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Find video protocols related to scientific articles indexed in Pubmed.
Advances in porcine miRNAome.
Yi Chuan
PUBLISHED: 11-20-2014
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MicroRNA (miRNA), a class of non-coding RNA (about 22 nt), widely exists in different organisms and plays an important role in growth, development, and apoptosis. Recently, many studies have shown that miRNAs serve as a regulatory mechanism in mediating the development of pig muscle, fat, reproductive and immunity traits. The next-generation of high-throughput sequencing technology plays a critical role on finding new miRNAs and identifying their different expressions in pig. In this review, we summarize the application of the next-generation of high-throughput sequencing technology in the study of pig miRNAs as well as the regulatory roles of several important miRNAs in fat metabolism, muscle development, oocyte maturation and development of B cells and T cells. This review will provide insight into the research on pig miRNAs, and some ideas on how to improve pork quality, growth, reproductive and immunity performance.
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Inhibitory Effects of JEUD-38, a New Sesquiterpene Lactone from Inula japonica Thunb, on LPS-Induced iNOS Expression in RAW264.7 Cells.
Inflammation
PUBLISHED: 11-17-2014
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We isolated JEUD-38, a new sesquiterpene lactone from Inula japonica Thunb. JEUD-38 dramatically attenuated lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Consistent with this finding, the protein expression of inducible nitric oxide synthase (iNOS) was blocked by JEUD-38 in a concentration-dependent manner. To elucidate the mechanism, we examined the effect of JEUD-38 on LPS-stimulated nuclear factor-?B (NF-?B) nuclear translocation, inhibitory factor-?B (I?B) phosphorylation, and degradation. JEUD-38 reduced the translocation of p65, via abrogating I?B-? phosphorylation and degradation. In addition, JEUD-38 inhibited LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Since iNOS as well as the upstream NF-?B and MAPKs are known to be closely involved in inflammation, these results suggest that JEUD-38 is a promising candidate for prevention and therapy of inflammatory diseases.
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Extracellular lumican inhibits pancreatic cancer cell growth and is associated with prolonged survival after surgery.
Clin. Cancer Res.
PUBLISHED: 10-23-2014
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Purpose:To evaluate the relevance between lumican expression patterns and the clinical course of PDAC patients, and to investigate the role of lumican in PDAC progression. Experimental Design:131 patient tumors were chosen for tissue microarray staining and Cox regression analysis was used to test the associations between lumican expression and clinical, pathologic, and oncologic outcomes in all patients. Primary PDAC cells and recombinant human lumican protein were used to establish a working model to mimic the in vivo interactions between stromal lumican and PDAC cells. Using this model, we tested the effects of lumican on EGFR signaling via Akt and HIF-1? and its subsequent influence on glucose consumption, lactate production, intracellular ATP, and apoptotic cell death. Results:Lumican was present in the stroma surrounding PDAC cells in roughly one-half of primary tumors and the direct xenografts. Patients with stromal lumican were associated with a profound reduction in metastatic recurrence after surgery and three-fold longer survival than patients without stromal lumican. In PDAC cells, extracellular lumican reduced EGFR expression and phosphorylation through enhanced dimerization and internalization of EGFR and the resultant inhibition of Akt kinase activity. Lumican also reduced HIF-1? expression and activity via Akt. PDAC cells with enhanced HIF-1? activity were resistant to lumican-induced inhibition of glucose consumption, lactate production, intracellular ATP, and apoptosis. Conclusions:There is a positive association between stromal lumican in primary PDAC tumors and prolonged survival after tumor resection. Lumican plays a restrictive role in EGFR-expressing pancreatic cancer progression.
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Effects of toxicologically relevant xenobiotics and the lipid-derived electrophile 4-hydroxynonenal on macrophage cholesterol efflux: silencing carboxylesterase 1 has paradoxical effects on cholesterol uptake and efflux.
Chem. Res. Toxicol.
PUBLISHED: 10-09-2014
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Cholesterol cycles between free cholesterol (unesterified) found predominantly in membranes and cholesteryl esters (CEs) stored in cytoplasmic lipid droplets. Only free cholesterol is effluxed from macrophages via ATP-binding cassette (ABC) transporters to extracellular acceptors. Carboxylesterase 1 (CES1), proposed to hydrolyze CEs, is inactivated by oxon metabolites of organophosphorus pesticides and by the lipid electrophile 4-hydroxynonenal (HNE). We assessed the ability of these compounds to reduce cholesterol efflux from foam cells. Human THP-1 macrophages were loaded with [(3)H]-cholesterol/acetylated LDL and then allowed to equilibrate to enable [(3)H]-cholesterol to distribute into its various cellular pools. The cholesterol-engorged cells were then treated with toxicants in the absence of cholesterol acceptors for 24 h, followed by a 24 h efflux period in the presence of toxicant. A concentration-dependent reduction in [(3)H]-cholesterol efflux via ABCA1 (up to 50%) was found for paraoxon (0.1-10 ?M), whereas treatment with HNE had no effect. A modest reduction in [(3)H]-cholesterol efflux via ABCG1 (25%) was found after treatment with either paraoxon or chlorpyrifos oxon (10 ?M each) but not HNE. No difference in efflux rates was found after treatments with either paraoxon or HNE when the universal cholesterol acceptor 10% (v/v) fetal bovine serum was used. When the re-esterification arm of the CE cycle was disabled in foam cells, paraoxon treatment increased CE levels, suggesting the neutral CE hydrolysis arm of the cycle had been inhibited by the toxicant. However, paraoxon also partially inhibited lysosomal acid lipase, which generates cholesterol for efflux, and reduced the expression of ABCA1 protein. Paradoxically, silencing CES1 expression in macrophages did not affect the percent of [(3)H]-cholesterol efflux. However, CES1 mRNA knockdown markedly reduced cholesterol uptake by macrophages, with SR-A and CD36 mRNA reduced 3- and 4-fold, respectively. Immunoblots confirmed SR-A and CD36 protein downregulation. Together, these results suggest that toxicants, e.g., oxons, may interfere with macrophage cholesterol homeostasis/metabolism.
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Segment Based Decision Tree Induction With Continuous Valued Attributes.
IEEE Trans Cybern
PUBLISHED: 10-08-2014
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A key issue in decision tree (DT) induction with continuous valued attributes is to design an effective strategy for splitting nodes. The traditional approach to solving this problem is adopting the candidate cut point (CCP) with the highest discriminative ability, which is evaluated by some frequency based heuristic measures. However, such methods ignore the class permutation of examples in the node, and they cannot distinguish the CCPs with the same or similar frequency information, thus may fail to induce a better and smaller tree. In this paper, a new concept, i.e., segment of examples, is proposed to differentiate the CCPs with same frequency information. Then, a new hybrid scheme that combines the two heuristic measures, i.e., frequency and segment, is developed for splitting DT nodes. The relationship between frequency and the expected number of segments, which is regarded as a random variable, is also given. Experimental comparisons demonstrate that the proposed scheme is not only effective to improve the generalization capability, but also valid to reduce the size of the tree.
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Skull defect reconstruction based on a new hybrid level set.
Biomed Mater Eng
PUBLISHED: 09-18-2014
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Skull defect reconstruction is an important aspect of surgical repair. Historically, a skull defect prosthesis was created by the mirroring technique, surface fitting, or formed templates. These methods are not based on the anatomy of the individual patient's skull, and therefore, the prosthesis cannot precisely correct the defect. This study presented a new hybrid level set model, taking into account both the global optimization region information and the local accuracy edge information, while avoiding re-initialization during the evolution of the level set function. Based on the new method, a skull defect was reconstructed, and the skull prosthesis was produced by rapid prototyping technology. This resulted in a skull defect prosthesis that well matched the skull defect with excellent individual adaptation.
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Genistein potentiates the antitumor effect of 5-Fluorouracil by inducing apoptosis and autophagy in human pancreatic cancer cells.
Anticancer Res.
PUBLISHED: 09-10-2014
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Although 5-fluorouracil (5-FU)-based combination chemotherapy (i.e. FOLFIRINOX) has demonstrated effectiveness against pancreatic cancer, novel therapeutic strategies must be developed to increase the therapeutic window of these cytotoxic agents. Genistein is a soy-derived isoflavone with pleiotropic biological effects that can enhance the antitumor effect of chemotherapeutic agents.
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Anti-oxidative stress effect of loading-dose rosuvastatin prior to percutaneous coronary intervention in patients with acute coronary syndrome: a prospective randomized controlled clinical trial.
Clin Drug Investig
PUBLISHED: 09-05-2014
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Administration of a loading dose of a statin (HMG-CoA reductase inhibitor) prior to percutaneous coronary intervention (PCI) contributes to protection from myocardial ischemic-reperfusion injury. This trial was designed to investigate the effect and mechanism of loading-dose rosuvastatin therapy before PCI in patients with acute coronary syndrome.
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A critical role for interferon regulatory factor 9 in cerebral ischemic stroke.
J. Neurosci.
PUBLISHED: 09-05-2014
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The failure of past efforts to develop effective stroke treatments is at least partially because these treatments often interfered with essential physiological functions, even though they are targeted toward pathophysiological events, such as inflammation, excitotoxicity, and oxidative stress. Thus, the direct targeting of endogenous neuroprotective or destructive elements holds promise as a potential new approach to treating this devastating condition. Interferon regulatory factor 9 (IRF9), a transcription factor that regulates innate immune responses, has been implicated in neurological pathology. Here, we provide new evidence that IRF9 directly mediates neuronal death in male mice. In response to ischemia/reperfusion (I/R), IRF9 accumulated in neurons. IRF9 deficiency markedly mitigated both poststroke neuronal death and neurological deficits, whereas the neuron-specific overexpression of IRF9 sensitized neurons to death. The histone deacetylase Sirt1 was identified as a novel negative transcriptional target of IRF9 both in vivo and in vitro. IRF9 inhibits Sirt1 deacetylase activity, culminating in the acetylation and activation of p53-mediated cell death signaling. Importantly, both the genetic and pharmacological manipulation of Sirt1 effectively counteracted the pathophysiological effects of IRF9 on stroke outcome. These findings indicate that, rather than activating a delayed innate immune response, IRF9 directly activates neuronal death signaling pathways through the downregulation of Sirt1 deacetylase in response to acute I/R stress.
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Surface plasmon resonance temperature sensor based on photonic crystal fibers randomly filled with silver nanowires.
Sensors (Basel)
PUBLISHED: 08-29-2014
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We propose a temperature sensor design based on surface plasmon resonances (SPRs) supported by filling the holes of a six-hole photonic crystal fiber (PCF) with a silver nanowire. A liquid mixture (ethanol and chloroform) with a large thermo-optic coefficient is filled into the PCF holes as sensing medium. The filled silver nanowires can support resonance peaks and the peak will shift when temperature variations induce changes in the refractive indices of the mixture. By measuring the peak shift, the temperature change can be detected. The resonance peak is extremely sensitive to temperature because the refractive index of the filled mixture is close to that of the PCF material. Our numerical results indicate that a temperature sensitivity as high as 4 nm/K can be achieved and that the most sensitive range of the sensor can be tuned by changing the volume ratios of ethanol and chloroform. Moreover, the maximal sensitivity is relatively stable with random filled nanowires, which will be very convenient for the sensor fabrication.
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Molecular cloning and functional characterization of the lycopene ?-cyclase gene via virus-induced gene silencing and its expression pattern in Nicotiana tabacum.
Int J Mol Sci
PUBLISHED: 08-22-2014
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Lycopene ?-cyclase (?-LCY) is a key enzyme that catalyzes the synthesis of ?-branch carotenoids through the cyclization of lycopene. Two cDNA molecules encoding ?-LCY (designated Nt?-LCY1 and Nt?-LCY2) were cloned from Nicotiana tabacum. Nt?-LCY1 and Nt?-LCY2 are encoded by two distinct genes with different evolutionary origins, one originating from the tobacco progenitor, Nicotiana sylvestris, and the other originating from Nicotiana tomentosiformis. The two coding regions are 97% identical at the nucleotide level and 95% identical at the amino acid level. Transcripts of Nt?-LCY were detectable in both vegetative and reproductive organs, with a relatively higher level of expression in leaves than in other tissues. Subcellular localization experiments using an Nt?-LCY1-GFP fusion protein demonstrated that mature Nt?-LCY1 protein is localized within the chloroplast in Bright Yellow 2 suspension cells. Under low-temperature and low-irradiation stress, Nt?-LCY transcript levels substantially increased relative to control plants. Tobacco rattle virus (TRV)-mediated silencing of ?-LCY in Nicotiana benthamiana resulted in an increase of ?-branch carotenoids and a reduction in the levels of ?-branch carotenoids. Meanwhile, transcripts of related genes in the carotenoid biosynthetic pathway observably increased, with the exception of ?-OHase in the TRV-?-lcy line. Suppression of ?-LCY expression was also found to alleviate photoinhibition of Potosystem II in virus-induced gene silencing (VIGS) plants under low-temperature and low-irradiation stress. Our results provide insight into the regulatory role of ?-LCY in plant carotenoid biosynthesis and suggest a role for ?-LCY in positively modulating low temperature stress responses.
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Compositional redistribution and dynamic heterogeneity in mixed lipid membrane induced by polyelectrolyte adsorption: effects of chain rigidity.
Eur Phys J E Soft Matter
PUBLISHED: 08-22-2014
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Monte Carlo simulation is employed to investigate the interaction between a polyelectrolyte and a fluid mixed membrane containing neutral (phosphatidyl-choline, PC), monovalent anionic (phosphatidylserine, PS), and multivalent anionic (phosphatidylinositol, PIP2) lipids. The effects of the intrinsic polyelectrolyte rigidity and solution ionic strength on the lateral rearrangement and dynamics of different anionic lipid species are systematically studied. Our results show that, the increase of polyelectrolyte chain rigidity reduces the loss of polyelectrolyte conformational entropy and the energy gains in electrostatic interaction, but raises the demixing entropy loss of the segregated anionic lipids. Therefore, the polyelectrolyte/membrane adsorption strength exhibits a non-monotonic dependence on the polyelectrolyte rigid parameter k ang, and there exists a certain optimal k ang for which the adsorption strength is maximal. Because the less loss of chain conformational entropy dominates the increase of the demixing entropy loss of the segregated anionic lipids and the decreases of the electrostatic energy gains, the semiflexible polyelectrolyte adsorbs onto the membrane more firmly than the flexible one. Whereas, for the adsorption of rigid polyelectrolyte, larger anionic lipid demixing entropy loss and less energy gain in the electrostatic interaction dominate over the decrease of the polyelectrolyte conformation entropy loss, leading to the desorption of the chain from the membrane. By decreasing the ionic concentration of the salt solution, the certain optimal k ang shifts to larger values. The cooperative effects of the adsorbing polyelectrolyte beads determine the concentration gradients and hierarchical mobility of the bound anionic lipids, as well as the polyelectrolyte dynamics.
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Astrocyte elevated gene-1 (AEG-1) promotes osteosarcoma cell invasion through the JNK/c-Jun/MMP-2 pathway.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-21-2014
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Osteosarcoma is the most common primary malignant bone tumour in children and adolescents and is characterised by high malignant and metastatic potentials. However, the molecular mechanism underlying this invasiveness remains unclear. In this study, we determined that PD98059 and SP600125, the two mitogen-activated protein kinase (MAPK) family inhibitors, decreased the osteosarcoma cell U2OS-AEG-1 migration and invasion that was enhanced by astrocyte elevated gene-1 (AEG-1) in an in vitro wound-healing and Matrigel invasion assay independently of cell viability. These findings indicate that AEG-1 promoted osteosarcoma cell invasion is relevant to the MAPK pathways. The up-regulation of AEG-1 increased the levels of phosphor-c-Jun N-terminal kinase (JNK) and phosphor-c-Jun; however, there were no marked changes in the levels of phosphor-extracellular regulated kinase (ERK) 1/2 or phosphor-c-Fos due to the activation of AEG-1 in U2OS. SP600125 (a JNK inhibitor) decreased phosphor-c-Jun and MMP-2 in U2OS-AEG-1, while PD98059 (a ERK1/2 inhibitor) had no influence on the levels of phosphor-c-Jun or MMP-2 in U2OS-AEG-1. Further study revealed that the down-regulation of phosphor-c-Jun not only obviously decreased the MMP-2 protein level and the MMP-2 transcriptional activity that were up-regulated by AEG-1 in Western-blot and luciferase reporter assays, but also inhibited the migration and invasion abilities of the U2OS-AEG-1 cells, which suggests that AEG-1 mediated U2OS invasion at least partially via the JNK/c-Jun/MMP-2 pathway. Consistent with these observations, immunohistochemical (IHC) staining revealed that AEG-1 expression was associated with the protein levels of phosphor-c-Jun and MMP-2 in needle biopsy paraffin-embedded archival human osteosarcoma tissues. Taken together, our findings suggest that AEG-1 plays a crucial role in the aggressiveness of osteosarcoma via the JNK/c-Jun/MMP-2 pathway.
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Interferon Regulatory Factor 9 is a Key Mediator of Hepatic Ischemia/Reperfusion Injury.
J. Hepatol.
PUBLISHED: 08-21-2014
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Hepatic ischemia/reperfusion (I/R) injury is characterised by anoxic cell injury and the generation of inflammatory mediators, leading to hepatic parenchymal cell death. The activation of interferon regulatory factors (IRFs) has been implicated in hepatic I/R injury, but the role of IRF9 in this progression is unclear.
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The Canary in the Coal Mine: The Growth of Patient-Derived Tumorgrafts in Mice Predicts Clinical Recurrence after Surgical Resection of Pancreatic Ductal Adenocarcinoma.
Ann. Surg. Oncol.
PUBLISHED: 08-19-2014
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Recurrence after resection of pancreatic ductal adenocarcinoma (PDAC) is common, thus postoperative surveillance is critical for detection and treatment of recurrent disease. The development of biologically based techniques for early recurrence detection may enable more timely and effective treatment of such recurrences.
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Comparative proteomics of milk fat globule membrane proteins from transgenic cloned cattle.
PLoS ONE
PUBLISHED: 08-18-2014
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The use of transgenic livestock is providing new methods for obtaining pharmaceutically useful proteins. However, the protein expression profiles of the transgenic animals, including expression of milk fat globule membrane (MFGM) proteins, have not been well characterized. In this study, we compared the MFGM protein expression profile of the colostrum and mature milk from three lines of transgenic cloned (TC) cattle, i.e., expressing recombinant human ?-lactalbumin (TC-LA), lactoferrin (TC-LF) or lysozyme (TC-LZ) in the mammary gland, with those from cloned non-transgenic (C) and conventionally bred normal animals (N). We identified 1, 225 proteins in milk MFGM, 166 of which were specifically expressed only in the TC-LA group, 265 only in the TC-LF group, and 184 only in the TC-LZ group. There were 43 proteins expressed only in the transgenic cloned animals, but the concentrations of these proteins were below the detection limit of silver staining. Functional analysis also showed that the 43 proteins had no obvious influence on the bovine mammary gland. Quantitative comparison revealed that MFGM proteins were up- or down-regulated more than twofold in the TC and C groups compared to N group: 126 in colostrum and 77 in mature milk of the TC-LA group; 157 in colostrum and 222 in mature milk of the TC-LF group; 49 in colostrum and 98 in mature milk of the TC-LZ group; 98 in colostrum and 132 in mature milk in the C group. These up- and down-regulated proteins in the transgenic animals were not associated with a particular biological function or pathway, which appears that expression of certain exogenous proteins has no general deleterious effects on the cattle mammary gland.
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Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations.
Chen Wu, Zhaoming Wang, Xin Song, Xiao-Shan Feng, Christian C Abnet, Jie He, Nan Hu, Xian-Bo Zuo, Wen Tan, Qimin Zhan, Zhibin Hu, Zhonghu He, Weihua Jia, Yifeng Zhou, Kai Yu, Xiao-Ou Shu, Jian-Min Yuan, Wei Zheng, Xue-Ke Zhao, She-Gan Gao, Zhi-Qing Yuan, Fu-You Zhou, Zong-Min Fan, Ji-Li Cui, Hong-Li Lin, Xue-Na Han, Bei Li, Xi Chen, Sanford M Dawsey, Linda Liao, Maxwell P Lee, Ti Ding, You-Lin Qiao, Zhihua Liu, Yu Liu, Dianke Yu, Jiang Chang, Lixuan Wei, Yu-Tang Gao, Woon-Puay Koh, Yong-Bing Xiang, Ze-Zhong Tang, Jin-Hu Fan, Jing-jing Han, Sheng-Li Zhou, Peng Zhang, Dong-Yun Zhang, Yuan Yuan, Ying Huang, Chunling Liu, Kan Zhai, Yan Qiao, Guangfu Jin, Chuanhai Guo, Jianhua Fu, Xiaoping Miao, Changdong Lu, Haijun Yang, Chaoyu Wang, William A Wheeler, Mitchell Gail, Meredith Yeager, Jeff Yuenger, Er-Tao Guo, Ai-li Li, Wei Zhang, Xue-Min Li, Liang-Dan Sun, Bao-Gen Ma, Yan Li, Sa Tang, Xiu-Qing Peng, Jing Liu, Amy Hutchinson, Kevin Jacobs, Carol Giffen, Laurie Burdette, Joseph F Fraumeni, Hongbing Shen, Yang Ke, Yixin Zeng, Tangchun Wu, Peter Kraft, Charles C Chung, Margaret A Tucker, Zhi-Chao Hou, Ya-Li Liu, Yan-Long Hu, Li Wang, Guo Yuan, Li-Sha Chen, Xiao Liu, Teng Ma, Hui Meng, Li Sun, Xin-Min Li, Xiu-Min Li, Jian-Wei Ku, Ying-Fa Zhou, Liu-Qin Yang, Zhou Wang, Yin Li, Qirenwang Qige, Wen-jun Yang, Guang-Yan Lei, Long-qi Chen, En-Min Li, Ling Yuan, Wen-Bin Yue, Ran Wang, Lu-Wen Wang, Xue-Ping Fan, Fang-Heng Zhu, Wei-Xing Zhao, Yi-min Mao, Mei Zhang, Guo-Lan Xing, Ji-Lin Li, Min Han, Jing-Li Ren, Bin Liu, Shu-Wei Ren, Qing-Peng Kong, Feng Li, Ilyar Sheyhidin, Wu Wei, Yan-Rui Zhang, Chang-Wei Feng, Jin Wang, Yu-Hua Yang, Hong-Zhang Hao, Qi-De Bao, Bao-Chi Liu, Ai-Qun Wu, Dong Xie, Wan-Cai Yang, Liang Wang, Xiao-Hang Zhao, Shu-Qing Chen, Jun-Yan Hong, Xue-Jun Zhang, Neal D Freedman, Alisa M Goldstein, Dongxin Lin, Philip R Taylor, Li-dong Wang, Stephen J Chanock.
Nat. Genet.
PUBLISHED: 08-17-2014
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We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 × 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 × 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 × 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.
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Physical Activity and Chronic Prostatitis/Chronic Pelvic Pain Syndrome.
Med Sci Sports Exerc
PUBLISHED: 08-10-2014
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Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urologic disorder among men, but its etiology is still poorly understood. Our objective was to examine the relationship between physical activity and incidence of CP/CPPS in a large cohort of male health professionals.
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Sex-specific effects of long-term exposure to bisphenol-A on anxiety- and depression-like behaviors in adult mice.
Chemosphere
PUBLISHED: 08-08-2014
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Humans are routinely exposed to low levels of bisphenol A (BPA), an environmental endocrine disruptor, which is widely used in the production of polycarbonate plastics. The effects of perinatal exposure to BPA have been shown to affect various aspects of social behaviors such as anxiety and depression in adult offspring. Because sex hormones play a critical role in neurobehavior in adulthood, it is possible that long-term exposure to BPA has widespread effects on these emotional behaviors in adulthood. In the present study, adult mice were exposed to BPA at dosages of 0.04, 0.4, 4, 40mgkg(-1)d(-1) for 12weeks. A behavioral assay was performed using the open field test (OFT), mirrored maze, the elevated plus maze (EPM), and the forced swim task. The results showed that, after exposure to BPA at 0.4-40mgkg(-1)d(-1), the number of open arm entries and the time spent in them in the elevated plus maze task were reduced in males but increased in females, and thus eliminating or reversing sex differences in these behaviors. BPA at 0.04-40mgkg(-1)d(-1) increased the immobility of male mice in the forced swimming test. Furthermore, BPA (0.4-40mgkg(-1)d(-1)) significantly decreased brain level of testosterone in males, but no significant influence was found in serum and the brain levels of estradiol in females. Western blot analysis further indicated that BPA at 0.4, 4, or 40mgkg(-1)d(-1) significantly down-regulated the protein level of estrogen receptor ? (ER?) in the hippocampus of the adult males but not females, and inhibited the protein level of GABA(A)?2 receptor in hippocampus of males but promoted that of females. These results suggest that long-term exposure to BPA sex specifically affects anxiety- and depression-like behaviors in adult mice. Changes in the levels of GABA(A)?2 receptor and ER? proteins of hippocampus might be associated with BPA-induced changes in these emotional behaviors.
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Advances in miRNA research related to testis development and spermatogenesis.
Yi Chuan
PUBLISHED: 07-31-2014
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MicroRNA (miRNA), a class of non-coding RNA (about 22 nt), widely exists in different organisms and plays an important role in regulating cell growth, development, and apoptosis. Recently, various studies have demonstrated that miRNA also serves as a key mediator during testis development and spermatogenesis both in human beings and animals. However, the expression of miRNA in different testis from different species showed significant differences. Meanwhile, it also showed different expression patterns in different spermatogenesis stages. In this review, we summarize different miRNA expression patterns during testis development, spermatogenesis, as well as their roles in regulating spermatogenesis, which provids insight into the further research on miRNA in testis, and ideas for regulating and improving animal sperm quality by using miRNA.
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Characterization and partial genomic analysis of a lytic Myoviridae bacteriophage against Staphylococcus aureus isolated from dairy cows with mastitis in Mid-east of China.
Virus Genes
PUBLISHED: 07-22-2014
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Using bacteriophages as a tool to the control of pathogens is a complementary to antibiotic therapy. We have isolated a lytic bacteriophage, designated vB_SauM_JS25, from sewage effluent on a dairy farm in Jiangsu, Mid-east of China for use as a biocontrol agent against Staphylococcus aureus infections. Phage vB_SauM_JS25 was morphologically classified as Myoviridae. The phage showed broad host ranges within S. aureus strains, lysing 51 of 56 strains (91.1 %). Its latent period and burst size were approximately 20 min and 21 PFU/cell, respectively. Phage vB_SauM_JS25 was able to survive in a pH range between 6 and 9. However, a treatment of 70 or 80 °C for 10 min completely inactivated the phage. Moreover, morphologic analysis of vB_SauM_JS25 revealed that it was closely related to other Myoviridae phages infecting Staphylococcus species. The bacteriolytic activity of phage vB_SauM_JS25 at a multiplicity infection (MOI) 1 indicted its efficiency for reducing bacterial growth. These findings suggest that phage vB_SauM_JS25 could be considered a potential therapeutic or prophylactic candidate against S. aureus infection.
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Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress.
Nat. Med.
PUBLISHED: 07-18-2014
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In type 2 diabetes, hyperglycemia is present when an increased demand for insulin, typically due to insulin resistance, is not met as a result of progressive pancreatic beta cell dysfunction. This defect in beta cell activity is typically characterized by impaired insulin biosynthesis and secretion, usually accompanied by oxidative and endoplasmic reticulum (ER) stress. We demonstrate that multiple inflammatory cytokines elevated in diabetic pancreatic islets induce beta cell oxidative and ER stress, with interleukin-23 (IL-23), IL-24 and IL-33 being the most potent. Conversely, we show that islet-endogenous and exogenous IL-22, by regulating oxidative stress pathways, suppresses oxidative and ER stress caused by cytokines or glucolipotoxicity in mouse and human beta cells. In obese mice, antibody neutralization of IL-23 or IL-24 partially reduced beta cell ER stress and improved glucose tolerance, whereas IL-22 administration modulated oxidative stress regulatory genes in islets, suppressed ER stress and inflammation, promoted secretion of high-quality efficacious insulin and fully restored glucose homeostasis followed by restitution of insulin sensitivity. Thus, therapeutic manipulation of immune regulators of beta cell stress reverses the hyperglycemia central to diabetes pathology.
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Effects of silencing connexin43 on expression of pituitary tumor-transforming gene in prolactinomas.
Neurol. Res.
PUBLISHED: 07-16-2014
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Objectives: Pituitary tumor transforming gene (PTTG) is thought to play an important role in prolactinomas, and its overexpression is influenced by estrogen action in the pituitary. Changes in estrogen levels in the rat anterior pituitary increase the number of gap junctions (GJs) increasing both Connexin43 (Cx43) expression and intercellular communication, contributing to pituitary tumor growth. The aim of this study was to investigate the effect of Cx43 on PTTG expression by silencing Cx43 expression using RNA interference (RNAi) in vivo. Methods: An experimental rat model of prolactinoma induced by estradiol (E2) treatment was used. Connexin43 RNAi was applied in vivo through the arachnoid space by injection of double-stranded RNA (dsRNA). Pituitary Cx43 immunostaining was examined using immunofluorescence and Cx43 and PTTG expression by both reverse-transcription-PCR (RT-PCR) and western blotting, respectively. Results: (1) Pituitaries treated with E2 were hypertrophic, but this was reduced by dsRNA treatment. (2) Pituitary Cx43 immunofluorescence increased following E2 treatment, but returned to normal levels following dsRNA treatment. (3) Estradiol induced Cx43 and PTTG expression, which decreased following dsRNA treatment. Discussion: Altered Cx43 expression modulates PTTG expression, which correlates with prolactinoma development. Thus, inhibiting gap junction intercellular communication (GJIC) as a means of weakening the pathologic role PTTG in prolactinomas may be of therapeutic interest.
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[Pharmacologic ascorbate treatment of influenza in vivo].
Zhonghua Jie He He Hu Xi Za Zhi
PUBLISHED: 07-12-2014
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To investigate the effects of pharmacologic ascorbate (vitamin C) against Influenza A/CA/7/09 (H1N12009).
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Resveratrol protects neurons and the myocardium by reducing oxidative stress and ameliorating mitochondria damage in a cerebral ischemia rat model.
Cell. Physiol. Biochem.
PUBLISHED: 07-08-2014
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Resveratrol has shown potent antioxidant activity in ischemia models. The present study was performed to determine whether resveratrol protects against cerebral ischemia-induced neuronal and myocardial injury by interfering with mitochondrial homeostasis.
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Topological effects on capsomer-polyion co-assembly.
J Chem Phys
PUBLISHED: 07-03-2014
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On the basis of a T = 1 icosahedral capsid model, the capsomer-polyion co-assembly process has been investigated by molecular dynamics simulations using capsomers with different net charge and charge distribution as well as linear, branched, and hyper-branched polyions. The assembly process was characterized in terms of the time-dependent cluster size probabilities, averaged cluster size, encapsulation efficiency, and polyion extension. The kinetics of the capsid formation displayed a two-step process. The first one comprised adsorption of capsomers on the polyion, driven by their electrostatic attraction, whereas the second one involved a relocation and/or reorientation of adsorbed capsomers, which rate is reduced upon increasing electrostatic interaction. We found that increased polyion branching facilitated a more rapid encapsulation process towards a higher yield. Moreover, the hyper-branched polyions were entirely encapsulated at all polyion-capsid charge ratios considered.
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Synthesis, characterization, cytotoxicity of mixed ligand complexes of palladium(II) with dipyrido[3,2-d:2',3'-f]quinoxaline/dipyrido[3,2-a:2',3'-c](6,7,8,9-tetrahydro)phenazine and 4-toluensulfonyl-L-amino acid dianion.
Eur J Med Chem
PUBLISHED: 07-02-2014
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Ten novel palladium(II) complexes with dipyrido[3,2-d:2',3'-f]quinoxaline (Dpq)/dipyrido[3,2-a:2',3'-c](6,7,8,9-tetrahydro)phenazine (Dpqc) and 4-toluensulfonyl-L-amino acid dianion, [Pd(Dpq)(TsvalNO)]·H2O (1a), [Pd(Dpq)(TsileNO)]·H2O (1b), [Pd(Dpq)(TsserNO)] (1c), [Pd(Dpq)(TsthrNO)]·1.5H2O (1d), [Pd(Dpq)(TsleuNO)]·0.5H2O (1e), [Pd(Dpq)(TspheNO)] (1f), [Pd(Dpqc)(TsvalNO)] (2a), [Pd(Dpqc)(TsileNO)] (2b), [Pd(Dpqc)(TsserNO)]·H2O (2c) and [Pd(Dpqc)(TsthrNO)]·0.5H2O (2d) have been synthesized and characterized by elemental analysis, IR, UV, (1)H NMR and mass spectrometry techniques. Crystal structure of the complex 1f has been determined by X-ray diffraction. The cytotoxicity was tested by MTT assay. The results indicated that the complexes 1a and 2a showed better cytotoxicity than cisplatin against MCF-7. The complex 1e had higher cytotoxicity than cisplatin against K562. Both the N donating ligands and the amino acid have important effects on the cytotoxicity.
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Activation of Liver X Receptor Improves Viability of Adipose-Derived Mesenchymal Stem Cells to Attenuate Myocardial Ischemia Injury Through TLR4/NF-?B and Keap-1/Nrf-2 Signaling Pathways.
Antioxid. Redox Signal.
PUBLISHED: 06-11-2014
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Abstract Aims: Clinical application of cellular therapy for cardiac regeneration is significantly hampered by the low retention of engrafted cells, mainly attributable to the poor microenvironment dominated by inflammation and oxidative stress in the host's infarcted myocardium. This study aims at investigating whether liver X receptor (LXR) agonist T0901317 will improve survival of adipose-derived mesenchymal stem cells (AD-MSCs) after transplantation into infarcted hearts. Results: Noninvasive in vivo bioluminescence imaging and histological staining showed that LXR agonist T0901317 improved the retention and survival of intramyocardially injected AD-MSCs. Moreover, combined therapy of LXR agonist and AD-MSCs inhibited host cardiomyocyte apoptosis, reduced fibrosis, and improved cardiac function, while it concomitantly decreased inflammatory cytokines (e.g., tumor necrosis factor-? and interleukin-6) and increased growth factor (e.g., vascular endothelial growth factor and basic fibroblast growth factor) expression in infarct myocardium. To reveal possible mechanisms, AD-MSCs were subjected to hypoxia/serum deprivation (H/SD) injury to simulate ischemic conditions in vivo. The LXR agonist (10(-7) mM) improved AD-MSC survival under H/SD condition. Western blot revealed that the LXR agonist reduced TLR4, TRAF-6, and MyD88 protein expression, inhibited I?B? phosphorylation and NF-?B-p65 nuclear translocation, which resulted in accelerated Keap-1 protein degradation, enhanced Nrf-2 nuclear translocation, and increased HO-1 protein expression. Innovation and Conclusion: LXR agonist can enhance the functional survival of transplanted AD-MSCs in infarcted myocardium, at least partially, via modulation of the TLR4/NF-?B and Keap-1/Nrf-2 signaling pathways. Moreover, combined therapy of LXR agonist and AD-MSCs has a synergetic effect on cardiac repair and functional improvement after infarction. Antioxid. Redox Signal. 00, 000-000.
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Interferon regulatory factor 9 is critical for neointima formation following vascular injury.
Nat Commun
PUBLISHED: 06-02-2014
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Interferon regulatory factor 9 (IRF9) has various biological functions and regulates cell survival; however, its role in vascular biology has not been explored. Here we demonstrate a critical role for IRF9 in mediating neointima formation following vascular injury. Notably, in mice, IRF9 ablation inhibits the proliferation and migration of vascular smooth muscle cells (VSMCs) and attenuates intimal thickening in response to injury, whereas IRF9 gain-of-function promotes VSMC proliferation and migration, which aggravates arterial narrowing. Mechanistically, we show that the transcription of the neointima formation modulator SIRT1 is directly inhibited by IRF9. Importantly, genetic manipulation of SIRT1 in smooth muscle cells or pharmacological modulation of SIRT1 activity largely reverses the neointima-forming effect of IRF9. Together, our findings suggest that IRF9 is a vascular injury-response molecule that promotes VSMC proliferation and implicate a hitherto unrecognized 'IRF9-SIRT1 axis' in vasculoproliferative pathology modulation.
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Genetic variant in the 3'-untranslated region of VEGFR1 gene influences chronic obstructive pulmonary disease and lung cancer development in Chinese population.
Mutagenesis
PUBLISHED: 06-02-2014
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Lung inflammation and epithelial to mesenchymal transition (EMT) are two pathogenic features for the two contextual diseases: chronic obstructive pulmonary disease (COPD) and lung cancer. VEGFR1 (or FLT1) plays a certain role in promoting tumour growth, inflammation and EMT. To simultaneously test the association between the single nucleotide polymorphisms (SNPs) in VEGFR1 and risk of COPD and lung cancer would reveal genetic mechanisms shared by these two diseases and joint aetiology. We conducted a two-population hospital-based case-control study. Three potential functional SNPs (rs664393, rs7326277 and rs9554314) were genotyped in southern Chinese and validated in eastern Chinese to explore their associations with COPD risk in 1511 COPD patients and 1677 normal lung function controls, and with lung cancer risk in 1559 lung cancer cases and 1679 cancer-free controls. We also detected the function of the promising SNP. Individuals carrying the rs7326277C (CT+CC) variant genotypes of VEGFR1 had a significant decrease in risk of both COPD (OR = 0.78; 95% CI = 0.68-0.90) and lung cancer (OR = 0.79; 95% CI = 0.64-0.98), compared with those carrying the rs7326277TT genotype. Functional assays further showed that the rs7326277C genotypes had lower transcriptional activity and caused decreased VEGFR expression, compared with the rs7326277TT genotype. However, no significant association was observed for the other two SNPs (rs664393 and rs9554314) and either COPD or lung cancer risk. Our data suggested that the rs7326277C variant of VEGFR1 could reduce both COPD and lung cancer risk by lowering VEGFR1 mRNA expression; the SNP might be a common susceptible locus for both COPD and lung cancer.
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In vitro antitumor activity of stellettin B, a triterpene from marine sponge Jaspis stellifera, on human glioblastoma cancer SF295 cells.
Mar Drugs
PUBLISHED: 05-21-2014
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Stellettin B was isolated from marine sponge Jaspis stellifera. In vitro antitumor activities were investigated on 39 human cancer cell lines. Stellettin B exhibited highly potent inhibition against the growth of a human glioblastoma cell line SF295, with a GI50 of 0.01 ?M. In contrast, stellettin B showed very weak inhibitory activity on normal cell lines including HMEC, RPTEC, NHBE and PrEC, with GI50s higher than 10 ?M, suggesting its relatively selective cytotoxicity against human cancer cells compared to normal human cell lines. We then focused on the antitumor activity of this compound on SF295 cells. Flow cytometric analysis indicated that stellettin B induced apoptosis in SF295 cells in a concentration-dependent manner. Further study indicated that stellettin B increased the production of ROS, the activity of caspase 3/7, as well as the cleavage of PARP, each of which is known to be involved in apoptosis. To investigate the molecular mechanism for cell proliferation inhibition and apoptosis induction, effect on the phosphorylation of several signal proteins of PI3K/Akt and RAS/MAPK pathways was examined. Stellettin B inhibited the phosphorylation of Akt potently, with no activity on p-ERK and p-p38, suggesting that inhibition of PI3K/Akt pathway might be involved in the antiproliferative and apoptosis-inducing effect. However, homogenous time-resolved fluorescence (HTRF) assay indicated that stellettin B did not inhibit PI3K activity, suggesting that the direct target might be signal protein upstream of Akt pathway other than PI3K.
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Ultrasonic-assisted enzymatic extraction of phenolics from broccoli (Brassica oleracea L. var. italica) inflorescences and evaluation of antioxidant activity in vitro.
Food Sci Technol Int
PUBLISHED: 05-20-2014
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An efficient ultrasonic-assisted enzymatic extraction technique was applied to extracting phenolics from broccoli inflorescences without organic solvents. The synergistic model of enzymolysis and ultrasonication simultaneously was selected, and the enzyme combination was optimized by orthogonal test: cellulase 7.5?mg/g FW (fresh weight), pectinase 10?mg/g FW, and papain 1.0?mg/g FW. The operating parameters in ultrasonic-assisted enzymatic extraction were optimized with response surface methodology using Box-Behnken design. The optimal extraction conditions were as follows: ultrasonic power, 440?W; liquid to material ratio, 7.0:1?mL/g; pH value of 6.0 at 54.5?? for 10?min. Under these conditions, the extraction yield of phenolics achieved 1.816?±?0.0187?mg gallic acid equivalents/gram FW. The free radical scavenging activity of ultrasonic-assisted enzymatic extraction extracts was determined by 1,1-diphenyl-2-picrylhydrazyl·assay with EC50 values of 0.25, and total antioxidant activity was determined by ferric reducing antioxidant power assay with ferric reducing antioxidant power value of 0.998?mmol FeSO4/g compared with the referential ascorbic acid of 1.184?mmol FeSO4/g.
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Mesenchymal stem cells suppress T cells by inducing apoptosis and through PD-1/B7-H1 interactions.
Immunol. Lett.
PUBLISHED: 05-19-2014
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Mesenchymal stem cells (MSCs) exert a suppressive role toward T cells which has been widely studied in recent decades. However, the underlying mechanisms utilized by MSCs are still not fully elucidated. Herein, we performed traditional suppressive assays using co-cultured MSCs and conventional CD4(+)CD25(-) T cells (Tconv) with and without transwell systems. We showed that the expression of programmed cell death-1 receptor (PD-1) on activated Tconv was significantly elevated after they were exposed to MSCs. And we demonstrated that PD-1/B7-H1 pathway was involved in the suppression of MSCs on activated Tconv. Further analysis revealed that the up-regulation of PD-1 was related to an increasing apoptosis of activated Tconv. Finally, we demonstrated that the PD-1/B7-H1 pathway was not related to the elevated immunosuppressive cytokines including IL-10 and TGF-?1 which in turn played dispensable roles in the up-regulation of PD-1 on activated Tconv in MSC-Tconv co-culture systems.
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Resonantly pumped acousto-optic Q-switched Er:YAG lasers at 1617 and 1645 nm.
Appl Opt
PUBLISHED: 05-03-2014
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Resonantly pumped acousto-optic Q-switched Er:YAG lasers at 1617 and 1645 nm are demonstrated. An etalon was used to obtain 1617 nm output. Laser pulses with 4.02 mJ energy at 1617 nm and 5.64 mJ energy at 1645 nm were generated, with pulse duration more than 400 ns at a pulse repetition rate of 1000 Hz.
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[Wood smoke condensate induced epithelial-mesenchymal transition in human airway epithelial cells].
Zhonghua Jie He He Hu Xi Za Zhi
PUBLISHED: 04-04-2014
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To observe the detrimental effects of wood smoke condensate (WSC) exposure on human bronchial epithelial cells (HBEC), and to explore the expression of epithelial-mesenchymal transition (EMT) markers in HBEC exposed to WSC.
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Interleukin-23 mediates the intestinal response to microbial ?-1,3-glucan and the development of spondyloarthritis pathology in SKG mice.
PUBLISHED: 03-18-2014
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Spondyloarthritides (SpA) occur in 1% of the population and include ankylosing spondylitis (AS) and arthropathy of inflammatory bowel disease (IBD), with characteristic spondylitis, arthritis, enthesitis, and IBD. Genetic studies implicate interleukin-23 (IL-23) receptor signaling in the development of SpA and IBD, and IL-23 overexpression in mice is sufficient for enthesitis, driven by entheseal-resident T cells. However, in genetically prone individuals, it is not clear where IL-23 is produced and how it drives the SpA syndrome, including IBD or subclinical gut inflammation of AS. Moreover, it is unclear why specific tissue involvement varies between patients with SpA. We undertook this study to determine the location of IL-23 production and its role in SpA pathogenesis in BALB/c ZAP-70(W163C)-mutant (SKG) mice injected intraperitoneally with ?-1,3-glucan (curdlan).
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[Association of GSTM1 and GSTT1 polymorphisms with noise-induced hearing loss: a meta-analysis].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
PUBLISHED: 03-18-2014
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To evaluate the association of glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) polymorphisms with noise-induced hearing loss.
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Primary study on the lesions and specific proteins in BEAS-2B cells induced with the 2009 A (H1N1) influenza virus.
Appl. Microbiol. Biotechnol.
PUBLISHED: 03-17-2014
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In order to investigate the lesions and proteins with differential expression in cells infected with the 2009 A (H1N1) virus and to determine the specific proteins involved in cell damage, the present study has been performed. BEAS-2B cells were infected with the 2009 A (H1N1) influenza virus or the seasonal H1N1 influenza virus for 12, 24, 48, and 72 h, and cell cycle and apoptosis were analyzed with flow cytometry. Total cellular proteins were extracted and underwent two-dimensional gel electrophoresis. The differentially expressed proteins underwent mass spectrometry for identification. The results showed that after 12 h, cells infected with the virus strain sourced from severe cases had the highest apoptosis rate (P?
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Duplicated copy of CHRNA7 increases risk and worsens prognosis of COPD and lung cancer.
Eur. J. Hum. Genet.
PUBLISHED: 03-16-2014
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Recent genome-wide association studies implicated that the nicotinic acetylcholine receptors (nAChRs) are common susceptible genes of two contextual diseases: chronic obstructive pulmonary disease (COPD) and lung cancer. We aimed to test whether the copy number variations (CNVs) in nAChRs have hereditary contributions to development of the two diseases. In two, two-stage, case-control studies of southern and eastern Chinese, a common CNV-3956 that duplicates the cholinergic receptor, nicotinic, ?7 (CHRNA7) gene was genotyped in a total of 7880 subjects and its biological phenotype was assessed. The ?4-copy of CNV-3956 increased COPD risk (?4-copy vs 2/3-copy: OR=1.44, 95% CI=1.23-1.68) and caused poor lung function, and it similarly augmented risk (OR=1.49, 95% CI=1.29-1.73) and worsened prognosis (hazard ratio (HR)=1.25, 95% CI=1.07-1.45) of lung cancer. The ?4-copy was estimated to account for 1.56% of COPD heritability and 1.87% of lung cancer heritability, respectively. Phenotypic analysis further showed that the ?4-copy of CNV-3956 improved CHRNA7 expression in vivo and increased the carriers' smoking amount. The CNV-3956 of CHRNA7 contributed to increased risks and poor prognoses of both COPD and lung cancer, and this may be a genetic biomarker of the two diseases.European Journal of Human Genetics advance online publication, 19 November 2014; doi:10.1038/ejhg.2014.229.
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Dragon's blood and its extracts attenuate radiation-induced oxidative stress in mice.
J. Radiat. Res.
PUBLISHED: 03-14-2014
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Dragon's blood (DB) possesses great medicinal values due to the presence of several phenolic compounds. This study was designed to investigate the effects of DB and its extracts (DBEs) on oxidative stress in mice exposed to whole body (60)Co-? irradiation (4 Gy). DB and DBEs were intragastrically administered to mice for 5 d prior to radiation. The antioxidant activities, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels in liver and spleen were measured using kits. Furthermore, DB and DBE effects were determined by organ indices and histology of liver and spleen. Our results indicated that the DB and DBE-treated groups showed a significant decrease (P < 0.05) in levels of MDA in liver and spleen compared with the irradiation-only group. Moreover, the activity of SOD, CAT and the level of GSH in liver and spleen tissue were enhanced significantly (P < 0.05) in the DB and DBE groups. DB and DBE also had a significant effect on the recovery of thymus indices. The histological observations of groups having treatment with DB and DBE indicated significant reduction in the radiation-induced damage to the liver and spleen, together with improvement in the morphology of the liver and spleen. These results suggest that DB and DBE treatment prevents radiation-induced oxidative stress injury and restores antioxidant status and histopathological changes in the liver and spleen, but there is need for further study to explore the precise molecular mechanism and strategy for optimal practical application of DB and DBE.
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Immunomodulation of mesenchymal stromal cells on regulatory T cells and its possible mechanism.
Exp. Cell Res.
PUBLISHED: 03-13-2014
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Mesenchymal stromal cells (MSCs) and regulatory T cells (Tregs) have both garnered abundant interests from immunologists worldwide, as both MSCs and Tregs can be considered immunosuppressive in their own right. But a little attention has been paid to the impacts of MSCs on Tregs. To clarify the effects of MSCs on Tregs, we performed the coculture systems within MSCs and Tregs. We confirmed that MSC-exposed Tregs are capable of more immunosuppressive than Tregs without coculturing with MSCs. And this augmenting suppressive capacity was accompanied with an upregulation of programmed cell death 1 receptor (PD-1) on Tregs. Importantly, we found that cell viability of Tregs was excluded from the influences of MSCs. Finally, we showed that PD-1/B7-H1 interactions and IL-10 might be responsible for the enhanced suppressive capability of MSC-exposed Tregs. Further analysis revealed that PD-1/B7-H1 interactions were not responsible for the productions of IL-10 and TGF-?1 in the MSC-Treg coculture systems; in contrast, IL-10 rather than TGF-?1 played a role in the upregualtion of PD-1. Furthermore, this is the first explorative study to evaluate the immunomodulation of MSCs on the suppressive capacity of Tregs in MSC-Treg in vitro coculture setting.
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Generation of bi-transgenic pigs overexpressing human lactoferrin and lysozyme in milk.
Transgenic Res.
PUBLISHED: 03-11-2014
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Intensive swine production industry uses antibiotics to treat diseases and improve pig growth. This can not only cause antibiotic resistance, but can also pollute the environment or eventually affect human public health. To date, human lactoferrin (hLF) and human lysozyme (hLZ) have been known as non-adaptive but interactive antimicrobial members and could act in concert against bacteria, which contribute to host defense. Therefore, their expression in pigs might be an alternative strategy for replacing antibiotics in the pig production industry. In our study, we produced hLF and hLZ bi-transgenic pigs and assessed the milk's antibacterial ability. Integration of both transgenes was confirmed by PCR and southern blot. Both the hLF and hLZ were expressed in the mammary gland of bi-transgenic pigs, as detected by western blotting. The expression amounts were 6.5 g/L for hLF and 1.1 mg/L for hLZ using ELISA. Interestingly, pig milk containing hLF and hLZ had synergistic antimicrobial activity. Our results suggest an alternative approach for avoiding the use of antibiotics in the pig industry, which would be of great benefit to the commercial swine production.
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Lung function and incidence of chronic obstructive pulmonary disease after improved cooking fuels and kitchen ventilation: a 9-year prospective cohort study.
PLoS Med.
PUBLISHED: 03-01-2014
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Biomass smoke is associated with the risk of chronic obstructive pulmonary disease (COPD), but few studies have elaborated approaches to reduce the risk of COPD from biomass burning. The purpose of this study was to determine whether improved cooking fuels and ventilation have effects on pulmonary function and the incidence of COPD.
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Radioprotective effects of dragon's blood and its extracts on radiation-induced myelosuppressive mice.
J Ethnopharmacol
PUBLISHED: 02-23-2014
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Dragon?s blood, a traditional Chinese herb, has been used to "panacea of blood activating" and its major biological activity appears to be from phenolic compounds. In this study, our research aims to examine the effects of Dragon?s blood (DB) and its extracts (DBE) on radiation-induced myelosuppressive mice.
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Effect of polyelectrolyte adsorption on lateral distribution and dynamics of anionic lipids: a Monte Carlo study of a coarse-grain model.
Eur. Biophys. J.
PUBLISHED: 02-22-2014
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We employ Monte Carlo simulations to investigate the interaction between an adsorbing linear flexible cationic polyelectrolyte and a ternary mixed fluid membrane containing neutral (phosphatidylcholine, PC), monovalent (phosphatidylserine, PS), and multivalent (phosphatidylinositol, PIP2) anionic lipids. We systematically explore the influences of polyelectrolyte chain length, polyelectrolyte charge density, polyelectrolyte total charge amount, and salt solution ionic strength on the static and dynamic properties of different anionic lipid species. Our results show that the multivalent PIP2 lipids dominate the polyelectrolyte-membrane interaction and competitively inhibit polyelectrolyte-PS binding. When the total charge amount of the polyelectrolyte is less than that of the local oppositely charged PIP2 lipids, the polyelectrolyte can drag the bound multivalent lipids to diffuse on the membrane, but cannot interact with the PS lipids. Under this condition, the diffusion behaviors of the polyelectrolyte closely follow the prediction of the Rouse model, and the polyelectrolyte chain properties determine the adsorption amount, concentration gradients, and hierarchical mobility of the bound PIP2 lipids. However, when the total charge amount of the polyelectrolyte is larger than that of the local PIP2 lipids, the polyelectrolyte further binds the PS lipids around the polyelectrolyte-PIP2 complex to achieve local electrical neutrality. In this condition, parts of the polyelectrolyte desorb from the membrane and show faster mobility, and the bound PS presents much faster mobility than the segregated PIP2. This work provides an explanation for heterogeneity formation in different anionic lipids induced by polyelectrolyte adsorption.
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Early intervention with tiotropium in Chinese patients with GOLD stages I-II chronic obstructive pulmonary disease (Tie-COPD): study protocol for a multicentre, double-blinded, randomised, controlled trial.
BMJ Open
PUBLISHED: 02-20-2014
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Owing to the high and increasing morbidity and mortality, chronic obstructive pulmonary disease (COPD) has become a major public health problem worldwide. Although the majority of patients with COPD are in the early stages, little attention has been paid to them, in particular regarding to early intervention. Tiotropium bromide can significantly relieve symptoms and reduce the incidence of acute exacerbations of COPD. Therefore, we hypothesise that therapy with tiotropium bromide will benefit patients with COPD with early-stage disease.
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MicroRNA-23a expression in paraffin-embedded specimen correlates with overall survival of diffuse large B-cell lymphoma.
Med. Oncol.
PUBLISHED: 02-08-2014
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It has been demonstrated that aberrant expression of microRNAs (miRNAs) is strongly associated with carcinogenesis. Recently, specific miRNAs may serve as potential biomarkers for the diagnosis and prognosis of various types of tumor. MiR-23a is known to play important role in the development of cancers and deregulated in various hematological malignancies. The aim of the present study is to explore miR-23a as potential diagnostic and/or prognostic marker of diffuse large B-cell lymphoma (DLBCL). We compared the expression level of miR-23a in DLBCL patients (n = 104) and reactive lymph nodes as controls (n = 28) from formalin-fixed, paraffin-embedded tissues using quantitative reverse transcription-polymerase chain reaction. The expression level of miR-23a was significantly higher in DLBCL patients than in controls (P = 0.001). No significant association was observed between the miR-23a expression level and clinical features such as age, gender, Ann Arbor stage, performance status, lactate dehydrogenase, extranodal sites and International Prognostic Index score (IPI). Kaplan-Meier analysis showed that higher expression level of miR-23a was significantly associated with a poor overall survival (OS) in DLBCL patients (log-rank test, P = 0.029), and multivariable Cox regression revealed the expression of miR-23a (adjusted P = 0.034) and IPI (adjusted P = 0.021) was independently associated with OS. To our knowledge, we provide here the first evidence that miR-23a may represent a diagnostic and prognostic marker for DLBCL. DLBCL patients with a high expression level of miR-23a had a shorter OS than patients with a lower expression level. Further investigation of the changes may be of prognostic significance in clinical practice.
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Brush biopsy with DNA-image cytometry: a useful and noninvasive method for monitoring malignant transformation of potentially malignant oral disorders.
Eur Arch Otorhinolaryngol
PUBLISHED: 02-04-2014
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Oral and pharyngeal cancer is the sixth most common cancer worldwide, the 5-year survival rate has not yet increased. A key factor in rates not having improved is the lack of early detection. This study was undertaken to estimate the diagnostic accuracy of brush biopsy with DNA-image cytometry (a noninvasive method) for potentially malignant oral disorders compared with tissue biopsy pathology in China. Exfoliative cells were obtained using a cytobrush cell collector from oral mucosa of 52 subjects, followed by scalpel biopsy from the same region. Nuclear DNA contents (ploidy) were measured after Feulgen restaining, using an automated DNA image cytometer. Exfoliative cytology with DNA-image cytometry and histopathological diagnosis were performed separately at different institutions. Histological investigation was considered the gold standard. We reported that the sensitivity of DNA aneuploidy for the detection of cancer cells in potentially malignant oral disorders was 86.36 %, its specificity was 90.00 %, its positive predictive value was 86.36 %, and its negative predictive value was 90.00 %. Brush biopsy with DNA-image cytometry is a useful method for monitoring potentially malignant oral disorders.
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Detection of copper ions in drinking water using the competitive adsorption of proteins.
Biosens Bioelectron
PUBLISHED: 01-27-2014
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Heavy metal ions, i.e., Cu(2+), are harmful to the environment and our health. In order to detect them, and circumvent or alleviate the weaknesses of existing detecting technologies, we contrive a unique Surface Plasmon Resonance (SPR) biosensor combined with competitive adsorption of proteins, termed the Vroman effect. This approach adopts native proteins (albumin) as bio-receptors that interact with Cu(2+) to be denatured. Denaturation disrupts the conformation of albumin so that it weakens its affinity to adsorb on the sensing surface. Through the competitive adsorption between the denatured albumins and the native ones, the displacement occurs adjacent to the sensing surface, and this process is real-time monitored by SPR, a surface-sensitive label-free biosensor. The affinities of native albumin is significantly higher than that of denatured albumin, demonstrated by measured KD of native and denatured albumin to gold surafce, 5.8±0.2×10(-5) M and 5.4±0.1×10(-4) M, respectively. Using our biosensor, Cu(2+) with concentration down to 0.1mg/L is detected in PBS, tap water, deionized water, and bottled water. The SPR biosensor is characterized for 5 different heavy metal ions, Cu(2+), Fe(3+), Mn(2+), Pb(2+), and Hg(2+), most common heavy metal ions found in tap water. At the maximum contaminant level (MCL) suggested by the United States Environmental Protection Agency (EPA), the SPR biosensor produces 13.5±0.4, 1.5±0.4, 0, 0, and 0 mDeg, respectively, suggesting the biosensor may be used to detect Cu(2+) in tap water samples.
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Dominant fitness costs of abamectin resistance in Plutella xylostella.
Pest Manag. Sci.
PUBLISHED: 01-16-2014
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The TH-Abm strain of Plutella xylostella, exhibiting 23 670-fold resistance to abamectin, was selected from a field-evolved multiresistant population. By repeated backcrossing to a susceptible strain (Roth) and selection with abamectin, the resistance trait of TH-Abm was introgressed into Roth to generate a near-isogenic strain (Roth-Abm). Fitness costs associated with abamectin resistance were examined in Roth-Abm.
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Overexpression of muscarinic receptor 3 promotes metastasis and predicts poor prognosis in non-small-cell lung cancer.
J Thorac Oncol
PUBLISHED: 01-15-2014
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Chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer development, but the mechanism is not fully understood. Muscarinic receptor 3 (M3R) has been found to be involved in the progression of small-cell lung cancer and the pathological process of COPD. We hypothesized that M3R may contribute to lung cancer development, especially in patients with COPD.
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Nicotine elevated intracellular Ca²? in rat airway smooth muscle cells via activating and up-regulating ?7-nicotinic acetylcholine receptor.
Cell. Physiol. Biochem.
PUBLISHED: 01-08-2014
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Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling with airway smooth muscle (ASM) hypertrophy and hyperplasia. Since tobacco use is the key risk factor for the development of COPD and intracellular Ca(2+) concentration ([Ca(2+)]i) plays a major role in both cell proliferation and differentiation, we hypothesized that nicotinic acetylcholine receptor (nAChR) activation plays a role in the elevation of [Ca(2+)]i in airway smooth muscle cells (ASMCs).
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Molecular cloning of a novel tryptophyllin peptide from the skin of the orange-legged monkey frog, Phyllomedusa hypochondrialis.
Chem Biol Drug Des
PUBLISHED: 01-06-2014
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Tryptophyllins are a group of small (4-14 amino acids), heterogenous peptides, mostly from the skins of hylid frogs from the genera, Phyllomedusa and Litoria. To date, more than forty TPHs have been discovered in species from these two genera. Here, we describe the identification of a novel tryptophyllin type 3 peptide, PhT-3, from the extracts of skin of the orange-legged monkey frog, Phyllomedusa hypochondrialis, and molecular cloning of its precursor-encoding cDNA from a cDNA library constructed from the same skin sample. Full primary structural characterization was achieved using a combination of direct Edman degradation, mass spectrometry and deduction from cloned skin-derived cDNA. The open-reading frame of the precursor cDNA was found to consist of 63 amino acid residues. The mature peptide arising from this precursor contains a post-translationally modified N-terminal pyroglutamate (pGlu) residue, formed from acid-mediated cyclization of an N-terminal Gln (Q) residue, and with the structure: pGlu-Asp-Lys-Pro-Phe-Trp-Pro-Pro-Pro-Ile-Tyr-Pro-Met. Pharmacological assessment of a synthetic replicate of this peptide on phenylephrine preconstricted rat tail artery segments, revealed a reduction in relaxation induced by bradykinin. PhT-3 was also found to mediate antiproliferative effects on human prostate cancer cell lines.
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Circulating MicroRNAs as a Novel Class of Diagnostic Biomarkers in Gastrointestinal Tumors Detection: A Meta-Analysis Based on 42 Articles.
PLoS ONE
PUBLISHED: 01-01-2014
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MicroRNAs (miRNAs) have become the focus of most recent efforts in cancer research. However, there have been inconsistencies in the literature regarding the suitability of circulating miRNAs for early detection of gastrointestinal cancers. This study aims to assess the diagnostic performance of circulating miRNAs in detection of gastrointestinal cancer through a meta-analysis.
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Association of single nucleotide polymorphisms in ADAM12 gene with susceptibility to knee osteoarthritis: a case-control study in a Chinese Han population.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Genetic factors play an important role in osteoarthritis (OA) etiology and ADAM12 gene polymorphisms may be involved. This study tried to examine the single-nucleotide polymorphisms (SNPs) of ADAM12 for their association with knee OA susceptibility in a Chinese Han population.
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Effects of chitosan on intestinal inflammation in weaned pigs challenged by enterotoxigenic Escherichia coli.
PLoS ONE
PUBLISHED: 01-01-2014
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The aim of this study was to investigate whether supplementation with chitosan (COS) could reduce diarrhea and to explore how COS alleviates intestinal inflammation in weaned pigs. Thirty pigs (Duroc×Landrace×Yorkshire, initial BW of 5.65±0.27) weaned at age 21 d were challenged with enterotoxigenic Escherichia coli during a preliminary trial period, and then divided into three treatment groups. Pigs in individual pens were fed a corn-soybean meal diet, that contained either 0 (control), 50 mg/kg chlortetracycline, or 300 mg/kg COS for 21 days. The post-weaning diarrhea frequency, calprotectin levels and TLR4 protein expression were decreased (P<0.05) in both the COS and chlortetracycline groups compared with control. Simultaneously, supplemental COS and chlortetracycline had no effect on the mRNA expression of TNF-? in the jejunal mucosa, or on the concentrations of IL-1?, IL-6 and TNF-? in serum. However, COS supplementation improved (P<0.05) the mRNA expression of IL-1? and IL-6 in the jejunal mucosa. The results indicate that supplementation with COS at 300 mg/kg was effective for alleviating intestinal inflammation and enhancing the cell-mediated immune response. As feed additives, chitosan and chlortetracycline may influence different mechanisms for alleviating inflammation in piglets.
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Plasma HSPA12B is a potential predictor for poor outcome in severe sepsis.
PLoS ONE
PUBLISHED: 01-01-2014
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Endothelium-derived molecules may be predictive to organ injury. Heat shock protein (HSP) A12B is mainly located in endothelial cells, which can be detected in the plasma of septic patients. Whether it is correlated with prognosis of sepsis remains unclear.
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Role of Interleukin-17 in defense against pseudomonas aeruginosa infection in lungs.
Int J Clin Exp Med
PUBLISHED: 01-01-2014
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Pseudomonas aeruginosa may cause severe or even fatal infection in hosts with immunodeficiency. Interleukin-17 (IL-17) is a newly discovered pro-inflammatory cytokine, which promotes the recruitment and activation of neutrophils in the respiratory tract by inducing release of chemokine C-X-C.
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Upregulation of gelatinases and epithelial-mesenchymal transition in small airway remodeling associated with chronic exposure to wood smoke.
PLoS ONE
PUBLISHED: 01-01-2014
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Peribronchiolar fibrosis is an important feature of small airway remodeling (SAR) in cigarette smoke-induced COPD. The aim of this study was to investigate the role of gelatinases (MMP9, MMP2) and epithelial-mesenchymal transition (EMT) in SAR related to wood smoke (WS) exposure in a rat model.
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High-intensity interval training and ?-hydroxy-?-methylbutyric free acid improves aerobic power and metabolic thresholds.
J Int Soc Sports Nutr
PUBLISHED: 01-01-2014
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Previous research combining Calcium ?-hydroxy-?-methylbutyrate (CaHMB) and running high-intensity interval training (HIIT) have shown positive effects on aerobic performance measures. The purpose of this study was to examine the effect of ?-hydroxy-?-methylbutyric free acid (HMBFA) and cycle ergometry HIIT on maximal oxygen consumption (VO2peak), ventilatory threshold (VT), respiratory compensation point (RCP) and time to exhaustion (Tmax) in college-aged men and women.
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The pro-proliferative effects of nicotine and its underlying mechanism on rat airway smooth muscle cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Recent studies have shown that nicotine, a major component of cigarette smoke, can stimulate the proliferation of non-neuronal cells. Cigarette smoking can promote a variety of pulmonary and cardiovascular diseases, such as chronic obstructive pulmonary disease (COPD), atherosclerosis, and cancer. A predominant feature of COPD is airway remodeling, which includes increased airway smooth muscle (ASM) mass. The mechanisms underlying ASM remodeling in COPD have not yet been fully elucidated. Here, we show that nicotine induces a profound and time-dependent increase in DNA synthesis in rat airway smooth muscle cells (RASMCs) in vitro. Nicotine also significantly increased the number of RASMCs, which was associated with the increased expression of Cyclin D1, phosphorylation of the retinoblastoma protein (RB) and was dependent on the activation of Akt. The activation of Akt by nicotine occurred within minutes and depended upon the nicotinic acetylcholine receptors (nAchRs). Activated Akt increased the phosphorylation of downstream substrates such as GSK3?. Our data suggest that the binding of nicotine to the nAchRs on RASMCs can regulate cellular proliferation by activating the Akt pathway.
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[Extraction and analysis of solar-induced chlorophyll fluorescence of wheat with ground-based hyperspectral imaging system].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 12-28-2013
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Dataset simulated with FluorMOD and images of wheat in heading stage taken by a ground-based hyperspectral imaging system with 3.3 nm spectral resolution and 0. 71-0. 74 nm spectral sampling interval were used test the feasibility and accuracy of three FLD methods (named FLD, 3FLD and iFLD). The results show that when spectral resolution is 3.3 nm, solar-induced chlorophyll fluorescence could be extracted effectively in O2-A band (around 760 nm) instead of O2-B band (around 687 nm). As to the extraction results of data with noises, both FLD and 3FLD are stabler than iFLD method. The results of FLD tend to be higher than true value.
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The Glycosyltransferase Involved in Thurandacin Biosynthesis Catalyzes Both O- and S-Glycosylation.
J. Am. Chem. Soc.
PUBLISHED: 12-16-2013
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The S-glycosyltransferase SunS is a recently discovered enzyme that selectively catalyzes the conjugation of carbohydrates to the cysteine thiol of proteins. This study reports the discovery of a second S-glycosyltransferase, ThuS, and shows that ThuS catalyzes both S-glycosylation of the thiol of cysteine and O-glycosylation of the hydroxyl group of serine in peptide substrates. ThuS-catalyzed S-glycosylation is more efficient than O-glycosylation, and the enzyme demonstrates high tolerance with respect to both nucleotide sugars and peptide substrates. The biosynthesis of the putative products of the thuS gene cluster was reconstituted in vitro, and the resulting S-glycosylated peptides thurandacin A and B exhibit highly selective antimicrobial activity toward Bacillus thuringiensis.
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A Modified Molecular Beacons-Based Multiplex Real-Time PCR Assay for Simultaneous Detection of Eight Foodborne Pathogens in a Single Reaction and Its Application.
Foodborne Pathog. Dis.
PUBLISHED: 12-14-2013
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Abstract Foodborne disease outbreaks are often caused by one of the major pathogens. Early identification of the causal pathogen is crucial for disease control and prevention. We describe a real-time polymerase chain reaction (rtPCR) assay that can identify, in a single reaction, up to eight common foodborne bacterial pathogens, including Salmonella enterica subsp. enterica, Listeria monocytogenes, Escherichia coli O157, Vibrio parahaemolyticus, V. vulnificus, Campylobacter jejuni, Enterobacter sakazakii, and Shigella spp. This multiplex rtPCR assay takes advantage of modified molecular beacons and the multicolor combinational probe coding strategy to discriminate each pathogen and the homo-tag assisted non-dimer (HAND) system to prevent dimer formation. The detection limits of the assay ranged from 1.3×10(3) colony-forming units (CFU)/g stool (L. monocytogenes) to 1.6×10(4) CFU/g stool (Shigella spp.). The target genes were 100% specific as assessed on 986 reference strains covering 41 species since no cross-reactions were observed. The assay was applied to the detection of foodborne pathogens in 11,167 clinical samples and the results were compared with culture methods for further validation. The sensitivity and specificity of the rtPCR were 100% and 99%, respectively. When performed in a 96-well rtPCR system, more than 90 samples could be analyzed within 3?h. Given the high accuracy, sensitivity, specificity, and short turn-around time, the established assay could be used for the rapid and reliable identification of the causative pathogens responsible for a certain foodborne disease outbreak and rapid screening of these major foodborne pathogens in laboratory-based surveillance of outpatient clinical samples or even food samples.
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Effect of Chronic Exposure to Cigarette Smoke on Canonical Transient Receptor Potential Expression in Rat Pulmonary Arterial Smooth Muscle.
Am. J. Physiol., Cell Physiol.
PUBLISHED: 12-11-2013
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To clarify the possible mechanism of cigarette smoking-induced pulmonary hypertension, furthermore providing effective targets for prevention and treatment, the effects of chronic cigarette smoking on rat pulmonary arterial smooth muscle in vivo, and nicotine treatment on rat pulmonary arterial smooth muscle cells (PASMCs) in vitro were investigated. In this study, we demonstrated that chronic cigarette smoke (CS) exposure leads to rat weight loss, right ventricular hypertrophy, and pulmonary artery remodeling. A fluorescence microscope was used to measure intracellular calcium concentration ([Ca(2+)]i) in rat distal PASMCs. Results showed that basal [Ca(2+)]i and store-operated calcium entry (SOCE) level in PASMCs from 3 and 6 months CS exposed rats were higher than those in the unexposed control group, among which the increase in 6 months CS group was more significant than that in 3 months group. Furthermore, chronic exposure to CS also increased TRPC1 and TRPC6 expression in both mRNA and protein levels. Simultaneously, in vitro study showed that nicotine treatment (10 nM) significantly increased basal [Ca(2+)]i and SOCE in cultured rat distal PASMCs, accompanied with upregulated TRPC1 and TRPC6 expression. Knochdown of TRPCs with specific siRNA indicated nicotine increased basal [Ca(2+)]i and SOCE in PASMC is TRPCs dependent. These results suggested that chronic cigarette smoking induced vascular tone changes in pulmonary arteries and the development of pulmonary hypertension might largely relate to the enhanced Ca(2+) entry and upregulation of TRPC1 and TRPC6 in PASMCs, in which nicotine played an indispensable role.
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Interferon Regulatory Factor 8 Modulates Phenotypic Switching of Smooth Muscle Cells through Regulating the Activity of Myocardin.
Mol. Cell. Biol.
PUBLISHED: 11-18-2013
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Interferon regulatory factor 8 (IRF8), a member of IRF transcription factor family, was recently implicated in vascular diseases. In the present study, using the mouse left carotid artery wire injury model, we unexpectedly observed that the expression of IRF8 was greatly enhanced in SMCs by injury. Compared with wild-type controls, IRF8 global knockout mice exhibited reduced neointimal lesions and maintained SMC-marker gene expression. We further generated SMC-specific IRF8 transgenic mice using an SM22?-driven IRF8 plasmid construct. In contrast to the knockout mice, the SMCs-overexpressing IRF8 exhibited a synthetic phenotype and enhanced neointima formation in the mice. Mechanistically, IRF8 inhibited SMC-marker gene expression through regulating serum response factor (SRF) transactivation in a myocardin-dependent manner. Furthermore, co-immunoprecipitation assay indicated a direct interaction of IRF8 with myocardin, in which a specific region of myocardin was essential for recruiting acetyltransferase p300. Altogether, IRF8 is crucial in modulating SMC phenotype switching and neointima formation in response to vascular injury via direct interaction with SRF/myocardin complex.
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Modulation of Lipogenesis and Glucose Consumption in HepG2 Cells and C2C12 Myotubes by Sophoricoside.
Molecules
PUBLISHED: 11-04-2013
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Sophoricoside, an isoflavone glycoside isolated from Sophora japonica (Leguminosae), has been widely reported as an immunomodulator. In this study, the effects of sophoricoside on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were investigated. Treatment with sophoricoside at concentrations of 1-10 ?M inhibited lipid accumulation in HepG2 cells in a dose-dependent manner. At the same concentration range, no effect on cell viability was observed in the MTT assay. Inhibition of lipogenesis was associated with the downregulation of SREBP-1a, SREBP-1c, SREBP-2 and their downstream target genes (FAS, ACC, HMGR) as revealed by realtime quantitative PCR. The lipid-lowering effect was mediated via the phosphorylation of AMPK. Further investigation of the activities of this isoflavone showed that sophoricoside has the capability to increase glucose uptake by C2C12 myotubes. It also effectively inhibited the activities of ?-glucosidase and ?-amylase in vitro and remarkably lowered postprandial hyperglycaemia in starch-loaded C57BL6/J mice. These results suggest that sophoricoside is an effective regulator of lipogenesis and glucose consumption and may find utility in the treatment of obesity and type 2 diabetes.
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Interferon regulatory factor 9 protects against cardiac hypertrophy by targeting myocardin.
Hypertension
PUBLISHED: 10-21-2013
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Pathological cardiac hypertrophy is a major risk factor for heart failure. In this study, we identified interferon regulatory factor 9 (IRF9), a member of the IRF family, as a previously unidentified negative regulator of cardiac hypertrophy. The level of IRF9 expression was remarkably elevated in the hearts from animals with aortic banding-induced cardiac hypertrophy. IRF9-deficient mice exhibited pronounced cardiac hypertrophy after pressure overload, as demonstrated by increased cardiomyocyte size, extensive fibrosis, reduced cardiac function, and enhanced expression of hypertrophy markers, whereas transgenic mice with cardiac-specific overexpression of murine IRF9 exhibited a significant reduction in the hypertrophic response. Mechanistically, IRF9 competes with p300 for binding to the transcription activation domain of myocardin, a coactivator of serum response factor (SRF). This interaction markedly suppresses the transcriptional activity of myocardin because IRF9 overexpression strongly inhibits the ability of myocardin to activate CArG box-dependent reporters. These results provide compelling evidence that IRF9 inhibits the development of cardiac hypertrophy by suppressing the transcriptional activity of myocardin in the heart.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.