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OBJECTIVE Long noncoding RNAs (lncRNAs) are involved in diabetogenesis in experimental models, yet their role in humans is unclear. We investigated whether circulating lncRNAs associate with incident type 2 diabetes in older adults. RESEARCH DESIGN AND METHODS A preselected panel of lncRNAs was measured in serum of individuals without diabetes (n = 296) from the Vienna Transdanube Aging study, a prospective community-based cohort study. Participants were followed up over 7.5 years. A second cohort of individuals with and without type 2 diabetes (n = 90) was used to validate our findings. RESULTS Four lncRNAs (ANRIL, MIAT, RNCR3, and PLUTO) were associated with incident type 2 diabetes and linked to hemoglobin A1c trajectories throughout the 7.5-year follow-up. Similar results (for MIAT and PLUTO also in combined analysis) were obtained in the validation cohort. CONCLUSIONS We found a set of circulating lncRNAs that independently portends incident type 2 diabetes in older adults years before disease onset.

Additional file 1: Figure S1. Generation of the atherosclerosis-prone hepatocyte-specific Ncor1 knockout mouse model. Figure S2. Validation of the hepatocyte-specific Ncor1 knockout mouse model. Figure S3. Food intake. 24 hours average food intake in L-Ncor1Hep+/+ and L-Ncor1Hep-/-mice. n = 11 L-Ncor1Hep+/+; n = 12 L-Ncor1Hep-/-. Figure S4. Hepatocyte-specific Ncor1 knockouts display a trend for increased plasma cholesterol and triglyceride levels. A Plasma total cholesterol concentrations in L-Ncor1Hep+/+ and L-Ncor1Hep-/- mice n = 6 L-Ncor1Hep+/+; n = 9 L-Ncor1Hep-/-. B TC levels in lipoprotein subfractions of L-Ncor1Hep+/+ and L-Ncor1Hep-/- mice. n = 6 L-Ncor1Hep+/+; n = 8 L-Ncor1Hep-/-. C TC levels in lipoprotein subfractions of L-Ncor1Hep+/+mice fed HCD or chow diets. Pooled samples of 5–7 mice per diet group. D TC levels in lipoprotein subfractions of L-Ncor1Hep-/-mice fed HCD or chow diets. Pooled samples of 5–7 mice per diet group. Figure S5. Hepatocyte Ncor1 deficiency alters biliary bile acid composition. Percentage of CA- and CDCA-derived bile acids in bile collected through cannulation in L-Ncor1Hep+/+ (WT) and L-Ncor1Hep-/- (KO) mice n = 11 L-Ncor1Hep+/+; n = 11 L-Ncor1Hep-/-. *p < 0.001 relative to L-Ncor1Hep+/+. Figure S6. Total fecal bile acid excretion. L-Ncor1Hep+/+ and L-Ncor1Hep-/- mice. n = 12 L-Ncor1Hep+/+; n = 10 L-Ncor1Hep-/-. Figure S7. Relative expression of transcripts at the indicated times points: 24h (Zeitgeber ZT 17), 8h (ZT 1) and 16h (ZT 9). L-Ncor1Hep+/+ and L-Ncor1Hep-/- mice. n = 3 L-Ncor1Hep+/+; n = 3 L-Ncor1Hep-/-.

In the current study, the temporal distribution of both soil water and soil NO3–N under several conservation agriculture (CA) practices during the wheat crop growth were characterized by HYDRUS-2D model. Treatments comprised of conventional tillage (CT), permanent broad beds (PBB), zero tillage (ZT), PBB with residue (PBB+R) and ZT with residue (ZT+R). Hydraulic inputs of the model, comprising the measured value of Kfs, α and n, obtained as the output of Rosetta Lite model were optimized through inverse modeling. Model predicted the daily change in soil water content (SWC) of the profile during the simulated period (62–91 DAS) with good accuracy (R2 = 0.75; root mean squared error (RMSE) = 0.038). In general, soil water balance simulated from the model showed 50% lower cumulative drainage, 50% higher cumulative transpiration along with higher soil water retention, in PBB+R than CT. Reported values of the first-order rate constants, signify nitrification of urea to NH4–N (μa) (day−1) nitrification of NH4–N to NO3–N (μn) (day−1) and the distribution coefficient of urea (Kd−in cm3 mg−1) were optimized through inverse modeling. Later they were used as solute transport reaction input parameters of the model, to predict the daily change in NO3–N of the profile with better accuracy (R2 = 0.83; RMSE = 4.62). Since NH4–N disappears fast, it could not be measured frequently. Therefore, not enough data could be generated for their use in the calibration and validation of the model. Results of simulation of daily NO3–N concentration indicated a higher concentration of NO3–N in the surface layer and its leaching losses beyond the root zone were relatively lesser in PBB+R, than CT, which resulted in less contamination of the belowground water. Thus, the study clearly recommended PBB+R to be adopted for wheat cultivation in maize–wheat cropping system, as it enhances the water and nitrogen availability in the root zone and reduce their losses beyond the root zone.

Therapeutic modulation of blood vessel growth holds promise for the prevention of limb ischemia in diabetic (DM) patients with peripheral artery disease (PAD). Epigenetic changes, namely posttranslational histone modifications, participate in angiogenic response suggesting that chromatin-modifying drugs could be beneficial in this setting. Apabetalone (APA), a selective inhibitor of bromodomain (BRD) and extra-terminal (BET) proteins, prevents BRD4 interactions with chromatin thus modulating transcriptional programs in different organs. We sought to investigate whether APA affects angiogenic response in diabetes. Results:As compared to vehicle, APA restored tube formation and migration in human aortic endothelial cells (HAECs) exposed to high glucose (HG) levels. Expression profiling of angiogenesis genes showed that APA prevents HG-induced upregulation of the anti-angiogenic molecule Thrombospondin-1 (THBS1). ChIP-seq and chromatin immunoprecipitation (ChIP) assays in HG-treated HAECs showed the enrichment of both BRD4 and active marks (H3K27ac) on THBS1 promoter, whereas BRD4 inhibition by APA prevented chromatin accessibility and THBS1 transcription. Mechanistically, we show that THBS1 inhibits angiogenesis by suppressing VEGFA signaling, while APA prevents these detrimental changes. In diabetic mice with hindlimb ischemia, epigenetic editing by APA restored THSB1/VEGFA axis thus improving limb vascularization and perfusion as compared to vehicle-treated animals. Finally, epigenetic regulation of THSB1 by BRD4/H3K27ac was also reported in DM patients with PAD as compared to non-diabetic controls. Innovation:This is the first study showing that BET protein inhibition by APA restores angiogenic response in experimental diabetes. Conclusions:Our findings set the stage for preclinical studies and exploratory clinical trials testing APA in diabetic PAD.

Overlapping pandemics of lifestyle-related diseases pose a substantial threat to cardiovascular health. Apart from coronary artery disease, metabolic disturbances linked to obesity, insulin resistance and diabetes directly compromise myocardial structure and function through independent and shared mechanisms heavily involving inflammatory signals. Accumulating evidence indicates that metabolic dysregulation causes systemic inflammation, which in turn aggravates cardiovascular disease. Indeed, elevated systemic levels of pro-inflammatory cytokines and metabolic substrates induce an inflammatory state in different cardiac cells and lead to subcellular alterations thereby promoting maladaptive myocardial remodeling. At the cellular level, inflammation-induced oxidative stress, mitochondrial dysfunction, impaired calcium handling, and lipotoxicity contribute to cardiomyocyte hypertrophy and dysfunction, extracellular matrix accumulation and microvascular disease. In cardiometabolic patients, myocardial inflammation is maintained by innate immune cell activation mediated by pattern recognition receptors such as Toll-like receptor 4 (TLR4) and downstream activation of the NLRP3 inflammasome and NF-κB-dependent pathways. Chronic low-grade inflammation progressively alters metabolic processes in the heart, leading to a metabolic cardiomyopathy (MC) phenotype and eventually to heart failure with preserved ejection fraction (HFpEF). In accordance with preclinical data, observational studies consistently showed increased inflammatory markers and cardiometabolic features in patients with HFpEF. Future treatment approaches of MC may target inflammatory mediators as they are closely intertwined with cardiac nutrient metabolism. Here, we review current evidence on inflammatory processes involved in the development of MC and provide an overview of nutrient and cytokine-driven pro-inflammatory effects stratified by cell type.

In traditional system of medicine, various parts of Delonix regia have been used for many ailments. The objective of the present study was to evaluate the memory enhancing activity of Ethanolic Extract of Delonix regia leaves (EEDRL) against scopolamine induced amnesia by using Elevated Plus Maze, Y Maze and Morris Water Maze Models. Ethanolic Extract of Delonix regia was prepared then subjected to phytochemical analysis revealed the presence of flavonoids, alkaloids, carbohydrates, tannins, steroids, terpenoids, phenols and saponins. Acute oral toxicity was performed as per OECD guidelines 423. Based on this, two dose levels of EEDRL were chosen as 200 mg/kg and 400 mg/kg for pharmacological screening. Swiss albino mice were divided into five groups of six animals each. EEDRL at a dose levels 200 mg/kg & 400 mg/kg showed increase in inflexion ratio in Elevated Plus Maze, increase in Percentage alterations in Y Maze & decrease in Escape latency in Morris Water Maze Model compared to disease control in dose dependent manner which indicates that the EEDRL reverses the scopolamine induced amnesia in mice. The memory enhancing activity in mice might be due to facilitation of cholinergic transmission. Hence it can be concluded that Delonix regia appears to be a promising candidate for improving memory, and it would be worthwhile to explore the potential of this plant in the management of Alzheimer patient.

Despite significant advances in our understanding of cardiovascular disease (CVD) we are still far from having developed breakthrough strategies to combat coronary atherosclerosis and heart failure, which account for most of CV deaths worldwide. Available cardiovascular therapies have failed to show to be equally effective in all patients, suggesting that inter-individual diversity is an important factor when it comes to conceive and deliver effective personalized treatments. Genome mapping has proved useful in identifying patients who could benefit more from specific drugs depending on genetic variances; however, our genetic make-up determines only a limited part of an individual's risk profile. Recent studies have demonstrated that epigenetic changes - defined as dynamic changes of DNA and histones which do not affect DNA sequence - are key players in the pathophysiology of cardiovascular disease and may participate to delineate cardiovascular risk trajectories over the lifetime. Epigenetic modifications include changes in DNA methylation, histone modifications and non-coding RNAs and these epigenetic signals have shown to cooperate in modulating chromatin accessibility to transcription factors and gene expression. Environmental factors such as air pollution, smoking, psychosocial context, and unhealthy diet regimens have shown to significantly modify the epigenome thus leading to altered transcriptional programs and CVD phenotypes. Therefore, the integration of genetic and epigenetic information might be invaluable to build individual maps of cardiovascular risk and hence, could be employed for the design of customized diagnostic and therapeutic strategies. In the present review, we discuss the growing importance of epigenetic information and its putative implications in cardiovascular precision medicine.

Highly photoluminescent carbon quantum dots (CQDs) were synthesized by microwave assisted hydrothermal method. Emission wavelength of the CQDs depends on the excitation wavelength but is independent of the size of the CQDs.