Treating Arterial Ageing in Patients with Diabetes: From Mechanisms to Effective Drugs

Diabetes mellitus is a major healthcare problem. It is not only characterized by hyperglycemia and chronic complications, but in longer lasting diabetes and a longer living population, it is also associated with accelerated arterial ageing, which importantly contributes to cardiovascular complications. The accelerated arterial ageing in patients with diabetes should be considered separately from arterial ageing in patients without diabetes. Basic and clinical research have allowed better insight into the mechanisms of arterial ageing. In a simplified mechanistic way, it could be considered that the three tightly connected cornerstone characteristics of arterial ageing in patients with diabetes are: phenotypic presentation as endothelial dysfunction and arterial stiffness, and the underlying basic ageing-facilitating mechanism represented as the impaired expression of genetic longevity pathways. Currently, specific drugs for preventing/treating arterial ageing are not available. Therefore, we aimed to review the capacity of available drugs, particularly antidiabetic drugs, to interfere with the arterial ageing process. In the near future, these characteristics could help to guide therapy in patients with diabetes. Overall, it appears that arterial ageing could become a new target in diabetes. The expanding knowledge regarding the capability of antidiabetic drugs and other available drugs to inhibit/delay arterial aging is therefore essential.     

Bacteriocin-producing Enterococcus faecalis KT2W2G isolated from mangrove forests in southern Thailand: Purification,characterization and safety evaluation

The aim of this work was to purify and characterize the bacteriocin produced by Enterococcus faecalis KT2W2G isolated from the mangrove forest in southern Thailand, in order to evaluate its potential as a new food protective agent. The active peptide from the cell-free supernatant of Ent. faecalis KT2W2G was purified in 4 steps: (i) precipitation with 70% saturated ammonium sulfate, (ii) elution on a reversed phase cartridge (Sep-Pak C₈) using different concentrations of acetonitrile, (iii) cation-exchange chromatography and (iv) final purification by reversed phase-HPLC on a C₈ column. Each purification step increased the specific activity and reduced the amount of contaminating non-bacteriocin proteins. The specific activity of purified bacteriocin was 13,470.53 AU/mg of protein, which corresponded to a 48.10-fold increase. Tricine–SDS-PAGE of the purified bacteriocin gave molecular weight ranging between 3.5 and 6.5 kDa. The activity of the partially purified bacteriocin was unaffected by pH (2.0–12.0) and thermostable, but was sensitive to proteolytic enzymes. This bacteriocin maintained full stability after storage at −20, 4 and 37 °C for 2 months. It was stable when incubated for 1 month at 4 °C in 0–30% NaCl. Inhibitory spectrum of this bacteriocin showed a wide range of activities against other LAB, food-spoilage and food-borne pathogens. Ent. faecalis KT2W2G was sensitive to kanamycin, tetracycline and vancomycin but resistant to ampicillin, gentamicin and penicillin. PCR amplification demonstrated that Ent. faecalis KT2W2G does not harbor virulence genes cylA, cylB and esp but has virulence genes ace, asa1 and efaAfs. The bacteriocin and its producing strain may find application as bio-preservatives for reduction of food-spoilage and food-borne pathogens in food products.     

High-Resolution Chromosome Ideogram Representation of Currently Recognized Genes for Autism Spectrum Disorders

Recently, autism-related research has focused on the identification of various genes and disturbed pathways causing the genetically heterogeneous group of autism spectrum disorders (ASD). The list of autism-related genes has significantly increased due to better awareness with advances in genetic technology and expanding searchable genomic databases. We compiled a master list of known and clinically relevant autism spectrum disorder genes identified with supporting evidence from peer-reviewed medical literature sources by searching key words related to autism and genetics and from authoritative autism-related public access websites, such as the Simons Foundation Autism Research Institute autism genomic database dedicated to gene discovery and characterization. Our list consists of 792 genes arranged in alphabetical order in tabular form with gene symbols placed on high-resolution human chromosome ideograms, thereby enabling clinical and laboratory geneticists and genetic counsellors to access convenient visual images of the location and distribution of ASD genes. Meaningful correlations of the observed phenotype in patients with suspected/confirmed ASD gene(s) at the chromosome region or breakpoint band site can be made to inform diagnosis and gene-based personalized care and provide genetic counselling for families.     

Development of a prognostic signature for esophageal cancer based on a novel 7-DNA damage repair genes signature

Esophageal cancer (EC) was an aggressive malignant neoplasm characterized by high morbidity and poor prognosis. Identifying the changes in DNA damage repair genes helps to better understand the mechanisms of carcinoma progression. In this study, by comparing EC samples and normal samples, we found a total of 132 DDR expression with a significant difference. Moreover, we revealed higher expression of POLN, PALB2, ATM, PER1, TOP3B and lower expression of HMGB1, UBE2B were correlated to longer OS in EC. In addition, a prognostic risk score based on 7 DDR gene expression (POLN, HMGB1, TOP3B, PER1, UBE2B, ATM, PALB2) was constructed for the prognosis of EC. Meanwhile, EC cancer samples were divided into 3 subtypes based on 132 DDR genes expressions. Clinical profile analysis showed cluster C1 and C2 showed a similar frequency of T2, which was remarked higher than that in cluster 3. Moreover, we found the immune cell inflation levels were significantly changed in different subtypes of EC. The infiltration levels of T cell CD8+, B cell and NK cells were greatly higher in cluster 2 than that in cluster 1 and cluster 3. The results showed T cell CD4+ infiltration levels were dramatically higher in cluster 1 than that in cluster 2 and cluster 3. Finally, we perform bioinformatics analysis of DEGs among 3 subtypes of EC and found DDR genes may be related to multiple signaling, such as Base excision repair, Cell cycle, Hedgehog signaling pathway, and Glycolysis/Gluconeogenesis. These results showed DDR genes may serve as new target for the prognosis of EC and prediction of the potential response of immune therapy in EC.     

The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.