抵抗素在肥胖及糖尿病中的作用

Increased evidences indicate that resistin is a new hormone secreted from adipose tissue,it is reported to be an important signal molecule linking between obesity, insulin resistance and type 2 diabetes.Many factors can affect the gene expression of resistin. However, the detailed function of resistin still remainsmys terious and much work needs to be undertaken.     

眼白化病1型的分子病理生理基础

Ocular albinism type 1 (OA1), the most form of the ocular albinism, is an X-linked disorder mainly characterized by a severe reduction of visual acuity, hypopigmentation of the retina, photophobia, strabismus and nystagmus. The OA1 gene is located on chromosome Xp22.32 and the coding sequence is divided into nine exons. The OA1 gene codes for a 404 amino acid protein thought to be a melanosomal transmembrane glycoprotein. The OA1 protein is similar to the G protein-coupled receptors, but it‘s exact function is not clear. There are many mutations and deletions of the OA1 gene have been found.     

Construction of a Mammary-specific Expression Vector of Human α- defensin- 1 ( HNP- 1) Gene

1 Introduction Defensins, also called human neutrophil peptides(HNP), are small cationic peptides with broad antimicrobial activity[1]. Human defensins are highly abundant in the cytoplasmic granules of polymorphonuclear neutrophils. Alpha-defensin-1 is an important mediator in either innate immunity or anti-infection. It can be developed to be an ideal new type antibiotic and may provide a better solution for the present situation of extensive antibiotics-resistence. It is difficult to achieve amount of antimicrobial peptides from nature sources. Transgenic mammary gland bioreactors offer a safe and cost effective source to produce important proteins. The purpose of this study was to construct a mammary-specific expression plasmid containing beta-lactoglobulin (BLG) gene promoter and human α-defensin-1 (HNP-1) gene.     

Protection of Mice from Lethal Endotoxemia by Chimeric Human BPI-Fcγ1 Gene Delivery

To evaluate the potentiality of applying gene therapy to endotoxemia in high-risk patients, we investigated the effects of transferring an adeno-associated virus serotype 2 (AAV2)-mediated BPI-Fcγ1 gene on protecting mice from challenge of lethal endotoxin. The chimeric BPI-Fcγ1 gene consists of two parts, one encods functional N-terminus (1 to 199 amino acidic residues) of human BPI, which is a bactericidal/permeability-increasing protein, and the other encodes Fc segment of human immunoglobulin G1(Fcγ1). Our results indicated that the target protein could be expressed and secreted into the serum of the gene-transferred mice. After lethal endotoxin challenge, the levels of endotoxin and TNF-αin the gene-transferred mice were decreased. The survival rate of the BPI-Fcγ1 gene-transferred mice was markedly increased. Our data suggest that AAV2-mediated chimeric BPI-Fcγ1 gene delivery can potentially be used clinically for the protection and treatment of endotoxemia and endotoxic shock in high-risk individuals.     

Src蛋白研究进展

Src is a non - receptor protein tyrosine kinase activated by a number of extracellular signal moleculars. It is recruited to peripheral sites through myristoylation and the SH3 domain. Src initiates intracel-lular signal trandsduction pathways that influence cell adhesion, migration, growth, differentiation and survival though catalytic domain. Src is normally maintained in an inactive conformation because of carboxy terminal Src kinase, but can be activated transiently during cellular events such as mitosis or constitutively by abnormal events such as mutation and some cancers. In additions, c - Sre protein is found to be highly activated and the Src gene is frequently over- expressed in many cancers. These findings suggest that the relationship between c- Src activation/over - expression and cancer progression appears to be significant.     

中国人圆锥角膜患者的TGFBI基因编码区点突变及多态性的检测和分析

Objective To investigate the point mutations and polymorphisms of transforming growth factor β-induced gene (TGFBI) in Chinese patients with keratoconus and discuss the relationship between the feature of gene mutations and single nucleotide polymorphisms of TGFBI gene and keratoconus. Methods Polymerase chain reaction-single strand conformation polymorphism and DNA direct sequencing were performed in 30 keratoconus cases and 30 healthy controls. All 17 exons of the TGFBI gene were analyzed for point mutations and single nucleotide polymorphisms. Results Totally two heterozygous nucleotide changes were identified in exon 12 of the TGFBI gene. The codon 535 is changed from GGA to TGA in 1 patient, leading to a substitution of glycine to a stop codon at the protein level (G535X). The codon 540 is changed from TTT to TTC in 2 patients and 1 control individual, resulting in a nonsense mutation (F54F),and is a single nucleotide polymorphism of the gene. Conclusion Mutation and polymorphisms of the TGFBI gene were detected in Chinese patients with keratoconus in this study. The results suggest that TGFBI gene might play an important role in the pathogenesis of keratoconus.     

中国人圆锥角膜患者的TGFBI基因编码区点突变及多态性的检测和分析

Objective To investigate the point mutations and polymorphisms of transforming growth factor β-induced gene (TGFBI) in Chinese patients with keratoconus and discuss the relationship between the feature of gene mutations and single nucleotide polymorphisms of TGFBI gene and keratoconus. Methods Polymerase chain reaction-single strand conformation polymorphism and DNA direct sequencing were performed in 30 keratoconus cases and 30 healthy controls. All 17 exons of the TGFBI gene were analyzed for point mutations and single nucleotide polymorphisms. Results Totally two heterozygous nucleotide changes were identified in exon 12 of the TGFBI gene. The codon 535 is changed from GGA to TGA in 1 patient, leading to a substitution of glycine to a stop codon at the protein level (G535X). The codon 540 is changed from TTT to TTC in 2 patients and 1 control individual, resulting in a nonsense mutation (F54F),and is a single nucleotide polymorphism of the gene. Conclusion Mutation and polymorphisms of the TGFBI gene were detected in Chinese patients with keratoconus in this study. The results suggest that TGFBI gene might play an important role in the pathogenesis of keratoconus.     

Therapeutic gene editing strategies using CRISPR-Cas9 for theβ-hemoglobinopathies

With advancements in gene editing technologies,our ability to make precise and efficient modifications to the genome is increasing at a remarkable rate,paving the way for scientists and clinicians to uniquely treat a multitude of previously irremediable diseases.CRISPR-Cas9,short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9,is a gene editing platform with the ability to alter the nucleotide sequence of the genome in living cells.This technology is increasing the number and pace at which new gene editing treatments for genetic disorders are moving toward the clinic.Theβ-hemoglobinopathies are a group of monogenic diseases,which despite their high prevalence and chronic debilitating nature,continue to have few therapeutic options available.In this review,we will discuss our existing comprehension of the genetics and current state of treatment forβ-hemoglobinopathies,consider potential genome editing therapeutic strategies,and provide an overview of the current state of clinical trials using CRISPR-Cas9 gene editing.     

Protection of mice from lethal endotoxemia by chimeric human BPI-Fcgamma1 gene delivery

To evaluate the potentiality of applying gene therapy to endotoxemia in high-risk patients, we investigated the effects of transferring an adeno-associated virus serotype 2 （AAV2）-mediated BPI-Fcγ1 gene on protecting mice from challenge of lethal endotoxin. The chimeric BPI-Fcγ1 gene consists of two parts, one encods functional N-terminus （1 to 199 amino acidic residues） of human BPI, which is a bactericidal/permeability-increasing protein, and the other encodes Fc segment of human immunoglobulin G1 （Fcγ1）. Our results indicated that the target protein could be expressed and secreted into the serum of the gene-transferred mice. After lethal endotoxin challenge, the levels of endotoxin and TNF-a in the gene-transferred mice were decreased. The survival rate of the BPI-Fcγ1 gene-transferred mice was markedly increased. Our data suggest that AAV2-mediated chimeric BPI-Fcγ1 gene delivery can potentially be used clinically for the protection and treatment of endotoxemia and endotoxic shock in high-risk individuals. Cellular ＆ Molecular Immunology. 2006;3（3）：221-225.     

结缔组织生长因子在肾间质纤维化中的表达及其调控

CTGF, a member of the CCN family of immediate early genes, is a recently discovered profibrotic growth factor, which is involved in many pathophysiologic procedures. CTGF acts as a downstreame ffector of TGF-β acting on interstitial ceils to enhance the progression of fibrotic renal diseases. It has been shown that CTGF gene expression can be induced or blocked by some kinds of cytokine and drugs. It is an interesting candidate target for future intervention strategies of renal interstitial fibrosis.