Mutations in the coding regions of the hepatocyte nuclear factor 4 alpha in Iranian families with maturity onset diabetes of the young

Hepatocyte nuclear factor 4α (HNF4α) is a nuclear receptor involved in glucose homeostasis and is required for normal β cell function. Mutations in the HNF4α gene are associated with maturity onset diabetes of the young type 1 (MODY1). The aim of the present study was to determine the prevalence and nature of mutations in HNF4α gene in Iranian patients with a clinical diagnosis of MODY and their family members. Twelve families including 30 patients with clinically MODY diagnosis and 21 members of their family were examined using PCR-RFLP method and in case of mutation confirmed by sequencing techniques. Fifty age and sex matched subjects with normal fasting blood sugar (FBS) and Glucose tolerance test (GTT) were constituted the control group and investigated in the similar pattern. Single mutation of V255M in the HNF4α gene was detected. This known mutation was found in 8 of 30 patients and 3 of 21 individuals in relatives. Fifty healthy control subjects did not show any mutation. Here, it is indicated that the prevalence of HNF4α mutation among Iranian patients with clinical MODY is considerable. This mutation was present in 26.6% of our patients, but nothing was found in control group. In the family members, 3 subjects with the age of ≤25 years old carried this mutation. Therefore, holding this mutation in this range of age could be a predisposing factor for developing diabetes in future

The frequency of HBeAg and relation with serum level of aminotransferase in chronic hepatitis B

زمینه و هدف: ویروس هپاتیت B (HBV) شایع ترین علت بیماری کبدی حاد و مزمن در جهان به شمار می رود. در افراد ناقل HBV می بایست وضعیت تکثیر ویروسی با استفاده از مارکرهای مناسب از جمله HbeAg مورد بررسی قرار گیرد تا در صورت مثبت بودن و همچنین بالا بودن آنزیم های کبدی افراد مبتلا به هپاتیت مزمن شناسایی شده و سپس تحت درمان قرار گیرند. لذا این مطالعه با هدف تعیین فراوانی مارکر HBeAg و ارتباط آن با سطح ترانس آمینازهای کبدی در افراد HBsAg مثبت انجام گرفت. روش بررسی: در این مطالعه توصیفی – تحلیلی 144 فرد آلوده به ویروس هپاتیت B در مراجعین به بیمارستان امام رضا(ع) شهر مشهد در سال 1385 انتخاب و سپس در سرم این افراد، HBeAg و آنزیم های کبدی با روش الایزا و تست های بیوشیمیایی اندازه گیری شدند. داده ها با استفاده از آزمون های آماری من ویتنی و کای دو تجزیه و تحلیل شد. یافته ها: فراوانی افراد 94 نفر مذکر و 50 نفر مونث بود. این افراد در محدوده سنی 85-2 با میانگین 3/2±4/37 سال قرار داشتند. 18 (26 نفر) دارای HBeAg در سرم بودند. میانگین آنزیم آسپارتات آمینو ترانسفراز (AST) در گروه HBeAg مثبت IU/L 83 و در گروه HBeAg منفی IU/L 2/56 بود (01/0

Thiamine as a peripheral neuro-protective agent in comparison with N-acetyl cysteine in axotomized rats

Objective(s): In this study, the impact of thiamine (Thi), N-acetyl cysteine (NAC), and dexamethasone (DEX) were investigated in axotomized rats, as a model for neural injury.Materials and Methods: Sixty-five axotomized rats were divided into two different experimental approaches, the first experiments included five study groups (n=5): intrathecal Thi (Thi.it), intraperitoneal (Thi), NAC, DEX, and control. Cell survival was assessed in L5DRG in the 4th week by histological assessment. In the second study, 40 animals were engaged to assess Bcl-2, Bax, IL-6, and TNF-α expression in L4-L5DRG in the 1st and 2nd weeks after sural nerve axotomy under treatment of these agents (n=10).Results: Ghost cells were observed in morphological assessment of L5DRG sections, and following stereological analysis, the volume and neuronal cell counts significantly were improved in the NAC and Thi.it groups in the 4th week (P<0.05). Although Bcl-2 expression did not show significant differences, Bax was reduced in the Thi group (P=0.01); and the Bcl-2/Bax ratio increased in the NAC group (1st week, P<0.01). Furthermore, the IL-6 and TNF-α expression decreased in the Thi and NAC groups, on the 1st week of treatment (P≤0.05 and P<0.01). However, in the 2nd week, the IL-6 expression in both Thi and NAC groups (P<0.01), and the TNF-α expression in the DEX group (P=0.05) were significantly decreased. Conclusion: The findings may classify Thi in the category of peripheral neuroprotective agents, in combination with routine medications. Furthermore, it had strong cell survival effects as it could interfere with the destructive effects of TNF-α by increasing Bax

An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis

Background Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that significantly affected spinal cord, nevertheless, the pathogenesis pathway and reliable biomarkers have not been well determined. This study aimed to employ high throughput meta-analysis to find major genes that are possibly involved in the pathogenesis of HAM/TSP. Results High-throughput statistical analyses identified 832, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. The protein-protein interactions between DEGs were identified in STRING and further network analyses highlighted 24 and 6 hub genes for normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. Moreover, four biologically meaningful modules including 251 genes were identified for normal vs. ACs. Biological network analyses indicated the involvement of hub genes in many vital pathways like JAK-STAT signaling pathway, interferon, Interleukins, and immune pathways in the normal vs. HAM/TSP group and Metabolism of RNA, Viral mRNA Translation, Human T cell leukemia virus 1 infection, and Cell cycle in the normal vs. ACs group. Moreover, three major genes including STAT1, TAP1, and PSMB8 were identified by network analysis. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P = 0.01 and P = 0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P = 0.04 and P = 0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P = 0.008 and P = 0.02, respectively). No significant difference was found among three groups in terms of the percentage of T helper and cytotoxic T lymphocytes (P = 0.55 and P = 0.12). Conclusions High-throughput data integration disclosed novel hub genes involved in important pathways in virus infection and immune systems. The comprehensive studies are needed to improve our knowledge about the pathogenesis pathways and also biomarkers of complex diseases.Peer reviewe

National, sub-national, and risk-attributed burden of thyroid cancer in Iran from 1990 to 2019

An updated exploration of the burden of thyroid cancer across a country is always required for making correct decisions. The objective of this study is to present the thyroid cancer burden and attributed burden to the high Body Mass Index (BMI) in Iran at national and sub-national levels from 1990 to 2019. The data was obtained from the GBD 2019 study estimates. To explain the pattern of changes in incidence from 1990 to 2019, decomposition analysis was conducted. Besides, the attribution of high BMI in the thyroid cancer DALYs and deaths were obtained. The age-standardized incidence rate of thyroid cancer was 1.57 (95% UI: 1.33–1.86) in 1990 and increased 131% (53–191) until 2019. The age-standardized prevalence rate of thyroid cancer was 30.19 (18.75–34.55) in 2019 which increased 164% (77–246) from 11.44 (9.38–13.85) in 1990. In 2019, the death rate, and Disability-adjusted life years of thyroid cancer was 0.49 (0.36–0.53), and 13.16 (8.93–14.62), respectively. These numbers also increased since 1990. The DALYs and deaths attributable to high BMI was 1.91 (0.95–3.11) and 0.07 (0.04–0.11), respectively. The thyroid cancer burden and high BMI attributed burden has increased from 1990 to 2019 in Iran. This study and similar studies’ results can be used for accurate resource allocation for efficient management and all potential risks’ modification for thyroid cancer with a cost-conscious view

Phosphate Ion Release and Alkalizing Potential of Three Bioactive Dental Materials in Comparison with Composite Resin

Aim. Several new bioactive compounds were recently introduced to the market with favorable ion release, tooth remineralization, and alkalizing potential. This study sought to compare the phosphate ion release and alkalizing potential of three bioactive materials in comparison with composite resin. Methods. Thirty-six discs (2 × 6 mm) were fabricated from Fuji II LC resin modified glass ionomer (RMGI), Activa BioActive, Cention N, and Z250 composite in plastic molds. The specimens were stored in distilled water for 24 and 48 h and 6 months. Half of the specimens were used to assess the phosphate ion release while the other half were used to assess the alkalizing potential 1 h after pH drop from 6.8 to 4. Phosphate ion release was quantified by a spectrophotometer while the pH value was measured by a pH meter. Data were analyzed using two-way ANOVA, one-way ANOVA, and Tukey’s HSD test (for pairwise comparisons) at 0.05 level of significance. Results. At 24 h, the maximum phosphate ion release in distilled water occurred in the Fuji II LC group followed by Cention N, Activa BioActive, and Z250. At 6 months, Cention N followed by Activa BioActive showed higher phosphate ion release than Fuji II LC and Z250. No significant difference was noted between Activa BioActive and Cention N at any time point. All materials, except for Z250, increased the pH of the environment. Fuji II LC had maximum alkalizing effect at all time points followed by Cention N and Activa BioActive. Conclusion. Use of bioactive compounds is a promising method to ensure phosphate ion release, and can have a positive effect on tooth remineralization over time. Also, bioactive compounds can alkalize an acidic environment

Lifetime and 5 years risk of breast cancer and attributable risk factor according to Gail model in Iranian women

Introduction: Breast cancer is the most commonly diagnosed cancers in women worldwide and in Iran. It is expected to account for 29% of all new cancers in women at 2015. This study aimed to assess the 5 years and lifetime risk of breast cancer according to Gail model, and to evaluate the effect of other additional risk factors on the Gail risk. Materials and Methods: A cross sectional study conducted on 296 women aged more than 34-year-old in Qom, Center of Iran. Breast Cancer Risk Assessment Tool calculated the Gail risk for each subject. Data were analyzed by paired t-test, independent t-test, and analysis of variance in bivariate approach to evaluate the effect of each factor on Gail risk. Multiple linear regression models with stepwise method were used to predict the effect of each variable on the Gail risk. Results: The mean age of the participants was 47.8 ± 8.8-year-old and 47% have Fars ethnicity. The 5 years and lifetime risk was 0.37 ± 0.18 and 4.48 ± 0.925%, respectively. It was lower than the average risk in same race and age women (P < 0.001). Being single, positive family history of breast cancer, positive history of biopsy, and radiotherapy as well as using nonhormonal contraceptives were related to higher lifetime risk (P < 0.05). Moreover, a significant direct correlation observed between lifetime risk and body mass index, age of first live birth, and menarche age. While an inversely correlation observed between lifetimes risk of breast cancer and total month of breast feeding duration and age. Conclusion: Based on our results, the 5 years and lifetime risk of breast cancer according to Gail model was lower than the same race and age. Moreover, by comparison with national epidemiologic indicators about morbidity and mortality of breast cancer, it seems that the Gail model overestimate the risk of breast cancer in Iranian women

Evaluation of HTLV-1 activity in HAM/TSP patients using proviral load and Tax mRNA expression after In Vitro lymphocyte activation

Objective(s):HTLV-1 is the first human retrovirus that has been recognized and is associated with HAM/TSP and ATLL. Studies have shown that less than five percent of HTLV-1 infected carriers develop HAM/TSP or ATLL and about ninety-five percent remain asymptomatic. Therefore, the proviral load with Tax may affect cellular genes such as cytokines and oncogenes, as well as involve in pathogenicity. Materials and Methods:Thirty HAM/TSP patients, thirty HTLV-1 healthy carriers, and MT-2 cell line were evaluated for HTLV-1 activity. PBMCs were isolated and activated using PMA and ionomycine. Real-time PCR and TaqMan methods were performed using specific primers and fluorescence probes for Tax expression and proviral load assessment. Β2microglobulin (β2m) and albumin were used as controls in Tax expression and in proviral load, respectively. Results: An insignificant increase in Tax expression was observed in rest PBMCs of HAM/TSP patients compared to healthy carriers. However, after lymphocyte activation there was a significant increase in Tax expression in HAM/TSP patients (P=0.042). The Proviral load in patients was significantly higher than in carriers. Moreover, there was a significant correlation between Tax mRNA expression in activated PBMCs and proviral load (R=0.37, P=0.012). Conclusion: Although proviral load had been addressed as a valuable index for monitoring HTLV-1 infected subjects, the results of this study demonstrated that Tax expression in activated PBMCs along with proviral load assessment in HAM/TSP patients are a more reliable factor for determining the prognosis and monitoring healthy carriers and HAM/TSP patients

Coevolution of HTLV-1-HBZ, Tax, and proviral load with host IRF-1 and CCNA-2 in HAM/TSP patients

Background HTLV-1-associated myelopathy (HAM/TSP) is a progressive neurodegenerative inflammatory condition of HTLV-1 infection. Viral-host interactions are a significant contributor to the symptoms of HTLV-1-associated diseases. Therefore, in this study, the expression of the main regulatory viral factors and proviral load (PVL) and two host transcription molecules were evaluated in HAM/TSP patients. Materials and methods The study population included 17 HAM/TSP patients, 20 asymptomatic carriers (ACs), and 19 healthy controls (HCs). RNA and DNA were extracted from PBMCs for assessment of the gene expressions and PVL assessment using RT-qPCR and TaqMan method. Results HTLV-1-PVL was higher in HAM/TSPs (395.80 ± 99.69) than ACs (92.92 ± 29.41) (P = 0.001). The Tax expression in HAM/TSPs (7.8 ± 5.7) was strongly higher than ACs (0.06 ± 0.04) (P = 0.02), while HTLV-1-HBZ was only increased around three times in HAM/TSPs (3.17), compared to ACs (1.20) and not significant. The host IRF1 expression in HAM/TSPs (0.4 ± 0.31) was higher than ACs (0.09 ± 0.05) (P = 0.02) and also HCs (0.16 ± 0.07) (P = 0.5), but lower in ACs than HCs (p = 0.01). Although, in HAM/TSPs (0.13 ± 0.09) and ACs (0.03 ± 0.02) CCNA-2 expression was statistically fewer than HCs (0.18 ± 0.06) (P = 0.03, P = 0.001, respectively), in HAM/TSP was higher than ACs (P = 0.1), but did not meet a 95% confidence interval. Conclusion The study showed that HTLV-1-PVL and Tax, along with host IRF-1, could be considered biomarkers in HAM/TSP development. Furthermore, IRF-1, as an essential transcription factor, can be considered a pivotal target in HAM/TSPs treatment