A Systematic Study of Dysregulated MicroRNA in Type 2 Diabetes Mellitus.

MicroRNAs (miRNAs) are small noncoding RNAs that modulate the cellular transcriptome at the post-transcriptional level. miRNA plays important roles in different disease manifestation, including type 2 diabetes mellitus (T2DM). Many studies have characterized the changes of miRNAs in T2DM, a complex systematic disease; however, few studies have integrated these findings and explored the functional effects of the dysregulated miRNAs identified. To investigate the involvement of miRNAs in T2DM, we obtained and analyzed all relevant studies published prior to 18 October 2016 from various literature databases. From 59 independent studies that met the inclusion criteria, we identified 158 dysregulated miRNAs in seven different major sample types. To understand the functional impact of these deregulated miRNAs, we performed targets prediction and pathway enrichment analysis. Results from our analysis suggested that the altered miRNAs are involved in the core processes associated with T2DM, such as carbohydrate and lipid metabolisms, insulin signaling pathway and the adipocytokine signaling pathway. This systematic survey of dysregulated miRNAs provides molecular insights on the effect of deregulated miRNAs in different tissues during the development of diabetes. Some of these miRNAs and their mRNA targets may have diagnostic and/or therapeutic utilities in T2DM.

Influence of four polymorphisms in ABCA1 and PTGS2 genes on risk of Alzheimer's disease: a meta-analysis.

We preformed this meta-analysis to investigate the influence of ABCA1 (ATP-binding cassette sub-family A member 1) rs2422493 (C-477T), rs1800977 (C-14T), rs2066718 (V771M), and PTGS2 (Prostaglandin-endoperoxide synthase 2) rs20417 (G-765C) polymorphisms on the risk of Alzheimer's disease (AD). Seventeen eligible case-control studies were acquired from PubMed, Embase, Alzgene, Chinese National Knowledge Infrastructure and Wanfang databases. The pooled odds ratios (ORs) with 95 % confidence intervals (95 % CI) were calculated to evaluate the association under five genetic models. Combined data indicated that ABCA1 rs2422493 polymorphism was statistically significant associated with increasing AD risk in three genetic models (allelic T vs C: OR = 1.12, 95 % CI: 1.01-1.24; homozygous TT vs CC: OR = 1.26, 95 % CI: 1.03-1.55; and recessive TT vs TC + CC: OR = 1.33, 95 % CI: 1.12-1.58) while no association was found between two other ABCA1 polymorphisms and AD susceptibility. Nevertheless, a further risk-stratification analysis showed that ApoE-ε4 carriers with any ABCA1 polymorphism suffered a much higher probability to be AD patients. Meanwhile, PTGS2 rs20417 polymorphism was linked to decreasing AD risk with a P < 0.0001 in five genetic models (e.g., allelic C vs G: OR = 0.59, 95 % CI: 0.50-0.70; homozygous CC vs GG: OR = 0.31, 95 % CI: 0.18-0.52; and heterozygous CG vs GG: OR = 0.64, 95 % CI: 0.52-0.78). In summary, our meta-analysis results showed that ABCA1 rs2422493 polymorphism was a risk factor for AD while PTGS2 rs20417 variant showed a protective effect on AD risk. In addition, ABCA1 rs2066718 and rs1800977 polymorphisms might not contribute to AD susceptibility in general population, but they should play a role on AD development when interacted with ApoE-ε4.

Effects of Resveratrol on the Mechanisms of Antioxidants and Estrogen in Alzheimer's Disease.

OBJECTIVE: To observe the effects of resveratrol (Res) on the antioxidative function and estrogen level in an Alzheimer's disease (AD) mouse model. METHODS: First, we examined the effects of Res on an AD mice model. SAMP8 mice were selected as the model, and normal-aging SAMR1 mice were used as the control group. The model mice were randomly divided into three groups: a model group, high-dose Res group (40mg/kg, intraperitoneal (ip)), and low-dose Res group (20mg/kg, ip). After receiving medication for 15 days, the mice were subjected to the water maze test to assess their spatial discrimination. The spectrophotometric method was used to detect the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) as well as the malondialdehyde (MDA) content. Quantitative PCR (q-PCR) was used to detect SOD, GSH-Px, CAT, and heme oxygenase-1 (HO-1) mRNA level changes. Western blot analysis detected HO-1 and Nrf2 protein expression. Second, we researched the effect of Res on the estrogen level in the SAMP8 model mice. The model mice were randomly divided into four groups: a model group, estrogen replacement group (0.28 mg/kg, intramuscular (im), estradiol benzoate), high-dose Res group (5 mg/kg, im), and low-dose Res group (2.5 mg/kg, im). The mice were injected, once every three days, for 5 weeks. Q-PCR was used to detect brain tissue mRNA expression changes. Western blot analysis detected ERα, ERß, and ChAT protein expression. An enzyme-linked immunosorbent assay (ELISA) kit was used to detect the expression of E2 and amyloid ß protein (Aß) in brain tissue. RESULTS: Compared with the control treatment, Res could improve the spatial abilities of the mice to a certain extent and also increase the expression of SOD, GSH-Px, CAT, and HO-1 at the mRNA level (P<0.05). In addition, enhanced SOD, GSH-Px, and CAT activities and HO-1 protein levels and decreased MDA content (P<0.05) were detected in the brain tissue of the Res-treated mice. The cytoplasmic Nrf2 content in the Res-treated mice was also decreased while the nuclear Nrf2 content and the nuclear translation rate of Nrf2 were increased (P<0.05). Res could decrease the expression of ERß in the brain tissue at the mRNA and protein levels and the expression of Aß in the brain tissue at the protein level. Res could also increase the mRNA and protein expression of ERα and ChAT and the protein expression of estradiol in the brain tissue. CONCLUSION: Res can increase the antioxidant capacity of AD models through the Nrf2/HO-1 signaling pathway. In addition, Res can enhance estrogen levels in an AD model. These findings provide a new idea for the treatment of AD.

Potential applications of MEG3 in cancer diagnosis and prognosis.

LncRNAs are emerging as integral functional and regulatory components of normal biological activities and are now considered as critically involved in the development of different diseases including cancer. In this review, we summarized recent findings on maternally expressed gene 3 (MEG3), a noncoding lncRNA, locates in the imprinted DLK1-MEG3 locus on human chromosome 14q32.3 region. MEG3 is expressed in normal tissues but is either lost or decreased in many human tumors and tumor derived cell lines. Studies have demonstrated that MEG3 is associated with cancer initiation, progression, metastasis and chemo-resistance. MEG3 may affect the activities of TP53, MDM2, GDF15, RB1 and some other key cell cycle regulators. In addition, the level of MEG3 showed good correlation with cancer clinicopathological grade. In summary, MEGs is an RNA-based tumor suppressor and is involved in the etiology, progression, and chemosensitivity of cancers. The alteration of MEG3 levels in various cancers suggested the possibility of using MEG3 level for cancer diagnosis and prognosis.

Association of Polymorphisms in STRA6 and RARRES2 Genes with Type 2 Diabetes in Southern Han Chinese.

Stimulated by retinoic acid gene homolog 6 (STRA6) and retinoic acid receptor responder 2 (RARRES2) are candidate genes involved in the pathogenesis of type 2 diabetes mellitus (T2DM). Three tag-SNPs in STRA6 and one in RARRES2 gene were selected and genotyped with TaqMan or PCR-RFLP method in 603 populations (571 patients with T2D versus 632 control subjects) in Southern Han Chinese. We estimated the interactions between T2DM risk and genetic variants in the STRA6 and RARRES2 genes using polymerase chain reaction. Rs736118 in STRA6 gene were significantly associated with T2DM occurrence in the recessive genetic model. The genotype of rs974456 was significantly associated with T2DM in the dominant genetic model correlated to sex, MBI, and triglyceride. However, the association of other SNPs with T2DM was not found. Furthermore, smoking history and other factors may be independent risk factors for the incidence of T2DM. This study suggested that a role of STRA6 polymorphism could also be of value in predicting the risk of T2DM while RARRES2 polymorphism could not predict the risk of T2DM.