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101.
A series of 1,2,4-triazole derivatives containing thiosemicarbazone linkage was synthesized and evaluated for their in vitro antiamoebic activity against HM1:IMSS strain of Entamoeba histolytica. All the compounds were capable of inhibiting the growth of E. histolytica out of which four compounds (IC(50)=0.28-1.38 μM) were found to have better efficacy than the standard drug Metronidazole (IC(50)=1.8 μM). Cytotoxicity of the active compounds was assessed by MTT assay using human breast cancer MCF-7 cell line, which revealed that all the compounds were low cytotoxic in the concentration range of 2.5-250 μM. 相似文献
102.
Majid Shahbazi Hamid Ebadi Davood Fathi Danial Roshandel Mana Mahamadhoseeni Azam Rashidbaghan Narges Mahammadi Mahammad Reza Mahammadi Mahdi Zamani 《Cellular and molecular neurobiology》2009,29(8):1205-1209
The 32-base pair deletion on the C–C chemokine receptor 5 gene (CCR5-delta32) is known as a protective allele against immune
system disorders. We have studied this variation in Iranian multiple sclerosis (MS) patients and healthy controls. DNA samples
were prepared from the whole blood of 254 patients with MS and 380 healthy controls. We amplified the fragment including the
CCR5-delta32 polymorphism and visualized the products in a documentation system after agarose gel electrophoresis. Data were
analysed using one-way ANOVA and Fisher’s exact tests with SPSS-v13 and STATA-v8 software. The delta32 allele was more frequent
in MS patients when compared with controls (OR = 2.3, P < 0.0001). Also, we found a significant difference in the frequency of the delta32/delta32 genotype among patients and controls
(OR = 7.4, P < 0.001). The mean age at onset and progression index was not significantly different between patients with various genotypes.
According to our study, the delta32 allele of the CCR5 gene might be a predisposing factor for MS development in the Iranian
population. However, there were no associations between this polymorphism and the clinical course of the disease in this study. 相似文献
103.
Background
The coral holobiont includes the coral animal, algal symbionts, and associated microbial community. These microbes help maintain the holobiont homeostasis; thus, sustaining robust mutualistic microbial communities is a fundamental part of long-term coral reef survival. Coastal pollution is one major threat to reefs, and intensive fish farming is a rapidly growing source of this pollution.Methodology & Principal Findings
We investigated the susceptibility and resilience of the bacterial communities associated with a common reef-building coral, Porites cylindrica, to coastal pollution by performing a clonally replicated transplantation experiment in Bolinao, Philippines adjacent to intensive fish farming. Ten fragments from each of four colonies (total of 40 fragments) were followed for 22 days across five sites: a well-flushed reference site (the original fragment source); two sites with low exposure to milkfish (Chanos chanos) aquaculture effluent; and two sites with high exposure. Elevated levels of dissolved organic carbon (DOC), chlorophyll a, total heterotrophic and autotrophic bacteria abundance, virus like particle (VLP) abundances, and culturable Vibrio abundance characterized the high effluent sites. Based on 16S rRNA clone libraries and denaturing gradient gel electrophoresis (DGGE) analysis, we observed rapid, dramatic changes in the coral-associated bacterial communities within five days of high effluent exposure. The community composition on fragments at these high effluent sites shifted towards known human and coral pathogens (i.e. Arcobacter, Fusobacterium, and Desulfovibrio) without the host corals showing signs of disease. The communities shifted back towards their original composition by day 22 without reduction in effluent levels.Significance
This study reveals fish farms as a likely source of pathogens with the potential to proliferate on corals and an unexpected short-term resilience of coral-associated bacterial communities to eutrophication pressure. These data highlight a need for improved aquaculture practices that can achieve both sustainable industry goals and long-term coral reef survival. 相似文献104.
The deregulated tyrosine kinase activity of BCR-ABL is necessary and sufficient to induce chronic myelogenous leukemia (CML). This observation has paved the way for the development of small-molecule inhibitors specifically targeting the kinase activity of the BCR-ABL protein. Indeed, the amazing success of imatinib has revolutionized the whole area of targeted cancer therapeutics. However, enthusiasm for the striking efficacy of imatinib has been tempered by the development of clinical resistance. In essentially all cases, resistance results from kinase domain mutations and/or overexpression of the BCR-ABL gene. To overcome resistance, several novel BCR-ABL inhibitors have been developed and are in clinical trials, though it is inevitable that resistance to second-generation inhibitors will occur as well. Nonetheless, kinases represent an attractive target for therapeutic intervention in several diseases and, at present, some 50 different kinase inhibitors are in clinical trials. We anticipate that resistance to these compounds will follow mechanisms similar to those observed with imatinib. Resistance mutations cause their effect either by direct steric hindrance to drug binding or by allosterically modulating kinase dynamics. This review highlights the principal mechanisms underlying point mutations from these two different classes to confer drug resistance. 相似文献
105.
106.
Bacterium-bacterium interactions occur at intimate spatial scales on the order of micrometers, but our knowledge of interactions at this level is rudimentary. Antagonism is a potential interaction in such microenvironments. To study the ecological role of antibiosis, we developed a model system involving an antibiotic-producing isolate (SWAT5) derived from a marine particle and its dominant antibiotic product, 2-n-pentyl-4-quinolinol (PQ). This system was used to address questions about the significance of this antibiotic for microbial ecology and carbon cycling on particles. We characterized the chemical and inhibitory properties of PQ in relation to the mechanisms used by particle-associated bacteria in interacting with particles and with other attached bacteria. PQ was produced by SWAT5 only on surfaces. When SWAT5 was grown in polysaccharide matrices, PQ diffused within the matrices but not into the surrounding seawater. SWAT5 might thus be able to generate a localized zone of high antibiotic concentration on particles suspended or sinking through seawater. Target bacterial respiration was most sensitive to PQ (75 nM), while inhibition of DNA synthesis, protein synthesis, and bacterial motility required higher (micromolar) PQ levels. The presence of PQ altered the composition of the bacterial community that colonized and developed in a model particle system. PQ also inhibited Synechococcus and phytoplankton growth. Our results suggest that antibiosis may significantly influence community composition and activities of attached bacterial and thus regulate the biogeochemical fate of particulate organic matter in the ocean. 相似文献
107.
Tofaris GK Razzaq A Ghetti B Lilley KS Spillantini MG 《The Journal of biological chemistry》2003,278(45):44405-44411
Lewy bodies are intracellular fibrillar inclusions composed of alpha-synuclein. They constitute the pathological hallmark of Parkinson's disease, dementia with Lewy bodies, and other neurodegenerative diseases. Although the majority of Lewy bodies are stained for ubiquitin by immunohistochemistry, the substrate for this modification is poorly understood. Insoluble, urea-soluble alpha-synuclein was separated from soluble fractions and subjected to two-dimensional gel electrophoresis to further characterize pathogenic alpha-synuclein species from disease brains. By using this approach, we found that in sporadic Lewy body diseases a highly modified, disease-associated 22-24-kDa alpha-synuclein species is ubiquitinated. Conjugation of one, two, and, to a lesser extent, three ubiquitins was detected. This 22-24-kDa alpha-synuclein species represents partly phosphorylated protein. Furthermore, no generalized impairment of the proteolytic activity of the proteasome was detected in brain regions with Lewy body pathology. Because unmodified alpha-synuclein is degraded by the proteasome in a ubiquitin-independent manner, these data suggest that accumulation of modified 22-24-kDa alpha-synuclein is a disease-specific event which may overwhelm the proteolytic system, leading to aberrant ubiquitination. Accordingly, carboxyl-terminal-truncated alpha-synuclein, presumably the result of aberrant proteolysis, is found only in association with alpha-synuclein aggregates. 相似文献
108.
Wolk K Kunz S Asadullah K Sabat R 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(11):5397-5402
This study investigated the expression of five novel human IL-10-related molecules and their receptors in blood mononuclear cells. IL-19 and IL-20 were found to be preferentially expressed in monocytes. IL-22 and IL-26 (AK155) expression was exclusively detected in T cells, especially upon type 1 polarization, and in NK cells. IL-24 (melanoma differentiation-associated gene 7) expression was restricted to monocytes and T cells. Detection of these molecules in lymphocytes was predominantly linked to cellular activation. Regarding T cells, IL-26 was primarily produced by memory cells, and its expression was independent on costimulation. In contrast to the high expression of receptors for IL-10 homologs in different tissues and cell lines, monocytes and NK, B, and T cells showed clear expression only of IL-10R1, IL-10R2, and IL-20R2. In these cells, IL-20R2 might be part of a still-unknown receptor complex. Therefore, immune cells may represent a major source but a minor target of the novel IL-10 family members. 相似文献
109.
2-n-Pentyl-4-Quinolinol Produced by a Marine Alteromonas sp. and Its Potential Ecological and Biogeochemical Roles
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Bacterium-bacterium interactions occur at intimate spatial scales on the order of micrometers, but our knowledge of interactions at this level is rudimentary. Antagonism is a potential interaction in such microenvironments. To study the ecological role of antibiosis, we developed a model system involving an antibiotic-producing isolate (SWAT5) derived from a marine particle and its dominant antibiotic product, 2-n-pentyl-4-quinolinol (PQ). This system was used to address questions about the significance of this antibiotic for microbial ecology and carbon cycling on particles. We characterized the chemical and inhibitory properties of PQ in relation to the mechanisms used by particle-associated bacteria in interacting with particles and with other attached bacteria. PQ was produced by SWAT5 only on surfaces. When SWAT5 was grown in polysaccharide matrices, PQ diffused within the matrices but not into the surrounding seawater. SWAT5 might thus be able to generate a localized zone of high antibiotic concentration on particles suspended or sinking through seawater. Target bacterial respiration was most sensitive to PQ (75 nM), while inhibition of DNA synthesis, protein synthesis, and bacterial motility required higher (micromolar) PQ levels. The presence of PQ altered the composition of the bacterial community that colonized and developed in a model particle system. PQ also inhibited Synechococcus and phytoplankton growth. Our results suggest that antibiosis may significantly influence community composition and activities of attached bacterial and thus regulate the biogeochemical fate of particulate organic matter in the ocean. 相似文献
110.
Roya Naderi Bagher Pourheydar Azam Moslehi 《Journal of biochemical and molecular toxicology》2023,37(3):e23272
As a serotonin antagonist, tropisetron positively affects blood glucose lowering, insulin synthesis, pancreas inflammation, and apoptosis in diabetes. Reproductive disorders are one of the diabetes-induced chronic complications. The present study aimed to evaluate the effect of tropisetron on diabetes-induced testicular inflammation, its signaling pathway, and mir146a. To this end, animals were assigned to the control, tropisetron, diabetes (DM), DM-tropisetron, and DM-glibenclamide groups. Streptozotocin (50 mg/kg) was intraperitoneally injected to provide diabetes. Tropisetron and glibenclamide were then administrated intraperitoneally for 2 weeks after diabetes induction. Testes histology, real-time polymerase chain reaction, western blot analysis, ELISA, and immunohistochemistry assays were also performed. The finding revealed that tropisetron significantly improved diabetes-induced testis damages, lowered TLR4, TRAF6, IRAK1, NF-κB, and caspase3 protein expressions, and decreased TNF-α and IL-1 levels. Moreover, the mir146a expression declined following the tropisetron treatment. This study demonstrated that the significant role of tropisetron in lowering testicular inflammation and apoptosis might have been due to the inhibition of the TLR4/IRAK1/TRAF6 signaling pathway and thereby the attenuation of NF-κB and caspase3 expression and inflammatory cytokines. Furthermore, the downregulation of mir146a, as an inflammatory microRNA interacting with TLR4, showed another pathway, through which tropisetron improved diabetes-induced testicular injuries. 相似文献