Influence of ischemia before vein grafting on early hyperplasia of the graft and the dynamic changes of the intima after grafting

BACKGROUND: To investigate both the influence of ischemia before grafting on early hyperplasia of the vein grafts, and the dynamic changes of the intima after grafting in a rabbit model of vein graft disease. METHODS: We performed paired vein graft experiments under different ischemic conditions (15 vs. 60 min; 15 vs. 90 min) in the neck of the rabbits and compared the differences between the grafts. Clopidogrel, an anti-platelet agent, was administered before and after surgery. Twenty-eight days after the grafting procedure, the veins were evaluated microscopically. The dynamic changes of the intima after grafting were evaluated by scanning electron microscopy over time. RESULTS: The vein grafts subjected to 60- or 90-min ischemia exhibited no differences compared to those subjected to 15-min ischemia in terms of the mean thickness of the intimal, medial, and adventitial layers of the graft. Similarly, there was no difference in the Ki-67 labeling index (proliferation marker) between the vein grafts. Vein grafts with 15-min ischemia lost endothelial cells (ECs) but healed by 3 days post graft, whereas vein grafts with 90-min ischemia suffered serious EC loss, which was restored with new ECs during days 2 to 14 post graft. CONCLUSIONS: Ninety-minute ischemia before vein grafting can cause serious EC loss, but does not increase early intimal hyperplasia when clopidogrel is administered. Protecting the vein from ischemia and reperfusion injury preserves ECs

Detection of copy number variations and their effects in Chinese bulls

BACKGROUND: Copy number variations (CNVs) are a main source of genomic structural variations underlying animal evolution and production traits. Here, with one pure-blooded Angus bull as reference, we describe a genome-wide analysis of CNVs based on comparative genomic hybridization arrays in 29 Chinese domesticated bulls and examined their effects on gene expression and cattle growth traits. RESULTS: We identified 486 copy number variable regions (CNVRs), covering 2.45% of the bovine genome, in 24 taurine (Bos taurus), together with 161 ones in 2 yaks (Bos grunniens) and 163 ones in 3 buffaloes (Bubalus bubalis). Totally, we discovered 605 integrated CNVRs, with more “loss” events than both “gain” and “both” ones, and clearly clustered them into three cattle groups. Interestingly, we confirmed their uneven distributions across chromosomes, and the differences of mitochondrion DNA copy number (gain: taurine, loss: yak & buffalo). Furthermore, we confirmed approximately 41.8% (253/605) and 70.6% (427/605) CNVRs span cattle genes and quantitative trait loci (QTLs), respectively. Finally, we confirmed 6 CNVRs in 9 chosen ones by using quantitative PCR, and further demonstrated that CNVR22 had significantly negative effects on expression of PLA2G2D gene, and both CNVR22 and CNVR310 were associated with body measurements in Chinese cattle, suggesting their key effects on gene expression and cattle traits. CONCLUSIONS: The results advanced our understanding of CNV as an important genomic structural variation in taurine, yak and buffalo. This study provides a highly valuable resource for Chinese cattle’s evolution and breeding researches. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-480) contains supplementary material, which is available to authorized users

The Efficacy of Acupuncture on Anthropometric Measures and the Biochemical Markers for Metabolic Syndrome: A Randomized Controlled Pilot Study

Background. Many previous studies have shown the potential therapeutic effect of acupuncture for metabolic syndrome (MetS). However, most of these studies were limited by short durations of observation and a lack of sham acupuncture as control. We designed a randomized controlled trial, used sham acupuncture as the control, and evaluated the efficacy over 12 weeks of treatment and 12 weeks of follow-up. Methods/Design. The study was designed as a multicentre, parallel-group, randomized, double-blinded trial. 40 patients were randomly assigned to two groups: treatment group (treated with acupuncture) and control group (treated with sham acupuncture). Outcomes were measured at 4, 8, and 12 weeks and 3 months after treatment. Results. 33 participants (17 in acupuncture group and 16 in control group) completed the treatment and the follow-up. Decreases from baseline in mean waist circumference (WC) and weight at the end of treatment were 4.85 cm (95% CI [2.405,5.595]) and 4.00 kg (95% CI [1.6208,4.4498]) in acupuncture group and 1.62 cm and 1.64 kg in control group (P<0.01). The changes in mean glycosylated haemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), and blood pressure in acupuncture group were greater than the changes in control group (P<0.05, P<0.01). Conclusion. Acupuncture decreases WC, HC, HbA1c, TG, and TC values and blood pressure in MetS

In Silico Identification of Structure Requirement for Novel Thiazole and Oxazole Derivatives as Potent Fructose 1,6-Bisphosphatase Inhibitors

Fructose 1,6-bisphosphatase (FBPase) has been identified as a drug discovery target for lowering glucose in type 2 diabetes mellitus. In this study, a large series of 105 FBPase inhibitors were studied using a combinational method by 3D-QSAR, molecular docking and molecular dynamics simulations for a further improvement in potency. The optimal 3D models exhibit high statistical significance of the results, especially for the CoMFA results with rncv2, q2 values of 0.986, 0.514 for internal validation, and rpred2, rm2 statistics of 0.902, 0.828 statistics for external validation. Graphic representation of the results, as contoured 3D coefficient plots, also provides a clue to the reasonable modification of molecules. (1) Substituents with a proper length and size at the C5 position of the thiazole core are required to enhance the potency; (2) A small and electron-withdrawing group at the C2 position linked to the thiazole core is likely to help increase the FBPase inhibition; (3) Substituent groups as hydrogen bond acceptors at the C2 position of the furan ring are favored. In addition, the agreement between 3D-QSAR, molecular docking and molecular dynamics simulation proves the rationality of the developed models. These results, we hope, may be helpful in designing novel and potential FBPase inhibitors

Attenuation of epigenetic regulator SMARCA4 and ERK-ETS signaling suppresses aging-related dopaminergic degeneration

How complex interactions of genetic, environmental factors and aging jointly contribute to dopaminergic degeneration in Parkinson's disease (PD) is largely unclear. Here, we applied frequent gene co‐expression analysis on human patient substantia nigra‐specific microarray datasets to identify potential novel disease‐related genes. In vivo Drosophila studies validated two of 32 candidate genes, a chromatin‐remodeling factor SMARCA4 and a biliverdin reductase BLVRA. Inhibition of SMARCA4 was able to prevent aging‐dependent dopaminergic degeneration not only caused by overexpression of BLVRA but also in four most common Drosophila PD models. Furthermore, down‐regulation of SMARCA4 specifically in the dopaminergic neurons prevented shortening of life span caused by α‐synuclein and LRRK2. Mechanistically, aberrant SMARCA4 and BLVRA converged on elevated ERK‐ETS activity, attenuation of which by either genetic or pharmacological manipulation effectively suppressed dopaminergic degeneration in Drosophila in vivo. Down‐regulation of SMARCA4 or drug inhibition of MEK/ERK also mitigated mitochondrial defects in PINK1 (a PD‐associated gene)‐deficient human cells. Our findings underscore the important role of epigenetic regulators and implicate a common signaling axis for therapeutic intervention in normal aging and a broad range of age‐related disorders including PD

An Imperfect Repair Model with Delayed Repair under Replacement and Repair Thresholds

Based on the extended geometric process, a repair replacement model of a degradation system is studied, in which the delayed repair time depends on the working time after the last repair. Replacement and repair thresholds describe when the system will be replaced and when the system can be repaired, respectively. Two kinds of replacement policies are studied. One policy is jointly determined by the moment of the Nth failure and the first hitting time of the working time after the last repair for the replacement threshold, and the system is replaced, whichever occurs first; the other is the special case of the first policy, and the system is replaced when the working time after the last repair first hits the replacement threshold. The exact expressions of the long-run average cost rate are obtained. The optimal policies exist and can be ascertained by numerical methods. Finally, numerical examples are presented to demonstrate the application of the results obtained in the paper

Current Research Status of Azaspiracids

The presence and impact of toxins have been detected in various regions worldwide ever since the discovery of azaspiracids (AZAs) in 1995. These toxins have had detrimental effects on marine resource utilization, marine environmental protection, and fishery production. Over the course of more than two decades of research and development, scientists from all over the world have conducted comprehensive studies on the in vivo metabolism, in vitro synthesis methods, pathogenic mechanisms, and toxicology of these toxins. This paper aims to provide a systematic introduction to the discovery, distribution, pathogenic mechanism, in vivo biosynthesis, and in vitro artificial synthesis of AZA toxins. Additionally, it will summarize various detection methods employed over the past 20 years, along with their advantages and disadvantages. This effort will contribute to the future development of rapid detection technologies and the invention of detection devices for AZAs in marine environmental samples