Role of puerarin in pathological cardiac remodeling: A review.

Pathological cardiac remodeling normally involves changes in structure, function, and energy metabolism of the heart induced by cardiac injury or load, terminally leading to heart failure. Cardiac remodeling plays an essential role in the progression of cardiovascular disease, thus increasingly identified as an important therapeutic target for heart failure of all pathogenesis. Puerarin, as a natural isoflavone mainly from Pueraria lobata （Willd.）Ohwi, has been developed as injections, eye drops, microemulsions, etc., and is widely used in the clinical treatment of cardiovascular diseases in eastern Asia countries. In recent years, a growing number of studies have shown that puerarin significantly inhibits myocardial hypertrophic growth, myocyte death, fetal gene expression, fibroblast proliferation and activation, improves energy metabolism, promotes post-infarction angiogenesis, and suppresses inflammation and oxidative stress, consequently attenuating or preventing cardiac remodeling in response to multiple stimuli ( e.g., pressure overload, MIRI, MI, Iso, and Ang II stimulation). This review summarized the roles and underlying molecular mechanisms of puerarin in cardiac remodeling induced by diverse etiologies, aiming to help develop novel therapeutic strategies to prevent or reverse pathological ventricular remodeling.

Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-ß1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction.

BACKGROUND/AIMS: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. METHODS: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-ß1 (TGF-ß1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. RESULTS: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-ß1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. CONCLUSIONS: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-ß1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

[Effects of Qili Qiangxin Capsule on Lung Structural Remodeling in Heart Failure Rats after Myocardial Infarction and Its Mechanism].

Objective To observe the effect of Qili Qiangxin Capsule (QQC) in improving lung struc- tural remodeling on heart failure (HF) rats after myocardial infarction (Ml) and to study its possible mecha- nism. Methods The proximal left anterior descending branch of coronary artery was ligated using a terylene suture to establish acute myocardial infarction (AMI) rat model. After successful AMI modeling rats were ran- domly divided into the model group (intragastrically administered with distilled water at 1 mL/100 g, n =13) and the QQC group (intragastrically administered with QQC at the daily dose of 1 g/kg, n =9). And the sham-opera- tion group (intragastrically administered with distilled water at 1 mL/100 g, n =10) was also set up. After four weeks intervention heart functions of rats were detected using echocardiography. The pathological changes of lung structures were observed by HE and Masson staining method. Protein expressions of lung α-SMA, Collagen I, TGF-ß1, and p-Smad3 of the lung tissue were detected by immunohistochemistry and Western blot. Re- sults Compared with the sham-operation group, ejection fraction (EF) and fraction shortening (FS) decreased (P <0. 05) , protein expressions of lung left ventricular internal diastolic diameter (LVIDd), left ventric- ular internal systolic diameter (LVIDs), end diastolic volume (EDV), end systolic volume (ESV), α-smooth muscle actin (a-SMA), Collagen I, tumor growth factor-ß1 (TGF-ß1), and p-Smad3 increased (P <0.05) in the model group. The muscularized small arteries ratio and collagen area of the lung tissue increased in the model group (P <0. 05). Compared with the model group, EF and FS increased (P <0. 05), protein expressions of LVIDs, ESV, α-SMA, Collagen I, TGF-ß, , and p-Smad3 decreased (P <0.05) in the QQC group. The muscular- ized small arteries ratio and collagen area of the lung tissue decreased in the QQC group (P <0. 05). Conclusion QQC could improve lung structural remodeling degree of HF rats after MI, and its possible mechanism might be achieved by regulating TGF-beta,/Smad3 signaling pathways.

Genetic prediction of the causal relationship between schizophrenia and tumors: a Mendelian randomized study.

Background: Patients with schizophrenia are at a higher risk of developing cancer. However, the causal relationship between schizophrenia and different tumor types remains unclear. Methods: Using a two-sample, two-way Mendelian randomization method, we used publicly available genome-wide association analysis (GWAS) aggregate data to study the causal relationship between schizophrenia and different cancer risk factors. These tumors included lung adenocarcinoma, lung squamous cell carcinoma, small-cell lung cancer, gastric cancer, alcohol-related hepatocellular cancer, tumors involving the lungs, breast, thyroid gland, pancreas, prostate, ovaries and cervix, endometrium, colon and colorectum, and bladder. We used the inverse variance weighting (IVW) method to determine the causal relationship between schizophrenia and different tumor risk factors. In addition, we conducted a sensitivity test to evaluate the effectiveness of the causality. Results: After adjusting for heterogeneity, evidence of a causal relationship between schizophrenia and lung cancer risk was observed (odds ratio [OR]=1.001, 95% confidence interval [CI], 1.000-1.001; P=0.0155). In the sensitivity analysis, the causal effect of schizophrenia on the risk of lung cancer was consistent in both direction and degree. However, no evidence of causality or reverse causality between schizophrenia and other tumors was found. Conclusion: This study elucidated a causal relationship between the genetic predictors of schizophrenia and the risk of lung cancer, thereby providing a basis for the prevention, pathogenesis, and treatment of schizophrenia in patients with lung cancer.

The role of matrix metalloproteinase 9 in fibrosis diseases and its molecular mechanisms.

Fibrosis is a process of tissue repair that results in the slow creation of scar tissue to replace healthy tissue and can affect any tissue or organ. Its primary feature is the massive deposition of extracellular matrix (mainly collagen), eventually leading to tissue dysfunction and organ failure. The progression of fibrotic diseases has put a significant strain on global health and the economy, and as a result, there is an urgent need to find some new therapies. Previous studies have identified that inflammation, oxidative stress, some cytokines, and remodeling play a crucial role in fibrotic diseases and are essential avenues for treating fibrotic diseases. Among them, matrix metalloproteinases (MMPs) are considered the main targets for the treatment of fibrotic diseases since they are the primary driver involved in ECM degradation, and tissue inhibitors of metalloproteinases (TIMPs) are natural endogenous inhibitors of MMPs. Through previous studies, we found that MMP-9 is an essential target for treating fibrotic diseases. However, it is worth noting that MMP-9 plays a bidirectional regulatory role in different fibrotic diseases or different stages of the same fibrotic disease. Previously identified MMP-9 inhibitors, such as pirfenidone and nintedanib, suffer from some rather pronounced side effects, and therefore, there is an urgent need to investigate new drugs. In this review, we explore the mechanism of action and signaling pathways of MMP-9 in different tissues and organs, hoping to provide some ideas for developing safer and more effective biologics.

Regulatory mechanism of icariin in cardiovascular and neurological diseases.

Cardiovascular diseases (CVDs) and neurological diseases are widespread diseases with substantial rates of morbidity and mortality around the world. For the past few years, the preventive effects of Chinese herbal medicine on CVDs and neurological diseases have attracted a great deal of attention. Icariin (ICA), the main constituent of Epimedii Herba, is a flavonoid. It has been shown to provide neuroprotection, anti-tumor, anti-osteoporosis, and cardiovascular protection. The endothelial protection, anti-inflammatory, hypolipidemic, antioxidative stress, and anti-apoptosis properties of ICA can help stop the progression of CVDs and neurological diseases. Therefore, our review summarized the known mechanisms and related studies of ICA in the prevention and treatment of cardio-cerebrovascular diseases (CCVDs), to better understand its therapeutic potential.

The Effects of Velvet Antler of Deer on Cardiac Functions of Rats with Heart Failure following Myocardial Infarction.

Velvet antler of deer (VAD) is a commonly-used kidney-Yang supplementing traditional Chinese medication. According to the heart-kidney-related theory, heart Yang originates in kidney Yang and heart failure due to heart Yang deficiency can be treated by tonifying kidney Yang. In this study, we investigated therapeutic effects of VAD on cardiac functions in rats with heart failure following myocardial infarction. Forty-eight male Wistar rats were subjected either to left coronary artery ligation (N = 36) or to sham operation (N = 12). One week after the surgery, rats with heart failure received daily treatment of double-distilled water, captopril or VAD by gavage for consecutively four weeks, while sham-operated animals were given double-distilled water. Ultrasonic echocardiography was adopted to examine cardiac structural and functional parameters and serum brain natriuretic peptide (BNP) concentration was measured using radioimmunoassay. We found that VAD partially reversed changes in cardiac functional parameters and serum BNP levels in rats with heart failure. These results provide further evidence for the heart-kidney-related theory and suggest that VAD might be a potentially alternative and complementary medicine for the treatment of heart failure.

[Effects of herbs capable of activating blood circulation or inducing diuresis on the expressions of tumor necrosis factor-alpha, nuclear factor-kappaB, and aquaporin-4 in rats with intracerebral hemorrhage].

OBJECTIVE: To investigate the effects of herbs capable of activating blood circulation or inducing diuresis on the expressions of tumor necrosis factor-alpha (TNF-alpha), nuclear factor-kappaB (NF-kappaB), and aquaporin-4 (AQP-4) in rats with intracerebral hemorrhage (ICH), and to study their possible mechanisms. METHODS: The ICH rat model was established by injecting autologous arterial blood into the right caudate nucleus. The 168 male rats were randomly divided into four groups, the sham-operative group, the model group, the blood activating group, and the diuresis inducing group, 42 in each group. Chinese compound decoction (consisting of 0.2 g rhubarb, 0.02 g leech, and 0.3 g notoginseng in each milliliter decoction) was given to rats in the blood activating group by gastrogavage at the dose of 10 mL/kg, once daily. Chinese compound decoction (consisting of 0.2 g poria, 0.2 g water plantain tuber, and 0.2 g acori graninei in each milliliter decoction) was given to rats in the diuresis inducing group by gastrogavage at the dose of 10 mL/kg, once daily. 4.0 mL/kg normal saline was given to rats in the model group and the sham-operative group by gastrogavage, once daily. A series of brain samples were obtained on the 1st, 3rd, and 5th day, respectively. The mRNA and protein expressions of TNFalpha, NF-kappaB p65, and AQP-4 were determined by immunohistochemical staining and Real-time fluorescent quantitative PCR respectively. RESULTS: After ICH, TNF-alpha, NF-KB, and AQP-4 protein positive cells in the brain tissue and their protein and mRNA expressions significantly increased in rats of the model group at each time point when compared with the sham-operative group (P < 0.01, P < 0.05). The gene and protein expressions of TNF-alpha and AQP-4 significantly decreased in the blood activating group and the diuresis inducing group at each time point when compared with the model group (PP < 0.05). The expression of NF-kappaB p65 in the blood activating group obviously decreased when compared with the model group (P < 0.05), but there was no statistical difference in the NF-KB expression when compared with the diuresis inducing group (P > 0.05). Compared with the model group, the water content of the brain tissue decreased to some degree in the blood activating group and the diuresis inducing group at each time point. There was statistical difference between the blood activating group and the diuresis inducing group (P < 0.05). CONCLUSIONS: Chinese herbs capable of activating blood circulation or inducing diuresis could inhibit the release of TNF-alpha, down-regulate the expression of AQP-4, and alleviate the brain edema around hematoma. But the action strength and the effect links were different.

ROS and Endoplasmic Reticulum Stress in Pulmonary Disease.

Pulmonary diseases are main causes of morbidity and mortality worldwide. Current studies show that though specific pulmonary diseases and correlative lung-metabolic deviance own unique pathophysiology and clinical manifestations, they always tend to exhibit common characteristics including reactive oxygen species (ROS) signaling and disruptions of proteostasis bringing about accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER). ER is generated by the unfolded protein response. When the adaptive unfolded protein response (UPR) fails to preserve ER homeostasis, a maladaptive or terminal UPR is engaged, leading to the disruption of ER integrity and to apoptosis, which is called ER stress. The ER stress mainly includes the accumulation of misfolded and unfolded proteins in lumen and the disorder of Ca2+ balance. ROS mediates several critical aspects of the ER stress response. We summarize the latest advances in of the UPR and ER stress in the pathogenesis of pulmonary disease and discuss potential therapeutic strategies aimed at restoring ER proteostasis in pulmonary disease.

Plin5, a New Target in Diabetic Cardiomyopathy.

Abnormal lipid accumulation is commonly observed in diabetic cardiomyopathy (DC), which can create a lipotoxic microenvironment and damage cardiomyocytes. Lipid toxicity is an important pathogenic factor due to abnormal lipid accumulation in DC. As a lipid droplet (LD) decomposition barrier, Plin5 can protect LDs from lipase decomposition and regulate lipid metabolism, which is involved in the occurrence and development of cardiovascular diseases. In recent years, studies have shown that Plin5 expression is involved in the pathogenesis of DC lipid toxicity, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and insulin resistance (IR) and has become a key target of DC research. Therefore, understanding the relationship between Plin5 and DC progression as well as the mechanism of this process is crucial for developing new therapeutic approaches and exploring new therapeutic targets. This review is aimed at exploring the latest findings and roles of Plin5 in lipid metabolism and DC-related pathogenesis, to explore possible clinical intervention approaches.

Efficacy and safety of whole-lung lavage for pulmonary alveolar proteinosis: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is an ultrarare disorder characterised by the accumulation of alveolar surfactant and the dysfunction of alveolar macrophages that results in hypoxemic respiratory failure. Whole-lung lavage (WLL) is currently the primary therapy for PAP. However, systematic evaluation of the clinical efficacy of WLL is lacking. We aim to perform a systematic review and meta-analysis of existing evidence to support WLL for the clinical treatment of PAP. METHODS AND ANALYSIS: We will search the PubMed (MEDLINE), Cochrane Library, Embase, Web of Science and Google Scholar databases from inception to December 2021 for observational studies using WLL for the treatment of PAP. Two authors will independently screen the eligible studies, assess the quality of the included papers and extract the required information. Review Manager V.5.4 will be used to perform the meta-analysis. We will evaluate the overall quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. All steps of this protocol will be performed using the Cochrane Handbook for Preferred Reporting Items for Systematic Review and Meta-analysis statement. ETHICS AND DISSEMINATION: This systematic review and meta-analysis will be based on published data. Therefore, ethical approval is not required. We will publish our results in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022306221 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022306221).

Qiliqiangxin Modulates the Gut Microbiota and NLRP3 Inflammasome to Protect Against Ventricular Remodeling in Heart Failure.

Aims: Pathological left ventricular (LV) remodeling induced by multiple causes often triggers fatal cardiac dysfunction, heart failure (HF), and even cardiac death. This study is aimed to investigate whether qiliqiangxin (QL) could improve LV remodeling and protect against HF via modulating gut microbiota and inhibiting nod-like receptor pyrin domain 3 (NLRP3) inflammasome activation. Methods: Rats were respectively treated with QL (100 mg/kg/day) or valsartan (1.6 mg/kg/day) by oral gavage after transverse aortic constriction or sham surgery for 13 weeks. Cardiac functions and myocardial fibrosis were assessed. In addition, gut microbial composition was assessed by 16S rDNA sequencing. Furthermore, rats' hearts were harvested for histopathological and molecular analyses including immunohistochemistry, immunofluorescence, terminal-deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphated nick end labeling, and Western blot. Key findings: QL treatment preserved cardiac functions including LV ejection fractions and fractional shortening and markedly improved the LV remodeling. Moreover, HF was related to the gut microbial community reorganization like a reduction in Lactobacillus, while QL reversed it. Additionally, the protein expression levels like IL-1ß, TNF-α, NF-κB, and NLRP3 were decreased in the QL treatment group compared to the model one. Conclusion: QL ameliorates ventricular remodeling to some extent in rats with HF by modulating the gut microbiota and NLRP3 inflammasome, which indicates the potential therapeutic effects of QL on those who suffer from HF.

The Molecular Mechanisms of Defective Copper Metabolism in Diabetic Cardiomyopathy.

Copper is an essential trace metal element that significantly affects human physiology and pathology by regulating various important biological processes, including mitochondrial oxidative phosphorylation, connective tissue crosslinking, and antioxidant defense. Copper level has been proved to be closely related to the morbidity and mortality of cardiovascular diseases such as atherosclerosis, heart failure, and diabetic cardiomyopathy (DCM). Copper deficiency can induce cardiac hypertrophy and aggravate cardiomyopathy, while copper excess can mediate various types of cell death, such as autophagy, apoptosis, cuproptosis, pyroptosis, and cardiac hypertrophy and fibrosis. Both copper excess and copper deficiency lead to redox imbalance, activate inflammatory response, and aggravate diabetic cardiomyopathy. This defective copper metabolism suggests a specific metabolic pattern of copper in diabetes and a specific role in the pathogenesis and progression of DCM. This review is aimed at providing a timely summary of the effects of defective copper homeostasis on DCM and discussing potential underlying molecular mechanisms.

The molecular mechanisms of ferroptosis and its role in cardiovascular disease.

Ferroptosis is a programmed iron-dependent cell death characterized by accumulation of lipid peroxides (LOOH) and redox disequilibrium. Ferroptosis shows unique characteristics in biology, chemistry, and gene levels, compared to other cell death forms. The metabolic disorder of intracellular LOOH catalyzed by iron causes the inactivity of GPX4, disrupts the redox balance, and triggers cell death. Metabolism of amino acid, iron, and lipid, including associated pathways, is considered as a specific hallmark of ferroptosis. Epidemiological studies and animal experiments have shown that ferroptosis plays an important character in the pathophysiology of cardiovascular disease such as atherosclerosis, myocardial infarction (MI), ischemia/reperfusion (I/R), heart failure (HF), cardiac hypertrophy, cardiomyopathy, and abdominal aortic aneurysm (AAA). This review systematically summarized the latest research progress on the mechanisms of ferroptosis. Then we report the contribution of ferroptosis in cardiovascular diseases. Finally, we discuss and analyze the therapeutic approaches targeting for ferroptosis associated with cardiovascular diseases.

Roles and mechanisms of puerarin on cardiovascular disease：A review.

Cardiovascular diseases (CVDs) are now the leading cause of mortality and morbidity worldwide，resulting in a large global economic burden. Recently, complementary and alternative medicine, such as traditional Chinese medicine (TCM) have received great attention. Puerarin (Pue) is an isoflavone isolated from the roots of Pueraria lobata (Willd.) Ohwi (also named "Ge gen" in China), and is a versatile TCM herb used for the treatment of fever, diarrhea, diabetes mellitus CVDs and cerebrovascular diseases. Numerous lines ofin vitro studies, as well as in vivo animal experiments have established that Pue offers beneficial roles against the progression of atherosclerosis, ischemic heart diseases, heart failure hypertension and arrhythmia by inhibiting pathological processes, such as the mitigation of endothelium injury, protection against inflammation, the disturbance of lipid metabolism, protection against ischemic reperfusion injury, anti-myocardial remodeling and other effects. Here, we provide a systematic overview of the pharmacological actions and molecular targets of Pue in cardiovascular disease prevention and treatment, to provide insights into the therapeutic potential of Pue in treating cardiovascular diseases.

Microbiota-derived short-chain fatty acids: Implications for cardiovascular and metabolic disease.

Cardiovascular diseases (CVDs) have been on the rise around the globe in the past few decades despite the existing guidelines for prevention and treatment. Short-chain fatty acids (SCFAs) are the main metabolites of certain colonic anaerobic bacterial fermentation in the gastrointestinal tract and have been found to be the key metabolites in the host of CVDs. Accumulating evidence suggest that the end-products of SCFAs (including acetate, propionate, and butyrate) interact with CVDs through maintaining intestinal integrity, anti-inflammation, modulating glucolipid metabolism, blood pressure, and activating gut-brain axis. Recent advances suggest a promising way to prevent and treat CVDs by controlling SCFAs. Hence, this review tends to summarize the functional roles carried out by SCFAs that are reported in CVDs studies. This review also highlights several novel therapeutic interventions for SCFAs to prevent and treat CVDs.

Tongxinluo capsule as supplementation and cardiovascular endpoint events in patients with coronary heart disease: A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo Capsule(TXLC) is a well-known traditional Chinese medicine prescription with effects of tonifying Qi and activating blood based on the Chinese herbal medicine theory that has been recommended as routine adjuvant treatment in patients with coronary heart disease (CHD) in China. AIM OF THE STUDY: This meta-analysis aimed to evaluate the efficacy and safety of TXLC as supplementation in the prevention of adverse cardiovascular events in patients with CHD. MATERIALS AND METHODS: We performed a literature search in Pubmed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan Fang Database, and Chinese Biomedical Database (CBM) from their inceptions to March 2020. Only randomized controlled trials (RCTs) that assessed supplementation with TXLC or placebo and with adverse cardiovascular outcomes, were included in this meta-analysis. Primary end points were myocardial infarction (MI), target vessel revascularization (TVR) or in-stent restenosis (ISR), and cardiovascular death. Secondary end points included cerebrovascular accidents, heart failure (HF), and unscheduled readmission for cardiovascular diseases (CVDs). Adverse drug events were also evaluated. Trial sequential analysis (TSA) was conducted to reduce random errors introduced by possible insufficient sample size. RESULTS: Eleven RCTs involving 1505 patients were analyzed. The mean(SD) age of included patients were 59.03(9.7) years. Treatment duration varied from 2 months to 12 months. Compared with placebo, TXLC supplementation showed significant effects on reducing the risk of MI (RR = 0.44, [95% CI, 0.24-0.80]), TVR or ISR (RR = 0.43, [95% CI, 0.31-0.58]), cerebrovascular accidents(RR = 0.17, [95% CI, 0.06-0.46]), HF (RR = 0.41, [95% CI, 0.21-0.79]), and unscheduled readmission for CVDs (RR = 0.72, [95% CI], P = 0.04), but did not have associations with incidence of cardiovascular death (RR = 0.53, [95% CI, 0.15-1.91]). Subgroups of trials with 2-month (MI: RR = 0.44, [95% CI, 0.13-1.53]; cardiovascular death: RR = 0.30, [95% CI, 0.01-7.67]; cerebrovascular accidents: RR = 0.04, [95% CI, 0.01-0.26]; unscheduled readmission for CVDs: RR = 0.43, [95% CI, 0.20-0.94]) and 12-month (MI: RR = 0.42, [95% CI, 0.20-0.89]; TVR or ISR: RR = 0.42, [95% CI, 0.31-0.58]; HF: RR = 0.34, [95% CI, 0.14-0.78]; unscheduled readmission for CVDs: RR = 0.85, [95% CI, 0.59-1.22]) intervention period were analyzed. The adverse drug reactions were mild with no significant difference between TXLC and placebo. CONCLUSIONS: This meta-analysis indicated that TXLC supplementation had beneficial effects on the prevention of cardiovascular adverse events, especially in TVR or ISR after coronary revascularization and may possibly lower the incidence of first or recurrent MI and HF within 12 months in patients with CHD, while insufficient sample size implied that these results lacked certain stability. And the effects of TXLC on cardiovascular mortality, cerebrovascular events, and unscheduled readmission for CVDs could not be confirmed due to insufficient cases. Clinical trials with large-sample sizes and extended follow-up time are of interest in the future researches.

Neuregulin-1, a potential therapeutic target for cardiac repair.

NRG1 (Neuregulin-1) is an effective cardiomyocyte proliferator, secreted and released by endothelial vascular cells, and affects the cardiovascular system. It plays a major role in heart growth, proliferation, differentiation, apoptosis, and other cardiovascular processes. Numerous experiments have shown that NRG1 can repair the heart in the pathophysiology of atherosclerosis, myocardial infarction, ischemia reperfusion, heart failure, cardiomyopathy and other cardiovascular diseases. NRG1 can connect related signaling pathways through the NRG1/ErbB pathway, which form signal cascades to improve the myocardial microenvironment, such as regulating cardiac inflammation, oxidative stress, necrotic apoptosis. Here, we summarize recent research advances on the molecular mechanisms of NRG1, elucidate the contribution of NRG1 to cardiovascular disease, discuss therapeutic approaches targeting NRG1 associated with cardiovascular disease, and highlight areas for future research.

Glutamate excitotoxicity: Potential therapeutic target for ischemic stroke.

Glutamate-mediated excitotoxicity is an important mechanism leading to post ischemic stroke damage. After acute stroke, the sudden reduction in cerebral blood flow is most initially followed by ion transport protein dysfunction and disruption of ion homeostasis, which in turn leads to impaired glutamate release, reuptake, and excessive N-methyl-D-aspartate receptor (NMDAR) activation, promoting neuronal death. Despite extensive evidence from preclinical studies suggesting that excessive NMDAR stimulation during ischemic stroke is a central step in post-stroke damage, NMDAR blockers have failed to translate into clinical stroke treatment. Current treatment options for stroke are very limited, and there is therefore a great need to develop new targets for neuroprotective therapeutic agents in ischemic stroke to extend the therapeutic time window. In this review, we highlight recent findings on glutamate release, reuptake mechanisms, NMDAR and its downstream cellular signaling pathways in post-ischemic stroke damage, and review the pathological changes in each link to help develop viable new therapeutic targets. We then also summarize potential neuroprotective drugs and therapeutic approaches for these new targets in the treatment of ischemic stroke.

Beneficial effects of psyllium on the prevention and treatment of cardiometabolic diseases.

Cardiometabolic diseases are reaching epidemic proportions worldwide. Dietary fiber intake can improve the risk factors associated with CMD. Psyllium, especially its husk, is one of the most widely used dietary fiber supplements, which is often used to enrich cereals and other food products. Numerous pharmacological studies have investigated the active ingredients and therapeutic effects of psyllium and its extracts, including antioxidant, anti-tumor, antidiabetic, hypotensive, anti-inflammation, neuroprotection, antidiarrheal, and antiviral activities. In this review, we will summarize the available studies on the therapeutic potential and possible mechanisms of psyllium in treating CMDs, such as hyperlipidemia, diabetes mellitus, and its complications, hypertension, hyperuricemia and obesity, and its applications in food systems.