Long noncoding RNA CDKN2B-AS1 interacts with transcription factor BCL11A to regulate progression of cerebral infarction through mediating MAP4K1 transcription.

The effective therapeutic approach of cerebral infarction is limited because of its underlying complexity. Recently, multiple long noncoding RNAs (lncRNAs) have been identified in the pathogenesis of cerebral infarction. Here, the current study aims to explore the interaction among lncRNA cyclin-dependent kinase inhibitor-2B-antisense RNA 1 (CDKN2B-AS1), transcription factor B-cell lymphoma/leukemia 11A (BCL11A), and MAPKK kinase kinase 1 (MAP4K1) and further investigate whether they affect cerebral infarction progression. The expression of CDKN2B-AS1, BCL11A, and MAP4K1 was altered in lymphocytes extracted from patients with cerebral infarction. In order to identify their roles in regulatory T (Treg) cells, the proliferation and apoptosis of the CD4+CD25+ Treg cells were examined, and levels of IL-4, IL-10, and TGF-ß were determined. Also, the RNA crosstalk among CDKN2B-AS1, BCL11A, and MAP4K1 was validated. Finally, we established a rat model of middle cerebral arterial occlusion to evaluate the neurologic impairment and cerebral infarction volume. The results revealed that lymphocytes in patients with cerebral infarction presented with the up-regulated expression of CDKN2B-AS1. Moreover, BCL11A could specifically bind to CDKN2B-AS1 and MAP4K1 promoter so as to inhibit MAP4K1. Moreover, it was observed that down-regulated CDKN2B-AS1 inhibited CD4+CD25+ Treg-cell proliferation, reduced levels of IL-4, IL-10, and TGF-ß and cerebral infarction volume, and elevated MAP4K1 expression. Collectively, our study provides evidence that CDKN2B-AS1 silencing could increase MAP4K1 expression to inhibit the CD4+CD25+ Treg-cell proliferation by reducing enrichment of transcription factor BCL11A, thereby protecting against cerebral infarction progression, highlighting a promising therapeutic strategy for treating cerebral infarction.-Lei, J.-J., Li, H.-Q., Mo, Z.-H., Liu, K.-J., Zhu, L.-J., Li, C.-Y., Chen, W.-L., Zhang, L. Long noncoding RNA CDKN2B-AS1 interacts with transcription factor BCL11A to regulate progression of cerebral infarction through mediating MAP4K1 transcription.

The relationship between exposure to hepatitis B virus and increased atherosclerosis-associated morbidity - a meta-analysis.

BACKGROUND AND AIM: The relationship between exposure to hepatitis B virus (HBV) and atherosclerosis-associated disease morbidity has not been clearly elucidated. We performed a meta-analysis to explore whether exposure to HBV is a risk factor for atherosclerosis-associated diseases. METHODS: We searched the PubMed, Web of Science, Cochrane Library, Embase, and Scopus databases for related studies. We then chose the eligible studies for meta-analysis and assessed quality assessment and risk of bias. RESULTS: The meta-analysis of the included studies showed that exposure to HBV tends to increase atherosclerosis-associated disease morbidity, but this increase was not statistically significant. CONCLUSIONS: Hepatitis B virus may not be a risk factor for atherosclerosis-associated diseases, but further studies that employ more sensitive clinical parameters are needed to verify this result.

China Medical Team: Medical rescue for "4.25" Nepal earthquake.

In recent years, global natural disasters have been frequent and resulted in great casualties and property loss. Since Wenchuan earthquake, the disaster emergency rescue system of China has obtained considerable development in various aspects including team construction, task scheduling, personnel training, facilities and equipments, logistics, etc. On April 25, 2015, an earthquake that measured 8.1 on the Richter scale attacked Nepal. Chinese government firstly organized a medical team, named China Medical Team, and sent it to the attacked region in Nepal to implement medical rescue. The medical team completed the rescue mission successfully and creatively based on their experiences.

Inhibition of SENP3 by URB597 ameliorates neurovascular unit dysfunction in rats with chronic cerebral hypoperfusion.

Disruption of the neurovascular unit (NVU), induced by chronic cerebral hypoperfusion (CCH), has been broadly found in various neurological disorders. SUMO-specific protease 3 (SENP3) is expressed in neurons, astrocytes, and microglia, and regulates a variety of cell events. However, whether SENP3 is involved in neurovascular injury under the condition of CCH is still elusive. To address this issue, we investigated the effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on NVU and the role of SENP3 in this process, as well as the underling mechanisms. The expression of SENP3 was detected by immunochemistry. The function and structure of the NVU was assessed by Western blot analysis and transmission electron microscopy. CCH caused the upregulation of SENP3, the disruption of cell and non-cell components at the protein level within the NVU, and ultrastructural deterioration. The NVU impairment as well as overexpression of SENP3 were reversed by treatment with URB597. These results reveal a novel neuroprotective role in URB597, which implicates URB597 in the amelioration of CCH-induced NVU impairment by inhibiting SENP3.

Association between RAD51 polymorphism and breast cancer susceptibility: a meta analysis.

BACKGROUND: RAD51 interacting with BRCA1 and BRCA2 could modulate the penetrance of BRCA1/BRCA2 mutations, which may increase susceptibility for breast cancer by inhibiting DNA repair and genome stability. The purpose of this study was to provide refined statistical evidence for the association between RAD51 polymorphism and breast cancer risk. DESIGN AND RESULTS: We conducted a meta-analysis of 15 publications with a total of 11,766 cancer cases and 11,227 controls. We summarized the data on the association of RAD51 polymorphism with breast cancer risk and performed subgroup analyses by ethnicity and control source. The pooled ORs based on fixed-effects model did not indicate a modified risk of breast cancer associated with RAD51 polymorphism in the overall population. Nor did we find a significant association in any stratified analysis. CONCLUSIONS: This meta-analysis suggested that RAD51 polymorphism did not appear to represent a significant risk factor for breast cancer.

De-SUMOylation of FOXC2 by SENP3 promotes the epithelial-mesenchymal transition in gastric cancer cells.

The impact of cellular oxidative stress in promoting the epithelial-mesenchymal transition (EMT) has been noticed. Our previous study shows that SENP3, a redox-sensitive SUMO2/3-specific protease, accumulates in a variety of cancers, but whether SENP3 and SUMOylation involve in the regulation of EMT is unclear. The present study uncovers a novel role of SENP3 in promoting the EMT process in gastric cancer via regulating an EMT-inducing transcription factor, forkhead box C2 (FOXC2). We demonstrate that the expression of mesenchymal marker genes and cell migration ability are enhanced in SENP3-overexpressing gastric cancer cells and attenuated in SENP3-knockdown cells. A nude mouse model and a set of patient's specimens suggest the correlation between SENP3 and gastric cancer metastasis. Biochemical assays identify FOXC2 as a substrate of SENP3. Meanwhile N-cadherin is verified as a target gene of FOXC2, which is transcriptionally activated by a SUMO-less FOXC2. Additionally, reactive oxygen species-induced de-SUMOylation of FOXC2 can be blocked by silencing endogenous SENP3. In conclusion, SENP3, which is increased in gastric cancer cells, potentiates the transcriptional activity of FOXC2 through de-SUMOylation, in favor of the induction of specific mesenchymal gene expression in gastric cancer metastasis.