[Show abstract][Hide abstract] ABSTRACT: Three different concentrations of Nigella sativa (N. sativa) ethanolic extract, thymoquinone (TQ), dexamethasone, and saline were examined to see whether they had any effects on cell viability, proliferation, and interleukin 4 (IL-4) and interferon-γ (IFN-γ) secretion in non-stimulated, phytohemagglutinin (PHA) and concavaline A (Con A)-stimulated splenocytes. In PHA and Con A-stimulated splenocytes, cell viability and proliferation were increased and Con A shifted cytokine profile towards Th2 balance. Dexamethasone treatment showed a suppression in viability, IFNγ and IL-4 secretion in non-stimulated and stimulated splenocytes. Extract and TQ reduced the viability and inhibited the proliferation of stimulated and non-stimulated splenocytes concentration-dependently. Higher concentrations of N. sativa (1000 mg/ml) and TQ (5 and 10 mg/ml) reduced the secretion of IL-4 in stimulated cells. Two higher concentrations of N. sativa had decreased IFNγ secretion in both stimulated and non-stimulated cells. In non-stimulated cells, only the highest and in Con A-stimulated cells, all TQ concentrations had inhibited IFNγ secretion. The highest concentration of N. sativa increased IFNγ/IL-4 ratio in both stimulated and non-stimulated cells while higher concentrations of TQ only had the same effect on stimulated cells. N. sativa and TQ showed cytotoxic inhibitory effect on rat splenocytes and on Th1/Th2 cytokines concentration-dependently. Higher concentrations of extract and TQ increased cytokines balance in Th1/Th2.
[Show abstract][Hide abstract] ABSTRACT: Lymphocytes have demonstrated complex molecular responses to induced stress by ionizing radiation. Many of these reactions are mediated through modifications in gene expressions, including the genes involved in apoptosis. The primary aim of this study was to assess the effects of low doses of ionizing radiation on the apoptotic genes, expression levels. The secondary goal was to estimate the time-effect on the modified gene expression caused by low doses of ionizing radiation. Mononuclear cells in culture were exposed to various dose values ranged from 20 to 100 mGy by gamma rays from a Cobalt-60 source. Samples were taken for gene expression analysis at hours 4, 24, 48, 72, and 168 following to exposure. Expression level of two apoptotic genes; BAX (pro-apoptotic) and Bcl-2 (anti-apoptotic) were examined by relative quantitative real-time polymerase chain reaction (PCR), at different time intervals . Radio-sensitivity of peripheral blood mononucleated cells (PBMCs) was measured by the Bcl-2/BAX ratio (as a predictive marker for radio-sensitivity). The non-parametric two independent samples Mann-Whitney U-test were performed to compare means of gene expression. The results of this study revealed that low doses of gamma radiation can induce early down-regulation of the BAX gene of freshly isolated human PBMCs; however, these changes were restored to near normal levels after 168 hours. In most cases, expression of the Bcl-2 anti-apoptotic gene was up-regulated. Four hours following to exposure to low doses of gamma radiation, apoptotic gene expression is modified, this is manifested as adaptive response. Modification of these gene expressions seems to be a principle pathway in the early radioresistance response. In our study, we found that these changes were temporary and faded completely within a week.
Journal of Medical Physics 07/2015; 40:38-44. DOI:10.4103/0971-6203.152249
[Show abstract][Hide abstract] ABSTRACT: Suitable methods for clinical monitoring of HIV-infected patients are very crucial in resource-poor setting areas. Demographic data, clinical staging and laboratory findings for 112 HIV asymptomatic subjects were assessed at the first admission and the last visit from 2002 to 2010. On Cox regression analysis, hemoglobin (Hb) (HR=0.643, p=0.021) was predictive indicator for disease progression, however; in spite of having significant probability values, CD4, CD8 and platelet counts showed low hazard ratios. Hb and total lymphocyte count (TLC) demonstrated a phase of rapid declining rates (10.9 and 29.6%, respectively) from stage II to III. Lower count of CD4, platelet and Hb at the stage-I were associated with disease progression, and TLC was correlated with CD4 count at the last follow-up (p<0.001). However, WHO cutoff point of 1200 cell/mm(3) for TLC had 26.1% sensitivity and 98.6% specificity. Using ROC curve, TLC count of 1800 cell/mm(3) was more reliable in this region. Statistical analysis and data mining findings showed that Hb, TLC and their rapid decline from stage II to III and lower platelet count could be considered as valuable markers for introducing a surrogate algorithm for monitoring of HIV-infected subjects and starting anti-viral therapy in the absence of sophisticated detection assays.
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) is the world's second most common infectious disease after Human Immunodeficiency Virus Infection/Acquired Immunodeficiency Syndrome (HIV/AID) and the most frequent cause of mortality especially in developing countries. T regulatory (Treg) cells, which have suppressive activity and express forkhead winged-helix family transcriptional repressor p3 (FoxP3), suppress the immune responses against pathogens such as Mycobacterium tuberculosis. There are controversial results regarding the role of FoxP3 expressing cells in the blood of patients with TB.
The aim of this study was to evaluate the frequency CD4+ CD25+ Treg cells, and FoxP3 and Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) gene expressions in peripheral blood of patients with tuberculosis and patients with positive tuberculin skin test before and after Peripheral Blood Mononuclear Cells (PBMCs) activation with Purified Protein Derivative (PPD).
In this cross-sectional study, Peripheral Mononuclear Cells (PBMCs) were isolated from peripheral blood of 29 patients with newly diagnosed pulmonary TB and 19 patients with positive tuberculin skin test. The PBMCs were activated with PPD for 72 hours. Activated cells were harvested, RNA was extracted and cDNA was synthesized. A real-time Taqman method was designed and optimized for evaluation of Foxp3 gene expression and SYBR Green method was used and optimized for evaluation of CTLA-4 gene expression. A flow cytometry analysis was used to evaluate the frequency of CD4+ CD25+ Foxp3+ regulatory T cells in both groups.
There was no significant difference in the frequency of CD4+ CD25+ FoxP3+ regulatory T cells between the two groups. Expression of FoxP3 and CTLA-4 in peripheral blood of patients with newly diagnosed TB was significantly lower than the control group after and before activation with PPD.
The expression of FoxP3 and CTLA-4 in PBMCs of patients with newly diagnosed TB was low, which might suggest that Treg cells may be sequestered in the lungs.
[Show abstract][Hide abstract] ABSTRACT: Globally, almost 20% of cancers are related to infectious agents that can be prevented. Oncogenicity refers to viruses that may cause cancers, more importantly in immunocompromised subjects such as transplant and hemodialysis patients. Therefore, epidemiological studies are the first line for understanding the importance of these agents in public health, particularly, in mobile populations, tourism and pilgrimage regions.
Oncogenic viral infections, such as hepatitis B virus (HBV), hepatitis C virus (HCV) and Epstein-barr virus (EBV) are the most common viral agents in immunocompromised patients. Furthermore, human T lymphocyte virus type I (HTLV-I), due to endemicity in Khorasan Razavi province located northeast of Iran as a pilgrimage region, and Kaposi's sarcoma associated herpes virus (KSHV), as an oncogenic herpesvirus in immunocompromised subjects have been investigated among the general population and those with end-stage renal diseases (ESRD).
A cross-sectional study was carried out among 1227 randomly selected individuals; 25 donors and 195 patients with ESRD, including 60 kidney transplant recipients and 135 dialysis patients from the Khorasan Razavi province, Iran. Serological tests were carried out using commercial enzyme-immunoassay kits. To confirm positive serology tests, the extracted viral DNA or RNA was examined for the presence of KSHV, HTLV-I and HCV by conventional PCR.
The prevalence of KSHV infection in the general population was 1.71% (21/1227); 2.60% (10/384) males and 1.30% (11/843) females. In kidney transplants, viral infections occurred in 23.3% of subjects; including EBV, HTLV-I and HBV-HCV co-infection in 8.3%, 3.3% and 1.7%, respectively. In patients on hemodialysis, viral infections were present in 29.6% including EBV, HTLV-I and HBV-HCV co-infection in 2.2%, 5.9% and 16.3%, respectively. Seroprevalence of KSHV in patients with kidney transplants was 1.7% and in patients on dialysis was 3.0%. Furthermore, KSHV and HTLV-I genome was detected in 25% and 100% of seropositive subjects, respectively.
In conclusion, this study demonstrated that these tumor virus infections including HTLV-I, KSHV and particularly hepatitis viruses (HBV plus HCV) are prevalent in the general population and in patients on hemodialysis, which might be an important health concern in this region due to the mobile population.
[Show abstract][Hide abstract] ABSTRACT: The role of transforming growth factor (TGF)-β1, interferon (IFN)-γ, interleukin (IL)-2, IL-3, and IL-6 in the pathogenesis of Alzheimer's Disease (AD) has long been reported in literature. In this case-control study, the concentrations of these cytokines in altered T lymphocytes, as well as serum vitamin B12, have been compared in terms of factors such as, age, the clinical course and the patients' disease risk. 40 patients who met the DSM-IV-TR criteria of AD were selected and an age- and gender-matched control group was recruited. The participants' cognitive performance was measured according to the Mini Mental State Examination (MMSE), the Global Deterioration Scale (GDS) and Clinical Dementia Ratio (CDR). The levels of cytokines were measured in supernatants of lymphocytes culture, using assays of ELISA and atomic absorption. Higher levels of IL-6 and IFN-γ were found more in the altered T lymphocytes of the AD patients rather than in the control individuals. Furthermore, a marginal significant difference was found between the TGF-β levels of the two study groups. Regression analysis of CDR score and cytokines showed the inverse significant correlation between CDR score and IFN-γ levels. Furthermore, the relation between MMSE scores and IFN-γ was significant, meaning that by increasing MMSE score, IFN-γ level was significantly increased. This study suggests that the levels of IL-6 and IFN-γ are significantly increased in altered T lymphocytes of AD patients, as compared to those who are not inflicted with AD, and that they are related to the patient's age. Also, IFN-γ is related to the severity stage of the AD.
Iranian journal of allergy, asthma, and immunology 12/2014; 13(6):433-439.. · 0.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
Gastric cancer is the second leading cause of cancer-related deaths worldwide and the most common gastrointestinal cancer in Iran. Chemokine ligand 5 (CCL5/RANTES) is one of the most potent angiogenic factors that plays an important role in tumor growth, invasion, and metastasis. We aimed to assess the serum level of CCL5 in patients with gastric adenocarcinoma and its relation with histological grade and tumor stage, as well as the disease prognosis.
Seventy-four patients with gastric adenocarcinoma that had undergone gastrectomy and 96 non-tumoral cases in which gastric cancer was ruled out by gastroscopy and biopsy were enrolled. Demographic and epidemiological characteristics and patient survival data were reviewed. Histological type, grade, and tumor stage (TNM) were determined by a single expert pathologist. Helicobacter pylori infection status and CCL5 serum level were measured by ELISA. Data were analyzed using SPSS software version 16.
Patients with gastric adenocarcinoma had significantly higher serum CCL5 level compared with control group (P
Journal of Gastrointestinal Cancer 10/2014; 45(4). DOI:10.1007/s12029-014-9652-5 · 0.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a third leading cause of death.
In this case control study, we prepared 5 cc bloods from the antecubital vein of 100 COPD patients and 40 healthy individuals as control group. Vascular endothelial growth factor (VEGF) expression protein level was measured by ELISA in both groups.
We found that concentration of VEGF in blood serum of patients with COPD (189.9±16pg/ml) was significantly higher than the control group (16.4±3.48pg/ml) (p<0.001). While VEGF serum level in emphysematous patients wasn't significantly different with control group (p=0.07). Furthermore VEGF serum level in COPD patients was proportionally increased with severity of disease (p<0.001). Besides all COPD patients, regardless of their smoking status, were experienced significantly higher levels of VEGF than healthy ones (p=0.001; z=4.3).
Our results suggest VEGF serum concentration as the sensitive index for severity and activity of COPD and its prognosis.
Medical journal of the Islamic Republic of Iran 08/2014; 28:85.
[Show abstract][Hide abstract] ABSTRACT: Background: The role of vitamin D in the pathogenesis of rheumatoid arthritis is under investigation. This study was designed to evaluate the correlation between serum values of 25(OH) vitamin D [25(OH)D] and disease activity in rheumatoid arthritis (RA) patients according to Disease Activity Score 28 joints and ESR (DA S28 ESR).
Methods: Ninety-nine patients according to ACR classification criteria for RA and 68 healthy controls were included in this study. The participants with known confounding risk factors affecting serum values of 25(OH)D were excluded. All patients were under treatment with supplementary calcium carbonate (1500mg), 25(OH)D (800U), and Hydroxychloroquine (6mg/kg). The control group was mostly recruited from patients’ relatives who lived with them to minimize the impact of diverse lifestyles on 25(OH)D status. Disease activity was assessed by DA S28 ESR. Serum concentrations of 25(OH)D were measured. Serum values of 25(OH)D less than 50 nmol/L were considered 25(OH)D deficiency.
Results: The mean 25(OH)D serum values were 83.74±46.45 nmol/L in patients and 46.53±34.07 nmol/L in controls. After adjustment for age, sex and BMI, multivariate analysis showed no correlation between 25(OH)D serum levels and DAS in RA (P=0.29, rp=0.11). However, 25(OH)D serum values were significantly lower in patients with early diagnosed RA compared with the other patients (p=0.012). In the early diagnosed patients, 25(OH)D and anti-CCP serum values were negatively correlated (P=0.04, rs=-0.5).
Conclusion: This study showed that there was no correlation between 25(OH)D serum values and DAS over a short duration of disease course. However, in early RA, 25(OH) D serum values were lower than the established RA.
Caspian Journal of Internal Medicine 05/2014; 5(3):148-55.
[Show abstract][Hide abstract] ABSTRACT: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints that has a strong correlation with HLA-DRB1. Family history is considered a known risk factor for RA. The aims of this study were to compare the frequency of HLA-DRB1 alleles between patients with sporadic and familial RA and also between healthy controls with RA patients (sporadic and familial) and clarify if familial RA is more severe than sporadic RA. This study included 129 consecutive patients with sporadic and 48 cases with familial (first-degree siblings) RA who visited a rheumatology unit. Demographic data, including extra-articular involvement, mean disease activity according to DAS28 (ESR) criteria, and main laboratory findings, were compared between patients with sporadic and familial RA. HLA-DRB1 typing was carried out using the PCR-SSP method, and the frequency of each allele was determined in all cases and compared with the results of HLA-DRB1 frequencies in 72 healthy controls who were previously reported by our group in northeast Iran. Patients with sporadic and familial RA were matched in age and sex, most of the cases in both groups were females. The mean age of patients was 45 years. Ocular involvement was the most frequent extra-articular manifestation of our patients. There was no significant difference between the two groups in visual analogue scale (VAS) index, number of inflamed or tender joints, extra-articular involvements, and main laboratory findings. HLA-DRB1* 01 (55 %), 04 (48 %), and 03 (43 %) alleles were the most frequent alleles in both sporadic and familial diseases. The frequency of HLA-DRB1*11 and HLA-DRB1*13 was significantly higher in normal participants compared with RA (p = 0.001). There was no significant difference in the HLA-DRB1 allele's frequency between sporadic and familial RA. Therefore, familial aggregation was not associated with RA severity.
[Show abstract][Hide abstract] ABSTRACT: Asthma is the most common chronic inflammatory disorder characterized by cough, wheezing and dyspnea in children. Nutrition is an important factor which influences on induction and exacerbation of asthma. There are controversies to use Vitamin E in asthmatic patients. The aim of this study was to evaluate the effect of vitamin E supplement in children with moderate asthma. This is a randomized double blind placebo-controlled trial performed on children (age 2-17 years old) with moderate asthma (5-17 years old) from March 2010 to March 2012. Case group were treated with fluticasone and vitamin E (50mg/day) and control group received fluticasone plus placebo for 8 weeks. Out of 300 cases, 240 cases completed the study. Female to male ratio was 0.84. Serum level of Vitamin E significantly increased after treatment in intervention group. FEV1 and FEV1/FVC ratio was significantly improved in case group compared to the control group. It can be concluded that vitamin E supplement could improve clinical manifestations and pulmonary function test in children with moderate asthma.
Iranian journal of allergy, asthma, and immunology 04/2014; 13(2):98-103. · 0.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Titanium dioxide nanoparticles (TiO2-NPs) are massively produced in the environment, and because of their wide usage, they are a potential risk of damage to human health. TiO2-NPs are often used as additives for paints, papers, and foods. The central nervous system (CNS), including hippocampal regions, is potentially susceptible targets for TiO2-NPs. This study aimed to determine the effects of exposure to TiO2-NPs during pregnancy on hippocampal cell proliferation and the learning and memory of offspring. Pregnant Wistar rats received intragastric TiO2-NPs (100mg/kg body weight) daily from gestational day (GD) 2 to (GD) 21. Animals in the control group received the same volume of distilled water via gavage. After delivery, the one-day-old neonates were deeply anesthetized and weighed. They were then killed and the brains of each group were collected. Sections of the brains from the rat offspring were stained using Ki-67 immunolabeling and the immunohistochemistry technique. Some of the male offspring (n=12 for each group) were weaned at postnatal day (PND21), and housed until adulthood (PND60). Then the learning and memory in animals of each group were evaluated using passive avoidance and Morris water maze tests. The immunolabeling of Ki-67 protein as a proliferating cell marker showed that TiO2-NPs significantly reduced cell proliferation in the hippocampus of the offspring (P<0.05). Moreover, both the Morris water maze test and the passive avoidance test showed that exposure to TiO2-NPs significantly impaired learning and memory in offspring (P<0.05). These results may provide basic experimental evidence for a better understanding of the neurotoxic effects of TiO2-NPs on neonatal and adult brains.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the impact of thromboangiitis obliterans (TAO) sera on activation of primary cultures of human umbilical vein endothelial cells (HUVECs) as a model for vascular endothelial cells.
Study subjects included 21 TAO patients as the case group and 20 healthy smokers and 17 healthy non-smokers as control groups. Case and control groups were matched based on their age, socioeconomic status and smoking habit. HUVECs were incubated with the sera of case and control groups and gene expression of intercellular adhesion molecule (ICAM-1) and vascular adhesion molecule (VCAM-1) were evaluated by real-time polymerase chain reaction, TaqMan method.
The expression of ICAM-1 and VCAM-1 were significantly higher in HUVECs after incubation with TAO sera compared to control groups (P < 0.05). VCAM-1 had a significant correlation with duration of smoking (P < 0.001, R = 0.672), while the expression of ICAM-1 had a significant correlation with the number of cigarettes smoked daily (P = 0.04, R = 0.421).
Sera from TAO patients could activate HUVECs. This same activation might occur in vivo by the responsible cytokines, in particular those released from activated platelets, free oxygen radicals, and possibly low levels of nitric oxide (NO) of the sera of TAO patients, as a consequences of chronic cigarette smoking and of endothelial NO synthase polymorphism. Therefore, plasma exchange might be helpful in acute phase of the disease for saving the limbs and administration the combinations of exogenous NO with anti-oxidants might be helpful in long-term management of TAO patients to reduce the risk and rate of amputation.
International Journal of Rheumatic Diseases 01/2014; 17(1):106-12. DOI:10.1111/1756-185X.12214 · 1.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective(s): HTLV-I and HIV virus quantification is an important marker for assessment of virus activities. Since there is a direct relationship between the number of virus and disease progression, HTLV-I and HIV co-infection might have an influence on the development of viral associated diseases, thus, viral replication of these viruses and co-infection were evaluated.
Materials and Methods: In this study, 40 subjects were selected; 14 HIV infected, 20 HTLV-I infected and 6 HTLV-I/HIV co-infected subjects. The amount of viruses was measured using qPCR TaqMan method and CD4 and CD8 lymphocytes were assessed by flow cytometry.
Results: The mean viral load of HIV infected subjects and HTLV-I infected individuals were 134626.07±60031.07 copies/ml and 373.6±143.3 copies/104 cells, respectively. The mean HIV viral load in co-infected group was 158947±78203.59 copies/ml which is higher than HIV infected group. The mean proviral load of HTLV-I in co-infected group was 222.33±82.56 copies/ml which is lower than HTLV-I infected group (P<0.05). Also, the mean white blood cell count was higher in co-infected group (5666.67±1146.49 cells/μl). However, the differences between these subjects did not reach to a statistical significance within 95% confidence interval level (P =0.1). No significant differences were observed regarding CD4 and CD8 positive lymphocytes between these groups.
Conclusion: HTLV-I/HIV co-infection might promote HIV replication and could reduce the HTLV-I proviral load, in infected cells. Considering the presence of both viruses in Khorasan provinces, it encourages researchers and health administrators to have a better understanding of co-infection outcome.
Iranian Journal of Basic Medical Science 01/2014; 17(1):49-54. · 1.23 Impact Factor