The atheroprotective role of fucoidan involves the reduction of foam cell formation by altering cholesterol flux-associated factors in macrophages.

Atherosclerosis is characterized by the accumulation of lipid-laden cells in the arterial walls, resulting from dysregulation of cholesterol homeostasis in the macrophage, triggered by oxidized low-density lipoprotein (oxLDL). Previous studies have shown that fucoidan, a sulfated polysaccharide from brown seaweeds, has several atheroprotective activities, however, the mechanism of fucoidan protection is not fully understood. Thus, we investigated the effect of fucoidan on atherogenesis in apolipoprotein E-deficient (ApoE-/-) mice, on oxLDL uptake by macrophages, and on the expression of the flux-associated scavenger receptors by macrophages. Also, we examined the absorption and biodistribution of orally administered fucoidan. ApoE-/- mice fed on a cholesterol-rich diet supplemented with 1% fucoidan showed reduced dyslipidemia and atherosclerosis. Fucoidan was detected in blood and peripheral tissue after gavage, suggesting that it can exert direct systemic effects. In vitro, fucoidan reduced macrophage oxLDL uptake, which resulted in lower foam cell formation. This effect was associated with downregulation of the cholesterol influx-associated scavenger receptor (SR)-A expression, and upregulation of the cholesterol efflux-associated SR-B1 expression. In conclusion, fucoidan prevented oxLDL-mediated foam cell formation in macrophages by downregulating SR-A1/2 and by up-regulating SR-B1.

Surgeons' Perspectives on Valve Surgery in People With Drug Use-Associated Infective Endocarditis.

BACKGROUND: Hospitalizations for drug-use associated infective endocarditis (DUA-IE) have led to increasing surgical consultation for valve replacement. Cardiothoracic surgeons' perspectives about the process of decision making around operation for people with DUA-IE are largely unknown. METHODS: This multisite semiqualitative study sought to gather the perspectives of cardiothoracic surgeons on initial and repeat valve surgery for people with DUA-IE through purposeful sampling of surgeons at 7 hospitals: University of Alabama, Tufts Medical Center, Boston Medical Center, Massachusetts General Hospital, University of North Carolina-Chapel Hill, Vanderbilt University Medical Center, and Rhode Island Hospital-Brown University. RESULTS: Nineteen cardiothoracic surgeons (53% acceptance) were interviewed. Perceptions of the drivers of addiction varied as well as approaches to repeat valve operations. There were mixed views on multidisciplinary meetings, although many surgeons expressed an interest in more efficient meetings and more intensive postoperative and posthospitalization multidisciplinary care. CONCLUSIONS: Cardiothoracic surgeons are emotionally and professionally impacted by making decisions about whether to perform valve operation for people with DUA-IE. The use of efficient, agenda-based multidisciplinary care teams is an actionable solution to improve cross-disciplinary partnerships and outcomes for people with DUA-IE.

Signaling Targets Related to Antiobesity Effects of Capsaicin: A Scoping Review.

The search for new antiobesogenic agents is increasing because of the current obesity pandemic. Capsaicin (Caps), an exogenous agonist of the vanilloid receptor of transient potential type 1 (TRPV1), has shown promising results in the treatment of obesity. This scoping review aims to verify the pathways mediating the effects of Caps in obesity and the different methods adopted to identify these pathways. The search was carried out using data from the EMBASE, MEDLINE (PubMed), Web of Science, and SCOPUS databases. Studies considered eligible evaluated the mechanisms of action of Caps in obesity models or cell types involved in obesity. Nine studies were included and 100% (n = 6) of the in vivo studies showed a high risk of bias. Of the 9 studies, 66.6% (n = 6) administered Caps orally in the diet and 55.5% (n = 5) used a concentration of Caps of 0.01% in the diet. In vitro, the most tested concentration was 1 µM (88.9%; n = 8). Capsazepine was the antagonist chosen by 66.6% (n = 6) of the studies. Seven studies (77.8%) linked the antiobesogenic effects of Caps to TRPV1 activation and 3 (33.3%) indicated peroxisome proliferator-activated receptor (PPAR) involvement as an upstream connection to TRPV1, rather than a direct metabolic target of Caps. The main secondary effects of Caps were lower weight gain (33.3%; n = 3) or loss (22.2%; n = 2), greater improvement in lipid profile (33.3%; n = 3), lower white adipocyte adipogenesis (33.3%; n = 3), browning process activation (44.4%; n = 4), and higher brown adipocyte activity (33.3%; n = 3) compared with those of the control treatment. Some studies have shown that PPAR agonists modulate TRPV1 activity, and no study has evaluated the simultaneous antagonism of these 2 receptors. Consequently, further studies are necessary to elucidate the role of each of these signaling molecules in the antiobesogenic effects of Caps.

Vildagliptin ameliorates oxidative stress and pancreatic beta cell destruction in type 1 diabetic rats.

BACKGROUND AND AIMS: It is believed that oxidative stress plays a role in the pathogenesis of diabetes mellitus. Several strategies have been developed with the objective of minimizing diabetic complications. Among these, inhibitors of dipeptidyl peptidase-IV (DPP-IV), which act by blocking degradation of incretin hormones, glucagon-like peptide hormone (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), have been the focus of many studies. It is known that, among the effects of incretins, we highlight its insulinotropic and cytoprotective effects on pancreatic ß-cells. The objective of this study was to evaluate the possible protective effects of treatment with vildagliptin, a DPP-IV inhibitor, in ß-cells in an experimental model of type 1 diabetes induced by streptozotocin (STZ). METHODS: Rats were treated for 4 weeks with vildagliptin at concentrations of 5 and 10 mg/kg. In order to observe the pancreatic damage and the possible protective effects of vildagliptin treatment, we measured stress markers TBARS and protein carbonyl, antioxidant enzymes SOD and catalase, and analyzed pancreatic histology. RESULTS: The treatment was effective in modulating stress in pancreatic tissue, both by reducing levels of stress markers as well as by increasing activity of SOD and catalase. After analyzing the pancreatic histology, we found that vildagliptin was also able to preserve islets and pancreatic ß-cells, especially at the concentration of 5 mg/kg. CONCLUSION: Thus, our results suggest that vildagliptin ameliorates oxidative stress and pancreatic beta cell destruction in type 1 diabetic rats. However, to evaluate the real potential of this medication in type 1 diabetes, further studies are needed.