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Cytokine and apoptosis gene polymorphisms influence the outcome of hepatitis C virus infection

Hepatobiliary & Pancreatic Diseases International 2011年第3期10卷 280-288页

作者： Leila Ksiaa Cheikhrouhou Imen Sfar Hajer Aounallah-Skhiri Houda Aouadi Salwa Jendoubi-Ayed Taieb Ben Abdallah Khaled Ayed yousr lakhoua-gorgi Immunology Research Laboratory of Kidney Transplantation and Immunopathology (Laboratoire de Recherche:LR03SP01) Charles Nicolle Hospital National Health Institute

BACKGROUND:Hepatitis C virus (HCV) infection is thought to be chronic and the factors leading to viral clearance or persistence are poorly understood.This study was undertaken to investigate the possibility of a significant relationship between the spontaneous clearance or the persistence of hepatitis C virus (HCV) infection and cytokine and apoptosis gene polymorphisms in Tunisian patients on hemodialysis.METHODS:Polymorphisms of the genes IL-1 (-889 IL-1α,-511 and +3954 IL-1β,IL-1Ra),IL-18 (-137 and-607),IL-12 (-1188) and Apo1/Fas (-670) were determined by PCR-RFLP,PCR-SSP and PCR-VNTR in 100 healthy blood donors and 100 patients infected with HCV and undergoing hemodialysis.The patients were classified into two groups:G1 consisted of 76 active chronic hepatitis patients (positive for HCV RNA) and G2 consisted of 24 hemodialysed patients who spontaneously eliminated the virus (negative for HCV RNA).RESULTS:The frequency of genotype association [-137GC/-607CA] IL-18 was higher in G2 (41.7%) than in G1 (15.8%) (P=0.008;OR=0.26;95% CI,0.10-0.73).We also found a higher frequency of the AA genotype of the Apo1/Fas gene in G2 (41.6%) than in G1 (17.5%) (P=0.026;OR=3.49;95% CI,1.13-10.69).Adjustment for known covariate factors (age,gender and genotype) confirmed these univariate findings and revealed that the genotype association GC-CA of the (-137 and-607) IL-18 gene and the AA genotype of the Apo1/Fas gene were associated with the clearance of HCV (P=0.041 and 0.017,respectively).CONCLUSION:The two genotypes GC-CA of the (-137 and-607) IL-18 polymorphism and the AA genotype of the Apo1/Fas gene influence the outcome of HCV infection in Tunisian patients on hemodialysis.

关键词： hepatitis C virus spontaneous clearance cytokine gene polymorphisms Apo1/Fas gene polymorphisms

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Natural evolution of hepatitis C virus infection in hemodialysis Tunisian patients and CTLA-4 SNP's

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World Journal of Gastroenterology 2015年第35期21卷 10150-10158页

作者： Leila Ksiaa Cheikhrouhou yousr lakhoua-gorgi Imen Sfar Salwa Jendoubi-Ayed Houda Aouadi Mouna Makhlouf Khaled Ayed Taieb Ben Abdallah Immunology Research Laboratory of Kidney Transplantation and Immunopathology Laboratoire de Recherche Laboratory of Immunology Charles Nicolle Hospital

AIM: To analyze the polymorphisms of CTLA-4 gene involved in the response against hepatitis C virus(HCV) infection.METHODS: We recruited 500 hemodialysed patients from several hemodialysis centers, all HCV-antibody positive, spread over different regions of Tunisia, as part of a national survey in 2008 conducted in the laboratory of immunology at the Charles Nicolle hospital Tunisia, classified into two groups G1(PCR+) and G2(PCR-) according to the presence or absence of viral RNA. Of these patients, 307 were followed prospectively on a viral molecular level over a period from 2002 to 2008, divided into two groups based on the persistence and viral clearance. PCR-RFLP was performed for the analysis of SNPs(+49) A/G and(+6230) G/A CTLA-4 for these 500 patients and 358 healthy controls.RESULTS: Analysis of clinical and virological charac-teristics of our cohort suggests a nosocomial infection in our hemodialysed patients with transfusion history as a primary risk factor and a predominance of genotype 1b. The haplotype analysis revealed an increase of frequencies of GG(+49)/(CT60) CTLA-4 in the entire patients group compared to controls(P = 0.0036 and OR = 1.42; 95%CI: 1.12-1.79, respectively). This haplotype is therefore associated with susceptibility to HCV infection. CONCLUSION: Our study suggests a possible role of CTLA-4 polymorphisms in the outcome of HCV infection in the Tunisian hemodialysed population.

关键词： Hepatitis C virus Hemodialysis Natural evolution C

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Association of Fas/Apo1 gene promoter (-670 A/G) polymorphism in Tunisian patients with IBD

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World Journal of Gastroenterology 2009年第29期15卷 3643-3648页

作者： Walid Ben Aleya Imen Sfar Leila Mouelhi Houda Aouadi Mouna Makhlouf Salwa Ayed-Jendoubi Samira Matri Azza Filali Taoufik Najjar Taeib Ben Abdallah Khaled Ayed yousr gorgi Laboratory of Immunology EPS Charles Nicolle 1006 Bab Saadoun Tunis 1006 Tunisia Department of Gastroenterology EPS Charles Nicolle Tunis 1006 Tunisia Department of Gastroenterology La Rabta Tunis 1006 Tunisia

AIM: To detect a possible association between the polymorphism of the (-670 A/G) Fas/Apo1 gene promoter and susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) in the Tunisian population. METHODS: The (-670 A/G) Fas polymorphism was analyzed in 105 patients with CD, 59 patients with UC, and 100 controls using the polymerase chain reaction restriction fragment length polymorphism method. RESULTS: Significantly lower frequencies of the Fas -670 A allele and A/A homozygous individuals were observed in CD and UC patients when compared with controls. Analysis of (-670 A/G) Fas polymorphism with respect to sex in CD and UC showed a significant difference in A/A genotypes between female patients and controls (P corrected = 0.004 in CD patients and P corrected = 0.02 in UC patients, respectively). Analysis also showed a statistically significant association between genotype AA of the (-670 A/G) polymorphism and the ileum localization of the lesions (P corrected = 0.048) and between genotype GG and the colon localization (Pcorrected = 0.009). The analysis ofinflammatory bowel disease patients according to clinical behavior revealed no difference. CONCLUSION: Fas-670 polymorphism was associated with the development of CD and UC in the Tunisian population.

关键词：溃疡性结肠炎多态性分析基因启动子突尼斯患者限制性片段长度多态性 Fas 协会

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Lymphoid tyrosine phosphatase R620W variant and inflammatory bowel disease in Tunisia

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World Journal of Gastroenterology 2010年第4期16卷 479-483页

作者： Imen Sfar Walid Ben Aleya Leila Mouelhi Houda Aouadi Thouraya Ben Rhomdhane Mouna Makhlouf Salwa Ayed-Jendoubi Houda Gargaoui Taoufik Najjar Taieb Ben Abdallah Khaled Ayed yousr gorgi Laboratory of Immunology Charles Nicolle HospitalTunis 1006Tunisia Department of Gastroenterology Charles Nicolle HospitalTunis 1006Tunisia

AIM:To assess the possible association between PTPN22(R620W) gene polymorphism and inflammatory bowel disease(IBD).METHODS:One hundred and sixty-four patients with IBD 105 Crohn's disease(CD) and 59 ulcerative colitis(UC) and 100 healthy controls were recruited.Genotyping of the PTPN22 gene 1858C→T polymorphism was performed by restriction fragment length polymorphism-polymerase chain reaction with Rsa Ⅰ digestion.RESULTS:The genotypic and allelic frequencies of(R620W) PTPN22 gene polymorphism reveal a significant association of the PTPN22 620-W allele with IBD,compared to the healthy control group(OR:17.81,95% CI:4.18-21.86,P = 0.00001).Nevertheless,nodifference in this polymorphism was found between CD and UC patients.No significant association was found between the frequencies of genotypes of the PTPN22 gene with either the clinical features such as sex,age,age at disease onset,and extent of colitis,or the production of serological markers(anti-Saccharomyces cerevisiae antibody in CD and perinuclear anti-neutrophil cytoplasmic antibody in UC).CONCLUSION:These observations confirm the association of IBD susceptibility with the PTPN22 1858T(620-W) allele in Tunisian patients.

关键词： Inflammatory bowel disease PTPN22 Genetic polymorphism Genetic susceptibility

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COVID-19 and congenital heart disease:a case series of nine children

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World Journal of Pediatrics 2021年第1期17卷 71-78页

作者： Elmira Haji Esmaeil Memar Babak Pourakbari Mojtaba gorgi Meisam Sharifzadeh Ekbatani Amene Navaeian Mahmoud Khodabandeh Shima Mahmoudi Setareh Mamishi Pediatrics Center of Excellence Children's Medical CenterTehran University of Medical SciencesTehranIran Pediatric Infectious Disease Research Center Tehran University of Medical ScienceTehranIran Division of Pediatric Intensive Care Unit Pediatrics Center of ExcellenceChildren's Medical CenterTehran University of Medical SciencesTehranIran Department of Infectious Diseases Pediatrics Center of ExcellenceChildren's Medical CenterTehran University of Medical SciencesTehranIran

Background Coronavirus disease 2019(COVID-19)is the current pandemic disease without any vaccine or efficient treat-ment to rescue the patients.Underlying diseases predispose the patients to a more severe disease and to a higher mortality rate.However,little evidence exists about COVID-19 outcomes in the pediatric population with congenital heart disease(CHD).Here,we report nine children with COVID-19 and concomitant CHD.Methods Our study included nine children with COVID-19 and concomitant CHD who were admitted to Children Medical Center Hospital during March and April 2020.The patients were classified based on the final outcome(death),and their clinical sign and symptoms,type of CHD,and drugs administered were compared.Results Among the nine patients,two died and we compared different characteristics,laboratory results and clinical findings of these cases based on the mortality.The deceased patients had severe types of CHD,worse arterial blood gases,severe clinical symptoms,higher mean level of partial thromboplastin time and C-reactive protein,and required more medications.Conclusions The present study showed that the general consideration of mild COVID-19 in children does not include patients with CHD and that it is necessary to pay greater attention to children with CHD to determine guidelines for treatment of COVID-19 in these children.Owing to the scarcity of CHD and COVID-19,we reported only nine cases.However,further studies are highly required in this regard.

关键词： Congenital heart disease Coronavirus disease 2019 Pediatrics

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Antioxidant Activity of Pomegranate Juice and Punicalagin

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Natural Science 2016年第6期8卷 235-246页

作者： Akram Aloqbi Ulfat Omar Marwa yousr Mary Grace Mary Ann Lila Nazlin Howell Biology Department Faculty of Sciences and Arts-Alkamel University of Jeddah Jeddah KSA Division of Nutrition and Metabolism Faculty of Health and Medical Sciences University of Surrey Guildford Surrey UK Present Address: Biochemistry Department Faculty of Science King Abdulaziz University Jeddah KSA Plants for Human Health Institute Kannapolis NC USA

Plant polyphenols are reported to have bioactive properties, which may be used for protection against diseases. Therefore, the aim of this research was to investigate the antioxidant activities of a pomegranate tannin polyphenol compound, punicalagin and pomegranate juice. The presence of punicalagin in pomegranate husk (US) and pomegranate juice (US & UK) was compared with a punicalagin standard using high performance liquid chromatography (HPLC) and liquid chromatography-mass spectroscopy (LC-MS) which are highly sensitive and selective analytical methods for the separation and identification of phenolic compounds and anthocyanins. Antioxidant mechanisms involving DPPH radical scavenging activity, hydrogen peroxide scavenging, ferrous chelating and reducing ability were also studied on pomegranate juice and standard punicalagin. The present study shows a high degree of similarity of HPLC and LC-MS results between the punicalagin commercial standard (Sigma Aldrich) and US pomegranate husk extracted with methanol. In contrast, in the methanol juice extract obtained from US and UK, higher hydrogen peroxide scavenging activity was achieved by 0.1 mg/ml from both punicalagin and pomegranate juice when compared with butylated hydroxytoluene (BHT) or trolox (p ≤ 0.01). Punicalagin and pomegranate juice exhibited ferrous chelating ability significantly lower than Ethylenediaminetetraacetic acid. These findings confirmed that punicalagin was present in pomegranate husk compared to pomegranate juice, as measured using a punicalagin standard. The antioxidant mechanism experiments concluded that, the pomegranate juice has a significantly higher radical scavenging activity in comparison with punicalagin (p ≤ 0.01). However, punicalagin showed significant ferrous chelating activity and reducing power ability in a dose-dependent manner as compared with pomegranate juice.

关键词： HPLC LC-MS Punicalagin Radical Scavenger Ferrous Ion Chelating

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The Monitoring Interest of BK Virus Load in Renal Allograft Tunisian Recipients: Prospective Study

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Open Journal of Organ Transplant Surgery 2012年第4期2卷 56-61页

作者： yousr gorgi Mohamed M. Bacha Imen Sfar A. Ben Mohamed Hajer Aounallah-Skhiri Tarak Dhaouadi Rafika Bardi N. Skouri Ezzeddine Abderrahim M. Makhlouf T.Ben Romdhane S. Jendoubi-Ayed K. Ayed Taieb Ben Abdallah 1Immunology Research Laboratory (LR03SP01). University Tunis El Manar Charles Nicolle Hospital. Tunis.Tunisia Department of Internal Medecine. Charles Nicolle Hospital. Tunis.Tunisia Immunology Research Laboratory (LR03SP01). University Tunis El Manar Charles Nicolle Hospital. Tunis.Tunisia National Public Health Institute. Tunisia

BK virus (BKV) may cause nephropathy in renal transplant recipients receiving immunosuppressive therapy, resulting in renal dysfunction and, possibly graft loss. However, the positive and negative predictive values of BK viral load are still controversial. In this prospective, single-center study, BKV DNA was measured 1, 3 and 6 months after transplantation. The viral load in urine and plasma was quantified with the real-time Q-PCR (Argen kit) in 73 renal allograft recipients Three of them showed acute rejection. To determine the cutoff value of viral load, 60 sera samples of healthy blood donors, matched for age and sex, were tested. The mean plasmatic viral load one month post-transplantation was statistically higher in renal transplant recipients (17.23 copies/ml) compared to that in controls (2 copies/ml) (p: 0.06). This difference of the distribution of viremia values is more evident in the third and sixth month (p: 0.002 and 0.010 respectively). Furthermore, analysis of the kinetic of viral load revealed an average rise of viremia at 3 months (1589.14 copies/ml) followed by its decrease at 6 months (249.75 copies/ml). However, the difference was not statistically significant. The same is true for the distribution of values of viruria and in all cases the average viral load was statistically higher in urine than in plasma. In addition, this study did not shown significant relationsheep between viremia/viruria and the occurrence of acute rejection, the renal function deterioration, the source of allograft or immunosuppressive therapy protocol. If the results of this study demonstrate the importance of the replication of BKV in renal transplant patients from the first month compared to that in immunocompetent subjects, the screening of the DNA of this virus does not appear to have a prognostic value in the occurrence of acute rejection. However, the plasma and urine monitoring of BKV load beyond 6 months , not appear to exclude the relationsheep between these two biomarkers and the occurrence of chronic graft

关键词： BK Virus Renal Transplantation Urine and Plasma Viral Load Allograft Dysfunction

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