NF-κB mediated enhancement of potassium currents by the chemokine CXCL1/growth related oncogene in small diameter rat sensory neurons

<p>Abstract</p> <p>Background</p> <p>Inflammatory processes play important roles in both neuropathic and inflammatory pain states, but the effects of inflammation <it>per se </it>within the sensory ganglia are not well understood. The cytokine growth-related oncogene (GRO/KC; CXCL1) shows strong, rapid upregulation in dorsal root ganglion (DRG) in both nerve injury and inflammatory pain models. We examined the direct effects of GRO/KC on small diameter DRG neurons, which are predominantly nociceptive. Whole cell voltage clamp technique was used to measure voltage-activated potassium (K) currents in acutely cultured adult rat small diameter sensory neurons. Fluorescently labeled isolectin B4 (IB4) was used to classify cells as IB4-positive or IB4-negative.</p> <p>Results</p> <p>In IB4-negative neurons, voltage-activated K current densities of both transient and sustained components were increased after overnight incubation with GRO/KC (1.5 nM), without marked changes in voltage dependence or kinetics. The average values for the slow and fast decay time constants at 20 mV were unchanged by GRO/KC. The amplitude of the fast inactivating component increased significantly with no large shifts in the voltage dependence of inactivation. The increase in K currents was completely blocked by co-incubation with protein synthesis inhibitor cycloheximide (CHX) or NF-κB inhibitors pyrrolidine dithiocarbamate (PDTC) or quinazoline (6-Amino-4-(4-phenoxypheny lethylamino;QNZ). In contrast, the voltage-activated K current of IB4-positive neurons was unchanged by GRO/KC. GRO/KC incubation caused no significant changes in the expression level of eight selected voltage-gated K channel genes in quantitative PCR analysis.</p> <p>Conclusion</p> <p>The results suggest that GRO/KC has important effects in inflammatory processes via its direct actions on sensory neurons, and that activation of NF-κB is involved in the GRO/KC-induced enhancement of K currents.</p

Do mutual funds have consistency in their performance?

Using a comprehensive data set of 714 Chinese mutual funds from 2004 to 2015, the study investigates these funds’ performance persistence by using the Capital Asset Pricing model, the Fama-French three-factor model and the Carhart Four-factor model. For persistence analysis, we categorize mutual funds into eight octiles based on their one year lagged performance and then observe their performance for the subsequent 12 months. We also apply Cross-Product Ratio technique to assess the performance persistence in these Chinese funds. The study finds no significant evidence of persis- tence in the performance of the mutual funds. Winner (loser) funds do not continue to be winner (loser) funds in the subsequent time period. These findings suggest that future performance of funds cannot be predicted based on their past performance.info:eu-repo/semantics/publishedVersio

Anti-epileptic effect of Ganoderma lucidum polysaccharides by inhibition of intracellular calcium accumulation and stimulation of expression of CaMKII a in epileptic hippocampal neurons

Purpose: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II a expression in a model of epileptic neurons were investigated. Method: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II a protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope. Results: The CaMK II a expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. Conclusion: GLP may inhibit calcium overload and promote CaMK II a expression to protect epileptic neuron

Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells

The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene. © 2013 Zhang et al

Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models

The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example during chromosome organization. Describing phenomena that cover such diverse length, and also time scales, requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA, and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure

White rice consumption and risk of esophageal cancer in Xinjiang Uyghur Autonomous Region, northwest China: a case-control study

This study investigated the association between white rice consumption and the risk of esophageal cancer in remote northwest China, where the cancer incidence is known to be high. A case-control study was conducted during 2008-2009 in Urumqi and Shihezi, Xinjiang Uyghur Autonomous Region of China. Participants were 359 incident esophageal cancer patients and 380 hospital-based controls. Information on habitual white rice consumption was obtained by personal interview using a validated semi-quantitative food frequency questionnaire. Logistic regression analyses were performed to assess the association between white rice consumption and the esophageal cancer risk. Confounding variables including socio-demographics, family history, dietary and lifestyle factors were adjusted in the multivariate model. The esophageal cancer patients reported lower consumption levels of white rice-based products, including cooked white rice and porridge, when compared to the control group. Overall, regular consumption of white rice foods was inversely associated with the esophageal cancer risk, the adjusted OR being 0.34 (95 % CI 0.23 to 0.52) for the highest (&gt;250 g) versus the lowest (&lt;92 g) tertile of daily intake. Similar reductions in risk were also apparent for high consumption levels of cooked white rice and porridge. In conclusion, habitual white rice consumption was associated with a reduced risk of esophageal cancer for adults residing in northwest China. Our findings provide evidence to support the continued consumption of white rice

Exome Sequencing Identifies ZNF644 Mutations in High Myopia

Myopia is the most common ocular disorder worldwide, and high myopia in particular is one of the leading causes of blindness. Genetic factors play a critical role in the development of myopia, especially high myopia. Recently, the exome sequencing approach has been successfully used for the disease gene identification of Mendelian disorders. Here we show a successful application of exome sequencing to identify a gene for an autosomal dominant disorder, and we have identified a gene potentially responsible for high myopia in a monogenic form. We captured exomes of two affected individuals from a Han Chinese family with high myopia and performed sequencing analysis by a second-generation sequencer with a mean coverage of 30× and sufficient depth to call variants at ∼97% of each targeted exome. The shared genetic variants of these two affected individuals in the family being studied were filtered against the 1000 Genomes Project and the dbSNP131 database. A mutation A672G in zinc finger protein 644 isoform 1 (ZNF644) was identified as being related to the phenotype of this family. After we performed sequencing analysis of the exons in the ZNF644 gene in 300 sporadic cases of high myopia, we identified an additional five mutations (I587V, R680G, C699Y, 3′UTR+12 C>G, and 3′UTR+592 G>A) in 11 different patients. All these mutations were absent in 600 normal controls. The ZNF644 gene was expressed in human retinal and retinal pigment epithelium (RPE). Given that ZNF644 is predicted to be a transcription factor that may regulate genes involved in eye development, mutation may cause the axial elongation of eyeball found in high myopia patients. Our results suggest that ZNF644 might be a causal gene for high myopia in a monogenic form

Persistent problems of access to appropriate, affordable TB services in rural China: experiences of different socio-economic groups

BACKGROUND: Large-scale Tuberculosis (TB) control programmes in China have been hailed a success. Concerns remain, however, about whether the programme is reaching all sections of the population, particularly poorer groups within rural communities, and whether there are hidden costs. This study takes a household perspective to investigate receipt of appropriate care and affordability of services for different socio-economic groups with TB symptoms in rural China. METHODS: Secondary analysis of Chinese National Household Health Survey for 2003: 40,000 rural households containing 143,991 individuals, 2,308 identified as TB suspects. Outcomes: use of services and expenditure of TB suspects, by gender and socio-economic position, indicated by household income, education, material assets, and insurance status. RESULTS: 37% of TB suspects did not seek any professional care, with low-income groups less likely to seek care than more affluent counterparts. Of those seeking care, only 35% received any of the recommended diagnostic tests. Of the 182 patients with a confirmed TB diagnosis, 104 (57%) received treatment at the recommended level, less likely if lacking health insurance or material assets. The burden of payment for services amounted to 45% of annual household income for the low-income group, 16% for the high-income group. CONCLUSION: Access to appropriate, affordable TB services is still problematic in some rural areas of China, and receipt of care and affordability declines with declining socio-economic position. These findings highlight the current shortcomings of the national TB control programme in China and the formidable challenge it faces if it is to reach all sections of the population, including the poor with the highest burden of disease