Cognitive functions such as working memory and psychomotor function are impaired during chronic high-altitude exposure. The putamen may play an important role in chronic hypoxia-induced cognitive impairment. Hum Brain Mapp 38:3865-3877, 2017. © 2017 Wiley Periodicals, Inc.

Exosomes, microvesicles, and other extracellular vesicles are released by many cell types, including cancer cells and cancer-related immune cells. Extracellular vesicles can directly or indirectly facilitate the transfer of bioinformation to recipient cells or to the extracellular environment. In cancer, exosomes have been implicated in tumor initiation, proliferation, and metastasis. Extracellular vesicles can transmit proteins and nucleic acids that participate in DNA methylation, histone modification, and posttranscriptional regulation of RNA. Factors transmitted by extracellular vesicles reflect the donor cell status, and extracellular vesicles derived from tumor cells may be also responsible for altering expression of tumor promoting and tumor suppressing genes in recipient cells. Thus, circulating extracellular vesicles may act as biomarkers of cancer, and detection of these biomarkers may be applied to diagnosis or assessment of prognosis in patients with cancer.

Children are known to be venerable to lead (Pb) toxicity. The blood-brain barrier (BBB) in immature brain is particularly vulnerable to Pb insults. This study was designed to test the hypothesis that Pb exposure damaged the integrity of the BBB in young animals and iron (Fe) supplement may prevent against Pb-induced BBB disruption. Male weanling Sprague-Dawley rats were divided into four groups. Three groups of rats were exposed to Pb in drinking water containing 342 μg Pb/mL as Pb acetate, among which two groups were concurrently administered by oral gavage once every other day with 7 mg Fe/kg and 14 mg Fe/kg as FeSO 4 solution as the low and high Fe treatment group, respectively, for 6 weeks. The control group received sodium acetate in drinking water. Pb exposure significantly increased Pb concentrations in blood by 6.6-folds (p<0.05) and brain tissues by 1.5-2.0-folds (p<0.05) as compared to controls. Under the electron microscope, Pb exposure in young animals caused an extensive extravascular staining of lanthanum nitrate in brain parenchyma, suggesting a leakage of cerebral vasculature. Western blot showed that Pb treatment led to 29-68% reduction (p<0.05) in the expression of occludin as compared to the controls. Fe supplement among Pb-exposed rats maintained the normal ultrastructure of the BBB and restored the expression of occludin to normal levels. Moreover, the low dose Fe supplement significantly reduced Pb levels in blood and brain tissues. These data suggest that Pb exposure disrupts the structure of the BBB in young animals. The increased BBB permeability may facilitate the accumulation of Pb. Fe supplement appears to protect the integrity of the BBB against Pb insults, a beneficial effect that may have significant clinical implications.

No abstract

Summary Introduction Astrocytoma is among the most common intracranial tumors and radiotherapy is typically used after its resection. One of the outstanding problems encountered in the treatment is radioresistance. The lack of efficient biomarkers for evaluating the radiosensitivity of glioma precludes advances in treatment of astrocytoma and remains the most fatal cancer. Methods To identify potential biomarkers for assessing the radioresistance of astrocytomas, the following study investigated the proteome of astrocytoma in surgical samples from 15 typical patients. The patients were divided into 2 groups: radioresistant vs. radiosensitive (controls). Proteome was assessed using two‐dimensional liquid chromatography tandem mass spectrometry (2D‐LC–MS/MS). Western blot was adopted to confirm the differential expression of proteins. Results A total of 36 proteins were expressed differently between the 2 groups, represented by cofilin‐1 and phosphoglycerate kinase 1 (PGK1), which up‐regulated significantly in radioresistant astrocytomas though there was no obvious morphological change of tumors. Western blot analysis revealed elevated levels of protein extracts in radioresistant astrocytomas compared with the radiosensitive group. Conclusions The results indicated cofilin‐1 enhances the motility of tumor cells which is important invasive potential of malignancy. PGK1 is metabolic enzyme and seems to be correlated with the negative prognosis following radiotherapy. Thus, cofilin‐1 and PGK1 might be involved in the radioresistant phenotype and are potential biomarkers for developing better therapeutic methods.

Background-Obesity and allergic diseases have increased dramatically in recent decades. While adiposity has been associated with asthma, associations with allergic sensitization have been inconsistent.

Neonatal hypoxia is the leading cause of brain damage with birth complications. Many studies have reported proliferation-promoting effect of mild hypoxia on neural stem cells (NSCs). However, how severe hypoxia influences the behavior of NSCs has been poorly explored. In the present study, we investigated the effects of 5, 3, and 1 % oxygen exposure on NSCs in vitro. MTT, neurosphere assay, and 5-ethynyl-2′-deoxyuridine (EdU) incorporation revealed a quick growth arrest of C17.2 cells and primary NSCs induced by 1 % oxygen exposure. Cell cycle analysis showed that this hypoxia exposure caused a significant increase of cells in G0/G1 phase and decrease of cells in S phase that is associated with decrease of Cyclin D1. Interestingly, the expression of cold inducible RNA-binding protein (CIRBP), a cold responsive gene reacting to multiple cellular stresses, was decreased in parallel with the 1 % oxygen-induced proliferation inhibition. Forced expression of CIRBP under hypoxia could restore the proliferation of NSCs, as showed by EdU incorporation and cell cycle analysis. Furthermore, the expression of Cyclin D1 under hypoxia was also restored by CIRBP overexpression. Taken together, these data suggested a growth-suppressing effect of severe hypoxia on NSCs and, for the first time, revealed a novel role of CIRBP in hypoxia-induced cell cycle arrest, suggesting that modulating CIRBP may be utilized for preventing hypoxia-induced neonatal brain injury.

Background: Neuron apoptosis mediated by hypoxia inducible factor 1α (HIF-1α) in hippocampus is one of the most important factors accounting for the chronic hypobaric hypoxia induced cognitive impairment. As a neuroprotective molecule that is up-regulated in response to various environmental stress, CIRBP was reported to crosstalk with HIF-1α under cellular stress. However, its function under chronic hypobaric hypoxia remains unknown.Objective: In this study, we tried to identify the role of CIRBP in HIF-1α mediated neuron apoptosis under chronic hypobaric hypoxia and find a possible method to maintain its potential neuroprotective in long-term high altitude environmental exposure.Methods: We established a chronic hypobaric hypoxia rat model as well as a tissue culture model where SH-SY5Y cells were exposed to 1% hypoxia. Based on these models, we measured the expressions of HIF-1α and CIRBP under hypoxia exposure and examined the apoptosis of neurons by TUNEL immunofluorescence staining and western blot analysis of apoptosis related proteins. In addition, by establishing HIF-1α shRNA and pEGFP-CIRBP plasmid transfected cells, we confirmed the role of HIF-1α in chronic hypoxia induced neuron apoptosis and identified the influence of CIRBP over-expression upon HIF-1α and neuron apoptosis in the process of exposure. Furthermore, we measured the expression of the reported hypoxia related miRNAs in both models and the influence of miRNAs' over-expression/knock-down upon CIRBP in the process of HIF-1α mediated neuron apoptosis.Results: HIF-1α expression as well as neuron apoptosis was significantly elevated by chronic hypobaric hypoxia both in vivo and in vitro. CIRBP was induced in the early stage of exposure (3d/7d); however as the exposure was prolonged (21d), CIRBP level of the hypoxia group became significantly lower than that of control. In addition, HIF-1α knockdown significantly decreased neuron apoptosis under hypoxia, suggesting HIF-1α may be pro-apoptotic in the process of exposure. CIRBP over-expression significantly suppressed HIF-1α up-regulation in hypoxia and inhibited HIF-1α mediated neuron apoptosis. Interestingly, miR-23a was also induced by hypoxia exposure and showed the same changing tendency with CIRBP (increasing in 3d/7d, decreasing in 21d). In addition, over-expressing miR-23a up-regulated CIRBP, down-regulated HIF-1α and attenuated neuron apoptosis.Conclusion: Cold inducible RNA binding protein is involved in chronic hypoxia induced neuron apoptosis by down-regulating HIF-1α expression, and MiR-23a may be an important tool to maintain CIRBP level and function.