Churchnissen8627

VNP20009, an attenuated mutant of Salmonella, is potentially applied for tumor therapy due to its specific accumulation and proliferation in the hypoxic zone of tumor. However, studies have shown that human immunity system and the associated toxicities of attenuated Salmonella evidently alleviated the anti-tumor effect when tumor is reduced. As apoptosis-inducing factor (AIF) can directly induce nuclear apoptosis in the absence of caspases to avoid unwished apoptosis in normal cells, therefore, a eukaryotic expressing VNP20009-AbVec-Igκ-AIF (V-A-AIF) strain was constructed in the present study, and its anti-melanoma effects were evaluated in vitro and in vivo. The results showed that AIF expressed by the V-A-AIF strain significantly enhanced the apoptosis of B16F10 cells in vitro, seen as remarkable decrease of tumor volume, formation of larger necrotic areas, and prolongation of the lifespan in a melanoma-bearing mouse model. Furthermore, we observed that the colonization of the V-A-AIF strain and the massive expression of AIF in tumors significantly promoted apoptosis of tumor cells by upregulating the expression ratio of Bcl-2-associated X protein/B cell lymphoma-2 (Bax/Bcl-2), suppressed the inflammatory response by downregulating toll-like receptor-4/nuclear factor kappa-B (TLR-4/NFκB) signaling pathway, seen as reduction of the expressions of phosphorylated phosphoinositide 3 kinase (PI3K) and protein kinase B (AKT), and decrease of the production of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Our study demonstrated that the colonization of the V-A-AIF strain in tumor triggers a decent anti-tumor effect in vivo and in vitro, suggesting that the engineered strain may provide a potential reagent for cancer therapy.Alzheimer's disease (AD) is a neurodegenerative disease with increasing prevalence worldwide, while there are no effective drugs at present. Curcumin, a natural polyphenolic substance isolated from turmeric, is a promising natural compound to combat AD, but its pharmacology remains to be fully understood for its poor in vivo bioavalibility. Inspired by the recently reported associations between gut microbiota and AD development, the present study investigated the interactions of curcumin with gut microbiota of APP/PS1 double transgenic mice from two directions (i) curcumin influences gut microbiota, and (ii) gut microbiota biotransform curcumin. It was found that curcumin administration tended to improve the spatial learning and memory abilities and reduce the amyloid plaque burden in the hippocampus of APP/PS1 mice. On the one hand, curcumin administration altered significantly the relative abundances of bacterial taxa such as Bacteroidaceae, Prevotellaceae, Lactobacillaceae, and Rikenellaceae at family level, and Prevotella, Bacteroides, and Parabacteroides at genus level, several of which have been reported to be key bacterial species associated with AD development. On the other hand, a total of 8 metabolites of curcumin biotransformed by gut microbiota of AD mice through reduction, demethoxylation, demethylation and hydroxylation were identified by HPLC-Q-TOF/MS, and many of these metabolites have been reported to exhibit neuroprotective ability. The findings provided useful clues to understand the pharmacology of curcumin and microbiome-targeting therapies for AD.The biosynthesis of the valuable antibiotic enduracidin by Streptomyces fungicidicus TXX3120 is a complex multistep process. To identify the rate-limiting step of the entire biosynthetic process, we carried out a deep RNA sequencing towards the mycelia of TXX3120 at different fermentation stages. Comparative RNA-seq analysis indicated that the expression level of the endC gene during the enduracidin production phase was evidently lower than that of the other relevant genes to enduracidin biosynthesis. This result was further confirmed by quantitative RT-PCR, and the giant non-ribosomal peptide synthase (NRPS) encoded by endC was predicated to be the rate-limiting enzyme in enduracidin biosynthesis. To increase the expression of endC during the enduracidin production phase, a reporter-based selection system was developed by genetically replacing the initial part of the endC gene with a thiostrepton resistance gene (tsr), which will then act as a selectable marker to report the expression level of the rate-limiting gene endC, thereby facilitating the selection of enduracidin-overproducing mutants following random mutagenesis. After one round of mutagenesis, thiostrepton resistance selection, and restoration of the endC gene, three mutant strains with improved endC expression levels were obtained. Their highest enduracidin titers reached 9780.54, 9272.46, and 8849.06 U/mL, respectively representing 2.31-, 2.19-, and 2.09-fold of the initial industrial strain TXX3120. Our research provides a useful strategy for the rational breeding of industrial strains that synthesize complex natural products.Bacterially induced precipitation of minerals leading to cementation of natural geological formations has been well recorded in a variety of environments. A range of microbial pathways and geochemical processes have been found to influence the cementation processes; but detailed formation mechanisms and biogeochemical relationships are still not very clear. There has been a growing demand for the application of bacterially driven biocementation in a number of geotechnical engineering applications recently. Here, we aimed to unpin the mechanisms behind the formation of actively mineralising beachrock sediments at Lucky Bay in Western Australia to understand the natural accretionary processes and potential of indigenous bacterial communities in biocementation. We observed ferruginous, aluminosilicate and carbonate cements along with extensive extra polymeric substances, borings with possible microbial activities in certain sections of native beachrock sediments. Cement precipitation under calcium- and iron-rich microenvironments sourced from seawater and iron creek seems to be driven by both biogenic and abiogenic processes in nature. Native microbial communities with a dominance of the genera Halococcus and Marinobacter were recorded. Enrichment of native bacterial communities under seawater media conditions was conducted which lead to successful biomineralisation of calcitic and ferruginous cements under in vitro conditions although the community composition changed significantly. Nanomechanical properties of natural and laboratory synthesised cement crystals showed that engineered biocement is highly promising. The results of this study clearly demonstrate biological influence in the formation of natural cements and hint significant potential of biostimulation which can be harnessed for different engineering applications including coastal erosion.PURPOSE This study aimed to examine the correlation between right posteroinferior bile duct (RPBD) angulation and the occurrence of bile duct stones in patients with hepatolithiasis. METHODS Patients presenting with hepatolithiasis in our hospital from January 2011 to July 2016 were divided into two groups according to whether their RPBD was affected by stones. A statistical analysis for the relevant factors associated with bile duct stone formation in the RPBD was performed. RESULTS The binary logistic regression results showed that stenosis of the right hepatic duct [odds ratio (OR) 7.313; 95% confidence interval (CI) 4.131-12.945)] and the angle of the RPBD (OR 0.896; 95%CI 0.877-0.916) were risk factors associated with the formation of RPBD stones. Further, the receiver operating characteristic curve indicated that, when the angle of the RPBD was less than 44.58°, stones were able to form more easily in the RPBD. CONCLUSION The occurrence of bile duct stones is well correlated with sharp bile duct angulation.PURPOSE To evaluate the efficacy and safety of covered stent placement for the treatment of hepatic artery pseudoaneurysm (HAP). METHODS Between March 2006 and March 2019, 17 consecutive patients underwent emergency covered stent placement for treatment of HAP. There were 12 men and 5 women aged 24-71 years, with an average age of 49.4 years. Eleven patients had undergone Whipple procedure, 3 had hepatic abscess following hepatectomy, 2 had undergone hepatectomy under extracorporeal circulation, and 1 had received surgical exploration after a car accident. The average interval from surgical intervention to massive bleeding was 15.3 days (range 6-35 days). After HAP was confirmed by angiography, 1-3 covered stent grafts (3-8 mm in diameter and 13 mm-5 cm in length) were implanted. Adequate drainage, anti-infection treatment, and symptomatic treatment were offered after stent placement, and no anticoagulation or antiplatelet drug was used. RESULTS The interventions were successful in all 17 patients. this website Angiographpatients died of tumor progression. No bleeding recurred during the follow-up period, and routine color Doppler ultrasound revealed that the common hepatic artery was patent and the blood flow was smooth at the stent implantation site. CONCLUSION Covered stent placement is a safe and effective alternative for treating HAP patients with high risk of severe complications after hepatic artery embolization. Larger stent grafts (> 4 mm in diameter) may achieve better prognosis.BACKGROUND Old age is a known prognostic factor for mortality in patients with papillary thyroid carcinoma (PTC). This study aimed to investigate the relationship between cause-specific survival (CSS) following PTC and the extent of old age. METHODS We enrolled 4692 patients aged ≥ 55 years with PTC who underwent surgery between 1989 and 2009 at Kuma Hospital (median follow-up period 140 months). The presence of at least one of the following was used to classify the patients as high risk (1) tumor sizes > 4 cm, (2) node metastasis ≥ 3 cm, (3) significant extrathyroid extension corresponding to T4a, (4) extranodal tumor extension, and (5) distant metastasis. T1N0M0 PTC was classified as low risk, and all other patients were classified as intermediate risk. We divided all patients into three categories based on age 55-64, 65-74, and ≥ 75 years. RESULTS One low-risk patient (0.04%), 18 intermediate-risk patients (1.5%), and 105 high-risk patients (9.4%) died of PTC, and CSS of high-risk patients was poorer than that of others (p  less then  0.0001). The CSS of low and intermediate-risk patients did not differ with age. However, CSS of high-risk patients became significantly poorer with advancing age (p = 0.0017 for 55-64 years vs. 65-74 years, and p = 0.0109 for 65-74 years vs. ≥ 75 years). CONCLUSIONS Advanced age has a significant prognostic impact on CSS only for high-risk patients with PTC.BACKGROUND The outcomes of liver resection (LR) with a narrow margin in patients with transplantable hepatocellular carcinoma (HCC) have not been studied. The aim was to assess whether narrow margin following up-front LR impacts the incidence, timing, pattern, and transplantability of tumor recurrence in patients with initially transplantable HCC. METHODS All initially transplantable HCC patients undergoing hepatectomy with either narrow ( less then 10 mm) or wide (≥10 mm) margins from 2007 to 2016 at four Western university centers were compared in terms of recurrence, transplantability of recurrence, recurrence-free survival (RFS), and intention-to-treat overall survival (ITT-OS). Independent predictors of non-transplantability of recurrence were assessed. RESULTS This study included 187 patients (narrow group, n = 107 vs. wide group, n = 80). Recurrence was significantly more frequent in the narrow margin group (44% vs. 26%; p = 0.01) with a shorter RFS (p = 0.03). The transplantability of recurrence and ITT-OS were, however, not different between the two groups.