Application of nanotechnology in thrombus therapy.

The diseases caused by two pathological processes, thrombosis, and thromboembolism, are clinically known as thrombotic diseases, which seriously threaten human life and health, and their incidence rate is the highest among various diseases. Research on thrombotic diseases is one of the focuses and hotspots of contemporary medical research. Nanomedicine is a new branch of nanotechnology used in the medical field, and nanomaterials are widely used in medical imaging and drug delivery to help diagnose and treat major diseases such as cancer. With the gradual maturity of nanotechnology, new nanomaterials have recently been used in antithrombotic drugs and released accurately at lesions, which has improved antithrombotic therapy safety. Nanosystems can be employed for cardiovascular diagnosis in future as they can aid in diagnosing pathological diseases and treat them with targeted delivery systems. Unlike other reviews, we herein aim to illustrate the progress of nanosystems in thrombosis therapy. This paper mainly describes how a drug-loaded nanosystem can control drug release under various conditions and accurately treat thrombus, summarizing the research progress of nanotechnology in antithrombotic therapy so that clinicians can better understand nanotechnology and its applications and provide new ideas for treating thrombosis.

Pathogenic role of microRNAs in atherosclerotic ischemic stroke: Implications for diagnosis and therapy.

Ischemic stroke resulting from atherosclerosis (particularly in the carotid artery) is one of the major subtypes of stroke and has a high incidence of death. Disordered lipid homeostasis, lipid deposition, local macrophage infiltration, smooth muscle cell proliferation, and plaque rupture are the main pathological processes of atherosclerotic ischemic stroke. Hepatocytes, macrophages, endothelial cells and vascular smooth muscle cells are the main cell types participating in these processes. By inhibiting the expression of the target genes in these cells, microRNAs play a key role in regulating lipid disorders and atherosclerotic ischemic stroke. In this article, we listed the microRNAs implicated in the pathology of atherosclerotic ischemic stroke and aimed to explain their pro- or antiatherosclerotic roles. Our article provides an update on the potential diagnostic use of miRNAs for detecting growing plaques and impending clinical events. Finally, we provide a perspective on the therapeutic use of local microRNA delivery and discuss the challenges for this potential therapy.

Exploring the Potential Molecular Mechanism of Scutellaria baicalensis Georgi in the Treatment of Gastric Cancer Based on Network Pharmacological Analysis and Molecular Docking Technology.

Objective: To explore the molecular mechanism of Scutellaria baicalensis Georgi in treating gastric cancer by network pharmacological analysis and molecular docking. Methods: Taking Scutellaria baicalensis Georgi as the object, the active components and corresponding potential drug targets in Scutellaria baicalensis Georgi were obtained from the database of TCM Pharmacological System Analysis Platform (TCMSP). GeneCards/OMIM/DrugBank and other databases were used to collect gastric cancer-related genes, and the obtained genes were intersected with drug targets to obtain the target genes of Scutellaria baicalensis Georgi on gastric cancer. Furthermore, the interaction network of Scutellaria baicalensis Georgi-active ingredients-target-gastric cancer-related genes was constructed. Protein-protein interaction analysis and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on target genes. The PubChem website was used to screen the compounds corresponding to the target genes, and the target protein and 3D structure pdb format files were obtained from the PDB database. Finally, the molecular docking calculation was performed by the AutoDock Vina program. The in vivo cell experiments on the effect of Scutellaria baicalensis on proliferation and migration of gastric cancer cells were used to determine the therapeutic effect of Scutellaria baicalensis on gastric cancer, and the two genes ESR1 and FOS are the key targets of Scutellaria baicalensis on gastric cancer. Results: A total of 10 gastric cancer-related target genes were screened out, and Scutellaria baicalensis Georgi contained 10 active compounds targeting 10 gene sites. There are 30 effective compounds in Scutellaria baicalensis Georgi targeted to treat gastric cancer, and there are 91 corresponding targeting gene sites, involving a total of 10 pathways. The results of molecular docking show that ESR1, FOS, and Scutellaria baicalensis Georgi have good binding free energy and docking fraction. The docking fraction of FOS is -4.200 and the binding free energy is -27.893 kcal/mol. The docking fraction of ESR1 is -5.833 and the binding free energy is -30.001 kcal/mol. The effect of Scutellaria baicalensis Georgi on gastric cancer was verified by in vitro cell experiments and Western blotting. Conclusion: Scutellaria baicalensis Georgi can target and regulate multiple signal pathways by acting on ESR1 and FOS gene loci, thus having a potential therapeutic effect on gastric cancer.

Comparative Genome and Transcriptome Integration Studies Reveal the Mechanism of Pectoral Muscle Development and Function in Pigeons.

Pigeon breed resources provide a genetic model for the study of phenomics. The pectoral muscles play a key role for the meat production performance of the meat pigeon and the athletic ability of the High flyers. Euro-pigeons and Silver King pigeons are commercial varieties that exhibit good meat production performance. In contrast to the domestication direction of meat pigeons, the traditional Chinese ornamental pigeon breed, High flyers, has a small and light body. Here, we investigate the molecular mechanism of the pectoral muscle development and function of pigeons using whole-genome and RNA sequencing data. The selective sweep analysis (F ST and log2 (θπ ratio)) revealed 293 and 403 positive selection genes in Euro-pigeons and Silver King, respectively, of which 65 genes were shared. With the Silver King and Euro-pigeon as the control group, the High flyers were selected for 427 and 566 genes respectively. There were 673 differentially expressed genes in the breast muscle transcriptome between the commercial meat pigeons and ornamental pigeons. Pigeon genome selection signal combined with the breast muscle transcriptome revealed that six genes (SLC16A10, S100B, SYNE1, HECW2, CASQ2 and LOC110363470) from commercial varieties of pigeons and five genes (INSC, CALCB, ZBTB21, B2M and LOC110356506) from Chinese traditional ornamental pigeons were positively selected which were involved in pathways related to muscle development and function. This study provides new insights into the selection of different directions and the genetic mechanism related to muscle development in pigeons.

Five immune-gene-signatures participate in the development and pathogenesis of Kawasaki disease.

OBJECTIVE: To screen for immune genes that play a major role in Kawasaki disease and to investigate the pathogenesis of Kawasaki disease through bioinformatics analysis. METHODS: Kawasaki disease-related datasets GSE18606, GSE68004, and GSE73461 were downloaded from the Gene Expression Omnibus database. Three microarrays were integrated and standardized to include 173 Kawasaki disease samples and 101 normal samples. The samples were analyzed using CIBERSORT to obtain the infiltration of 22 immune cells and analyze the differential immune cells in the samples and correlations. The distribution of the samples was analyzed using principal component analysis (PCA). Immune-related genes were downloaded, extracted from the screened samples and analyzed for differential analysis (different expression genes [DEG]) and weighted gene co-expression network analysis (WGCNA). We constructed coexpression networks, and used the cytohobbe tool in Cytoscape to analyze the coexpression networks and select the immune genes that played a key role in them. RESULTS: Immune cell infiltration analysis showed that B cells naive, T cells CD8, natural killer (NK) cells activated, and so forth were highly expressed in normal samples. T cells CD4 memory activated, monocytes, neutrophils, and so forth were highly expressed in Kawasaki disease samples. PCA results showed a significant difference in the distribution of normal and Kawasaki disease samples. From the screened samples, 97 upregulated and 103 downregulated immune-related genes were extracted. WGCNA analysis of DEG yielded 10 gene modules, of which the three most relevant to Kawasaki disease were red, yellow, and gray modules. They were associated with cytokine regulation, T-cell activation, presentation of T-cell receptor signaling pathways, and NK cell-mediated cytotoxicity. CXCL8, CCL5, CCR7, CXCR3, and CCR1 were identified as key genes by constructing a coexpression network. CONCLUSION: Our study shows that we can distinguish normal samples from Kawasaki disease samples based on the infiltration of immune cells, and that CXCL8, CCL5, CCR7, CXCR3, and CCR1 may play important roles in the development of Kawasaki disease.

[pcDPG parathyroid hormone gene therapy of hypoparathyroidism: an experimental study].

OBJECTIVE: To construct recombination eukaryote expression plasmid for human parathyroid hormone (PTH) gene, assay PTH expression and biological activity after transfection in vitro and evaluate gene therapy effect on hypoparathyroidism (HPT). METHODS: (1) PTH gene was amplified from human embryonic parathyroid gland tissue, and plasmid pcDNA3.1-PTH-GFP (pcDPG) was constructed by TOPO recombination technique. Digestion, PCR and sequencing were used to identify the positive vectors. (2) pcDPG was transformed into 293 cells by Lipofectamine 2000(TM), fluorescent inverted microscope was used to observe GFP expression, and PTH gene expression was assayed by RT-PCR technique. (3) PTH protein in supernatant was purified and evaluated biological activity. (4) HPT rabbit models were developed and plasmid pcDPG was injected in skeletal muscles, respectively. Serum calcium, phosphonium and PTH were assayed and pathological changes observed. RESULTS: (1) The findings in digestion and PCR were accorded to anticipation and sequences in report were identified to reference at 99.30%. (2) 24 h after transfection GFP expression could be detected and enhanced with time prolonged arriving to 38.91% and 62.45% at 48 h. PTH gene expression could be detected by RT-PCR. (3) Purified PTH protein made the signs of HPT disappear. (4) Serum calcium and PTH levels were lower than those of pre-operation (P < 0.05) and serum phosphonium enhanced to normal standard 48 h after treatment at the plasmid pcDPG doses of 300 microg/kg and 500 microg/kg. CONCLUSION: Recombination plasmid pcDPG was transformed effectively in vitro and the transfected cells produced PTH protein with biological activity. Besides, the satisfactory therapeutic effect of HPT rabbits was attained by pcDPG plasmid, which provided a foundation for further study of HPT gene therapy.