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Qingjie-Tuire (QT) granule was approved for clinical use and its combination was reported to treat influenza infection. To explore its active component and mechanism, the components of QT granule were retrieved from UPLC-UC-Q-TOF/MS analysis. The genes corresponding to the targets were retrieved using GeneCards and TTD database. The herb–compound–target network was constructed by Cytoscape. The target protein–protein interaction network was built using STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of QT granule to IAV were performed for further study. The regulation to different signaling transduction events and cytokine/chemokine expression of QT granule was evaluated using Western blotting and real-time qPCR. Totally, 47 compounds were identified and effect of QT granule on cell STAT1/3 signaling pathways was confirmed by A549 cell model. The efficiency of QT granule on host cell contributes to its clinical application and mechanism research.

Doxorubicin (DOX), an anthracycline type of chemotherapy, is an effective therapy for several types of cancer, but serious side effects, such as severe hepatotoxicity, limit its use currently. Accordingly, an effective therapeutic strategy to prevent DOX-related hepatotoxicity is urgently needed. Through the inhibition of oxidative stress, fibroblast growth factor 1 (FGF1) is an effect therapy for a variety of liver diseases, but its use is limited by an increased risk of tumorigenesis due to hyperproliferation. Resveratrol (RES), a natural product, inhibits the growth of many cancer cell lines, including liver, breast, and prostate cancer cells. Therefore, this study explored whether and how RES in combination with FGF1 can alleviate DOX-induced hepatotoxicity. The results showed that RES or FGF1 alone improved DOX-induced hepatic inflammation, apoptosis and oxidative stress, and these adverse effects were further attenuated after treatment with both RES and FGF1. Mechanistically, both in vivo and in vitro results showed that RES/FGF1 reduced oxidative stress and thereby alleviated liver injury by promoting nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and subsequently upregulating expression of antioxidant proteins in an adenosine monophosphate-activated protein kinase (AMPK)-dependent manner. Together, our results not only demonstrate that co-treatment with RES and FGF1 significantly inhibited DOX-induced hepatic inflammation and apoptosis, but also that co-treatment with RES and FGF1 markedly suppressed DOX-induced hepatic oxidative stress, via targeting the AMPK/NRF2 pathway and subsequently ameliorating hepatic dysfunction. Thus, the combination of RES and FGF1 may provide a new therapeutic strategy for limiting DOX-induced hepatotoxicity.

Although it is known that the expression and activity of sirtuin 1 (SIRT1) significantly decrease in doxorubicin (DOX)-induced cardiomyopathy, the role of interaction between SIRT1 and sestrin 2 (SESN2) is largely unknown. In this study, we investigated whether SESN2 could be a crucial target of SIRT1 and the effect of their regulatory interaction and mechanism on DOX-induced cardiac injury. Here, using DOX-treated cardiomyocytes and cardiac-specific Sirt1 knockout mice models, we found SIRT1 deficiency aggravated DOX-induced cardiac structural abnormalities and dysfunction, whereas the activation of SIRT1 by resveratrol (RES) treatment or SIRT1 overexpression possessed cardiac protective effects. Further studies indicated that SIRT1 exerted these beneficial effects by markedly attenuating DOX-induced oxidative damage and apoptosis in a SESN2-dependent manner. Knockdown of Sesn2 impaired RES/SIRT1-mediated protective effects, while upregulation of SESN2 efficiently rescued DOX-induced oxidative damage and apoptosis. Most importantly, SIRT1 activation could reduce DOX-induced SESN2 ubiquitination possibly through reducing the interaction of SESN2 with mouse double minute 2 (MDM2). The recovery of SESN2 stability in DOX-impaired primary cardiomyocytes by SIRT1 was confirmed by Mdm2-siRNA transfection. Taken together, our findings indicate that disrupting the interaction between SESN2 and MDM2 by SIRT1 to reduce the ubiquitination of SESN2 is a novel regulatory mechanism for protecting hearts from DOX-induced cardiotoxicity and suggest that the activation of SIRT1-SESN2 axis has potential as a therapeutic approach to prevent DOX-induced cardiotoxicity.

Osteoblast dysfunction, induced by high glucose (HG), negatively impacts bone homeostasis and contributes to the pathology of diabetic osteoporosis (DOP). One of the most widely recognized mechanisms for osteoblast dysfunction is oxidative stress. Resveratrol (RES) is a bioactive antioxidant compound to combat oxidative damage. However, its role in the protection of HG-induced osteoblast dysfunction has not been clarified. Therefore, our study aimed to explore potential regulatory mechanisms of RES for attenuating HG-induced osteoblast dysfunction. Our results showed that osteoblast dysfunction under HG condition was significantly ameliorated by RES via the activation of nuclear factor erythroid 2-related factor (NRF2) to suppress oxidative stress. Furthermore, using Nrf2-shRNA and wortmannin, we identified that activation of NRF2 via RES was regulated by the AKT/glycogen synthase kinase 3β (GSK3β)/FYN axis.

A cumulative and progressively developing cardiomyopathy induced by adriamycin (ADR)-based chemotherapy is a major obstacle for its clinical application. However, there is a lack of safe and effective method to protect against ADR-induced cardiotoxicity. Here, we found that mRNA and protein levels of FGF1 were decreased in ADR-treated mice, primary cardiomyocytes and H9c2 cells, suggesting the potential effect of FGF1 to protect against ADR-induced cardiotoxicity. Then, we showed that treatment with a FGF1 variant (FGF1ΔHBS) with reduced proliferative potency significantly prevented ADR-induced cardiac dysfunction as well as ADR-associated cardiac inflammation, fibrosis, and hypertrophy. The mechanistic study revealed that apoptosis and oxidative stress, the two vital pathological factors in ADR-induced cardiotoxicity, were largely alleviated by FGF1ΔHBS treatment. Furthermore, the inhibitory effects of FGF1ΔHBS on ADR-induced apoptosis and oxidative stress were regulated by decreasing p53 activity through upregulation of Sirt1-mediated p53 deacetylation and enhancement of murine double minute 2 (MDM2)-mediated p53 ubiquitination. Upregulation of p53 expression or cardiac specific-Sirt1 knockout (Sirt1-CKO) almost completely abolished FGF1ΔHBS-induced protective effects in cardiomyocytes. Based on these findings, we suggest that FGF1ΔHBS may be a potential therapeutic agent against ADR-induced cardiotoxicity.

Ganlanye (GLY), the leaf of Canarium album (Lour.) DC., is a traditional Chinese medicinal herb for warm disease treatment. We found that its aqueous extract could inhibit the influenza A virus. To find and characterize anti-influenza virus phytochemicals from GLY, we performed (1) bioassay-guided isolation, (2) a cell and animal assay, and (3) a mechanism study. Bioassay-guided isolation was used to identify the effective components. Influenza virus-infected MDCK cell and BALB/c mouse models were employed to evaluate the anti-influenza virus activities. A MUNANA assay was performed to find the NA inhibitory effect. As a result, urolithin M5 was obtained from the crude extract of GLY. It inhibited influenza virus activities in vitro and in vivo by suppressing the viral NA activity. In the MDCK cell model, urolithin M5 could inhibit an oseltamivir-resistant strain. In a PR8-infected mouse model, 200 mg/kg/d urolithin M5 protected 50% of mice from death and improved lung edema conditions. GLY was recorded as a major traditional herb for warm disease treatment. Our study identified GLY as a potent anti-influenza herb and showed urolithin M5 as the active component. We first report the in vivo activity of urolithin M5 and support the anti-influenza application of GLY.

Fibroblast growth factor 21 (FGF21), is an emerging metabolic regulator mediates multiple beneficial effects in the treatment of metabolic disorders and related complications. Recent studies showed that FGF21 acts as an important inhibitor in the onset and progression of cardiovascular complications of diabetes mellitus (DM). Furthermore, evidences discussed so far demonstrate that epigenetic modifications exert a crucial role in the initiation and development of DM-related cardiovascular complications. Thus, epigenetic modifications may involve in the function of FGF21 on DM-induced cardiovascular complications. Therefore, this review mainly interprets and delineates the recent advances of role of FGF21 in DM cardiovascular complications. Then, the possible changes of epigenetics related to the role of FGF21 on DM-induced cardiovascular complications are discussed. Thus, this article not only implies deeper understanding of the pathological mechanism of DM-related cardiovascular complications, but also provides the possible novel therapeutic strategy for DM-induced cardiovascular complications by targeting FGF21 and related epigenetic mechanism.

Diabetes mellitus (DM) is a highly prevalent chronic disease that is accompanied with serious complications, especially cardiac and vascular complications. Thus, there is an urgent need to identify new strategies to treat diabetic cardiac and vascular complications. Nuclear factor erythroid 2-related factor 2 (NRF2) has been verified as a crucial target for the prevention and treatment of diabetic complications. The function of NRF2 in the treatment of diabetic complications has been widely reported, but the role of NRF2-related epigenetic modifications remains unclear. The purpose of this review is to summarize the recent advances in targeting NRF2-related epigenetic modifications in the treatment of cardiac and vascular complications associated with DM. We also discuss agonists that could potentially regulate NRF2-associated epigenetic mechanisms. This review provides a better understanding of strategies to target NRF2 to protect against DM-related cardiac and vascular complications.

Diabetes mellitus (DM) has been one of the largest health concerns of the 21st century due to the serious complications associated with the disease. Therefore, it is essential to investigate the pathogenesis of DM and develop novel strategies to reduce the burden of diabetic complications. Sirtuin 1 (SIRT1), a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase, has been reported to not only deacetylate histones to modulate chromatin function but also deacetylate numerous transcription factors to regulate the expression of target genes, both positively and negatively. SIRT1 also plays a crucial role in regulating histone and DNA methylation through the recruitment of other nuclear enzymes to the chromatin. Furthermore, SIRT1 has been verified as a direct target of many microRNAs (miRNAs). Recently, numerous studies have explored the key roles of SIRT1 and other related epigenetic mechanisms in diabetic complications. Thus, this review aims to present a summary of the rapidly growing field of epigenetic regulatory mechanisms, as well as the epigenetic influence of SIRT1 on the development and progression of diabetic complications, including cardiomyopathy, nephropathy, and retinopathy.

Abstract Background Sheng Jiang San (SJS), a multi-herb formulation, is used in treating high fever, thirsty and anxiety in ancient China and it is sometimes used to treat seasonal influenza nowadays. However, there is no evidence-based investigation and mechanism research to support the anti-influenza efficacy of SJS. This study aims at evaluating the anti-influenza effect of SJS and investigating its possible mechanism. Methods The inhibitory effect of SJS against different influenza virus strains on MDCK cells was examined. Influenza virus infected BALB/c mice were employed to evaluate the efficacy as in vivo model. Mice challenged with A/PR/8/34 (H1N1) were orally administrated 1 g/kg/day of SJS for seven days and monitored for 14 days. The survival rate, body weight changes, lung index, lung viral load, histopathologic changes and immune regulation of the mice were measured. The underlying anti-influenza virus mechanism of SJS was studied by a series of biological assays to determine if hemagglutinin, ribonucleoprotein complex or neuraminidase were targets of SJS. Results Results showed SJS exerted a broad-spectrum of inhibitory effects on multiple influenza strains in a dose-dependent manner. IC50 of SJS against A/WSN/33 (H1N1) was lower than 35 μg/ml. SJS also protected 50% of mice from A/PR/8/34 (H1N1) infection. The lung index and the lung viral load of SJS treated mice were significantly decreased compared with untreated mice. Meanwhile, SJS targeted on neuraminidase of influenza virus as SJS at 2 mg/ml inhibited 80% of neuraminidase enzymatic activity. SJS also significantly down-regulated TNF-α and up-regulated IL-2 of influenza virus induced mice. Conclusions Thus, SJS is a useful formulation for treating influenza virus infection.

A field experiment with four treatments (chemical fertilizer alone, CK; manure plus chemical fertilizer, CM; Trichoderma harzianum plus chemical fertilizer, CF; T. harzianum plus manure plus chemical fertilizer, CMF) was conducted to investigate changes in soil bacterial community and cotton yield in 2020 and 2021. Soil aggregate stability and economic feasibility of the four treatments were evaluated. Manure and T. harzianum application significantly improved soil organic carbon (SOC) and total nitrogen and increased soil aggregate stability. Increases of Proteobacteria abundance were 31.62% and 23.51% in 2020 and 2021, respectively, while the increases of Actinobacteria were increased by 21.65% in 2020 and 19.19% in 2021. Manure effects contributed to 46.15% variation of soil bacterial community while T. harzianum contributed to 40.67% variation. Relative abundances of Acidobacteria and Actinobacteria were negatively correlated with SOC. Differently, Chloroflexi was positively correlated with SOC. Concerning the economic feasibility, maximum appreciation was also obtained when manure combined with T. harzianum, which was better than sole manure or T. harzianum. Co-application of manure and T. harzianum improved soil fertility and regulated soil bacterial community which contributed to increases of cotton yield. Thus, it can be applied as a promising measure for promoting cotton production. [ABSTRACT FROM AUTHOR]