Brucellosis is a bacterial zoonotic disease which can be easy to misdiagnose in clinical microbiology laboratories.In the present study, we have tried to improve the current clinical method for detecting Brucella spp.and its antibiotic characteristics.Our method begins with detecting the clinical isolate through traditional biochemical methods and automatic identification systems.Then, we move on to editing the sequence for BLAST allows us to compare 16s rRNA sequences with sequences from other species, allowing the gene level to be determined.Next, the phylogenetic analysis of multiple genetic loci is able to determine the evolutionary relationships between our bacteria strain and those from other locations.Finally, an anti-microbial susceptibility test hones in on the level of antibacterial activity that the bacteria displays.Employing these four steps in concert is extremely effective in identifying rare bacteria.Thus, when attempting to determine the identity of rare bacteria such as Brucella, utilizing these four steps from our research should be highly effective and ultimately prevent further identification errors and misdiagnoses.The standards we have suggested to identify rare bacteria strains is applicable not only to Brucella, but also to other rarely encountered bacteria.
Cisplain, a platinum-containing anticancer drug, has been shown to enhance DNA repair and to inhibit cell apoptosis, leading to drug resistance. Thus, the combination of anticancer drugs with nutritional factors is a potential strategy for improving the efficacy of cisplatin chemotherapy. In this study, we investigated the anti-proliferative effects of a combination of fucoxanthin, the major non-provitamin A carotenoid found in Undaria Pinnatifida, and cisplatin in human hepatoma HepG2 cells. We found that fucoxanthin (1–10 μΜ) pretreatment for 24 h followed by cisplatin (10 μΜ) for 24 h significantly decreased cell proliferation, as compared with cisplatin treatment alone. Mechanistically, we showed that fucoxanthin attenuated cisplatin-induced NFκB expression and enhanced the NFκB-regulated Bax/Bcl-2 mRNA ratio. Cisplatin alone induced mRNA expression of excision repair cross complementation 1 (ERCC1) and thymidine phosphorylase (TP) through phosphorylation of ERK, p38 and PI3K/AKT pathways. However, fucoxanthin pretreatment significantly attenuated cisplatin-induced ERCC1 and TP mRNA expression, leading to improvement of chemotherapeutic efficacy of cisplatin. The results suggest that a combined treatment with fucoxanthin and cisplatin could lead to a potentially important new therapeutic strategy against human hepatoma cells.
Introduction Schizophrenia increases the risk of mortality and cardiovascular disease (CVD) risk. However, the correlation between antipsychotics (APs) and CVD remains controversial. Hyperlipidemia is a significant risk factor for CVD. Methods We conducted a nationwide population-based retrospective cohort study to investigate the effects of APs on the risk of hyperlipidemia and lipid homeostasis gene expression. We used data from the Longitudinal Health Insurance Database of Taiwan on new-onset schizophrenia patients and a comparison cohort without schizophrenia. We used a Cox proportional hazards regression model to analyze the differences in hyperlipidemia development between the two cohorts. Furthermore, we examined the effects of APs on the hepatic expression of lipid homeostasis-related genes. Results After adjusting for potential interrelated confounding factors, the case group ( N = 4,533) was found to have a higher hyperlipidemia risk than the control cohort ( N = 4,533) [adjusted hazard ratio (aHR), 1.30, p < 0.001]. Patients with schizophrenia without APs had a significantly higher risk of hyperlipidemia (aHR, 2.16; p < 0.001). However, patients receiving APs had a significantly lower risk of hyperlipidemia than patients not receiving APs (all aHR ≤ 0.42, p < 0.001). First-generation antipsychotics (FGAs) induce the expression of hepatic lipid catabolism genes in an in vitro model. Discussion Patients with schizophrenia had a higher risk of hyperlipidemia than controls; however, compared with non-treated patients, AP users had a lower risk of hyperlipidemia. Early diagnosis and management of hyperlipidemia may help prevent CVD.
Inconsistent expression and regulation of drug-metabolizing enzymes (DMEs) are common causes of adverse drug effects in some drugs with a narrow therapeutic index (TI). An important cytochrome, cytochrome P450 3A4 (CYP3A4), is predominantly regulated by a nuclear receptor, pregnane X receptor (PXR). Sesamin, a major lignan constituent in sesame seeds and oil, exhibits a variety of biological functions; however, the effect of sesamin on the modulation of CYP3A4 is not well understood. In this study, the effects of sesamin on the PXR-CYP3A4 pathway were characterized, as well as the underlying mechanisms of those effects. Sesamin potently attenuated CYP3A4 induction in a dose-dependent manner by blocking the activation of PXR. The PXR inducer-mediated inhibition of CYP3A4 was further evidenced by the ability of sesamin to attenuate the effects of several PXR ligands in the CYP3A4 reporter assay. Further mechanistic studies showed that sesamin inhibited PXR by interrupting the interacting with coregulators. These results may lead to the development of new therapeutic and dietary approaches to reduce the frequency of inducer-drug interaction. Sesamin was established as a novel inhibitor of PXR and may be useful for modulating DMEs expression and drug efficacies. Modification of CYP3A4 expression and activity by consumption of sesamin may have important implications for drug safety.
Background The human pregnane X receptor is a ligand-dependent transcription factor that plays critical roles in regulating detoxification genes such as CYP3A4 by recruiting transcriptional coactivators such as steroid receptor coactivator-1 in a ligand-dependent manner. In a previous study (Pharmacogenetics and Genomics 2005, 15: 337–341), we reported a novel pregnane X receptor single nucleotide polymorphism, Q158K, which impaired transactivation of CYP3A4. Methods and results By using DNA affinity precipitation assay and electrophoretic mobility shift assay, we have now shown that Q158K does not alter the binding affinity of pregnane X receptor for the CYP3A4 promoter. Instead, as shown using a mammalian two-hybrid assay, it decreased the interaction of pregnane X receptor with steroid receptor coactivator-1 in the presence of rifampin, clotrimazole, paclitaxel, or nifedipine but not in their absence. Rifampin treatment markedly increased pregnane X receptor protein in the wild-type pregnane X receptor-transfected cells as shown by coimmunoprecipitation but not in Q158K pregnane X receptor-transfected cells. The impaired transactivation of the CYP3A4 promoter was reversed by transfecting steroid receptor coactivator-1 expression plasmids. An additional nine pregnane X receptor variants were isolated and selected by random mutagenesis. Mutations Q158, W223, F257, I346, and L424 also reduced CYP3A4 transactivation and interaction in mammalian two-hybrid assays only in the presence of ligands. Although Q158K did not greatly affect the interaction of pregnane X receptor to silencing mediator of retinoid and thyroid hormone receptor, pregnane X receptor-silencing mediator of retinoid and thyroid hormone receptor interaction was impaired in the F257L and I346T variants with or without the presence of pregnane X receptor ligands. Conclusion Our data indicate that the impaired induction by the Q158K variant is probably due to defective steroid receptor coactivator-1 interaction in the presence of a pregnane X receptor ligand. As the whole ligand binding domain of pregnane X receptor is required for the interaction with steroid receptor coactivator-1, we propose that, not only the Q158K variant found in Chinese, but also in native pregnane X receptor variants in other ethnic groups (D163G, A370T, R381W, and I403V) affect CYP3A4 induction by altering steroid receptor coactivator-1 recruitment.
Cisplatin is used as a treatment for various types of solid tumors. Renal injury severely limits the use of cisplatin. Renal cell apoptosis, oxidative stress, and inflammation contribute to cisplatin-induced nephrotoxicity. Previously, we found that an extract of Rhodobacter sphaeroides (Lycogen™) inhibited proinflammatory cytokines and the production of nitric oxide in activated macrophages in a dextran sodium sulfate (DSS)-induced colitis model. Here, we evaluated the effect of Lycogen™, a potent anti-inflammatory agent, in mice with cisplatin-induced renal injury. We found that attenuated renal injury correlated with decreased apoptosis due to a reduction in caspase-3 expression in renal cells. Oral administration of Lycogen™ significantly reduced the expression of tumor necrosis factor-α and interleukin-1β in mice with renal injury. Lycogen™ reduces renal dysfunction in mice with cisplatin-induced renal injury. The protective effects of the treatment included blockage of the cisplatin-induced elevation in serum urea nitrogen and creatinine. Meanwhile, Lycogen™ attenuated body weight loss and significantly prolonged the survival of mice with renal injury. We propose that Lycogen™ exerts anti-inflammatory activities that represent a promising strategy for the treatment of cisplatin-induced renal injury.
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