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Target Identification of Active Constituents of Shen Qi Wan to Treat Kidney Yang Deficiency Using Computational Target Fishing and Network Pharmacolo…
2019
Background: Kidney yang deficiency syndrome (KYDS) is one of the most common syndromes treated with traditional Chinese medicine (TCM) among elderly patients. Shen Qi Wan (SQW) has been effectively used in treating various diseases associated with KYDS for hundreds of years. However, due to the complex composition of SQW, the mechanism of action remains unknown. Purpose: To identify the mechanism of the SQW in the treatment of KYDS and determine the molecular targets of SQW. Methods: The potential targets of active ingredients in SQW were predicted using PharmMapper. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out using the …
N-Desmethyldauricine Induces Autophagic Cell Death in Apoptosis-Defective Cells via Ca2+ Mobilization
2017
Resistance of cancer cells to chemotherapy remains a significant problem in oncology. Mechanisms regulating programmed cell death, including apoptosis, autophagy or necrosis, in the treatment of cancers have been extensively investigated over the last few decades. Autophagy is now emerging as an important pathway in regulating cell death or survival in cancer therapy. Recent studies demonstrated variety of natural small-molecules could induce autophagic cell death in apoptosis-resistant cancer cells, therefore, discovery of novel autophagic enhancers from natural products could be a promising strategy for treatment of chemotherapy-resistant cancer. By computational virtual docking analysis,…
Tetrandrine, an Activator of Autophagy, Induces Autophagic Cell Death via PKC-α Inhibition and mTOR-Dependent Mechanisms
2017
Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes. In addition, tetrandrine induces cell death in a panel of apoptosis-resistant…
Detection of Vasodilators From Herbal Components by a Transcriptome-Based Functional Gene Module Reference Approach
2019
Vasodilatation is one of the key therapeutic strategies for the treatment of various cardiovascular diseases with high blood pressure. Therefore, development of drugs assisting blood vessel dilation is promising. It has been proved that many drugs display definite vasorelaxant effects. However, there are very few studies that systemically explore the effective vasodilators. In this work, we build a transcriptome-based functional gene module reference approach for systematic pursuit of agents with vasorelaxant effects. We firstly curate two functional gene modules that specifically involved in positive and negative regulation of vascular diameter based on the known gene functional interactio…
The EP300/TP53 pathway, a suppressor of the Hippo and canonical WNT pathways, is activated in human hearts with arrhythmogenic cardiomyopathy in the …
2021
Aim Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease that typically manifests with cardiac arrhythmias, progressive heart failure and sudden cardiac death (SCD). ACM is mainly caused by mutations in genes encoding desmosome proteins. Desmosomes are cell-cell adhesion structures and hubs for mechanosensing and mechanotransduction. The objective was to identify the dysregulated molecular and biological pathways in human ACM in the absence of overt heart failure. Methods and results Transcriptomes in the right ventricular endomyocardial biopsy samples from three independent individuals carrying truncating mutations in the DSP gene and 5 control samples were analyzed by RNA-S…
Activin Receptor Ligand Blocking and Cancer Have Distinct Effects on Protein and Redox Homeostasis in Skeletal Muscle and Liver
2019
Muscle wasting in cancer cachexia can be alleviated by blocking activin receptor type 2 (ACVR2) ligands through changes in protein synthesis/degradation. These changes in cellular and protein metabolism may alter protein homeostasis. First, we elucidated the acute (1–2 days) and 2-week effects of blocking ACVR2 ligands by soluble activin receptor 2B (sACVR2B-Fc) on unfolded protein response (UPR), heat shock proteins (HSPs) and redox balance in a healthy mouse skeletal muscle. Second, we examined UPR, autophagy and redox balance with or without sACVR2B-Fc administration in muscle and liver of C26 tumor-bearing mice. The indicators of UPR and HSPs were not altered 1–2 days after a single sAC…
Mesenchymal Stem Cells Improve Glycometabolism and Liver Regeneration in the Treatment of Post-hepatectomy Liver Failure
2019
Background The mortality rate of post-hepatectomy liver failure (PHLF) remains very high, and liver transplantation is the only effective treatment regimen for PHLF. Cell transplantation is a potential treatment for liver diseases. Previous studies have proved that mesenchymal stem cells (MSCs) have immunomodulatory functions. In the present study, we found that MSCs promoted glycogen synthesis and liver regeneration in the treatment of PHLF. MSC transplantation also improved the survival rate of rats after 90% partial hepatectomy (PH). In our current study, we aimed to determine the efficacy and mechanism of MSC transplantation in the treatment of PHLF. Methods Mesenchymal stem cells were …
Dextransucrase Expression Is Concomitant with that of Replication and Maintenance Functions of the pMN1 Plasmid in Lactobacillus sakei MN1
2017
The exopolysaccharide synthesized by Lactobacillus sakei MN1 is a dextran with antiviral and immunomodulatory properties of potential utility in aquaculture. In this work we have investigated the genetic basis of dextran production by this bacterium. Southern blot hybridization experiments demonstrated the plasmidic location of the dsrLS gene, which encodes the dextransucrase involved in dextran synthesis. DNA sequencing of the 11,126 kbp plasmid (pMN1) revealed that it belongs to a family which replicates by the theta mechanism, whose prototype is pUCL287. The plasmid comprises the origin of replication, repA, repB, and dsrLS genes, as well as seven open reading frames of uncharacterized f…
Human-Driven Microbiological Contamination of Benthic and Hyporheic Sediments of an Intermittent Peri-Urban River Assessed from MST and 16S rRNA Gene…
2017
International audience; Rivers are often challenged by fecal contaminations. The barrier effect of sediments against fecal bacteria was investigated through the use of a microbial source tracking (MST) toolbox, and by Next Generation Sequencing (NGS) of V5-V6 16S rRNA gene (rrs) sequences. Non-metric multi-dimensional scaling analysis of V5-V6 16S rRNA gene sequences differentiated bacteriomes according to their compartment of origin i.e., surface water against benthic and hyporheic sediments. Classification of these reads showed the most prevalent operating taxonomic units (OTU) to be allocated to Flavobacterium and Aquabacterium. Relative numbers of Gaiella, Haliangium, and Thermoleophilu…
Sex-Specific Genetic Effects Associated with Pigmentation, Sensitivity to Sunlight, And Melanoma in a Population of Spanish Origin
2016
Background Human pigmentation is a polygenic quantitative trait with high heritability. In addition to genetic factors, it has been shown that pigmentation can be modulated by oestrogens and androgens via up- or down-regulation of melanin synthesis. Our aim was to identify possible sex differences in pigmentation phenotype as well as in melanoma association in a melanoma case-control population of Spanish origin. Methods Five hundred and ninety-nine females (316 melanoma cases and 283 controls) and 458 males (234 melanoma cases and 224 controls) were analysed. We genotyped 363 polymorphisms (single nucleotide polymorphisms (SNPs)) from 65 pigmentation gene regions. Results When samples were…