- 作者列表："Peng Q","Ding R","Wang X","Yang P","Jiang F","Chen X
BACKGROUND:Irisin has been considered a prognostic factor in several cardiovascular diseases. Nevertheless, no data are available on the role of irisin in cardiac remodeling. AIM OF THE STUDY:This study aimed to determine the potential role of irisin in cardiac remodeling and explore potential mechanisms. METHODS:A total of 40 rats that underwent transverse abdominal aortic constriction (TAC) surgery or sham operation were divided into four groups: sham + saline (NS), sham + irisin, TAC + NS, and TAC + irisin. After 6 weeks of treatment, echocardiography was performed to assess in vivo cardiac morphology. The left ventricular myocardium was prepared and observed by pathological examination. The effect of irisin on cardiomyocyte apoptosis and the expression of oxidative stress and cardiac hypertrophy markers were observed. Then, the effect of irisin on the Akt signaling system was also detected. RESULTS:The rats in the TAC group displayed obvious signs of cardiac dysfunction and cardiac hypertrophy, and irisin treatment could reverse these changes. Irisin could inhibit the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 and xanthine oxidase in TAC rats and increase the expression of antioxidant enzymes. Furthermore, the expression of phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and phosphorylated glycogen synthase kinase 3β (p-GSK3β) was much higher in the cardiac remodeling groups (p <0.05 vs. sham rats). Irisin could relieve the inhibition effect and reduce the expression level of these three proteins. CONCLUSIONS:Irisin treatment could significantly improve cardiac remodeling by inhibiting oxidative stress via attenuating the Akt signaling activation.
背景: Irisin被认为是多种心血管疾病的预后因素。然而，没有关于irisin在心脏重塑中的作用的数据。 研究目的: 本研究旨在确定irisin在心脏重塑中的潜在作用并探讨潜在机制。 方法: 40只接受腹主动脉缩窄术 (TAC) 或假手术的大鼠分为4组: 假手术 + 生理盐水 (NS) 、假手术 + irisin、TAC + NS和TAC + irisin。治疗6周后，进行超声心动图以评估体内心脏形态。制备左心室心肌，并进行病理观察。观察irisin对心肌细胞凋亡及氧化应激和心肌肥厚标志物表达的影响。然后，还检测了irisin对Akt信号系统的影响。 结果: TAC组大鼠出现明显的心功能障碍和心肌肥厚征象，irisin治疗可逆转这些变化。Irisin可抑制TAC大鼠烟酰胺腺嘌呤二核苷酸磷酸氧化酶2和黄嘌呤氧化酶的表达，增加抗氧化酶的表达。此外，心脏重塑组中磷酸化蛋白激酶B (p-Akt) 、磷酸化哺乳动物雷帕霉素靶蛋白 (p-mTOR) 和磷酸化糖原合成酶激酶3β (p-GSK3β) 的表达明显高于假手术组 (p <0.05)。Irisin可以减轻抑制作用并降低这三种蛋白的表达水平。 结论: Irisin治疗可通过抑制Akt信号活化抑制氧化应激而显著改善心脏重构。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.