Publications by authors named "Mohammad Mehdi Naghizadeh"

71 Publications

Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality.

Iran J Allergy Asthma Immunol 2021 Feb 11;20(1):46-66. Epub 2021 Feb 11.

Department of Biostatistics and Social Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spread rapidly all over the world in late 2019 and caused critical illness and death in some infected patients. This study aimed at examining several laboratory factors, especially inflammatory and immunological mediators, to identify severity and mortality associated biomarkers. Ninety-three hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) were classified based on disease severity. The levels of biochemical, hematological, immunological, and inflammatory mediators were assessed, and their association with severity and mortality were evaluated. Hospitalized patients were mostly men (77.4%) with an average (standard deviation) age of 59.14 (14.81) years. The mortality rate was significantly higher in critical patients (85.7%). Increased serum levels of blood sugar, urea, creatinine, uric acid, phosphorus, total bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-oxaloacetic transaminase, lactic dehydrogenase, C-reactive protein, ferritin, and procalcitonin were significantly prevalent (p=0.002, p<0.001, p<0.001, p=0.014, p=0.047, p=0.003, p<0.001, p<0.001, p<0.001, p<0.001, P<0.001, and p<0.001, respectively) in COVID-19 patients. Decreased red blood cell, hemoglobin, and hematocrit were significantly prevalent among COVID-19 patients than healthy control subjects (p<0.001 for all). Troponin-I, interleukin-6, neutrophil/lymphocyte ratio (NLR), procalcitonin, and D-dimer showed a significant association with the mortality of patients with specificity and sensitivity more than 60%. Age, sex, underlying diseases, blood oxygen pressure, complete blood count along with C-reactive protein, lactic dehydrogenase, procalcitonin, D-dimer, and interleukin-6 evaluation help to predict the severity and required management for COVID-19 patients. Further investigations are highly recommended in a larger cohort study for validation of the present findings.
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http://dx.doi.org/10.18502/ijaai.v20i1.5412DOI Listing
February 2021

A methylation signature at the CpG island promoter of estrogen receptor beta (ER-β) in breasts of women may be an early footmark of lack of breastfeeding and nulliparity.

Pathol Res Pract 2021 Feb 28;218:153328. Epub 2020 Dec 28.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Although little is known regarding the mechanisms behind the onset of breast cancer (BC) through reproductive risk factors, new researches have highlighted some early tumor-related methylation footmarks in the breast tissue of apparently clinically healthy women as their potential epigenetic mechanism. Previous evidence supports that the estrogen receptor beta (ER-β), whose anti-cancer roles had already been revealed in BC, is downregulated in the breasts of healthy nulliparous women. Nevertheless, data on such a link about its methylation alterations have not been reported. The goal of current study was to determine possible methylation alterations at CpG island promoter of the ER-β gene, including promoter 0 N and exon 0 N, in relation to aspects of reproductive history in the healthy breasts. The DNA was extracted from the breasts of 120 subjects undergoing cosmetic mammoplasty. Thereafter, the methylation levels of targeted regions in ER-β gene were determined by using MeDIP-qPCR assay. The results revealed that ER-β exon 0 N had no methylation in 84.2 % of the women, whereas the rest, comprising 2.5 % and 13.3 % of the samples, showed a lower and higher of its methylation, respectively. Interestingly, nulliparous women were found to have an elevated methylation level of the ER-β exon 0 N than parous women (P = 0.036). Moreover, we observed a high methylation of the ER-β exon 0 N in the breasts of non-breastfeeding women compared to breastfeeding subgroup (P = 0.048). Likewise, the non-breastfeeding subgroup showed exon 0N high methylation in comparison to women with breastfeeding >24 months (P = 0.023). Finally, although we found that 6.67 % of the samples had a high methylation level at the promoter 0N, no any relationship was found between its methylation and reproductive history. These results may provide key clues to revealing the epigenetic mechanism through which the nulliparity and lack of breastfeeding influencing the risk factor of BC as well as introducing the potential new early prediction and prevention strategies. Although further investigations need to be done in order to gain a better understanding the roles of these epigenetic signatures.
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http://dx.doi.org/10.1016/j.prp.2020.153328DOI Listing
February 2021

Investigating the prevalence of hypertension and its associated risk factors in a population-based study: Fasa PERSIAN COHORT data.

BMC Cardiovasc Disord 2020 12 1;20(1):503. Epub 2020 Dec 1.

Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.

Background: A high prevalence rate of hypertension (HTN) and its subsequent serious complications made this disease a major health-treatment concern in many societies. The current study aimed to investigate the prevalence of hypertension and its associated risk factors in Fasa PERSIAN COHORT in south of Iran in 2019.

Methods: This was an analytical-cross sectional study. The study population were the individuals covered by Fasa cohort. Information of the first phase of Fasa Persian cohort in south of Iran was used in this study. Independent t test, chi-square test, analysis of variances, Pearson correlation coefficient, and multiple stepwise regression were used to analyze the obtained data. Thereafter, the data was analyzed using SPSS software version 22, and P value < 0.05 was considered as statistically significant.

Results: Out of 10,111 individuals included in the study, 5546 (54.86%) subjects were women and 4565 (45.16%) other were men. The overall prevalence rate of hypertension was estimated as 46.6%. In the present study, (16/1%) of the participants were with HTN stage 1, and (17/9%) of them were with HTN stage 2. The results show that there were significant positive correlations among HTN and age, BMI, HDL, TG, BUN, ALP, smoking, physical activity, cardiovascular diseases, diabetes, and renal failure (P < 0.5).

Conclusions: Prevalence of HTN in this study population is considerable. Therefore, it is suggested that health system should program some plans to prevent hypertension's prevalence and eliminate its risk factors.
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http://dx.doi.org/10.1186/s12872-020-01797-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706226PMC
December 2020

Evaluation of the potential role of long non-coding RNA LINC00961 in luminal breast cancer: a case-control and systems biology study.

Cancer Cell Int 2020 2;20:478. Epub 2020 Oct 2.

Medical Genetic Ward, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.

Background: Luminal subtype is the most common subgroup of breast cancer (BC), accounting for more than 70% of this cancer. Long non-coding RNAs (lncRNAs) are a group of RNAs which play critical roles in diverse cellular processes. It is proved that dysregulation of them can contribute to the development of various cancers, including BC. LINC00961 was reported to be downregulated in several cancers, however, its expression level in BC remains largely unknown. The purpose of the present study was to investigate the possible role of LINC00961 in luminal A and B subtypes of BC.

Methods: To obtain novel lncRNAs associated with different cancers and differentially expressed lncRNAs (DElncRNAs) between BC tumor and normal tissues, Lnc2Cancer and GDC databases were used, respectively. After performing literature review, the expression level of the selected lncRNA (LINC00961) was evaluated in 79 luminal A and B BC specimens and adjacent non-cancerous tissues by Quantitative Reverse Transcription PCR (qRT-PCR). LINC00961 expression was also evaluated in two luminal A BC cell lines, compared to a normal breast cell line. The comparison of the differences between tumor and adjacent non-tumor samples was performed by paired sample t-test. Moreover, correlation analysis between LINC00961 expression and clinicopathological features was performed using the chi-square, fisher exact, and independent t-test. In order to investigate the possible roles of LINC00961 in luminal A and B BC, different bioinformatics analyses such as functional annotation of the LINC00961 co-expressed genes and protein-protein interaction (PPI) networks construction were also performed.

Results: LINC00961 was selected as a significant DElncRNA which had not been studied in BC. According to q-RT PCR assay, LINC00961 was downregulated in luminal BC tissues and cell lines. Its expression was correlated with smoking status and the age of menarche in luminal BC patients. Also, the results of the bioinformatics analysis were consistent with the data obtained from q-RT PCR assay. The final results indicated that LINC00961 might be involved in multiple cancer-associated pathways such as chemokine, Ras and PI3K-Akt signaling pathways, GPCR ligand binding, and signal transduction in luminal subtypes of BC. CDH5, GNG11, GNG8, SELL, S1PR1, CCL19, FYN, ACAN, CD3E, ACVRL1, CAV1, and PPARGC1A were identified as the top hub genes of the PPI networks across luminal subgroup.

Conclusion: Our findings suggested that LINC00961 was significantly downregulated in luminal A and B subtypes of BC. Moreover, bioinformatics analysis provided a basis for better identification of the potential role of LINC00961 in luminal subtype of BC.
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http://dx.doi.org/10.1186/s12935-020-01569-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531117PMC
October 2020

Expression of ADR-α1, 2 and ADR-β2 in cumulus cell culture of infertile women with polycystic ovary syndrome and poor responder who are a candidate for IVF: the novel strategic role of clonidine in this expression.

J Recept Signal Transduct Res 2021 Jun 2;41(3):263-272. Epub 2020 Sep 2.

Nonproliferative Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.

Objective: Alpha and beta-adrenoceptors (ADR-α1, 2, and β2) play a regulatory role in the folliculogenesis and steroidogenesis in the ovarian follicles. This study aimed to measure these adrenoceptors mRNA and its protein levels in cumulus cells (CCs) culture of poor ovarian reserve (POR) and polycystic ovarian syndrome (PCOS) infertile women (IVF candidate) and the effect of clonidine treatment at CCs culture.

Methods: This case/control study was conducted in 2017 includes a control (donation oocytes) and two studies (PCO and POR) groups. The ovulation induction drugs were prescribed in all groups. After the oocyte puncture, the follicular fluid was collected and CCs were isolated were cultured. RNA was extracted and cDNA was synthesized and designed the primer for the ADR-α1, 2 and ADR-β2 gene expression. The protein levels were investigated by Western Blot.

Results: The results showed a high level of three adrenergic expressions in PCO women compared to the control group (-value <.001), which can be reduced by clonidine. POR group showed a significant decrease in the gene expression of ADR-α1 (-value = .004) and ADR-α2 (-value = .003) compared to the control group and clonidine treatment had no effect.

Conclusion: The significant increase of three adrenoceptors gene expression and protein levels in CCs culture indicate to the hyperactivity of the ovarian sympathetic nervous system at the receptor levels in women with PCOS, and clonidine confirmed it by reducing this expression. In POR women, the reduction of ADR-α1, 2 expressions maybe lead to the aging process in the ovary.
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http://dx.doi.org/10.1080/10799893.2020.1806320DOI Listing
June 2021

Two dimensional proteomic analysis of serum shows immunological proteins exclusively expressed in sulfur mustard exposed patients with long term pulmonary complications.

Int Immunopharmacol 2020 Nov 24;88:106857. Epub 2020 Aug 24.

Immunoregulation Research Center, Shahed University, Tehran, Iran, Department of Immunology, Shahed University, Tehran, Iran, Department of Immunology, Shahed University, Tehran 3319118651, Iran. Electronic address:

Background: Despite more than 30 years after utilization of sulfur mustard or bis (2-chloroethyl) sulfide (SM) by Iraqi troops against Iranian military members and civilians, there are a lot of reported delayed complications for the exposed people. Nonetheless, the molecular mechanism of action from this chemical warfare agent is not recognized yet.

Material And Method: In this study, we employed two dimensional gel electrophoresis (2DE) technique to investigate the serum proteins from chemical exposed people compared to non-exposed individuals to provide an inside into molecular mechanism of this chemical agent. Each group was divided into two subgroups including individuals with, and without respiratory complications. For each group, 10 individuals were included after informed consent.

Result: The results showed protein spots, which were exclusively/mainly expressed in chemical exposed patients with complications, including T cell receptor alpha, and hematopoietic cell signal transducer. Also there were protein spots that were expressed only in all exposed groups (with and without complications). On the other hand, we could identify protein spots that were exclusively expressed/altered only in non-exposed group with complications including Pre T-cell antigen receptor, CD40 ligand, and multidrug and toxin extrusion proteins.

Conclusion: Our investigation could result in identification of proteins that are associated to chemical exposure, as well as those specific for respiratory complications irrespective of chemical exposure. These candidate proteins can be used as biomarker, as well as a base for understanding the molecular mechanism of this chemical agent.
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http://dx.doi.org/10.1016/j.intimp.2020.106857DOI Listing
November 2020

The efficacy of topical sesame oil in patients with knee osteoarthritis: A randomized double-blinded active-controlled non-inferiority clinical trial.

Complement Ther Med 2019 Dec 22;47:102183. Epub 2019 Aug 22.

Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran; Department of Persian Medicine, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran. Electronic address:

Objective: Sesame oil is an herbal product that has been used to treat the joints pain in several traditional medicines. In this study, we evaluated the efficacy of topical sesame oil versus diclofenac gel in patients with knee osteoarthritis (OA).

Methods: One hundred and four patients were randomly enrolled in two arms of the trial. Patients were treated by topical sesame oil or diclofenac (three times a day) for 4 weeks. Outcome measures were knee pain via visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, knee joint's flexion angle, 8-meter walk test and number of used analgesics. Patients were evaluated at baseline, 2 and then 4 weeks after the intervention.

Results: At the follow-up visits, sesame oil was not inferior to diclofenac regarding scores of WOMAC pain, 8-meter walk test, and knee flexion angle. Although, its non-inferiority was not proved regarding scores of VAS, WOMAC stiffness, and WOMAC total at the 4 week. Moreover, sesame oil was not inferior to diclofenac regarding consumed analgesics.

Conclusion: It seems that the topical sesame oil was non-inferior to diclofenac gel on the reduction of the knee OA pain and improvement of some indicators of its function.
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http://dx.doi.org/10.1016/j.ctim.2019.08.017DOI Listing
December 2019

The immunomodulatory effects of mesenchymal stem cells on long term pulmonary complications in an animal model exposed to a sulfur mustard analog.

Int Immunopharmacol 2020 Mar 22;80:105879. Epub 2019 Nov 22.

Immunoregulation Research Center, Shahed University, Tehran, Iran; Department of Immunology, Shahed University, Tehran, Iran. Electronic address:

Introduction: Sulfur Mustard (SM) is one of the most lethal chemicals with major complications manifested in the lungs. Although the pathogenesis behind SM-induced lung injury still remains poorly understood, prolonged activation and the imbalance of two major macrophage populations (M1 and M2) have been suggested to be involved. Here, we tried to investigate the effectiveness of adipose-derived mesenchymal stem cells (AD-MSC) on long-term lesions induced by CEES, an SM analog. The modulation of pulmonary immune cells and alveolar macrophage phenotype alteration was studied in the animal model used.

Methods: Histopathological changes were investigated in the lungs and analysis of surface markers of alveolar macrophages as well as their cytokine expression in the BAL fluid was carried out by flow cytometry and ELISA, respectively.

Results: Treatment of mice with AD-MSC after intraperitoneal administration of CEES (10 mg/kg) reduces progressive histopathologic changes in the lung. Flow cytometric analysis of isolated alveolar macrophages in the bronchoalveolar lavage showed that the accumulation of both M1 and M2 macrophages in response to CEES was reduced by MSC administration. AD-MSCs caused a marked reduction in the CD86- and CD206-expressing macrophages compared to the untreated groups. The modulating effect of AD-MSCs in the M1-subset was much more significant compared to M2. These findings suggest that AD-MSCs understand their environment and restore the balance in disorders associated with Th1 or Th2 imbalance. Our results indicate that MSCs may represent an effective approach to repair lung injury induced by mustards.
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http://dx.doi.org/10.1016/j.intimp.2019.105879DOI Listing
March 2020

SP-A and TLR4 localization in lung tissue of SM-exposed patients.

Int Immunopharmacol 2020 Mar 11;80:105936. Epub 2019 Nov 11.

Immunoregulation Research Center, Shahed University, Tehran, Iran; Department of Immunology, Shahed University, Tehran, Iran. Electronic address:

Introduction: Long-term pulmonary complications are one of the major long-term consequences of sulfur mustard (SM) exposure. Toll-like receptor 4 (TLR4) involves in the pathogenesis of several pulmonary disorders. Surfactant protein-A (SP-A) regulates LPS-induced TLR4 localization and activation responses. However, the intensity and significance of TLR4 and SP-A expression by lung cells in SM-exposed patients is not clear.

Methods: The gene expression of TLR4 (through real-time PCR) and TLR4 and SP-A positive cells and alveolar type II cells, as SP-A producers, (using IHC) were assessed in formalin fixed paraffin embedded (FFPE) specimens from SM-exposed (n = 17), and non-SM exposed individuals (n = 12).

Results: TLR4 gene expression did not change between study groups. However, its cell surface presentation was significantly reduced in SM-exposed patients and particularly in which with constrictive bronchiolitis compared with the control group (P < 0.001 and P = 0.002, respectively). Frequency of alveolar type II cells was lower in the case group rather than the control group while the number of SP-A positive cells did not alter.

Conclusions: These findings suggest that reduced TLR4 cell surface presentation may have anti-inflammatory function and SP-A may have a critical role in regulation of inflammatory responses in SM-exposed patients. Further investigation on other possible mechanisms involved in TLR4 internalization maybe help to illustrate the modulatory or inflammatory activity of TLR4 in these patients.
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http://dx.doi.org/10.1016/j.intimp.2019.105936DOI Listing
March 2020

Angiogenesis modulatory factors in subjects with chronic ocular complications of Sulfur Mustard exposure: A case-control study.

Int Immunopharmacol 2019 Nov 16;76:105843. Epub 2019 Oct 16.

Immunoregulation Research Center, Shahed University, Tehran 3319118651, Iran. Electronic address:

Background: Chronic ocular complications of Sulfur Mustard (SM) exposure leads to severe ocular morbidity during time. The aim of this study was to compare serum levels of Interleukin 17 (IL-17), IL-12, vascular endothelial growth factor (VEGF)-C, VEGF-D and nitric oxide (NO) in SM-exposed patients versus the control group and to measure tear concentration of VEGF-C only in the SM-exposed group.

Methods: In this prospective case control, 128 SM-exposed patients and 31 healthy control subjects were included. In the case group ocular manifestations were classified to three subgroups of mild (19 cases), moderate (31 cases) and severe (78 cases) forms of disease. Serum levels of IL-17, IL-12, NO, VEGF-C and VEGF-D, in all subjects and tear concentration of VEGF-C in SM-exposed group was evaluated.

Results: All subjects were male and mean ± standard deviation (SD) of age in the case and control groups were 44.9 ± 8.8 and 40.9 ± 10.1 years, respectively. Except for significantly lower serum level of IL-17 (p < 0.001) and NO (p = 0.003), other values were not significantly different. The tear concentration of VEGF-C and serum level of IL-12 were not different between subgroups in the SM-exposed group, yet were significantly lower among those with abnormally dilated and tortuous conjunctival vessels and corneal pannus, respectively (p = 0.01, p = 0.015).

Conclusions: Exposure to SM significantly reduced serum level of IL-17 and NO in the delayed phase, yet did not influence VEGF-C; VEGF-D or IL-12.
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http://dx.doi.org/10.1016/j.intimp.2019.105843DOI Listing
November 2019

Serum Concentration of Thyroid Hormones Long-Term after Sulfur Mustard Exposure.

Iran J Public Health 2019 May;48(5):949-955

Endocrine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Despite several reports on the clinical manifestations of sulfur mustard (SM) intoxication, there is no study on serum concentrations of thyroid hormones long-term after SM exposure. In this study, the changes in thyroid functioning parameters 20 yr after SM exposure were evaluated.

Methods: This study is a part of a larger historical cohort study conducted in 2007 following 20 years of the exposure to SM, called Sardasht-Iran cohort study (SICS). We (SICS) comprised an SM-exposed group from Sardasht City, West Azerbaijan Province, Iran (n=169 as hospitalized group and n=203 as non-hospitalized exposed group); and control participants were selected from Rabat, a town near Sardasht (n=126). Peripheral blood samples were taken in fasting state and then the sera were separated. T4, T3, TSH, antithyroglobulin (anti-Tg), and antithyroid peroxidase (anti-TPO) concentrations in the sera were measured by the ELISA method.

Results: The mean of T3 concentration was significantly higher in the exposed than control group (0.88 ± 0.26 nmol/L vs 0.8 ± 0.25 nmol/L, <0.001). The levels of TSH, T4, and T3up were not significantly different between the exposed and control groups. Thyroglobulin level was significantly higher in the exposed non-hospitalized group (56.07 ± 140.22 μg/L vs 17.66 ± 41.49 μg/L, =0.004), but the level of anti-Tg and anti-TPO showed no significant differences between the two groups.

Conclusion: More studies are needed on the alterations in thyroid hormones, their gene expressions, and mechanisms involved in SM exposure to clarify the causes of these alterations.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717423PMC
May 2019

Alteration in serum levels of ICAM-1 and P-, E- and L-selectins in seriously eye-injured long-term following sulfur-mustard exposure.

Int Immunopharmacol 2019 Nov 31;76:105820. Epub 2019 Aug 31.

Immunoregulation Research Center, Shahed University, Tehran, Iran; Department of Immunology, Shahed University, Tehran, Iran. Electronic address:

Introduction: In this study, the serum levels of soluble intercellular adhesion molecule 1 (ICAM-1), P-, E-, and L-selectins were investigated in seriously eye-injured patients exposed to sulfur mustard (SM).

Material And Methods: A total of 128 individuals with SM-induced serious eye injuries and 31 healthy male controls were included in this study. The serum concentration of soluble forms of adhesion molecules was measured by enzyme-linked immunosorbent assay (ELISA) method.

Result: The serum level of soluble ICAM-1 was significantly higher in the SM-exposed individuals with an abnormality in tear meniscus height, corneal verticillata, and pannus compared with SM-exposed individuals without these abnormalities. There were no significant differences in the level of all three measured selectins between the SM-exposed group and the control groups. SM-exposed individuals with corneal defect had a significantly higher level of soluble E-selectin than SM-exposed individuals without this abnormality. The serum level of soluble P-selectin in the SM-exposed group with limbal abnormality was significantly lower than that in the SM-exposed without this abnormality; also it was significantly higher in SM-exposed group with fundus abnormality compared to that in the control group or SM-exposed group without this abnormality.

Conclusion: The changes in the levels of selectins and ICAM-1 in the SM-exposed group with various ocular abnormalities is a defense mechanism against the toxicity of SM. Further analysis is required to understand the molecular mechanisms of the relationship between adhesion molecules with ocular complications in SM-exposed individuals.
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http://dx.doi.org/10.1016/j.intimp.2019.105820DOI Listing
November 2019

Investigation of the Association between 5-Hydroxytryptamine Transporter Gene-Linked Polymorphic Region with Type 2 Diabetes Mellitus, Obesity and Biochemical Profiles of Serum in Iranian Population.

Avicenna J Med Biotechnol 2019 Jul-Sep;11(3):239-244

Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.

Background: Type 2 Diabetes Mellitus (T2DM) is a serious problem in the world. 5-Hydroxytryptamine (5-HT, serotonin) plays an important role in obesity, glucose control and insulin resistance. The polymorphism of the serotonin transporter gene linked promoter region (5-HTTLPR) might influence 5-HTT expression and serotonin uptake. The polymorphism results in two alleles of L (Long) and S (Short). The aim of the present study was to evaluate the association between 5-HTTLPR genotypes in type 2 diabetes mellitus (T2DM), obesity as well as serum biochemical profiles in Iranian population from 2012 until 2015.

Methods: 180 patients with T2DM and 180 controls were selected and the frequency of S and L alleles was determined by PCR. Then, the relationship between genotypes, body mass index (BMI) and serum biochemical variables was investigated.

Results: The frequency of S and L alleles in experimental and control groups was the same [for the L allele p=0.754, OR (95%CI)=1.103 (0.597 to 2.041) and for the S allele p=0.906, OR (95%CI)=(0.490 to 1.676)]. However, the mean triglyceride, cholesterol, LDL-C, systolic and diastolic blood pressure levels in the diabetic subjects with LL genotype were significantly higher than LS and SS genotypes (p<0.001) in this population.

Conclusion: The L allele of 5-HTTLPR was related to the increased serum lipids and blood pressure in the diabetic patients. However, there was no relationship between the polymorphism of 5-HTTLPR L/S and T2DM in Iranian population.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626511PMC
August 2019

Altered levels of GST activity, Vit C, TPX and Cu in individuals with long-term sulfur mustard-induced lung complications.

Inhal Toxicol 2018 Nov - Dec;30(13-14):483-491. Epub 2019 Mar 8.

d Immunoregulation Research Center , Shahed University , Tehran , Iran.

Context: Sulfur mustard (SM) as a cytotoxic and blistering agent can alkylate a variety of cellular components, causing the incidence of ongoing oxidative stress.

Objective: The present study was conducted to assess oxidative stress index (OSI) in SM-exposed veterans with long-term pulmonary complications.

Methods: Participants consisted of 289 SM-exposed individuals with pulmonary complications (classified into three groups: mild, moderate and severe) and 66 healthy individuals as the control group. Enzymatic and non-enzymatic antioxidant and also trace elements were measured in the study groups. Moreover, some of oxidative stress indicators consist of malondialdehyde (MDA), protein carbonyl (CO), total antioxidant (TA) and total peroxide (TPX) were measured and then OSI was calculated.

Results: Glutathione-S-transferase (GST) activity and vitamin C (Vit C) were significantly decreased in SM-exposed patients as compared with controls. Besides, Cu level and Cu/Zn ratio in SM-exposed veterans showed a significant correlation with the severity of the diseases. Serum TPX was significantly increased in SM-exposed individuals, as a result of which the OSI was slightly higher in them than controls. This can be considered as an indicative for oxidative stress in SM-exposed patients.

Conclusion: This study suggests a particular role for TPX, Cu, Vit C and GST in SM-induced pulmonary complications. Therefore, a special attention should be paid to these factors in designing therapeutic protocols, which can reduce the progression risk of the disease.
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http://dx.doi.org/10.1080/08958378.2018.1545809DOI Listing
September 2019

Methylation of progesterone receptor isoform A promoter in normal breast tissue: An epigenetic link between early age at menarche and risk of breast cancer?

J Cell Biochem 2019 08 28;120(8):12393-12401. Epub 2019 Feb 28.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Emerging evidence indicates that some altered patterns of methylation that occur in breast tumors may also be found in breast tissue of healthy women in relation to the breast cancer (BC) risk factors. Progesterone receptor (PR) isoform α is a crucial regulator of breast hormone responsiveness and its hypermethylation plays an important role in the initiation and development of breast tumors. However, such a methylation change in healthy women and its link with the different risk factors has not yet been investigated. In the present study, we aimed to examine the relationship of possible methylation changes within a critical region in the promoter CpG island of PGR-α (progesterone receptor α) gene in the healthy women with a set of reproductive and nonreproductive BC risk factors. The breast tissues were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. The genomic DNA was extracted from the breast tissues and the methylation level of PGR-α promoter CpG island was determined by using MeDIP-qPCR assay. Using regression analysis, we found that increasing menarche age is inversely associated with the high methylation of PGR-α promoter ( β = -0.790, SE = 0.362; P = 0.031). Although lactating women had more methylation than nonlactating women (P = 0.026, the t test), this result was not confirmed by regression models. Such an observation may be helpful in better understanding of the underlying mechanisms by which early age at menarche increases the risk of BC. However, this perspective requires further validations in larger studies of more subjects as well as the inclusion of other related genes.
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http://dx.doi.org/10.1002/jcb.28505DOI Listing
August 2019

Association of Sulfur Mustard-Induced Ocular Problems with Serum and Blood Biochemical Parameters Changes.

Iran J Pathol 2018 17;13(2):157-166. Epub 2018 Jul 17.

Immunoregulation Research Center, Shahed University, Tehran, Iran.

Background & Objective: Many biochemical features of sulfur mustard (SM) intoxication have remained unknown. So far, the direct association between biochemical parameter changes and ocular problems in patients exposed to SM is not evaluated. The current study aimed at evaluating the associations between the ocular findings in patients with SM intoxication and the changes of serum and blood biochemical parameters.

Methods: In the current study, 372 patients exposed to SM and 128 matched controls were compared concerning the association between their ocular problems and biochemical parameters. Ocular problems include photophobia, ocular surface discomfort (OSD), etc. Biochemical parameters include uric acid, creatinine (Cr), hematocrit (HCT), total, direct and indirect bilirubin, high-density lipoproteins (HDL), alanine aminotransferase (ALT), calcium (Ca), fasting blood sugar (FBS), mean corpuscular hemoglobin concentration (MCHC), etc.

Results: The SM-exposed group with photophobia, OSD, tearing, blurred vision, abnormal tear status, and slit-lamp findings had significantly higher mean serum and blood levels of uric acid, Cr, HCT, and total and indirect bilirubin than the controls. The SM-exposed group with photophobia, tearing, ocular pain, blurred vision, bulbar conjunctival and limbal abnormalities had significantly higher mean serum and blood levels of HDL, ALT, Ca, FBS, MCHC, and HDL, indirect and total bilirubin, compared to the control group.

Conclusion: The association of photophobia with uric acid, OSD and tearing with Cr, photophobia with HDL, ocular pain with Ca, and blurred vision with FBS may be explained for their known ocular effects in the SM-exposed subjects. SM-induced biochemical changes may intensify the ocular problems induced by the direct effects of SM.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339492PMC
July 2018

Assessment of Preventive Behavior for Cervical Cancer with the Health Belief Model

Asian Pac J Cancer Prev 2018 Aug 24;19(8):2155-2163. Epub 2018 Aug 24.

Department of Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran. Email:

Introduction: Cervical cancer is a leading cause of death in developing countries. However, taking regular Pap smears screening, one of the most effective screening tests, can reduce chance of cervical cancer remarkably. The first step in health education is choosing the right model, one of the best known being the Health Belief Model (HBM). Here, we evaluated different HBM factors with regard to cervical cancer preventive behavior in Fasa, Iran. Materials and methods: This cross-sectional study included 200 married women between the ages of 17 and 64 in Fasa during 2013. Participants were selected through stratified sampling from urban health centers. The questionnaire of the HBM included four sections and was filled out by interview. Data analysis was with SPSS 21, ANOVA and t-tests and Internal correlations between components of model were analyzed in terms of the Spearman Pearson correlation coefficient. Results: The mean age of the participants was 35.6±9.89 years. Some 52% had undergone a Pap test. The percentage values for participants’ knowledge and perceived susceptibility were 49.5% and 46%, respectively, considered as moderate. Perceived severity and benefits were good at 56.5% and 73%, respectively, while perceived barriers was moderate (46.5%). Also, 57.1% demonstrated a good self-efficacy and 61% good behavior. Discussion: We found that the most predictable factors for knowledge and behavior were age, income level, perceived benefits, perceived severity and self-efficacy according to the HBM. These factors should be taken into account for achieving acceptable preventive behaviors in health programs.
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http://dx.doi.org/10.22034/APJCP.2018.19.8.2155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171406PMC
August 2018

Expression levels of breast cancer-related GAS5 and LSINCT5 lncRNAs in cancer-free breast tissue: Molecular associations with age at menarche and obesity.

Breast J 2018 11 21;24(6):876-882. Epub 2018 May 21.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Long noncoding RNAs (lncRNAs) constitute a major class of the human transcriptome which play crucial roles in the key biological processes of both normal and malignant breast cells. Although the aberrant expression of lncRNAs has been well-documented in breast cancer (BC), little is currently known about the association between their expression levels in the breast tissue of healthy women and BC risk factors, especially the reproductive or demographic characteristics that are among the most well-known BC risk modifiers. This study was an attempt to investigate the correlation between the expression levels of 2 breast cancer-related lncRNAs, including GAS5 and LSINCT5, and reproductive and demographic characteristics in 145 normal breast tissues that were obtained from women without breast cancer undergoing cosmetic surgery. Total RNA was extracted from fresh normal breast tissues, and the expression level of target lncRNAs was quantified using real-time qPCR. Differences in the mean normalized gene expression among the subgroups of different variables were analyzed. The expression levels of both genes was lower in the overweight-obese (BMI ≥ 25) subgroup than that in the normal BMI (BMI < 25) subgroup (GAS5 P = .019, LSINCT5 P = .036). Moreover, the expression level of GAS5 was negatively correlated with BMI (r: -.170, P: .041). The expression level of GAS5 was higher in women with late menarche (>13 years) than that with early menarche (≤13 years; P = .017). These findings may assist to obtain insights into the molecular mechanisms through which the reproductive or obesity-related estrogen changes contribute to the breast carcinogenesis. In conclusion, this study presents the first evidence for the presence of a link between the lncRNA expression and the reproductive or obesity related factors in the breast tissue of healthy women.
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http://dx.doi.org/10.1111/tbj.13067DOI Listing
November 2018

A link between expression level of long-non-coding RNA in breast tissue of healthy women and obesity.

Int J Biol Markers 2018 Nov 24;33(4):500-506. Epub 2018 Apr 24.

Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Epidemiological and experimental literature indicates that the risk of breast cancer incidence is strongly linked to hormone-dependent factors, including reproductive history and obesity. However, the molecular mechanisms underlying the association between these factors and breast cancer risk are poorly understood. The aim of this study, therefore, was to determine whether obesity and reproductive history are associated with expression levels of two breast cancer-related long non-coding RNAs (lncRNAs), namely and in cancer-free breast tissues of women.

Methods: In the current research, 145 healthy women were recruited, and the quantitative expression levels of the two lncRNAs were determined through qPCR assay after gathering the mammoplasty breast tissue samples.

Results: It was found that women with body mass index (BMI)≥30 kg/m and BMI 25-29 kg/m show a low expression of compared to the BMI<25 kg/m (=0.031 and =0.027, respectively). Then, the correlation analysis disclosed a negative correlation of low expression with increasing BMI (r=-0.194, =0.019). Interestingly, this analysis demonstrated a negative correlation between low expression of the and high BMI in women with menarche age below 14 (r=-221; =0.028). Lastly, it was also revealed that there was a negative association of the low expression level of with increasing BMI in women through regression models (B=-0.048, =0.019).

Conclusions: These findings suggest interesting clues about the links between high BMI and the expression levels of in non-diseased breasts that may help us better understand the underlying mechanisms through which obesity contributes to breast carcinogenesis. However, such results need more validations in future research.
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http://dx.doi.org/10.1177/1724600818762258DOI Listing
November 2018

Dietary pattern in pregnancy and risk of gestational diabetes mellitus (GDM).

Diabetes Metab Syndr 2018 May 16;12(3):399-404. Epub 2018 Mar 16.

Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran.

Aim: Among the most common metabolic disorders during pregnancy is gestational diabetes mellitus (GDM). This research was conducted to examine the dietary pattern in women with GDM.

Material And Methods: In this case-study, 204 pregnant women (104 cases and 100 control women) were chosen through convenient sampling and random sampling. The subjects' food intakes were assessed using semi-quantitative food frequency questionnaire, while their activities evaluated by physical activity questionnaire. Anthropometric indices were measured based on standard instructions, and the body mass index was calculated. The dietary patterns were determined using principal component analysis and its relationship with preeclampsia was tested using logistic regression method.

Results: Unhealthy and healthy dietary patterns were found among the pregnant women. In the unhealthy group, after modifying the effect of confounding variables, a significant relationship was observed between dietary pattern and having gestational diabetes (OR = 2.838,95% CI:1.039-7.751). In the healthy group, on the other hand, the people in the fourth quartile had 149% and 184% higher chance not to catch gestational diabetes before and after modification with confounders, respectively (OR = 0.284,95% CI:0.096-0.838), when compared with people in the first quartile.

Conclusion: The findings indicated that selection of foods including fruits, vegetables, low-fat dairies, etc. as healthy dietary pattern is associated with diminished risk of GDM among pregnant women. Determining healthy dietary pattern during pregnancy, considering the foods consumed among pregnant women, as a useful and practical guide during this period can be publicized for training and nutritional interventions.
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http://dx.doi.org/10.1016/j.dsx.2018.03.004DOI Listing
May 2018

Waist circumference is a mediator of dietary pattern in Non-alcoholic fatty liver disease.

Sci Rep 2018 03 19;8(1):4788. Epub 2018 Mar 19.

Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.

Non-alcoholic fatty liver disease (NAFLD) is an example of pathological fat accumulation in the liver and one of the major health conditions in the world. This study aimed to examine the independent role of dietary patterns in the development of NAFLD. In a cross-sectional study, 1500 individuals referred to a nutrition clinic were randomly selected, their demographic, anthropometric and blood metabolic indices were obtained, and food frequency questionnaires were completed for them. Liver stiffness was calculated using the NAFLD score formula and fibroscan. The two dominant dietary patterns identified were the "healthy" and "unhealthy dietary patterns". A significant percentage of those with NAFLD (45%) were in the upper quartile of the unhealthy model; however, only 10% had the healthy pattern (p < 0.001). In this study, 32.9 and 13.9% of the healthy and unhealthy participants were in the upper quartile of the healthy diet pattern. Also, it was shown that waist circumference is a strong mediator of dietary patterns and NAFLD relationship, and the indirect effect of diet through abdominal circumference is 28 times greater than the direct effect on NAFLD. The results suggested that healthy and unhealthy dietary patterns are respectively associated with lower- and higher-risk of NAFLD but the role of waist circumference as a mediator deserves more consideration.
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http://dx.doi.org/10.1038/s41598-018-23192-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859081PMC
March 2018

Evaluation of Association Between the Serum Levels of MMP-9 and MMP-9/TIMPs With Soluble Forms of Selectins and Itching Induced by Sulfur Mustard.

Iran J Pathol 2017 27;12(3):257-264. Epub 2017 Jan 27.

Dept. of Immunology, Tarbiat Moddares University, Tehran, Iran.

Background & Objective: Pruritus is the most frequent chronic dermal complication of sulfur mustard (SM), which negatively influences the quality of life. Exact pathophysiology of SM-induced itching is unknown. The current study aimed at evaluating the possible association between SM-induced itching and the serum levels of matrix metalloproteinase (MMP)-9 and their endogenous inhibitors, and serum levels of soluble forms of selectins (sL-, sP-, and sE-selectins) as adhesion molecules involved in the development of different inflammatory reactions.

Methods: Serum levels of MMP-9, MMP-9/ tissue inhibitors of metalloproteinases (TIMPs), and selectins were measured by the enzyme-linked immunosorbent assay (ELISA), and compared between the groups (n=368) with and without itching, and matched control groups (n=126).

Results: Serum levels of MMP-9 were significantly higher in the SM exposed group with itching, compared with that of the group without itching (medians: 894 and 624 pg/mL respectively; P-value =0.034). There was no relationship between the serum levels of MMP-9/TIMP-1, MMP-9/TIMP-2, MMP-9/TIMP-4, and itching in the patients exposed to SM. Median serum levels of sE- and sL-selectins in the exposed group with itching were higher than those of the exposed group without itching. These differences were statistically insignificant (P-values =0.084 and 0.095, respectively).

Conclusion: According to the results of the current study, the increased serum levels of MMP-9 and selectins 20 years after exposure may play role in the pathogenesis and persistence of SM-induced itching in the exposed individuals.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835374PMC
January 2017

Association of glutathione S-transferase polymorphisms with the severity of mustard lung.

Bioimpacts 2017 30;7(4):255-261. Epub 2017 Aug 30.

Immunoregulation Research Center, Shahed University, Tehran, Iran.

Glutathione S-transferase (GST) is one of the major detoxifiers in alveoli. Polymorphism in GST genes can influence the ability of individuals to suppress oxidative stress and inflammation. The present study was aimed to explore the hypothesis that the genetic polymorphisms of GST , and are associated with the severity of the mustard lung in the sulfur mustard-exposed individuals. Blood samples were taken from 185 sulfur mustard-exposed and 57 unexposed subjects. According to the stage of the mustard lung, sulfur mustard-exposed patients were categorized in the mild/moderate and severe/very severe groups. A multiplex PCR method was conducted to identify and null genotypes. To determine the polymorphisms of GSTP1 in exon 5 (Ile105Val) and exon 6 (Ala114Val), RFLP-PCR method was performed. The frequency of homozygous deletion was significantly higher in the severe/very severe patients compared with the mild/moderate subjects (66.3% vs. 48%, = 0.013). The null genotype was associated with the severity of mustard lung (adjusted odds ratio [OR], 2.257; 95% CI, 1.219-4.180). There was no significant association between and polymorphisms with the severity of the mustard lung. The different distribution of null genotype in severe/very severe and mild/moderate groups indicated that the severity of the mustard lung might be associated with the genetic polymorphism(s).
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http://dx.doi.org/10.15171/bi.2017.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801537PMC
August 2017

Polycystic ovary syndrome and circulating inflammatory markers.

Int J Reprod Biomed 2017 Jun;15(6):375-382

Reproductive Health Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Human and experimental studies suggest that the sympathetic regulatory drive in the ovary may be unbalanced (hyperactivity) in polycystic ovary syndrome (PCOS). Dysfunctional secretion of interleukin (IL) -1 (α & β) or related cytokines may thus be related to abnormal ovulation and luteinization.

Objective: The aim of this study was the evaluation of cytokines' pattern in PCOS women and discussion about the explanation of cross-talk between two super systems: sympathetic and immune systems and explanation sympatho-excitation and relationship with interleukins.

Materials And Methods: In this study, 171 PCOS women aged between 20-40 years were studied the. Their body mass index was <28. The patients were divided into two groups: study group (n=85, PCOS women) and control group (n=86 normal women). The blood sample was obtained on the 3 day of menstruation cycle. IL-17, IL-1α, IL-1β, and TNF-α concentrations were determined in both groups.

Results: The median serum level of IL-1α in the PCOS group was higher than the control group (293.3 and 8.0, respectively, p<0.001). Also, the median serum level of IL-1β was higher than the control group (5.9 and 3.1 respectively). But the median serum of level IL-17 in women with PCOS was significantly lower than the control group (p<0.001).

Conclusion: Our results confirm that PCOS is a low-level chronic inflammation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605859PMC
June 2017

Epigenetic Changes of the ESR1 Gene in Breast Tissue of Healthy Women: A Missing Link with Breast Cancer Risk Factors?

Genet Test Mol Biomarkers 2017 Aug 14;21(8):464-470. Epub 2017 Jul 14.

1 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences , Tehran, Iran .

Background: Reproductive history and obesity are among the well-recognized risk factors in the development of breast cancer, which are partially mediated by the increased exposure of breast tissues to estrogens. However, only a few studies have investigated the link between these risk factors and the pattern of methylation signatures in the breast tissue of healthy women. The role of the estrogen receptor 1 (ESR1) gene hypermethylation is reportedly important in the development of breast cancer. Thus, it is speculated that such ESR1 epigenetic changes may be influenced or shaped by obesity and reproductive history-related factors before and during breast carcinogenesis.

Materials And Methods: Breast samples were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. DNA was extracted from the breast tissues and, then, the methylation levels at the promoter and exon 1 regions of the ESR1 gene CpG island were determined by using the methylated DNA immunoprecipitation-quantitative PCR assay.

Results: The methylation level of the ESR1 promoter observed in women with a body mass index (BMI) ≥30 kg/m (p ≤ 0.001) was higher than in the subgroups of women of BMI <25 kg/m (p < 0.001) and BMI 25-29 kg/m (p < 0.001) and was also higher in postmenopausal women compared with that in premenopausal women (p = 0.046). Pearson correlation coefficient analyses also showed that the high methylation of the ESR1 promoter was correlated with increasing age (r = -0.246, p = 0.007) and BMI (r = -0.331, p ≤ 0.001). Finally, linear multivariate regression revealed a significant association between high methylation rates in the ESR1 gene promoter and increased BMI (β = -0.285, 95% CI = -0.457 to -0.113, p = 0.001). Furthermore, a higher methylation level at the ESR1 gene exon 1 was found in the BMI ≥ 30 kg/m subgroup compared to the BMI 25-29 kg/m subgroup (p = 0.023).

Conclusion: These findings provide new hints about the relationship between epigenetic changes within the ESR1 gene CpG island and postmenopausal obesity and aging in cancer-free women. In terms of lifestyle intervention opportunities, this study also highlights the significance and feasibility of such interventions for BMI as a modifiable risk factor.
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http://dx.doi.org/10.1089/gtmb.2017.0028DOI Listing
August 2017

Quality of life and general health of infertile women.

Health Qual Life Outcomes 2017 Jul 12;15(1):139. Epub 2017 Jul 12.

Department of English, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.

Background: Measuring the quality of life (QOL) is a benchmark in today's world of medicine. The aim of the present study was to determine the general health and QOL of infertile women and certain affecting conditions.

Methods: In a cross-sectional study, 161 infertile women referring to Dr. Rostami's Infertility Center of Shiraz, Southern Iran, in 2013 were enrolled by the convenience sampling method. Data were collected via a socio-demographic, general health (GHQ28), and the QOL Questionnaire of Infertile Couples and analyzed using descriptive and analytical statistics.

Results: According to 146 completely filled-out questionnaires, the mean age of the participants and their spouses were 29.4 ± 5.4 and 33.8 ± 5.8 years, respectively. Moreover, the general health of 57 (39%) patients was normal and that of 89 (61%) patients showed a degree of impairment. The scores for depression and physical symptoms were the highest and lowest, respectively. In addition, quite positive, positive, neutral, and negative specific QOL of infertile women were detected in 4 (2.8%), 72 (49.3%), 70 (47.9%), and 0 (0%) individuals, respectively. The total QOL scores had maximum correlation with GHQ anxiety (r = -0.596, P < 0.001) and general health scores had the highest correlation with physical QOL (r = -0.637, P < 0.001). The QOL was economically (P = 0.027), emotionally (P = 0.004), sexually (P = 0.017), physically (P = 0.037), and psychologically (P = 0.001) less for the women living in rural areas than other infertile women. However, university education (P = 0.015) and higher income per month (P = 0.008) had positive associations with QOL.

Conclusion: General health of more than half of the infertile women indicated a degree of disorder. These women face the risk of anxiety, social dysfunction, and depression. Educational status, monthly income, and rural/urban residency are the major factors influencing the QOL.
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http://dx.doi.org/10.1186/s12955-017-0712-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508693PMC
July 2017

Relationship between metabolic syndrome and osteoarthritis: The Fasa Osteoarthritis Study.

Diabetes Metab Syndr 2017 Dec 3;11 Suppl 2:S827-S832. Epub 2017 Jul 3.

Department of Pathology and Lab Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.

Background: An association between metabolic syndrome (MeS) and osteoarthritis (OA) has been reported in recent years; however, conflicting findings have been reported regarding this matter. Inhere we evaluated the relationship between different components of MeS and OA in a Fasa osteoarthritis registry (FOAS).

Methods: The registry includes all OA cases who referred to Fasa hospital (Iran) since 2013. Overall, 131 patients with OA with a Kellgren & Lawrence (K&L) score >1 and 261 controls were compared.

Results: Overall, 82.4% of individuals in the OA group and 40.8% of participants in the control group had MeS (P<0.001). Patients with OA had a 6.8 (95% CI: 4.1-11.4) higher chance of acquiring MeS. After adjusting for sex, age, and BMI, odds' ratio (OR) for acquiring MeS in OA group increased to 10.9 (95% CI: 5.5-21.8). Among MeS criteria's, high waist circumference (WC) has strongest correlation for acquiring OA (OR=27.535, 95% CI: 6.003-126.306).

Conclusion: Our findings revealed that metabolic markers are strongly associated with OA and the addition of each component of the MeS, significantly increases the risk of developing OA, therefore control of metabolic factors and appropriate screening must be considered in health policy making and prevention programs.
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http://dx.doi.org/10.1016/j.dsx.2017.07.002DOI Listing
December 2017

The SDF1 A/G Gene Variant: A Susceptibility Variant for Myocardial Infarction.

Genet Test Mol Biomarkers 2017 Aug 26;21(8):506-511. Epub 2017 Jun 26.

2 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences , Tehran, Iran .

Background: Although environmental factors play an important role in susceptibility to myocardial infarction (MI), genetic determinants also provide a significant contribution. This study aimed to determine whether or not MI susceptibility is influenced by the SDF1-rs1801157A/G and HHEX-rs1111875 A/G polymorphisms in an Iranian population.

Methods: A total of 120 patients with MI and 120 healthy controls were enrolled. Blood samples were collected from all the participants for genomic DNA extraction and testing. Polymorphism genotyping was determined by the polymerase chain reaction-restriction fragment length polymorphism technique.

Results: Multiple logistic regression analysis revealed that the A allele and AA genotype of the SDF1-rs1111875 polymorphism produce a significant risk of MI both before (crude odds ratio [OR] = 8.83, 95% confidence interval [95% CI] = 1.05-73.76, p = 0.025) and after adjustment (adjusted OR = 8.12, 95% CI = 5.02-19.42, p = 0.04). In contrast, the GG genotype of the SDF1-rs1111875 polymorphism provides a protective effect on MI in a recessive model (GG vs. AA+AG) before (crude OR = 0.57, 95% CI = 0.34-0.97, p = 0.037) and after adjustment (adjusted OR = 0.53, 95% CI = 0.3-0.82, p = 0.021). No association was found between the HHEX-rs1111875 A/G polymorphism alleles and the susceptibility to MI.

Conclusion: Taken together, the current findings suggest that the SDF1-rs1801157A/G gene variant may play an important role in relation to MI in this Iranian population. Nevertheless, more replication studies and meta-analyses should be carried out in this area.
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http://dx.doi.org/10.1089/gtmb.2017.0023DOI Listing
August 2017

Influences of IL-1b-3953 C>T and MMP-9-1562C >T Gene Variants on Myocardial Infarction Susceptibility in a Subset of the Iranian Population.

Genet Test Mol Biomarkers 2017 Jan 8;21(1):33-38. Epub 2016 Nov 8.

2 Noncommunicable Diseases Research Center, Fasa University of Medical Sciences , Fasa, Iran .

Aims: IL-1b-3953 C>T and MMP-9-1562C>T variants have been shown to be linked to the development of myocardial infarction (MI), although previous studies have reported inconsistent results. The aim of the present study was to determine whether these genetic variations are associated with MI susceptibility in an Iranian population.

Methods: In the current study, 117 patients with MI and 120 control group members were selected as participants. Peripheral blood samples were taken from all the subjects for genomic DNA extraction. Single nucleotide polymorphism (SNP) genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays.

Results: Multiple logistic regression analysis revealed that the TT genotype of the IL-1b-3953 C>T polymorphism is associated with a significant MI protective effect in: the homozygote model after adjustment for MI risk factors (odds ratio [OR]: 0.18, confidence interval [95% CI] = 0.04-0.72; p = 0.01); and also in the recessive genetic model both before (OR: 0.39, 95% CI: 0.15-0.96, p = 0.04) and after (OR: 0.15, 95% CI: 0.04-0.58, p = 0.006) adjustment for MI risk factors. Furthermore, multiple logistic regression analysis indicated that the individuals with the TT genotype of the MMP-9-1562C>T polymorphism were significantly protected against MI in comparison with the CC genotype (OR: 0.01, 95% CI: 0.002-0.68, p = 0.03).

Conclusion: The findings suggest that the minor alleles of the two polymorphisms under study both have protective effects with respect to MI susceptibility in the Iranian population.
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http://dx.doi.org/10.1089/gtmb.2016.0240DOI Listing
January 2017

Increased Serum Levels of IL-17A and IL-23 Are Associated with Decreased Vitamin D3 and Increased Pain in Osteoarthritis.

PLoS One 2016 7;11(11):e0164757. Epub 2016 Nov 7.

Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.

Introduction: Osteoarthritis (OA) is the most common type of arthritis and proinflammatory cytokines have been considered as the main etiologic factor in the pathogenesis of the disease. Serum levels of cytokines, that are associated with innate immunity and TH1 cells, have been analyzed in OA patients, however, there is limited research that profiles cytokines associated with Th17 cells and their relation to vitamin D3 and pain.

Material And Methods: The sera from 131 patients with OA and 262 healthy controls were evaluated for serum levels of IL-17A, IL-21, IL-23 and vitamin D3 using ELISA.

Results: Serum levels of IL-17A, and IL-23 were statistically higher in OA patients than in healthy controls, while IL-21 and vitamin D3 were significantly lower in OA patients when compared to controls. A significant positive correlation was found between the serum levels of IL-17A and IL-23 using WOMAC pain scores and vitamin D3 serum levels.

Discussion: The results suggest that IL-17A plays a significant role in OA pathogenesis and the induction of pain. Decreased serum levels of vitamin D3 may reflect a positive role played by the factor in the regulation of immune responses in OA patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0164757PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098728PMC
September 2017