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Objective: This study aimed to compare the predictive value of carotid or femoral artery ultrasound for coronary artery disease (CAD) in type 2 Diabetes mellitus (T2DM) patients free from known CAD, and to assess the relationship with the severity of coronary artery stenosis. Methods: Cross-sectional study in adults with a T2DM duration of at least 5 years and without established CAD. Carotid plaque score (CPS) and Gensini score were used to measure the severity of carotid and coronary artery stenosis, respectively, and patients were divided into no or mild group, moderate group, and severe group according to the tertile of the score. Univariate and multivariate logistic regression analysis was used to explore the possible risk factors for CAD. Receiver operating characteristic (ROC) curves were created to determine the most accurate assessment for detecting significant CAD (≥ 50% stenosis). Results: 245 patients (137 male) aged 68.21± 9.5 years (range: 36– 95 years), with T2DM duration 12.04± 6.17 years (range: 5– 34 years), and without CVD were included. CAD was diagnosed in 165 patients (67.3%). Multiple regression analysis showed that CPS, femoral plaque, and smoking were independently and positively correlated with CAD. CPS yielded the highest area under the curve for detecting significant coronary disease (AUC=0.7323). In contrast, the area under the curve of femoral artery plaque and carotid intima-media thickness was lower than 0.7, which was at a lower prediction level. Conclusion: In patients with long T2DM duration, CPS has a higher ability to predict the occurrence and severity of CAD. However, femoral artery plaque has special value in predicting moderate to severe coronary artery disease in patients with long-term T2DM. [ABSTRACT FROM AUTHOR]

BACKGROUND: Accumulating evidence shows that the increase in blood viscosity (BV) is an independent risk factor for atherosclerosis and its related diseases, but as far as we know, there are few studies on the relationship between blood viscosity and carotid plaque severity. Therefore, we aimed to investigate the relationship between blood viscosity and the presence of carotid plaques, and further explore its relationship with the severity of carotid plaques. METHODS: We retrospectively analyzed the data of consecutive subjects in the physical examination center of the Affiliated Hospital of Ningbo University Medical College from January 2022 to May 2022. The parameters of blood viscosity include the whole blood viscosity (WBV) at high, middle, and low shear rate, plasma viscosity (PV), hematocrit (HCT), rigidity "k", rigidity index (RI), aggregation index (AI) and electrophoresis rate (ER), and standardized BV calculated by Quemada's equation were included in the study. Carotid plaque score (CPS) was used to measure the severity of carotid artery disease, and participants were divided into mild, moderate, and severe groups according to the quartile of the score. Independent samples t-test and one-way ANOVA were used to compare normally distributed continuous variables between two or more independent groups, respectively. Binary logistic regression was used to evaluate the risk factors of carotid plaque. RESULTS: 314 men were enrolled in the study, of which 165 participants were diagnosed with Carotid artery plaque (CAP) (66.9%). Compared with the CAP- group, the WBV and PV of the CAP+group decreased, but the difference only existed in the PV (p = 0.001). However, standardized BV values (HCT set at 0.45) were higher in the CAP+group than in the CAP- group (3.8643±0.35431vs 3.9542±0.64871, p = 0.188). Regarding the rigidity and aggregation of RBC, the parameters including rigidity "k", RI, AI and ER increased in the CAP+group compared with the CAP- group. The difference was statistically significant in k and ER (p = 0.04, p = 0.009). To assess the severity of carotid plaque, we divided the participants into mild, moderate, and severe groups by using the tertile of CPS value. The mild group was defined as CPS≤0.5 (n = 108), the moderate group as 0.5 < CPS≤1.7 (n = 105), and the severe group as CPS > 1.7 (n = 101). It was found that WBV and PV decreased with the increase of plaque severity, but the difference among the three groups was significant in PV (F = 8.073, p < 0.0001). In addition, with the severity of plaque from mild to severe, standardized BV gradually increased, which were 3.8611±0.34845, 3.8757±0.36637, 3.9007±0.38353 respectively. The difference between the groups was close to statistically significant (F = 2.438, p = 0.089). The values of parameters describing erythrocyte aggregation and rigidity increased among the mild, moderate, and severe groups. The difference was statistically significant in RBC rigidity "k" and ER of RBC (F = 3.863, p = 0.022; F = 5.897, p = 0.003, respectively). CONCLUSION: Increased blood viscosity is a risk factor for carotid plaque, but its increase may be hidden by decreased hematocrit. Therefore, it is necessary to comprehensively analyze various parameters of blood viscosity, such as the standardized BV calculated by Quemada's equation, which may provide more useful reference value. [ABSTRACT FROM AUTHOR]

The correlation between diabetes and systematic well-being on human life has long established. As a common complication of diabetes, the prevalence of diabetic nephropathy (DN) has been increasing globally. DN is known to be a major cause of end-stage kidney disease (ESKD). Till now, the molecular mechanisms for DN have not been fully explored and the effective therapies are still lacking. Noncoding RNAs are a class of RNAs produced by genome transcription that cannot be translated into proteins. It has been documented that ncRNAs participate in the pathogenesis of DN by regulating inflammation, apoptosis, autophagy, cell proliferation, and other pathological processes. In this review, the pathological roles and diagnostic and therapeutic potential of three types of ncRNAs (microRNA, long noncoding RNA, and circular RNA) in the progression of DN are summarized and illustrated. [ABSTRACT FROM AUTHOR]

Endothelial nitric oxide synthase (eNOS) is a multifunctional enzyme with roles in diverse cellular processes including angiogenesis, tissue remodeling, and the maintenance of vascular tone. Monomeric and dimeric forms of eNOS exist in various tissues. The dimeric form of eNOS is considered the active form and the monomeric form is considered inactive. The activity of eNOS is also regulated by many other mechanisms, including amino acid phosphorylation and interactions with other proteins. However, the precise mechanisms regulating eNOS dimerization, phosphorylation, and activity remain incompletely characterized. We utilized purified eNOS and bovine aorta endothelial cells (BAECs) to investigate the mechanisms regulating eNOS degradation. Both eNOS monomer and dimer existed in purified bovine eNOS. Incubation of purified bovine eNOS with protein phosphatase 2A (PP2A) resulted in dephosphorylation at Serine 1179 (Ser1179) in both dimer and monomer and decrease in eNOS activity. However, the eNOS dimer∶monomer ratio was unchanged. Similarly, protein phosphatase 1 (PP1) induced dephosphorylation of eNOS at Threonine 497 (Thr497), without altering the eNOS dimer∶monomer ratio. Different from purified eNOS, in cultured BAECs eNOS existed predominantly as dimers. However, eNOS monomers accumulated following treatment with the proteasome inhibitor lactacystin. Additionally, treatment of BAECs with vascular endothelial growth factor (VEGF) resulted in phosphorylation of Ser1179 in eNOS dimers without altering the phosphorylation status of Thr497 in either form. Inhibition of heat shock protein 90 (Hsp90) or Hsp90 silencing destabilized eNOS dimers and was accompanied by dephosphorylation both of Ser1179 and Thr497. In conclusion, our study demonstrates that eNOS monomers, but not eNOS dimers, are degraded by ubiquitination. Additionally, the dimeric eNOS structure is the predominant condition for eNOS amino acid modification and activity regulation. Finally, destabilization of eNOS dimers not only results in eNOS degradation, but also causes changes in eNOS amino acid modifications that further affect eNOS activity. [ABSTRACT FROM AUTHOR]

Aims: The goal of our study is to investigate the combined contribution of 10 genetic variants to diabetes susceptibility. Methods: Bibliographic databases were searched from 1970 to Dec 2012 for studies that reported on genetic association study of diabetes. After a comprehensive filtering procedure, 10 candidate gene variants with informative genotype information were collected for the current meta-anlayses. Using the REVMAN software, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the combined contribution of the selected genetic variants to diabetes. Results: A total of 37 articles among 37,033 cases and 54,716 controls were involved in the present meta-analyses of 10 genetic variants. Three variants were found to be significantly associated with type 1 diabetes (T1D): NLRP1 rs12150220 (OR = 0.71, 95% CI = 0.55–0.92, P = 0.01), IL2RA rs11594656 (OR = 0.86, 95% CI = 0.82–0.91, P<0.00001), and CLEC16A rs725613 (OR = 0.71, 95% CI = 0.55–0.92, P = 0.01). APOA5 −1131T/C polymorphism was shown to be significantly associated with of type 2 diabetes (T2D, OR = 1.27, 95% CI = 1.03–1.57, P = 0.03). No association with diabetes was showed in the meta-analyses of other six genetic variants, including SLC2A10 rs2335491, ATF6 rs2070150, KLF11 rs35927125, CASQ1 rs2275703, GNB3 C825T, and IL12B 1188A/C. Conclusion: Our results demonstrated that IL2RA rs11594656 and CLEC16A rs725613 are protective factors of T1D, while NLRP1 rs12150220 and APOA5 −1131T/C are risky factors of T1D and T2D, respectively. [ABSTRACT FROM AUTHOR]

Abstract: Type 2 diabetes (T2D) and coronary artery disease (CAD) are closely related chronic diseases with high prevalence and morbidity. However, a comprehensive comparison of the two diseases is lacking. Recent genome-wide association studies (GWAS) have identified a handful of single nucleotide polymorphisms (SNPs) that are significantly associated with the risk of T2D and CAD. These most significant findings may help interpret the pathogenesis of T2D and CAD. However, tremendous results from these GWAS are ignored. Here we revisited the raw datasets of these GWAS and performed an integrated gene network analysis to unveil the relationship between T2D and CAD by combining multiple datasets including protein–protein interaction (PPI) database, publication libraries, and pathway datasets. Our results showed that majority of genes were involved in the first module (1122 genes in T2D and 895 in CAD). Four pathways were found to be common in both T2D and CAD, including regulation of actin cytoskeleton, calcium signaling pathway, MAPK signaling pathway and focal adhesion (all P<0.00001). MAX which was involved in small cell lung cancer pathway was a hub gene unique to T2D (OR=1.2, P=0.006) but not in CAD. In contrast, three hub genes including PLEKHG5 (T2D: OR=1, P=1; CAD: OR=1.12, P=0.006), TIAM1 (T2D: OR=1, P=1; CAD: OR=1.48, P=0.004) and AKAP13 (T2D: OR=1, P=1; CAD: OR=1.38, P=0.001) were hub genes unique to CAD. Moreover, for some hub genes (such as SMAD3) that were susceptible to both T2D and CAD, their associated polymorphisms were unique to each of the two diseases. Our findings might provide a landscape of the relationship between T2D and CAD. [Copyright &y& Elsevier]