A drug delivery system of HIF-1α siRNA nanoparticles loaded by mesenchymal stem cells on choroidal neovascularization.

Aim: To assess mesenchymal stem cells (MSCs) as carriers for HIF-1α siRNA-loaded nanoparticles (NPs) for targeted therapy of experimental choroidal neovascularization (CNV).Materials & methods: A poly (lactic-co-glycolic acid) (PLGA)-core/lipid-shell hybrid NP was designed. The transfection efficacy of MSCs with the hybrid NPs was assessed. Mice were intravenously injected with MSCs after laser photocoagulation and CNV was assessed at 7 days post-injection.Results & conclusion: The transfection efficiency of hybrid NPs into MSCs was 72.7%. HIF-1α mRNA expression in 661w cells co-cultured with MSC-hybrid-siRNA NPs was significantly lower. Intravenous delivery of MSC-hybrid-siRNA NPs greatly reduced CNV area and length. Intravenous injection of MSC-hybrid-siRNA NPs achieved therapeutic efficacy in reducing CNV area. The MSC-mediated homing enabled targeted inhibition of ocular angiogenesis.

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Retinitis pigmentosa with iris coloboma due to miR-204 gene variant in a Chinese family.

PURPOSE: To characterize the phenotype and genotype of a Chinese family with autosomal-dominant retinitis pigmentosa (RP) accompanied by iris coloboma. METHODS: The proband, a 34-year-old male, was examined with his family by using fundus photography, optical coherence tomography (OCT), autofluorescence, and full-field electroretinography (ffERG). Genetic analyses were conducted through whole-exome sequencing (WES) to screen for variations. RESULTS: Three members of this Chinese family were shown to be bilateral iris coloboma. The male proband and his mother exhibited typical RP feature. The proband's late grandfather had been documented manifestation of iris coloboma. The mode of inheritance was confirmed to be autosomal dominance. Through linkage analysis and WES, a heterozygous variation in the miR-204 gene (n.37C>T), a noncoding RNA gene, was identified in these three members. CONCLUSIONS: In this third independent and the first Asian family, the existence of a miR-204 variant associated with RP accompanied by iris coloboma was confirmed. Our findings reinforce the significance of miR-204 as an important factor influencing visual function in the retina. When phenotypes like RP accompanied by iris coloboma in an autosomal-dominant pattern, including in Chinese patients, miR-204 aberrations should be considered.

A new analysis of testicular proteins through integrative bioinformatics.

The testis is the male gonad responsible for spermatogenesis and steroidogenesis. Much remains to be known about the control of these events. In this study, we performed a new bioinformatic enrichment analysis of human testicular proteins selected from a protein database. Integrated function and pathway analyses were performed by Database for Annotation, Visualization and Integrated Discovery and Ingenuity Pathway Analysis programmes, and significant features were found to be clustered. Protein membrane organization and gene density on chromosomes were analyzed and discussed. The analysis could provide a basis for the understanding of testicular physiology and function, and facilitating biological interpretation of testicular functions in a network context.

Expression of MicroRNA-146a in peripheral blood mononuclear cells in patients with systemic lupus erythematosus.

OBJECTIVE: To explore the expression pattern of microRNAs in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), with an attempt to identify the role of microRNA in the pathogenesis of SLE. METHODS: SLE-related genes were searched from the published literatures. Using the microRNA target gene prediction databases, we predicted the putative microRNA targets in these SLE-related genes. For some of the corresponding microRNAs (hsa-miR-146a), quantitative real-time polymerase chain reaction was performed to determine the expression levels of these microRNAs in PBMCs of SLE patients (SLE group) and healthy controls (control group). RESULT: The discrepancy of cycle threshold of hsa-miR-146a in PBMCs was significantly higher in SLE group (4.52±1.18) than in control group (2.76±1.38) (P=0.02), and the expression level of hsa-miR-146a was significantly lower in SLE group. CONCLUSION: The expression of hsa-miR-146a decreases in SLE patients, indicating that hsa-miR-146a may play a role in the pathogenesis of SLE.

Evidence that geniposide abrogates norepinephrine-induced hypopigmentation by the activation of GLP-1R-dependent c-kit receptor signaling in melanocyte.

Geniposide (GP) as an agonist of glucagon-like peptide-1 receptor (GLP-1R) is an iridoid glycoside from the fruit of Gardenia jasminoides Ellis used as a Chinese traditional medicine for treatment of vitiligo vulgaris. Interaction of c-kit receptor with its ligand-SCF potent enhances the melanocytic melanogenesis, which can be repressed by norepinephrine (NE). To discover economic and efficient drug against vitiligo vulgaris, this paper addresses the action and mechanism of GP abrogating the NE-induced hypopigmentation in melanocyte. Flow cytometry exhibited the up-regulation effect of GP on NE-suppressed production of c-kit by normal human epidermal melanocyte (HEMn) in a concentration-dependent manner, and exendin-(9-39) (selective GLP-1R antagonist) appeared to alleviate the GP-stimulated expression of c-kit. However, neither NE nor GP affected the production of SCF by normal human epidermal keratinocyte (HEKn) assessed by cellular enzyme-linked immunosorbent assay. Spectrophotometry documented that GP abrogated the repression effect of NE on tyrosinase activity and melanin production in HEMn in the presence of recombination SCF significantly. The response of melanocytic melanogenesis to GP was blocked by exendin-(9-39) or K44.2 antibody (c-kit inhibitory antibody). Data from this paper provide the evidence that GP abrogates the NE-induced hypopigmentation by the activation of GLP-1R-dependent c-kit receptor signaling in which c-kit expression is augmented in HEMn.