Wednesday 1st February 2017
Recent studies suggest there is a high incidence of elevated low-density lipoprotein (LDL) levels in Chronic Lymphocytic Leukemia (CLL) patients and a survival benefit from cholesterol-lowering statin drugs. The mechanisms of these observations and the kinds of patients they apply to are unclear. Using an in vitro model of the pseudofollicles where CLL cells originate, LDLs were found to increase plasma membrane cholesterol, signaling molecules such as tyrosine-phosphorylated STAT3, and activated CLL cell numbers. The signaling effects of LDLs were not seen in normal lymphocytes or glycolytic lymphoma cell-lines but were restored by transduction with the nuclear receptor PPARδ, which mediates metabolic activity in CLL cells. Breakdown of LDLs in lysosomes was required for the amplification effect, which correlated with down-regulation of HMGCR expression and long lymphocyte doubling times (LDTs) of 53.6 ± 10.4 months. Cholesterol content of circulating CLL cells correlated directly with blood LDL levels in a subgroup of patients. These observations suggest LDLs may enhance proliferative responses of CLL cells to inflammatory signals. Prospective clinical trials are needed to confirm the therapeutic potential of lowering LDL concentrations in CLL, particularly in patients with indolent disease in the “watch-and-wait” phase of management.
Monday 2nd January 2017
Examination of 330 food samples (meat, white raw sausage, smoked meat and cheeses) was conducted and the Salmonella spp. and Y. enterocolitica prevalence were determined. For isolated strains of Salmonella spp., it was determined whether they were of S. Typhi, S. Typhimurium or S. Enteritidis serotypes. Isolated Y. enterocolitica strains were biotyped. Moreover, the strains' ability to form a biofilm and presence of virulence factors was determined. Salmonella spp. were found in 16 (5.5%) samples, whereas
Yersinia enterocolitica in 7 (2.1%) samples. Serotyping resulted in classifying 4 strains as S. Typhimurium, 2 as S. Enteritidis and none as S. Typhi. Ten strains were not classified as any of the determined serotypes. The gene invA was found in all Salmonella strains and spvC was found in 3 (18.7%) strains. All of the Y. enterocolitica were classified as biotype 1A, none of the strains had the genes ail or ystA, and the ystB gene was found in five strains. None of the 16 strains of Salmonella spp. and the 7 strains of Y. enterocolitica showed any strong ability to form a biofilm, while 7 strains of Salmonella spp. and 3 strains of Y. enterocolitica showed a moderate ability to form a biofilm
Monday 2nd January 2017
Gastric cancer is the fourth most common malignant cancer and the third most frequent cause of cancer-related deaths worldwide. The molecular mechanism underlying gastric carcinogenesis and progression is still unknown. Methyl-CpG binding protein 2 (MeCP2) has recently been characterized as an oncogene frequently amplified in several types of cancer. However, its precise role and the molecular mechanism of MeCP2 regulation in gastric cancer are largely unknown. Our results show that MeCP2 promotes gastric cancer cell proliferation via FOXF1-mediated Wnt5a/β-Catenin signaling pathway and suppresses cell apoptosis through MYOD1-mediated Caspase-3 signaling pathway. MeCP2 represents a promising therapeutic target for gastric cancer treatment.
Monday 2nd January 2017
Obesity is a component of the metabolic syndrome, mechanistically linked to diabetes, fatty liver disease, and cardiovascular disease. Proteins that regulate the metabolic fate of intracellular lipid droplets are potential therapeutic candidates to treat obesity and its related consequences. CIDEC (cell death-inducing DFFA-like effector C), also known in mice as Fsp27 (fat-specific protein 27), is a lipid droplet-associated protein that prevents lipid mobilization and promotes intracellular lipid storage. The consequences of complete loss of FSP27 on hepatic metabolism and on insulin resistance are controversial, as both healthy and deleterious lipodystrophic phenotypes have been reported in Fsp27−/− mice. To test whether therapeutic silencing of Fsp27 might be useful to improve obesity, fatty liver, and glycemic control, we used antisense oligonucleotides (ASOs) in both nutritional (high-fat diet) and genetic (leptin-deficient ob/ob) mouse models of obesity, hyperglycemia, and hepatosteatosis. We show that partial silencing Fsp27 in either model results in the robust decrease in visceral fat, improved insulin sensitivity and whole-body glycemic control, and tissue-specific changes in transcripts controlling lipid oxidation and synthesis. These data suggest that partial reduction of FSP27 activity (e.g., using ASOs) might be exploited therapeutically in insulin-resistant obese or overweight patients.
Monday 23rd January 2017
The aim of this study was to investigate the effect of metformin on endothelial progenitor cells (EPCs) angiogenesis under physiology condition and to explore the possible mechanisms. Methods: EPCs were treated with metformin and angiogenesis of EPCs were evaluated by capillary tube formation assay in Matrigel. Moreover, we also assessed AMPK-mTOR-autophagy pathway to explore the possible mechanisms. Results: Metformin treatment could significantly down-regulate metal matrix Proteinase 2 (MMP2), MMP9 and urokinase-type plasminogen activator (uPA) expression, and subsequently decrease angiogenesis of EPCs. Increased levels of phospho-AMPK and LC3II expression, as well as decreased phospho-mTOR, contribute to this phenomenon. Down-regulated autophagy by autophagy protein 5 siRNA could reverse the effect exerted by metformin. Conclusions: Our results here showed that metformin could inhibit EPCs angiogenesis through inhibiting the expression of MMP2, MMP9 and uPA via AMPK-mTOR-autophagy pathway.
Wednesday 11th January 2017
Salmonella enterica serovar Typhimurium has the ability to use molecular hydrogen as a respiratory electron donor. This is facilitated by three [NiFe]-hydrogenases termed Hyd-1, Hyd-2, and Hyd-5. Hyd-1 and Hyd-5 are homologous oxygen-tolerant [NiFe]-hydrogenases. A critical step in the biosynthesis of a [NiFe]-hydrogenase is the proteolytic processing of the catalytic subunit. In this work, the role of the maturation protease encoded within the Hyd-5 operon, HydD, was found to be partially complemented by the maturation protease encoded in the Hyd-1 operon, HyaD. In addition, both maturation proteases were shown to form stable complexes, in vivo and in vitro, with the catalytic subunit of Hyd-5. The protein–protein interactions were not detectable in a strain that could not make the enzyme metallocofactor.
Friday 27th January 2017
Members of the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein (MAP) kinases, and the upstream kinase MKK7, have all been strongly linked with synaptic plasticity and with the development of the neocortex. However, the impact of disruption of this pathway on cognitive function is unclear.
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