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131.
To evaluate the role of host IL28B (interleukin 28B; interferon lambda 3) single nucleotide polymorphisms (SNPs) in predicting hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) susceptibility, three SNPs in the IL28B gene (rs12979860C/T, rs8099917G/T and rs12980275G/A) were examined in 330 subjects (including 154 HBV-related HCC patients, 86 non-HCC patients with chronic hepatitis B (CHB), 43 HBV self-limited infections and 47 healthy controls). Notably, the frequency of CC homozygosity was 91.5% in healthy controls and 72.9% in CHB, the difference being statistically significant (χ(2) = 6.40, P = 0.01). The statistically difference was seen between healthy controls (91.5%) and HCC (74.7%) (χ(2) = 6.05, P = 0.01). However, this significant finding was not seen between HBV self-limited and healthy controls. Carriers of the minor T allele in rs12979860 had a higher risk of HCC compared with non-carriers (χ(2) = 4.44, P = 0.04). Haplotype analyses revealed significant association between haplotype C-T-A and healthy controls, but not with the HCC group (96.6 vs. 82.0%, χ(2) = 6.08, P = 0.01). Analyses of genotype combination and gene-gene interaction showed that there was a positive interaction between rs12979860 and rs12980275, with an OR rate of 11.79 (likelihood test, P = 0.04). Our results suggest that the IL28B rs12979860 C/T polymorphism might affect susceptibility to the chronic HBV infection and progression of HCC. Of note, the T allele and non-CC genotypes have strong predictive effect of increasing susceptibility of chronic HBV infection and HCC.  相似文献   
132.
133.
The branching angle and diameter ratio in epicardial coronary artery bifurcations are two important determinants of atherogenesis. Murray's cubed diameter law and bifurcation angle have been assumed to yield optimal flows through a bifurcation. In contrast, we have recently shown a 7/3 diameter law (HK diameter model), based on minimum energy hypothesis in an entire tree structure. Here, we derive a bifurcation angle rule corresponding to the HK diameter model and critically evaluate the streamline flow through HK and Murray-type bifurcations. The bifurcations from coronary casts were found to obey the HK diameter model and angle rule much more than Murray's model. A finite element model was used to investigate flow patterns for coronary artery bifurcations of various types. The inlet velocity and pressure boundary conditions were measured by ComboWire. Y-bifurcation of Murray type decreased wall shear stress-WSS (10%-40%) and created an increased oscillatory shear index-OSI in atherosclerosis-prone regions as compared with HK-type bifurcations. The HK-type bifurcations were found to have more optimal flow patterns (i.e., higher WSS and lower OSI) than Murray-type bifurcations which have been traditionally believed to be optimized. This study has implications for changes in bifurcation angles and diameters in percutaneous coronary intervention.  相似文献   
134.
Increasing evidence demonstrates the dissociation of fat deposition, the inflammatory response, and insulin resistance in the development of obesity-related metabolic diseases. As a regulatory enzyme of glycolysis, inducible 6-phosphofructo-2-kinase (iPFK2, encoded by PFKFB3) protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance independently of adiposity. Using aP2-PFKFB3 transgenic (Tg) mice, we explored the ability of targeted adipocyte PFKFB3/iPFK2 overexpression to modulate diet-induced inflammatory responses and insulin resistance arising from fat deposition in both adipose and liver tissues. Compared with wild-type littermates (controls) on a high fat diet (HFD), Tg mice exhibited increased adiposity, decreased adipose inflammatory response, and improved insulin sensitivity. In a parallel pattern, HFD-fed Tg mice showed increased hepatic steatosis, decreased liver inflammatory response, and improved liver insulin sensitivity compared with controls. In both adipose and liver tissues, increased fat deposition was associated with lipid profile alterations characterized by an increase in palmitoleate. Additionally, plasma lipid profiles also displayed an increase in palmitoleate in HFD-Tg mice compared with controls. In cultured 3T3-L1 adipocytes, overexpression of PFKFB3/iPFK2 recapitulated metabolic and inflammatory changes observed in adipose tissue of Tg mice. Upon treatment with conditioned medium from iPFK2-overexpressing adipocytes, mouse primary hepatocytes displayed metabolic and inflammatory responses that were similar to those observed in livers of Tg mice. Together, these data demonstrate a unique role for PFKFB3/iPFK2 in adipocytes with regard to diet-induced inflammatory responses in both adipose and liver tissues.  相似文献   
135.
Cysteine-rich protein 61 (Cyr61)/CCN1 is a product of an immediate early gene and functions in mediating cell adhesion and inducing cell migration. We previously showed that increased production of Cyr61 by fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) promotes FLS proliferation and participates in RA pathogenesis with the IL-17-dependent pathway. However, whether Cyr61 in turn regulates Th17 cell differentiation and further enhances inflammation of RA remained unknown. In the current study, we explored the potential role of Cyr61 as a proinflammatory factor in RA pathogenesis. We found that Cyr61 treatment dramatically induced IL-6 production in FLS isolated from RA patients. Moreover, IL-6 production was attenuated by Cyr61 knockdown in FLS. Mechanistically, we showed that Cyr61 activated IL-6 production via the αvβ5/Akt/NF-κB signaling pathway. Further, using a coculture system consisting of purified CD4(+) T cells and RA FLS, we found that RA FLS stimulated Th17 differentiation, and the pro-Th17 differentiation effect of RA FLS can be attenuated or stimulated by Cyr61 RNA interference or addition of exogenous Cyr61, respectively. Finally, using the collagen-induced arthritis animal model, we showed that treatment with the anti-Cyr61 mAb led to reduction of IL-6 levels, decrease of Th17 response, and attenuation of inflammation and disease progression in vivo. Taken together, our results reveal a novel role of Cyr61 in promoting Th17 development in RA via upregulation of IL-6 production by FLS, thus adding a new layer into the functional interplay between FLS and Th17 in RA pathogenesis. Our study also suggests that targeting of Cyr61 may represent a novel strategy in RA treatment.  相似文献   
136.
Yang L  Ding Y  Chen Y  Zhang S  Huo C  Wang Y  Yu J  Zhang P  Na H  Zhang H  Ma Y  Liu P 《Journal of lipid research》2012,53(7):1245-1253
Lipid droplets are cellular organelles that consists of a neutral lipid core covered by a monolayer of phospholipids and many proteins. They are thought to function in the storage, transport, and metabolism of lipids, in signaling, and as a specialized microenvironment for metabolism in most types of cells from prokaryotic to eukaryotic organisms. Lipid droplets have received a lot of attention in the last 10 years as they are linked to the progression of many metabolic diseases and hold great potential for the development of neutral lipid-derived products, such as biofuels, food supplements, hormones, and medicines. Proteomic analysis of lipid droplets has yielded a comprehensive catalog of lipid droplet proteins, shedding light on the function of this organelle and providing evidence that its function is conserved from bacteria to man. This review summarizes many of the proteomic studies on lipid droplets from a wide range of organisms, providing an evolutionary perspective on this organelle.  相似文献   
137.
As most gramineous plants, guinea grass (Panicum maximum) comprise cellulosic biomass, which may be used as a feedstock for bioenergy. In order to develop such potential energy plants on copper-polluted lands, the hydroponic experiments with Cu, Paclobutrazol (PP333, a kind of antigibberellin) and plant growth-promoting bacterial endophyte (PGPB) treatments were carried out in a greenhouse. The seedlings of two cultivars of guinea grass, GG1 (P. maximum var. Natsukomaki) and GG2 (P. maximum var. Natsukaze) in 3 weeks old were treated, respectively, with different Cu treatments [0(CK), 100, 200, 300, 400, 500 μM l−1 Cu] for estimating Cu toxicity. The results showed that elevated Cu restrained plant growth and reduced biomass. According to the EC50 value [the Cu concentration when the relative gain in fresh weight ratio was 50% of control] of two tested cultivars, the concentration of Cu for further experiments was decided as 300 μM l−1. Both pretreatments of PP333 (200, 400, 600 mg l−1) and PGPB (Pantoea sp.) significantly alleviated the negative affect caused by stress of 300 μM l−1 Cu. The pretreatment of 400 mg l−1 PP333 promoted both two cultivars in biomass, compared to 300 μM l−1 Cu treat. The inoculation of Pantoea sp. Jp3-3 increased shoot dry weight, compared to Cu treat. The results suggested that the main reason for both PP333 and Pantoea sp. Jp3-3 enhanced Cu tolerance in guinea grass was that their pretreatments significantly decreased Cu absorption and accumulation under excessive Cu stress. The present study has provided a new insight into the exploitation of energy plant in heavy metal polluted condition by the way of plant growth regulation for increasing heavy metal tolerance.  相似文献   
138.
Paenibacillus polymyxa SQR-21, which is antagonistic against Fusarium oxysporum, is used as a biocontrol agent and, when mixed with organic substances for solid fermentation, produces a bioorganic fertilizer. The spores of P. polymyxa prepared at different temperatures were characterized with respect to the dipicolinic acid content, heat resistance, fatty acid composition and germination. Spores prepared at 37°C showed higher heat resistance than those prepared at 25 and 30°C. However, the germination rate was negatively correlated with the sporulation temperature. The maximum germination rate of the spores prepared at 25°C was 1.3-times higher than the spores prepared at 30°C. The sporulation temperature thus affects the resistance and germination properties of P. polymyxa spores. These results are useful for the production of improved bio-organic fertilizer.  相似文献   
139.
Huo L  Fielding AJ  Chen Y  Li T  Iwaki H  Hosler JP  Chen L  Hasegawa Y  Que L  Liu A 《Biochemistry》2012,51(29):5811-5821
The previously reported crystal structures of α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) show a five-coordinate Zn(II)(His)(3)(Asp)(OH(2)) active site. The water ligand is H-bonded to a conserved His228 residue adjacent to the metal center in ACMSD from Pseudomonas fluorescens (PfACMSD). Site-directed mutagenesis of His228 to tyrosine and glycine in this study results in a complete or significant loss of activity. Metal analysis shows that H228Y and H228G contain iron rather than zinc, indicating that this residue plays a role in the metal selectivity of the protein. As-isolated H228Y displays a blue color, which is not seen in wild-type ACMSD. Quinone staining and resonance Raman analyses indicate that the blue color originates from Fe(III)-tyrosinate ligand-to-metal charge transfer. Co(II)-substituted H228Y ACMSD is brown in color and exhibits an electron paramagnetic resonance spectrum showing a high-spin Co(II) center with a well-resolved (59)Co (I = 7/2) eight-line hyperfine splitting pattern. The X-ray crystal structures of as-isolated Fe-H228Y (2.8 ?) and Co-substituted (2.4 ?) and Zn-substituted H228Y (2.0 ? resolution) support the spectroscopic assignment of metal ligation of the Tyr228 residue. The crystal structure of Zn-H228G (2.6 ?) was also determined. These four structures show that the water ligand present in WT Zn-ACMSD is either missing (Fe-H228Y, Co-H228Y, and Zn-H228G) or disrupted (Zn-H228Y) in response to the His228 mutation. Together, these results highlight the importance of His228 for PfACMSD's metal specificity as well as maintaining a water molecule as a ligand of the metal center. His228 is thus proposed to play a role in activating the metal-bound water ligand for subsequent nucleophilic attack on the substrate.  相似文献   
140.

Background

Liver injuries are important medical problems that require effective therapy. Stem cell or hepatocyte transplantation has the potential to restore function of the damaged liver and ameliorate injury. However, the regulatory factors crucial for the repair and regeneration after cell transplantation have not been fully characterized. Our study investigated the effects and the expression of the regulatory factors in mouse models of acute liver injury either transplanted with the induced pluripotent stem cells (iPS) or the hepatocytes that differentiated from iPS cells (iHL).

Methods/Principal Findings

Mice received CCl4 injection and were randomized to receive vehicle, iPS, or iHL transfusions vial tail veins and were observed for 24, 48 or 72 hours. The group of mice with iPS transplantation performed better than the group of mice receiving iHL in reducing the serum alanine aminotransferase, aspartate aminotransferase, and liver necrosis areas at 24 hours after CCl4 injury. Moreover, iPS significantly increased the numbers of proliferating hepatocytes at 48 hours. Cytokine array identified that chemokine IP-10 could be the potential regulatory factor that ameliorates liver injury. Further studies revealed that iPS secreted IP-10 in vitro and transfusion of iPS increased IP-10 protein and mRNA expressions in the injured livers in vivo. The primary hepatocytes and non-parenchyma cells were isolated from normal and injured livers. Hepatocytes from injured livers that received iPS treatment expressed more IP-10 mRNA than their non-hepatocyte counter-parts. In addition, animal studies revealed that administration of recombinant IP-10 (rIP-10) effectively reduced liver injuries while IP-10-neutralizing antibody attenuated the protective effects of iPS and decreased hepatocyte proliferation. Both iPS and rIP-10 significantly reduced the 72-hour mortality rate in mice that received multiple CCl4-injuries.

Conclusions/Significance

These findings suggested that IP-10 may have an important regulatory role in facilitating the repair and regeneration of injured liver after iPS transplantation.  相似文献   
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