Studies suggest T cells modulate arterial pressure. Since robust sex differences exist in the immune system and in hypertension, we investigated sex differences in T cell modulation of angiotensin II (Ang II)-induced increases in mean arterial pressure (MAP) in male (M) and female (F) wild type (WT) and recombination-activating-gene-1-deficient (Rag1−/−) mice. Sex-differences in peak MAP in WT were lost in Rag1−/− mice [mmHg: WT-F, 136±4.9 vs. WT-M, 153±1.7; P<0.02; Rag1−/−-F, 135±2.1 vs. Rag1−/−-M, 141±3.8]. Peak MAP was 13 mmHg higher after adoptive transfer of male (CD3M→Rag1−/−-M) vs. female (CD3F→Rag1−/−-M) T-cells. CD3M→Rag1−/−-M mice exhibited higher splenic frequencies of pro-inflammatory interleukin-17A (2.4-fold) and tumor-necrosis factor-α (2.2-fold)-producing T cells and lower plasma levels (13-fold) and renal mRNA expression (2.4-fold) of interleukin-10 while CD3F→Rag1−/−-M mice displayed a higher activation state in general and T-helper 1-biased renal inflammation. Greater T cell infiltration into perivascular adipose tissue and kidney associated with increased pressor responses to Ang II if the T cell donor was male but not female and these sex differences in T cell subset expansion and tissue infiltration were maintained for 7–8 weeks within the male host. Thus, the adaptive immune response and role of pro- and anti-inflammatory cytokine signaling in hypertension is distinct between the sexes and needs to be understood to improve therapeutics for hypertension-associated disease in both men and women.

The interaction of amyloid-β (Aβ) and redox-active metals, two important biomarkers present in the senile plaques of AD brain, has been suggested to either enhance the Aβ aggregation or facilitate the generation of reactive oxygen species (ROS). The present study investigates the nature of the interaction between the metal-binding domain of Aβ, viz,, and the Fe(III) or Fe(II) complex with nitrilotriacetic acid (NTA). Using electrospray ionization mass spectrometry (ESI-MS), the formation of a ternary complex of Aβ(1-16), Fe(III), and NTA with a stoichiometry of 1:1:1 was identified. MS also revealed that the NTA moiety can be detached via collision-induced dissociation. The cumulative dissociation constants of both Aβ-Fe(III)-NTA and Aβ-Fe(II)-NTA were deduced to be 6.3 × 10 -21 M 2 and 5.0 × 10 -12 M 2 , respectively, via measuring the fluorescence quenching of the sole tyrosine residue on Aβ upon the complex formation. The redox properties of these two complexes were investigated by cyclic voltammetry. The redox potential of the Aβ-Fe(III)-NTA complex was found to be 0.03 V vs. Ag/AgCl, which is negatively shifted by 0.54 V when compared to the redox potential of free Fe(III)/Fe(II). Despite such a large potential modulation, the redox potential of the Aβ-Fe(III)-NTA complex is still sufficiently high for occurrence of a range of redox reactions with cellular species. Aβ-Fe(II)-NTA electrogenerated from Aβ-Fe(III)-NTA was also found to catalyze the reduction of oxygen to produce H 2 O 2 . These findings provide significant insight into the role of iron and Aβ in the development of AD. The binding of iron by Aβ modulates the redox potential to a level where its redox cycling occurs. In the presence of a biological reductant (antioxidant), redox cycling of iron could disrupt the redox balance within the cellular milieu. As a consequence, not only ROS is continuously produced, but also oxygen and biological reductants can be depleted. A cascade of biological processes can therefore be affected. In addition, the strong binding affinity of Aβ toward Fe(III) and Fe(II) indicates Aβ could compete for iron against other iron-containing protein. Particularly, its strong affinity to Fe(II), which is eight orders of magnitude stronger than transferrin, would greatly interfere with the iron homeostasis.A major hallmark of Alzheimer's disease (AD) is the deposition of aggregates of amyloid-β (Aβ) peptides in the senile plaques.(1) The in vivo aggregation/deposition of Aβ peptides is suggested to either enhance neurotoxicity or be a result of aberrant cellular processes.(2) The

In view of the high incidence of diabetic retinopathy and the functionality of long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) in different disease models, the present study aimed to investigate the role of MEG3 in diabetic retinopathy. In the study, patients with diabetic retinopathy, diabetic patients without retinopathy as well as healthy people were included. Fasting blood was extracted from each participant. Serum MEG3 levels were detected by everse transcription-quantitative polymerase chain reaction (RT-qPCR) and serum vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) levels were detected by ELISA. Also, the effects of high glucose treatment on the expression of MEG3 and VEGF and the effects of MEG3 overexpression on expression of VEGF and TGF-β1 in high glucose-treated ARPE-19 cells were detected by RT-qPCR and western blot analysis to determine the mRNA and protein levels, respectively. It was indicated that serum levels of MEG3 were significantly lower, while the serum levels of VEGF and TGF-β1 were significantly higher in patients with diabetic retinopathy and diabetic patients without retinopathy compared with the healthy controls. Furthermore, slight differences were found between patients with diabetic retinopathy and diabetic patients without retinopathy; however, these differences were not significant. The findings indicated that high glucose upregulated the expression of VEGF mRNA and downregulated the expression of MEG3, MEG3 overexpression reduced the increased expression levels of VEGF and TGF-β1 induced by high glucose treatment. Therefore, it was concluded that lncRNA MEG3 overexpression may inhibit the development of diabetic retinopathy by inhibiting TGF-β1 and VEGF expression.

No abstract

Background In China, the prevalence of diabetes has increased significantly over recent decades, owing to the county's rapidly aging population. Although many studies have examined the prevalence of diabetes worldwide, there has been little analysis of the inequalities in its prevalence and treatment among middle-aged and elderly people. Objectives This study evaluates influence factors and inequality in respect to the prevalence of diabetes and medication treatment among middle-aged and elderly Chinese adults. Methods Data were obtained from the China Health and Retirement Longitudinal Study, a nationally representative household survey of middle-aged and elderly people (i.e., 45 years of age or older). Logistic regression models and the concentration index were used to estimate socioeconomic factors and inequalities in diabetes prevalence and treatment. Results The prevalence of self-reported diabetes among middle-aged and elderly Chinese adults was 8.4%; this figure was significantly higher in urban areas than in rural areas. Concentrations of prevalence were observed among the poor in urban areas and among the rich in rural areas. Overall, the incidence of receiving antidiabetic medication among diabetes patients was 64.3%; this was significantly higher for individuals in urban areas than those in rural areas, suggesting that awareness of diabetes treatment in urban areas is better than that in rural areas. A disproportionate concentration of incidence of receiving antidiabetic medication was observed among the rich in both urban and rural areas. Socioeconomic factors significantly affected the prevalence of diabetes and the likelihood of receiving medication and are major contributors to inequality. Conclusion In China, policies and strategies regarding diabetes prevention and control should further focus on associated socioeconomic factors and major contributors to reduce diabetes prevalence, improve diabetes treatment and management, and alleviate current inequality in the prevalence and treatment of diabetes among middle-aged and elderly adults.

No abstract

The aim of this study was to examine in vitro the response of human mesenchymal stem cells (hMSCs) on the novel biomimetic bioglass-collagen-hyaluronic acid-phosphatidylserine (BG-COL-HYA-PS) composite scaffold for potential use in bone tissue engineering. The initial attachment, the proliferation, migration and differentiation behavior of the cells on the BG-COL-HYA-PS composites were assessed in comparison with those on pure 58sBG, BG-COL, and BG-COL-HYA composites in either growth medium (L-DMEM supplemented with 10% fetal bovine serum) or osteogenic medium (growth medium supplemented with 0.1 microM dexamethasone, 10 mM beta-glycerophosphate, and 50 microM ascorbic acid). HMSCs attached, and subsequently proliferated and migrated on the BG-COL-HYA-PS composites to a significantly higher degree. The alkaline phosphatase (ALP) staining, ALP activity and the expression of the bone associated gene ALP, osteocalcin (OC), and osteopontin (OPN) was also significantly higher in the hMSCs on the BG-COL-HYA-PS scaffolds than those on the BG-COL, BG-COL-HYA composites and the pure 58sBG. These findings suggest that the BG-COL-HYA-PS composite porous scaffolds have high potential for use as scaffolds in bone tissue engineering and repair.

DNA 5-hydroxymethylcytosine (5hmC) is an important epigenetic modification found in various mammalian cells. Immunofluorescence imaging analysis essentially provides visual pictures for the abundance and distribution of DNA 5hmC in single cells. However, nuclear DNA is usually wrapped around nucleosomes, packaged into chromatins, and further bound with many functional proteins. These physiologically relevant events would generate barriers to the anti-5hmC antibody to selectively recognize 5hmC in DNA. By taking advantage of these naturally generated barriers, here, we present a strategy to evaluate the accessibility of DNA 5hmC in chromatins in situ. We demonstrate that a few of the 5hmC sites in DNA are exposed or accessible to anti-5hmC antibody under nondenaturing conditions, suggesting that these 5hmC sites are not covered by functional DNA-binding proteins in mouse embryonic stem cells. Consistently, these 5hmC foci were distributed in open euchromatin regions as revealed by the 4',6-diamidino-2-phenylindole (DAPI) staining. By overexpressing TET1 catalytic domain (responsible for oxidation 5mC to produce 5hmC) in human MCF-7 cells, we observed a significant increase in accessible 5hmC along with an increase in total 5hmC sites. Collectively, by the use of the nondenaturing immunofluorescence imaging approach, we could obtain a visual landscape on the accessibility of DNA 5hmC in chromatins.