The Roles of Hypoxia-Inducible Factors in Regulating Neural Stem Cells Migration to Glioma Stem Cells and Determinating Their Fates

The mortality of patients with malignant gliomas remains high despite the advancement in multi-modal therapy including surgery, radio- and chemotherapy. Glioma stem cells (GSCs), sharing some characteristics with normal neural stem cells (NSCs), contribute to the cellular origin for primary gliomas and the recurrence of malignant gliomas after current conventional therapy. Accordingly, targeting GSCs proves to be a promising avenue of therapeutic intervention. The specific tropism of NSCs to GSCs provides a novel platform for targeted delivery of therapeutic agents. Tropism and mobilization of NSCs are enhanced by hypoxia through upregulating chemotactic cytokines and activating several signaling pathways. Moreover, hypoxia-inducible factors (HIFs) produced under hypoxic microenvironment of the stem cell niche play critical roles in the growth and stemness phenotypes regulation of both NSCs and GSCs. However, the definite cellular and molecular mechanisms of HIFs involvement in the process remain obscure. In this review, we focus on the pivotal roles of HIFs in migration of NSCs to GSCs and potential roles of HIFs in dictating the fates of migrated NSCs and targeted GSCs.     

Characterization of fibroblasts recruited from bone marrow-derived precursor in neonatal bronchopulmonary dysplasia mice

We sought to determine whether the extrapulmonary origin of fibroblasts derived from bone marrow (BM) progenitor cells is essential to lung fibrosis in bronchopulmonary dysplasia (BPD). Neonate mice were durably engrafted with BM isolated from transgenic reporter mice that expressed green fluorescent protein (GFP). Such chimera mice were subjected to 60% O(2) exposure for 14 days. A large number of fibroblast-specific protein-1 (FSP1) and GFP-positive fibroblasts were identified in active fibrotic lesions. More surprisingly, however, FSP1(+) fibroblasts also arose in considerable numbers from BM-derived alveolar type II cells (AT2) through epithelial-mesenchymal transition (EMT) during lung fibrogenesis. Cultured lung fibroblasts could express the CXC chemokine receptor (CXCR4) and responded chemotactically to their cognate ligand, chemokine (C-X-C motif) ligand 12 (CXCL12), which were elevated in the serum of BPD mice. These data suggest that lung fibroblasts in BPD fibrosis could variably arise from BM progenitor cells. This finding, which suggests the pathophysiological process of fibrosis, could contribute to a therapy for BPD that is characterized by extensive interstitial fibrosis.     

三种不同方法固定的石蜡切片中RNA的分析

研究在 10 %中性福尔马林、丙酮、甲醇 氯仿 冰醋酸 3种方法固定的石蜡切片中提取RNA的质量和数量 .取 2 5 0g体重的Wistar大鼠的肾脏 ,分别采用 10 %中性福尔马林、丙酮、甲醇 氯仿 冰醋酸 3种方法固定 ,石蜡包埋 ,H E染色 ;采用RNA裂解液、TRIZOL试剂 2种方法提取切片RNA ,逆转录为cDNA ,采用普通PCR和SYBRGREEN 1定量PCR分析RNA质量和数量 .结果表明 ,3种固定方法都可保持组织良好的结构和形态 ;采用 2种提取方法 ,均可经RT PCR扩增出 180bp大鼠磷酸甘油醛脱氢酶 (G3PDH)、5 6 5bpβ肌动蛋白 (β actin)、10 0bp纤溶酶系活化剂抑制物 1(PAI 1) ;但采用RNA裂解液时 ,比TRIZOL试剂可提取更多的RNA .     

Relationships between musk extraction, social rank and tail-rubbing in male Alpine musk deer, Moschus sifanicus

Musk deer (Moschus spp.) are small, solitary forest ruminants well-known for the musk secreted by adult males. Because of illegal hunting and habitat degradation and loss, the five species of musk deer are classified as endangered. Musk deer farming has been a positive example of ex situ conservation, maintaining deer numbers whilst sustaining musk production. This study was conducted at the Xinglongshan Musk Deer Farm in Gansu Province in northwest China, and was designed to explore the relationships among musk extraction, fighting ability and social rank in captive, male alpine musk deer (Moschus sifanicus). Results showed that musk production was related to a male’s rank in the dominance hierarchy. Males in the middle rank of the dominance hierarchy tended to produce more musk than deer of higher and lower ranks. This is due to the time-energy budgeting patterns and captive stress of males with different status in the dominance hierarchy. That is, high-ranking males need to budget more time and energy to maintain their higher rank, while low-ranking males are exposed to more aggression from higher-ranking individuals, thus limiting their access to resources such as food and shelter. Accordingly, high-ranking and low-ranking males endured more stress than middle-ranking males, negatively affecting their annual musk production. Supporting the correlation between musk production and the frequency of tail-rubbing behavior was not significant, average musk extraction could not be predicted based on the frequency of tail-rubbing alone. Status in the dominance hierarchy, however, was positively correlated with tail-rubbing frequency, with males of higher rank tending to tail-rub more frequently. Conflict winners tended to initiate tail-rubbing after the conflict; tail-rubbing accounted for 83.33% of the post-conflict behavior expressed by the winner. Tail-rubbing was one of the behavioral rewards of winning a conflict and was also related to releasing aggression; not solely for scent marking territory and trails. Based on the results of this study, there was no direct relationship between musk production and captive males’ status in the dominance hierarchy (and, therefore, in the intensity of aggression displayed). If the sole aim of musk deer farms is to domesticate musk deer for maximum production of musk, we suggest that highly aggressive males be removed from the population. Musk production will remain unchanged, however, aggression level and intensity of fighting could be lessened thus reducing farming costs.     

Miniaturized lensless imaging systems for cell and microorganism visualization in point-of-care testing

Low-cost, robust, and user-friendly diagnostic capabilities at the point-of-care (POC) are critical for treating infectious diseases and preventing their spread in developing countries. Recent advances in micro- and nanoscale technologies have enabled the merger of optical and fluidic technologies (optofluidics) paving the way for cost-effective lensless imaging and diagnosis for POC testing in resource-limited settings. Applications of the emerging lensless imaging technologies include detecting and counting cells of interest, which allows rapid and affordable diagnostic decisions. This review presents the advances in lensless imaging and diagnostic systems, and their potential clinical applications in developing countries. The emerging technologies are reviewed from a POC perspective considering cost effectiveness, portability, sensitivity, throughput and ease of use for resource-limited settings.