Transforming growth factor beta (TGFβ) plays a crucial role in tissue fibrosis. A number of studies have shown that TGFβ3 significantly attenuated tissue fibrosis. However, the mechanism involved in this effect is poorly understood. In this study we found that the expression level of TGFβ3 was higher in human myocardial infarction (MI) tissues than in normal tissues, and interestingly, it increased with the development of fibrosis post‐myocardial infarction (post‐MI). In vitro, human cardiac fibroblasts (CFs) were incubated with angiotensin II (Ang II) to mimic the ischaemic myocardium microenvironment and used to investigate the anti‐fibrotic mechanism of TGFβ3. Then, fibrosis‐related proteins were detected by Western blot. It was revealed that TGFβ3 up‐regulation attenuated the proliferation, migration of human CFs and the expression of collagens, which are the main contributors to fibrosis, promoted the phenotype shift and the cross‐linking of collagens. Importantly, the expression of collagens was higher in the si‐smad7 groups than in the control groups, while silencing smad7 increased the phosphorylation level of the TGFβ/smad signalling pathway. Collectively, these results indicated that TGFβ3 inhibited fibrosis via the TGFβ/smad signalling pathway, possibly attributable to the regulation of smad7, and that TGFβ3 might serve as a potential therapeutic target for myocardial fibrosis post‐MI.

Background: TMEM59L is a newly discovered transmembrane protein; its functions in cancer remain unknown. This study was designed to reveal the prognostic value and the functional role of TMEM59L in cancer.Methods: The gene expression profiles, methylation data, and corresponding clinical data of TMEM59L were retrieved from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression database. Survival analysis was employed to calculate the pan-cancer prognostic value of TMEM59L. The correlation between TMEM59L expression and tumor immune microenvironment, as well as DNA methylation dynamics and genomic heterogeneity across cancers were assessed based on data from TCGA.Results: Our findings revealed that distinct differences of TMEM59L mRNA expression were observed in different cancer types and that higher TMEM59L expression was observed in the advanced pathological stage and associated with worse prognosis in kidney renal papillary cell carcinoma, bladder urothelial carcinoma, colon adenocarcinoma, and kidney renal clear cell carcinoma. Pathway analysis indicated that TMEM59L exerted a key influence in cancer development and in immune- and cancer-associated pathways such as epithelial–mesenchymal transition and TGF-β signaling. Moreover, correlation analysis hinted at a negative correlation of TMEM59L expression with CD8 T cells, activated CD4 T cells, and several immunomodulators, including IDO1, TIGIT, PD-L1, CTLA-4, and BTLA in various cancers. Survival analysis indicated that the hypermethylation of TMEM59L gene was associated with longer survival times. A significant correlation was also observed between TMEM59L expression and immunophenoscore, homologous recombination deficiency, loss of heterozygosity, tumor stemness score, and neoantigens in various cancers. Importantly, we also identified numerous potential agents that may target TMEM59L.Conclusion: Our study revealed the prognostic value as well as the genomic and immunological characteristics of TMEM59L in cancers, highlighting the promising potential for TMEM59L as a prognostic cancer biomarker and a therapeutic target.

Peroxiredoxin 2 (PRDX2), an inhibitor of reactive oxygen species (ROS), is potentially involved in the progression of atherosclerosis (AS). The aim of this study was to explore the role and mechanism of PRDX2 in AS. The expression of PRDX2 was evaluated in 14 human carotid artery tissues with or without AS. The results showed that the positive reaction of PRDX2 was observed in the carotid artery vascular smooth muscle cells (CAVSMCs). To assess the mechanism by which PRDX2 may function in AS, the CAVSMCs were transfected with pEX4-PRDX2 and si-PRDX2. The catalase, hydrogen peroxide (H₂O₂) scavenger, was used to further confirm that PRDX2-induced inhibitory effects might be mediated through reducing ROS levels. Phenotype alteration and functional testing included transcription testing, immunostaining, and expression studies. The drug of MAPK signaling pathway inhibitors SB203580, SP600125, and PD98059 was used to evaluate the underlying mechanism. In this study, we found that the protein level of PRDX2 and the level of H₂O₂ were higher in the human AS carotid artery tissues than in the normal carotid artery tissues, accompanied with the activation of MAPK signaling pathway. The up-regulation of PRDX2 in the CAVSMCs significantly decreased the expression of ROS, collagen type I (COL I), collagen type III (COL III), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) and inhibited the proliferation, migration, and transformation of the CAVSMCs. The up-regulation of PRDX2 reversed the effect of the CAVSMCs treated with tumor necrosis factor-α (TNF-α). In addition, PRDX2 down-regulation promoted the protein levels of p-p38, p-JNK, and p-ERK, which was confirmed in relevant MAPK inhibitor treatment experiments. Our results suggest a protective role of PRDX2, as a scavenger of ROS, in AS progression through inhibiting the VSMC phenotype alteration and function via MAPK signaling pathway.

The tRNA-derived fragments (tRFs) are a new class of regulatory noncoding RNAs and have different biological functions in cancer. This article investigated the expression and clinicopathological significance of tRF-Glu-TTC-2 in prostate carcinoma (PCa), and its effect on tumor growth. Expression profiles of tRFs and tiRNAs were analyzed by tRF and tiRNAs microarray in PCa samples, and then the expression was confirmed by qRT-PCR; RNA in situ hybridization was used to detect the positive expression of tRF-Glu-TTC-2 and to analyze the correlation between the expression level of tRF-Glu-TTC-2 and clinicopathological parameters. CCK-8 experiment was used to detect the effect of tRF-Glu-TTC-2 on the proliferation of PCa cells, and nude mice subcutaneous tumor model was used to detect the effect of tRF-Glu-TTC-2 on the growth of PCa cells. The results showed that tRF-Glu-TTC-2 was mainly positive and its expression level increased in PCa. The high expression was closely related to the tumor size ( p < .05). Overexpression of tRF-Glu-TTC-2 promoted the proliferation of PCa cells, and decreased expression of tRF-Glu-TTC-2 inhibited the proliferation of PCa cells ( p < .05). The results of subcutaneous tumor transplantation in nude mice showed that the tumor volume and weight of the knockdown group were smaller than those of the control group(all ps < .05). Ki-67 staining showed that the proportion of Ki-67-positive cells in the reduced tRF-Glu-TTC-2 group was lower than that in the control group ( p < .05). The tRF-Glu-TTC-2 may be a new oncogene that can promote growth and proliferation of PCa. It provides a new idea for the treatment of PCa.

Background and Aim: Ischemic heart disease (IHD) remains a critical global public health challenge, yet comparative studies on its burden between younger (20–54 years) and older (55+ years) adults are limited. This study aims to quantify differential IHD burden trajectories across these age groups globally, thereby informing tailored prevention strategies. Methods: Using data from the Global Burden of Disease Study 2021 (GBD), we evaluated the IHD burden through prevalence, disability‐adjusted life years (DALYs), and mortality. Trends from 1990 to 2021 were analyzed via estimated annual percentage change (EAPC), and proportional risk contributions were assessed via population attribution scores. Future trends were projected for the next 30 years via a Bayesian age‐period‐cohort model. Results: From 1990 to 2021, the global DALY rates and mortality rates decreased, whereas the prevalence increased, particularly among younger adults (EAPC = 0.98 [0.93–1.02]). Males presented a greater IHD burden than females did. Low‐ and medium‐socio‐demographic index (SDI) regions experienced greater disease burdens than high‐SDI regions did (EAPC = 1.63 [1.57–1.68]). Metabolic and behavioral risk factors, including high low‐density lipoprotein (LDL) cholesterol (52.74%) and tobacco use (33.90%), are predominant among younger adults, whereas older adults face greater risks from high blood pressure (53.74%) and elevated fasting glucose (16.88%). Projections suggest that mortality will decline in both age groups (20–54 years: 22.92/100,000 population [95% UI: 17.73–28.11]; ≥ 55 years: 404.28/100,000 population [95% UI: 274.18–534.35]), whereas the prevalence will stabilize in older adults but rise and later decline in younger populations. Conclusion: The global IHD burden was associated with decreasing mortality and DALY rates but increasing prevalence, with notable disparities by gender, SDI, and region. Prioritizing age‐specific and targeted interventions is crucial to reversing the prevalence trend and sustaining mortality reductions, ultimately mitigating the global IHD burden.