Effects of dual-gene modification on biological characteristics of vascular endothelial cells and their significance as reserving cells for chronic wound repair.

bFGF is a commonly used and reliable factor for improving chronic wound healing, and hSulf-1 expression is abundant in surrounding cells of chronic wound tissue and vascular endothelial cells, which can reverse the effect of bFGF and inhibit the signalling activity of cell proliferation. In this study, an adenovirus, Ad5F35ET1-bFGF-shSulf1, was designed for establishing the dual-gene modified vascular endothelial cells, which were used as the repair cells for skin chronic wound. Ad5F35ET1-bFGF-shSulf1 infected ECV304 cells in vitro and mediated the overexpression of bFGF and the knockdown of hSulf-1, which effectively activated the AKT and ERK signal transduction pathways, facilitate cell proliferation and migration, with the cell viability to 128.

Comparison of biological and mechanical properties of different paranasal sinus mucosa in goat.

Objective: The present study was designed to explore endurable pressure intensity of different paranasal sinus mucosa in goats.

Method: Mucosa commonly involved in maxillary sinus augmentation, including mucosa from maxillary sinus crest, maxillary sinus floor, and frontal sinus, were harvested in a computed tomography-guided manner. The obtained mucosa was then sectioned into square and irregular ones for maximum endurable pressure intensity determination and morphological observation, respectively.

Discovery of Small-Molecule CD33 Pre-mRNA Splicing Modulators.

CD33/Siglec 3 is a myeloid lineage cell surface receptor that is known to regulate microglia activity. Multiple genome-wide association studies (GWAS) have identified genetic variants in the CD33 gene that convey protection from late-onset Alzheimer's disease. Furthermore, mechanistic studies into GWAS-linked variants suggest that disease protection is attributed to the alternative splicing of exon 2 of the CD33 pre-mRNA.

Comparison of Biological Characteristics of Different Paranasal Sinus Mucosa in Goats.

Background/purpose: Prosthetic implants are the primary treatment for patients with edentulism. This study aims to explore and compare the biological characteristics of mucosal thickness and tensile strength of the paranasal sinuses (maxillary and frontal sinuses) in goats, thereby providing a theoretical basis and guidance for mucosa-related problems involved in maxillary sinus lifting.

Materials And Methods: The paranasal sinus mucosa (maxillary sinus crest, maxillary sinus floor and frontal sinus mucosa) was obtained from the goats for use in maxillary sinus lifting.

DNA sequencing and CRISPR-Cas9 gene editing for target validation in mammalian cells.

Identification and validation of drug-resistant mutations can provide important insights into the mechanism of action of a compound. Here we demonstrate the feasibility of such an approach in mammalian cells using next-generation sequencing of drug-resistant clones and CRISPR-Cas9-mediated gene editing on two drug-target pairs, 6-thioguanine-HPRT1 and triptolide-ERCC3. We showed that disrupting functional HPRT1 allele or introducing ERCC3 point mutations by gene editing can confer drug resistance in cells.

Targeted genome editing tools for disease modeling and gene therapy.

The development of custom-designed nucleases (CDNs), including zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), has made it possible to perform precise genetic engineering in many cell types and species. More recently, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system has been successfully employed for genome editing. These RNA-guided DNA endonucleases are shown to be more efficient and flexible than CDNs and hold great potential for applications in both biological studies and medicine.

A functional polymorphism in MIR196A2 is associated with risk and progression of nasopharyngeal carcinoma in the Chinese population.

Background: Genetic variations in microRNAs may alter their processing, expression, and binding to target mRNAs, consequently affecting many cancer-related biological processes. Recently, a polymorphism rs11614913 in MIR196A2 was shown to affect the processing of the precursor microRNA into its mature forms and the repertoire of target mRNAs with which it interacts. We examined whether this polymorphism was relevant to the risk of occurrence or progression of nasopharyngeal carcinoma (NPC) in the Chinese population.

A non-synonymous SNP in the NOS2 associated with septic shock in patients with sepsis in Chinese populations.

Sepsis represents a systemic inflammatory response to infection and its sequelae include severe sepsis, septic shock, multiple organ dysfunction syndrome (MODS) and death. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS, NOS2) plays an important role in the development of sepsis and its sequelae. It was reported that several single nucleotide polymorphisms (SNPs) within NOS2 could influence the production or activity of NOS2.

Dual actions of Meis1 inhibit erythroid progenitor development and sustain general hematopoietic cell proliferation.

Myeloid ecotropic viral integration site 1 (Meis1) forms a heterodimer with Pbx1 that augments Hox-dependent gene expression and is associated with leukemogenesis and HSC self-renewal. Here we identified 2 independent actions of Meis1 in hematopoietic development: one regulating cellular proliferation and the other involved in megakaryocyte lineage development. First, we found that endogenous Mesp1 indirectly induces Meis1 and Meis2 in endothelial cells derived from embryonic stem cells.

Snail promotes the cell-autonomous generation of Flk1(+) endothelial cells through the repression of the microRNA-200 family.

Expression of the transcription factor Snail is required for normal vasculogenesis in the developing mouse embryo. In addition, tumors expressing Snail have been associated with a more malignant phenotype, with both increased invasive properties and angiogenesis. Although the relationship between Snail and vasculogenesis has been noted, no mechanistic analysis has been elucidated.

Snail and the microRNA-200 family act in opposition to regulate epithelial-to-mesenchymal transition and germ layer fate restriction in differentiating ESCs.

The reprogramming of somatic cells to inducible pluripotent stem cells requires a mesenchymal-to-epithelial transition. While differentiating ESCs can undergo the reverse process or epithelial-to-mesenchymal transition (EMT), little is known about the role of EMT in ESC differentiation and fate commitment. Here, we show that Snail homolog 1 (Snail) is expressed during ESC differentiation and is capable of inducing EMT on day 2 of ESC differentiation.

Functional polymorphism -31C/G in the promoter of BIRC5 gene and risk of nasopharyngeal carcinoma among chinese.

Background: Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5, also called as survivin) is a member of the inhibitor of apoptosis protein (IAP) family, which plays an important role in the occurrence and progression of cancer. Recently, a polymorphism in the promoter of BIRC5, -31C/G (rs9904341), was shown to influence BIRC5 expression.

Methods: We examined whether the -31C/G was related to the risk of developing nasopharyngeal carcinoma (NPC) in a case-control population from Guangxi province in southern China, which consists of 855 patients with NPC and 1036 controls.

Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers.

To identify susceptibility variants for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we conducted a genome-wide association study by genotyping 440,794 SNPs in 355 chronic HBV carriers with HCC and 360 chronic HBV carriers without HCC, all of Chinese ancestry. We identified one intronic SNP (rs17401966) in KIF1B on chromosome 1p36.22 that was highly associated with HBV-related HCC and confirmed this association in five additional independent samples, consisting of 1,962 individuals with HCC, 1,430 control subjects and 159 family trios.

Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs.

Wnt signaling is required for development of mesoderm-derived lineages and expression of transcription factors associated with the primitive streak. In a functional screen, we examined the mesoderm-inducing capacity of transcription factors whose expression was Wnt-dependent in differentiating ESCs. In contrast to many inactive factors, we found that mesoderm posterior 1 (Mesp1) promoted mesoderm development independently of Wnt signaling.

Development of a microscopy-based assay for protein kinase Czeta activation in human breast cancer cells.

Protein kinase Czeta (PKCzeta) plays a critical role in cancer cell chemotaxis. Upon activation induced by epidermal growth factor (EGF) or chemoattractant SDF-1alpha, PKCzeta redistributes from cytosol to plasma membrane. Based on this property, we developed a rapid cell-based assay for inhibitors of ligand-induced PKCzeta activation.