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1Lipopolysaccharide induces and activates the Nalp3 inflammasome in the liver显示文摘AIM:To examine the activation of the Nalp3 inflammasome and its downstream targets following lipopolysaccharide(LPS) -induced stimulation in the liver. METHODS:Six-to-eight-week-old C57BL/6 chow fed mice were injected intraperitoneally with 0.5μg/g bodyweight LPS and sacrificed 2,4,6,18 or 24 h later. LPS-induced liver damage was confirmed by a biochemical assay to detect alanine aminotransferase(ALT) levels.To determine if LPS stimulation in the liver led to activation of the inflammasome,real-time quantitative polymerase chain reaction was used to evaluate the mRNA expression of components of the Nalp3 inflammasome.Enzyme-linked immunosorbent assays were used to determine the protein expression levels of several downstream targets of the Nalp3 inflammasome,including caspase-1 and two cytokine targets of caspase-1,interleukin(IL) -1βand IL-18. RESULTS:We found that LPS injection resulted in liver damage as indicated by elevated ALT levels.This was associated with a significant increase in both mRNA and protein levels of the proinflammatory cy-tokine tumor necrosis factor(TNF) -αin the liver,as well as increased levels of TNFs in serum.We showed that LPS stimulation led to upregulation of mRNA levels in the liver for all the receptor components of the inflammasome,including Nalp3,Nalp1,pannexin-1 and the adaptor molecule apoptosis-associated specklike,caspase recruitment domain-domain containing protein.We also found increased levels of mRNA and protein for caspase-1,a downstream target of the inflammasome.In addition,LPS challenge led to increased levels of both mRNA and protein in the liver for two cytokine targets of caspase-1,IL-1βand IL-18. Interestingly,substantial baseline expression of pre-IL1βand pre-IL-18 was found in the liver.Inflammasome and caspase-1 activation was indicated by the significant increase in the active forms of IL-1βand IL-18 after LPS stimulation. CONCLUSION:Our results show that the Nalp3 inflammasome is upregulated and activated in the liver in response to LPS stimulation.Michal Ganz Timea Csak Bharath Nath Gyongyi Szabo 2011World Journal of Gastroenterology2011,17,43:14
2High fat diet feeding results in gender specific steatohepatitis and inflammasome activation显示文摘AIM:To develop an animal model that encompasses the different facets of non-alcoholic steatohepatitis(NASH),which has been a challenge.METHODS:In this study,we used a high fat diet(HFD)feeding supplemented with fructose and sucrose in the water mimicking the high-fructose corn syrup that is abundant in the diet in the United States.We used C57Bl/6 wild-type mice for short and long-term feedings of 6 and 16 wk respectively,and evaluated the extent of liver damage,steatosis,and inflammasome activation.Our methods included histopathological analysis to assess liver damage and steatosis,which involved H and E and oil-red-o staining;biochemical studies to look at ALT and triglyceride levels;RNA analysis using quantitative polymerase chain reaction;and cytokine analysis,which included the enzyme-linked immunosorbent assay method to look at interleukin(IL)-1βand tumor necrosis factor-α(TNFα)levels.Furthermore,at each length of feeding we also looked at insulin resistance and glucose tolerance using insulin tolerance tests(ITT)and glucose tolerance tests.RESULTS:There was no insulin resistance,steatosis,or inflammasome activation at 6 wk.In contrast,at16 wk we found significant insulin resistance demonstrated by impaired glucose and ITT in male,but not female mice.In males,elevated alanine aminotransferase and triglyceride levels,indicated liver damage and steatosis,respectively.Increased liver TNFαand monocyte chemoattractant protein-1 mRNA and protein,correlated with steatohepatitis.The inflammasome components,adaptor molecule,Aim2,and NOD-like receptor 4,increased at the mRNA level,and functional inflammasome activation was indicated by increased caspase-1 activity and IL-1βprotein levels in male mice fed a long-term HFD.Male mice on HFD had increasedα-smooth muscle actin and pro-collagen-1 mRNA indicating evolving fibrosis.In contrast,female mice displayed only elevated triglyceride levels,steatosis,and no fibrosis.CONCLUSION:Our data indicate gender differences in NASH.Male mice fed a long-term HFD display steatohepatitis and inflammasome activation,whereas female mice have steatosis without inflammation.Michal Ganz Timea Csak Gyongyi Szabo 2014World Journal of Gastroenterology2014,20,26:8
3Inflammasomes in liver diseases显示文摘Gyongyi Szabo Timea Csak 2012Journal of Hepatology2012,,3:5
4IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice显示文摘Petrasek Jan Bala Shashi Csak Timea Lippai Dora Kodys Karen Menashy Victoria Barrieau Matthew Min So-Yun Kurt-Jones Evelyn A Szabo Gyongyi 2012EN2012,,10:4
5STING-IRF3 pathway links endoplasmic reticulum stress with hepatocyte apoptosis in early alcoholic liver disease显示文摘Jan Petrasek Arvin Iracheta-Vellve Timea Csak Abhishek Satishchandran Karen Kodys Evelyn A. Kurt-Jones Katherine A. Fitzgerald Gyongyi Szabo 2013Proceedings of the National Academy of Sciences2013,,41:2
6Autonomic and sensory nerve dysfunction in primary biliary cirrhosis显示文摘AIM: Cardiovascular autonomic and peripheral sensory neuropathy is a known complication of chronic alcoholic and non-alcoholic liver diseases. We aimed to assess the prevalence and risk factors for peripheral sensory nerve and autonomic dysfunction using sensitive methods in patients with primary biliary cirrhosis (PBC). METHODS: Twenty-four AMA M2 positive female patients with clinical, biochemical and histological evidence of PBC and 20 age matched healthy female subjects were studied. Five standard cardiovascular reflex tests and 24-h heart rate variability (HRV) analysis were performed to define autonomic function. Peripheral sensory nerve function on median and peroneal nerves was characterized by current perception threshold (CPT), measured by a neuroselective diagnostic stimulator (Neurotron, Baltimore, MD). RESULTS: Fourteen of 24 patients (58%) had at least one abnormal cardiovascular reflex test and thirteen (54%) had peripheral sensory neuropathy. Lower heart rate response to deep breathing (P=0.001), standing (P=0.03) and Valsalva manoeuvre (P=0.01), and more profound decrease of blood pressure after standing (P=0.03) was found in PBC patients than in controls. As a novel finding we proved that both time domain and frequency domain parameters of 24-h HRV were significantly reduced in PBC patients compared to controls. Each patient had at least one abnormal parameter of HRV. Lower CPT values indicated hyperaesthesia as a characteristic feature at peroneal nerve testing at three frequencies (2000 Hz: P=0.005; 250 Hz: P=0.002; 5 Hz: P=0.004) in PBC compared to controls. Correlation of autonomic dysfunction with the severity and duration of the disease was observed. Lower total power of HRV correlated with lower CPT values at median nerve testing at 250 Hz (P = 0.0001) and at 5 Hz (P=0.002), as well as with those at peroneal nerve testing at 2000 Hz (P=0.01). CONCLUSION: Autonomic and sensory nerve dysfunctions are frequent in PBC. Twenty-four-hour HRV analysis is more sensitive than standard cardiovascular tests for detecting of both parasympathetic and sympathetic impairments. Our novel data suggest that hyperaesthesia is a characteristic feature of peripheral sensory neuropathy and might contribute to itching in PBC. Autonomic dysfunction is related to the duration and severity of PBC.Katalin Keresztes lldikó Istenes Aniko Folhoffer Peter L Lakatos Andrea Horvath Timea Csak Peter Varga Peter Kempler Ferenc Szalay 2004World Journal of Gastroenterology2004,10,20:2
7Holmes-Adie syndrome, autoimmune hepatitis and celiac disease: A case report显示文摘与 Holmes-Adie 的下列症状介绍的一个 35 岁的女病人:畏光,对光无答复的左学生的增大,阿奇里斯无反射。毛果芸香硷测试是阳性的。没有肿瘤或另外的神经病学的反常被发现。她有自体免疫的肝炎的 19 年的历史。闪光在上面被观察跟随每 3 交货。在 31 的年龄,她与腹泻和重量损失介绍了。腹的肿瘤被超声检测。通过手术移开的肿瘤是组织学地良性的 mes 伤寒多膀胱的淋巴管瘤。同时,乳糜泻是 diagnosed.Gluten 免费的饮食导致了乳糜泻,然而并非自体免疫的肝炎的重要改进。自治神经病被标准心血管的测试证明。病人是为为乳糜泻特征、为在自体免疫的肝疾病经常的 HLA DR3 B8 异质接合的 HLA DQ2 抗原的一个同型结合的搬运人。我们有自体免疫的肝炎和乳糜泻的 Holmes-Adie 的协会上的新奇观察为为在有 mes 伤寒的一个病人在场的所有三个实体的一个普通免疫学的背景是暗示的多膀胱的淋巴管瘤。Timea Csak Aniko Folhoffer Andrea Horvath Judit Halász Csaba Diczházi Zsuzsa Schaff Ferenc Szalay 2006World Journal of Gastroenterology2006,12,9:1
8Angiogene- sis in rheumatoid arthritis 显示文摘ZOLTAN S TIMEA B GYORGY P 2009Autoimmunity2009,42,7:1
9Molecular chiral recognition in supercritical solvents显示文摘Elemer F Maria A Timea S 1994Tetrahedron Lett1994,35,2:1
10Effectiveness of cervical cerclage for a sonographically shortened cervix: a systematic review and meta-analysis 显示文摘Timea Belej-Rak Nan Okun Rory Windrim 2003Am J Obstet Gynecol2003,189,6:1
11Effect of two Chinese herbs (Astragalus radix and Scutellaria radix ) on non-spe- cific immune response of tilapia,Oreochromis niloticus显示文摘YIN G J GALINA J TIMEA R 2006Aq- uaculture2006,253,1:1
12The role of hyalu-ronic acid binding assay in choosing the fertilization method for patients undergoing 1VF for unexplained infertility 显示文摘Kovacs P Timea Kovata T Sajgo A 2011Assis- ted Reproduction Technologies2011,28,:1
13Comparison of serum and follicu- lar fluid hormone levels with recombinant and urinary human ehorion- ic gonadotropin during in vitro fertilization 显示文摘Peter K Timea K Artur B 2008Fertil Steril2008,90,:1
14Evidence-based pharmacological treatment of neuropathic pain syndromes显示文摘Beniczky S Tajti J Timea Varga E 2005Journal of Neural Transmission2005,,112:1
15Molecular chiral recognition in supercritical solvents 显示文摘Elemer F Maria A Timea S 1994Tetrahedron Lett1994,35,2:1
16Molecular chiral recognition in supercritical solvents 显示文摘Elemer F Maria A Timea S 1994Tetrahedron Letters1994,35,2:1
17Effect of two Chinese herbs (Astragalus radix and Scutellaria radix) on non-specific immune response of tilapia,Oreochromis niloticus显示文摘Guojun Yin Galina Jeney Timea Racz 2006Aquaculture2006,253,:1
18Evidence based pharmacological treatment of neuropathic pain syndromes 显示文摘Beniczky S Tajti J Timea Varga E 2005J Neural Transm2005,112,:1
19Training Multi-Layer Perceptron with Enhanced Brain Storm Optimization Metaheuristics显示文摘In the domain of artificial neural networks,the learning process represents one of the most challenging tasks.Since the classification accuracy highly depends on theweights and biases,it is crucial to find its optimal or suboptimal values for the problem at hand.However,to a very large search space,it is very difficult to find the proper values of connection weights and biases.Employing traditional optimization algorithms for this issue leads to slow convergence and it is prone to get stuck in the local optima.Most commonly,back-propagation is used formulti-layer-perceptron training and it can lead to vanishing gradient issue.As an alternative approach,stochastic optimization algorithms,such as nature-inspired metaheuristics are more reliable for complex optimization tax,such as finding the proper values of weights and biases for neural network training.In thiswork,we propose an enhanced brain storm optimization-based algorithm for training neural networks.In the simulations,ten binary classification benchmark datasets with different difficulty levels are used to evaluate the efficiency of the proposed enhanced brain storm optimization algorithm.The results show that the proposed approach is very promising in this domain and it achieved better results than other state-of-theart approaches on the majority of datasets in terms of classification accuracy and convergence speed,due to the capability of balancing the intensification and diversification and avoiding the local minima.The proposed approach obtained the best accuracy on eight out of ten observed dataset,outperforming all other algorithms by 1-2%on average.When mean accuracy is observed,the proposed algorithm dominated on nine out of ten datasets.Nebojsa Bacanin Khaled Alhazmi Miodrag Zivkovic K.Venkatachalam Timea Bezdan Jamel Nebhen 2022Computers, Materials & Continua2022,,2:1
20Effect of two Chinese Scutellaria radix) on non- specific immune response of tilapia, Oreochromis nilot- icus显示文摘Yin G J Galina J Timea R herbs (Astragalus radix and 2006Aquaculture2006,253,14:1
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