Background: Traumatic brain injury (TBI) is a common complication of acute and severe neurosurgery. Remodeling of N6-methyladenosine (m6A) stabilization may be an attractive treatment option for neurological dysfunction after TBI. In the present study, the authors explored the epigenetic methylation of RNA-mediated NLRP3 inflammasome activation after TBI. Methods: Neurological dysfunction, histopathology, and associated molecules were examined in conditional knockout (CKO) WTAP[flox/flox, Camk2a-cre], WTAPflox/flox, and pAAV-U6-shRNA-YTHDF1-transfected mice. Primary neurons were used in vitro to further explore the molecular mechanisms of action of WTAP/YTHDF1 following neural damage. Results: The authors found that WTAP and m6A levels were upregulated at an early stage after TBI, and conditional deletion of WTAP in neurons did not affect neurological function but promoted functional recovery after TBI. Conditional deletion of WTAP in neurons suppressed neuroinflammation at the TBI early phase: WTAP could directly act on NLRP3 mRNA, regulate NLRP3 mRNA m6A level, and promote NLRP3 expression after neuronal injury. Further investigation found that YTH domain of YTHDF1 could directly bind to NLRP3 mRNA and regulate NLRP3 protein expression. YTHDF1 mutation or silencing improved neuronal injury, inhibited Caspase-1 activation, and decreased IL-1β levels. This effect was mediated via suppression of NLRP3 protein translation, which also reversed the stimulative effect of WTAP overexpression on NLRP3 expression and inflammation. Conclusions: Our results indicate that WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after TBI and that WTAP/m6A/YTHDF1 downregulation therapeutics is a viable and promising approach for preserving neuronal function after TBI, which can provide support for targeted drug development.
1 January 2018 in Journal of Pharmacological Sciences
Xing-Nao-Jing (XNJ) is a well-known injection that has been extensively applied in clinical treatment of stroke in China. However, the underlying mechanism of clinical administration of XNJ in stroke remains unclear. In this study, a systems pharmacology strategy based on pharmacokinetic and pharmacodynamics data was applied to analyze the pharmacological effect of XNJ on stroke. Sixteen active compounds were filtered from XNJ through Drug-likeness (DL) and Brain-blood-barrier (BBB) evaluations. Ninety-four potential targets of these active components were identified by SysDT and SEA. Biological process and pathway enrichment analyses of these targets demonstrated that XNJ exerted anti-stroke effects by biological processes and pathways, such as the response to oxidative stress, regulation of blood pressure, calcium signaling pathway, and apoptosis. Integrating the compound-target network and stroke-related PPI network, we found that Akt1, HIF-1α and ITGB2 may play key roles in the treatment of stroke. The experiments demonstrated that oxycurcumenol may prevent PC12 cells from oxidative stress-induced cell damage. Our study indicates that XNJ has an effect on stroke by protecting neuro cells from oxidative stress-induced cell damage via HIF1α, and the research strategy at the systems pharmacology level is feasible to reveal the mechanisms of novel lead compounds from natural products.
Cervical cancer is a common malignant tumor and a leading cause of death in women worldwide. It plays a crucial role in tumorigenesis and progression of cervical cancer. A total of 1606 references on inflammation in cervical cancer were retrieved from the Web of Science Core Collection and visual analysis was performed using VOSviewer. Inflammation in cervical cancer has attracted the attention of researchers. Even though China is the country that publishes the most papers, with the most of the top-ranking institutions, there is no extensive collaboration and exchange of papers by Chinese scholars. PLOS One is a popular journal on inflammation in cervical cancer. Instead, authors from other countries perform better, for example, the Sjoerd H. Van Der Burg is the most widely cited author and “M2 macrophages induced by prostaglandin E2 and IL-6 from cervical carcinoma are switched to activated M1 macrophages by CD4 + Th1 cells” (Moniek Heusinkveld, Leiden University Medical Center) is the most cited article of inflammation in cervical cancer. Keywords associated with “apoptosis,” “HPV,” “NF-κB,” and “oxidative stress have been used in many studies, and keywords associated with “apoptosis,” “human papillomavirus (HPV),” “NF-κB,” and “oxidative stress” are involved in many studies, and there may be more research ideas in the future. From the perspective of precision medicine, more substantive research articles can promote scientific value, strengthen communication and cooperation, produce more extensive research results, and greatly promote the clinical diagnosis and treatment of cervical cancer. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Background: Cesarean section (CS) has become an effective means to solve dystocia and some obstetric complications, and to save the lives of women and perinatal women. Disparities in quality obstetric care and rehabilitation in CS result from differences in health care systems across regions, and more scientific and reasonable rehabilitation programmes and management measures will benefit more parturient and newborns worldwide who must take CS. In this study, we performed a bibliometric analysis to collect a graphical representation of the CS recovery.Methods: A total of 995 documents of CS recovery were retrieved from the Web of Science Core Collection (WOSCC) on December 31, 2021, and then VOS viewer 1.6.18 was used for visual analysis.Results: Over the last 20 years, the researches of CS recovery have gradually increased and it will continue to grow in the next period. Anesthesia and Analgesia is the most popular journal in CS recovery. Most of the representative achievements are concentrated in the relevant institutions of European and American countries, Brendan Carvalho and Ian J. Wrench are among the outstanding scholars in this field, but the overall outcome is limited by limited regional work and lack of broad cooperation and representation. “CS,” “surgery,” “management,” “recovery,” “enhanced recovery,” and “risk factors” are high frequency keywords, and there is a close relationship between “management” and “enhanced recovery” around the CS and they also become one of the key factors to regulate the condition of patients.Conclusion: This work firstly analyzed the research condition of CS recovery by a bibliometric analysis. According to the practice guideline, it produces some outstanding representative productions, which involves enhanced recovery after surgery (ERAS) and will continue to be the focus of researchers. More substantive research articles and large-scale clinical studies may greatly enhance the scientific value, and it is necessary to strengthen the ERAS guideline and cooperation between researchers, generate broader consensus and results, and ultimately provide help for CS recovery.