Downregulation of Nrf2 and HO-1 expression contributes to oxidative stress in type 2 diabetes mellitus: A study in Juana Koslay City, San Luis, Argentina

Oxidative stress is associated with diabetes mellitus, a condition characterized by increased prevalence and progression rate of cardiovascular disease. NFE2-related factor 2 (Nrf2) is a master regulator of cellular detoxification responses and redox status. The aim of this study was to examine associations between type 2 Diabetes Mellitus (T2DM), oxidative stress and the expression of NFE2-related factor 2 (Nrf2) in a population of diabetic patients living in Juana Koslay City, San Luis, Argentina. In addition, we evaluated the functional relevance of Nrf2 by measuring the HO-1 expression among persons with type 2 diabetes. We measured clinical and biochemical parameters related to lipid metabolism and oxidative stress in a population of Type 2 Diabetes Mellitus patients (T2DM, n = 40) and controls (Co, n = 30). Compared to Co, T2DM patients had higher fasting serum glucose, glycated hemoglobin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and thiobarbituric acid reactive substances and lower high-density lipoprotein cholesterol. T2DM individuals had also higher atherogenic index and body mass index than controls. We also founded that HO-1 mRNA in whole blood was lower in T2DM than controls, suggesting that T2DM may have an altered antioxidant response to oxidative stress. Interestingly, we found reduced Nrf2 mRNA in whole blood from T2DM compared to Co. The results from this study provide novel evidence that genes associated to antioxidant defense mechanisms are markedly reduced in patients with type 2 diabetes, and that the reduction in the expression of these genes could be associated to hyperglycemia and increased levels of MDA. Linear regression analysis revealed that there was a strong and positive correlation between the changes of Nrf2 and HO-1 expression levels.

Soybean Flour Improves Fatty Acid Profile and Decreases Hepatic Triglyceride Deposition in Rats Fed with Normocaloric and Hypercaloric Diet

This study investigated the effects of replacing casein with soy flour on the fatty acids profile and triglycerides metabolism in the liver of rats that were previously fed with normocaloric and hypercaloric diets based on casein. Wistar male rats were used;one group was fed with control diet (AIN-93) and another with hypercaloric diet (AIN-93 with 34.15% sucrose, 42% fat calories) for 9 weeks. Each group was then divided into two subgroups and casein was replaced with soybean in one of them, obtaining CC (control casein), CS (control soy), HC (hypercaloric casein) and HS (hypercaloric soy), which were fed for 6 weeks. We measured triglycerides in serum, and triglycerides, total lipids, fatty acids profile, the expression of apolipoprotein B (Apo B), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), sterol-regulatory element-binding protein 1c (SREBP-1c), mitochondrial glycerol-3-phosphate acyltransferase (mGPAT), diacylglycerol acyltransferase 2 (DGAT-2), carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator-activated receptors alpha (PPARα) in liver. Histological studies were also performed. When comparing HS vs. HC, a positive effect of soybean flour on hepatic triglycerides deposits was found, possibly through the reduction in DGAT-2 expression (P < 0.01) and the increase in Apo B (P < 0.001) expression. Soybean flour also decreased fat deposits in control diets when compared with casein, decreasing the DGAT-2 (P < 0.001) expression and increasing Apo B (P < 0.001), CPT-1 (P < 0.05) and PPARα (P < 0.01) expressions. Both soy diet subgroups increased unsaturated fatty acids respect to casein diets (P < 0.01). Hepatocytes showed few lipid droplets in HS, whereas a fat deposit in HC was observed. These results suggest that replacing casein with soybean flour in normocaloric and hypercaloric diets reduces triglycerides and improves fatty acids profile in rat liver.

Taq1B CETP Polymorphism and Cardiovascular Risk in an Endogamous Pop-ulation of Diabetic Men: A Study in Santa Rosa Del Conlara, San Luis, Argentina

Objectives: Type 2 diabetes mellitus (T2DM) patients are at increased risk of cardiovascular diseases (CVDs). Several polymorphisms in the cholesterol ester transfer protein (CETP) gene have been reported. The aim of this study was to determine the distribution and effect of the Taq1B polymorphism in the CETP gene on clinical and biochemical indicators of CVD risk in a population of endogamous-T2DM men. Methods: 102 men (57.5 ± 9.3 years old) inhabitants of Santa Rosa del Conlara, San Luis, Argentina, were recruited and assigned into two groups (22 control and 80 T2DM). Further, these two groups were subdivided according to their Taq1B CETP gene genotypes (i.e., B1B1, B1B2 and B2B2). Clinical and fasting-plasma biochemical indicators of CVD risk were measured and their association with the B1 allele was determined. Results: Compared to control, T2DM men had more central obesity, hypertension, atherogenic index, insulin resistance and poorly controlled diabetes. Compared to T2DM men having the B2 allele, those T2DM men having the B1 allele have increased risk of CVD as assessed by systolic blood pressure (156 ± 16.0 vs 135.8 ± 19.2, p = 0.015), atherogenic index (6.15 ± 1.3 vs 4.4 ± 0.7, p = 0.0008), HDL-c levels (38.9 ± 5.3 vs 64.4 ± 8.2, p ± 3.0 vs 2.4 ± 0.78, p = 0.004). Interestingly, only body mass index (r = ﹣0.559, p = 0.01) and HDL-c concentration (r = ﹣0.492, p = 0.02) negatively correlated with CVD risk in the endogamous population of B1B1 and B1B2 T2DM men. Conclusion: The B1 allele of the CETP gene predicts cardiovascular complications in an endogamous population of T2DM men.

Heficobacter pylori Biofilm Formation and Gene Expression on Abiotic Surfaces Using a Cyanobacterial Extract

The effects of a cyanobacterial extract （CE） on Helicobacter pylori biofilm formation onto hydrophobic and hydrophilic abiotic surfaces and the expression of luxS, flaA, omp18, lpxD and ureA genes associated to biofilm were studied. NCTC11638 reference strain and HP796, a resistant clinical isolate, were grown in Mueller-Hinton broth supplemented with 5% fetal calf serum （FCS） or 1% CE. The ability to form biofilm, viability, morphological changes and gene expression of adhered H. pylori cells were determined. The strains were able to form biofilm on both surfaces with the nutritional supplements analyzed. H. pylori conserved a characteristic bacillary morphology and viability with CE. Cells attachment was higher with CE than FCS regardless of strains and surfaces. The most remarkable increase in gene expression was observed with the ompl8 gene using the CE supplement, indicating the important participation of outer membrane proteins in biofilm establishment. The clinical isolate showed similar and even greater gene expression than the reference strain. The results obtained indicated that the nutrients provided by CE favored biofilm formation with retained pathogenicity that under certain conditions can occur in natural aquatic environments.

Hyperglycemia promotes overexpression of SR-BII isoform of the scavenger receptor class B type I in type 2 diabetes mellitus: A study in Juana Koslay City, San Luis, Argentina

The scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor involved in reverse cholesterol transport. Some studies reported the association to be stronger in the presence of diabetes. The full length gene encoding SR-BI is comprised in 13 exons that are alternatively spliced to produce two major transcripts: the full length SR-BI and the splice variant SR-BII, in which exon 12 is skipped. Considering that type 2 diabetes status is characterized by changes in the concentration of plasma lipids, modifications in lipoprotein size and composition, which may be important modulators of the SR-BI expression;the aims of the study were to examine the influence of SR-BI polymorphism (rs838895) on lipid profile and SR-BI mRNA expression in a population of diabetic patients living in Juana Koslay City. Blood samples were drawn from controls (n = 40) and Type 2 diabetic patients (n = 66) and DNA and total RNA were obtained. SR-BI mRNA expression was measured by RT-PCR and SR-BI polymorphism was detected by Tetra Primer ARMSPCR. Compared to controls, diabetic patients had higher fasting serum glucose, glycated hemoglobin, triglycerides, total cholesterol, lowdensity lipoprotein cholesterol, and lower highdensity lipoprotein cholesterol. SR-BI mRNA expression was lower in T2DM when compared to controls, suggesting that the hyperglycemia presents in T2DM patients down-regulates SR-BI mRNA expression. Interestingly, we found that decreased SR-BI expression resulted in markedly increased plasma LDL concentrations in T2DM subjects, and the overexpression of SRBII isoform is responsible for the markedly increased plasma LDL-c concentrations. The polymorphism (rs838895) did not modify the mRNA level of SR-BI in leucocytes from control and diabetic patients. This study provides novel evidence suggesting that hyperglycemia may affect reverse cholesterol transport by controlling SRBI expression in diabetic patients. LDL cholesterol levels are associated with low SR-BI mRNA expression in T2DM.

Gut microbes limit growth in house sparrow nestlings(Passer domesticus)but not through limitations in digestive capacity

Recent research often lauds the services and beneficial effects of host-associated microbes on animals.However,hosting these microbes may come at a cost.For example,germ-free and antibiotic-treated birds generally grow faster than their conventional counterparts.In the wild,juvenile body size is correlated with survival,so hosting a microbiota may incur a fitness cost.Avian altricial nestlings represent an interesting study system in which to investigate these interactions,given that they exhibit the fastest growth rates among vertebrates,and growth is limited by their digestive capacity.We investigated whether reduction and restructuring of the microbiota by antibiotic treatment would:(i)increase growth and food conversion efficiency in nestling house sparrows(Passer domesticus);(ii)alter aspects of gut anatomy or function(particularly activities of digestive carbohydrases and their regulation in response to dietary change);and(iii)whether there were correlations between relative abundances of microbial taxa,digestive function and nestling growth.Antibiotic treatment significantly increased growth and food conversion efficiency in nestlings.Antibiotics did not alter aspects of gut anatomy that we considered but depressed intestinal maltase activity.There were no significant correlations between abundances of microbial taxa and aspects of host physiology.Overall,we conclude that microbial-induced growth limitation in developing birds is not driven by interactions with digestive capacity.Rather,decreased energetic and material costs of immune function or beneficial effects from microbes enriched under antibiotic treatment may underlie these effects.Understanding the costs and tradeoffs of hosting gut microbial communities represents an avenue of future research.