Hereditas最新文献

Aim: This study explored the diagnostic value and molecular mechanism of lncRNA MEG8 in deep vein thrombosis (DVT).

Methods: This study included 120 patients with DVT and 100 healthy individuals as research subjects. Expression of lncRNA MEG8 and miR-296-5p in subjects' serum were detected by RT-qPCR. Diagnostic ability of MEG8 for DVT occurrence analyzed by ROC curve. Logistic analysis was used to identify risk factors for DVT. Associations between MEG8 and other parameters were explored by Pearson correlation analysis. Migration, viability and apoptosis of transfected HUVECs were detected by Transwell method, CCK-8 assay and flow cytometry, respectively. In addition, inflammatory cytokines were detected using ELISA kits. The luciferase reporter assay established the interaction between MEG8 and miR-296-5p.

Results: In patients with DVT, lncRNA MEG8 levels were significantly upregulated, and ROC curves showed high diagnostic ability. In addition, MEG8 was positively associated with TAT and D-dimer. In vitro experiments showed that overexpression of MEG8 inhibited HUVECs migration and viability, promoted apoptosis, and upregulated inflammatory factors such as IL-6, IL-1β, and TNF-α, while silencing of MEG8 showed the opposite effect. In addition, MEG8 regulated miR-296-5p expression by sponging it, and the dual luciferase reporter assay verified a direct interaction between them. Clinical samples revealed that serum miR-296-5p levels were diminished in DVT patients as well as negatively correlated with MEG8. Furthermore, miR-296-5p inhibitor reversed the role of MEG8 silencing on regulation of HUVECs migration, viability and inflammatory cytokines.

Conclusion: This study revealed that MEG8 acts critically in DVT development through sponging miR-296-5p for the first time, providing a new molecular target for early diagnosis and targeted therapy of DVT.

Artificial propagation is an important conservation technique to mitigate the loss of native freshwater mussel diversity. In vitro propagation is an alternative method of metamorphosing freshwater mussel larvae (glochidia) to juveniles without a host fish, but the methodology is still evolving in its rates of metamorphosis. This study provides the first comparison of gene expression in freshwater mussel glochidia metamorphosed in different culture media: M199, L-15, and M199 supplemented with lipids. Compared to the commonly used M199, 1.2% of the transcriptome of glochidia reared in the other culture media showed significantly altered expression levels. Of these differentially expressed transcripts, 86% were the same regardless of whether glochidia were metamorphosed in the different basal culture medium L-15 or in M199 supplemented with lipids. We discuss the Gene Ontology categories with the highest number of differentially expressed transcripts, as well as those categories that were over-represented in the different culture media compared to the whole transcriptome. Our results suggest that the external environment can have a significant impact on the physiology of metamorphosing glochidia and may potentially impact the health and survival of juveniles.

Background and objectives: As the etiology of intracranial aneurysm (IA) remains uncertain and unruptured IA management continues to be debated, investigating biomarkers of the disease remains critical. This study thus evaluated the involvement of miR-188-5p in IA diagnosis, prognosis, and development to advance understanding of IA pathophysiology and treatment strategies.

Materials and methods: A case-control study involving 73 IA patients and 79 healthy controls was conducted to assess the diagnostic and prognostic value of miR-188-5p in IA. A PDGF-BB-induced VSMC dedifferentiation model was constructed to explore the mechanisms. The qRT-PCR was employed to test the expression of biomolecules, while dual luciferase reporter assays were performed to ensure biomolecule interaction.

Results: The serum expression of miR-188-5p was relatively higher in IA patients than in healthy controls. High serum expression of miR-188-5p exhibited both diagnostic utility for IA detection and predictive capacity for assessing rupture risk. MiR-188-5p inhibited α-SMA and SM22α expression, promoted MMP-2 and MMP-9 expression, and facilitated oxidative stress and proinflammatory cytokine expression in phenotypically switched VSMCs. MiR-188-5p negatively regulated IL6ST expression in phenotypically switched VSMCs. IL6ST mediated the modification of miR-188-5p in phenotypically switched VSMCs.

Conclusion: MiR-188-5p was a biomarker for IA and its rupture. MiR-188-5p might assist IA progression by inducing VSMC phenotypic switching and cell damage. MiR-188-5p affected VSMCs by downregulating IL6ST. MiR-188-5p might be the potential target for predicting and controlling the development of IA.

Background: Carboplatin resistance represents a critical therapeutic challenge in non-small cell lung cancer (NSCLC) treatment. Although KHSRP has been implicated in lung cancer progression, its molecular mechanisms and impacts on chemotherapy sensitivity remain elusive. Notably, KHSRP has the capacity to activate the transcription of HMGB1, an oncogene known to influence chemotherapy sensitivity. However, it remains to be determined whether KHSRP affects chemotherapy response in NSCLC via HMGB1.

Methods: KHSRP expression in NSCLC cells was analyzed using qRT-PCR. Cell proliferation, apoptosis, and migration were evaluated using colony formation, flow cytometry and wound healing assays. A luciferase reporter assay was conducted to assess whether KHSRP transcriptionally regulates HMGB1. Additionally, A549 cell xenografts were established in nude mice to investigate the tumor growth-promoting effects of KHSRP in vivo.

Results: KHSRP expression was notably elevated in NSCLC cells. Overexpression of KHSRP remarkably promoted A549 cell proliferation, migration, and epithelial-mesenchymal transition (EMT); while KHSRP knockdown exhibited the opposite effects. Mechanically, KHSRP notably promoted the transcription of HMGB1 and upregulated its expression in A549 cells. Importantly, deficiency of KHSRP remarkably enhanced the suppressive effects of carboplatin on A549 cell proliferation, migration, EMT and HMGB1 expression. Meanwhile, in vivo experiments demonstrated that downregulation of KHSRP potentiated the inhibitory effect of carboplatin on tumor growth in tumor-bearing nude mice.

Conclusion: These findings demonstrate that silencing of KHSRP enhances the drug sensitivity of carboplatin in NSCLC, potentially mediated through the inhibition of HMGB1. Targeting KHSRP may represent a promising therapeutic strategy to improve chemotherapy efficacy in NSCLC.

Objective: Cisplatin (DDP) is the major chemotherapeutic drug used to treat gastric cancer (GC). However, DDP-associated side effects and resistance chemoresistance have limited its clinical application. Psoralidin (PSO) is the main extract of Psoralea corylifolia and has antitumor effects. The present study is designed to investigate the antitumor functions and mechanisms of PSO and DDP in GC.

Methods: GC cells (HGC-27 and MKN-45 cells) were treated with PSO (2.5 to 120 µM) and/or DDP. A CCK-8 assay, colony formation assay, and EdU staining were used to test cell proliferation. Cell migration and invasion were tested via a transwell assay. An in vivo assay in nude mice was carried out to analyze the influence of PSO and DDP on tumor growth. H&E staining was conducted to test the histopathological changes of organs and tumor tissues. Ferroptosis-associated indicators, including GSH, MDA, Fe²⁺ levels, were examined. Western blotting was conducted to determine the profiles of ACSL4, GPX4, AIFM2, and SLC7A11.

Results: PSO impeded GC cell proliferation, migration, invasion, and growth in vivo. PSO exhibited no significant toxic effects on organs and mitigated DDP-mediated liver and kidney injuries. The combination of PSO and DDP exhibited enhanced inhibitory functions. PSO and DDP can significantly promote GC cell ferroptosis. Moreover, PSO promoted ACSL4 expression and suppressed GPX4, AIFM2, and SLC7A11.

Conclusion: The combination of PSO and DDP has synergistic antitumor effects on GC cells by inducing ACSL4-mediated ferroptosis. PSO may serve as a nontoxic adjuvant to enhance DDP's efficacy and reduce side effects in GC.

Background: Protein disulfide isomerase family A member 4 (PDIA4), a member of the protein disulfide isomerase family, has been associated with the progression of cancer. Nevertheless, its specific function in oral squamous cell carcinoma (OSCC) is not yet well understood.

Methods: To assess the prognostic significance and functional profile of the PDIA4, survival analysis and GSEA were conducted. Additionally, we examined the differences in immune infiltration and immunotherapy response between groups with low and high expression levels of PDIA4. Subsequently, RT-qPCR and western blot assays were employed to verify PDIA4 expression in OSCC tissues. The functional implications of PDIA4 in OSCC cells were also investigated.

Results: Analysis of the TCGA-OSCC dataset revealed a notable increase in PDIA4 expression in OSCC tissues, as verified by RT-qPCR and western blot analyses. Additionally, elevated PDIA4 levels were associated with poor prognosis in OSCC patients. GSEA results showed that the cellular senescence, FoxO and Hippo signaling pathways were remarkably inactivated in the high PDIA4 expression group. Moreover, a negative correlation was observed between PDIA4 levels and the infiltration of CD4, CD8 and natural killer T cells. Conversely, a positive correlation was observed between PDIA4 levels and M0 macrophage and regulatory T cell infiltration. Meanwhile, OSCC patients exhibiting elevated PDIA4 expression demonstrated elevated TIDE scores, implying a reduced responsiveness to immunotherapy in these individuals. Functionally, the suppression of PDIA4 significantly suppressed both proliferation and migration of OSCC cells, potentially through activating the FoxO1/p21^CIP1 pathway.

Conclusion: These findings suggest that PDIA4 may potentially serve as both a prognostic biomarker and a therapeutic target for OSCC patients.

Background: Endometriosis (EMs), a common gynecological disorder, involves complex molecular mechanisms. Metabolic reprogramming (MR) has been recognized as a hallmark of EMs, contributing to lesion survival and immune microenvironment remodeling. This study aimed to identify MR-associated hub genes and pathways associated with EMs through integrated multi-omics analyses.

Methods: EMs-related datasets were downloaded from the Gene Expression Omnibus database, including training sets (GSE51981 and GSE7305) and validation sets (GSE25628 and GSE141549). MR related genes were retrieved from the Genecards database. EMs-related differentially expressed genes (DEGs) were identified, and WGCNA was performed to identify module genes. Protein-protein interaction (PPI) networks were constructed. The expression of key genes was validated in an external dataset and clinical samples (immunohi0stochemistry). The CIBERSORT and ssGSEA tools were utilized to explore immune cell infiltration. In vitro experiments involving overexpression and RT-qPCR in Z12 cells were conducted to explore gene function on MR.

Results: A total 107 MR-associated candidate genes were identified. PPI network analysis identified top 10 hub genes. External validation confirmed significant downregulation of key genes in ectopic endometrium, with HNRNPR, SYNCRIP, HSP90B1, HSPA4, HSPA8, CCT2 and CCT5 demonstrating high diagnostic value (AUC > 0.8). Immune infiltration analysis revealed associations between key genes and CD8 + T cells, regulatory T cells, and mast cells. Immunohistochemistry confirmed reduced expression of CCT2, HSP90B1, and SYNCRIP in EMs lesions. In vitro validation confirmed that HSP90B1 overexpression upregulated GLUT1, LDH, and COX-2 expression in Z12 cells.

Conclusion: This study identified several MR-related genes, as potential diagnostic biomarkers and mechanistic contributors to EMs.

Objective: The aim of this study is to evaluate the therapeutic efficacy of Bushen Chushi Formula (BSCSF) in a rat model of knee osteoarthritis (KOA), with a focus on the modulation of ferroptosis-related signaling pathways and inflammatory responses, and to assess its effects on cartilage integrity and subchondral bone microstructure.

Methods: A total of 66 male Sprague-Dawley rats were randomly assigned to six groups: control, model, diclofenac sodium (DCF), and BSCSF high-dose (BSCSF-H), medium-dose (BSCSF-M), and low-dose (BSCSF-L) groups. KOA was induced via intra-articular injection of monosodium iodoacetate. Following induction, BSCSF or DCF was administered orally for 4 weeks. Therapeutic outcomes were assessed through Lequesne MG scores, body weight measurements, histopathological evaluation (hematoxylin and eosin, Safranin O-Fast Green staining), and micro-computed tomography of the subchondral bone. Expression levels of ferroptosis-associated proteins (SLC7A11, GPX4, p38 MAPK, MMP-13), glutathione (GSH), and iron accumulation (Fe²⁺), as well as inflammatory cytokines (IL-1β, TNF-α), were also measured.

Results: When compared to the model group, rats in the BSCSF-H and BSCSF-M groups exhibited significantly lower Lequesne MG scores, improved cartilage morphology, and enhanced subchondral bone microstructure, as indicated by increased bone volume fraction, trabecular thickness, trabecular number, and connectivity density along with decreased bone surface-to-volume ratio and trabecular separation. These groups also demonstrated increased expression of SLC7A11 and GPX4, elevated GSH levels, and reduced Fe²⁺ accumulation in cartilage, suggesting attenuation of ferroptosis. Inflammatory mediators, including IL-1β, TNF-α, MMP-13, and p38 MAPK, were significantly downregulated, indicating reduced inflammation and extracellular matrix degradation. The BSCSF-L group indicated modest improvements, primarily in inflammatory parameters and joint function.

Conclusion: BSCSF attenuated KOA progression in rats by inhibiting ferroptosis through the MAPK/SLC7A11/GPX4 signaling axis and suppressing inflammatory responses. The observed preservation of cartilage structure and enhancement of subchondral bone quality highlight its therapeutic potential in the management of KOA.