Investigation of RFLP Haplotypes ß-Globin Gene Cluster in Beta-Thalassemia Patients in Central Iran.

Introduction: Beta-thalassemia is one of the most prevalent inherited blood diseases among Iranians. The aim of this study was to elucidate the chromosomal background of beta-thalassemia mutations in Esfahan province, Iran. Materials and Methods: In this study, we investigated three frequent mutations (c.315+1G>A, c.93-21G>A and c.92+5G>C in ß-globin gene, the frequency of RFLP haplotypes, and LD between markers at ß-globin gene cluster) in 150 beta-thalassemia patients and 50 healthy individuals. The molecular and population genetic investigations were performed on RFLP markers HindIII in the c.315+1G>A of Gγ (HindIIIG) and Aγ (HindIIIA) genes, AvaII in the c.315+1G>A of ß-globin gene and BamHI 3' to the ß-globin gene. All statistical analyses were performed using Power Marker software and SISA server. Results: Fifty percent of beta-thalasemia patients were associated with these mutations. Haplotype I was the most prevalent haplotype among beta-thalassemia patients (39.33%) and normal individuals (46%). The commonest c.315+1G>A mutation in our population was tightly linked with haplotype III (43.75%) and haplotype I (31.25%). The second prevalent mutation, c.92+5G>C, was 90%, 6.66%, and 3.33% in linkage disequilibrium with haplotypes I, VII, and III, respectively. The c.93-21G>A mutation indicated a strong association with haplotype I (80%). Conclusion: Our study participants like beta-thalassemia patients from Kermanshah province was found to possess a similar haplotype background for common mutations. The emergence of most prevalent mutations on chromosomes with different haplotypes can be explained by gene conversion and recombination. High linkage of a mutation with specific haplotype is consistent with the hypothesis that chromosomes carrying beta-thalassemia mutations experienced positive selection pressure, probably because of the protection against malaria experienced by beta-thalassemia carriers.

Valproic Acid Promotes Apoptosis and Cisplatin Sensitivity Through Downregulation of H19 Noncoding RNA in Ovarian A2780 Cells.

Cisplatin resistance is one of the main limitations in the treatment of ovarian cancer, which is partly mediated by long noncoding RNAs (lncRNAs). H19 is a lncRNA involving in cisplatin resistance in cancers. Valproic acid (VPA) is a commonly used drug for clinical treatment of seizure disorders. In addition, this drug may display its effects through regulation of noncoding RNAs controlling gene expression. The aim of the present study was the investigation of VPA treatment effect on H19 expression in ovarian cancer cells and also the relation of the H19 levels with apoptosis and cisplatin resistance. Briefly, treatment with VPA not only led to significant increase in apoptosis rate, but also increased the cisplatin sensitivity of A2780/CP cells. We found that following VPA treatment, the expression of H19 and EZH2 decreased, but the expression of p21 and PTEN increased significantly. To investigate the involvement of H19 in VPA-induced apoptosis and cisplatin sensitivity, H19 was inhibited by a specific siRNA. Our results demonstrate that H19 knockdown by siRNA induced apoptosis and sensitized the A2780/CP cells to cisplatin-induced cytotoxicity. These data indicated that VPA negatively regulates the expression of H19 in ovarian cancer cells, which subsequently leads to apoptosis induction, cell proliferation inhibition, and overwhelming to cisplatin resistance. The implication of H19→EZH2→p21/PTEN pathway by VPA treatment suggests that we could repurpose an old drug, valproic acid, as an effective drug for treatment of ovarian cancer in the future.

Impact of garlic tablets on nosocomial infections in hospitalized patients in intensive care units.

BACKGROUND: Nosocomial infections are one of the main causes of mortality and morbidity in hospitals, especially in intensive care units (ICUs). OBJECTIVE: The aim of this study was to examine the impact of garlic tablets on nosocomial infections in hospitalized patients in intensive care units. METHODS: This clinical trial was carried out on 94 patients, admitted to the intensive care units in Kashani and Al-Zahra hospitals from January 21, 2014 to December 20, 2014. Firstly, the patients were randomly selected by simple sampling, then they were assigned into case and control groups. The case group administered one 400 mg garlic tablet daily for 6 days and the control group received placebo. During the study, inflammatory blood factors and infection occurrence in the two groups were compared. The Data were analyzed by SPSS software version 22 through descriptive tests such as independent t-test, Chi-square test, ANOVA and exact Fisher test for the analyses of primary and secondary outcomes. RESULTS: During the study period, 78 cases of intravenous catheter tip were sent to laboratory for culture, of which, 37 cases were in the intervention group and 41 in the control group. Culture results of Catheter tips was positive in 5 cases and all five cases were in the control group. Frequency distribution of catheter tip culture was significantly higher in the control group than that of the intervention group (p=0.03). CONCLUSION: Based on the results of our study, in people with weakened immune systems and in people with high incidence of opportunistic infections, it is necessary to strengthen their body's immune system stimulants before dealing with these infectious agents, and cause decrease in the diseases insusceptible people. It was suggested that garlic supplementation has shown to be effective in patients admitted to ICU, who are highly susceptible to nosocomial infection, and it can be used for the prevention of septicemia and urinary tract infections. However, further research with larger sample size is needed. TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: IRCT207406156480N6. FUNDING: Shahrekord University of Medical Sciences financially supported this research.