Obesity is a growing global health concern that leads to metabolic imbalances and progressive cardiac remodelling. This study investigated whether semaglutide (SMG) can counteract the disruption to the gut-heart-metabolic axis and associated myocardial injury caused by obesity. Twenty-one male Wistar rats were assigned to control, obese (OB), and obese+semaglutide (OB + SMG) groups. The control group was fed a normal diet, while the obese groups were given a cafeteria diet for 16 weeks. In addition, the OB + SMG group received 150 mcg/kg of SMG subcutaneously once a week for the last four weeks. The following were measured alongside HOMA indices: Lipid profile, cardiac enzymes, leptin, insulin, TMAO and LPS levels. Myocardial and intestinal samples were assessed biochemically and histopathological for the levels of MMP-2/MMP-9, TIMP-1, TGF-β, IL-1β, HO-1, occludin, ZO-1 and claudin. Obesity markedly increased body weight, fasting glucose, leptin, insulin resistance, the atherogenic index and cardiac risk, while also increasing LPS, TMAO, TGF-β, IL-1β, MMP-2/MMP-9 activity and decreasing TIMP-1. Semaglutide significantly reversed these abnormalities, improving metabolic indices, restoring the balance between MMPs and TIMPs, and reducing inflammatory mediators. Histological analysis revealed reduced cardiomyocyte degeneration and enhanced intestinal epithelial architecture in the OB + SMG group. Semaglutide notably enhanced the expression of occludin, claudin, and ZO-1, supporting strengthened intestinal barrier integrity, and restored HO-1 expression, indicating improved antioxidant defenses. These findings suggest that semaglutide provides cardioprotection in obesity by restoring gut barrier function, reducing inflammation and normalizing extracellular matrix turnover. By stabilizing the gut-heart-metabolic axis and mitigating structural myocardial injury, semaglutide may interrupt the progression from metabolic dysfunction to cardiomyopathy. This highlights its therapeutic potential in the treatment of obesity-related cardiovascular disease, extending beyond glycemic control.

The dysregulation of the Hippo signaling pathway leads to the aberrant activation of oncogenic YAP and TAZ, driving tumor progression. In breast cancer, this disruption promotes proliferation and metastasis. This study investigates the effects of CA3, a selective YAP inhibitor, on the proteome of triple-negative breast cancer MDA-MB-231 and luminal-A-like MCF7 cells. Proteomic changes were analyzed via nano-LC-MS/MS, while cytotoxicity, apoptosis, and autophagy were assessed through WST-1 assays, flow cytometry, and Western blot analyses. Bioinformatics tools were employed to identify enriched pathways. MDA-MB-231 cells exhibited an increased expression of DNA repair proteins (p < 0.05), indicating a compensatory response to maintain genomic stability. In contrast, MCF7 cells showed a downregulation of DNA repair factors (p < 0.005). Additionally, metabolic reprogramming was apparent in MCF7 cells (p < 0.001). Apoptosis assays revealed a rise in cell death, while cell cycle analysis indicated pronounced G1-phase arrest in MDA-MB-231 cells (p < 0.01). Moreover, autophagic suppression was particularly evident in MCF7 cells. This study, for the first time, provides evidence that breast cancer subtypes exhibit distinct dependencies on YAP-driven pathways, revealing potential therapeutic vulnerabilities. Targeting Hippo signaling alongside DNA repair in triple-negative breast cancer or combining YAP inhibition with metabolic blockade in luminal breast cancer holds significant potential to enhance treatment efficacy.

Objective: ACE2 and TMPRSS2 proteins have received increased attention gained emphasis together with the pandemic COVID-19. These proteins have roles in respiratory and hypertension disorders as well as cardiovascular and renal diseases. The objective of this work was to examine the mRNA and protein levels of ACE2 and TMPRSS2 in cell lines derived from various tissue origins. Methods: After the growth of 14 different cell lines, protein and mRNA were isolated from the cell pellets. The amounts of mRNAs and proteins were then determined and quantified using RT-PCR and ELISA. Results: Findings showed that VERO, HEK293T, and VERO E6 cell lines significantly differed from others in the mRNA levels of both the ACE2 and TMPRSS2 genes. In protein levels obtained using ELISA, PNT1A cell line had the highest level of ACE2 protein expression, while for TMPRSS2, A549 had the highest level of protein expression. Conclusion: It was showed in this study how the expressions of ACE2 and TMPRSS2 depend on the cell type. This may be an explanation for why virulence entrance differs in different types of tissues. It is thought that HEK293T cells with high levels of both genes may be a suitable option for studies at the RNA level by using these two genes. MCF7 may be a good option for studies at the protein level. Given the high levels of mRNA expression of both genes, it may be inferred that cells derived from the kidney were among those that were most susceptible to virus entry.