The present study explored the mechanism of Fagopyri Dibotryis Rhizoma(FDR) and its main active components in the treatment of acute lung injury(ALI) based on the network pharmacology and the in vitro experiments. The main active components of FDR were obtained from the TCMSP database and screened by oral bioavailability and drug-likeness. The related target proteins of FDR were retrieved from the PubChem database, and the target genes related to ALI were screened out from the GeneCards database. A protein-protein interaction(PPI) network of compound target proteins and ALI target genes was constructed using STRING 11.0. Ingenuity Pathway Analysis(IPA) platform was used to analyze the common pathways of the potential compound target proteins of FDR and ALI target genes, thereby predicting the key targets and potential signaling pathways of FDR for the treatment of ALI. Finally, the potential pathways and key targets were verified by the in vitro experiments of lipopolysaccharide-induced RAW264.7 cells intervened by epicatechin(EC), the active component of FDR. The results of network pharmacology showed that 15 potential active components such as EC, procyanidin B1, and luteolin presumedly functioned in the treatment of ALI through nuclear transcription factor-κB(NF-κB) signaling pathway, transforming growth factor-β(TGF-β) signaling pathway, and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway through key targets, such as RELA(P65). The results of in vitro experiments showed that 25 μmol·L~(-1) EC had no toxicity to cells and could inhibit the expression of the p65-phosphorylated protein in the NF-κB signaling pathway to down-regulate the expression of downstream inflammatory cytokines, including tumor necrosis factor-α(TNF-α), IL-1β and nitric oxide(NO), and up-regulate the expression of IL-10. These results suggested that the therapeutic efficacy of FDR on ALI was achieved by inhibiting the phosphorylation of p65 protein in the NF-κB signaling pathway and down-regulating the level of proinflammatory cytokines downstream of the signaling pathways.
Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the cell migration and invasion assay data featured in Figs. 2B, 5C, 6B and C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been submitted elsewhere prior to the submission of this paper to Oncology Reports, or were under consideration for publication at around the same time (one of which has been retracted). In view of the fact that certain of these data had already apparently been submitted for publication prior to the submission of this article to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 967‑976, 2018; DOI: 10.3892/or.2018.6204]
Influenza is an infectious respiratory disease that can cause severe inflammatory reactions and threaten human life. Chaishi Tuire Granules (CSTRG), a Chinese patent medicine widely used clinically in the treatment of respiratory diseases in China, has a definite anti-inflammatory effect. However, the mechanism of CSTRG in the treatment of influenza is still unclear. This study aimed to demonstrate the anti-inflammatory effect of CSTRG on influenza A treatment and potential mechanisms.Influenza-associated mice pneumonia model was used to explore the antiviral and anti-inflammatory effects of CSTRG in vivo. Bioinformatics analysis methods such as network pharmacology and molecular docking were carried out to predict the main active components and potential anti-inflammatory targets of CSTRG. The anti-inflammatory activity of CSTRG was determined using the lipopolysaccharide (LPS)-induced macrophages RAW264.7 cells in vitro.In vivo results showed that CSTRG can reduce the viral load in the lung tissue of infected mice, reduce the expression of TNF-α and IL-6 in lung tissue and serum, and regulate the host inflammatory response. Additionally, CSTRG treatment markedly improves the sick signs, weight loss, lung index, and lung pathological changes. Bioinformatics analysis predicted that six active compounds of CSTRG including quercetin, kaempferol, luteolin, beta-sitosterol, sitosterol, and stigmasterol could contribute to the anti-influenza activity through regulating the TRAF6/MAPK14 axis. The following research confirmed that CSTRG significantly inhibited pro-inflammatory cytokines (TNF-α and IL-6) by suppressing the expression of TRAF6 and MAPK14 in LPS-stimulated macrophages RAW264.7 cells.CSTRG might inhibit the inflammatory response by mediating the TRAF6/MAPK14 axis. In the future, in-depth research is still needed to verify the mechanism of CSTRG in the treatment of influenza.
Background: Recently, Chinese patent medicines (CPMs) have been widely used to treat children with influenza in China, with curative effects. Therefore, the efficacy and safety of such treatment require further evaluation. The present meta-analysis integrated data from several independent studies to determine overall treatment trends in children with influenza. Methods: The following databases were searched for randomized controlled trials (RCTs) published from their inception to December 12, 2020: CNKI, Wanfang, SinoMed, PubMed, Cochrane library, and Embase. Two researchers independently extracted the data, assessed the methodological quality of the studies, and conducted a meta-analysis of the results using Review Manager 5.2. The results were assessed using forest plots, and publication bias was evaluated using a funnel plot. Results: A total of 21 RCTs involving 2960 cases were included. Compared to oseltamivir alone, CPMs combined with oseltamivir reduced the duration of symptoms, including that of fever (mean difference [MD] = −0.64, 95% confidence interval [CI]: −0.86 to −0.41, P < 0.00001), cough (MD = −0.82, 95% CI: −1.02 to −0.62, P < 0.00001), nasal obstruction (MD = −0.88, 95% CI: −1.15 to −0.61, P < 0.00001), and sore throat (MD = −0.92, 95% CI: −1.26 to −0.57, P < 0.00001). Combined therapy also reduced the time of viral shedding (MD = −0.53, 95% CI: −0.70 to −0.36, P < 0.00001) and the occurrence of adverse drug reactions (ADRs) (RR=0.53, 95% CI: 0.34 to 0.83, P = 0.005). Conclusions: CPMs combined with oseltamivir reduced the duration of symptoms, shortened the time of viral shedding, and reduced the number of ADRs. However, these results should be considered with caution because there was marked heterogeneity and publication bias in the research data. More rigorous RCTs should be designed to verify the effect of CPMs in children with influenza.
Background: Few studies have examined the association between treatment given time and clinical outcomes, which is indeed of great importance to clinical management of coronavirus disease 2019 (COVID-19). We performed this study to explore whether early treatment brings favorable clinical outcomes. Methods: In this retrospective multicenter study, we included patients aged 18 to 87 years with confirmed COVID-19 on admission from 54 hospitals in nine provinces of China from 21 January to 10 March, 2020. Final date of follow-up was March 17, 2020. All patients were treated by Lung cleansing & detoxifying decoction combined with western medicine. Patients were divided into four groups according to the interval from the first date of onset of symptoms to the date of starting a treatment, i.e., ≤1 week group (≤7 days), 1-2 weeks group (>7 days and ≤14 days), 2-3 weeks group (>14 days and ≤21 days) and >3 weeks group (>21 days). Multivariable Cox proportional hazard ratio (HR) models were used to estimate unadjusted and adjusted HRs and 95% confidence intervals (CIs) for the association between the treatment given time and clinical outcomes (time to recovery, days of viral shedding, duration of hospital stay, course of disease, fever and CT images). Findings: Of the 782 patients (median age was 46 years old, and 405 (52%) were male), there were 321 (41%) patients in ≤1 week group, 221 (28%) in 1-2 weeks group, 123 (16%) in 2-3 weeks group and 117 (15%) in >3 weeks group. Compared to patients in later treatment group (greater than 3 weeks), patients in earlier treatment groups of less than 1 week, 1 to 2 weeks, or 2 to 3 weeks had higher likelihood of recovery, with adjusted HR (95% CI) of 3.81 (2.65-5.48), 2.63 (1.86-3.73) and 1.92 (1.34-2.75), respectively. The median days of viral shedding was 13 days and 12 days in 2-3 weeks group and <2 weeks group respectively, shorter than that in >3 weeks group (P=0.0137). The median course of disease decreased from 34 days to 24 days, 21 days and 18 days when treatment was given every one week in advance compared to that was given later than 3 weeks from the onset of symptoms (P<0.0001). Treatment within 1 week since onset of symptoms was related with a decrease of 1 to 4 days in terms of median duration of hospital stay compared to later treatment (P<0.0001). Interpretation: Earlier treatment was associated with favorable outcomes, including sooner recovery, shorter time to viral shedding, and shorter duration of hospital stay. This paper demonstrated that early treatment could be an effective strategy in the epidemic control, and can provide evidence for government and international organizations to develop the policy of COVID-19.Funding Statement: This study was supported by "National Science and Technology Major Project" (2018ZX10101001-005-003, 2018ZX10101001-005-004).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The study was approved by National Administration of Traditional Chinese Medicine, Administration of Traditional Chinese Medicine of nine provinces and the institutional board of 54 participating setting. Due to the urgency of the treatment of COVID-19, the requirement for informed consent from study participants was replaced by verbal consent.
Abstract BackgroundThe occurrence of CRC is believed to be related to a variety of factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. Our previous studies indicated that the extract of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS), had potent anticancer activities by significantly inhibiting intestinal tumor development in Apc Min/+ mice. However, knowledge regarding the mechanism and effect of YYFZBJS in the prevention of colorectal cancer is limited.MethodsIn this study, we investigated the preventive effects of oral administration of YYFZBJS in enterotoxigenic Bacteroides fragilis (ETBF)-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. Here, the tumor load, tumor number, histology, and the severity of disease activity index (DAI) scores were reduced as expected.Resultsthe intragastric administration of YYFZBJS in AOM/DSS model significantly decreased ETBF abundance, immunity and some M2 macrophage markers, including CD206, Arg-1, IL-10, and TGF-β. Additionally, reversing polarized macrophages, which has been modified by YYFZBJS, could suppressed CRC cell proliferation and infiltration, as demonstrated by decreasing some tumor proliferation-related proteins in a dose-dependent manner, including c-Met, cyclinD1 and MMPs. Importantly, ETBF dysbiosis can contribute to the development of colon tumor by stimulating p-STAT3 medicated M2 macrophages polarization to promote chronic inflammation and adenoma malignant transformation, which effectively constrained by YYFZBJS.ConclusionAltogether, we demonstrate that ETBF dysbiosis may contribute to M2 macrophages-promoted colon carcinogenesis and progression of CRC cells, and indicating that YYFZBJS could be employed as a promising protective agent against ETBF-mediated colorectal cancer.
Influenza infection is a highly contagious, acute febrile respiratory disease caused by the influenza virus. Traditional Chinese Medicine(TCM) has dominated plenty of theoretical and practical approaches in the treatment of influenza. It is, therefore, important to highlight the effects of TCM in the clinical treatment of influenza and their impact on inhibiting the growth of this virus in laboratory experiments. We scrutinized existing evidence on whether TCM is effective in clinical applications. Moreover, we described the potential mechanisms of TCM against the influenza virus. Our findings provide analytical evidence that supports the effectiveness of TCM in treating influenza infections as well as their mechanisms against this virus.
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