Network Analysis for the Identification of Hub Genes and Related Molecules as Potential Biomarkers Associated With the Differentiation of Bone Marrow-derived Stem Cells Into Hepatocytes

The incidence of liver diseases has been increasing steadily. However, it has some shortcomings, such as high cost and organ donor scarcity. The application of stem cell research has brought new ideas for the treatment of liver diseases. Therefore, it is particularly important to clarify the molecular and regulatory mechanisms of differentiation of bone marrow-derived stem cells (BMSCs) into liver cells. Herein, we screened differentially expressed genes between hepatocytes and untreated BMSCs to identify the genes responsible for the differentiation of BMSCs into hepatocytes. GSE30419 gene microarray data of BMSCs and GSE72088 gene microarray data of primary hepatocytes were obtained from the Gene Expression Omnibus database. Transcriptome Analysis Console software showed that 1896 genes were upregulated and 2506 were downregulated in hepatocytes as compared with BMSCs. Hub genes were analyzed using the STRING, revealing that two hub genes, Cat and Cyp2e1, play a pivotal role in oxidation-reduction process. The results indicate that the lncRNA-miRNA-mRNA interaction chain may play an important role in the differentiation of BMSCs into hepatocytes, which provides a new therapeutic target for liver disease treatment.

Case Report: Two Newly Diagnosed Patients With KBG Syndrome—Two Different Molecular Changes

Mutations or deletions of ANKRD11 gene are responsible for the symptoms of KBG syndrome. The KBG syndrome is a rare genetic disorder which is inherited in an autosomal dominant manner. Affected patients usually have characteristic facial features, macrodontia of the upper central incisors, hand abnormalities, developmental delay and short stature. In the present article we would like to report a clinical and molecular case study of two patients affected by KBG syndrome. The diagnosis of the first patient was confirmed by the identification of the novel pathogenic variant in ANKRD11 gene by next-generation sequencing. The second patient was diagnosed after the detection of a 16q24.2q24.3 deletion encompassing the ANKRD11 gene microarray.

Exploration of SQC Formula Effect on Type 2 Diabetes Mellitus by Whole Transcriptome Profile in Rats

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that has turned up as dimensions of the pandemic all over the world. In China, some traditional Chinese herbal formulas have enjoyed a high reputation in T2DM treatment for centuries. Methods: In this study, ShenQi compound (SQC) is proposed, a formula has been performed on T2DM clinical therapeutics in China for many years. The efficacy of SQC in diabetic rat model by measuring food and water intake and examining islet microcirculatory index involves islets microvessel quantity and density, islets size, pancreatic microvascular wall thickness is evaluated. Meanwhile, gene microarray experiments were performed to explore the molecular mechanism of SQC treatment. In addition, a western medicine, metformin was employed as a comparison. Results: The results indicated that SQC could effectively improve polydipsia, polyphagia and weight loss caused by diabetes as well as pancreatic tissue damage and vascular injury for T2DM. Meanwhile, the gene microarray experiments indicated that SQC may improve the T2DM through affecting the biological functions related to detection of chemical stimulus involved in sensory perception of smell, G-protein coupled receptor signaling pathway, cytoplasmic translation. In addition, SQC presented curative effect by regulated function associated with translation, while metformin presented curative effect by regulated function associated coagulation. Conclusion: SQC is an effective therapeutic drug on T2DM, and present curative effect by regulated function associated with translation.

The hUCMSCs Exerts Excellent Anti-inflammation Effect which is Different from TCZ IL-6 Antagonist by Inducing High IL-6 Secretion

BACKGROUND The biologic and cellular IL-6-related therapies have been used to treat the autoimmune diseases (AID), which prompting us to furtherly explore the IL-6 role in human umbilical cord mesenchymal stem cells (hUCMSCs) therapy.MATERIALS & METHODS Peripheral blood mononuclear cells (PBMCs) were responder co-cultured with hUCMSCs or exogenous IL-6. PBMC suppression assay was used to analyze the anti-inflammatory effects by using the MTT assay. The IL-6 concentration in supernatant was measured using ELISA. The correlation between anti-inflammation effect of hUCMSCs and IL-6 levels, and the relevant roles of IL-6, IL-6 mRNA expression was analyzed using the MetaCore functional network constructed from gene microarray data. The location of IL-6 and IL-6 receptor (IL-6R) expression was furtherly evaluated.RESULTS Initially, hUCMSCs did not exert any inhibitory effect on PBMCs, however, a potent inhibitory effect on PBMCs was observed and the IL-6 concentration reached about 1000 ng/mL after 72 hours. Exogenous 1000 ng/mL IL-6 could inhibit PBMCs inflammations but less than that of hUCMSCs. The hUCMSCs exerts excellent anti-inflammation effect by inducing higher IL-6 level which is different from TCZ IL-6 antagonistCONCLUSIONS High concentration IL-6 cytokine secretion plays an important role in the anti-inflammation effect of hUCMSCs cell therapy.

Identification of Core Gene Biomarkers in Patients With Hypertrophic Cardiomyopathy

Objective：Hypertrophic cardiomyopathy (HCM) is a kind of common hereditary myocardial disease. However, there is still a lack of detailed research in the specific mechanism of HCM. In the present study, gene microarray data were used for bioinformatics analysis to explore differentially expressed genes (DEGs) and signaling pathways between HCM patients and normal control, which would provide suggestion for the prevention and treatment for the further study of HCM.Methods: Gene microarray data of HCM patients and normal control were obtained from the Gene Expression Omnibus (GEO) database affiliated to National Center for Biotechnology Information (NCBI). Gene microarray data of 15 HCM patients and 10 normal people were respectively included. We compared the number of DEGs between the two groups, performed gene ontology (GO) enrichment analysis, kyoto encyclopedia of genes and genomes (KEGG) analysis, construct a protein-protein interaction (PPI) network based on the DEGs detected above.Results: A total of 501 DEGs were selected through analysis, among which 275 were up-regulated and 226 were down-regulated. The DEGs are mainly concentrated in ribosomes, myocardial contractions and various signaling pathways. The down-regulated cellular components and molecular functions of HCM patients were mainly associated with ribosome-related components, and PPI network also found that the DEGs were mainly derived from the ribosome family. Upregulated pathways were mainly enriched in Hippo signaling pathway, PI3K-Akt signaling pathway, AMPK signaling pathway, and adrenergic signaling in cardiomyocytes.Conclusion: By analyzing the DEGs between HCM and normal patients, differentially expressed genes, cellular components and biological processes were found. By exploring the specific mechanism of these DEGs and intervening HCM through various medical procedures, useful suggestions can be provided for targeted prevention, precise treatment and outcome improvement of HCM patients.

The inflammation-resolution promoting molecule resolvin-D1 prevents atrial proarrhythmic remodelling in experimental right heart disease

Aims Inflammation plays a role in atrial fibrillation (AF), but classical anti-inflammatory molecules are ineffective. Recent evidence suggests that failure of inflammation-resolution causes persistent inflammatory signalling and that a novel drug-family called resolvins promotes inflammation-resolution. Right heart disease (RHD) is associated with AF; experimental RHD shows signs of atrial inflammatory-pathway activation. Here, we evaluated resolvin-therapy effects on atrial arrhythmogenic remodelling in experimental RHD. Methods and results Pulmonary hypertension and RHD were induced in rats with an intraperitoneal injection of 60 mg/kg monocrotaline (MCT). An intervention group received daily resolvin-D1 (RvD1), starting 1 day before MCT administration. Right atrial (RA) conduction and gene-expression were analysed respectively by optical mapping and qPCR/gene-microarray. RvD1 had no or minimal effects on MCT-induced pulmonary artery or right ventricular remodelling. Nevertheless, in vivo transoesophageal pacing induced atrial tachyarrhythmias in no CTRL rats vs. 100% MCT-only rats, and only 33% RvD1-treated MCT rats (P < 0.001 vs. MCT-only). Conduction velocity was significantly decreased by MCT, an effect prevented by RvD1. RHD caused RA dilation and fibrosis. RvD1 strongly attenuated RA fibrosis but had no effect on RA dilation. MCT increased RA expression of inflammation- and fibrosis-related gene-expression pathways on gene-microarray transcriptomic analysis, effects significantly attenuated by RvD1 (334 pathways enriched in MCT-rats vs. control; only 177 dysregulated by MCT with RvD1 treatment). MCT significantly increased RA content of type 1 (proinflammatory) CD68-positive M1 macrophages without affecting type 2 (anti-inflammatory) M2 macrophages. RvD1-treated MCT-rat RA showed significant reductions in proinflammatory M1 macrophages and increases in anti-inflammatory M2 macrophages vs. MCT-only. MCT caused statistically significant increases in protein-expression (western blot) of COL3A1, ASC, CASP1, CASP8, IL1β, TGFβ3, CXCL1, and CXCL2, and decreases in MMP2, vs. control. RvD1-treatment suppressed all these MCT-induced protein-expression changes. Conclusion The inflammation-resolution enhancing molecule RvD1 prevents AF-promoting RA remodelling, while suppressing inflammatory changes and fibrotic/electrical remodelling, in RHD. Resolvins show potential promise in combating atrial arrhythmogenic remodelling by suppressing ongoing inflammatory signalling.

GENOTYPE-SYMPTOMATOLOGY CORRELATION STUDIES IN PATIENTS WITH ANXIETY

Projects: To explore the relationship of lncRNAs with altered expression in peripheral blood with symptomatogy in anxiety patients. Methods: Gene microarray was carried on to screen the lncRNAs with altered expressions between anxiety patients (GAD) and healthy people (NC), and qPCR was performed to validate these screened lncRNAs. GAD was assessed by HAMA to analyze differently-expressed lncRNAs and its relationship with symptomatology. Results: 1. The expression levels of PR1-PR10 were positively relayed to psychic anxiety and the total score of HAMA (r=0.187~0.253，P< 0.01 or P< 0.05), the expression level of PR7 was positively related to somatic anxiety (r=0.171，P< 0.05); 2. ROC curve combined analysis showed that the AUC value of ten lncRNAs arrived at 0.808, at chic YI=YImax, sensitivity and specificity was 66.3%, 90.5% respectively; 3. High expression group of PR7 (NONHSAG049179) was significantly higher than that in low expression group accounting for psychic anxiety, aromatic anxiety and total score of HAMA. Conclusion: lncRNA with altered expression may be involved in MDD, and NONHSAG049179 is closely associated with psychic anxiety and somatic anxiety.