Vascular Aging and Atherosclerosis: A Perspective on Aging.

Vascular aging (VA) is recognized as a pivotal factor in the development and progression of atherosclerosis (AS). Although various epidemiological and clinical research has demonstrated an intimate connection between aging and AS, the candidate mechanisms still require thorough examination. This review adopts an aging-centric perspective to deepen the comprehension of the intricate relationship between biological aging, vascular cell senescence, and AS. Various aging-related physiological factors influence the physical system's reactions, including oxygen radicals, inflammation, lipids, angiotensin II, mechanical forces, glucose levels, and insulin resistance. These factors cause endothelial dysfunction, barrier damage, sclerosis, and inflammation for VA and promote AS via distinct or shared pathways. Furthermore, the increase of senescent cells inside the vascular tissues, caused by genetic damage, dysregulation, secretome changes, and epigenetic modifications, might be the primary cause of VA.

Sheng Mai Yin shows anti-fatigue, anti-hypoxia and cardioprotective potential in an experimental joint model of fatigue and acute myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular disease (CVD) and fatigue are two common diseases endangering human life and health that may interact and reinforce one another. Myocardial infarction survivors frequently experience fatigue, and acute myocardial infarction (AMI) is one of the most common cardiovascular diseases that cause fatigue-induced sudden death. Sheng Mai Yin (SMY), a Chinese medicine prescription, is traditionally used for the treatment of diabetes and cardiovascular disease, and has been demonstrated to reduce fatigue and safeguard cardiac function. AIM OF THE STUDY: This study aims to investigate the effects and underlying mechanisms of SMY in treating fatigue and AMI. MATERIALS AND METHODS: The pharmacological mechanisms of SMY in treating fatigue and AMI were predicted by bioinformatics and network pharmacology methods. After administering SMY at high, medium and low doses, the swimming time to exhaustion, hemoglobin level, serological parameters and hypoxia tolerance time were detected in C57BL/6N mice, and the left ventricular ejection fractions (LVEF), left ventricular fractional shortening (LVFS), grasp strength, cardiac histopathology, serological parameters and the expression of PINK1 and Parkin proteins were examined in Wistar rats. RESULTS: 371 core targets for SMY and 282 disease targets for fatigue and AMI were obtained using bioinformatics and network pharmacology methods. Enrichment analysis of target genes revealed that SMY might interfere with fatigue and AMI through biological processes such as mitochondrial autophagy, apoptosis, and oxidative stress. For in vivo experiments, SMY showed significant anti-fatigue and hypoxia tolerance effects in mice; It also improved the cardiac function and grasp strength, decreased their cardiac index, myocardial injury and fibrosis degree, and induced serological parameters levels and the expression of PTEN-induced putative kinase 1 (PINK1) and Parkin proteins in myocardium, suggesting that SMY may exert cardioprotective effects in a joint rat model of fatigue and AMI by inhibiting excessive mitochondrial autophagy. CONCLUSION: This study revealed the anti-fatigue, anti-hypoxia and cardioprotective effects of SMY in a joint model of fatigue-AMI, and the pharmacological mechanism may be related to the inhibition of mitochondrial autophagy in cardiomyocytes through the PINK1/Parkin pathway. The discoveries may provide new ideas for the mechanism study of traditional Chinese medicine, especially complex prescriptions, in treating fatigue and AMI.

[Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model].

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.

Antiviral effect and mechanism of Phillyrin and its reformulated FS21 against influenza.

Background: Influenza virus causes significant morbidity and mortality with pandemic threat. Oleaceae Fructus Forsythiae is a medicinal herb. This study aimed to investigate antiviral effect of Phillyrin, a purified bioactive compound from this herb, and its reformulated preparation FS21 against influenza and its mechanism. Methods: Madin-Darby Canine Kidney (MDCK) cells were infected by one of six influenza viruses: five influenza A viruses (IAVs: three H1N1 and two H3N2) and one influenza B virus (IBV). Virus-induced cytopathic effects were observed and recorded under microscope. Viral replication and mRNA transcription were evaluated by quantitative polymerase chain reaction (qPCR) and protein expression by Western blot. Infectious virus production was assessed using TCID50 assay, and IC50 was calculated accordingly. Pretreatment and time-of-addition experiments with Phillyrin or FS21 added 1 h before or in early (0-3 h), mid (3-6 h), or late (6-9 h) stages of viral infection were performed to assess their antiviral effects. Mechanistic studies included hemagglutination and neuraminidase inhibition, viral binding and entry, endosomal acidification, and plasmid-based influenza RNA polymerase activity. Results: Phillyrin and FS21 had potent antiviral effects against all six IAV and IBV in a dose-dependent manner. Mechanistic studies showed that both suppressed influenza viral RNA polymerase with no effect on virus-mediated hemagglutination inhibition, viral binding or entry, endosomal acidification, or neuraminidase activity. Conclusions: Phillyrin and FS21 have broad and potent antiviral effects against influenza viruses with inhibition of viral RNA polymerase as the distinct antiviral mechanism.

Identification of a Novel Angiogenesis Signalling circSCRG1/miR-1268b/NR4A1 Pathway in Atherosclerosis and the Regulatory Effects of TMP-PF In Vitro.

Angiogenesis contributes to plaque instability in atherosclerosis and further increases cardio-cerebrovascular risk. Circular RNAs (circRNAs) are promising biomarkers and potential therapeutic targets for atherosclerosis. Previous studies have demonstrated that tetramethylpyrazine (TMP) and paeoniflorin (PF) combination treatment (TMP-PF) inhibited oxidized low-density lipoprotein (ox-LDL)-induced angiogenesis in vitro. However, whether circRNAs regulate angiogenesis in atherosclerosis and whether TMP-PF can regulate angiogenesis-related target circRNAs in atherosclerosis are unknown. In this study, human RNA sequencing (RNA-seq) data were analysed to identify differentially expressed (DE) circRNAs in atherosclerosis and to obtain angiogenesis-associated circRNA-microRNA (miRNA)-messenger RNA (mRNA) networks. Target circRNA-related mechanisms in angiogenesis in atherosclerosis and the regulatory effects of TMP-PF on target circRNA signalling were studied in ox-LDL-induced human umbilical vein endothelial cells (HUVECs) by cell proliferation, migration, tube formation, and luciferase reporter assays, real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. A novel circRNA (circular stimulator of chondrogenesis 1, circSCRG1) was initially identified associated with angiogenesis in atherosclerosis, and circSCRG1 silencing up-regulated miR-1268b expression, increased nuclear receptor subfamily 4 group A member 1 (NR4A1) expression and then promoted ox-LDL-induced angiogenesis. TMP-PF (1 µmol/L TMP combined with 10 µmol/L PF) up-regulated circSCRG1 expression, mediated miR-1268b to suppress NR4A1 expression and then inhibited ox-LDL-induced angiogenesis. However, circSCRG1 silencing abolished the inhibitory effects of TMP-PF on ox-LDL-induced angiogenesis, which were rescued by the miR-1268b inhibitor. In conclusion, circSCRG1 might serve as a new target regulating angiogenesis in atherosclerosis via the circSCRG1/miR-1268b/NR4A1 axis and TMP-PF could regulate the circSCRG1/miR-1268b/NR4A1 axis to inhibit angiogenesis in atherosclerosis in vitro, indicating a novel angiogenesis signalling circSCRG1/miR-1268b/NR4A1 pathway in atherosclerosis and the regulatory effects of TMP-PF, which might provide a new pharmaceutical strategy to combat atherosclerotic plaque instability.

Lactoferrin modification of berberine nanoliposomes enhances the neuroprotective effects in a mouse model of Alzheimer's disease.

Previous studies have shown that berberine has neuroprotective effects against Alzheimer's disease, including antagonizing tau phosphorylation, and inhibiting acetylcholinesterase activity and neural cell apoptosis. However, its low bioavailability and adverse reactions with conventional administration limit its clinical application. In this study, we prepared berberine nanoliposomes using liposomes characterized by low toxicity, high entrapment efficiency, and biodegradability, and modified them with lactoferrin. Lactoferrin-modified berberine nanoliposomes had uniform particle size and high entrapment efficiency. We used the lactoferrin-modified berberine nanoliposomes to treat a mouse model of Alzheimer's disease established by injection of amyloid-beta 1-42 into the lateral ventricle. Lactoferrin-modified berberine nanoliposomes inhibited acetylcholinesterase activity and apoptosis in the hippocampus, reduced tau over-phosphorylation in the cerebral cortex, and improved mouse behavior. These findings suggest that modification with lactoferrin can enhance the neuroprotective effects of berberine nanoliposomes in Alzheimer's disease.

[Effect and mechanism of Huangqi Shengmai Decoction in treatment of joint rat model of fatigue and myocardial injury].

This study aims to investigate the effects and the underlying mechanism of Huangqi Shengmai Decoction(HQSMD) in the treatment of fatigue and myocardial injury in a joint rat model. Wistar rats were assigned into 4 groups: sham, model, diltiazem hydrochloride(positive control), and HQSMD. The joint model of fatigue and myocardial injury was established by 14-day exhausted swimming followed by high ligation of the left anterior descending coronary artery. The rats in the sham group underwent a sham operation without coronary artery ligation or swimming. Since the fourth day after the ligation, swimming was continued in the model group and the drug-treated groups for the following 4 weeks. Meanwhile, the rats in the positive control group and the HQSMD group were respectively administrated intragastrically with diltiazem hydrochloride(20 mg·kg~(-1)·d~(-1)) and HQSMD(0.95 g·kg~(-1)·d~(-1)) for 4 weeks, while the shams and the models were given the same volume of normal saline. The left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), grip strength, and myocardial pathophysiological changes were measured to evaluate the anti-fatigue and cardioprotective effects of HQSMD. The protein levels of PTEN-induced putative kinase 1(PINK1) and parkin in the myocardium were measured by Western blot to preliminarily elucidate the mechanism of HQSMD in ameliorating myocardial injury by suppressing mitochondrial autophagy. Compared with the shams, the models showed weakened heart function(LVEF and LVFS, P<0.01), decreased grasping ability(P<0.05), elevated blood urea nitrogen(BUN) and aldosterone(ALD) levels(P<0.01), aggravated myocardial fibrosis and connective tissue hyperplasia(P<0.01), and up-regulated protein levels of PINK1(P<0.01) and parkin(P<0.05). Four-week treatment with HQSMD increased the LVEF and LVFS levels(P<0.01), enhanced the grip strength(P<0.01), reduced the serum levels of BUN(P<0.01) and ALD(P<0.05), alleviated the pathological injury and fibrosis in the myocardium(P<0.01), and down-regulated the protein levels of PINK1(P<0.01) and parkin(P<0.05) in heart tissue. The results demonstrate that HQSMD may alleviate myocardial fibrosis and protect myocardium by suppressing the excessive mitochondrial auto-phagic activity and reducing the excessively elevated ALD level, thereby ameliorating fatigue and myocardial injury.

Effects of Tai Chi on health status in adults with chronic heart failure: A systematic review and meta-analysis.

Background: Chronic heart failure (CHF) is among the top causes of cardiovascular morbidity, and most patients with CHF have poor health status. Tai Chi, a mind-body exercise that originated in China, is beneficial for health status. This study was conducted to evaluate the effects of Tai Chi on health status in adults with CHF. Methods: The Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Database, and Chinese Scientific Journal Database were searched from the inception to 22 October 2021. This meta-analysis was performed using the fixed- or random-effects model. Continuous outcomes were carried out using mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI). Dichotomous outcomes were determined using risk ratio (RR) with 95%CI. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE)pro Guideline Development Tool (GDT) online software was used to present outcome-specific information regarding overall certainty of evidence from studies. Results: In total, 15 studies including 1,236 participants were finally included. Compared with usual care alone, Tai Chi combined with usual care achieved efficacy in improving Minnesota Living with Heart Failure Questionnaire (MD = -8.51; 95% CI: -10.32 to -6.70; p < 0.00001), 6-min walk test (MD = 43.47; 95% CI: 33.38 to 54.10; p < 0.00001), left ventricular ejection fraction (MD = 6.07; 95% CI: 3.44 to 8.70; p < 0.00001), B-type natriuretic peptide/N-terminal fragment of pro-BNP (SMD = -1.12; 95% CI: -1.70 to -0.54; p = 0.0002), Hamilton Depression Rating Scale (MD = -2.89; 95% CI: -4.87 to -0.91; p = 0.004), Pittsburgh Sleep Quality Index (MD = -2.25; 95% CI: -3.88 to -0.61; p = 0.007), timed up and go test (MD = -1.34; 95% CI: -2.50 to -0.19; p = 0.02), and reduced the risk of heart failure hospitalization (RR = 0.47; 95% CI: 0.25 to 0.88; p = 0.02). However, there was no difference in the outcome of peak oxygen uptake (MD = 1.38; 95% CI: -1.51 to 4.28; p = 0.35). All-cause mortality or cardiovascular death could not be evaluated due to insufficient data. The certainty of evidence ranged from very low to moderate due to the risk of bias, inconsistency, imprecision, and publication bias. Conclusion: Tai Chi might be safe and showed beneficial effects on health status in patients with CHF. However, more high-quality and long-term studies are still needed to further evaluate the effects of Tai Chi.

A Bibliometric Analysis of Research on the Links Between Gut Microbiota and Atherosclerosis.

Background: Emerging evidence has linked gut microbiota (GM) and its related metabolites to atherosclerosis (AS). This study aimed to analyze the evolution of GM in AS in the past decades, and provide valuable insights in this field. Methods: Web of Science Core Collection (WoSCC) was applied to retrieve the publications related to GM in AS from their inception until 2 December 2021, and the data was analyzed in Microsoft Excel, Scimago Graphica, CiteSpace, and VOSviewer. Results: In total, 560 documents were extracted from the WoSCC databases. The publications have shown rapid growth since 2008. China and Cleveland Clin were the most prolific country and institution, respectively. The journal with the most publications is Nutrients, and Nature was the most co-cited journal. Among 3556 related authors, Hazen, Stanley L., Tang, W. H. Wilson, and Wang, Zeneng were the top 3 contributing authors in this field. Aside from "gut microbiota," "atherosclerosis," the terms "TMAO," "metabolite," "obesity," and "phosphatidylcholine" were frequently occurred in the abstract and title of articles. Burst detection of keywords indicated that "metabolic syndrome," "acid," and "bile acid" were hot topics in recent years. According to the co-citation analysis of references, the research focus in this area has changed over time, and recent researches focus on choline, hypertension, butyrate, and berberine. Conclusion: Our study showed that the researches of GM in AS have been flourishing, and the content themes were constantly deepened. Human GM is critical to atherosclerotic diseases, and this hot topic is still worthy of more focus in the future.

Efficacy and Safety of Different Courses of Tongxinluo Capsule as Adjuvant Therapy for Coronary Heart Disease after Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Tongxinluo capsule (TXLC) is a widely used traditional Chinese medicine for coronary heart disease (CHD). However, the efficacy and safety of different courses of TXLC for CHD after percutaneous coronary intervention (PCI) have not been systematically evaluated yet. The Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database were searched from the inception to 26 August 2021. A meta-analysis was performed using a fixed- or random-effects model. The risk of adverse cardiovascular events, mortality, or adverse effects was evaluated by risk ratio (RR) with 95% confidence interval (CI). Thirty-four studies involving 3652 patients were finally included. After the 6-month treatment, compared with conventional treatment alone, TXLC combined with conventional treatment achieved better efficacy in lowering the risk of angiographic restenosis (RR = 0.37, 95% CI = 0.28−0.48, p < 0.001), myocardial infarction (RR = 0.38, 95% CI = 0.25−0.60, p < 0.001), heart failure (RR = 0.32, 95% CI = 0.18−0.56, p < 0.001), angina (RR = 0.26, 95% CI = 0.17−0.38, p < 0.001), revascularization (RR = 0.20, 95% CI = 0.09−0.46, p < 0.001), all-cause mortality (RR = 0.24, 95% CI = 0.10−0.58, p = 0.001), and mortality due to any cardiovascular event (RR = 0.27, 95% CI = 0.09−0.80, p = 0.018). After the 12-month treatment, TXLC reduced the recurrence risk of angina (RR = 0.40, 95% CI = 0.20−0.80, p = 0.009). However, there was no difference in any outcomes after the 3-month treatment. Besides, no difference was found in the incidence of adverse effects after the 3-month and 6-month treatments (3 months: RR = 0.73, 95% CI = 0.35−1.56, p = 0.418; 6 months: RR = 1.71, 95% CI = 0.74−3.93, p = 0.209). The certainty of evidence ranged from very low to moderate due to the risk of bias, inconsistency, and imprecision. TXLC showed beneficial effects on reducing the adverse cardiovascular events without compromising safety for CHD patients after PCI on the 6-month course. However, due to the unavoidable risk of bias, more high-quality and long-term studies are still needed to further evaluate the efficacy and safety of TXLC in many countries, not only in China.

Pantao Pill Improves the Learning and Memory Abilities of APP/PS1 Mice by Multiple Mechanisms.

Background: To explore the effect and mechanisms of Pantao Pill (PTP) on cognitive impairment. Methods: Network pharmacology was performed to analyze the mechanism of PTP treating cognitive impairment. The targets of PTP and cognitive impairment were predicted and used to construct protein-protein interaction (PPI) networks. The intersection network was selected, and the core network was obtained through topological analysis. Enrichment analysis was conducted to obtain the GOBP terms and KEGG pathways. We then performed experiments to validate the results of the network pharmacology by using an APP/PS1 transgenic mouse model. The APP/PS1 mice were divided into four groups: the model group, the high-dose PTP (3.6 g/kg·d) group, the low-dose PTP (1.8 g/kg·d) group, and the positive control group (donepezil hydrochloride, 2 mg/kg·d). Wild-type (WT) C57 mice served as a normal control group. PTP and donepezil were administered by gavage for 8 weeks. Results: Network pharmacology showed that PTP might improve cognitive impairment by regulating autophagy, apoptosis, and oxidative stress. For the Morris water maze test, a significant difference was shown in the total swimming distance among groups (p < 0.05) in the positioning navigation experiment, and with training time extension, the swimming speed increased (p < 0.01). In the space probe test, PTP administration significantly reduced the swimming path length and the escape latency of APP/PS1 mice (p < 0.05 or p < 0.01), whereas it had no effect on the swimming speed (p > 0.05). PTP (3.6 g/kg/d) rescued the reduction of norepinephrine and acetylcholine levels (p < 0.05), and increased the acetylcholinesterase concentration (p < 0.05) in the brain tissue. PTP (1.8 g/kg/d) increased the norepinephrine level (p < 0.01). PTP rescued the activity reduction of superoxide dismutase in the brain tissue (p < 0.01) and the neuron cell pyknosis in the hippocampal CA region (p < 0.05). PTP reduced ATG12 and PS1 expression (p < 0.05 or p < 0.01), and increased Bcl-2 expression in the brain tissue (p < 0.05). Conclusion: PTP can significantly improve the learning and memory abilities of APP/PS1 mice, and the mechanism may be related to the increase of neurotransmitter acetylcholine and norepinephrine levels, the reduction of the excessive autophagic activation, and the suppression of oxidative stress and excessive apoptotic activity.

Red Yeast Rice Preparations Reduce Mortality, Major Cardiovascular Adverse Events, and Risk Factors for Metabolic Syndrome: A Systematic Review and Meta-analysis.

Background: Metabolic syndrome (MetS) is characterized by the cooccurrence of obesity, insulin resistance, dyslipidaemia, and hypertension. Red yeast rice (RYR) preparations might be beneficial for the prevention and treatment of MetS. Objective: To implement a systematic review and meta-analysis to determine whether RYR preparations improve clinical endpoints and reduce risk factors for MetS. Methods: The PubMed, Cochrane Library, EMBASE, Scopus, China National Knowledge Infrastructure, Chinese VIP Information, and WanFang databases were searched for randomized controlled trials (published up to September 2020), and a meta-analysis was performed using fixed- or random-effects models. The primary outcome measures were mortality and major adverse cardiovascular events (MACEs), and the secondary outcome measures were biochemical parameters of blood glucose, blood lipids, and blood pressure. The registration number is CRD42020209186. Results: A total of 921 articles were identified, of which 30 articles were included in this article. RYR preparations group demonstrated significant improvements in MetS compared with control group. RYR preparations reduced the mortality and MACEs (RR = 0.62, 95% CI [0.49, 0.78]; RR = 0.54, 95% CI [0.43, 0.66]). In terms of blood glucose metabolism, fasting plasma glucose (FPG) (MD = -0.46 mmol/L, 95% CI [-0.71, -0.22]), haemoglobin A1c (HbA1c) (MD = -0.49, 95% CI [-0.71, -0.26]) and the homeostasis model assessment of insulin resistance (HOMA-IR) (MD = -0.93, 95% CI [-1.64, -0.21]) were decreased. Regarding the lipid metabolism, total cholesterol (TC) (MD = -0.74 mmol/L, 95% CI [-1.02, -0.46]), triglycerides (TG) (MD = -0.45 mmol/L, 95% CI [-0.70, -0.21]), and low-density lipoprotein cholesterol (LDL) (MD = -0.42 mmol/L, 95% CI [-0.78, -0.06]) were decreased, while high-density lipoprotein cholesterol (HDL) (MD = 0.14 mmol/L, 95% CI [0.09, 0.20]) was increased. Regarding blood pressure, the mean arterial pressure (MAP) (MD = -3.79 mmHg, 95% CI [-5.01, -2.57]) was decreased. In addition, RYR preparations did not increase the incidence of adverse reactions (RR = 1.00, 95% CI [0.69, 1.43]). Conclusion: RYR preparations reduce mortality, MACEs, and multiple risk factors for MetS without compromising safety, which supports its application for the prevention and treatment of MetS. However, additional high-quality studies are needed to provide more evidence for the effect of RYR on MetS due to the heterogeneity in this study. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO, identifier CRD42020209186.

[Effects of components in stasis-resolving and collateral-dredging Chinese herbal medicines on angiogenesis and inflammatory response of human umbilical vein endothelial cells induced by VEGF].

The present study investigated the mechanism of components in stasis-resolving and collateral-dredging Chinese herbal medicines, including scutellarin(Scu), paeonol(Pae), and hydroxy safflower yellow A(HSYA), in the treatment of psoriasis by regulating angiogenesis and inflammation. The human umbilical vein endothelial cells(HUVECs) cultured in vitro were divided into a normal group, a model group, a VEGFR tyrosine kinase inhibitor Ⅱ(VRI) group, and Scu, Pae, and HSYA groups with low, me-dium, and high doses. Cell viability was detected by the CCK-8 assay. Cell migration was detected by wound healing assay. Tube formation assay was used to measure the tube formation ability. Western blot was used to detect the protein expression of the VEGFR2/Akt/ERK1/2 signaling pathway. The secretion levels of inflammatory cytokines IFN-γ, IL-1ß, IL-6, and TNF-α were detected by ELISA. The results showed that compared with the model group, all the Scu, Pae, and HSYA groups could reduce cell viability, inhibit cell migration and tube formation(P<0.05, P<0.01), and down-regulated the protein expression of VEGFR2, p-VEGFR2, Akt, p-Akt, ERK1/2, and p-ERK1/2. Scu and Pae could down-regulate VEGFR2 expression(P<0.05, P<0.01), while other groups only showed a downward trend. Scu and Pae significantly reduced IFN-γ and IL-6 levels(P<0.01), and HSYA significantly reduced the levels of IFN-γ, IL-1ß, and IL-6(P<0.01). Scu, Pae, and HSYA had no significant effect on TNF-α. The results suggested that Scu, Pae, and HSYA may exert a therapeutic role in psoriasis-related angiogenesis and inflammation by inhibiting VEGFR2/Akt/ERK1/2 signaling pathway and inhibiting the secretion of IFN-γ, IL-1ß, and IL-6.

Efficacy and Safety of Tongxinluo Capsule as Adjunctive Treatment for Unstable Angina Pectoris: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Tongxinluo capsule (TXLC) is a commonly used Chinese medicine for unstable angina pectoris (UA). This article aimed to clarify the safety and efficacy of TXLC as an adjunctive treatment for UA. Two reviewers searched 7 databases from inception to August 2021, and performed literature screening and information extraction independently. The meta-analysis was implemented after evaluating the methodological quality of each randomized controlled trial (RCT) by the Cochrane Risk of Bias tool. Sensitivity analyses were conducted for testing the stability of the results, and the Begg and Egger tests were performed for any potential publication bias. After eligibility assessment, 42 RCTs with a total of 5,421 participants were included. Evidence showed that TXLC reduced the rate of cardiovascular events [RR = 0.29, 95% CI (0.19, 0.45), p < 0.00001, I 2 = 0%] {including cardiovascular mortality [RR = 0.16, 95% CI (0.03, 0.88), p = 0.03, I 2 = 20%], the incidence of acute myocardial infarction [RR = 0.27, 95% CI (0.13, 0.57), p = 0.0006, I 2 = 0%] and the occurrence of revascularization [RR = 0.28, 95% CI (0.15,0.54), p = 0.0001, I 2 = 0%]}, all-cause mortality [RR = 0.25, 95% CI (0.06, 0.99), p = 0.05, I 2 = 19%], recurrence of angina [RR = 0.25, 95% CI (0.11, 0.61), p = 0.002, I 2 = 0%], the number of ST-segment depression [MD = -0.45, 95% CI (-0.69, -0.20), p = 0.0005, I 2 = 0%], the summation of ST-segment depression [MD = -0.70, 95% CI (-1.08, -0.32), p = 0.0003, I 2 = 70%] and the hypersensitive C-reactive protein level [MD = -2.86, 95% CI (-3.73, -1.99), p < 0.00001, I 2 = 86%], increased the nitric oxide level [MD = 11.67, 95% CI (8.33, 15.02), p < 0.00001, I 2 = 33%], improved the electrocardiogram change [RR = 1.23, 95% CI (1.16, 1.30), p < 0.00001, I 2 = 0%] and the clinical efficacy in UA [RR = 1.26, 95% CI (1.21, 1.32), p < 0.00001, I 2 = 24%], and relieved the symptoms of angina pectoris {including chest pain or tightness [RR = 1.13, 95% CI (0.97, 1.32), p = 0.12, I 2 = 30%], palpitations [RR = 1.47, 95% CI (1.18, 1.84), p = 0.0007, I 2 = 0%], shortness of breath [RR = 1.53, 95% CI (1.24, 1.88), p < 0.0001, I 2 = 0%], and asthenia [RR = 1.69, 95% CI (0.83, 3.43), p = 0.15, I 2 = 90%]}. The most common adverse effect was gastrointestinal symptoms which could be relieved and eliminated through dose reduction, medication time adjustment and symptomatic remedy. Collectively, TXLC was effective and considerably safe for UA. However, due to the unavoidable risk of bias, these results must be interpreted with caution and further verified by large-scale and high-quality RCTs. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO/, identifier CRD42021232771.

Correlation of Platelet and Coagulation Function with Blood Stasis Syndrome in Coronary Heart Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: To investigate the correlation of platelet and coagulation function with blood stasis syndrome (BSS) in coronary heart disease (CHD). METHODS: The protocol for this meta-analysis was registered on PROSPERO (CRD42019129452). PubMed, Excerpta Medica Database (Embase), the Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to 1st June, 2020. Trials were considered eligible if they enrolled BSS and non-BSS (NBSS) patients with CHD and provided information on platelet and coagulation function. The platelet function, coagulation function, and fibrinolytic activity were compared between the BSS and NBSS groups. Forest plots were generated to show the SMDs or ESs with corresponding 95% CIs for each study. Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity. RESULTS: The systematic search identified 1,583 articles. Thirty trials involving 10,323 patients were included in the meta-analysis. The results showed that mean platelet volume, platelet distribution width, platelet aggregation rate, platelet P selectin, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), thromboxane B2 (TXB2), 6-keto-prostaglandin F1alpha (6-keto-PGF1 α), and TXB2/6-keto-PGF1 α were higher in the BSS group than in the NBSS group (P<0.05 or P<0.01). Activated partial thromboplastin time was lower in the BSS group than in the NBSS group in the acute phase of CHD (P<0.01). The R and K values in thromboelastography and tissue plasminogen activator (t-PA) and t-PA/PAI-1 were lower in the BSS group than in the NBSS group (all P<0.01). No difference was found in the results of platelet count, plateletcrit, maximum amplitude, von Willebrand factor, prothrombin time, thrombin time, international normalized ratio, etc. between groups. CONCLUSIONS: Increased platelet function, hypercoagulability, and decreased fibrinolytic activity were found among CHD patients with BSS.

Efficacy and safety of liraglutide in type 2 diabetes mellitus patients complicated with coronary artery disease: A systematic review and meta-analysis of randomized controlled trials.

To evaluate the efficacy and safety of liraglutide in patients with Type 2 Diabetes Mellitus (T2DM) complicated with Coronary Artery Disease (CAD), we searched PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), Wanfang Database and Chinese Biomedical Literature database (CBM) for relevant randomized controlled trials (RCTs) from inception to 7 October 2020. A total of 18 RCTs including 1557 patients with T2DM complicated with CAD were included. Meta-analysis revealed liraglutide reduced hemoglobin A1c (HbA1c) (WMD = -0.67; 95% CI[-0.94 to -0.39]; P < 0.00001), fasting plasma glucose (FPG) (WMD = -0.80; 95% CI[-1.06 to -0.54]; P < 0.00001) and 2 h plasma glucose (2hPG) (WMD = -1.64; 95% CI[-2.12 to -1.16]; P＜0.00001); improved left ventricular ejection fraction(LVEF) (WMD = 4.79; 95% CI[4.08-5.51]; P < 0.00001), left ventricular end-diastolic diameter (LVEDD) (WMD = -5.70; 95% CI[-6.67 to -4.72]; P＜0.00001), E/A (WMD = 0.13; 95% CI[0.11-0.14]; P < 0.00001) and left ventricular posterior wall thickness (LVPWT) (WMD = -1.86; 95% CI[-2.16 to -1.55]; P < 0.00001); reduced total cholesterol (TC) (WMD = -0.48; 95% CI[-0.56 to -0.39]; P < 0.00001), triglycerides (TG) (WMD = -0.42; 95% CI[-0.59 to -0.26]; P < 0.00001), low-density lipoprotein cholesterol (LDL-C) (WMD = -0.41; 95% CI[-0.55 to -0.26]; P < 0.00001), and increased high-density lipoprotein cholesterol (HDL-C) (WMD = -0.19; 95% CI[0.13-0.24]; P = 0.0005). As for safety assessment, liraglutide did not increase the incidence of hypoglycemia (OR = 0.75, 95% CI[0.32-1.77], P = 0.51) and gastrointestinal (OR = 1.15, 95% CI[0.72-1.85], P = 0.55) events. Consequently, liraglutide had favorable effects on blood glucose, cardiac function, lipid profile and an acceptable safety profile.

A New Therapeutic Candidate for Cardiovascular Diseases: Berberine.

Cardiovascular diseases (CVD) are the leading cause of death in the world. However, due to the limited effectiveness and potential adverse effects of current treatments, the long-term prognosis of CVD patients is still discouraging. In recent years, several studies have found that berberine (BBR) has broad application prospects in the prevention and treatment of CVD. Due to its effectiveness and safety for gastroenteritis and diarrhea caused by bacterial infections, BBR has been widely used in China and other Asian countries since the middle of the last century. The development of pharmacology also provides evidence for the multi-targets of BBR in treating CVD. Researches on CVD, such as arrhythmia, atherosclerosis, dyslipidemia, hypertension, ischemic heart disease, myocarditis and cardiomyopathy, heart failure, etc., revealed the cardiovascular protective mechanisms of BBR. This review systematically summarizes the pharmacological research progress of BBR in the treatment of CVD in recent years, confirming that BBR is a promising therapeutic option for CVD.

Neovascularization: The Main Mechanism of MSCs in Ischemic Heart Disease Therapy.

Mesenchymal stem cell (MSC) transplantation after myocardial infarction (MI) has been shown to effectively limit the infarct area in numerous clinical and preclinical studies. However, the primary mechanism associated with this activity in MSC transplantation therapy remains unclear. Blood supply is fundamental for the survival of myocardial tissue, and the formation of an efficient vascular network is a prerequisite for blood flow. The paracrine function of MSCs, which is throughout the neovascularization process, including MSC mobilization, migration, homing, adhesion and retention, regulates angiogenesis and vasculogenesis through existing endothelial cells (ECs) and endothelial progenitor cells (EPCs). Additionally, MSCs have the ability to differentiate into multiple cell lineages and can be mobilized and migrate to ischemic tissue to differentiate into ECs, pericytes and smooth muscle cells in some degree, which are necessary components of blood vessels. These characteristics of MSCs support the view that these cells improve ischemic myocardium through angiogenesis and vasculogenesis. In this review, the results of recent clinical and preclinical studies are discussed to illustrate the processes and mechanisms of neovascularization in ischemic heart disease.

Oxyphylla A ameliorates cognitive deficits and alleviates neuropathology via the Akt-GSK3ß and Nrf2-Keap1-HO-1 pathways in vitro and in vivo murine models of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a progressive brain disorder, and one of the most common causes of dementia and amnesia. Due to the complex pathogenesis of AD, the underlying mechanisms remain unclear. Although scientists have made increasing efforts to develop drugs for AD, no effective therapeutic agents have been found. Objectives: Natural products and their constituents have shown promise for treating neurodegenerative diseases, including AD. Thus, in-depth study of medical plants, and the main active ingredients thereof against AD, is necessary to devise therapeutic agents. Methods: In this study, N2a/APP cells and SAMP8 mice were employed as in vitro and in vivo models of AD. Multiple molecular biological methods were used to investigate the potential therapeutic actions of oxyphylla A, and the underlying mechanisms. Results: Results showed that oxyphylla A, a novel compound extracted from Alpinia oxyphylla, could reduce the expression levels of amyloid precursor protein (APP) and amyloid beta (Aß) proteins, and attenuate cognitive decline in SAMP8 mice. Further investigation of the underlying mechanisms showed that oxyphylla A exerted an antioxidative effect through the Akt-GSK3ß and Nrf2-Keap1-HO-1 pathways.Conclusions.Taken together, our results suggest a new horizon for the discovery of therapeutic agents for AD.

Amelioration of AOM/DSS-Induced Murine Colitis-Associated Cancer by Evodiamine Intervention is Primarily Associated with Gut Microbiota-Metabolism-Inflammatory Signaling Axis.

Evodiamine (EVO), an indole alkaloid derived from Rutaceae plants Evodia rutaecarpa (Juss.) Benth.、Evodia rutaecarpa (Juss.) Benth. Var. bodinieri (Dode) Huang or Evodia rutaecarpa (Juss.) Benth. Var. officinalis (Dode) Huang, has anti-inflammatory and anti-tumor activities. Our previous study found that EVO attenuates colitis by regulating gut microbiota and metabolites. However, little is known about its effect on colitis-associated cancer (CAC). In this study, the protective effects of EVO on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis and tumor mice were observed, and the underlying potential mechanism was clarified. The results suggested that EVO ameliorated AOM/DSS-induced colitis by inhibiting the intestinal inflammation and improving mucosal barrier function. And EVO significantly reduced the number and size of AOM/DSS-induced colorectal tumors along with promoted apoptosis and inhibited proliferation of epithelial cell. Moreover, EVO promoted the enrichment of SCFAs-producing bacteria and reduced the levels of the pro-inflammatory bacteria, which contributes to the changes of microbiota metabolism, especially tryptophan metabolism. Furthermore, inflammatory response (like Wnt signaling pathway、Hippo signaling pathway and IL-17 signaling pathway) were effectively alleviated by EVO. Our study demonstrated that the protective therapeutic action of EVO on CAC is to inhibit the development of intestinal inflammation-cancer by regulating gut microbiota metabolites and signaling pathways of colon intestinal epithelial, which may represent a novel agent for colon cancer prevention via manipulation of gut microbiota.