Huiqing Wang

Microarray Profiling and Co-Expression Network Analysis of LncRNAs and mRNAs in Neonatal Rats Following Hypoxic-ischemic Brain Damage.

Long noncoding RNAs (lncRNAs) play critical roles in cellular homeostasis. However, little is known about their effect in developing rat brains with hypoxic-ischemic brain damage (HIBD). To explore the expression and function of lncRNA in HIBD, we analyzed the expression profiles of lncRNAs in hypoxic-ischemic (HI) brains and sham control using microarray analysis. The results showed a remarkable difference in lncRNA between HI and sham brains. A total of 322 lncRNAs were found to be differentially expressed in HI brains, compared to sham control. Among these, BC088414 was one of the most significantly urpregulated lncRNAs. In addition, 375 coding genes were differentially expressed between HI brains and sham control. Pathway and gene ontology analysis indicated that the upregulated coding genes mostly involved in wounding, inflammation and defense, whereas the downregulated transcripts were largely associated with neurogenesis and repair. Moreover, coding non-coding co-expression network analysis showed that the BC088414 lncRNA expression was correlated with apoptosis-related genes, including Casp6 and Adrb2. Silencing of lncRNA BC088414 in PC12 cells caused reduced mRNA level of Casp6 and Adrb2, decreased cell apoptosis and increased cell proliferation. These results suggested lncRNA might participate in the pathogenesis of HIBD via regulating coding genes.

Nitric oxide synthase in hypoxic or ischemic brain injury.

Abstract Hypoxic or ischemic stress causes many serious brain injuries, including stroke and neonatal hypoxia ischemia encephalopathy. During brain hypoxia ischemia processes, nitric oxide (NO) may play either a neurotoxic or a neuroprotective role, depending upon factors such as the NO synthase (NOS) isoform, the cell type by which NO is produced, and the temporal stage after the onset of the hypoxic ischemic brain injury. Excessive NO production can be neurotoxic, leading to cascade reactions of excitotoxicity, inflammation, apoptosis, and deteriorating primary brain injury. In contrast, NO produced by endothelial NOS plays a neuroprotective role by maintaining cerebral blood flow and preventing neuronal injury, as well as inhibiting platelet and leukocyte adhesion. Sometimes, NO-derived inducible NOS and neuronal NOS in special areas may also play neuroprotective roles. Therefore, this review summarizes the different roles and the regulation of the three NOS isoforms in hypoxic or ischemic brain injury as revealed in research in recent years, focusing on the neurotoxic role of the three NOS isoforms involved in mechanisms of hypoxic or ischemic brain injury.

RIPK3 interactions with MLKL and CaMKII mediate oligodendrocytes death in the developing brain

Oligodendrocyte progenitor cells (OPCs) death is a key contributor to cerebral white matter injury (WMI) in the developing brain. A previous study by our group indicated that receptor-interacting proteins (RIPs) are crucial in mediating necroptosis in developing neurons. However, whether this mechanism is involved in OPCs death is unclear. We aimed to explore the mechanisms of RIP-mediated oligodendrocytes (OLs) death in the developing brain. Oligodendrocytes necroptosis was induced by oxygen-glucose deprivation plus caspase inhibitor zVAD treatment (OGD/zVAD) in vitro. Western blotting and immunofluorescence were used to detect RIPK1, RIPK3, mixed lineage kinase domain-like protein (MLKL), and Ca2+ and calmodulin-dependent protein kinase IIδ (CaMKIIδ). Immunoprecipitation was used to assess the interactions between RIPK3 and RIPK1, MLKL, and CaMKIIδ. Necrostatin-1 was used to disturb the RIPK3–RIPK1 interaction, and siRNA was used to inhibit RIPK3 or MLKL expression. Oligodendrocytes death was examined using PI staining, EM, and cell membrane leakage assays. In vivo, brain damage in neonatal rats was induced by hypoxia–ischemia (HI). This was followed by an examination of myelin development. We found that OGD/zVAD treatment upregulates the expression of RIPK3 and the interaction of RIPK3 with RIPK1, MLKL, and CaMKIIδ. Inhibition of the RIPK3-MLKL or RIPK3-CaMKIIδ interaction attenuates OLs death induced by OGD/zVAD. These protective mechanisms involve the translocation of MLKL to the OLs membrane, and the phosphorylation of CaMKIIδ. However, inhibition of the RIPK3–RIPK1 interaction did not protect OLs death induced by OGD/zVAD. In vivo studies indicated that the disrupted development of myelin was attenuated after the inhibition of RIPK3-MLKL or RIPK3-CaMKIIδ interaction. Taken together, our data indicate that RIPK3 is a key factor in protection against OLs death and abnormal myelin development via its interaction with MLKL and CaMKIIδ after HI. This suggests that RIPK3 may be a potential target for the treatment of WMI in neonates.

The effect of miR-30d on apoptosis and autophagy in cultured astrocytes under oxygen-glucose deprivation

MiR-30d has been demonstrated to regulate autophagy in human cancer cells. However, the role of miR-30d in astrocytes exposed to hypoxia-ischemia is not clear. In this study, we established model of oxygen and glucose deprivation (OGD) with rat primary astrocytes and evaluated the role of miR-30d in the cross-talk between autophagy and apoptosis in astrocytes after OGD. We found that miR-30d inhibited Beclin1 expression in astrocytes. Inhibition of miR-30d by antagomir significantly increased cell autophagy but decreased cell apoptosis in astrocytes exposed to OGD. Knockdown of Beclin1 reversed the upregulation of autophagy and downregulation of apoptosis induced by miR-30d inhibition in astrocytes subjected to OGD. These results strongly indicated that miR-30d played critical roles in the cross-talk between autophagy and apoptosis of astrocytes subjected to OGD by targeting Beclin1. MiR-30d is a novel target to attenuate cell injury under hypoxia-ischemia condition.

Neonatal mortality in the urban and rural China between 1996 and 2013: A retrospective study

Background:One of the proposed United Nations post-2015 sustainable development goals is to eliminate avoidable neonatal deaths by 2030. This study aims to examine changes in neonatal mortality rate (NMR) and cause-specific NMR in urban and rural areas to guide renewed efforts to further reduce NMR in China.Methods:This retrospective study used 18 y of consecutive data from the National Under-5 Child Mortality Surveillance System.Results:Urban NMR decreased from 11.0 to 4.0 deaths per 1,000 live births, and rural NMR was decreased births from 26.0 to 8.1 deaths per 1,000 live births between the periods of 1996–1998 and 2011–2013. Rural NMR was about two times as much as urban NMR in 2011–2013. Approximately four-fifths of neonatal deaths occurred within less than 7 d after birth. In 2011–2013, the three leading causes of early neonatal death were premature delivery, intrapartum-related conditions, and congenital abnormalities; the three causes of death in late neonates were classification premature delivery, congenital abnormalities, and pneumonia.Conclusion:China has made substantive progress in reducing NMR; however, the disparity in NMR between urban and rural areas still exists. More effort should be made to prevent and manage premature delivery and congenital abnormalities, especially in rural areas.

Association between maternal HBsAg carrier status and neonatal adverse outcomes: meta-analysis

Abstract Objective: We conducted a meta-analysis to evaluate whether maternal hepatitis B virus (HBV) carrier status increases the risk of neonatal complications. Methods: Publications addressing the association between maternal HBV carrier status and neonatal outcomes were selected from the PubMed, EMBASE, Web of Science, Cochrane Library and China National Knowledge Infrastructure. Publication bias and heterogeneity across studies were evaluated and summary odds ratios, weighted mean difference or standardized mean difference and 95% confidence intervals were calculated and compared between groups. Results: Eighteen studies and 7600 pregnant HBV carriers were selected for analyses. A statistically association with maternal HBV carrier status was demonstrated for premature birth and asphyxia, with no difference found among perinatal mortality, gestational age, small for gestational age, large for gestational age, birth weight, low birth weight, macrosomia, Apgar sore at 1 min, jaundice and congenital anomaly. Heterogeneity across studies was found, and no publication bias was detected. Conclusion: Our analysis suggests that maternal hepatitis B carrier status is significantly associated with premature birth and asphyxia. Large-scale prospective studies are still warranted.