Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

Fatigue analysis of restored teeth longitudinally cracked under cyclic loading

ObjectiveTo investigate the fatigue behavior of restored teeth, in particular the mechanisms of longitudinal dentinal cracking under cyclic mechanical loading, using finite element analysis (FEA) and the stress-life (S-N) approach.MethodsTen root-filled premolars restored with resin composites were subjected to step-stress cyclic loading to produce longitudinal cracks. Fracture loads and number of cycles completed at each load level were recorded. FEA was used to predict the stress amplitude of each component under the global cyclic load. Both intact and debonded conditions were considered for the dentin-composite interface in the FEA. The predicted stress concentrations were compared with the fracture patterns to help elucidate the failure mechanisms. The S-N approach was further used to predict the lifetimes of the different components in the restored teeth. Cumulative fatigue damage was represented by the sum of the fractions of life spent under the different stress amplitudes.ResultsLongitudinal cracks were seen in ~50% of the samples with a mean fracture load of 770 ± 45 N and a mean number of cycles to failure of 32,297 ± 12,624. The longitudinal dentinal cracks seemed to start near the line angle of the cavity, and propagated longitudinally towards the root. The sum of fractions of life spent for the dentin-composite interface exceeded 1 after ~7000 cycles when that for dentin was much lower than 1, indicating that interfacial debonding would occur prior to dentin fracture. This was supported by micro-CT images showing widened interfacial space in the cracked samples. In the debonded tooth, FEA showed dentinal stress concentrations at the gingival wall of the cavity, which coincided with the longitudinal cracks found in the cyclic loading test. The sum of fractions of life spent for dentin was close to 1 at ~30,000 cycles, similar to the experimental value.SignificanceDebonding of the dentin-composite interface may occur prior to longitudinal cracking of dentin in root-filled teeth under cyclic loading. The approximate time of occurrence for these events could be estimated using fatigue analysis with stresses provided by FEA. This methodology can therefore be used to evaluate the longevity of restoration designs for root-filled teeth.     

Sickle cell nephropathy: A review of novel biomarkers and their potential roles in early detection of renal involvement

Whether the underlying mutations are homozygous, heterozygous, or co-inherited with other hemoglobinopathies, sickle cell disease is known to afflict the kidneys, leading to the clinical entity known as sickle cell nephropathy (SCN). Although common, SCN remains diagnostically elusive. Conventional studies performed in the context of renal disorders often fail to detect early stage SCN. This makes the quest for early diagnosis and treatment more challenging, and it increases the burden of chronic kidney disease-related morbidity among patients. Novel diagnostic tools have been employed to overcome this limitation. In this study, we discuss various biomarkers of SCN, including those employed in clinical practice and others recently identified in experimental settings, such as markers of vascular injury, endothelial dysfunction, tubulo-glomerular damage, and oxidative stress. These include kidney injury molecule-1, monocyte chemoattractant protein-1, N-acetyl-B-D-glucosaminidase, ceruloplasmin, orosomucoid, nephrin, and cation channels, among others. Furthermore, we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome. We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers. Finally, we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits, with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.     

有限元法生物力学分析在青少年特发性脊柱侧凸治疗及病因研究中的应用

青少年特发性脊柱侧凸发病率较高且病情复杂,对青少年身心健康可造成显著影响,但其因病因不明,临床尚未形成治疗共识。近年来基于患者医学影像进行仿真建模的有限元法生物力学分析在青少年特发性脊柱侧凸治疗及其病因研究中已经有了一系列的应用。本文即从非手术治疗、手术治疗、病因研究、现有局限等角度对有限元法生物力学分析在青少年特发性脊柱侧凸中的应用进行综述,以期为临床实践及相关研究提供参考。     

靶向MLL1-WDR5蛋白-蛋白相互作用抑制剂的研究进展

Mixed lineage leukemia 1(MLL1)是组蛋白甲基转移酶SET家族的成员之一。MLL1与WDR5、RbBP5、Ash2L和DPY-30组成MLL1甲基转移酶复合物调控组蛋白H3的第4位赖氨酸的甲基化水平，对造血系统的发育和血细胞的更新至关重要。部分白血病患者体内存在因MLL1基因易位而产生的致癌蛋白——MLL1融合蛋白，MLL1融合蛋白在发挥其致癌作用时需要功能完整的MLL1酶复合物，故靶向MLL1-WDR5的蛋白-蛋白相互作用成为治疗MLL1融合型白血病的潜在策略。本文对MLL1-WDR5蛋白-蛋白相互作用的生物学机制、结构信息以及抑制剂进行了系统的总结，并结合已报道数据对该领域进行了展望，以期为后续研究提供参考。