Cofactor-independent phosphoglycerate mutase is an essential gene in procyclic form <Emphasis Type="Italic">Trypanosoma brucei</Emphasis>

Glycolysis and gluconeogenesis are, in part, driven by the interconversion of 3- and 2-phosphoglycerate (3-PG and 2-PG) which is performed by phosphoglycerate mutases (PGAMs) which can be cofactor dependant (dPGAM) or cofactor independent (iPGAM). The African trypanosome, Trypanosoma brucei, possesses the iPGAM form which is thought to play an important role in glycolysis. Here, we report on the use of RNA interference to down-regulate the T. brucei iPGAM in procyclic form T. brucei and evaluation of the resulting phenotype. We first demonstrated biochemically that depletion of the steady state levels of iPGM mRNA correlates with a marked reduction of enzyme activity. We further show that iPGAM is required for cell growth in procyclic T. brucei.     

Nerve reinnervation and itch behavior in a rat burn wound model

In this study, we investigated whether postburn itch in rats, after a full thickness burn, is correlated to the nervous reinnervation of the burn wound area. For this purpose, we determined scratching duration (expressed as second/hour) at 24 hours, 2, 4, 8, and 12 weeks postburn and combined this with immunohistochemistry for protein gene product 9.5 (PGP9.5) to identify all nerve fibers, calcitonin gene related peptide (CGRP) to identify peptidergic fibers, tyrosine hydroxylase (TH) for sympathetic fibers, and growth‐associated protein 43 (GAP‐43) for regrowing fibers. We found a modest, but highly significant, increase in scratching duration of all burn wound rats from 3 to 12 weeks postburn (maximally 63 ± 9.5 second/hour compared to sham 3.1 ± 1.4 second/hour at 9 weeks). At 24 hours postburn, all nerve fibers had disappeared from the burn area. Around 4 weeks postburn PGP 9.5‐ and CGRP‐immunoreactive nerve fibers returned to control levels. TH‐ and GAP‐43‐IR nerve fibers, which we found to be almost completely colocalized, did not regrow. No correlation was found between scratching duration and nervous reinnervation of the skin. The present results suggest that in rat, like in human, burn wound healing will induce increased scratching, which is not correlated to the appearance of nervous reinnervation.     

Performance of creatinine- or cystatin C–based equations to estimate glomerular filtration rate in sub-Saharan African populations

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吗替麦考酚酯治疗系统性红斑狼疮的多中心前瞻性研究

目的观察吗替麦考酚酯(骁悉)治疗系统性红斑狼疮的疗效及安全性.方法通过观察治疗前后狼疮病情活动指数(SLEDAI)、24小时尿蛋白定量等指标的变化,对比分析骁悉与环磷酰胺的疗效和安全性.结果68例SIE患者完成为期6个月的研究,骁悉组36例,CTX组32例,骁悉组SLEDAI由治疗前的20.4±8.0减少至治疗后3.8±3.1(P＜0.01).CTX组由20.6±6.1减少至7.4±8.2(p＜0.01).治疗后两组对比实验组改善较对照组明显(P＜0.01).24小时尿蛋白的变化骁悉组由3.2土2.7g降至1.1±1.1g(p＜0.01).CTX组由2.6±2.4g降至1.3±1.4g(p＜0.01).治疗后两组对比无明显差别(p＞0.05).总有效率骁悉组为97.2%(35/36),CTX组为93.8%(30/32)(P＞0.05).骁悉组的副作用发生率为22.2%(8/36),CTX组为69.7%(23/33)(p＜0.05).结论骁悉作为一种免疫抑制剂治疗SLE和CTX一样有效,并且安全性更高,对于CTX无效的患者亦有效.     

The interaction of stem cells and vascularity in peripheral nerve regeneration

The degree of nerve regeneration after peripheral nerve injury can be altered by the microenvironment at the site of injury. Stem cells and vascularity are postulated to be a part of a complex pathway that enhances peripheral nerve regeneration; however, their interaction remains unexplored. This review aims to summarize current knowledge on this interaction, including various mechanisms through which trophic factors are promoted by stem cells and angiogenesis. Angiogenesis after nerve injury is stimulated by hypoxia, mediated by vascular endothelial growth factor, resulting in the growth of preexisting vessels into new areas. Modulation of distinct signaling pathways in stem cells can promote angiogenesis by the secretion of various angiogenic factors. Simultaneously, the importance of stem cells in peripheral nerve regeneration relies on their ability to promote myelin formation and their capacity to be influenced by the microenvironment to differentiate into Schwann-like cells. Stem cells can be acquired through various sources that correlate to their differentiation potential, including embryonic stem cells, neural stem cells, and mesenchymal stem cells. Each source of stem cells serves its particular differentiation potential and properties associated with the promotion of revascularization and nerve regeneration. Exosomes are a subtype of extracellular vesicles released from cell types and play an important role in cell-to-cell communication. Exosomes hold promise for future transplantation applications, as these vesicles contain fewer membrane-bound proteins, resulting in lower immunogenicity. This review presents pre-clinical and clinical studies that focus on selecting the ideal type of stem cell and optimizing stem cell delivery methods for potential translation to clinical practice. Future studies integrating stem cell-based therapies with the promotion of angiogenesis may elucidate the synergistic pathways and ultimately enhance nerve regeneration.