Efficacy and safety of Shufeng Jiedu capsule in the treatment of COVID-19: A protocol for systematic review and meta analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) epidemic is spreading worldwide. Shufeng Jiedu capsule (SFJDC) is a commonly used drug in the treatment of COVID-19. However, there is insufficient evidence for clinical efficacy and safety. METHODS: Two authors will independently search the Chinese National Knowledge Infrastructure (CNKI), VIP database, Wanfang database, the Cochrane Library, EMBASE, PubMed and Web of Science, in English and Chinese. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Review Manager 5.3 and Stata 16.0 software will be used to analyze the eligible data. RESULTS: This protocol will conduct a systematic review and meta-analysis of literature listed above, and reliable outcomes about the clinical efficacy and safety of SFJDC in the treatment of COVID-19 will be obtained. CONCLUSIONS: These findings will provide guidance for clinicians and patients using SFJDC for COVID-19 treatment. PROSPERO REGISTRATION NUMBER: CRD42020185764.

Exploring multiple mechanisms of Qingjie Fanggan prescription for prevention and treatment of influenza based on systems pharmacology.

Influenza is a type of acute disease characterized by strong contagiousness and short incubation period, which have posed a large potential threat to public health. Traditional Chinese Medicine (TCM) advocates to the aim of combating complex diseases from a holistic view, which has shown effectiveness in anti-influenza. However, the mechanism of TCM prescription remains puzzling. Here, we applied a system pharmacology approach to reveal the underlying molecular mechanisms of Qingjie Fanggan prescription (QFP) in the prevention and treatment of influenza. In this study, we identified 228 potential active compounds by means of absorption, distribution, metabolism, and excretion (ADME) evaluation system and literature research. Then, the targets of the potential active compounds were predicted by using the WES (Weighted Ensemble Similarity) method, and the influenza-related targets were obtained according to some existing gene databases. Next, an herb-component-target network was constructed to further dissect the multi-directional therapeutic approach for QFP. Meanwhile, we also performed gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analysis on 344 potential targets. Finally, a target-pathway network was constructed to further dissect the core pathways and targets in treatment of influenza for QFP. And the key components and targets were docked by AutoDock Vina to explore their binding mode. All of these demonstrated that QFP had multi-scale curative activity in regulating influenza-related biological processes, which facilitates the application of traditional medicine in modern medicine.

Therapeutic efficacy of Qingfei Paidu decoction combined with antiviral drugs in the treatment of corona virus disease 2019: A protocol for systematic review and meta analysis.

BACKGROUND: The corona virus disease 2019 (COVID-19) has caused a global pandemic, there are no specific drugs and vaccines for epidemic control at present. More and more clinical practice shows that traditional Chinese medicine has played an important role in the outbreak. Among them, Qingfei Paidu decoction (QPD) combined with antiviral drugs can enhance the therapeutic efficacy for COVID-19. However, there is still a lack of comprehensive and systematic evidence, which urgently requires us to verify its therapeutic efficacy. Hence, we provide a protocol for systematic review and meta-analysis. METHODS: We will search the studies in MEDLINE/PubMed, China National Knowledge Infrastructure, Wanfang database, VIP database, the Cochrane Library, Chinese Biomedical Database and Chinese Science Citation Database. Searches are limited to clinical studies published in Chinese and English. Next, the quality of each study is assessed according to the criteria of the Cochrane Handbook for Systematic Reviews of Interventions. Then, the outcome data are recorded and pooled by Review Manager 5.3 and STATA 16.0 software. RESULTS: The systematic review and meta-analysis aims to review and pool current clinical outcomes of QPD combined with antiviral drugs for the treatment of COVID-19. CONCLUSION: This study will provide a high-quality evidence of QPD for the treatment on COVID-19 patients. PROSPERO REGISTRATION NUMBER: CRD42020182409.

Efficacy and safety of Jinhua Qinggan granules for coronavirus disease 2019 (COVID-19): A protocol of a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome (SARS)-COV2 and represents the causative agent of a potentially fatal disease. Jinhua Qinggan granules has definite effect in treating COVID-19 patients, but it has not been systematically evaluated for efficacy and safety. METHODS: Retrieved the database, including the China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wan Fang database, PubMed, and EMBASE. Evaluate methodological quality and judge risk of bias through the Cochrane manual. RevMan 5.3 and STATA 16.0 software were used to perform the meta-analysis. RESULTS: This study will provide high-quality evidence of Jinhua Qinggan granules for COVID-19. CONCLUSION: The conclusion of this study will provide evidence to determine whether Jinhua Qinggan granules is an effective treatment for COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020182373.

Therapeutic efficacy of shenmai injection as an adjuvant treatment in dilated cardiomyopathy: A protocol for systematic review.

BACKGROUND: Shenmai injection (SMI) is a Traditional Chinese Medicine patent prescription consisting of extractions from ophiopogonis radix and ginseng radix rubra. Clinical studies showed that SMI combined with conventional medicine treatment (CMT) can enhance the therapeutic efficacy for dilated cardiomyopathy (DCM). However, there is still a lack of comprehensive and systematic evidence, which urgently requires us to verify its therapeutic efficacy. Hence, we provide a protocol for systematic review and meta-analysis. METHODS: The systematic search on the MEDLINE/PubMed, China National Knowledge Infrastructure (CNKI), Wanfang database, VIP database, the Cochrane Library, Embase and Chinese Biomedical Database (CBM) in Chinese and English language with dates ranging from the earliest record to August 8, 2019. Next, the quality of each trial was assessed according to the criteria of the Cochrane Handbook for Systematic Reviews of Interventions. Then, the outcome data were recorded and pooled by RevMan 5.3 software. RESULTS: The systematic review and meta-analysis aims to review and pool current clinical outcomes of SMI for the adjuvant treatment of DCM. CONCLUSION: This study will provide a high-quality evidence of SMI for the adjuvant treatment on DCM patients. PROSPERO REGISTRATION NUMBER: CRD42019146369.

MeCP2 enforces Foxp3 expression to promote regulatory T cells' resilience to inflammation.

Forkhead box P3(+) (Foxp3(+)) regulatory T cells (Tregs) are crucial for peripheral tolerance. During inflammation, steady Foxp3 expression in Tregs is essential for maintaining their lineage identity and suppressive function. However, the molecular machinery governing Tregs' resilience to inflammation-induced Foxp3 destabilization remains elusive. Here, we demonstrate that methyl-CpG binding protein 2 (MeCP2), an eminent epigenetic regulator known primarily as the etiological factor of Rett syndrome, is critical to sustain Foxp3 expression in Tregs during inflammation. In response to inflammatory stimuli, MeCP2 is specifically recruited to the Conserved Non-Coding sequence 2 region of the foxp3 locus, where it collaborates with cAMP responsive element binding protein 1 to promote local histone H3 acetylation, thereby counteracting inflammation-induced epigenetic silencing of foxp3. Consequently, Treg-specific deletion of MeCP2 causes spontaneous immune activation in mice and failure in protection against autoimmunity. Furthermore, we demonstrate that Foxp3 expression in MeCP2-deficient Tregs diminishes with time, resulting in their failure to suppress effector T-cell-mediated colitis. Thus, MeCP2 serves as a critical safeguard that confers Tregs with resilience against inflammation.

The chemokine CXCL12 and its receptor CXCR4 promote glioma stem cell-mediated VEGF production and tumour angiogenesis via PI3K/AKT signalling.

Chemokines and their receptors are actively involved in inflammation, immune responses, and cancer development. Here we report the detection of CD133(+) glioma stem-like cells (GSCs) co-expressing a chemokine receptor CXCR4 in human primary glioma tissues. These GSCs were located in areas adjacent to tumour vascular capillaries, suggesting an association between GSCs and tumour angiogenesis. To test this hypothesis, we isolated CD133(+) GSCs from surgical specimens of human primary gliomas and glioma cell lines. As compared to CD133(-) cells, CD133(+) GSCs expressed significantly higher levels of CXCR4 mRNA and protein, and migrated more efficiently in response to the CXCR4 ligand CXCL12. In addition, CXCL12 induced vascular endothelial growth factor (VEGF) production by CD133(+) GSCs via activation of the PI3K/AKT signalling pathway. Furthermore, knocking down of CXCR4 using RNA interference or inhibition of CXCR4 function by an antagonist AMD3100 not only reduced VEGF production by CD133(+) GSCs in vitro, but also attenuated the growth and angiogenesis of tumour xenografts in vivo formed by CD133(+) GSCs in SCID mice. These results indicate that CXCL12 and its receptor CXCR4 promote GSC-initiated glioma growth and angiogenesis by stimulating VEGF production.

An inhibitor of arachidonate 5-lipoxygenase, Nordy, induces differentiation and inhibits self-renewal of glioma stem-like cells.

Recent progress in cancer biology indicates that eradication of cancer stem cells (CSCs) is essential for more effective cancer therapy. Unfortunately, cancer stem cells such as glioma stem-like cells (GSLCs) are often resistant to either radio- or chemotherapy. Therefore, screening and development for novel therapeutic modalities against CSCs has been an important emerging field in cancer research. In this study, we report that a synthetic dl-nordihydroguaiaretic acid compound (dl-NDGA or "Nordy"), inhibited self-renewal and induced differentiation of GSLCs in vitro and in vivo. We found that Nordy inhibited an enzyme known to be involved in leukemia stem cell and leukemia progression, Alox-5, and attenuated the growth of GSLCs in vitro. Nordy reduced the GSLC pool through a decrease in the CD133(+) population and abrogated clonogenicity. Nordy appeared to exert its effect via astrocytic differentiation by up-regulation of GFAP and down-regulation of stemness related genes, rather than by inducing apoptosis of GSLCs. The growth inhibition of xenografted glioma by Nordy was more long-lasting compared with that of the akylating agent BCNU, which exhibited significant relapse on drug discontinuation resulting from an enrichment of GSLCs. Meanwhile, transient exposure to Nordy reduced tumorigenecity of GSLCs and induced differentiation of the xenografts. Taken together, we have identified Alox-5 as a novel target in GSLCs and its inhibition with Nordy exhibits therapeutic implications through inducing GSLC differentiation.