Translational research : the journal of laboratory and clinical medicine
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A deeper knowledge of the functional versatility and dynamic nature of the ECM has improved the understanding of cancer biology. Translational Significance: This work provides an in-depth view of the importance of the ECM to develop more mimetic breast cancer models, which aim to recreate the components and architecture of tumor microenvironment. Special focus is placed on decellularized matrices derived from tissue and cell culture, both in procurement and applications, as they have achieved great success in cancer research and pharmaceutical sector. ⋯ The decellularized ECMs (dECMs) have emerged as a promising in vitro 3D tumor model, whose recent advances in the processing and application could become the biomaterial by excellence for BC research and the pharmaceutical industry. This review offers a detailed view of the contribution of ECM in BC progression, and highlights the application of dECM-based biomaterials as promising personalized tumor models that more accurately mimic the tumorigenic mechanisms of BC and the response to treatment. This will allow the design of targeted therapeutic approaches adapted to the specific characteristics of each tumor that will have a great impact on the precision medicine applied to BC patients.
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Type 2 diabetes (T2D), a chronic metabolic disease, has attained the status of a global epidemic with steadily increasing incidence worldwide. Improved diagnosis, stratification and prognosis of T2D patients and the development of more effective treatments are needed. In this era of personalized medicine, the discovery and evaluation of innovative circulating biomarkers can be an effective tool for better stratification, prognosis and therapeutic selection/management of T2D patients. ⋯ The expression levels of miRNAs, correlation with clinical parameters, functional roles of miRNAs and their potential as biomarkers are reported. A systematic literature search and assessment of studies led to the selection and review of 10 miRNAs (miR-126-3p, miR-223-3p, miR-21-5p, miR-15a-5p, miR-24-3p, miR-34a-5p, miR-146a-5p, miR-148a-3p, miR-30d-5p and miR-30c-5p). We also present technical challenges and our thoughts on the potential validation of circulating miRNAs and their application as biomarkers in the context of T2D.
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Three types of capillaries, namely continuous, fenestrated, and sinusoidal, form the microvascular system; each type has a specialized structure and function to respond to the demands of the organs they supply. The endothelial glycocalyx, a gel-like layer of glycoproteins that covers the luminal surface of the capillary endothelium, is also thought to maintain organ and vascular homeostasis by exhibiting different morphologies based on the functions of the organs and capillaries in which it is found. Recent advances in analytical technology have enabled more detailed observations of the endothelial glycocalyx, revealing that it indeed differs in structure across various organs. ⋯ Thus, circulating glycocalyx components may be useful biomarkers of organ dysfunction and disease severity. Moreover, a recent study suggested that chronic injury to the glycocalyx reduces the production of these glycocalyx components and changes their structure, leading it to become more vulnerable to external stimuli. In this review, we have summarized the various endothelial glycocalyx structures and their functions.
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Pulmonary arterial hypertension (PAH) is a fatal disease with a well-established sexual dimorphism. Activated inflammatory response and altered redox homeostasis, both known to manifest in a sex-specific manner, are implicated in the pathogenic mechanisms involved in PAH development. This study aimed to evaluate the impact of sex and plasma redox status on circulating cytokine profiles. ⋯ Machine learning algorithms trained on the combined cytokine and redox profiles allowed the prediction of PAH mortality with 80% accuracy. We conclude that the profile of circulating cytokines in PAH patients is redox- and sex-dependent, suggesting the vital need to stratify the patient cohort subjected to anti-inflammatory therapies. Combined cytokine and/or redox profiling showed promising value for predicting the patients' survival.
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Dysferlin (DYSF) has drawn much attention due to its involvement in dysferlinopathy and was reported to affect monocyte functions in recent studies. However, the role of DYSF in the pathogenesis of atherosclerotic cardiovascular diseases (ASCVD) and the regulation mechanism of DYSF expression have not been fully studied. In this study, Gene Expression Omnibus (GEO) database and epigenome-wide association study (EWAS) literatures were searched to find the DNA methylation-driven genes (including DYSF) of ASCVD. ⋯ Besides, DYSF could enhance the phagocytosis, migration and adhesion ability of THP1 cells. Among DYSF related hub genes, SELL was proven to be the downstream target of DYSF by wet experiments. In conclusion, DYSF promoter hypermethylation upregulated its expression and promoted monocytes activation, which further participated in the pathogenesis of ASCVD.