Biosynthesis of copper oxide nanoparticles and their potential synergistic effect on alloxan induced oxidative stress conditions during cardiac injury in Sprague-Dawley rats.

Cistus incanus leaf extract was used to biologically synthesize Copper oxide nanoparticles (CuO NPs). The characteristic UV-vis spectral band of CuO NPs found at 290 nm revealed the successful formation of CuO NPs. By the analysis of TEM and SEM, it is confirmed that the obtained CuO NPs were in spherical structure. By the analysis of Fourier transform infrared (FTIR) spectroscopy, it is evident that the absorption peak was situated at a position of about 480 cm-1 of wavenumber, which is typically considered as an extremely pure CuO NPs. The images of Transmission Electron Microscopy exhibited that the formed CuO NPs were in the size of about 15-25 nm and were relatively uniform in distribution. When related with the treatment of nanomaterials only, the synergistic interaction among CuO NPs and oxidative stress conditions considerably decreased the cardiac-related function catalogs, which includes pathological progressions of myocardium along with an obvious rise in the levels of creatine kinase-MB and cardiac troponin I. When compared to the void reaction of micro-CuO and cardiac operations in alloxan-injected rats, aggravation in the conditions of oxidative stress could be playing a significant part in the heart injury after dual exposing CuO NPs and alloxan. By these results, it is confirmed that the conditions of oxidative stress improved the contrary effects of CuO NPs to the heart, signifying that the utilization of nanomaterials in conditions of stress such as, in the delivery of drug, required to be cautiously monitored.

CTLA-4 methylation regulates the pathogenesis of myasthenia gravis and the expression of related cytokines.

BACKGROUND: Myasthenia gravis (MG) is a progressive autoimmune disease that occurs as a result of the failure of neuromuscular transmission and is characterized by muscle weakness. There has been evidence on the correlations between the genetic predisposition of cytotoxic T lymphocyte and the antigen-4 (CTLA-4) and MG. Thus, the present study was conducted to study is designed to examine the effects of CTLA-4 methylation on the pathogenesis of MG and the expressions of related cytokines. METHODS: The CTLA-4 methylation levels in peripheral blood were quantified in 103 samples collected from MG patients and 86 samples from healthy individiuals. The expression of serum-related cytokines as well as the Treg cell ratio were examined so as to define the contributory role of CTLA-4 methylation in MG and to identify the interaction between CTLA-4 methylation and related factors, the expressions of DNA methyltransferase (DNMT)l, DNMT3A and DNMT3B, CTLA-4, AchR-Ab, Titin-Ab, RyR-Ab, IL-2, IL-10, IFN-γ, and TGF-ß, activity of P- acetylcholinesterase (AchE) and E-AchE. RESULTS: The results indicated that the incidence of CTLA-4 methylation was significantly higher in the control group when compared with the MG group, and CTLA-4 methylation was also found to be associated with the thymus status of MG patients. It was also observed from the experiment data that the expressions of DNMTl, DNMT3A, and DNMT3B, along with the expressions of AchR-Ab, Titin-Ab, RyR-Ab, IL-2, IL-10, IFN-γ and TGF-ß, and the activity of P-AchE and E-AchE were all higher in the MG group than in the control group, with a reduction of CTLA-4 expression. Another key finding from this study revealed that methylation interference can lead to the suppression in the expression of AchR-Ab, the activity of E-AchE, the expression of IL-2, IL-10, IFN-γ, and TGF-ß and the Treg cell ratio in lymphocytes. CONCLUSION: In conclusion, the results obtained from the present study highly indicated that CTLA-4 methylation might play a role in facilitating the occurrence of MG and increasing the expressions of related cytokines through the upregulation of AchR-Ab and E-Ach.

GLRB variants regulate nearby gene expression in human brain tissues.

A recent genome-wide association study (GWAS) identified four genetic variants rs78726293, rs191260602, rs17035816 and rs7688285 in GLRB gene to be associated with panic disorder (PD) risk. In fact, GWAS is an important first step to investigate the genetics of human complex diseases. In order to translate into opportunities for new diagnostics and therapies, we must identify the genes perturbed by these four variants, and understand how these variant functionally contributes to the underlying disease pathogenesis. Here, we investigated the effect of these four genetic variants and the expression of three nearby genes including PDGFC, GLRB and GRIA2 in human brain tissues using the GTEx (version 6) and Braineac eQTLs datasets. In GTEx (version 6) dataset, the results showed that both rs17035816 and rs7688285 variants could significantly regulate PDGFC and GLRB gene expression. In Braineac dataset, the results showed that rs17035816 variant could significantly regulate GLRB and GRIA2 gene expression. We believe that these findings further provide important supplementary information about the regulating mechanisms of rs17035816 and rs7688285 variants in PD risk.

EXOC3L2 rs597668 variant contributes to Alzheimer's disease susceptibility in Asian population.

Recent genome-wide association studies have established the association between EXOC3L2 rs597668 variant and Alzheimer's disease (AD) in European population. However, recent studies reported inconsistent results in Asian population. Here, we performed a systematic review and meta-analysis to evaluate the impact of rs597668 on AD risk in Asian population using a total of 8686 samples including 2855 cases and 5831 controls. Meanwhile, we selected 17,008 AD cases and 37,154 controls in European population to evaluate the potential heterogeneity between East Asian and European populations. In East Asian population, we identified no potential heterogeneity with P=0.31 and I2 = 15.8%. By meta-analysis, we identified positive association between rs597668 and AD risk with P=0.023, OR=0.93, 95% CI 0.87-0.99. We further found significant heterogeneity in pooled Asian and European populations with P<0.0001 and I2 = 87.7%. The meta-analysis indicated negative association with P=0.66, OR=0.97, 95% CI 0.85-1.11. In summary, all these findings indicate that rs597668 C allele is a risk factor for AD in European population with OR=1.18 and P=2.49E-13. However the rs597668 C allele played a protective role in AD with OR=0.93 and P=0.023 in East Asian population.

Influence of serum adiponectin level and SNP +45 polymorphism of adiponectin gene on myocardial fibrosis.

Adiponectin plays an important role in the development of hypertension, atherosclerosis, and cardiomyocyte hypertrophy, but very little was known about the influence of serum adiponectin or the adiponectin gene polymorphism on myocardial fibrosis. Our study investigates the influence of the SNP +45 polymorphism of the adiponectin gene and serum levels of adiponectin on myocardial fibrosis in patients with essential hypertension. A case-control study was conducted on 165 hypertensive patients and 126 normotensive healthy controls. The genotypes of adiponectin gene polymorphisms were detected by the polymerase chain reaction (PCR) method. Serum concentrations of procollagen were measured by a double antibody sandwich enzyme-linked immunosorbent assay (ELISA) in all subjects. The integrated backscatter score (IBS) was measured in the left ventricular myocardium using echocardiography. The serum levels of adiponectin in hypertensive patients were significantly lower than those in the normal control group ((2.69±1.0) µg/ml vs. (4.21±2.89) µg/ml, respectively, P<0.001). The serum levels of type-I procollagen carboxyl end peptide (PICP) and type-III procollagen ammonia cardinal extremity peptide (PIIINP) in the hypertension group were significantly higher than those in the control group. In the hypertension group, serum levels of adiponectin were significantly and negatively related to the average acoustic intensity and corrected acoustic intensity of the myocardium (r=0.46 and 0.61, respectively, P<0.05 for both). The serum levels of PICP and PIIINP were significantly different among the three genotypes of SNP +45 (P<0.01). Logistic regression analyses showed that sex and genotype (GG+GT) were the major risk factors of myocardial fibrosis in hypertensive patients (OR=5.343 and 3.278, respectively, P<0.05). These data suggest that lower levels of adiponectin and SNP +45 polymorphism of the adiponectin gene are likely to play an important role in myocardial fibrosis in hypertensive patients.

[Three preparations of compound Chinese herbal medicines for de-adaptation to high altitude: a randomized, placebo-controlled trial].

BACKGROUND: With the increase of troops entering the plateau for a variety of missions, the occurrence of de-adaptation increased significantly when the army returned to the plains, however, until now, there has been no effective treatment for de-adaptation to high altitude. OBJECTIVE: To observe the interventional effects of compound Chinese herbal preparations (Sankang Capsule, Rhodiola Rosea Capsule and Shenqi Pollen Capsule) on de-adaptation to high altitude, and provide scientific evidence for appropriate treatment methods in the army health care for future missions. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A randomized, single-blind, placebo-controlled trial design was used. Soldiers of a returning army unit who exhibited de-adaptation response symptoms were selected for observation after participating in earthquake relief at high altitude. A total of 543 soldiers were divided into a Sankang Capsule group, a Rhodiola Rosea Capsule group, a Shenqi Pollen Capsule group and a placebo group for drug intervention and administered with corresponding drugs. The course of treatment was 15 days. A self-evaluation scale for de-adaptation to high altitude was used to measure the signs and symptoms exhibited by the soldiers. MAIN OUTCOME MEASURES: Effective rate of signs and symptoms of de-adaptation to high altitude was analyzed after a 15-day treatment and the differences of improvement rate of symptoms between groups were compared to evaluate the efficacy of the drugs. RESULTS: All three drugs improved the symptoms of de-adaptation to high altitude. Compared with the placebo group, symptoms of de-adaptation to high altitude in the drug-treated groups were remitted (P<0.05). Compared with placebo, Sankang Capsule mainly had well-marked effects on dizziness, fatigue, palpitations, cough, sputum and sore throat (P<0.05); Rhodiola Rosea Capsule significantly reduced the symptoms of fatigue, drowsiness, chest tightness, palpitations, vertigo, lack of attention and memory loss (P<0.05); Shenqi Pollen Capsule significantly reduced the symptoms of dizziness, fatigue, weakness, chest tightness, palpitations, cough, sputum, sore throat, memory loss, unresponsiveness and limb numbness (P<0.05). The symptom improvement rate of Shenqi Pollen Capsule was significantly higher than those of the other two drugs. CONCLUSION: All the three drugs played an evident role in ameliorating symptoms of de-adaptation, and the use of Shenqi Pollen Capsule was more effective than Rhodiola Rosea Capsule and Sankang Capsule.

Value of left ventricular regional ejection fraction determined by real-time three-dimensional echocardiography in diagnosis of aneurysm: compared with left ventriculography.

BACKGROUND: Regional ejection fraction (EF(R)) measured by real-time three-dimensional echocardiography (RT-3DE) provides a novel method for quantifying left-ventricular (LV) regional systolic function. We aimed to explore the diagnostic value of regional ejection fraction (EFR) derived from RT-3DE in detecting LV aneurysms in patients with myocardial infarction. METHODS: Thirty-eight patients with myocardial infarction were prospectively enrolled and underwent electrocardiography (ECG), two-dimensional echocardiography (2-DE), RT-3DE and left ventriculography (LVG). Subjects with a negative EFR in at least one segment on RT-3DE were considered as having a ventricular aneurysm. We compared the sensitivity, specificity, Youden's index, and positive and negative predictive values of ECG, 2-DE and RT-3DE in determining LV aneurysm with detection by LVG. RESULTS: On LVG an LV aneurysm was diagnosed in 16 (42.1%) patients. The sensitivity and specificity were 62.5% and 86.4% for ECG, 81.2% and 95.4% for 2-DE, and 100.0% and 90.9% for RT-3DE in diagnosing LV aneurysm. Youden's indexes for ECG, 2-DE and RT-3DE were 0.49, 0.77 and 0.91, respectively. Positive and negative predictive values were 76.9% and 76.0% for ECG, 92.9% and 87.5% for 2-DE, and 88.9% and 100.0% for RT-3DE. CONCLUSIONS: RT-3DE-derived EFR provides a novel, reliable index in the diagnosis of LV aneurysm and has excellent sensitivity and specificity.

Value of radiographic esophageal imaging in determining an optimal atrial septal puncture site for percutaneous balloon mitral valvuloplasty.

OBJECTIVE: To investigate the value of radiographic esophageal imaging in facilitating transseptal catheterization in patients undergoing percutaneous balloon mitral valvuloplasty. SUBJECTS AND METHODS: A total of 468 patients were randomized into either the study group (n = 234), in which radiographic esophageal imaging by the oral administration of a contrast media took place, or the control group (n = 234), in which the Ross technique was used. Of the 468 patients, 203 were males and 265 were females. The average ages of the study and control groups were 53 +/- 16 and 51 +/- 17 years, respectively. The patients had severe left atrial enlargement, as measured using 2-dimensional echocardiography. RESULTS: In the study group, the left atrial impression on the esophagus was clearly seen, and was used to identify the puncture site on the right atrial side for the passage of the transseptal catheter. In the control group, the left atrial silhouette was not clearly shown by fluoroscopy in 112 patients (47.5%). The success rate of transseptal catheterization in the study group was higher than in the control group (99.6 vs. 45.7%, p = 0.0001). There were no complications in the study group, but pericardial tamponade occurred in 1 patient in the control group. CONCLUSION: Radiographic esophageal imaging facilitates the identification of an optimal atrial transseptal puncture site, and improves the success rate of transseptal catheterization in patients undergoing percutaneous balloon mitral valvuloplasty.