Current Protein and Peptide Science - Volume 20, Issue 10, 2019

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Rehmanniae Radix Praeparata (RRP) is a popular medicinal herb widely used in traditional Chinese medicine (TCM) to treat CVDs. However, the development of this novel therapeutic product has been stagnant, and its molecular mechanism of action remains unclear. This study aims to explore the effective ingredients of RRP against CVDs, especially atherosclerosis (AS). Using the AutoDock Vina software, the RRP’s ingredients were docked with the targets which can be collected by RCSB and UniProt. Then the screened ingredients and targets could be used to dispose the pathways by the Kyoto Encyclopedia of Genes and Genomes (KEGG). We used GEO, GCBI and DAVID databases to analyze the microarray data of AS which could be used to verify the results of molecular docking, all of which could show the molecular mechanism of RRP on CVDs. We also constructed a compound–target interaction network of CVD with 85 nodes and 272 edges on the basis of molecular docking analysis through Cytoscape. The network showed that forsythiaside, acteoside and stigmasterol are the most important compounds and 2HRR (ACAT (Acyl-CoA cholesterol acyl transferase) protein), 4ATB (MMP13) and 1JBQ (cystathionine beta-synthase) are the most valuable targets in the action of RRP against CVD. We also examined the biological functions involved in the biological process, molecular function and cellular components. In accordance with the analysis of GSE6054 microarray data of AS disease, the 20 most specifically expressed genes (differentially expressed genes [DEGs]) and the top 10 pathways of DEGs were discovered. Five key pathways, including non-alcoholic fatty liver disease (NAFLD), pathways in cancer and PI3K-Akt signalling pathway were also explored. Amongst these pathways, the top three were the pathways in cancer, MAPK signalling pathway and human T-cell lymphotropic virus infection. The pathways in cancer and PI3K-Akt signalling pathway were found simultaneously in the pathway analysis for CVD on RRP and for AS on microarray data. This study provided a new potential herbal medicine against CVD and has increased the understanding on the molecular mechanisms of RRPmediated protection against CVD, especially AS.

Diabetes mellitus (DM) has become an increasingly common disease with high disability and mortality rates. Diabetes complications are the main cause of diabetes death and about 50% of diabetic patients died from heart disease in developed countries reported by World Health Organization. Diabetic cardiomyopathy (DCM) has been considered as a high incidence and serious complication of DM and plays a key role in the incidence and development of diabetes related heart failure. Metabolism dysregulation is regarded as an important and earlier factor occurred in the pathogenesis of DCM. Insulin resistance, oxidative stress, inflammation and mitochondrial dysfunction also contribute to the development of DCM. Farnesoid X Receptor (FXR) is a member of nuclear receptor superfamily, and plays a critical role in regulating lipid and glucose metabolism, oxidative stress and inflammation. FXR is activated by primary bile acids (BAs) such as chenodeoxycholic acid, cholic acid and synthetic agonists such as obeticholic acid. BAs are the main active ingredients of many natural products and traditional medicines, especially bile or gallstones in animals, such as calculus bovis. Due to the regulatory effect of FXR on glucose and lipid metabolism, oxidative stress and inflammation, the treatment of BAs and FXR agonists for metabolic syndrome and DCM have gained more attention. This review will focus on the pathogenesis of diabetic cardiomyopathy and the regulatory effect of BAs and FXR on DCM.

Vitamin D, as a natural medicine, is known to regulate calcium and phosphate homeostasis. But abundant research has shown that vitamin D also plays a regulatory role in autoimmunity, inflammation, angiogenesis and vascular cell activity. Since the vitamin D receptor (VDR) is widely distributed in vascular endothelial cells, vascular smooth muscle cells and cardiomyocytes, the role of vitamin D and VDR in hypertension has received extensive attention. Hypertension is a disease with high incidence and high cardiovascular risk. In recent years, both clinical trials and animal experiments have shown that vitamin D plays a regulatory role in decreasing blood pressure (BP) through inhibiting renin-angiotensin-aldosterone system activity, modulating function of vascular wall and reducing vascular oxidative stress. A growing body of data suggest that vitamin D deficiency is associated with increased cardiovascular disease risk in hypertension, even short-term vitamin D deficiency may directly raise BP and promote target organ damage. Due to the high correlation between vitamin D and hypertension, vitamin D supplementation therapy may be a new insight in the treatment of hypertension. The aim of this review will explore the mechanisms of the vitamin D and VDR in regulating the BP and protecting against the target organ damage.

Abstract#154;Throughout the last decade, extensive efforts have been devoted to developing a percutaneous catheter ablation and implantable cardioverter-defibrillator technique for patients suffering from ventricular arrhythmia. Antiarrhythmic drug efficacy for preventing arrhythmias remains disappointing because of adverse cardiovascular effects. Allocryptopine is an isoquinoline alkaloid widely present in medicinal herbs. Studies have indicated that allocryptopine exhibits potential anti-arrhythmic actions in various animal models. The potential therapeutic benefit of allocryptopine in arrhythmia diseases is addressed in this study, focusing on multiple ion channel targets and reduced repolarization dispersion. The limitations of allocryptopine research are clear given a lack of parameters regarding toxicology and pharmacokinetics and clinical efficacy in patients with ventricular arrhythmias. Much remains to be revealed about the properties of allocryptopine.

Cardiovascular disease (CVD) is the biggest killer globally and atherosclerosis (AS) is the major trigger to this pathology. Abnormal cholesterol homeostasis is the starting point of AS, especially the aggregation of macrophage foam cells in the intra-arterial subcutaneous region. Reverse cholesterol transport (RCT) can remove excess cholesterol from macrophages and transport it to the liver for excretion, making this process vital to alleviate AS. MicroRNAs (miRNAs) are small, noncoding RNAs that play critical roles in various diseases including AS, by regulating post-transcriptional gene expression. Many natural compounds can exert anti-atherosclerotic effects by regulating different miRNAs that are implicated in RCT. Hence, targeting these miRNAs using natural functional compounds may be a safe, novel, and promising strategy to prevent and treat AS. This review describes the miRNAs involved in RCT and the potential uses of natural compounds to target RCT-related miRNAs to modulate AS.

Reversed micellar system (RMS) is an innovative technique used for the isolation, extraction and purification of proteins and enzymes. Studies have demonstrated that RMS is an efficient purification technology for extracting proteins and enzymes from natural plant materials or fermentation broth. Lately, reverse micelles have wider biological applications and the ease of scaling up and the possibility for the continuous process have made RMS a vital purification technique in various fields. In this study, an extensive review of RMS with the current application in biotechnology is examined. This review provides insights into the fundamental principles, key variables and parameters of RMS. In addition, a comparative study of RMS with other liquid-liquid extraction techniques is also included. The present review aims to provide a general overview of RMS by summarising the research works, since the introduction of the technology to current development.

Extracellular vesicles (EVs) are membranous structures surrounded by a lipid bilayer required for the export of fungal proteins, lipids, toxins, nucleic acids, pigments, and polysaccharides. Proteomic studies of the content of fungal EVs revealed the presence of molecules involved in cell metabolism, signal transduction, and virulence, among others. EVs are evolutionarily conserved in all three domains of life and play important roles in cell-cell communication. Recently, the bidirectional transport of EVs was characterized through the demonstration that EVs can be released and captured by fungal cells. In fungi, EVs participate in immunomodulation through the delivery of virulence factors, antigens and allergens, but further studies are necessary to investigate their potential roles as carriers of diagnostic biomarkers and in drug delivery or antifungal resistance transmission. In this review, we discuss the roles of fungal EVs and their cargo in cell-cell communication, host-pathogen interactions, and environmental perception. The functions of EVs as vehicles for transporting fungal proteins and virulence factors are also addressed, as well as their use as biomarkers for the diagnosis of diseases and possible participation in antifungal responses.