Wnt signaling pathway in aging-related tissue fibrosis and therapies

Fibrosis is the final hallmark of pathological remodeling, which is a major contributor to the pathogenesis of various chronic diseases and aging-related organ failure to fully control chronic wound-healing and restoring tissue function. The process of fibrosis is involved in the pathogenesis of the kidney, lung, liver, heart and other tissue disorders. Wnt is a highly conserved signaling in the aberrant wound repair and fibrogenesis, and sustained Wnt activation is correlated with the pathogenesis of fibrosis. In particular, mounting evidence has revealed that Wnt signaling played important roles in cell fate determination, proliferation and cell polarity establishment. The expression and distribution of Wnt signaling in different tissues vary with age, and these changes have key effects on maintaining tissue homeostasis. In this review, we first describe the major constituents of the Wnt signaling and their regulation functions. Subsequently, we summarize the dysregulation of Wnt signaling in aging-related fibrotic tissues such as kidney, liver, lung and cardiac fibrosis, followed by a detailed discussion of its involvement in organ fibrosis. In addition, the crosstalk between Wnt signaling and other pathways has the potential to profoundly add to the complexity of organ fibrosis. Increasing studies have demonstrated that a number of Wnt inhibitors had the potential role against tissue fibrosis, specifically in kidney fibrosis and the implications of Wnt signaling in aging-related diseases. Therefore, targeting Wnt signaling might be a novel and promising therapeutic strategy against aging-related tissue fibrosis.     

RGC-32与细胞周期调控

RGC-32(response gene to complement-32)是一种重要的补体应答分子,同时也参与了许多其他生物学功能.近来的研究发现RGC-32为细胞周期G2/M检测点关键调控分子,在细胞周期精细调控过程中发挥重要作用,并参与细胞增殖分化、再生修复、炎症反应、肿瘤形成等多种生物学过程.但RGC-32对细胞周期确切的调控机制有待阐明.该文就RGC-32基因及其生物学功能、细胞周期调控以及两者之间的调控关系等作一简要综述.     

Polymorphism in miRNA-1 target site and circulating miRNA-1 phenotype are associated with the decreased risk and prognosis of coronary artery disease

MiRNA molecules have been identified to play key roles in a broad range of physiologic and pathologic processes. Polymorphisms in microRNA target sites (PolymiRTSs) can disturb or obstruct miRNA binding and consequentially influence regulation of the target genes. A two-step study design was used in this study. A case-control study was designed to assess the relationship between miRNA-1 target site rs9548934C→T polymorphism in target gene (Component of Oligomeric Golgi Complex 6, COG6) and risk of coronary artery disease (CAD) in 1013 patients and 610 normal controls. This genetic variant was also evaluated for the association with major adverse cardiovascular events (MACE) of CAD in a follow-up study, including 785 (785/1013) patients followed up for 42 months. The phenotypes of circulating miRNA-1 levels in 34 cases were slightly lower than that of 40 controls but not significantly different (P = 0.090). The CT and CT/TT genotypes were associated with a 34% and 26% decreased risk of CAD, and the TT and CT/TT genotypes were associated with a 76% and 49% decreased risk of MACE of CAD. Cox regression analysis showed that rs9548937 C/T variant was associated with a decreased risk of MACE, while age, diabetes mellitus, higher levels of CRP (≥ 3.80 mg/L) and three pathological changes in the coronary artery were associated with an increased risk of MACE. Our findings implicate miRNA-1 target site rs9548934C→T genotypes, circulating miRNA-1 phenotype and CRP levels may modulate the occurrence and MACE of CAD.     

水凝胶负载pVAX1-SpaP/P防龋DNA疫苗以4种途径产生免疫效应

背景:防龋DNA疫苗价格低廉、安全有效,有望成为人类抵抗龋病的重要手段,因而学者在寻找一种能高效诱导抗体产生的免疫途径或保护疫苗效价的缓释系统及佐剂,成为近年研究的热点.目的:观察聚乳酸乙醇酸-聚乙二醇-聚乳酸乙醇酸水凝胶负载pVAX1-SpaP/P防龋基因疫苗的免疫效应.方法:以聚乳酸乙醇酸-聚乙二醇-聚乳酸乙醇酸水...     

Dual Pallidal and Thalamic Deep Brain Stimulation for Complex Ipsilateral Dystonia

PurposeGlobus pallidus pars interna (GPi) has become an established target for deep brain stimulation (DBS) in dystonia. Previous studies suggest that targeting the ventralis oralis (Vo) complex nucleus improves dystonic tremor or even focal dystonia. Research has also demonstrated that multi-target DBS shows some benefits over single target DBS. In this study, we reviewed patients who had undergone unilateral DBS targeting the GPi and Vo.Materials and MethodsFive patients diagnosed with medically refractory upper extremity dystonia (focal or segmental) underwent DBS. Two DBS electrodes each were inserted unilaterally targeting the ipsilateral GPi and Vo. Clinical outcomes were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Disability Rating Scale.ResultsBFMDRS scores decreased by 55% at 1-month, 56% at 3-month, 59% at 6-month, and 64% at 12-month follow up. Disability Rating Scale scores decreased 41% at 1-month, 47% at 3-month, 50% at 6-month, and 60% at 12-month follow up. At 1 month after surgery, stimulating both targets improved clinical scores better than targeting GPi or Vo alone.ConclusionUnilateral thalamic and pallidal dual electrode DBS may be as effective or even superior to DBS of a single target for dystonia. Although the number of patients was small, our results reflected favorable clinical outcomes.     

丙泊酚-舒芬太尼TCI全凭静脉麻醉用于非停跳冠脉搭桥手术的可行性和剂量探讨

靶控输注(TCI)已是一种较为成熟的全凭静脉麻醉(TIVA)技术,但针对冠脉搭桥手术(CABG)这一特殊群体的实际应用方面的观察研究尚不多。效应室靶浓度(Ce)的TCI调控更为快速有效,但血浆药物浓度有短时间的超高,对循环的稳定可能不利。目前用吸盘固定局部心肌行非停跳冠脉搭桥手术的     

Olea europea L. Leaves and Hibiscus sabdariffa L. Petals Extracts: Herbal Mix from Cardiovascular Network Target to Gut Motility Dysfunction Application

It is well known that diet and nutrition play a critical role in the etiopathogenesis of many disorders. On the other hand, nutrients or bioactive compounds can specifically target and control various aspects of the mechanism underlying the pathology itself, and, in this context, diseases related to intestinal motility disorders stand out. The Herbal Mix (HM) consisting of Olea europea L. leaf (OEE) and Hibiscus sabdariffa L. (HSE) extracts (13:2) has been proven to be a promising nutraceutical option for many diseases, but its potential in inflammatory-driven gastrointestinal disorders is still unexplored. In this study, HM effects on guinea-pig ileum and colon contractility (induced or spontaneous) and on human iNOS activity, as well as on human colorectal adenocarcinoma Caco-2 cells, were studied. Results showed that the HM can control the ileum and colon contractility without blocking the progression of the food bolus, can selectively inhibit iNOS and possesses a strong pro-apoptotic activity towards Caco-2 cells. In conclusion, the present results suggest that, in some diseases, such as those related to motility disorders, an appropriate nutritional approach can be accompanied by a correct use of nutraceuticals that could help not only in ameliorating the symptoms but also in preventing more severe, cancer-related conditions.