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1.
Artigo em Inglês | MEDLINE | ID: mdl-38303523

RESUMO

BACKGROUND: One of the main reasons for cancer resistance to chemotherapy is the presence of cancer stem cells (CSCs) in cancer tissues. It is also believed that CSCs are the unique originators of all tumor cells. On the other hand, the Epithelial-Mesenchymal Transition pathway (EMT) can act as the main agent of metastasis. Therefore, it is possible that targeting CSCs as well as the EMT pathway could help in cancer therapy. Considering that CSCs constitute only a small percentage of the total tumor mass, enrichment before study is necessary. In our previous study, CSCs were enriched in the human colon cancer cell line HT29 by induction of EMT. These CSC-enriched HT29 cells with mesenchymal morphology were named "HT29-shE". In the present study, these cells were used to investigate the effect of pioglitazone (Pio) and Cetuximab (Cet) in order to find CSC and EMT targeting agents. METHOD: The viability and IC50 rate of cells treated with different concentrations of Pio and Cet were evaluated using the MTT test. EMT and CSC markers and cell morphology were assessed in Pio and Cet treated and untreated HT29-shE cells using flow cytometry, realtime PCR, immunocytochemistry, and microscopic monitoring. RESULTS: The findings showed that Pio and Cet at concentrations of 250 µM and 40 µg/ml, respectively, decrease cell viability by 50%. Also, they were able to reduce the expression of CSC markers (CD133 and CD44) in the CSC enriched HT29 cell line. Furthermore, Pio and Cet could efficiently reduce the expression of vimentin as a mesenchymal marker and significantly upregulate the expression of E-cadherin as an epidermal marker of EMT and its reverse mesenchymal-- to-epithelial transition (MET). In addition, the mesenchymal morphology of HT29-shE changed into epithelial morphology after Cet treatment. CONCLUSION: Pio and Cet could inhibit EMT and reduce CSC markers in the EMT induced/CSC enriched cell line. We expect that focus on finding EMT/CSC-targeting agents like these drugs can be helpful for cancer treatment.

2.
Sci Rep ; 13(1): 21743, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38065969

RESUMO

Gastric cancer is a complex heterogeneous disease with different molecular subtypes that have clinical implications. It is characterized by high mortality rates and limited effective therapies. Microsatellite instability (MSI) has been recognized as a subgroup with a good prognosis based on TCGA and ACRG categorizations. Besides its prognostic and predictive value, gastric cancers with high MSI exhibit different clinical behaviors. The prevalence of high MSI has been assessed in gastric cancer worldwide, especially in East Asia, but there is a lack of such information in the Middle East. Therefore, this study aimed to investigate the incidence and status of MSI in Iranian gastric cancer patients using 53 samples collected from 2015 to 2020 at Taleghani Hospital Medical Center. DNA from tumoral and normal tissues were extracted and assessed through multiplex-PCR based on five mononucleotide repeats panel. Clinicopathological variables, including age, sex, Lauren classification, lymph node involvement, TNM stage, differentiation, localization, and tumor size, were also analyzed. With 2 males and 2 females, high microsatellite instability represented a small subgroup of almost 7.5% of the samples with a median age of 60.5 years. High microsatellite instability phenotypes were significantly associated with patients aged 68 years and older (p­value of 0.0015) and lower lymph node involvement (p­value of 0.0004). Microsatellite instability was also more frequent in females, with distal gastric location, bigger tumor size, and in the intestinal type of gastric cancer rather than the diffuse type.


Assuntos
Instabilidade de Microssatélites , Neoplasias Gástricas , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Incidência , Irã (Geográfico) , Prognóstico , Repetições de Microssatélites/genética
3.
Adv Biomed Res ; 12: 54, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37057238

RESUMO

Background: Ulcerative colitis (UC) and Crohn's disease (CD) are two major types of inflammatory bowel diseases (IBDs). Toll-like receptors (TLRs) are expressed in the innate immune system compartments, in charge of identifying a wide range of microorganisms. The aim of the present study was to evaluate the expression of TLR-2, -7, and -8 in peripheral blood mononuclear cells (PBMC) of UC patients as a novel non-invasive primary inflammation sensor for monitoring the clinical course of UC candidates. Materials and Methods: In this cross-sectional study, total RNA was extracted from the PBMC of 42 UC patients along with 20 healthy donors. The mRNA levels of TLR-2, -7, and -8 were assessed using the quantitative real-time polymerase chain (qRT-PCR) reaction. Results: The present research study demonstrated no significant changes in TLR-2 mRNA expression in UC patients in comparison with the control group (P = 0.1264), whereas significant elevation (P = 0.0008) was distinguished in the TLR-7 expression of UC participants specifically during the remission course compared with healthy donors and flareup patients (P = 0.0004 and P = 0.0063, respectively). The last selected TLR, TLR-8 was not shown remarkable changes either between UC patients and the control group or between clinical courses of the disease. Conclusion: Here, among three nominated TLRs for predicting UC patients, TLR-7 was potentially selected according to the significant difference in mRNA expression in flareup UC patients and control donors. TLR-7 could be used as a novel non-invasive biomarker for monitoring UC patients in the active course of the disease.

4.
Int J Prev Med ; 13: 66, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35706852

RESUMO

Background: Nutrition-related factors have been of great interest as one of risk factors of biliary stones. This study evaluated the association of dietary patterns with biliary stone among Iranians. Methods: This is a hospital-based case-control study, which was conducted in a general hospital in Tehran, Iran. A total of 110 patients with gallstone or common bile duct (CBD) stone confirmed by Ultrasonography within the last 6 months before collecting data were recruited. Controls were age-matched patients admitted to the other wards of the same hospital for a broad spectrum of disorders including traumas and orthopedic conditions, or elective surgeries, or throat/ear/nose disease and had no gallbladder disorders, participated in this study. We used a valid and reliable food frequency questionnaire to assess dietary intakes of participants. Dietary patterns were determined by factor analysis. Results: By design, age was similar in both groups (57.66 ± 16.39 years vs. 56.00 ± 10.64 years in cases and controls, respectively). Two dietary patterns were extracted; "Unhealthy" (high consumption of artificial juice, processed meats, refined grains, sweets and desserts, pickles, snacks, and red meats), and "Healthy" (high consumption of vegetable oils, vegetables, fruits, fish, legumes, and nuts, as well as low consumption of hydrogenated fats and salt). Participants in the highest tertile of "Healthy" dietary pattern were significantly less likely to have the gallstones disease (OR: 0.33, 95% CI = 0.120.89) compared to the reference group (low tertile of "Healthy" dietary pattern) (P = 0.02). Conclusions: High consumption of vegetable oils, vegetables, fruits, fish, legumes, and nuts, as well as low consumption of hydrogenated fats and salt in context of healthy dietary pattern are inversely associated with risk of gallstones.

5.
Arab J Gastroenterol ; 22(3): 220-223, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34538760

RESUMO

BACKGROUND AND STUDY AIMS: Unawareness about atypical forms of celiac disease (CD) leads to the underdiagnoses of CD. This study has investigated the prevalence of CD in patients with atypical presentations, such as idiopathic low bone mineral density (ILBMD) and dyspepsia, in the Iranian population. PATIENTS AND METHODS: Two separate groups of patients who have been diagnosed with dyspepsia and ILBMD (including either osteopenia or osteoporosis of unknown cause) were screened for CD during 2016-2019. Patients were serologically screened by means of IgA anti-tissue transglutaminase (IgA anti-tTG); in case of positive results, the patients underwent endoscopic intestinal biopsy to confirm the diagnosis of CD. RESULTS: Of 200 patients with ILBMD, six (3%) had a positive result for IgA anti-tTG; in five cases (2.5%), duodenal histology confirmed the CD diagnosis. Of 290 patients with dyspepsia, 25 (8.6%) had a positive result for anti-tTG IgA; nine cases (3.7%) were histologically compatible with CD. No significant differences were found between the two groups of patients. CONCLUSIONS: The prevalence of CD in patients with atypical presentations, such as ILBMD and dyspepsia, is consistent (pvalue = 0.788) and higher than that in the general population (p value = 0.001); therefore, screening program for CD in these patients is highly recommended.


Assuntos
Doença Celíaca , Autoanticorpos , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Humanos , Imunoglobulina A , Irã (Geográfico)/epidemiologia , Prevalência
6.
Gastroenterol Hepatol Bed Bench ; 13(4): 396-399, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33244384

RESUMO

Diarrhea is common after liver transplant. Although the majority of episodes are experienced during the first year of transplantation, they can occur any time after the procedure. Diarrhea can impose a major risk of morbidity and mortality on transplanted patients; so a careful evaluation is required to manage it. There are few studies highlighting the gastrointestinal manifestations of COVID-19, in particular among immunosuppressed patients. The predominant respiratory symptoms of coronavirus cause GI aspects of the virus to be overlooked. This study represents a young woman with a history of liver transplant who was referred to the hospital because of diarrhea, fever, and abdominal pain attributed to coronavirus infection.

7.
Pancreatology ; 20(6): 1195-1204, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32800647

RESUMO

Late diagnosis of pancreatic cancer (PC) due to the limited effectiveness of modern testing approaches, causes many patients to miss the chance of surgery and consequently leads to a high mortality rate. Pivotal improvements in circulating microRNA expression levels in PC patients make it possible to diagnose and treat patients at earlier stages. A list of circulating miRNAs was identified in this study using bioinformatics methods in association with pancreatic cancer through analyzing four GEO microarray datasets. The value of top miRNAs was then assessed via using a machine learning method. Taking the advantage of a combinatorial approach consisting of Particle Swarm Optimization (PSO) + Artificial Neural Network (ANN) and Neighborhood Component Analysis (NCA) iterations on a collection of top differentially expressed circulating miRNAs in PC patients, facilitated ranking them by significance. MiRNA's functional analysis in the final index was performed by predicting target genes and constructing PPI networks. Remarkably, the final model consist of miR-663a, miR-1469, miR-92a-2-5p, miR-125b-1-3p and miR-532-5p showed great diagnostic results on investigated cases and the validation set (Accuracy: 0.93, Sensitivity: 0.93, and Specificity: 0.92). Kaplan-Meier survival assessments of the top-ranked miRNAs revealed that three miRNAs, hsa-miR-1469, hsa-miR-663a and hsa-miR-532-5p, had meaningful associations with the prognosis of patients with pancreatic cancer. This miRNA index may serve as a non-invasive and potential PC diagnostic model, although experimental testing is needed.


Assuntos
MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Aprendizado de Máquina , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Algoritmos , Biologia Computacional , Detecção Precoce de Câncer , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , MicroRNAs , Análise em Microsséries , Redes Neurais de Computação , Valor Preditivo dos Testes , Análise de Componente Principal , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise de Sobrevida
8.
Sci Rep ; 10(1): 7559, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32371926

RESUMO

Pancreatic cancer (PC) is a malignancy with little/no warning signs before the disease reaches its ultimate stages. Currently early detection of PC is very difficult because most patients have non-specific symptoms leading to postponing the correct diagnosis. In this study, using multiple bioinformatics tools, we integrated various serum expression profiles of miRNAs to find the most significant miRNA signatures helpful in diagnosis of PC and constructed novel miRNA diagnosis models for PC. Altogether, 27 differentially expressed miRNAs (DEMs) showed area under curve (AUC) score >80%. The most promising miRNAs, miR-1469 and miR-4530, were individually able to distinguish two groups with the highest specificity and sensitivity. By using multivariate cox regression analyses, 5 diagnostic models consisting of different combinations of miRNAs, based on their significant expression algorithms and functional properties were introduced. The correlation model consisting of miR-125a-3p, miR-5100 and miR-642b-3p was the most promising model in the diagnosis of PC patients from healthy controls with an AUC of 0.95, Sensitivity 0.98 and Specificity 0.97. Validation analysis was conducted for considered miRNAs on a final cohort consist of the microarray data from two other datasets (GSE112264 & GSE124158) . These results provide some potential biomarkers for PC diagnosis after testing in large case-control and cohort studies.


Assuntos
Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Pancreáticas/diagnóstico , Área Sob a Curva , Biomarcadores/metabolismo , Estudos de Casos e Controles , Análise por Conglomerados , Perfilação da Expressão Gênica , Humanos , Análise Multivariada , Mapeamento de Interação de Proteínas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Microorganisms ; 7(11)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31766208

RESUMO

Colorectal cancer (CRC) is a worldwide health concern which requires efficient therapeutic strategies. The mechanisms underlying CRC remain an essential subject of investigations in the cancer biology field. The evaluation of human microbiota can be critical in this regard, since the disruption of the normal community of gut bacteria is an important issue in the development of CRC. However, several studies have already evaluated the different aspects of the association between microbiota and CRC. The current study aimed at reviewing and summarizing most of the studies on the modifications of gut bacteria detected in stool and tissue samples of CRC cases. In addition, the importance of metabolites derived from gut bacteria, their relationship with the microbiota, and epigenetic modifications have been evaluated.

10.
Artigo em Inglês | MEDLINE | ID: mdl-28331559

RESUMO

Colorectal cancer (CRC) is mostly due to a series of genetic alterations that are being greatly under the influence of the environmental factors. These changes, mutational or epigenetic modifications at transcriptional forefront and/or post-transcriptional effects via miRNAs, include inactivation and the conversion of proto-oncogene to oncogenes, and/or inactivation of tumor suppressor genes (TSG). Here, a thorough review was carried out on the role of TSGs with the focus on the APC as the master regulator, mutated genes and mal-/dysfunctional pathways that lead to one type of hereditary form of the CRC; namely familial adenomatous polyposis (FAP). This review provides a venue towards defining candidate genes that can be used as new PCR-based markers for early diagnosis of FAP. In addition to diagnosis, defining the modes of genetic alterations will open door towards genome editing to either suppress the disease or reduce its progression during the course of action.

11.
Arch Iran Med ; 19(1): 2-15, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26702742

RESUMO

BACKGROUND: The burden of inflammatory bowel disease (IBD) hasn't been reported in Iran. We aimed to estimate the prevalence and incidence of IBD and its trend in Iran at national and subnational level from 1990 to 2012. METHODS: We conducted a systematic review of English and Persian databases about the epidemiology of IBD. We also collected outpatient data from 17 provinces of Iran using almost all public and private referral gastroenterology clinics. Prevalence and incidence rate was calculated at national and subnational levels. The Kriging method was used to extrapolate provinces with missing data and GPR model to calculate time trends of rates at subnational level. RESULTS: We found 16 case series, two population-based studies, and two review articles. We collected 11,000 IBD cases from outpatient databases. Among them, 9,269 (84.26%) had ulcerative colitis (UC), 1,646 (14.96%) had Crohn's disease (CD), and 85 had intermediate colitis (IC). A total of 5,452 (49.56%) patients were male. Mean age at diagnosis was 32.80 years (CI: 13 - 61) for UC and 29.98 years (CI: 11 - 58) for CD. Annual incidences of IBD, UC, and CD in 2012 were 3.11, 2.70, and 0.41 per 100,000 subjects respectively. Prevalence of IBD, UC, and CD in 2012 were 40.67, 35.52, and 5.03 per 100,000 subjects respectively. The incidence of UC and CD showed a significant increase during the study period (P for trend < 0.05). CONCLUSIONS: The incidence and prevalence of IBD are increasing in Iran. Establishing a national IBD registry seems necessary for comprehensive care of IBD patients in Iran.


Assuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Bases de Dados Factuais , Humanos , Incidência , Irã (Geográfico)/epidemiologia , Sistema de Registros , Fatores de Risco , Fatores Socioeconômicos
12.
World J Gastroenterol ; 20(20): 6302-8, 2014 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-24876751

RESUMO

AIM: To assess the distribution of human leukocyte antigen (HLA)-DQ2 and -DQ8 in Iranian celiac disease (CD) patients and compare them to healthy Iranian controls. METHODS: To predict the HLA-DQA1 and -DQB1 genes, we used six previously reported HLA-tagging single nucleotide polymorphism to determine HLA genotypes in 59 Iranian patients with 'biopsy-confirmed' CD and in 151 healthy Iranian individuals. To test the transferability of the method, 50 cases and controls were also typed using a commercial kit that identifies individual carriers of DQ2, DQ7 and DQ8 alleles. RESULTS: In this pilot study 97% of CD cases (n = 57) and 58% of controls (n = 87) were carriers of HLA-DQ2 and/or HLA-DQ8 heterodimers, either in the homozygous or heterozygous state. The HLA-DQ pattern of these 57 CD patients: heterozygous DQ2.2 (n = 14) and homozygous DQ2.2 (n = 1), heterozygous DQ2.5 (n = 33) and homozygous DQ2.5 (n = 8), heterozygous DQ8 (n = 13) and homozygous DQ8 (n = 2). Two CD patients were negative for both DQ2 and DQ8 (3%). CONCLUSION: The prevalence of DQ8 in our CD population was higher than that reported in other populations (25.4%). As reported in other populations, our results underline the primary importance of HLA-DQ alleles in the Iranian population's susceptibility to CD.


Assuntos
Doença Celíaca/genética , Frequência do Gene , Antígenos HLA-DQ/genética , Haplótipos , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Genótipo , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Adulto Jovem
13.
Mol Biol Rep ; 41(5): 3127-33, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24464185

RESUMO

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor that regulates a number of genes involved in lipid and carbohydrate metabolism. The aim of this study was to investigate the association of C1431T and Pro12Ala polymorphisms of PPARγ gene and their haplotypes and diplotypes with risk of metabolic syndrome (MetS) in an Iranian population. A total of 340 unrelated Iranian subjects, including 175 MetS patients and 165 normal controls were enrolled. Each group was then divided into two subgroups according to the genotype (Pro/Pro and Pro/Ala+Ala/Ala for Pro12Ala, CC and CT+TT for C1431T). Genotypes were determined using a TaqMan method. Anthropometric indices, fasting plasma glucose and fasting lipid profile were measured by routine methods. A significant difference in the frequencies of the C1431T genotypes was observed between MetS and control subjects (P=0.014), whereas no association was found for the Pro12Ala. The T allele carriers had a significantly increased risk of MetS compared to the CC genotype (P=0.016) even after correction for multiple-testing and adjustment for age, sex and genotype. The T allele may therefore be considered as a risk factor for MetS (P=0.003). Analysis of combined groups showed that X/Ala-CC and Pro/Pro-X/T diplotypes were associated with a higher body weight, waist circumference and waist to hip ratio among the individuals with MetS. Moreover the Ala-T haplotype was weakly associated with a higher level of triglyceride and lower level of HDL, suggesting the possibility of an interaction between Ala and T alleles. This study suggests that the PPARγ C1431T polymorphism is related to an increased risk of MetS in an Iranian population and interacts with the Pro12Ala polymorphism, further increasing the risk of MetS.


Assuntos
Alelos , Substituição de Aminoácidos , Predisposição Genética para Doença , Haplótipos , Síndrome Metabólica/genética , PPAR gama/genética , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Adulto Jovem
14.
Ann Hum Biol ; 41(3): 214-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24180251

RESUMO

BACKGROUND: Obesity is a multifactorial disorder due to the complex interaction between genetic and environmental factors. Liver X receptor alpha (LXRα), encoded by the gene NR1H3, is involved in lipoprotein metabolism and its genetic variations may also play a role in the aetiology of obesity. AIM: To assess the association of two NR1H3 polymorphisms (rs11039155 and rs2279238) and their haplotypes with obesity in an Iranian population. SUBJECTS AND METHODS: A total of 447 unrelated subjects (including 206 overweight, 162 obese and 79 controls) were enrolled in the study and were genotyped by TaqMan assay using DNA from peripheral blood. The association of these two LXRα polymorphisms with the presence of obesity and overweight was assessed. RESULTS: There was no significant association between the two SNPs and obesity, even after adjustment for age and sex. By logistic regression using a dominant model, the odds ratios for obesity were: 1.32 (0.85-2.74) for rs11039155 and 0.77 (0.30--1.99) for rs2279238. Haplotype analyses identified three common haplotypes GC, GT and AC with frequency greater than 1%, but none of the haplotypes was associated with the risk of obesity. CONCLUSIONS: This study revealed that there was no significant association between LXRα polymorphisms and the presence of obesity in an Iranian population and suggests that these two SNPs are not major contributors to obesity risk in this population.


Assuntos
Obesidade/genética , Receptores Nucleares Órfãos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Receptores X do Fígado , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Receptores Nucleares Órfãos/metabolismo , Sobrepeso/epidemiologia , Sobrepeso/genética , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
15.
Iran J Public Health ; 43(5): 630-6, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-26060764

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology, in which genetic factors, seem to play an important role in the disease predisposition and course. Assessment of tumor necrosis factor (TNF-α) gene polymorphisms in many populations showed a possible association with IBD. Considering the genetic variety in different ethnic groups, the aim of the present study was to investigate the association of five important single nucleo-tide polymorphisms (SNPs) in the promoter region of (TNF-α) gene with IBD in Iran. METHODS: In this case-control study, 156 Ulcerative colitis (UC) patients, 50 Crohn's disease (CD) patients and 200 sex and age matched healthy controls of Iranian origin were enrolled. The study was performed during a two year period (2008-2010) at Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. DNA samples were evaluated for (TNF-α) gene polymorphisms (including -1031, -863, -857, -308 and -238) by PCR and RFLP methods. RESULTS: The frequency of the mutant allele of -1031 polymorphism was significantly higher in Iranian patients with Crohn's disease compared to healthy controls (P=0.01, OR=1.92; 95% CI: 1.14-3.23). None of the other evaluated polymorphisms demonstrated a significant higher frequency of mutant alleles in Iranian IBD patients compared to controls. CONCLUSION: Among the five assessed (SNPs), only -1031 polymorphism of (TNF-α) gene may play a role in disease susceptibility for Crohn's disease in Iran. This pattern of distribution of (TNF-α) gene polymorphisms could be specific in this population.

16.
Gene ; 532(2): 288-93, 2013 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-24100084

RESUMO

The metabolic syndrome (MetS) is considered to be a major risk factor for type 2 diabetes mellitus and cardiovascular diseases. It is characterized by central adiposity, high blood pressure, glucose intolerance and abnormalities of lipoprotein metabolism. The cause of MetS is likely to be due to a complex interaction between genetic and environmental factors. Liver X receptors alpha (NR1H3) and beta (NR1H2) play a key role in lipid and carbohydrate metabolism. The aim of this study was to investigate the contribution of genetic polymorphisms in the LXRs to risk of MetS and related traits. Two common SNPs in NR1H3 (rs11039155 and rs2279238) and in NR1H2 (rs17373080 and rs2695121) were genotyped using TaqMan assays in MetS patients (n=265) and controls (n=219). Logistic regression analyses were performed to calculate the odds ratios (ORs) as a measure of association of genotypes with the presence of MetS and related phenotypes. Although The NR1H2 polymorphism rs2695121 was nominally associated with MetS but correction for multiple-testing and adjustment for age, sex and number of MetS criteria, failed to identify any significant interactions associated with prevalence of MetS. However in the haplotype analysis, a LXRα haplotype AC, was more common in controls and was associated with a significant protective effect for MetS (OR [95% CI]=0.25 [0.07-0.88], p=0.031). In conclusion, this study suggests that the above-named variants in LXRα and LXRß genes are not potential contributors to the risk of MetS and related traits in an Iranian population.


Assuntos
Síndrome Metabólica/genética , Receptores Nucleares Órfãos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Haplótipos , Humanos , Irã (Geográfico)/epidemiologia , Desequilíbrio de Ligação , Receptores X do Fígado , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Prevalência
17.
Turk J Gastroenterol ; 24(2): 93-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23934454

RESUMO

BACKGROUND/AIMS: Gastrointestinal disorders are important side effects of aspirin therapy, even if the low-dose enteric-coated form is administered. The aim of the current study was to present the upper and lower endoscopic features of patients with gastrointestinal hemorrhage using low-dose enteric-coated aspirin. MATERIALS AND METHODS: This prospective study was conducted among 633 consecutive patients with gastrointestinal hemorrhage who admitted to our tertiary referral hospital for endoscopy assessment. Patients were divided into two groups as low-dose aspirin users (n=168) and non-aspirin users (n=495). Aspirin users included those who were taking 80-100 mg of enteric-coated aspirin per day. RESULTS: Ulcer lesions were found in 78 patients in the aspirin user group and in 113 patients in the control group. Prevalence of duodenal ulcer was statistically similar between the two groups; however, gastric ulcer was seen more in the aspirin-user group. The use of low-dose aspirin could strongly predict gastric ulcers in the patients examined by endoscopy (p<0.001). Overall prevalence of peptic ulcer disease in those with confirmed Helicobacter pylori infection was significantly higher than in non-infected ones (p<0.001). The presence of this infection was strongly associated with peptic ulcer disease in the aspirin-user group (p<0.001). Multivariable analysis also demonstrated that the use of aspirin had a main triggering effect on short-term mortality following gastrointestinal endoscopy (p=0.003). CONCLUSIONS: Low-dose enteric-coated aspirin causes significant gastric endoscopic lesions and even predicts mortality due to progression of gastrointestinal disorders.


Assuntos
Aspirina/administração & dosagem , Úlcera Duodenal/epidemiologia , Hemorragia Gastrointestinal/epidemiologia , Inibidores da Agregação Plaquetária/administração & dosagem , Úlcera Gástrica/epidemiologia , Estudos de Casos e Controles , Endoscopia Gastrointestinal , Feminino , Infecções por Helicobacter/epidemiologia , Hematemese/epidemiologia , Humanos , Masculino , Melena/epidemiologia , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos
18.
Arab J Gastroenterol ; 14(1): 1-5, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23622801

RESUMO

BACKGROUND & STUDY AIMS: Selection of the best drug regimens for eradication of Helicobacter pylori infection especially in patients at risk of peptic ulcer relapses and the development of complications is challenging. This study assessed and compared the efficacy of the two common PPI based triple therapies to a quadruple therapy including PPI, metronidazole, amoxicillin and a bismuth compound in Iranian population. PATIENTS & METHODS: Three hundred and thirty patients with peptic ulcer and H. pylori infection were included in the study. Patients were randomly assigned to one of the three treatment protocols all given twice daily: (a) A 14-day quadruple therapy (OMAB group) comprising omeprazole 20mg, metronicazole 500 mg, amoxicillin 1g, and bismuth subcitrate 240 mg; (b) A 14-day triple regimen (OCP group) comprising omeprazole 20mg plus clarithromycine 500 mg and penbactam 750 mg and (c) A 14-day triple regimen (OCA group) comprising omeprazole 20mg plus clarithromycine 500 mg and amoxicillin 1g. Cure was defined as a negative urea breath test at least six weeks after treatment. RESULTS: The per-protocol eradication rates achieved with both OCP regimen (87.0%) and OCA treatment (90.8%) were significantly higher than the OMAB treatment protocol (56.0%); however, no significant difference emerged in eradication rates between the two triple treatment schedules. No significant differences between the groups were found in most side-effects. CONCLUSION: Two-week quadruple therapy showed a lower eradication rate compared to common triple treatment schedules when used as first-line eradication treatment for H. pylori infection in Iranian population.


Assuntos
Antibacterianos/administração & dosagem , Antiulcerosos/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Úlcera Péptica/tratamento farmacológico , Inibidores da Bomba de Prótons/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amoxicilina/administração & dosagem , Ampicilina/administração & dosagem , Análise de Variância , Testes Respiratórios , Claritromicina/administração & dosagem , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/complicações , Humanos , Irã (Geográfico) , Masculino , Metronidazol/administração & dosagem , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Compostos Organometálicos/administração & dosagem , Úlcera Péptica/microbiologia , Sulbactam/administração & dosagem , Ureia/análise , Adulto Jovem
19.
Cancer Biomark ; 13(6): 427-32, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24595079

RESUMO

BACKGROUND: Single nucleotide polymorphisms in mismatch repair genes may be associated with different protein expression, production, and efficiency according to allele status and influence the risk of developing colorectal cancer. OBJECTIVE: This research aimed at analyzing two important polymorphisms in MLH1 gene and their association in colorectal cancer susceptibility. METHODS: In total, 219 CRC patients and 248 healthy controls were genotyped with PCR/RFLP for I219V and IVS12-169 C>T polymorphisms in MLH1 gene. Sequencing performed to ensure work flow and results. We used unconditional logistic regression after adjusting for age and sex to evaluate the association between each polymorphism and colorectal cancer. RESULTS: The MLH1 I219V polymorphism was associated with colorectal cancer susceptibility (P=0.01). Stratified data analysis for gender demonstrated association of AG (P=0.009) and GG (P=0.021) genotypes with risk of colorectal cancer in women. In contrast there is no association with IVS 12-169 C>T polymorphism and colorectal cancer risk. CONCLUSIONS: I219V SNP might be a susceptibility factor for CRC and gender is a factor that must be considered when it is analyzing. Further tests need to be done to define it as a dependable prognosis factor.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais/genética , Proteínas Nucleares/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteínas Nucleares/metabolismo , Polimorfismo de Nucleotídeo Único , Curva ROC , Fatores de Risco
20.
Indian J Hum Genet ; 19(4): 423-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24497707

RESUMO

BACKGROUND: Peroxisome proliferator activator receptor gamma (PPARγ) is a nuclear transcription factor regulating multiple genes involved in cell growth, differentiation, carbohydrate and lipid metabolism and energy production. Several genetic variations in the PPARγ gene have been identified to be associated with diabetes, obesity, dyslipidemia, insulin resistance, metabolic syndrome and coronary artery disease. The present study was designed to explore the distribution of two common single nucleotide polymorphisms of the PPARγ gene (C1431T and Pro12Ala) in an Iranian population. MATERIALS AND METHODS: Genotype frequencies for these two polymorphisms were compared for 160 healthy Iranian individuals with reports from other populations. The Genotyping was performed using real-time polymerase chain reaction. RESULTS: The genotype distribution of the C1431T PPARγ polymorphism was 0.869 for the CC genotype, 0.119 for the CT genotype and 0.013 for uncommon TT genotype. Allelic frequencies were 0.93 for C and 0.07 for T allele respectively. For the Pro12Ala polymorphism of PPARγ gene, genotypic distributions and allelic frequencies were, 0.813 for CC, 0.181 for CG and 0.06 for GG and 0.903 for C and 0.097 for G respectively. Allelic and genotypic frequencies for both polymorphisms of PPARγ gene were in Hardy-Weinberg equilibrium. CONCLUSIONS: Iran is a country with an ethnically diverse population and a comparison of allelic and genotypic frequencies of PPARγ C1431T and Pro12Ala polymorphisms between our population and others showed significant differences.

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