosis in AMI. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147485773","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":"A prognostic model for gastric cancer based on histamine-associated prognostic genes.","authors":"Yan Zhang, Na Liu, Xiao Dong, Yu Li, Jinrui Geng, Yonghong Li","doi":"10.1186/s41065-026-00659-w","DOIUrl":"10.1186/s41065-026-00659-w","url":null,"abstract":"<p><p>BACKGROUND: Histamine has various associations with gastric cancer (GC); however, the mechanisms underlying histamine functions in GC have not been established. This study aimed to examine histamine-linked prognostic genes and mechanisms in GC. Relevant data were sourced from public databases, and differential expression, multivariate Cox, univariate Cox, and machine learning regression analyses were performed to identify prognostic genes associated with histamine in GC. Subsequently, a prognostic model was constructed. Independent prognostic factors linked to GC prognosis were determined through regression analyses and used for nomogram model construction. Furthermore, Gene Set Enrichment Analysis (GSEA) and drug sensitivity and immune infiltration analyses were conducted to explore the potential function of these genes in GC from various perspectives. Finally, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the expression of GRP, NPPB, SERPINE1, GAMT, MMRN1, and SLC22A16 in GC and paracarcinoma tissue. RESULTS: GRP, NPPB, SERPINE1, GAMT, MMRN1, and SLC22A16 were identified as putative prognostic genes, and a prognostic model was constructed. Compared with the low-risk group (LRG), the survival rates in the high-risk group (HRG) were reduced. Moreover, only M, N, age, and risk scores could be used to construct the nomogram model, which could precisely predict the survival status of patients with GC. GSEA indicated that the development of GC may be associated with certain metabolic pathways. Furthermore, there were 23 distinct infiltrating immune cells between the HRG and LRG, including activated B cells. HRG and LRG showed remarkable variation in sensitivity to 100 drugs (e.g., AP.24534, pazopanib, and AZD8055). RT-qPCR revealed that GRP, NPPB, SERPINE1, GAMT, MMRN1, and SLC22A16 expression was markedly upregulated in GC tissues compared with paracarcinoma tissue. CONCLUSION: We identified six prognostic genes and constructed a prognostic model, which provides a theoretical basis for the relationship between histamine and GC as well as potential therapeutic targets for GC. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13093977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432591","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":"Investigating the role of lncRNA SNHG14 in early diagnosis and prognosis of acute pancreatitis: a bioinformatics exploration.","authors":"Qilin Zhu, Bin Liang, Dongqin Shen, Wei Chen, Hanqing Liao","doi":"10.1186/s41065-026-00656-z","DOIUrl":"10.1186/s41065-026-00656-z","url":null,"abstract":"<p><p>BACKGROUND: Acute pancreatitis (AP) is a severe inflammatory disease. Early and accurate assessment of disease severity remains intricate, highlighting the need for novel biomarkers. Long non-coding RNAs (lncRNAs) play crucial roles in AP pathogenesis. OBJECTIVE: This study aimed to investigate the clinical significance and mechanism functional of SNHG14 in AP. METHODS: A prospective cohort of 307 participants (148 AP patients, 159 controls) was recruited. Serum SNHG14 and miR-30a-5p levels were detected by qRT-PCR. An in vitro AP model was established using cerulein (100 nM, 24 h) treatment in AR42J and HPDE6-C7 cells. Functional assays (CCK-8, flow cytometry, ELISA) were performed following SNHG14 knockdown. Bioinformatics analysis was employed for target prediction (starBase, TargetScan, miRDB) and pathway enrichment (KEGG/GO). The SNHG14/miR-30a-5p interaction was confirmed by dual-luciferase assay. RESULTS: SNHG14 was significantly up-regulated in AP patients and correlated with disease severity. It showed diagnostic potential for AP (AUC = 0.835) and for identifying severe AP (AUC = 0.757). High SNHG14 level was an independent predictor of poor 28-day prognosis (HR = 4.31, P = 0.018). In vitro, SNHG14 knockdown alleviated cerulein-induced cell apoptosis and secretion of TNF-α, IL-10, and IL-6. SNHG14 functioned as a sponger for miR-30a-5p, and its effects were reversed by miR-30a-5p inhibition. Bioinformatic analysis showed that miR-30a-5p target genes are enriched in autophagy, ubiquitin-mediated proteolysis, and inflammatory pathways. CONCLUSIONS: SNHG14 is a promising biomarker for AP severity and prognosis. The SNHG14/miR-30a-5p axis plays a critical role in regulating inflammation and apoptosis in AP. SIGNIFICANCE: This study is the first to delineate the clinical and mechanistic role of the SNHG14/miR-30a-5p axis in AP. It provides a potential candidate for non-invasive RNA-based diagnostic strategies and identifies a potential molecular target for intervention of AP. However, it represents an auxiliary molecular therapy strategies rather than a replacement for existing management. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432549","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":"Cardamonin ameliorates neuroinflammation in Parkinson's disease by regulating NF-κB signaling.","authors":"Yezi Xia, Yinwei Zhang, Ying Li, Xiaojing Li, Yaling Wu, Qi Yao","doi":"10.1186/s41065-026-00660-3","DOIUrl":"10.1186/s41065-026-00660-3","url":null,"abstract":"<p><p>BACKGROUND: Neuroinflammation can accelerate neurodegeneration in Parkinson’s disease (PD). This study aims to identify biomarkers related to PD inflammation and investigate the function of cardamonin (CD) on microglia and neurons. METHODS: The differentially expressed genes (DEGs) in PD were screened out. Inflammation-related genes (IRGs) were obtained from the GSEA and GeneCards databases. The protein-protein interaction network was constructed, and three machine learning algorithms, least absolute shrinkage and selection operator (LASSO) regression analysis, random forest (RF) and support vector machine (SVM) were used to screen the core IRGs in PD pathogenesis. Potential drugs for core genes were screened through the ITCM and HERB databases, and the binding activity between the core targets and the drugs was verified by molecular docking. BV2 cells were induced with MPP + to construct a PD model. CCK-8 assay, flow cytometry, enzyme-linked immunosorbent assays, qPCR and western blotting were conducted to explore the function of CD on the activation of microglia and injury of neurons.. RESULTS: One thousand one hundred eighty-three DEGs and 518 IRGs were obtained, and 31 genes were in the intersection, among which v-rel reticuloendotheliosis viral oncogene homolog A (RELA, p65), a crucial component in NF-κB signaling, was upregulated in the PD samples and demonstrated good diagnostic efficacy. CD had good binding ability with RELA. CD significantly improved the viability, repressed apoptosis, reduced the production of pro-inflammatory factors (TNF-α, IL-6 and IL-1β) of BV2 cells, which were induced by MPP+. In addition, CD significantly inhibited the activation of the NF-κB signaling pathway and the nuclear translocation of RELA. CONCLUSION: CD inhibits the inflammatory response of PD induced by microglia by targeting RELA and regulating the activation of NF-κB signaling. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389790","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":"Integrated bioinformatics analysis and experimental validation reveal Pevonedistat as a promising therapeutic agent modulating the CRL4-DTL-p21/p53 axis in nasopharyngeal carcinoma.","authors":"Cong-Chao Jia, Zhen-Yi Li, Wei-Hua Jia, Cheng-Tao Jiang","doi":"10.1186/s41065-026-00661-2","DOIUrl":"10.1186/s41065-026-00661-2","url":null,"abstract":"<p><p>BACKGROUND: Nasopharyngeal carcinoma (NPC) continues to represent a significant therapeutic challenge. Despite the substantial success of radiotherapy, chemotherapy, and immunotherapy, their effectiveness remains limited in recurrent or advanced NPC. Hence, the urgent identification of new molecular targets and effective therapeutic agents is critically required. METHODS: Bulk and single-cell transcriptomic data were analyzed using bioinformatics approaches, and machine learning algorithms were employed to screen for hub genes in NPC. Functional validation of hub genes was performed through loss-of-function assays. Potential therapeutic agents were identified through molecular docking and subsequently evaluated for anti-NPC efficacy using both in vitro NPC cell line models and in vivo patient-derived xenograft (PDX) models. RESULTS: Bioinformatics analyses revealed DTL as a central gene with critical diagnostic and prognostic significance. Knockdown of DTL led to cell cycle arrest and apoptosis through stabilization of p21 and p53. Pevonedistat markedly inhibited DTL activity, recapitulating the effects of DTL knockdown. In vitro studies showed that Pevonedistat suppressed NPC cell proliferation, while in PDX models it significantly reduced tumor burden. Collectively, the data establish DTL as a key oncogenic driver in NPC and highlight Pevonedistat as a promising therapeutic candidate. CONCLUSION: Our work presents an integrated framework for target identification and therapeutic development in NPC. These findings deepen our understanding of NPC biology and highlight that Pevonedistat suppresses cell proliferation and tumor growth of NPC via the CRL4-DTL-p21/p53 axis. </p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13081564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372520","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":"Perillaldehyde inhibits oxidative stress, NLRP3-mediated inflammation and fibrosis in diabetic nephropathy through regulating HMOX1.","authors":"Wen Hao, Chunhua Liu, Jing Feng, Zhanliang Ren","doi":"10.1186/s41065-026-00657-y","DOIUrl":"10.1186/s41065-026-00657-y","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is a frequently occurred complication of diabetes mellitus (DM) worldwide. Perillaldehyde is a natural terpenoid compound exerted beneficial effects on diabetic cardiomyopathy (DCM), which is another important part of DM complication. However, the effect of perillaldehyde on DN has not been reported. In the present study, we demonstrated that perillaldehyde prevented ROS-driven oxidative stress, with decreased ROS and MDA levels and increased GSH level in high glucose (HG)-treated HK-2 cells. Perillaldehyde also reversed HG-induced NLRP3-mediated inflammation and fibrosis in HK-2 cells, as evidenced by decreased pro-inflammatory cytokines and fibrogenic factors. Furthermore, we observed that perillaldehyde directly targeted HMOX1 and regulated its expression in HK-2 cells. Knockdown of HMOX1 prevented the effects of perillaldehyde on HG-treated HK-2 cells, implying that perillaldehyde exerted its effects via regulating HMOX1. In a high fat diet (HFD)/streptozocin (STZ) mouse model, perillaldehyde also exerted renoprotective, antioxidant, anti-inflammatory and anti-fibrotic activities. In conclusion, our study clearly demonstrated the beneficial effects of perillaldehyde on DN both in vivo and in vitro, which indicated that perillaldehyde might serve as a potential application in treating or preventing DN.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369518","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}