Modular characteristics and mechanism of action of herbs for vascular calcification treatment in Chinese medicine: a data mining and network pharmacology-based identification.

OBJECTIVE: The aim of this study was to investigate the modular characteristics and mechanism of action of Chinese herbs for vascular calcification (VC) treatment. MATERIALS AND METHODS: Network pharmacology coupled with literature data mining was utilized to assess the Chinese herbal clinical performance as well as its similarity, characteristics, ingredient, target, and Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and network construction. RESULTS: The top 15 medications from the literature, according to the usage, and 190 active chemicals, 183 common targets between medication and VC-related targets were weeded out. Analysis of the relationships between the active ingredients, pharmacological targets, and signaling pathways helped to clearly define the therapeutic effect of Traditional Chinese Medicine (TCM). Importantly, we discovered seven most hub proteins (AKT1, CTNNB1, TNF, EGFR, TP53, JUN and IL-6) and two of the herbs' most fundamental ingredients (Formononetin and Luteolin) in TCM-mediated VC suppression. Mechanistically, the metabolic pathways [AGE-RAGE pathway, interleukin-17 (IL-17) pathway, and p53 pathway] as well as smooth muscle adaptation (functional remodeling) and oxidoreductase activity (redox homeostasis modulating) are also crucially implicated. CONCLUSIONS: Our work, accomplished by network pharmacology and data mining, increases our understanding of TCM in VC therapy and may offer insightful information for future drug discovery investigations.

[Characteristics of low frequency repetitive nerve stimulation in patients with myasthenia gravis and its correlation with clinical features].

Objective: To investigate the characteristics of low frequency repetitive nerve stimulation (RNS) in patients with myasthenia gravis (MG) and analyze the correlation between RNS results and clinical characteristics. Methods: The clinical and electrophysiological data of 107 MG patients who were admitted to Guangdong Provincial People's Hospital and underwent electromyography (EMG) between September 2015 to September 2020 were retrospectively reviewed. The characteristics of low frequency RNS in ocular MG and generalized MG patients were analyzed. Patients were divided into RNS-negative group and RNS-positive group according to the RNS results. The clinical features, serological and thymic CT findings, thymic pathology were collected and compared. Binary logistic regression analysis was used to analyze the related factors of low frequency RNS. Results: Generalized MG (73.0%, 46/63) showed a lower positive rate of low frequency RNS compared to ocular MG (34.1%, 15/44) (P<0.001). In generalized MG, the positive rate of low frequency RNS in accessory nerve (68.3%, 43 cases) and facial nerve (52.4%, 33 cases) was higher than that in ulnar nerve (14.3%, 9 cases) (P<0.001). The decrease rate of compound muscle action potential (CMAP) in facial nerve (32%±11%) was higher than that in ocular muscle type (22%±7%) in RNS-positive group (P=0.011). Patients with positive facial nerve RNS were more likely to involve the throat muscles than those with negative result [22 cases (52.4%) compared with 17 cases (26.2%), P=0.006]. RNS-positive group showed a significantly higher quantitative myasthenia gravis (QMG) score than that of negative group (P<0.001). In ocular MG, patients with positive RNS showed a later onset (P=0.021), higher acetylcholine receptor (AChR) antibody-positive rate (P=0.03) and QMG score (P<0.001). Additionally, In generalized MG, patients with positive RNS showed a significantly higher AChR antibody-positive rate (P=0.023) and QMG score (P<0.001). The logistic regression analysis showed that QMG score [OR(95%CI)=1.66(1.36-2.03), P<0.001] and positive AChR antibody [OR(95%CI)=5.45(1.28-23.14), P=0.022] were independently related to abnormal RNS. Conclusions: Low frequency RNS is more sensitive in generalized MG. The stimulation of facial and accessory nerves increases the positive rate of RNS in MG patients. Abnormal results of low frequency RNS tend to be combined with positive AChR antibody and higher QMG score, reflecting the severity of muscle weakness. Therefore, serological examination and early intervention are required for those with abnormal RNS.

Meta-analysis of the association between the rs7903146 polymorphism at the TCF7L2 locus and type 2 diabetes mellitus susceptibility.

Type 2 diabetes mellitus (T2DM) is a chronic disease caused by genetic and environmental factors. T2DM has been associated with specific polymorphisms in the TCF7L2 gene. This study evaluates the relationship between the rs7903146 locus polymorphism of the TCF7L2 gene and T2DM susceptibility through meta-analysis; the overall aim is to provide a basis for evidence-based medicinal treatment of T2DM. Cohort and case-control studies from Medline, PubMed, EMBASE, CBM, CNKI, and academic conferences/dissertations that examined the correlation between T2DM and rs7903146 polymorphisms were evaluated. We determined whether the TCF7L2 rs7903146 locus was associated with T2DM susceptibility by comparing alleles and genotypes. The Stata 11.0 software was applied for meta-analysis, and a random-effects model was adopted for heterogeneity testing and odds ratio (OR) calculation. A fixed-effect model was used for quantitative analysis of the heterogeneity between different studies, and for calculating the percentage of variability I(2). A total of 10 studies related to the rs7903146 loci and T2DM susceptibility were enrolled; this included 3404 cases of T2DM patients and 6473 control cases. Meta-analysis showed that the T allele of rs7903146 was significantly correlated with the risk of T2DM, with both a dominant fixed-effect model (OR = 1.653, 95%CI = 1.416-1.653) and a co-dominant-fixed effect model (OR = 1.525, 95%CI = 1.350-1.723). Meta-analysis revealed that the T allele of rs7903146 was also correlated with T2DM susceptibility.

Valproic acid attenuates the suppression of acetyl histone H3 and CREB activity in an inducible cell model of Machado-Joseph disease.

Machado-Joseph disease (MJD) is caused by a (CAG)n trinucleotide repeat expansion that is translated into an abnormally long polyglutamine tract. This disease is considered the most common form of spinocerebellar ataxia (SCA). In the present study, we developed stable inducible cell lines (PC12Tet-On-Ataxin-3-Q28/84) expressing ataxin-3 with either normal or abnormal CAG repeats under doxycycline control. The expression of acetyl histone H3 and the induction of c-Fos in response to cAMP were strongly suppressed in cells expressing the protein with the expanded polyglutamine tract. Treatment with valproic acid, a histone deacetylase inhibitor (HDACi), attenuated mutant ataxin-3-induced cell toxicity and suppression of acetyl histone H3, phosphorylated cAMP-responsive element binding protein (p-CREB) as well as c-Fos expression. These results indicate that VPA can stimulate the up-regulation of gene transcription through hyperacetylation. Thus, VPA might have a therapeutic effect on MJD.

Marrow mesenchymal stem cells transduced with TPO/FL genes as support for ex vivo expansion of hematopoietic stem/progenitor cells.

A new marrow-derived mesenchymal stem cell (hMSC) line that could support expansion of hematopoietic stem/progenitor cells (HSPCs) was developed. Primary hMSCs were infected with retrovirus containing Flt-3 ligand and thrombopoietin genes. CD34+ cells from cord blood were expanded with primary hMSCs or transduced hMSCs. The expansion of total nucleated cells, CD34+ cells and mixed colonies containing erythroid and myeloid cells and megakaryocytes for 2 weeks coculture with transduced hMSCs was remarkably increased. The outputs of long-term culture-initiating cells for 2 and 4 weeks coculture with transduced hMSCs were also largely increased. The expansion rates of HSPCs with transduced hMSCs were unchanged for 6 weeks. In contrast, the expansion rates of HSPCs with primary hMSCs declined drastically through 6 weeks. SCID-repopulating cell expansion with transduced hMSCs for 4 weeks was significantly higher than that of uncultured CD34,+ cells and HSPCs expanded with primary hMSCs.