Effect of anti-inflammatory drugs on the storm of inflammatory factors in respiratory tract infection caused by SARS-CoV-2: an updated meta-analysis.

Background: New reports suggest that anti-inflammatory drugs are widely used to treat respiratory tract infections caused by SARS-CoV-2. Anti-inflammatory drugs were the most frequently used treatment for the COVID-19-related cytokine storm in China. However, the efficacy of anti-inflammatory drugs has yet to be systematically analyzed, and clinicians are often uncertain which class of anti-inflammatory drug is the most effective in treating patients with respiratory tract infections caused by SARS-CoV-2, especially those with severe disease. Methods: From 1 October 2022, relevant studies were searched in the PubMed, Embase, Medline, Cochrane Library, and Web of Science databases. A total of 16,268 publications were retrieved and collated according to inclusion and exclusion criteria, and sensitivity analyses were performed using STATA 14 software. Publication bias was assessed using funnel plots and Egger's test. Study quality was assessed using the PEDro scale, and the combined advantage ratio was expressed as a 95% confidence interval (CI). In total, 19 randomized controlled trials were included in the study. STATA 14 software was used for all random effects model analyses, and the results are expressed as relative risk ratios (RR) with 95% CI. Results: Quantitative analyses were performed on 14,514 patients from 19 relevant randomized controlled clinical trials. Pooled estimates (RR = 0.59, 95% CI 0.44-0.80) revealed that the use of anti-inflammatory drugs resulted in a significant reduction in mortality in patients with respiratory tract infection caused by SARS-CoV-2 compared with controls, and methylprednisolone (RR = 0.14, 95% CI 0.03-0.56) was more effective than other anti-inflammatory drugs. Anti-inflammatory drugs were effective in reducing mortality in critically ill patients (RR = 0.67, 95% CI 0.45-0.98) compared with non-critically ill patients (RR = 0.50, 95% CI 0.34-0.76); however, more clinical evidence is needed to confirm these findings. Conclusion: The use of anti-inflammatory drugs in patients with respiratory infections caused by SARS-CoV-2 reduces patient mortality, especially in severe cases. In individual studies, methylprednisolone was more effective than other drugs.

The efficacy and safety of post-stroke cognitive impairment therapies: an umbrella review.

Background: Stroke survivors are at significantly increased risk of cognitive impairment, which affects patients' independence of activities of daily living (ADLs), social engagement, and neurological function deficit. Many studies have been done to evaluate the efficacy and safety of post-stroke cognitive impairment (PSCI) treatment, and due to the largely inconsistent clinical data, there is a need to summarize and analyze the published clinical research data in this area. Objective: An umbrella review was performed to evaluate the efficacy and safety of PSCI therapies. Methods: Three independent authors searched for meta-analyses and systematic reviews on PubMed, the Cochrane Library, and the Web of Science to address this issue. We examined ADL and Barthel index (BI), Montreal Cognitive Assessment (MoCA), neurological function deficit as efficacy endpoints, and the incidence of adverse events as safety profiles. Results: In all, 312 studies from 19 eligible publications were included in the umbrella review. The results showed that angiotensin-converting enzyme inhibitors (ACEI) and N-methyl-D-aspartate (NMDA) antagonists, cell therapies, acupuncture, and EGB76 can improve the MoCA and ADL, and the adverse effects were mild for the treatment of PSCI. Moreover, Vinpocetine, Oxiracetam, Citicoline, thrombolytic therapy, Actovegin, DL-3-n-Butylphthalide, and Nimodipine showed adverse events or low article quality in patients with PSCI. However, the research evidence is not exact and further research is needed. Conclusion: Our study demonstrated that ACEI inhibitors (Donepezil) and NMDA antagonists (Memantine), EGB761, and acupuncture are the ADL and BI, MoCA, and neurological function deficit medication/therapy, respectively, for patients with PSCI. Clinical Trial Registration: https://inplasy.com/inplasy-2022-11-0139/; Identifier: INPLASY2022110139.

Sanwei DouKou Decoction ameliorate Alzheimer disease by increasing endogenous neural stem cells proliferation through the Wnt/ß-catenin signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Sanwei DouKou decoction (SDKD) is a traditional Chinese medicine (TCM) prescription derived from the Tibetan medical book "Si Bu Yi Dian" and is clinically used for the treatment of Alzheimer's disease (AD). However, the potential mechanism of SDKD treatment for AD remains elusive. AIM OF THE STUDY: This study aims to explore the potential mechanism by which SDKD alleviates AD. MATERIALS AND METHODS: Extracts of SDKD were identified with Gas chromatograph-mass spectrometer (GC-MS). 5 × FAD mice were treated with SDKD for 8 weeks. The efficacy of SDKD against AD was evaluated by in-vivo experiments. Morris water maze and contextual fear conditioning tests were used to detect the learning and memory ability of mice. Hematoxylin-eosin staining (H&E) staining was used to observe the pathological changes of brain tissue. Immunohistochemistry was used to detect the positive expression of Nestin in hippocampus. In in-vitro experiments, the Cell Counting Kit 8 (CCK-8) technique was used to detect cell viability, the proliferation of neural stem cells was detected by immunofluorescence staining, the intracellular protein expression was detected by Western Blot. RESULTS: The results of this study suggested that SDKD may ameliorate AD. SDKD significantly shortened the escape latency of mice in the Morris water maze experiment, increased the number of times the mice crossed the target quadrant, and prolonged freezing time in the contextual fear memory experiment. SDKD also improved neuronal pathology in the hippocampus, decreased neuronal loss, and increased Nestin protein levels. Furthermore, in in-vitro experiments, SDKD could significantly increase Neural stem cells (NSCs) viability, promoted NSCs proliferation, and also effectively activated the Wnt/ß-catenin signalling pathway, increased Wnt family member 3A (Wnt3a), ß-catenin and CyclinD1 protein levels, activated the NSCs proliferation pathways in AD model mouse brain tissue. CONCLUSIONS: The present study demonstrated that sanwei doukou decoction can ameliorate AD by increasing endogenous neural stem cells proliferation through the Wnt/ß-catenin signalling pathway. Our observations justify the traditional use of SDKD for a treatment of AD in nervous system.

The Efficacy and Safety of Ischemic Stroke Therapies: An Umbrella Review.

Background: Ischemic stroke is a leading cause of morbidity and mortality in neurological diseases. Numerous studies have evaluated the efficacy and safety of ischemic stroke therapies, but clinical data were largely inconsistent. Therefore, it is necessary to summarize and analyze the published clinical research data in the field. Objective: We aimed to perform an umbrella review to evaluate the efficacy and safety of ischemic stroke therapies. Methods: We conducted a search for meta-analyses and systematic reviews on PubMed, the Cochrane Library, and the Web of Science to address this issue. We examined neurological function deficit and cognitive function scores, quality of life, and activities of daily living as efficacy endpoints and the incidence of adverse events as safety profiles. Results: Forty-three eligible studies including 377 studies were included in the umbrella review. The results showed that thrombolytic therapy (tPA; alteplase, tenecteplase, and desmoteplase), mechanical thrombectomy (MTE), edaravone with tPA, stem cell-based therapies, stent retrievers, acupuncture with Western medicines, autologous bone marrow stromal cells, antiplatelet agents (aspirin, clopidogrel, and tirofiban), statins, and Western medicines with blood-activating and stasis-dispelling herbs (NaoShuanTong capsule, Ginkgo biloba, Tongqiao Huoxue Decoction, Xuesaitong injection) can improve the neurological deficits and activities of daily living, and the adverse effects were mild for the treatment of ischemic stroke. Moreover, ligustrazine, safflower yellow, statins, albumin, colchicine, MLC601, salvianolic acids, and DL-3-n-butylphthalide showed serious adverse events, intracranial hemorrhage, or mortality in ischemic stroke patients. Conclusion: Our study demonstrated that tPA, edaravone and tPA, tPA and MTE, acupuncture and Western medicines, and blood-activating and stasis-dispelling herbs with Western medicines are the optimum neurological function and activities of daily living medication for patients with ischemic stroke. Systematic Review Registration: https://inplasy.com/, identifier [INPLASY202250145].

A CRISPR/Cas9 strategy for the generation of a FLNC knockout hESC line (WAe009-A-70) to model dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy.

The FLNC gene encodes the sarcomeric protein filamin C which plays a central role in cardiomyocytes. Truncating FLNC mutations (stop or frameshift etc.) also cause dilated cardiomyopathy (DCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). To further understand the exact role of FLNC in DCM, we have generated a human FLNC knockout cell line from the original embryonic stem cell line H9 by CRISPR/Cas9 gene editing technology in this study. The establishment cell line WAe009-A-70 have a compound heterozygous 4 bp deletion/13 bp deletion in the exon 1 of FLNC which resulted in a frameshift in the translation of FLNC. No filamin C protein was detected in cardiomyocytes differentiated from this cell line. Moreover, WAe009-A-70 also expressed pluripotency markers, maintained the ability to differentiate into the three germ layers in vitro and had a normal karyotype.

Reprogramming of a human induced pluripotent stem cell line from a Marfan syndrome patient harboring a heterozygous mutation of c.2939G > A in FBN1 gene.

Marfan syndrome (MFS) is a connective-tissue disorder caused mainly by heterozygous mutations in the FBN1 gene that encodes fibrillin-1. In this study, human induced pluripotent stem cell (iPSC) line ZZUSAHi003-A was generated from peripheral blood mononuclear cells (PBMCs) isolated from a female patient with MFS using non-integrative Sendai virus. The iPSC line carried the FBN1 gene mutation, showed the normal karyotype, expressed pluripotency markers and had the capacity to differentiate into three germ layers in vivo. This iPS line, ZZUSAHi003-A, could serve as a useful tool for studying pathogenic mechanisms of MFS.

CRISPR/Cas9 mediated establishment of a human CSRP3 compound heterozygous knockout hESC line to model cardiomyopathy and heart failure.

The role of muscle LIM protein (MLP), encoded by CSRP3, is not well understood in humans. CSRP3 knockout mice developed dilated cardiomyopathy with hypertrophy and heart failure after birth. Using CRISPR/Cas9, we generated an MLP deficient human ESC line WAe009-A-41 carrying a compound heterozygous 13 bp deletion/1 bp insertion in the CSRP3 gene. The WAe009-A-41 line exhibited a normal female karyotype (46, XX), expressed pluripotency markers and exhibited capability to differentiate into the three germ layers in vitro. MLP expression was not detectable in WAe009-A-41 line. This cell line can be a useful tool for studying the role of CSRP3 in cardiomyopathy and heart failure.

Quercetin increases macrophage cholesterol efflux to inhibit foam cell formation through activating PPARγ-ABCA1 pathway.

The accumulation of cholesterol in macrophages could induce the formation of foam cells and increase the risk of developing atherosclerosis. We wonder if quercetin, one of flavonoids with anti-inflammation functions in different cell types, could elevate the development of foam cells formation in atherosclerosis. We treated foam cells derived from oxLDL induced THP-1 cells with quercetin, and evaluated the foam cells formation, cholesterol content and apoptosis of the cells. We found that quercetin induced the expression of ABCA1 in differentiated THP-1 cells, and increased the cholesterol efflux from THP-1 cell derived foam cells. Eventually, cholesterol level and the formation of foam cell derived from THP-1 cells decreased after quercetin treatment. In addition, quercetin activated PPARγ-LXRα pathway to upregulate ABCA1 expression through increasing protein level of PPARγ and its transcriptional activity. Inhibition of PPARγ activity by siRNA knockdown or the addition of chemical inhibitor, GW9662, abolished quercetin induced ABCA1 expression and cholesterol efflux in THP-1 derived macrophages. Our data demonstrated that quercetin increased cholesterol efflux from macrophages through upregulating the expressions of PPARγ and ABCA1. Taken together, increasing uptake of quercetin or quercetin-rich foods would be an effective way to lower the risk of atherosclerosis.