分类: 生物学 >> 生态学 提交时间: 2017-11-17
摘要: It is urgent to discover new anti-influenza drugs considering the threat of so called swine flu and Spanish flu. Though Adamantane derivatives are the only M2 inhibitors as anti-influenza virus A drugs, they are limited to use in the US due to drug resistant. Herein we reported that multiple lead compounds as M2 inhibitors were rapidly generated through the screening of focused library designed with scaffold-hopping strategy based on Amantadine.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: A PCR-based subtractive hybridization technique was used to identify genes up-regulated in the hibernating bat brain to explore the molecular mechanism of hibernation. Three genes, Liprin-a2, PTP4A2 and CAMKKb were differentially expressed in hibernating bat brain tissue compared to active bat brain tissue. One of them, Liprin-a2, which has recently been shown to have the key function in the organization of presynaptic and postsynaptic multiprotein complexes was studied in detail. We demonstrated that the expression level of Liprin-a2 was up-regulated almost 4-fold in hibernating bat brains by RT-PCR compared to levels in active bats. The differential expression pattern of Liprin-a2 was also detected in muscle, fat, brain and heart tissue of hibernating bats by real-time quantitative PCR. The result indicated that Liprin-a2 was over-expressed in brain and heart tissue and down-regulated in muscle and fat. In brain tissue of hibernating bats, Liprin-a2 expression was statistically significantly higher than in brain tissue of active controls (P = 0.029). The precise control of transcriptional level and the distinctively differential expression pattern of Liprin-a2 in different organs during circannual hibernation may have important physiological significance, not only in maintaining normal function of many key organs but also in effectively conserving limited energy resources without physiological damage.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: Simple, accurate, and stable diagnostic tests are essential to control viral infectious diseases such as avian influenza virus. The current technologies are often inaccessible to people who need them, mainly because of the specialized equipment and the need for highly trained technologists. Here, we describe a rapid isothermal nucleic acid detection assay (RIDA) that can be used to detect both DNA and RNA targets. Using chemically modified probes, we designed a lateral-flow (LF) immunoassay that can be used in combination with RIDA for equipment-free nucleic acid target detection. RIDA is a “probe amplification” assay that uses the single-strand nicking activity of restriction nicking endonucleases to repeatedly cleave synthetic probes hybridizing to the same target sequences. In the RIDA-LF combined assay, chemically labeled probes are covalently conjugated to magnetic microbeads, which is propitious to separate cleaved probes from the reaction solution. The cleaved probes in the solution are then detected with an LF immunoassay. The real-time assay shows that RIDA is able to specifically detect target sequences in 5 to 15 min. The RIDA-LF combined assay can specifically detect nucleic acid targets without sophisticated equipment. In this report, our data suggest that RIDA is a flexible simple assay that could be applied for point-of-care detection. The modified-RIDA described in this report further extends the application of this technology. © 2008 Elsevier Inc. All rights reserved.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: To enhance therapeutic efficacy and reduce adverse effects, practitioners of traditional Chinese medicine (TCM) prescribe a combination of plant species/minerals, called formulae, based on clinical experience. Nearly 100,000 formulae have been recorded, but the working mechanisms of most remain unknown. In trying to address the possible beneficial effects of formulae with current biomedical approaches, we use Realgar-Indigo naturalis formula (RIF), which has been proven to be very effective in treating human acute promyelocytic leukemia (APL) as a model. The main components of RIF are realgar, Indigo naturalis, and Salvia miltiorrhiza, with tetraarsenic tetrasulfide (A), indirubin (I), and tanshinone IIA (T) as major active ingredients, respectively. Here, we report that the ATI combination yields synergy in the treatment of a murine APL model in vivo and in the induction of APL cell differentiation in vitro. ATI causes intensified ubiquitination/degradation of promyelocytic leukemia (PML)-retinoic acid receptor #1; (RAR#1;) oncoprotein, stronger reprogramming of myeloid differentiation regulators, and enhanced G1/G0 arrest in APL cells through hitting multiple targets compared with the effects of mono- or biagents. Furthermore, ATI intensifies the expression of Aquaglyceroporin 9 and facilitates the transportation of A into APL cells, which in turn enhances A-mediated PML-RAR#1; degradation and therapeutic efficacy. Our data also indicate A as the principal component of the formula, whereas T and I serve as adjuvant ingredients. We therefore suggest that dissecting the mode of action of clinically effective formulae at the molecular, cellular, and organism levels may be a good strategy in exploring the value of traditional medicine.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: MicroRNAs (miRNAs) are one class of short, endogenous RNAs which can regulate gene expression at the post-transcriptional level. Previous analysis revealed that mammalian miRNAs tend to cluster on chromosomes. However, the functional consequences of this clustering and conservation property are largely unknown. In this study we present a method to identify signaling pathways targeted by clustered miRNAs. We performed a computational screen for mouse signaling pathways targeted by miRNA clusters. Here, we report that the target genes of 3 miRNA clusters are overrepresented in 15 signaling pathways. We provided experimental evidence that one miRNA cluster, mmu-mir-183–96–182 targets Irs1, Rasa1, and Grb2, all of which are located in the insulin signaling pathway. Theses results suggest that by targeting components with different roles along a signaling pathway, different members of one miRNA cluster can act as a whole to coordinately control the signal transduction process.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: The synergy of the activities between chloroquine and various human immunodeficiency virus protease inhibitors was investigated in chloroquine-resistant and -sensitive malaria parasites. In both in vitro and in vivo assay systems, ritonavir was found to be the most potent in potentiating the antimalarial action of chloroquine.
分类: 生物学 >> 生物医药 提交时间: 2017-05-10
摘要: The role of AMP-activated protein kinase (AMPK) in adipocyte differentiation is not completely understood. Here we reported that an AMPK inhibitor, compound C, significantly inhibited adipogenic differentiation of 3T3-L1 cells in a dose dependent manner, and this inhibitory effect was primarily effective in the initial stage of differentiation. Compound C prevented the mitotic clonal expansion (NICE) of preadipocytes, probably by hibiting expression of CCAAT/enhancer-binding protein (C/EBP)beta and delta, and subsequently blocked the expression of C/EBP alpha and peroxisome proliferator-activated receptor (PPAR)gamma and transcriptional activation of genes that produce the adipocyte phenotype. AMPK activity was also suppressed by compound C treatment during the early phase of adipogenic differentiation, which indicated that suppressed activation of AMPK by compound C may inhibit the MCE process of preadipocytes. Our results suggest that compound C might serve as a useful molecule in both basic and clinical research on adipogenesis and as a potential lead compound for the treatment of, obesity.
分类: 生物学 >> 生物医药 提交时间: 2017-03-30
摘要: Efficient and selective palladium porphyrins-catalyzed olimerization of tert-butyl acetylene to form (3Z,5Z)-2,2,7,7-tetramethyl-3,6-dihalo-3,5-octadiene has been developed in environmentfriendly ionic liquids. The reaction proceeded readily with effective recycling of the ionic liquids and easy isolation of the products.
分类: 生物学 >> 生物医药 提交时间: 2017-03-30
摘要: Fungi have emerged as the fourth most common pathogens isolated in nosocomial bloodstream infections, and Candida albicans is the most common human fungal pathogen. Only a few antibiotics are effective in the treatment of fungal infections. In addition, the repetition and lengthy duration of fluconazole therapy has led to an increased incidence of azole resistance and treatment failure associated with C. albicans. To investigate the mechanism of drug resistance and explore new targets to treat clinically resistant fungal pathogens, we examined the large-scale gene expression profile of two sets of matched fluconazole-susceptible and -resistant bloodstream C. albicans isolates from bone marrow transplanted (BMT) patients for the first time by microarray analysis. More than 198 differentially expressed genes were identified and they were confirmed and validated by RT-PCR independently. Not surprisingly, the resistant phenotype is associated with increased expression of CDR mRNA, as well as some common genes involved in drug resistance such as CaIFU5, CaRTA2 and CaIFD6. Meanwhile, some special functional groups of genes, including ATP binding cassette (ABC) transporter genes (IPF7530, CaYOR1, CaPXA1), oxidative stress response genes (CaALD5, CaGRP1, CaSOD2, IPF10565), copper transport and iron mobilization-related genes (CaCRD1/2, CaCTR1/2, CaCCC2, CaFET3) were found to be differentially expressed in the resistant isolates. Furthermore, among these differentially expressed genes, some co-regulated with CaCDR1, CaCDR2 and CaIFU5, such as CaPDR16 and CaIFD6, have a DRE-like element and may interact with TAC1 in the promoter region. These findings may shed light on mechanisms of azole resistance in C. albicans and clinical antifungal therapy.