Role and mechanism of miRNA in cardiac microvascular endothelial cells in cardiovascular diseases.

The occurrence and development of myocardial dysfunction are associated with damage in the cardiac microvascular endothelial cells (CMECs), which can regulate nutrient exchange and oxy-gen-carbon cycling to protect cardiomyocytes. Interventions targeting microRNAs (miRNAs) can effectively mitigate CMEC injury and thus improve cardiovascular diseases. MiRNAs are a class of noncoding single-strand RNA molecules typically 21-23 nucleotides in length that are encoded by endogenous genes. They are critical regulators of organism development, cell differentiation, metabolism, and apoptosis. Current clinical trials on miRNA drugs indicate that patient-specific miRNA levels are now being used as one of the criteria for predicting heart disease. However, the cellular process of various miRNAs in CMECs in cardiovascular diseases has not been fully elucidated. These mechanisms are a field that immediately requires further investigation. Accordingly, this review summarizes the roles and mechanisms of various miRNAs in CMECs in cardiovascular disease and includes the process of CMEC crosstalk between miRNAs and other cell types in the heart. Our study serves as a theoretical basis for the formal introduction of miRNA use into the treatment of cardiovascular diseases in the future.

Shenxiang Suhe pill improves cardiac function through modulating gut microbiota and serum metabolites in rats after acute myocardial infarction.

CONTEXT: Shenxiang Suhe pill (SXSH), a traditional Chinese medicine, is clinically effective against coronary heart disease, but the mechanism of cardiac-protective function is unclear. OBJECTIVE: We investigated the cardiac-protective mechanism of SXSH via modulating gut microbiota and metabolite profiles. MATERIALS AND METHODS: Sprague-Dawley (SD) male rats were randomly divided into 6 groups (n = 8): Sham, Model, SXSH (Low, 0.063 g/kg; Medium, 0.126 g/kg; High, 0.252 g/kg), and Ato (atorvastatin, 20 mg/kg). Besides the Sham group, rats were modelled with acute myocardial infarction (AMI) by ligating the anterior descending branch of the left coronary artery (LAD). After 3, 7, 14 days' administration, ultrasound, H&E staining, serum enzymic assay, 16S rRNA sequencing were conducted to investigate the SXSH efficacy. Afterwards, five groups of rats: Sham, Model, Model-ABX (AMI with antibiotics-feeding), SXSH (0.126 g/kg), SXSH-ABX were administrated for 14 days to evaluate the gut microbiota-dependent SXSH efficacy, and serum untargeted metabolomics test was performed. RESULTS: 0.126 g/kg of SXSH intervention for 14 days increased ejection fraction (EF, 78.22%), fractional shortening (FS, 109.07%), and aortic valve flow velocities (AV, 21.62%), reduced lesion area, and decreased serum LDH (8.49%) and CK-MB (10.79%). Meanwhile, SXSH upregulated the abundance of Muribaculaceae (199.71%), Allobaculum (1744.09%), and downregulated Lactobacillus (65.51%). The cardiac-protective effect of SXSH was disrupted by antibiotics administration. SXSH altered serum metabolites levels, such as downregulation of 2-n-tetrahydrothiophenecarboxylic acid (THTC, 1.73%), and lysophosphatidylcholine (lysoPC, 4.61%). DISCUSSION AND CONCLUSION: The cardiac-protective effect and suggested mechanism of SXSH could provide a theoretical basis for expanding its application in clinic.

Polygonatum odoratum polysaccharide attenuates lipopolysaccharide-induced lung injury in mice by regulating gut microbiota.

Polygonatum odoratum is appreciated for its edible and medicinal benefits especially for lung protection. However, the contained active components have been understudied, and further research is required to fully exploit its potential application. We aimed to probe into the beneficial effects of Polygonatum odoratum polysaccharide (POP) in lipopolysaccharide-induced lung inflammatory injury mice. POP treatment could ameliorate the survival rate, pulmonary function, lung pathological lesions, and immune inflammatory response. POP treatment could repair intestinal barrier, and modulate the composition of gut microbiota, especially reducing the abundance of Klebsiella, which were closely associated with the therapeutic effects of POP. Investigation of the underlying anti-inflammatory mechanism showed that POP suppressed the generation of pro-inflammatory molecules in lung by inhibiting iNOS+ M1 macrophages. Collectively, POP is a promising multi-target microecological regulator to prevent and treat the immuno-inflammation and lung injury by modulating gut microbiota.

Remodeling of the gut microbiome by Lactobacillus johnsonii alleviates the development of acute myocardial infarction.

Introduction: The gut microbial community, which can be disturbed or repaired by changes in the internal environment, contributes to the development of acute myocardial infarction (AMI). Gut probiotics play a role in microbiome remodeling and nutritional intervention post-AMI. A newly isolated Lactobacillus johnsonii strain EU03 has shown potential as a probiotic. Here, we investigated the cardioprotective function and mechanism of L. johnsonii through gut microbiome remodeling in AMI rats. Methods: A rat model of left anterior descending coronary artery ligation (LAD)-mediated AMI was assessed with echocardiography, histology, and serum cardiac biomarkers to evaluate the beneficial effects of L. johnsonii. The immunofluorescence analysis was utilized to visualize the intestinal barrier changes. Antibiotic administration model was used for assessing the gut commensals' function in the improvement of cardiac function post-AMI. The underlying beneficial mechanism through L. johnsonii enrichment was further investigated by metagenomics and metabolomics analysis. Results: A 28-day treatment with L. johnsonii protected cardiac function, delayed cardiac pathology, suppressed myocardial injury cytokines, and improved gut barrier integrity. The microbiome composition was reprogrammed by enhancing the abundance of L. johnsonii. Microbiome dysbiosis by antibiotics abrogated the improvement of cardiac function post-AMI by L. johnsonii. L. johnsonii enrichment caused remodeling of gut microbiome by increasing the abundance of Muribaculaceae, Lactobacillus, and decreasing Romboutsia, Clostridia UCG-014, which were correlated with cardiac traits and serum metabolic biomarkers 16,16-dimethyl-PGA2, and Lithocholate 3-O-glucuronide. Conclusion: These findings reveal that gut microbiome remodeling by L. johnsonii ameliorates the cardiac function post-AMI and might advance microbiome-targeted nutritional intervention.Graphical Abstract.

Potential roles of gut microbes in biotransformation of natural products: An overview.

Natural products have been extensively applied in clinical practice, characterized by multi-component and multi-target, many pharmacodynamic substances, complex action mechanisms, and various physiological activities. For the oral administration of natural products, the gut microbiota and clinical efficacy are closely related, but this relationship remains unclear. Gut microbes play an important role in the transformation and utilization of natural products caused by the diversity of enzyme systems. Effective components such as flavonoids, alkaloids, lignans, and phenols cannot be metabolized directly through human digestive enzymes but can be transformed by enzymes produced by gut microorganisms and then utilized. Therefore, the focus is paid to the metabolism of natural products through the gut microbiota. In the present study, we systematically reviewed the studies about gut microbiota and their effect on the biotransformation of various components of natural products and highlighted the involved common bacteria, reaction types, pharmacological actions, and research methods. This study aims to provide theoretical support for the clinical application in the prevention and treatment of diseases and provide new ideas for studying natural products based on gut biotransformation.

Identification of Drug-Induced Liver Injury Biomarkers from Multiple Microarrays Based on Machine Learning and Bioinformatics Analysis.

Drug-induced liver injury (DILI) is the most common adverse effect of numerous drugs and a leading cause of drug withdrawal from the market. In recent years, the incidence of DILI has increased. However, diagnosing DILI remains challenging because of the lack of specific biomarkers. Hence, we used machine learning (ML) to mine multiple microarrays and identify useful genes that could contribute to diagnosing DILI. In this prospective study, we screened six eligible microarrays from the Gene Expression Omnibus (GEO) database. First, 21 differentially expressed genes (DEGs) were identified in the training set. Subsequently, a functional enrichment analysis of the DEGs was performed. We then used six ML algorithms to identify potentially useful genes. Based on receiver operating characteristic (ROC), four genes, DDIT3, GADD45A, SLC3A2, and RBM24, were identified. The average values of the area under the curve (AUC) for these four genes were higher than 0.8 in both the training and testing sets. In addition, the results of immune cell correlation analysis showed that these four genes were highly significantly correlated with multiple immune cells. Our study revealed that DDIT3, GADD45A, SLC3A2, and RBM24 could be biomarkers contributing to the identification of patients with DILI.

Therapeutic and Improving Function of Lactobacilli in the Prevention and Treatment of Cardiovascular-Related Diseases: A Novel Perspective From Gut Microbiota.

The occurrence and development of cardiovascular-related diseases are associated with structural and functional changes in gut microbiota (GM). The accumulation of beneficial gut commensals contributes to the improvement of cardiovascular-related diseases. The cardiovascular-related diseases that can be relieved by Lactobacillus supplementation, including hypercholesterolemia, atherosclerosis, myocardial infarction, heart failure, type 2 diabetes mellitus, and obesity, have expanded. As probiotics, lactobacilli occupy a substantial part of the GM and play important functional roles through various GM-derived metabolites. Lactobacilli ultimately have a beneficial impact on lipid metabolism, inflammatory factors, and oxidative stress to relieve the symptoms of cardiovascular-related diseases. However, the axis and cellular process of gut commensal Lactobacillus in improving cardiovascular-related diseases have not been fully elucidated. Additionally, Lactobacillus strains produce diverse antimicrobial peptides, which help maintain intestinal homeostasis and ameliorate cardiovascular-related diseases. These strains are a field that needs to be further investigated immediately. Thus, this review demonstrated the mechanisms and summarized the evidence of the benefit of Lactobacillus strain supplementation from animal studies and human clinical trials. We also highlighted a broad range of lactobacilli candidates with therapeutic capability by mining their metabolites. Our study provides instruction in the development of lactobacilli as a functional food to improve cardiovascular-related diseases.

Eucommia ulmoides leaf extract alters gut microbiota composition, enhances short-chain fatty acids production, and ameliorates osteoporosis in the senescence-accelerated mouse P6 (SAMP6) model.

The bark and the leaf of Eucommia ulmoides Oliv. content similar bioactive components, but the leaf of this medically important plant is mostly abandoned. In this study, we revealed that the aqueous extract of E. ulmoides leaf (EUL) can promote the growth of the probiotic Lactobacillus bulgaricus (LB) and inhibit the formation of osteoclast in vitro. This extract was next administrated to senescence-accelerated mice P6 to evaluate examine its influence on the composition of gut microbiota (GM), short-chain fatty acids (SCFAs), and osteoporosis (OP). The results showed that supplementation of the EUL aqueous extract to the mouse model: (a) increased bacterial diversity and Firmicutes/Bacteroidetes ratio in the gut, (b) increased SCFAs concentration in the feces and serum, and (c) ameliorated OP based on the results of bone mineral density (BMD), Dual-energy X-ray bone scan, and HE staining of distal femur.