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Deciphering the role of wound healing genes in skin cutaneous melanoma: Insights into expression, methylation, mutations, and therapeutic implications

Abstract

Skin Cutaneous Melanoma (SKCM) is a form of cancer that originates in the pigment-producing cells, known as melanocytes, of the skin. Delay wound healing is often correlated with the occurrence of and progression of SKCM. In this comprehensive study, we investigated the intricate roles of two important wound healing genes in SKCM, including Matrix Metalloproteinase-2 (MMP2) and Matrix Metalloproteinase-9 (MMP9). Through a multi-faceted approach, we collected clinical samples, conducted molecular experiments, including RT-qPCR, bisulphite sequencing, cell culture, cell Counting Kit-8, colony formation, and wound healing assays. Beside this, we also used various other databases/tools/approaches for additional analysis including, UALCAN, GEPIA, HPA, MEXPRESS, cBioPortal, KM plotter, DrugBank, and molecular docking. Our results revealed a significant up-regulation of MMP2 and MMP9 in SKCM tissues compared to normal counterparts. Moreover, promoter methylation analysis suggested an epigenetic regulatory mechanism. Validations using TCGA datasets and immunohistochemistry emphasized the clinical relevance of MMP2 and MMP9 dysregulation. Functional assays demonstrated their synergistic impact on proliferation and migration in SKCM cells. Furthermore, we identified potential therapeutic candidates, Estradiol and Calcitriol, through drug prediction and molecular docking analyses. These compounds exhibited binding affinities, suggesting their potential as MMP2/MMP9 inhibitors. Overall, our study elucidates the diagnostic, prognostic, and therapeutic implications of MMP2 and MMP9 in SKCM, shedding light on their complex interplay in SKCM occurrence and progression.

Beyond the burn: An observational study of cardiovascular risk in burn survivors in the north of Iran

Abstract

Burn survivors experience profound physiological changes following injury, which may have lasting implications for cardiovascular health. This study aims to investigate the cardiovascular risk profile among burn survivors treated at a burn center in northern Iran. This observational study was conducted from 2022 to 2023 at the burn centre affiliated with Guilan University of Medical Sciences, Rasht, Iran. This study assessed a cohort study of 210 burn survivors, focusing on individuals with ≥20% TBSA burn injuries who had recovered and returned to their daily lives. This study assessed patients' lipid profiles, Framingham General Cardiovascular Risk Score (FGCRS) and risk factors, including demographics, clinical variables and physical activity. Statistical analysis employed descriptive and inferential statistics. The mean age was 49.23 years, and the mean TBSA burned was 37.06%. The risk of cardiovascular disease in 66% of the study population was less than 10%, and in 13%, it was more than 20%. Significant associations were identified between CVD risk and sex, diabetes, hypertension, BMI, TBSA burned, years after burn, physical activity level and LDL. Of the lipid profile measures, LDL, triglycerides and TC/HDL exceeded the desirable levels. This research highlights the heightened cardiovascular risk in burn survivors, emphasizing the necessity for targeted interventions and regular monitoring. Identifying modifiable risk factors enables healthcare practitioners to develop tailored strategies, enhancing cardiovascular health in this vulnerable population and improving overall outcomes and quality of life.

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