ABSTRACT
The Cu(i)-catalyzed stereoconvergent borylative cyclization of ω-mesylate-α,ß-unsaturated compounds is facilitated by a simple Cu-bisphosphine catalyst. This reaction provides a novel route to cis-ß-boron-substituted five- and six-membered carbocycle and heterocycle esters. Mechanistic studies indicate that stereoconvergence and cis-substitution likely stem from the rapid enolation of the borylcopper adduct with the substrate double bond and the formation of a five-membered intermediate, respectively.
ABSTRACT
TLRs belong to a family of pattern recognition receptors (PRRs) that recognize highly conserved microbial antigens termed pathogen associated molecular patterns (PAMPs). So far, ten TLRs have been identified in human genome. Each TLR senses a different set of microbial stimuli, and recruits various of adaptors and activates a series of distinct signaling cascades, and drives specific responses against the pathogens. TLRs bridged innate and adaptive immunity. The discoveries of Toll-like receptors guided the field of innate immunity to its present era of accelerated advancement. In this review, we will focus on the recent progresses of TLRs-mediated signaling. A better understanding of the immunological and molecular mechanisms mediated by TLRs will obviously facilitate the exploiting molecular targets of immunotherapy to control TLR-mediated diseases.
Subject(s)
Adaptive Immunity/immunology , Immunity, Innate/immunology , Signal Transduction/physiology , Toll-Like Receptors/physiology , Animals , HumansABSTRACT
OBJECTIVE: To explore the effect of polymorphism in codon Ala54Thr of human intestinal fatty acid-binding protein gene (IFABP) on the therapeutic efficacy of fenofibrate. METHODS: Totally 147 patients with hyperlipidemia [72 men mean age: (56.2 +/- 8.63) years; 75 women mean age: (58.4 +/- 9.12) years] were enrolled. IFABP genotypes were detected by polymerase chain reaction, Hha I digestion, and sequencing. Four weeks before and after treatment, the levels of fasting serum total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), apolipoprotein A I (apoA I) and apolipoprotein B (apoB) were detected with biochemical techniques. RESULTS: The frequency of IFABP genotype was 0.47 for A/A, 0.37 for A/T, and 0.16 for T/T, and the allelic frequency was 0.65 for A and 0.35 for T. No significant different was found in lipid levels in every genotype before treatment (P > 0.05). After 4 weeks of treatment, the levels of TC, TG, LDL-C, and apoB significantly decreased (P < 00.01), and the levels of HDH-C and apoA I significantly increased (P < 0.01). The total therapeutic efficacy on A54A and A54T were 97% and 95%, respectively. In the patients with T54T genotype after treatment, no significant difference in lipids levels was found except TG (P < 0.05), and the total efficacy was only 38%. The total therapeutic efficacies of fenofibrate on A54A and A54T were higher than those of T54T, and there was significant different between A54A and T54T (P < 0.01). CONCLUSION: The polymorphism of human IFABP gene in hyperlipidemia is related with the therapeutic efficacy of fenofibrate, and the T54T IFABP genotype may have strong negative effect on such efficacy.
Subject(s)
Fatty Acid-Binding Proteins/genetics , Fenofibrate/therapeutic use , Hyperlipidemias/drug therapy , Hyperlipidemias/genetics , Hypolipidemic Agents/therapeutic use , Polymorphism, Genetic , Aged , Apolipoproteins/blood , Female , Gene Frequency , Genotype , Humans , Hyperlipidemias/blood , Lipids/blood , Male , Middle Aged , Treatment OutcomeABSTRACT
OBJECTIVE: To establish a mouse fibroblastic cell line stably transfected with PC-1 gene, and using such cell line to investigate tumor development and progression imposed by the ectopic expression of PC-1 gene. METHODS: Eukaryotic expression vector pcDNA3.1(-)/myc-his-pc-1 was transfected into mouse fibroblast cell line NIH3T3 by lipofectamine. Stable transfectants were selected by G418. The integration and expression of ectopic PC-1 gene were analyzed by PCR and RT-PCR. Cytomorphological analysis, MTT, soft agar colony formation and nude mice tumorigenesis assay were used to evaluate the effects of PC-1 gene expression on tumor development and progression. RESULTS: NIH 3T3 cell lines stably expressing PC-1 gene were successfully established and confirmed by PCR and RT-PCR analyses of the integration and expression of ectopic PC-1 gene. Comparing with the parental cell line and cells transfected with control vector, the PC-1 gene transfectants acquired several phenotypes of transformed cells: increasing growth rate, ability to grow and form cell colonies on soft agar, and becoming tumorigenic in nude mice. CONCLUSION: Ectopic expression of PC-1 gene in NIH3T3 cells can induce malignant transformation of mouse fibroblastic cells both in vitro and in vivo.
Subject(s)
Cell Transformation, Neoplastic , Genes, Neoplasm/physiology , Neoplasm Proteins/biosynthesis , Animals , Cell Line, Transformed , Gene Expression , Mice , Mice, Inbred BALB C , Mice, Nude , NIH 3T3 Cells , Neoplasm Proteins/genetics , Neoplasm Proteins/physiology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Random Allocation , TransfectionABSTRACT
OBJECTIVE: To investigate the expression characteristics of protooncogene c-jun and its related gene p38 in different developmental intestinal epithelial cells in rats, and to explore their biological roles in the intestinal wound healing after injury. METHODS: Immunohistochemical techniques were used to detect the expressions of c-jun, p38 and proliferating cell nuclear antigen (PCNA). RESULTS: The positive expression of c-jun in intestinal epithelial cells at the early development stage (from E14 d to P28 d) was much stronger and more extensive than that in mature rats, and migrated from bottom to top of villus with epithelial cellular development. The positive expression of PCNA was similar with c-jun during the same time, but the distinction between them was location of their expression. The expression of c-jun in mature rat only lay in the top of villus, while the expression of PCNA was limited to intestinal crypts. The expression of p38 during stages of development and mature, mainly was in mitogenic cells. CONCLUSION: The results indicate that the strong expression of tumor gene c-jun at the early development and mature stages of intestinal epithelial cells at the special region is related to cellular differentiation, and p38 is probable correlate with cellular mitogenesis.