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Introduction: Ankyrin repeat domain 27 (ANKRD27) has been found to be associated with certain cancers. However, its clinical potential in pan-cancer remains unclear. Methods: Public datasets (TCGA and GTEx) were applied to analyze ANKRD27 expression in multiple cancer types and its correlations with immune scores, immune checkpoint genes, and immune modulatory genes. We also examined ANKRD27 expression in hepatocellular carcinoma (HCC) patients using TCGA and GSE14520 datasets. The upregulation of ANKRD27 was verified via qRT-PCR in vitro. Based on TCGA-HCC, external, and GSE14520 cohorts, the associations between ANKRD27 expression and survival outcome were explored via the Kaplan-Meier survival curve. The effects of ANKRD27 reduction on HCC cell growth, movement, and invasion were evaluated by CCK-8, Wound healing, and Transwell assays. Results: ANKRD27 exhibited aberrant expression in multiple cancers and was correlated with immune traits, including immune infiltration, immune checkpoint genes, and immune modulatory genes. Elevated expression of ANKRD27 was found in TCGA-HCC and GSE14520 cohorts and was confirmed in HCC cell lines. HCC patients with high ANKRD27 expression had poorer prognosis. In vitro , reducing ANKRD27 decreased the capability of proliferation, migration, and invasion in HCC cells. High ANKRD27 expression was associated with sensitivity to certain drugs. Conclusion: ANKRD27 displays abnormal levels of expression in different cancer types and is linked to immune status in cancer. Furthermore, ANKRD27 may serve as a prognostic predictor for HCC. [ABSTRACT FROM AUTHOR]

Background and aims: Myofibroblasts, the primary producers of extracellular matrix, primarily originate from hepatic stellate cells (HSCs), and their activation plays a pivotal role in liver fibrosis. This study aimed to investigate the function of CXC motif ligand 14 (CXCL14) in the progression of liver fibrosis. Approach and results: CXCL14 knockdown significantly reduced the extent of liver fibrosis. Using Ingenuity pathway analysis and qRT‐PCR, activating transcription factor 3 (ATF3) was identified as a key upstream regulator of CXCL14 expression. Mechanistically, ATF3 was shown to bind to the CXCL14 promoter, promoting its transactivation by TGF‐β in HSCs. Notably, both global CXCL14 deletion (CXCL14−/−) and HSC/myofibroblast‐specific CXCL14 knockdown significantly attenuated liver fibrosis in mice. RNA‐seq comparisons between CXCL14−/− and WT mice highlighted Jak2 as the most significantly downregulated gene, implicating its role in the antifibrotic effects of CXCL14 suppression on HSC inactivation. Moreover, Jak2 overexpression reversed the inhibition of liver fibrosis caused by CXCL14 knockdown in vivo. Conclusions: These findings unveil a novel ATF3/CXCL14/Jak2 signalling axis in liver fibrosis, presenting potential therapeutic targets for the disease. [ABSTRACT FROM AUTHOR]

Introduction: Liver fibrosis is primarily driven by the activation of hepatic stellate cells (HSCs), which involves various epigenetic modifications. Objectives: N6‐methyladenosine (m6A), the most prevalent RNA modification in eukaryotic cells, influences numerous physiological and pathological processes. Nevertheless, the role of insulin‐like growth factor 2 mRNA‐binding protein 3 (IGF2BP3), a reader gene mediating m6A modifications, in liver fibrosis remains unclear. Methods and results: This study demonstrated that IGF2BP3 knockout reduces liver fibrosis by promoting HSC ferroptosis (FPT) and inactivating HSCs. Multi‐omics analysis revealed that HSC‐specific IGF2BP3 knockout decreased m6A content in Jagged1 (Jag1), a key component of the Notch signalling pathway. Furthermore, IGF2BP3 deficiency significantly reduced the expression of hairy and enhancer of split‐1 (Hes1), a transcription factor in the Notch/Jag1 signalling pathway, with mRNA levels declining to 35%–62% and protein levels to 28%–35%. Additionally, it suppressed glutathione peroxidase 4 (GPX4) (decreased to approximately 31%–38%), a negative regulator of FPT, thereby facilitating HSC FPT progression and reducing profibrotic gene expression. Conclusion: These findings uncover a novel IGF2BP3/Notch/Jag1 signalling pathway involving HSC FPT, suggesting promising targets for ameliorating liver fibrosis. Key Points/Highlights: IGF2BP3 deficiency inactivates Jag1 signalling.IGF2BP3 deficiency‐mediated m6A modifications promote HSC ferroptosis.IGF2BP3 inhibition facilitates ferroptosis in HSCs via the Hes1/GPX4 axis.IGF2BP3 deficiency inactivates Jag1/Notch1/3/Hes1 signalling pathway inactivation, leading to the decrease in GPX4, which contributes to HSC ferroptosis. [ABSTRACT FROM AUTHOR]

Objective(s): Tadalafil can restore endothelial function and treat atherosclerosis. However, the effect of tadalafil on transplant arteriosclerosis remains unclear. In this study, we explore the effects of tadalafil on allograft vasculopathy. Materials and Methods: Male Brow-Norway rats supplied aorta grafts for Male Lewis rats. All recipients were divided into 3 groups: saline as placebo (control) treated group, low dose tadalafil (0.5 mg/kg/day) treated group, and high dose tadalafil (1.0 mg/kg/day) treated group. Eight weeks after transplantation, the grafts were harvested at and analyzed by histological and Western blot analysis. An enzyme-linked immunosorbent assay (ELISA) was used for measure of plasma cyclic guanylate monophosphate (cGMP). Results:the treatment with tadalafil significantly alleviated the neointimal thickness of aortas compared with the control group (P

Objective To identify comorbid hub genes in psoriasis and atherosclerosis. Methods Transcriptomic datasets of three psoriatic samples and three atherosclerosis samples were downloaded from the GEO database. A deep learning algorithm (Batch Normalization) was utilized to merge and batch-correct the datasets of the two diseases. The limma package was employed to intersect the differentially expressed genes in the lesions and normal tissues of both diseases. The protein-protein interaction network was constructed using the STRING database and CytoHubba plugin to identify the hub genes. Results Intersection analysis revealed 132 up-regulated genes and 114 down-regulated genes in the lesions of these two diseases. Construction of the interaction network identified 10 hub genes: MX1, OASl, 0AS2, OASL, IFIT1, RSAD2, CXCL10, IFIT3, XAF1 and IL1B, among which the first six were enriched in the type I interferon signaling pathway. Two external validation sets independently verified the expression of CXCL10. Conclusions CXCL10 is a key comorbidity gene for psoriasis and atherosclerosis. The activation pattern of hub gene is similar to that of innate immune response to viral invasion. [ABSTRACT FROM AUTHOR]