Knockdown of circ_CLIP2 regulates the proliferation, metastasis and apoptosis of glioma cells through miR-641/EPHA3/STAT3 axis.

A great amount of reaches have confirmed that circular RNAs (circRNAs) are novel regulators in glioma progression. Here, our work aimed to probe the specific role of circ_CLIP2 in glioma. The mRNA and protein expressions were analyzed by qRT-PCR and western blot, respectively. Cell viability, migration, invasion and apoptosis were examined by MTT assay, tranwell and flow cytometry assays, respectively. Moreover, the binding relationships between circ_CLIP2, microRNA (miR)-641 and erythropoietin-producing human hepatocellular (Eph)A3 were verified by dual luciferase reporter gene assay and/or RIP assay. The following data showed that circ_CLIP2 and EPHA3 were markedly increased in glioma tissues and cells, while miR-647 was downregulated. Gain- and loss-of-function experiments discovered that circ_CLIP2 knockdown remarkably inhibited cell proliferation, migration and invasion and promoted cell apoptosis of glioma cells, while these effects of circ_CLIP2 knockdown were abolished by miR-641 inhibition. Circ_CLIP2 was proved as a sponge of miR-641 to competitively upregulate EPHA3 expression. In addition, EPHA3 overexpression could abolish the inhibitory effects of miR-641 overexpression on the malignant behaviors of glioma cells by activating the signal transducer and activator of transcription 3 (STAT3). These findings elucidated that circ_CLIP2 knockdown suppressed glioma development by regulation of the miR-641/EP HA3/STAT3 axis, which provided a novel mechanism for understanding the pathogenesis of glioma.

Xiaoyao powder alleviates the hippocampal neuron damage in chronic unpredictable mild stress-induced depression model rats in hippocampus via connexin 43Cx43/glucocorticoid receptor/brain-derived neurotrophic factor signaling pathway.

Xiaoyao Powder (XYP) has been widely applied in China to treat stress-related illnesses, such as migraine, depression, Parkinson's disease, insomnia, and hypertension. Herein, this study aims to explore the effect of XYP on chronic unpredictable mild stress (CUMS)-induced depression and its underlying mechanisms. CUMS-induced depression rat models were established, they were subsequently randomly divided and treated with various conditions. Results of this study indicated that supplementation of XYP observably abolished CUMS-induced hippocampal damage and serum corticosterone (CORT) elevation. In mechanism, we discovered that CUMS induction could cause a prominent downregulation in glucocorticoid receptor (GR), phosphorylated-GR (p-GR), connexin 43 (Cx43), and brain-derived neurotrophic factor (BDNF), a remarkable upregulation in c-Src. While the introduction of XYP could reverse the changes in all of these indicators mediated by CUMS. Furthermore, we proved that Cx43 could interact with GR, and the protective effect of XYP on hippocampal neurons is realized by up-regulating GR. Summarized, this study indicated that XYP could ameliorate hippocampal neuron damage in CUMS-induced depression model rats through acting on Cx43/GR/BDNF axis.

Enhanced empirical likelihood estimation of incubation period of COVID-19 by integrating published information.

Since the outbreak of the new coronavirus disease (COVID-19), a large number of scientific studies and data analysis reports have been published in the International Journal of Medicine and Statistics. Taking the estimation of the incubation period as an example, we propose a low-cost method to integrate external research results and available internal data together. By using empirical likelihood method, we can effectively incorporate summarized information even if it may be derived from a misspecified model. Taking the possible uncertainty in summarized information into account, we augment a logarithm of the normal density in the log empirical likelihood. We show that the augmented log-empirical likelihood can produce enhanced estimates for the underlying parameters compared with the method without utilizing auxiliary information. Moreover, the Wilks' theorem is proved to be true. We illustrate our methodology by analyzing a COVID-19 incubation period data set retrieved from Zhejiang Province and summarized information from a similar study in Shenzhen, China.

COP9 Signalosome Subunit 3 Restricts Neuroinflammatory Responses During Cerebral Ischemia/Reperfusion Injury Through Stabilizing Suppressor of Cytokine Signaling 3 Protein.

BACKGROUND: The suppressor of cytokine signaling 3 (SOCS3) is a specific negative regulator of signal transducer and activator of transcription 3 (STAT3) signaling, which is predominantly activated to induce neuroinflammatory response in microglia and functions essential roles during cerebral ischemia-reperfusion (I/R) injury. Constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is a signaling platform controlling protein stability by remodeling of cullin-RING ubiquitin ligases, which is recently reported to specifically recognize proteins with SOCS-box domains. However, whether SOCS3 is related to COP9 signalosome in neuroinflammation during cerebral I/R injury is completely unclear. METHODS: Mice subjected to transient middle cerebral artery occlusion (MCAO) and reperfusion, and BV2 microglia cells treated with oxygen-glucose deprivation and reoxygenation (OGD/R) were used to mimic cerebral I/R injury. Western blot, qRTPCR, immunofluorescence, and co-Immunoprecipitation assays were performed to explore the regulatory mechanism of SOCS3 on neuroinflammation and the relationship of SOCS3 and COP9 signalosome during cerebral I/R injury. RESULTS: SOCS3 expression is significantly upregulated in microglia during OGD/R treatment, and overexpression of SOCS3 suppresses OGD/R-induced STAT3 activation and inflammatory factor expression. Furthermore, we find that COP9 signalosome subunit 3 (CSN3) interacts with SOCS3 protein to enhance its stability, thereby resulting in restricting OGD/R-induced STAT3 activation and inflammatory response. Moreover, we find that knockdown of CSN3 evidently accelerates STAT3 activation, and aggravates cerebral I/R injury in vivo. CONCLUSION: CSN3 restricts neuroinflammatory responses during cerebral I/R injury through stabilizing SOCS3 protein and indicates that CSN3 a potential therapeutic target for cerebral I/R injury.

No Evidence for Widespread Positive Selection Signatures in Common Risk Alleles Associated with Schizophrenia.

Schizophrenia poses an evolutionary-genetic paradox as it exhibits strongly negative fitness effects (early mortality and decreased fecundity), yet it persists at a prevalence of approximately 1% worldwide. Evidence from several studies have suggested that schizophrenia is evolved and maintained in part as a maladaptive byproduct of recent positive selection and adaptive evolution in human beings. However, inconsistent results have been also proposed, challenging the recent positive selection theory to explain the high population frequency of schizophrenia-associated alleles. Here, we used public domain data to locate signatures of positive selection based on genetic diversity, derived allele frequency, differentiation between populations, and long haplotypes at schizophrenia-associated single nucleotide polymorphisms (SNPs) and randomly selected SNPs (as negative controls). We found evidence for positive selection at 10 out of the 105 schizophrenia-associated SNPs, while 5 of these SNPs involved positive selection for the protective allele. Taken together, the absence of widespread positive selection signals at the schizophrenia-associated SNPs, along with the fact that half of the positive selection favored the protective allele, provide little evidence supporting the positive selection theory in schizophrenia.

Long non-coding RNA SNHG6 promotes glioma tumorigenesis by sponging miR-101-3p.

INTRODUCTION: Glioma is the most common primary brain tumor. The small nucleolar RNA host gene (SNHG) SNHG6 is a potential oncogene in the development of several types of cancers. METHODS: In this study, we investigated the functional role of long non-coding RNA (lncRNA) SNHG6 in the malignancy of glioma in cell lines and transplanted nude mice. RESULTS: We found that the expression of lncRNA SNHG6 was higher in glioma tissues and cells than in normal brain tissues and cells. The expression of lncRNA SNHG6 was positively correlated with the malignancy and poor prognosis of glioma patients. microRNA (miR)-101-3p expression was decreased in glioma tissues and cells and was negatively correlated with the malignancy and poor prognosis of glioma patients. In glioma tissues, the expression of lncRNA SNHG6 was negatively correlated with the expression of miR-101-3p. SNHG6 contained a binding site of miR-101-3p. Knockdown of SNHG6 expression resulted in a significant increase of miR-101-3p expression. miR-101-3p mimic markedly decreased the luciferase activity of SNHG6. Knockdown of SNHG6 inhibited glioma cell proliferation, migration, and epithelial-mesenchymal transition (EMT), and increased apoptosis. miR-101-3p mimic enhanced knockdown of SNHG6-induced inhibition of cell proliferation, migration, and EMT, and an increase of apoptosis. Anti-miR-101-3p reversed the the effects of si-SNHG6 on cell malignancy. Knockdown of SNHG6 remarkably reduced the increase of tumor volumes in xenograft mouse models. In tumor tissues, knockdown of SNHG6 increased the expression of miR-101-3p and reduced EMT biomarker expression. CONCLUSIONS: Our study provides novel insights into the functions of lncRNA SNHG6/miR-101-3p axis in the tumorigenesis of glioma.

[Treatment of lumbar intervertebral disc protrusion and remaining bulk ligamentum flava by micro-endoscope].

OBJECTIVE: To investigate operative skill and recent clinical effects of remaining bulk ligamentum flava and treatment of lumbar intervertebral disc protrusion by micro-endoscope. METHODS: Fifty-two cases with lumbar intervertebral disc protrusion included 31 males, 21 females; aged from 28 to 45 years,mean 36 years; L(4,5) in 24 cases, L5S1 in 28 cases. Under the micro-endoscope, all patient were excised the vertebral plate partly, decompressed the nerve root, remaining bulk ligament flava and excised the herniated nucleus pulposus. RESULTS: Forty-six of 52 patients were followed up for 5 to 51 months with an average of 34.5. According to the effect of Nakai standards,the results were excellent in 34 cases, good in 9 cases, fair in 3 cases. The operation time was 45 to 75 minutes and bleeding was 40 to 80 ml. There were no nerve root injury and endorachis tear complications. CONCLUSION: The bulk ligamentum flava remaining cure intervertebral disc protrusion by micro-endoscope, demic natural anatomic structure is retained through technically manipulate and spinalis constancy is kept.