Reactive astrogliosis after spinal cord injury (SCI) contributes to glial scar formation that impedes axonal regeneration. The mechanisms underlying reactive astrocyte proliferation upon injury remain partially understood. MicroRNAs (miRNAs) function as a major class of post-transcriptional gene expression regulators that participate in many biological processes. However, miRNA function during reactive astrogliosis, particularly in injury-induced astrocyte proliferation, has not been carefully examined. In this study, we conditionally deleted Dicer1 gene encoding an enzyme that is required for mature miRNA generation, and examined the proliferative behavior of Dicer1-null reactive astrocytes in the transected mouse spinal cord. We found that injury-induced proliferation is blocked in Dicer1-null astrocytes. Previous reports indicate that miR-17-5p family members are upregulated during SCI. We therefore tested functional contribution of miR-17-5p to the proliferation of reactive astrocytes in vitro. Our results showed that a synthetic miR-17-5p mimic is able to rescue the proliferation defect of Dicer1-null astrocytes, while an antisense inhibitor of miR-17-5p blocked lipopolysaccharide-induced astrocytic proliferation. Similar results are also observed in leukemia inhibitory factor (LIF)-treated astroglial cultures suggesting that miR-17-5p particularly modulates reactive astrocyte proliferation initiated by LIF presumably via the JAK/STAT3 pathway. Furthermore, overexpression of miR-17-5p leads to decrease of several cell cycle regulators in cultured astroglia and astrocytoma cell line C6. Our conclusion is that miRNAs are indispensable to the injury-induced reactive astrocyte proliferation, and that miR-17-5p may be a major player regulating this pathological process by affecting cell cycle machinery.
Background CGRP monoclonal antibody (mAb) is a promising preventive treatment for episodic migraine and has been approved by US FDA recently. But the treatments for chronic migraine are rare. Therefore, we performed meta‐analysis to assess the efficacy and safety of CGRP mAbs in preventing chronic migraine. Methods Database including Cochrane Library and PubMed were systematically searched for randomized controlled trials (RCTs) which are about CGRP mAb in preventing treatment of chronic migraine. Evaluating the bias and quality of RCTs was carried out according to the Cochrane collaboration's tool for assessing risk of bias. The data analysis was carried out by reviewer manager 5.2. Results Totally, 6 articles enrolled in the present meta‐analysis, including 4 independent clinical trials and 3,166 patients. After pooled analysis, it indicated that CGRP mAb improved 50% responder rate (OR = 2.42, 95% CI = [2.04, 2.87], I 2 = 0%, p < 0.00001) and 75% responder rate (OR = 1.95, 95% CI = [1.30, 2.91], I 2 = 0%, p = 0.001), as compared with placebo. And there was no difference in incidence of adverse events between CGRP mAb group and placebo group except incidence of injection site discomfort. Conclusions CGRP mAb is an effective and safety preventive treatment for chronic migraine.
Valproic acid (VPA) is a broad-spectrum antiseizure drug used for a variety of clinical conditions, such as epilepsy and mood disorders. Drug-induced hypersensitivity syndrome (DRESS) accompanied by hyponatremia, thrombocytopenia, hypoalbuminemia and elevated aminotransferase has never been reported as an adverse effect of VPA monotherapy during titration for epilepsy in Asian population. Hereby, we present the case of a 73-year-old Chinese male who suffered from DRESS and other complications two weeks after initiating VPA treatment for epilepsy. Understanding the risk associated with VPA-induced DRESS, and taking effective measures to avoid the severe side effects are necessary.
Objectives To evaluate and compare the efficacy and safety of gepants for abortive treatment of migraine by network meta‐analysis. Materials & Methods Publications, which were randomized controlled trials (RCTs) about gepants for abortive treatment of migraine, were acquired from Pubmed and Cochrane Library. The literatures screening and quality assessment followed the Cochrane handbook. Review manager 5.3 and Addis v1.16.8 were utilized for data analyzing. Results Totally, 15 RCTs were included in the network meta‐analysis. The trials enrolled were with high quality. There are 7 treatments were analyzed: BI 44370 TA, MK‐3207, olcegepant, rimegepant, telcagepant, ubrogepant, and placebo. Of these trials, 11,118 patients and 10,917 patients were assigned to one of 7 treatments randomly for efficacy assessment and safety assessment, respectively. In meta‐analysis of direct comparisons, all gepants were superior to placebo in achieving pain freedom 2 hr postdose and only rimegepant and telcagepant were higher than placebo in incidence of any adverse events. In network meta‐analysis, the rank best 3 drugs were olcegepant, BI 44370 TA, and MK‐3207 for efficacy outcomes. And the rank best 3 drugs were BI 44370 TA, placebo, and ubrogepant for safety outcomes. Conclusion Gepants were effective for abortive treatment of migraine. The most effective treatment of gepants for migraine might be olcegepant which were administrated transvenously. And all of gepants were safe for migraine treatment with single dose.
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