The antiviral role of largemouth bass STING against iridovirus infection.

Stimulator of interferon gene (STING) plays a crucial role in the innate immune response against viral and bacterial pathogens. However, its function in largemouth bass iridovirus (LMBV) infection remains uncertain. Here, a STING homolog (MsSTING) from largemouth bass (Micropterus salmoides) was cloned and characterized. MsSTING encoded a 407-amino-acid polypeptide, which shared 84.08% and 41.45% identity with golden perch (Perca flavescens) and human (Homo sapiens) homologs, respectively. MsSTING contained four transmembrane domains and a conserved C-terminal domain. The mRNA level of MsSTING was significantly increased in response to LMBV infection in vitro. Subcellular localization observation indicated that MsSTING encoded a cytoplasmic protein, which co-localized predominantly with endoplasmic reticulum (ER) and partially with mitochondria. Moreover, its accurate localization was dependent on the N-terminal transmembrane motif (TM) domains. MsSTING was able to activate interferon (IFN) response, evidenced by the activation of IFN1, IFN3 and ISRE promoters by its overexpression in vitro. Mutant analysis showed that both the N-terminal and C-terminal domain of MsSTING were essential for its activation on IFN response. In addition, overexpression of MsSTING inhibited the transcription and protein levels of viral core genes, indicating that MsSTING exerted antiviral action against LMBV. Consistently, the inhibitory effects were significantly attenuated when the N-terminal or C-terminal domains of MsSTING was deleted. Furthermore, MsSTING overexpression upregulated the transcriptions of interferon-related genes and pro-inflammatory factors, including TANK-binding kinase 1(TBK1), interferon regulatory factor 3 (IRF3), interferon regulatory factor 7 (IRF7), interferon stimulated exonuclease gene 20 (ISG20), interferon-induced transmembrane protein 1(IFITM1), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6). Together, MsSTING exerted antiviral action upon LMBV infection through positive regulation the innate immune response.

The Effects of Foot Reflexology on Vital Signs: A Meta-Analysis of Randomized Controlled Trials.

Introduction: We evaluated the effects of foot reflexology on bodily vital signs. Methods: Randomized controlled trials (RCTs) evaluating the effects of foot reflexology on vital signs were collected for a meta-analysis. Statistical analysis was conducted using RevMan5.4 software and pooled estimates of the effects were reported as mean differences (MDs) with 95% confidence intervals (CIs). Results: Thirteen studies, including 819 patients, met our inclusion criteria. Our results showed that systolic blood pressure (SBP) (MD = -4.62, 95% CI: -5.58 to -3.66; P < 0.00001), diastolic blood pressure (DBP) (MD = -3.32, 95% CI: -4.48 to -2.17; P < 0.00001), heart rate (HR) (MD = -4.76, 95% CI: -6.49 to -3.04; P < 0.00001), respiratory rate (RR) (MD = -0.77, 95% CI: -1.50 to -0.48; P < 0.00001), and pulse oxygen saturation (SpO2) (MD = 0.95, 95% CI: 0.39 to 1.52; P = 0.0009) showed statistical significance in the foot reflexology group. Conclusions: Short-term followup results showed that foot reflexology exerted positive effects on vital signs, reduced BP, HR, and RR and increased SpO2.

Protective Effect of Fasudil on Hydrogen Peroxide-Induced Oxidative Stress Injury of H9C2 Cardiomyocytes.

OBJECTIVE: Oxidative damage is a pathological factor that causes cardiovascular damage in the clinic and is increasingly serious. This study focused on the effect of fasudil on H2O2-induced oxidative damage in cardiomyocytes. MATERIALS AND METHODS: H9C2 cardiomyocytes were cultured in vitro and divided into three groups: control group (Con group), H2O2 treatment (H2O2 group), and fasudil and H2O2 cotreatment (H2O2+fasudil group). The content levels of LDH and MDA in the supernatant were detected, and the morphology of H9C2 cardiomyocytes was observed by light microscopy. 8-OHdG staining was observed by a fluorescence inversion microscope. Cell Counting Kit (CCK-8), western blotting, real-time polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA) were used to investigate the effect of fasudil on the Rho/ROCK signaling pathway. RESULTS: Our results showed that after H2O2 treatment, the H9C2 cardiomyocytes were irregular in shape and elliptical. But the morphology of the H2O2+fasudil group was similar to that of the Con group. The green fluorescence of the H2O2 group was significantly enhancer than that of the Con group, while the green fluorescence of the H2O2+fasudil group was weaker than those of the H2O2 group. By detecting the supernatant, it was found that the contents of LDH were significantly increased, and the contents of SOD and CAT in the H2O2 group were significantly decreased. And the expression of antioxidant indicators in the H2O2 group was significantly decreased by western blotting. The results of RT-PCR showed that SOD1 and SOD2 mRNA in the H2O2 group was significantly reduced, and the contents of GPX1 and GPX3 in the H2O2 group were significantly decreased by enzyme-linked immunosorbent assay (ELISA). The expression of ROCK1, ROCK2, and downstream phosphorylation of myosin phosphatase target subunit-1 (p-MYPT-1) was significantly increased in the H2O2 group, while fasudil inhibited the increase of ROCK1, ROCK2, and p-MYPT-1. CONCLUSIONS: Fasudil can inhibit the Rho/ROCK signaling pathway induced by H2O2 and reduce oxidative stress response, inhibit apoptosis, and improve antioxidant enzyme activity in H9C2 cardiomyocytes thereby delaying cell senescence.

Liquiritigenin attenuates isoprenaline­induced myocardial fibrosis in mice through the TGF­ß1/Smad2 and AKT/ERK signaling pathways.

Myocardial fibrosis is a pathological process characterized by excessive accumulation of extracellular matrix in myocardial interstitial spaces. Myocardial fibrosis is a fundamental process in ventricular remodeling and a primary contributor to the progression of heart failure. Liquiritigenin (LQ) is a flavanone compound with anti­oxidative, anti­carcinogenic, anti­inflammatory and estrogenic properties. The present study aimed to investigate the regulatory potential of LQ treatment in a mouse model of isoprenaline (ISO)­induced cardiac fibrosis and in cultured H9C2 cardiomyocytes stimulated with angiotensin II (Ang II). The treatment of ISO­induced mice with LQ significantly decreased the levels of cardiac injury­related proteins in the serum and ECM accumulation in mouse heart tissues. LQ treatment also effectively alleviated cardiac dysfunction in ISO­treated mice. Further analyses revealed that LQ inhibited ISO­induced collagen formation and activation of the transforming growth factor­ß1 (TGF­ß1)/Smad2 and protein kinase B (AKT)/extracellular signal­regulated kinase (ERK) signaling pathways. As a major pathological event in myocardial fibrosis, the apoptosis of cardiomyocytes has been considered a key mechanism contributing to impaired left ventricle performance. The pretreatment of rat cardiomyocytes with LQ significantly reduced the apoptosis of H9C2 cells, and inhibited Ang II­induced activation of the TGF­ß1/Smad2 and AKT/ERK pathways. In conclusion, the present study revealed that LQ ameliorated ISO­induced myocardial fibrosis in mice and inhibited the apoptosis of cardiomyocytes in vitro by inhibiting the TGF­ß1/Smad2 and AKT/ERK signaling pathways. These results suggested the anti­fibrotic and cardioprotective potential of LQ in fibrosis, thus supporting the use of LQ for the management of cardiomyocyte injury and myocardial fibrosis in patients with cardiac diseases.

Hydroxysafflor Yellow A mitigated myocardial ischemia/reperfusion injury by inhibiting the activation of the JAK2/STAT1 pathway.

Hydroxysafflor Yellow A (HSYA) may reduce ischemia/reperfusion (I/R) injury. However, the underlying molecular mechanisms remain unclear. The present study explored the effect and the mechanisms of HSYA on myocardial injury in vivo and in vitro. Myocardial infarct size was assessed by Evans blue/2,3,5­triphenyltetrazoliumchloride staining. Levels of cardiac troponin I (cTnI), interleukin­6 (IL­6), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured using commercial kits. Alteration of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation was determined by fluorescent signals. Apoptosis was detected by terminal deoxynucleotidyl­transferase­mediated dUTP nick­end labeling staining, flow cytometry assay and caspase­3 activity. Expression levels of the apoptosis­associated proteins were detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. In vivo, animals treated with HSYA presented less severe myocardial injury and decreased janus kinase 2 (JAK2)/signal transducer and activator of transcription 1 (STAT1) activity, improved antioxidant capacity and decreased apoptosis. In vitro, compared with the hypoxia (H)/reoxygenation (R) + HSYA group, AG490 and S1491 treatment decreased the releases of cTnI, IL­6 and LDH and enhanced the resistance to oxidative stress by maintaining MMP and decreasing ROS generation. In addition, AG490 and S1491 were also identified to alleviate the H/R­induced apoptosis by inhibiting caspase 3 activity and modulating the expression levels of cleaved caspase­3, tumor necrosis factor receptor superfamily member 6 (Fas), Fas ligand, B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein. These data suggested that inactivation of the JAK2/STAT1 pathway strengthened the HSYA­induced protective effect in H/R­induced myocardial injury. In conclusion, the treatment of HSYA was effective in decreasing IR­induced myocardial injury, and this may be largely dependent on the JAK2/STAT1 pathway. Therefore, the present study provided a potential strategy to prevent myocardial I/R injury.

Hydroxysafflor yellow A protects against angiotensin II­induced hypertrophy.

Myocardial infarction (MI) is life­threatening and is generally accompanied by myocardial hypertrophy. Notably, Hydroxysafflor yellow A (HSYA) can prevent tissue injuries. The objective of this study was to investigate the effect of HSYA on hypertrophy after MI. Hematoxylin and eosin (H&E) staining assays were performed to measure cell area. The protein synthesis rate was assessed using the 3H Leucine incorporation assay. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR), western blot analysis and the immunohistochemical assay were used to detect the expression of target genes. The activity of superoxide dismutase (SOD), malondialdehyde (MDA) and the reactive oxygen species (ROS) generation were examined using commercial kits. Decreased myocardial hypertrophy was observed in animals treated with HSYA. Furthermore, the expression of nuclear factor (erythroid­derived 2)­like 2 (Nrf2) was higher in HSYA administration groups compared with that in the MI model group. In H9c2 cardiomyocytes, the pretreatment with HSYA increased the cell viability, however, it reduced protein synthesis rate, mitigated cell surface area and decreased the expression of Brain natriuretic factor (BNP) and ß­myosin heavy chain (ß­MHC). By contrast, the downregulation of Nrf2 deteriorated and reversed the effect of Ang II and HSYA. Furthermore, oxidative stress was alleviated by HSYA via inhibiting ROS generation, modulating the activities of SOD and MDA. In addition, the expression of NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase­1 (HO­1) were recovered by the pretreatment of HSYA that was combated by siNrf2. In conclusion, HSYA exerted anti­hypertrophic effects, which was pertinent with the activation of Nrf2/NQO­1/HO­1 signaling pathway. The findings of this study may inspire a novel strategy to combat MI.

Efficacy and safety of ticagrelor in patients with acute coronary syndrome: A meta-analysis of randomized controlled trials.

Acute coronary syndrome (ACS) is a dangerous and urgent clinical pattern of coronary artery disease. Aspirin and adenosine diphosphate P2Y12 receptor antagonists are the standard dual anti-platelet therapy for patients with ACS. Ticagrelor is a new oral antagonist of the adenosine diphosphate P2Y12 receptor. Randomized controlled trials (RCTs) have evaluated the efficacy and safety of ticagrelor compared to clopidogrel or prasugrel in patients with ACS, obtaining conflicting results. Thus, we conducted a meta-analysis of these RCTs to determine the efficacy and safety of ticagrelor in patients with ACS. Results of the meta-analysis indicate that ticagrelor decreased the risk of major adverse cardiovascular events (MACE) and all-cause death, but increased the risk of bleeding events. In Asiatic patients, analysis indicates that ticagrelor did not decrease the risk of MACE and all-cause death, while increasing the risk of bleeding events. Together, this meta-analysis suggests that ticagrelor was more effective, but less safe than clopidogrel and prasugrel in patients with ACS. Subgroup analysis indicates that ticagrelor was not more effective, although less safe than clopidogrel in Asiatic patients, thus more evidence is needed to further evaluate the efficacy and safety of ticagrelor in Asiatic patients.

Does Anterior Fat Pad Removal Reduce the Incidence of Atrial Fibrillation after CABG? A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Atrial fibrillation (AF) is a common complication after coronary artery bypass grafting (CABG). Several prospective randomized controlled trials (RCTs) have evaluated the effect of intact and removed anterior fat pads on the incidence of AF after CABG with conflicting results. We collected these RCTs and conducted a meta-analysis to determine whether anterior fat pad removal is effective in preventing the new onset of AF after CABG. METHODS AND RESULTS: Prospective RCTs were collected for analysis and the main outcomes include the occurrence of AF after CABG, total hospital stay, and major complications. Statistical analysis was conducted using RevMan 5.0.18 software (The Cochrane Collaboration), and pooled estimates of the effect were reported as risk ratios (RRs) or mean differences (MDs) with their 95% confidence intervals (CIs). The results of this meta-analysis indicate that anterior fat pad removal was not associated with a decreased risk of occurrence of AF after CABG (RR = 1.34, 95% CI: 0.88-2.03; P = 0.18), and it also did not increase the risk of major complications (RR = 1.05, 95% CI: 0.75-1.47; P = 0.79) or lengthen total hospital stay (MD = 0.06, 95% CI: -0.46 to 0.58; P = 0.83) compared with the control group. CONCLUSION: Anterior fat pad removal did not decrease the risk of the occurrence of AF after CABG despite its safety and convenience, and it should not be used to prevent new-onset AF after CABG unless new evidence is provided.

Meta-analysis of drug-eluting versus bare metal stents in patients with indications for oral anticoagulation undergoing coronary stenting.

BACKGROUND: Current expert consensus recommends the use of bare metal stent (BMS) for patients with an indication for oral anticoagulation (OAC) undergoing coronary stenting. The use of drug-eluting stents (DES) should be limited. However, there is a lack of evidence to support these recommendations. We performed a meta-analysis to compare the efficacy and safety of DES to BMS in these patients. METHODS: We searched PubMed, Embase, the Cochrane library, and relevant journals. Studies comparing the efficacy and safety of DES to BMS in patients with an indication for OAC undergoing coronary stenting were included. End points included major adverse cardiac events (MACE), death, bleeding complications, and stroke. The outcome assessments were measured by hazard ratio (HR) and its 95% confidence interval. RESULTS: We yielded 453 studies by primary searching. According to the inclusion criteria, four studies enrolling 1,522 patients were finally included. A pooled estimate of HR for MACE, all-cause mortality, myocardial infarction, and bleeding complications showed no significant differences between patients treated with DES and BMS. The risk of target vessel revascularization (TVR) was significantly decreased in the DES implanted patients in comparison with patients with a BMS implantation. CONCLUSION: For patients with an indication for OAC undergoing coronary stenting, DES might a DES can be as safely used as a BMS, and is superior in reducing the risk of TVR.

Landiolol hydrochloride for prevention of atrial fibrillation after cardiac surgery: a meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmic complication after cardiac surgery. Several studies have compared the efficacy of landiolol and placebo or other agents in preventing new-onset AF in patients after cardiac surgery. In this study, we conducted a meta-analysis to determine whether landiolol is effective in preventing new-onset AF after cardiac surgery. METHODS AND RESULTS: Five randomized controlled trials and two retrospective analyses were included in this study. The clinical outcomes of interest were the occurrence of AF after cardiac surgery and major complications. Meta-analysis was performed using RevMan 5.0.18 software, and pooled estimates of the effect were reported as risk ratios (RR) with 95% confidence intervals (CI). The results of this meta-analysis indicate that landiolol is significantly associated with a decreased risk of occurrence of AF after cardiac surgery (RR = 0.33; 95% CI: 0.23-0.48; P < 0.00001) and is not associated with an increased risk of major complications (RR = 0.79; 95% CI: 0.43-1.45; P = 0.45) compared with the control group. CONCLUSION: Landiolol administration in the perioperative period can reduce the occurrence of AF after cardiac surgery without increasing the risk of major complications. It can be used to prevent new-onset AF safely after cardiac surgery.

Impact of image integration on catheter ablation for atrial fibrillation using three-dimensional electroanatomic mapping: a meta-analysis.

BACKGROUND: Studies comparing the procedural and clinical outcomes of catheter ablation for atrial fibrillation (AF) guided by CartoMerge and that by Carto have achieved mixed results (Carto, Biosense Webster, Diamond Bar, CA, USA). We collected these studies and conducted a meta-analysis to determine whether CartoMerge results in better procedural and clinical outcomes. METHODS AND RESULTS: Three randomized controlled trials and two controlled observational studies were collected for analysis. The clinical and procedural outcomes of interest were AF recurrence after catheter ablation, major complications, procedure durations, and fluoroscopy time. Meta-analysis was performed using RevMan 5.0.18 software (The Cochrane Collaboration, Copenhagen, Denmark) and pooled estimates of effect were reported as risk ratios with 95% confidence intervals (CI). The overall results of this meta-analysis indicate that catheter ablation for AF guided by CartoMerge is insignificantly associated with a decreased risk of recurrences (RR = 0.76; 95% CI: 0.55-1.04; P = 0.09) and major complications (RR = 0.73; 95% CI: 0.37-1.45; P = 0.37) compared with that by Carto. CONCLUSION: The image integration using CartoMerge guiding catheter ablation for AF does not improve the main clinical outcomes significantly compared with that by Carto in centers with experienced operators.

Upregulation of heme oxygenase-1 expression by hydroxysafflor yellow A conferring protection from anoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes.

BACKGROUND: Reperfusion therapy is widely utilized for acute myocardial infarction (AMI), so ischemia/reperfusion (I/R) of the heart is frequently encountered in clinical practice. The curative effects of reperfusion therapy for AMI are favourable in most cases, but reperfusion can also cause harmful effect to cardiomyocytes. Hydroxysafflor yellow A (HSYA) is an effective therapeutic agent to alleviate I/R injury, but the mechanisms underlying this therapeutic effect are unknown. METHODS AND RESULTS: The H9c2 cardiomyocyte cell line was incubated with or without HSYA during hypoxia, then it was reoxygenated. In the presence of HSYA, reoxygenation resulted in the upregulated expression and activity of heme oxygenase-1 (HO-1), phosphorylation of Akt, translocation of nuclear factor Nrf2, and most importantly, a reduction in A/R-induced apoptosis. An HO-1 inhibitor completely suppressed HO-1 enzymatic activity upregulated by HSYA and notably diminished the anti-apoptotic effect of HSYA. An inhibitor of PI3K, completely blocked Akt phosphorylation induced by HSYA and partly negated HSYA-induced upregulation of HO-1, translocation of nuclear factor Nrf2 and suppression of apoptosis in the H9c2 cardiomyocytes. CONCLUSIONS: Our study suggests that HSYA can provide protection to H9c2 cardiomyocytes against A/R-induced apoptosis. This protective effect largely depends on the upregulation of HO-1 expression through the PI3K/Akt/Nrf2 signaling pathway.

Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1.

AIM: To explore the effect of neferine on angiotensin II (Ang II)-induced vascular smooth muscle cell (VSMC) proliferation. METHODS: Human umbilical vein smooth muscle cells (HUVSMCs) were used. Cell proliferation was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis. Heme oxygenase (HO)-1 protein expression was tested by Western blot analysis. Extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation was determined by using immunoblotting. RESULTS: Pre-incubation of HUVSMCs with neferine (0.1, 0.5, 1.0, and 5.0 micromol/L) significantly inhibited Ang II-induced cell proliferation in a concentration-dependent manner and neferine 5.0 micromol/L increased HO-1 expression by 259% compared with control. The antiproliferative effect of neferine was significantly attenuated by coapplication of zinc protoporphyrin IX (ZnPP IX, an HO-1 inhibitor) with neferine. Ang II-enhanced ERK1/2 phosphorylation was markedly reversed by neferine. By inhibiting HO-1 activity with ZnPP IX, the inhibitive effect of neferine on ERK1/2 phosphorylation was significantly attenuated. Cobalt-protoporphyrin (CoPP), an HO-1 inducer, significantly decreased Ang II-induced ERK1/2 phosphorylation and inhibited Ang II-induced cell proliferation. The ERK1/2 pathway inhibitor PD98059 significantly blocked Ang II-enhanced ERK1/2 phosphorylation and inhibited cell proliferation. CONCLUSION: These findings suggest that neferine can inhibit Ang II-induced HUVSMC proliferation by upregulating HO-1, leading to the at least partial downregulation of ERK1/2 phosphorylation.

[Study on changes of content of Tannin in Nodus Nelumbinis Rhizomatis Charcoal].

OBJECTIVE: To determine changes of content of Tannin in different Nodus Nelumbinis Rhizomatis Charcoal. METHODS: The content of Tannin of Nodus Nelumbinis Rhizomatis Charcoal was detected by UV and colorimetric method. RESULTS: The content of tannin in standard sample was the highest. CONCLUSION: It should be studied whether the tannin of Nodus Nelumbinis Rhizomatis Charcoal is the active ingredients of hemostasis.