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.

Recent Progress in Research on Mechanisms of Action of Natural Products against Alzheimer's Disease: Dietary Plant Polyphenols.

Alzheimer's disease (AD) is an incurable degenerative disease of the central nervous system and the most common type of dementia in the elderly. Despite years of extensive research efforts, our understanding of the etiology and pathogenesis of AD is still highly limited. Nevertheless, several hypotheses related to risk factors for AD have been proposed. Moreover, plant-derived dietary polyphenols were also shown to exert protective effects against neurodegenerative diseases such as AD. In this review, we summarize the regulatory effects of the most well-known plant-derived dietary polyphenols on several AD-related molecular mechanisms, such as amelioration of oxidative stress injury, inhibition of aberrant glial cell activation to alleviate neuroinflammation, inhibition of the generation and promotion of the clearance of toxic amyloid-ß (Aß) plaques, inhibition of cholinesterase enzyme activity, and increase in acetylcholine levels in the brain. We also discuss the issue of bioavailability and the potential for improvement in this regard. This review is expected to encourage further research on the role of natural dietary plant polyphenols in the treatment of AD.

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.

The Critical Role of Rab31 in Cell Proliferation and Apoptosis in Cancer Progression.

Rab31, a member of the Ras superfamily, is reported to play a role in tumor development and progression. However, the detailed role of Rab31 in proliferation and apoptosis of cancer cells is still unclear. Here, we used different cell lines, such as glioblastoma, and cervical cancer, to investigate the role of Rab31 in cancer progression. We found that Rab31 promotes U87 and SiHa cell proliferation via activation of G1/S checkpoint transitions, accompanied with an increase of cyclin D1, cyclin A, and cyclin B1. Meanwhile, Rab31 inhibits U87 and SiHa cell apoptosis, and decreased the BAX and PIG3 expression, but enhanced BCL2 expression. In addition, Rab31 induces N-cadherin, Vimentin, and Snail expression, and inhibits E-cadherin expression to regulate proliferation and migration. Besides, we observed that ERK1/2 and PI3k/AKT pathways are required for Rab31-induced cell proliferation and migration. In vivo, the knockdown of Rab31 suppresses tumor mass growth. In conclusion, our data highlight the crucial role of Rab31 in cancer progression, proliferation, and apoptosis, and indicates that Rab31 may be a useful and effective target for the clinical therapy of most cancers.

The critical role of HMGA2 in regulation of EMT in epithelial ovarian carcinomas.

The high mobility group A2 (HMGA2), an oncofetal protein, was shown to play a role in tumor development and progression. However, the molecular and clinical role of HMGA2 in epithelial ovarian carcinomas (EOCs) is still unknown. In the present study, EOC cell line SKOV3 was subjected to in vitro assays. Here, our findings showed that HMGA2 was highly expressed in EOC cell line SKOV3. HMGA2 knockdown promoted cell apoptosis and the cleavage of caspase 3, and decreased the B cell lymphoma 2 (Bcl-2)/Bax ratio in SKOV3. Functionally, HMGA2 knockdown resulted in reduction of SKOV3 cell migration and invasion. Mechanically, HMGA2 knockdown affected the occurrence of EMT by increasing E-cadherin gene and protein expression and decreasing the gene and protein expression of N-cadherin, slug, and vimentin. At the same time, HMGA2 also repressed the expression of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9), which was consistent with the decreased invasion capacity. In conclusion, HMGA2 is associated with migration and invasiveness and regulates the progression of EMT in the development of EOC, and HMGA2 gene and protein may be a novel therapeutic target against EOC in the clinical practice.

Involvement of nuclear protein C23 in activation of EGFR signaling in cervical cancer.

Nuclear protein C23 and epidermal growth factor receptor (EGFR) are reported to be correlated with cervical cancer (CC). However the correlations between C23 and EGFR were rarely reported. Here, this study explored the effects of C23 in activation of EGFR signaling pathway. In our study, immunohistochemistry was used to identify the expression of C23 or EGFR in CC tissues. The level of the phosphorylated EGFR was observed by western blot, and cell invasion capacity was detected by Transwell assay. In this study, we found that C23 and EGFR were highly expressed in cervical cancer tissues, while C23 on the cell surface mainly expressed in CC tissues with lymph node metastasis, and was correlated to EGFR statistically. In vitro, western blot showed that either anti-C23 or anti-EGFR antibodies can inhibit the phosphorlation of EGFR with significant differences (p < 0.01). Besides, based on Transwell assay, the number of membrane-invading cells was reduced significantly in anti-C23 group, and no significant difference was found compared with anti-EGFR treatment (p > 0.05). In conclusion, C23 on the cell surface may be a kind of indispensable component in activation of EGFR signaling, by which C23 can participate in the growth and invasion of tumors. C23 antagonists may provide a new field for cervical cancer therapy.