The incidence and prevalence of diabetes mellitus is rapidly increasing worldwide at an alarming rate. Type 2 diabetes mellitus (T2DM) is the most prevalent form of diabetes, accounting for approximately 90–95% of the total diabetes cases worldwide. Besides affecting the ability of body to use glucose, it is associated with micro-vascular and macro-vascular complications. Augmented atherosclerosis is documented to be the key factor leading to vascular complications in T2DM patients. The metabolic milieu of T2DM, including insulin resistance, hyperglycemia and release of excess free fatty acids, along with other metabolic abnormalities affects vascular wall by a series of events including endothelial dysfunction, platelet hyperactivity, oxidative stress and low-grade inflammation. Activation of these events further enhances vasoconstriction and promotes thrombus formation, ultimately resulting in the development of atherosclerosis. All these evidences are supported by the clinical trials reporting the importance of endothelial dysfunction and platelet hyperactivity in the pathogenesis of atherosclerotic vascular complications. In this review, an attempt has been made to comprehensively compile updated information available in context of endothelial and platelet dysfunction in T2DM.

P-selectin, an adhesion molecule, is encoded by SELP and known as biomarker of endothelial as well as platelet dysfunction. SELP polymorphisms (rs6136, rs6127, and rs6125) and raised levels of soluble P-selectin (sP-selectin) have been associated with several disease conditions. The present study was aimed to determine the association of SELP variants and sP-selectin levels as well as vascular risk in Type 2 diabetes mellitus (T2DM) patients. The frequency of rs6136, rs6127, and rs6125 was assessed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). sP-selectin levels were measured using commercially available kits. Haplotypes were constructed using PHASE software. The data obtained from the above-said analyses was subjected to suitable statistical analyses. sP-selectin levels (ng/ml) were significantly higher in patients as compared to controls (p < 0.001). Out of total, 22% of patients were found to have very high vascular risk, 43.2% with high vascular risk, while 34.4% with moderate vascular risk. For both rs6136 and rs6127, frequency of variant allele was found to be significantly higher in patients as compared to controls and accounted for 2.4- and 1.5-fold risk of disease development, respectively. CAG was found to be associated with 4.5-fold risk towards disease development. In contrast, AGG was conferring the protective effect. Significantly high sP-levels were observed in patients with homozygous wild genotype of rs6136, all genotypes of rs6127, and heterozygous genotype of rs6125 as compared to respective controls. Significant difference was observed in P-selectin levels within moderate-risk category for rs6136. When compared between the categories, significant difference was observed for rs6136 and rs6127. Furthermore, patients with haplotypes AAA, AGA, and AGG were found to have significantly high sP-selectin levels as compared to controls. Significant difference in sP-selectin levels was observed within very high-risk as well as high-risk category. When compared between the categories, significant difference was observed for AGA and AGG haplotypes. The studied polymorphisms of SELP have shown significant association with sP-selectin levels as well as vascular risk in T2DM patients.

Background Increase in the number of infections caused by Gram-negative bacteria in neutropenic cancer patients has prompted the search for novel therapeutic agents having dual anticancer and antimicrobial properties. Bacteriocins are cationic proteins of prokaryotic origin that have emerged as one of the most promising alternative antimicrobial agents with applications as food preservatives and therapeutic agents. Apart from their antimicrobial activities, bacteriocins are also being explored for their anticancer potential. Results In this study, a broad-spectrum, cell membrane-permeabilizing enterocin with a molecular weight of 65 kDa was purified and characterized from the culture supernatant of vaginal Enterococcus faecium 12a. Enterocin 12a inhibited multidrug-resistant strains of various Gram-negative pathogens such as Salmonella enterica, Shigella flexneri, Vibrio cholerae, Escherichia coli and Gram-positive, Listeria monocytogenes, but had no activities against different strains of gut lactobacilli. The mass spectrometric analysis showed that the enterocin 12a shared partial homology with 4Fe-4S domain-containing redox protein of E. faecalis R712. Further, enterocin 12a selectively inhibited the proliferation of various human cancer cell lines in a dose-dependent manner but not that of normal human peripheral blood mononuclear cells. Enterocin 12a-treated cancer cells showed apoptosis-like morphological changes. Conclusion Enterocin 12a is a novel bacteriocin that has anticancer properties against human cell lines and negligible activity towards non-malignant cells. Therefore, it should be further evaluated for its anticancer potential in animal models.

A series of biosafe mixed-ligand complexes of silver with heterocyclic thioamides have been studied for their antimicrobial/anticancer activity.