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991.
Association of GNLY Genetic Polymorphisms with Chronic Liver Disease in a Korean Population 总被引:1,自引:0,他引:1
Granulysin (GNLY) is found in cytotoxic granules of cytolytic T lymphocytes and natural killer (NK) cells, which are critical for hepatitis B virus (HBV) clearance. GNLY cytotoxicity plays an important role in the defense against viruses or intracellular bacteria. We hypothesized that genetic variation in the GNLY gene could affect the resistance of hosts against HBV infection. We compared the distribution frequencies of GNLY polymorphisms between an HBV-induced chronic liver disease (CLD) group and a spontaneous recovery (SR) control group to determine whether GNLY polymorphisms play a role in HBV clearance. A total of 117 patients in the SR group and 230 patients in the CLD group were enrolled. Samples derived from complex infections, including hepatitis C and human immunodeficiency virus, and those associated with insufficient clinical information (10 samples in SR and 24 samples in CLD) were excluded from the study. The final analysis included 107 SR and 206 CLD samples. DNA was extracted from peripheral blood, and GNLY genotypes were determined by the GoldenGate(?) method. The genotype distribution of the single-nucleotide polymorphisms (SNPs) rs2886767 (C>T), rs1561285 (G>C), and rs11127 (T>C) were significantly different between the SR and CLD groups in a recessive model (p<0.015). These three SNPs were in a complete linkage disequilibrium (LD) block. Diplotype distributions of haplotype (HT) 1 (C-G-T) and HT2 (T-C-C) were significantly different between the SR and CLD groups in a recessive model (p=0.025) and a dominant model (p=0.008). All p-values remained significant after multiple comparisons. GNLY polymorphism genotypes and diplotypes were associated with the chronicity of HBV. These data suggested that genetic variation of GNLY may be an important factor in HBV clearance through the CD8+ T or NK cell-mediated removal of HBV-infected cells from the host. 相似文献
992.
SH Lee MH Park SM Kang SC Ko MC Kang S Cho PJ Park BT Jeon SK Kim JS Han YJ Jeon 《Bioscience, biotechnology, and biochemistry》2012,76(8):1445-1451
Pancreatic β cells are very sensitive to oxidative stress and this might play an important role in β cell death with diabetes. The protective effect of dieckol, one of the phlorotannin polyphenol compounds purified from Ecklonia cava (E. cava), against high glucose-induced oxidative stress was investigated by using rat insulinoma cells. A high-glucose (30 mM) treatment induced the death of rat insulinoma cells, but dieckol, at a concentration 17.5 or 70 μM, significantly inhibited the high-glucose induced glucotoxicity. Treatment with dieckol also dose-dependently reduced thiobarbituric acid reactive substances (TBARS), the generation of intracellular reactive oxygen species (ROS), and the nitric oxide level increased by a high glucose concentration. In addition, the dieckol treatment increased the activities of antioxidative enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in high glucose-pretreated rat insulinoma cells. Dieckol protected rat insulinoma cells damage under high glucose conditions. These effects were mediated by suppressing apoptosis and were associated with increased anti-apoptotic Bcl-2 expression, and reduced pro-apoptotic cleaved caspase-3 expression. These findings indicate that dieckol might be useful as a potential pharmaceutical agent to protect against the glucotoxicity caused by hyperglycemia-induced oxidative stress associated with diabetes. 相似文献
993.
Kim GY Ligons DL Hong C Luckey MA Keller HR Tai X Lucas PJ Gress RE Park JH 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(12):5859-5866
All T cells are dependent on IL-7 for their development and for homeostasis. Foxp3(+) regulatory T cells (Tregs) are unique among T cells in that they are dependent on IL-2. Whether such IL-2 dependency is distinct from or in addition to an IL-7 requirement has been a confounding issue, particularly because of the absence of an adequate experimental system to address this question. In this study, we present a novel in vivo mouse model where IL-2 expression is intact but IL-7 expression was geographically limited to the thymus. Consequently, IL-7 is not available in peripheral tissues. Such mice were generated by introducing a thymocyte-specific IL-7 transgene onto an IL-7 null background. In these mice, T cell development in the thymus, including Foxp3(+) Treg numbers, was completely restored, which correlates with the thymus-specific expression of transgenic IL-7. In peripheral cells, however, IL-7 expression was terminated, which resulted in a general paucity of T cells and a dramatic reduction of Foxp3(+) Treg numbers. Loss of Tregs was further accompanied by a significant reduction in Foxp3(+) expression levels. These data suggest that peripheral IL-7 is not only necessary for Treg survival but also for upregulating Foxp3 expression. Collectively, we assessed the effect of a selective peripheral IL-7 deficiency in the presence of a fully functional thymus, and we document a critical requirement for in vivo IL-7 in T cell maintenance and specifically in Foxp3(+) cell homeostasis. 相似文献
994.
To provide insights into the molecular mechanisms underlying diabetes mellitus, we performed a proteomic study on two diabetic animal models, streptozotocin (STZ)-induced diabetic rats (T1DM) and genetically diabetic (C57BL/6J ob/ob) mice (T2DM). To better understand the recovery process of those diabetic rodents, we examined the effect of hypoglycemic dipeptide Cyclo (His-Pro) (CHP) treatment on the differential expression of pancreatic proteins in both animal models. Oral administration of CHP had an excellent hypoglycemic effect in both animal models, lowering the average plasma glucose level by over 50%. Pancreatic proteins were separated by two-dimensional gel electrophoresis (2-DE) and identified by MALDI-TOF mass spectrometry. This study allowed, for the first time, the identification of 34 proteins that are related to diabetes and potential targets of CHP, a potent anti-diabetic agent for both T1DM and T2DM. The alterations in the expression of these proteins could indicate a tendency for diabetic animals to overcome their diabetic state. These proteins are involved in cellular functions such as metabolism, cellular structure, oxidative stress, as well as signal and energy transduction. Some have already been linked to diabetes, suggesting that the newly identified proteins might also be significant in the etiology of this pathology and should be further investigated. Furthermore, CHP has emerged as a potent tool for both the treatment and study of the molecular mechanisms underlying diabetes. Thus, the findings presented here provide new insights into the study and potential treatment of this pathology. 相似文献
995.
Yun SH Seo MG Jung BY Kim TH Kwon OD Jeong KS Rhee MH Lee YJ Park SJ Kwon YS Kwak D 《Journal of helminthology》2012,86(3):363-367
While multiple DNase activities occur in the excretory/secretory products (ESPs) of the adult Haemonchus contortus, the DNase activities in ESPs of the infective larvae (L3) have not been studied. Thus, the DNase activities in ESPs of H. contortus L3 were investigated and compared to those of adults for developmental stage-specific analysis. The DNase activities had relative molecular masses (M rs) of 34 and 36 kDa upon zymographic analysis at pH 5.0 and 7.0 when the larvae were incubated for over 48 h. The 34 and 36 kDa DNases of L3 ESPs were also detected in adult ESPs with similar characteristics. However, the 37 and 38.5 kDa DNases of the adult ESPs were not detected in the L3 ESPs. Since the 37 and 38.5 kDa DNase activities were mainly detected in adult ESPs, these activities appear to be specific to the adult stage whereas the other ESP DNase activities appear to be expressed during multiple stages of the parasite's life cycle. While the difference in DNase activities of L3 and adults remains obscure, the role of DNase in larval development should be further clarified and the identification of stage-specific developmental markers will lead to the discovery of specific factors that stimulate larval development. 相似文献
996.
Ho Young Yune Sung Phil Chung Yoo Seok Park Hyun Soo Chung Hye Sun Lee Jong Wook Lee Jong Woo Park Je Sung You Incheol Park Hahn Shick Lee 《PloS one》2015,10(3)
Background
The post-resuscitation phase after out-of-hospital cardiac arrest (OHCA) is characterised by a systemic inflammatory response (e.g., severe sepsis), for which the immature granulocyte count is a diagnostic marker. In this study we evaluated the prognostic significance of the delta neutrophil index (DNI), which is the difference in leukocyte subfractions as assessed by an automated blood cell analyser, for early mortality after OHCA.Materials and Methods
OHCA records from the emergency department cardiac arrest registry were retrospectively analysed. Patients who survived at least 24 h after return of spontaneous circulation were included in the analysis. We evaluated mortality and cerebral performance category scores at 30 days.Results
A total of 83 patients with OHCA were included in the study. Our results showed that DNI >8.4% on day 1 (hazard ratio [HR], 3.227; 95% CI, 1.485–6.967; p = 0.001) and DNI >10.5% on day 2 (HR, 3.292; 95% CI, 1.662–6.519; p<0.001) were associated with increased 30-day mortality in patients with OHCA. Additionally, DNI >8.4% on day 1 (HR, 2.718; 95% CI, 1.508–4.899; p<0.001) and DNI >10.5% on day 2 (HR, 1.709; 95% CI, 1.051–2.778; p = 0.02) were associated with worse neurologic outcomes 30 days after OHCA.Conclusion
A higher DNI is a promising prognostic marker for 30-day mortality and neurologic outcomes after OHCA. Our findings indicate that patients with elevated DNI values after OHCA might be closely monitored so that appropriate treatment strategies can be implemented. 相似文献997.
Joshua Park Jacqueline Wicki Sue E. Knoblaugh Jeffrey S. Chamberlain Donghoon Lee 《PloS one》2015,10(4)
The objective of this study was to investigate the efficacy of using quantitative magnetic resonance imaging (MRI) as a non-invasive tool for the monitoring of gene therapy for muscular dystrophy. The clinical investigations for this family of diseases often involve surgical biopsy which limits the amount of information that can be obtained due to the invasive nature of the procedure. Thus, other non-invasive tools may provide more opportunities for disease assessment and treatment responses. In order to explore this, dystrophic mdx4cv mice were systemically treated with a recombinant adeno-associated viral (AAV) vector containing a codon-optimized micro-dystrophin gene. Multi-parametric MRI of T2, magnetization transfer, and diffusion effects alongside 3-D volume measurements were then utilized to monitor disease/treatment progression. Mice were imaged at 10 weeks of age for pre-treatment, then again post-treatment at 8, 16, and 24 week time points. The efficacy of treatment was assessed by physiological assays for improvements in function and quantification of expression. Tissues from the hindlimbs were collected for histological analysis after the final time point for comparison with MRI results. We found that introduction of the micro-dystrophin gene restored some aspects of normal muscle histology and pathology such as decreased necrosis and resistance to contraction-induced injury. T2 relaxation values showed percentage decreases across all muscle types measured (tibialis anterior, gastrocnemius, and soleus) when treated groups were compared to untreated groups. Additionally, the differences between groups were statistically significant for the tibialis anterior as well. The diffusion measurements showed a wider range of percentage changes and less statistical significance while the magnetization transfer effect measurements showed minimal change. MR images displayed hyper-intense regions of muscle that correlated with muscle pathology in histological sections. T2 relaxation, alongside diffusion and magnetization transfer effects provides useful data towards the goal of non-invasively monitoring the treatment of muscular dystrophy. 相似文献
998.
Jun Hyun Jeong Young Ran Lee Hee Geun Park Wang Lok Lee 《Journal of Exercise Nutrition & Biochemistry》2015,19(2):65-72
[Purpose]
The aim of this study was to compare the effectiveness of either resveratrol supplementation or exercise training on macrophage infiltration and switching from M1 to M2 kupffer cells in high fat diet mice.[Methods]
C57BL/6 mice were separated into 5 groups: normal diet (ND; n = 6), high-fat diet (HD; n = 6), high-fat diet with resveratrol (HR; n = 6), high-fat diet with exercise (HE; n = 6) or high-fat diet with resveratrol and exercise (HRE; n = 6). Resveratrol supplementation mice were orally gavaged with resveratrol (25mg/kg of body weight) dissolved in 50% propylene glycol. Exercise mice ran on a treadmill at 12-20 m/min for 30-60 min/day, 5 times/week for 12 weeks.[Results]
After 12 weeks of intervention, the liver was analyzed. F4/80 expression was evaluated by western blot while CD11c and CD163 mRNA expressions were evaluated by RT-PCR. The weights of the body and liver were significantly increased in the HD and HR group compared to the ND group (p < 0.01). However, the weights were most effectively reduced in the HE and HRE groups compared to the HD group (p < 0.05). The macrophage marker, F4/80 expression was significantly lower in the HE and HRE groups compared to the HD group (p < 0.05). mRNA expression of the M1 macrophage marker, CD11c, in the HD group was significantly increased compared to the ND group (p < 0.01). mRNA expression of the M2 macrophage specific marker, CD163, in the HE and HRE groups were significantly increased compared to the HD group (p < 0.05). The mRNA expressions of TLR4, ICAM-1 and VCAM-1, which induce pro-inflammatory cytokine production, were strongly decreased in the HR, HE, and HRE groups compared to the HD group.[Conclusion]
These results suggest that moderate exercise training inhibits macrophage infiltration and up regulation of CD163 expression. However, resveratrol supplementation is not enough to ameliorate obesity-induced macrophage infiltration and switching. 相似文献999.
Byoungchun Lee Younghee Ahn Sung-Myung Kang Youngjin Park You-Jin Jeon Jong M. Rho Sung-Woo Kim 《Molecular biology of the cell》2015,26(12):2156-2167
Deregulation of mitochondrial heat-shock protein 40 (mtHsp40) and dysfunction of mtHsp70 are associated with mitochondrial fragmentation, suggesting that mtHsp40 and mtHsp70 may play roles in modulating mitochondrial morphology. However, the mechanism of mitochondrial fragmentation induced by mtHsp40 deregulation and mtHsp70 dysfunction remains unclear. In addition, the functional link between mitochondrial morphology change upon deregulated mtHsp40/mtHsp70 and mitochondrial function has been unexplored. Our coimmunoprecipitation and protein aggregation analysis showed that both overexpression and depletion of mtHsp40 accumulated aggregated proteins in fragmented mitochondria. Moreover, mtHsp70 loss and expression of a mtHsp70 mutant lacking the client-binding domain caused mitochondrial fragmentation. Together the data suggest that the molecular ratio of mtHsp40 to mtHsp70 is important for their chaperone function and mitochondrial morphology. Whereas mitochondrial translocation of Drp1 was not altered, optic atrophy 1 (Opa1) short isoform accumulated in fragmented mitochondria, suggesting that mitochondrial fragmentation in this study results from aberration of mitochondrial inner membrane fusion. Finally, we found that fragmented mitochondria were defective in cristae development, OXPHOS, and ATP production. Taken together, our data suggest that impaired stoichiometry between mtHsp40 and mtHsp70 promotes Opa1L cleavage, leading to cristae opening, decreased OXPHOS, and triggering of mitochondrial fragmentation after reduction in their chaperone function. 相似文献
1000.
Seong Yong Park Won Jun Kang Arthur Cho Ju Ri Chae Ye Lim Cho Jung Young Kim Ji Woong Lee Kyung Young Chung 《PloS one》2015,10(6)