Thymol alleviates AGEs-induced podocyte injury by a pleiotropic effect via NF-κB-mediated by RhoA/ROCK signalling pathway

ABSTRACT

Advanced glycation end products (AGE) are those of the most powerful pathogenic factors that related to diabetic complications. In our study, we investigated the beneficial effects of thymol on AGE induced cell injury and apoptosis in human podocytes (HPCs) and attempted to clarify its mechanisms. Our results revealed that stimulation with AGE could significantly activate RhoA/NF-κB pathway. Results showed thymol could markedly suppress inflammatory responses, cell apoptosis and disordered cytoskeleton. Also thymol restored the expression of podocin, restrained migration capacity. Western blot analysis indicated that it could restore the expression of RhoA, ROCK and vimentin, nephrin, podocin and p65 and IκBα phosphorylation. Moreover, si-RhoA also suppressed the expression of pro-inflammatory cytokines, ROCK, and vimentin and the phosphorylation of p65 and IκBα. In conclusion, thymol inhibits AGE-induced cell injury in HPCs by suppressing the RhoA-NF-κB pathway and may be apromising therapeutic agent.     

Isolation and identification of sapotexanthin 5,6-epoxide and 5,8-epoxide from red mamey (Pouteria sapota)

Two new carotenoids, sapotexanthin 5,6-epoxide and sapotexanthin 5,8-epoxide, have been isolated from the ripe fruits of red mamey (Pouteria sapota). Sapotexanthin 5,6-epoxide was also prepared by partial synthesis via epoxidation of sapotexanthin, and the (5R,6S) and (5S,6R) stereoisomers were identified by high-performance liquid chromatography–electronic circular dichroism (HPLC-ECD) analysis. Spectroscopic data of the natural and semisynthetic derivatives obtained by acid-catalyzed rearrangement of cryptocapsin 5,8-epoxide stereoisomers were compared for structural elucidation.     

Recognition of gluconeogenic enzymes; Icl1, Fbp1, and Mdh2 by Gid4 ligase: A molecular docking study

The pro/N‐degron pathway is an evolved protein degradation pathway through the ubiquitin‐proteasome system. It is a vital pathway to attain protein homeostasis inside the liver cells with varying glucose levels. N‐terminal proline exists in more than 300 proteins in Saccharomyces cerevisiae, but only three of them are the gluconeogenic enzymes; isocitrate lyase (Icl1), fructose‐1,6‐bisphosphatase (Fbp1), and malate dehydrogenase (Mdh2). The present in silico study aims to structurally illustrate the binding of Icl1 enzyme to Gid4 ligase concerning its peers; Fbp1 and Mdh2. Based on the molecular docking scores and interactions, one can attribute the binding stability of Gid4 with degrons, to peptides of length six up to eight from the N‐terminal. Moreover, the percent change in the docking score provides a rationale for the unique Gid4‐Icl1^1‐4 interaction. The present study provides insights on the binding attitude of Gid4 ligase to degrons of different lengths, so one will consider in designing peptidomimetics to target Gid4 ligase.     

Cell-autonomous hepatic circadian clock regulates polyamine synthesis

Comment on: Atwood A, et al. Proc Natl Acad Sci U S A 2011; 108:18560-5.     

Human Fidgetin is a microtubule severing the enzyme and minus-end depolymerase that regulates mitosis

Fidgetin is a member of the AAA protein superfamily with important roles in mammalian development. Here we show that human Fidgetin is a potent microtubule severing and depolymerizing the enzyme used to regulate mitotic spindle architecture, dynamics and anaphase A. In vitro, recombinant human Fidgetin severs taxol-stabilized microtubules along their length and promotes depolymerization, primarily from their minus-ends. In cells, human Fidgetin targets to centrosomes, and its depletion with siRNA significantly reduces the velocity of poleward tubulin flux and anaphase A chromatid-to-pole motion. In addition, the loss of Fidgetin induces a microtubule-dependent enlargement of mitotic centrosomes and an increase in the number and length of astral microtubules. Based on these data, we propose that human Fidgetin actively suppresses microtubule growth from and attachment to centrosomes.     

DNA repair mechanisms in dividing and non-dividing cells

DNA damage created by endogenous or exogenous genotoxic agents can exist in multiple forms, and if allowed to persist, can promote genome instability and directly lead to various human diseases, particularly cancer, neurological abnormalities, immunodeficiency and premature aging. To avoid such deleterious outcomes, cells have evolved an array of DNA repair pathways, which carry out what is typically a multiple-step process to resolve specific DNA lesions and maintain genome integrity. To fully appreciate the biological contributions of the different DNA repair systems, one must keep in mind the cellular context within which they operate. For example, the human body is composed of non-dividing and dividing cell types, including, in the brain, neurons and glial cells. We describe herein the molecular mechanisms of the different DNA repair pathways, and review their roles in non-dividing and dividing cells, with an eye toward how these pathways may regulate the development of neurological disease.     

额底纵裂入路手术对鞍上第三脑室底垂体瘤的疗效分析

目的：分析经额底纵裂入路治疗鞍上第三脑室底垂体瘤的疗效,探讨其临床适用性。方法：选择从2011年1月~2013年1月与我院行额底纵裂入路手术治疗的30例鞍上第三脑室底垂体瘤的患者,术中行单侧额或双侧额弧形切口,根据术中所见肿瘤位置,由终板、视神经一颈内动脉等存在的生理间隙处切除肿瘤,观察所有患者的手术疗效。结果：所有患者术中可见肿瘤位于鞍内鞍上,部分或全部突入第三脑室底,其中有6例患者伴有脑积水。术中肿瘤全切23例,次全切5例,大部切除2例,无手术死亡病例。术前25例患者视力减退,术后23例患者视力均获得不同程度改善,仅1例暂无明显变化。术后19例出现电解质紊乱,患者经治疗后均已纠正;12例出现不同程度的尿崩症,给予患者药物治疗后,病情得到缓解。术后随访6个月,23例肿瘤全切患者病灶无复发,另外4例次全切者病灶也无明显变化,仅1例次全切和2例大部切除患者于术后行伽马刀再次治疗。结论：经额底纵裂入路治疗鞍上第三脑室底垂体瘤可以达到视野清晰,直观下进行肿瘤切除,手术效果好,并发症较少,适合临床长期推广应用。     

Transposable elements and human cancer: A causal relationship?

Transposable elements are present in almost all genomes including that of humans. These mobile DNA sequences are capable of invading genomes and their impact on genome evolution is substantial as they contribute to the genetic diversity of organisms. The mobility of transposable elements can cause deleterious mutations, gene disruption and chromosome rearrangements that may lead to several pathologies including cancer. This mini-review aims to give a brief overview of the relationship that transposons and retrotransposons may have in the genetic cause of human cancer onset, or conversely creating protection against cancer. Finally, the cause of TE mobility may also be the cancer cell environment itself.     

Characterization of the first adult de novo case of 46,X,der(Y)t(X;Y)(p22.3;q11.2)

Herein, we describe a case of an infertile man detected in postnatal diagnosis with FISH characterization and array-CGH used for genome-wide screening which allowed the identification of a complex rearrangement involving sex chromosomes, apparently without severe phenotypic consequences. The deletion detected in our patient has been compared with previously reported cases leading us to propose a hypothetical diagnostic algorithm that would be useful in similar clinical situations, with imperative multi disciplinary approach integrated with genetic counseling. Our patient, uniquely of reproductive age, is one of six reported cases of duplication of Xp22.3 (~ 8.4 Mb) segment and contemporary deletion of Yq (~ 42.9 Mb) with final karyotype as follows:

46,X,der(Y),t(X;Y)(Ypter → Yq11.221::Xp22.33 → Xpter).ish der(Y) (Yptel+,Ycen+,RP11-529I21+,RP11-506M9-Yqtel −,Xptel +). arrXp22.33p22.31(702–8,395,963, 8,408,289x1), Yq11.221q12 (14,569,317x1, 14,587,321–57,440,839x0)