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OBJECTIVE: War toxin, mustard gas, alkylating agent results in male infertility via inducing reactive oxygen species (ROS) production and DNA mutagenesis. SIRT1 and SIRT3 are multifunctional enzymes that involve in the DNA repair, oxidative stress responses. This study aim is to assess the correlation between serum levels of SIRT1, SIRT3 and both rs3758391T>C and rs185277566C>G gene polymorphisms with infertility in the war zones of Kermanshah province, Iran. MATERIALS AND METHODS: In this case-control study based on the semen analysis, samples were divided into two groups infertile (n=100) and fertile (n=100). High-performance liquid chromatography (HPLC) method was used to determine the malondialdehyde level, and also a sperm chromatin dispersion (SCD) test was used to evaluate the DNA fragmentation rate. Using the colorimetric assays, superoxide dismutase (SOD) activity was measured. SIRT1 and SIRT3 protein levels were determined by using ELISA. The genetic variants of SIRT1 rs3758391T>C, and SIRT3 rs185277566C>G, were detected by polymerase chain reaction-restriction fragment length (PCR-RFLP) technique. RESULTS: Malondialdehyde (MDA) level and the percentage of DNA fragmentation were higher in infertile samples, but serum levels of SIRT1 and SIRT3, and SOD activity was lower in infertile compared to fertile samples (P<0.001). The TC+CC genotypes and the C allele from SIRT1 rs3758391T>C polymorphism, and CG+GG genotypes and the G allele from SIRT3 rs185277566C>G polymorphism could increase risk of infertility (P<0.05). CONCLUSION: The results of this study suggest that war toxins through the impact on genotypes, decreasing levels of SIRT1 and SIRT3 and increasing levels of oxidative stress, lead to defects in the concentration, motility and morphology of sperms and thus, infertility in men.
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Background & objectives: Various studies have suggested a correlation between Fas cell surface death receptor/Fas ligand (FAS/FASL) variants and multiple types of cancers. The present study aimed to investigate the association between FAS-670A/G and FASL-844C/T and the synergistic effects of both variants on the risk of gastric cancer (GC) in the Kurdish population of west of Iran. Methods: This study was conducted by polymerase chain reaction-restriction fragment length polymorphism technique using MvaI and BsrDI restriction enzymes in 98 GC patients and 103 healthy control individuals. Results: According to the obtained results, a significant association (P=0.008) of FASL polymorphism among GC patients and the control group was detected. Furthermore, no significant differences were found in the FAS polymorphism frequencies between GC patients and the control group. Codominant and dominant models in FASL polymorphism showed significant protective effects against GC [odds ratio (OR)=0.307, 95% confidence interval (CI) (0.134-0.705), P=0.005; OR=0.205, 95% CI (0.058-0.718), P=0.013 and OR=0.295, 95% CI (0.129-0.673), P=0.004 for models of codominant CC vs. CT, codominant CC vs. TT and dominant, respectively]. Furthermore, the presence of both FAS-670G and FASL-844T alleles represented a significant protective effect against GC occurrence [OR=0.420, 95% CI (0.181-0.975), P=0.043]. Interpretation & conclusions: So far, we believe this is the first study, the results of which suggest that FASL gene variation and its synergistic effects with FAS gene could be associated with the risk of GC in the Kurdish population in the west of Iran.
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Proteína Ligando Fas , Neoplasias Gástricas , Receptor fas , Humanos , Estudios de Casos y Controles , Proteína Ligando Fas/genética , Receptor fas/genética , Predisposición Genética a la Enfermedad , Genotipo , Polimorfismo de Nucleótido Simple/genética , Neoplasias Gástricas/genéticaRESUMEN
The serum levels and activity of matrix metalloproteinases (MMPs) are associated with the risk of coronary artery calcification (CAC). We sought to investigate the association between MMP-2 -1575G>A (rs243866) and MMP-9 -1562 C>T (rs3918242) SNPs with MMP-2 and MMP-9 serum levels and activity in individuals with CAC. One hundred and fifty-five cases with CAC and 155 healthy individuals as control group from West of Iran were included and frequency of genotypes and alleles of rs243866 and rs3918242 in MMP-2 and MMP-9 genes were determined using PCR-RFLP. We also investigated the serum levels of MMP-2 and MMP-9 and their activity using ELISA and gelatin zymography, respectively. Additionally, serum biochemical parameters including FBS (fasting blood sugar), urea, creatinine, cholesterol, triglyceride, HDL (high-density lipoprotein), LDL (low-density lipoprotein), calcium, and phosphorus as well as blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)) were measured. Our results showed that both serum levels of MMP-2 and MMP-9 (P < 0.001) and their activity (P < 0.001) were higher in individuals with CAC when compared to the control group. Carrying A and T alleles in MMP-2 -1575G>A (rs243866) and MMP-9 -1562 C>T (rs3918242) SNPs, respectively, may predispose the individuals to CAC by acting as the risk factors. Serum levels and activity of MMP-2 and MMP-9 were found to be higher in CAC cases when compared to the healthy controls. Carriers of A allele in rs243866 SNP and T allele in rs3918242 SNP were shown to have higher MMP-2 and MMP-9 serum levels and activity that may result in increased ECM degradation and support the initiation and development of calcification.
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Enfermedad de la Arteria Coronaria/genética , Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Calcificación Vascular/genética , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Irán , Lípidos/sangre , Masculino , Persona de Mediana Edad , Fenotipo , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Regulación hacia Arriba , Calcificación Vascular/sangre , Calcificación Vascular/diagnósticoRESUMEN
OBJECTIVES: Gaucher disease (GD) is the most common autosomal recessive disorder of glycolipid storage. It results from mutations in the glucocerebrosidase (GBA) gene and leads to GBA deficiency. Different mutations are associated with different phenotypes in the three major types of GD. MATERIALS AND METHODS: The spectrum of mutations in GBA gene in 26 unrelated patients with GD from different Iranian populations was determined by DNA sequencing, polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), and amplification-refractory mutation system (ARMS) methods. An in silico analysis was also performed for novel mutations. RESULTS: Six new mutations were identified in this study. The newly detected mutations that could be theoretically harmful included p.I200T (c.599T>C), p.H312D (c.934C>G), p.L325S (c.974T>C), p.L393V (c.1177C>G), p.S439G (c.1315A>G), and p.M455R (c.1365G>A). Also, p.L483P, p.N409S, p.W420X, p.E379K, p.R398Q, p.N227S, p.R202Q, and p.D448H mutations were identified in the patients. Besides, two new complex mutations, namely, p.S439G/p.S439G+p.E379K/- and p.R202Q/p.R202Q+p.N227S/p.N227S, were detected. The most common GBA mutation in the population was p.L483P with an allele frequency of 32.7%, followed by p.N409S (19.2%). CONCLUSION: The present study detected six new mutations of GBA gene among GD patients. Two mutations (p.L483P and p.N409S) were especially common among Iranians; this finding can be used in implementing screening programs and understanding the molecular basis of GD.
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INTRODUCTION: Sickle cell disease (SCD) patients are susceptible to the development of vitamin D deficiency (VDD). Vitamin D through binding to vitamin D receptor (VDR) exerts its function and affects gene transcription in target tissues. VDR gene variants affect bone mineral density. METHODS: In a case-control study, 101 SCD patients including 61 sickle cell anemia (SCA), 39 S/ß-thalassemia, and 1 HbS/HbD (SD) along with 110 healthy individuals from Kurdistan of Iraq were studied. The lipid profile, vitamin D level, FokI, and TaqI variants of VDR and group-specific component (GC) were detected using the standard enzymatic method, the immunodiagnostic systems limited EIA kit and PCR-RFLP methods, respectively. RESULTS: Around 93% and 82% of SCA and S/ß-thalassemia patients, respectively, had VDD compared to 83% of healthy individuals. Severe VDD (<10 ng/ml) was detected in 78.7% of patients with HbSS. Plasma levels of total cholesterol, HDL-C, and LDL-C in SCD patients were significantly lower compared to controls. Vitamin D levels were negatively correlated to TG and positively correlated to total cholesterol and HDL-C. The frequencies of the C allele of FokI were 81.7% (p = 0.003), 80.3% (p = 0.034), and 84.6% (p = 0.011) in all SCD, SCA, and S/ß-thalassemia patients, respectively, compared to 69.1% in controls. However, no significant difference was detected comparing the frequencies of VDR TaqI and GC polymorphisms between SCD patients and controls. CONCLUSION: In the present study, we found hypocholesterolemia, high prevalence of VDR FokI C allele, and low vitamin D levels among children and adults with SCD from Kurdistan of Iraq.
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Anemia de Células Falciformes/diagnóstico , Biomarcadores/análisis , Lípidos/sangre , Polimorfismo Genético , Receptores de Calcitriol/genética , Vitamina D/sangre , Talasemia beta/diagnóstico , Adolescente , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/genética , Estudios de Casos y Controles , Niño , Femenino , Humanos , Irak/epidemiología , Masculino , Talasemia beta/sangre , Talasemia beta/epidemiología , Talasemia beta/genéticaRESUMEN
As a promising strategy in overcoming drug resistance, the nano drug co-delivery system (NDCDS) can transport two or more drugs into the cell. In this study, we sought to compare the dual and single drug-delivery system, to deliver the optimal dose of Resveratrol (RES) and Tretinoin (TTN) into the in vitro matured oocyte and morula-compact stage embryonic cells. The formation of single (RES/TTN) and dual-drug (RES + TTN)-SLN were confirmed by Uv-vis spectrophotometery, dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) technologies. In two experiments, the oocytes/presumptive zygotes were cultured under various concentrations of the single (RES/TTN) and dual-drug (RES + TTN)-SLN. In vitro toxicity studies, including nuclear staining (Aceto-orcein and Hoechst 33342), H2DCFDA fluorescent staining, chemiluminescence assay, and quantitative reverse transcription-PCR (qRT-PCR) techniques, indicated an excellent oocyte/embryo internalization of RES and TTN. Moreover, when oocytes/embryos were treated with the lowest concentration of RES + TTN-SLN, antioxidants-related genes were upregulated, apoptotic-related genes were downregulated, and intra/extracellular ROS production was reduced. In vitro cytotoxicity studies also demonstrated that single/dual-encapsulation of RES or TTN were safe even at the highest concentration (10 and 5 µM) compared to the control group. To sum it up, both delivery systems of RES and TTN by SLN (dual or single encapsulation) can deliver the optimal dose of RES and TTN into the oocyte/embryo. Where the dual-delivery of RES and TTN even at the lowest concentration (0.25 µM + 0.1 µm) showed a synergistic anti-oxidative effect in oocyte/embryo with a better inhibition of intra/extra-cellular ROS production by an enhanced/controlled intracellular penetration.
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Desarrollo Embrionario , Preparaciones Farmacéuticas , Animales , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Lípidos , Ratones , Mórula , Oocitos , Resveratrol/farmacologíaRESUMEN
Caveolin-1(cav-1) is overexpressed in prostate cancer (PC) and is associated with progression of the disease. We investigated the effects of CAV1-T29107A and endothelial nitric oxide synthase (eNOS) G894T polymorphisms on the serum levels of testosterone, NO and prostate-specific antigen (PSA) in patients with PC. We genotyped cav-1 and eNOS genes in 112 PC patients and 150 healthy controls by PCR-RFLP. Serum levels of NO2- and NO3- were measured using spectrophotometry, and serum levels of testosterone and PSA were measured by ELISA. The frequencies of CAV1 genotypes A/T vs. A/A according to the dominant model AT + TT vs. AA genotype and T allele were significantly higher in PC patients in comparison with the control group and considerably increased the risk of disease by 2.19-, 1.44- and 1.6-fold, respectively. AT + TT genotypes were associated significantly with the increased risk of PC in those with smoking or diabetes by 3.08-fold (P = .004). Individuals carrying concurrently the T allele of CAV1 A29107T and the T allele of eNOS G894T genes had a significantly increased risk of PC by 2.52-fold (P = .009). We did not find any significant relationship between eNOS G894T genotypes and alleles with susceptibility to PC. Our results highlighted the significance of CAV1-T29107A SNP but not (eNOS) G894T in the susceptibility to PC in our the population that we have studied.
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Caveolina 1/genética , Predisposición Genética a la Enfermedad , Óxido Nítrico Sintasa de Tipo III/genética , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética , Anciano , Alelos , Estudios de Casos y Controles , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Testosterona/sangreRESUMEN
BACKGROUND: Reactive oxygen species (ROS) play a crucial role in etiology of DNA fragmentation and lipid peroxidation in sperm, leading to infertility in men. The silent information regulators SIRT1 and SIRT3 are members of the sirtuins protein family known to be involved in cancer genetics, aging and oxidative stress responses. The aim ofthis study is to determine the correlation between SIRT1 and SIRT3 with antioxidants, oxidative stress biomarkers, and DNA fragmentation in the semen of asthenoteratozoospermic and normozoospermic men. MATERIALS AND METHODS: In this case-control study, after spermogram analysis the specimens were divided into two groups, normozospermic (n=40) and asthenoteratozoospermic (n=40), according to World Health Organization (WHO) standards. Sperm DNA fragmentation was evaluatedusing the sperm chromatin dispersion (SCD) test.Catalase activity was measured using the Aebi spectrophotometeric method. Total antioxidant capacity (TAC) level and superoxide dismutase (SOD) activitywere measured by using commercially available colorimetric assays. Enzyme-linked immune sorbent assay (ELISA) was used to measure SIRT1 and SIRT3 protein levels of seminal plasma. Malondialdehyde (MDA) level in seminal plasma was determined by high-performance liquid chromatography (HPLC). RESULTS: The asthenoteratozoospermic group had significantly lower catalase and SOD activities and TAC levels in comparison with the normozoospermic group (P<0.001).The percentage of DNA fragmentation and MDA level in the asthenoteratozoospermic group were remarkably higher than in the normozoospermic group. The SIRT1 and SIRT3 protein levels in seminal plasmawere remarkably lower in asthenoteratozoospermic group than the normozoospermic group (P<0.001). CONCLUSION: The results of this study suggest that SIRT1 and SIRT3 protein levels are negatively correlated with oxidative stress and DNA fragmentation in semen. The low levels of SIRT1 and SIRT3 in asthenoteratozoospermic men may lead to an increase in oxidative stress, DNA fragmentation, and lipid peroxidation that eventually result in immotile and immature spermatozoa (asthenoteratozoospermia).
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Matrix metalloproteinases (MMPs) are a group of zinc dependent enzymes that are involved in tumor cell invasion and metastasis. The role of MMP-2 and -9 genetic polymorphism in different malignancies has been the subject of numerous studies. The present research has attempted to discover any positive correlation between MMP-2 and MMP-9 SNPs and prostate cancer (PCa) in patients with a history of either diabetes or smoking habits. 112 PCa-patients and 150 unrelated healthy-controls that matched for age and sex were selected for present case-control study. MMP-2 -1575G/A and MMP-9 -1562 C/T polymorphisms detected by PCR-RFLP, serum tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), testosterone, prostate-specific antigen (PSA), free-prostate-specific-antigen (fPSA), and fPSA/PSA levels were detected by ELISA and enzyme assay, respectively. MMP-2 and MMP-9 activities were measured by gelatin-zymography. Covariates were considered as age, status of cigarette smoking, and a possible history of diabetes mellitus (DM). The frequency of -1575 MMP-2 A/A + A/G and -1562 MMP-9 C/T + T/T genotypes were higher in PCa-patients with DM (74.3%,p = 0.003) and with smoking habits (72.5%,p = 0.005). These genotypes were associated with the increased risk of prostate cancer in smokers (3.52-folds) and in individuals with history of DM (4.34-folds). A significant positive association was found between level of TIMPs (TIMP -1 and TIMP-2) and BMI in PCa-patients and also between testosterone levels and MMP-9 activity in healthy control subjects. For the first time, this study demonstrated that activities of MMP-2 -1575G/A and MMP-9 -1562C/T variants in association with smoking and diabetes are considered significant risk factors for PCa.
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Diabetes Mellitus/epidemiología , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Polimorfismo Genético , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/genética , Fumar/epidemiología , Adulto , Estudios de Casos y Controles , Comorbilidad , Genotipo , Humanos , Irán/epidemiología , Masculino , Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/sangre , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/enzimología , Factores de Riesgo , Testosterona/sangre , Inhibidor Tisular de Metaloproteinasa-1/sangre , Inhibidor Tisular de Metaloproteinasa-2/sangre , Adulto JovenRESUMEN
BACKGROUND: Glioblastoma Multiforme (GBM) is the most common and deadly type of primary brain tumor in adults. Magnetic Resonance Spectroscopy (MRS) is a noninvasive imaging technique used to study metabolic changes in the brain tumors. Some metabolites such as Phosphocholine, Creatine, NAA/Cr, and Pcho/Cr have been proven to show a diagnostic role in GBM. The present study was conducted to analyze important metabolites using MRS multivoxel in GBM tumor. METHODS: In this study, information was collected from 8 individuals diagnosed with GBM using Siemens multivoxel MRS with a magnetic field strength of 3 T. Data were obtained by Point-Resolved Spectroscopy (PRESS) protocol with TE=135 ms and TR=1570 ms. NAA, Pcho, Cr, Ala, Gln, Gly, Glu, Lac, NAAG, and Tau metabolites were extracted and evaluated statistically. RESULTS: Given total number of normal voxels and total number of all voxels, levels of Cr, Glu, NAA, NAAG, and Gly/Tau ratio in healthy voxels were significantly higher than tumoral voxels (p=0.005, p=0.03, p<0.001, p<0.001 and p=0.041, respectively). In contrast, levels of Gly, Gln, Tau, Lac/Cr, Pcho/Cr, Pcho/NAA, Lac/NAA, and Gln/Glu ratios in tumoral voxels were significantly more than healthy voxels (p=0.001, p= 0.037, p<0.001, p=0.010, p<0.001, p<0.001, and p=0.024, respectively). However, levels of Lac and Pcho had no significant difference in the two types of voxels. CONCLUSION: In summary, compared to patients with glioblastoma with 1H-MRS, the Pcho/Cr and Pcho/NAA ratios, and NAAG are the most important parameters to differentiate between tumoral and normal voxels.
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BACKGROUND: Human brucellosis is a multisystem disease with a wide range of clinical signs which often leads to misdiagnosis and treatment delay. Early diagnosis of this disease can prevent the serious complications and mismanagements. This study aimed to evaluate the hematological parameters with predictive value for the diagnosis of brucellosis. METHODS: In this prospective case-control study which was done during 2015-2017 in Imam Reza Hospital, Kermanshah Province, west Iran, 100 patients with a confirmed diagnosis of brucellosis (brucellosis group) and 100 healthy individuals (control group) were studied. The hematological parameters, including hemoglobin (Hb), red blood cell (RBC), white blood cell (WBC) count, lymphocyte count, neutrophil count, platelet count (PLTs), mean platelet volume (MPV), platelet distribution width (PDW), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) of both groups were recorded. The data were statistically compared between the brucellosis and the control groups. RESULTS: The mean age of patients and healthy groups was 44.04 ± 23.11 and 37.92 ± 24.80, respectively (P = 0.062). The WBC, CRP and neutrophil counts were significantly higher in the brucellosis group (P < 0.05). Based on the receiver operating characteristic (ROC) analysis, the sensitivity and specificity were 54% and 66% for the WBC, 45% and 71% for the neutrophil and 65% and 72% for the CRP, respectively. There was no statistically significant difference between the two groups in terms of Hb, RBC, WBC, lymphocyte and platelet count, MPV, PDW and ESR (P > 0.05). CONCLUSION: The results of this study indicate that WBC, CRP and neutrophil count can be used as valuable markers in the preliminary diagnosis of brucellosis. However, further researches are required to standardize these parameters for various forms of brucellosis.
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Fetuin-A (AHSG) is a multifunctional secretory protein and acts as an ectopic valve and artery calcification inhibitor. We assessed the correlation between serum levels of Fetuin-A and both exon 6 (248 C/T) and exon 7 (256 C/G) mutations in patients with coronary artery calcification (CAC), mitral annular calcification (MAC), and aortic valve calcification (AVC). 184 patients and 184 healthy individuals as control group were included. The genetic variants of rs4917 and rs4918 for the AHSG gene were determined by PCR-RFLP and T-ARMS PCR techniques. Fetuin-A levels, fasting blood sugar (FBS), urea, creatinine, calcium phosphorus, and lipid profile were measured. Fetuin-A levels were remarkedly lower in individuals with AVC, MAC, and CAC comparing to the control group (p < 0.001). The CT + TT genotypes and the T allele (AHSG Thr248Met) were associated with the risk of calcification of heart valves and coronary artery by 1.31 and 1.27 times in the patient group, respectively. The frequency of CT genotype and T allele was considerably higher in the patient group comparing to the control group. Patients with T allele (CT + TT) had higher levels of FBS, urea, low-density lipoproteins (LDL)-C, phosphorus, systolic blood pressure (SBP), diastolic blood pressure (DBP) while decreased levels of triglyceride, high-density lipoproteins (HDL)-C, calcium and fetuin-A in comparison to control group. Additionally, there was a positive correlation between serum FBS, urea, creatinine, HDL-C, calcium with fetuin-A, and a negative correlation between phosphorous level, SBP, and DBP with fetuin-A. T allele in rs4917 Single nucleotide polymorphism (SNP) is the risk allele of calcification of heart valves and coronary arteries and fetuin-A levels correlates negatively with the occurrence of the disease.
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Calcinosis/genética , Polimorfismo de Nucleótido Simple , alfa-2-Glicoproteína-HS/genética , alfa-2-Glicoproteína-HS/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Válvula Aórtica/metabolismo , Válvula Aórtica/patología , Estenosis de la Válvula Aórtica/genética , Estenosis de la Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/patología , Calcinosis/metabolismo , Calcinosis/patología , Estudios de Casos y Controles , Vasos Coronarios/metabolismo , Vasos Coronarios/patología , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Irán , Masculino , Persona de Mediana Edad , Válvula Mitral/patología , Calcificación Vascular/genética , Calcificación Vascular/metabolismo , Calcificación Vascular/patologíaRESUMEN
OBJECTIVES: Temporomandibular disorders (TMD) are characterized by pain or discomfort in the temporomandibular joint, periauricular region, masticatory muscles, and neck on one or both sides. It may also be associated with joint sounds, restricted mandibular movements and mandibular deviation. Oxidative agents may have a deleterious role in the pathogenesis of joint diseases, and oxidative stress can lead to TMD. The aim of this study was to assess the oxidative stress biomarkers in the saliva of TMD patients and healthy controls. MATERIALS AND METHODS: This case-control study was conducted on 30 patients with TMDs (5 males and 25 females) with a mean age of 30.7±13.2 years, and 30 healthy controls (5 males and 25 females) with a mean age of 29.16±11.2 years. Saliva samples were collected according to the standard protocol and the total antioxidant capacity of the saliva (non-enzymatic), catalase activity, and malondialdehyde (MDA) levels were measured using the ferric reducing ability of plasma, Aebi's method, and high-performance liquid chromatography, respectively. Finally, The MDA levels were analyzed by the Mann-Whitney test. Other quantitative parameters were analyzed by independent t-test. RESULTS: TMD patients had significantly higher salivary levels of MDA compared to the control group (P=0.001). But there were no significant differences in catalase (P=0.49) and total antioxidant capacity (P=0.22) of TMD patients and healthy controls. CONCLUSION: It seems that oxidative stress may be involved in the pathogenesis of TMDs.
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Gaucher disease (GD) is most frequent disorder of glycolipid storage. The glucosylceramide accumulation might lead to oxidative stress and changes in lipid profile. Regarding the main role of trace elements in hematopoiesis and oxidative stress, this study was aimed to evaluate the zinc and copper levels, three oxidative stress parameters, and lipid profile in GD. Thirty-three patients with GD along with 64 age- and sex-matched healthy controls participated in the study. The levels of zinc and copper were determined using atomic absorption/flame emission spectrophotometer. Malondialdehyde level was measured using HPLC. Total antioxidant capacity (TAC), catalase activity, and lipid profile were assessed using colorimetric methods. Data were analyzed using SPSS software version 16.0. Significant decrease in the serum levels of Zn (p < 0.001) and Cu (p < 0.001) was observed in patients with GD compared to controls. Subjects in control group showed significantly higher levels of TAC than patients with GD (p < 0.001). In contrast, plasma concentration of malondialdehyde was insignificantly higher in patients with GD than controls (p = 0.06). There was a direct correlation between TAC and hemoglobin concentration (p = 0.035; r = 0.369) in patients with GD. Furthermore, the calculated area under receiver operating characteristic curve for HDL cholesterol was equal to 0.938. The results showed that both zinc and copper levels decreased in patients with GD. Patients with GD showed decreased serum content of TAC. It was found that improving the deficiency of zinc and copper by supplementing them could be useful in management of patients with GD.
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Enfermedad de Gaucher/sangre , Lípidos/sangre , Oligoelementos/sangre , Adolescente , Adulto , Antioxidantes/metabolismo , Niño , Preescolar , Femenino , Humanos , Irán , Masculino , Persona de Mediana EdadRESUMEN
Background and Objectives: Studies suggest that FAS/FASL polymorphisms are associated with male infertility; however, their results are still inconclusive. Therefore, this systematic review and meta-analysis aimed to summarize and clarify the overall association of FAS/FASL polymorphisms and risk of male infertility. Materials and Methods: Our search was conducted on the databases of Science Direct, PubMed and Google Scholar. For performing the meta-analysis, pooled odds ratio (OR) values with 95% confidence interval (CI) was applied in order to analyze the strength of association between the FAS/FASL polymorphisms and risk of male infertility. A total of seven relevant studies published up to September 2018 were considered. Results: FASL-844C/T genotype results of 559 patients and 623 healthy individuals were included in our study. For FAS-670A/G genotype effect, 751 patients and 821 healthy individuals were explored. Results showed that all analysis models including dominant, recessive and allelic models of FASL-844C/T and FAS-670A/G polymorphism had no significant effect on infertility in men (p > 0.05 and p > 0.05, respectively). According to sensitivity analysis, our results were stable. Conclusion: We demonstrated that FAS/FASL polymorphisms might not be an effective factor on male reproductive health. For precise determination of FAS/FASL polymorphisms effects on male infertility, large-scale case-control studies should be performed.
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Proteína Ligando Fas/análisis , Infertilidad Masculina/genética , Polimorfismo Genético/fisiología , Receptor fas/análisis , Proteína Ligando Fas/sangre , Predisposición Genética a la Enfermedad , Humanos , Masculino , Factores de Riesgo , Receptor fas/sangreRESUMEN
BACKGROUND: Different studies have investigated TSGA10 expression in various cancerous tissues but, so far no study has been conducted on newly diagnosed (ND) AML patients. The association of TSGA10 gene expression with hypoxia inducible factor (HIF) and angiogenic factors has remained to be fully elucidated and is still a controversial issue. The present study was designed to investigate this association in patients newly diagnosed with AML. METHODS: We evaluated TSGA10, HIF-1α and VEGF mRNA levels in ND AML patients and healthy subjects using real-time PCR technique. Data were analyzed via comparative Livak method. RESULTS: Based on the results of this study, TSGA10 gene expression was decreased in 28 out of 30 (93.3%) samples while VEGF and HIF-1α expression levels were increased in all ND AML patients compared to healthy controls. Diagnostic evaluation was performed by receiver operating characteristic (ROC) curve and area under the curve (AUC) calculation. Respectively, using cut-off relative quantification of 1.604, 0.0329, and 0.0042, the sensitivity values of TSGA10, VEGF, and HIF-1α gene expression were 86.7%, 90%, and 100%. Also, specificity values were 100%, 100% and 100%, respectively. TSGA10 expression was shown to be reduced in ND AML patients compared with healthy subjects and we found a negative correlation between TSGA10 and VEGF expression. CONCLUSIONS: Since TSGA10 interacts with HIF-1 and affects its transcriptional activity, in ND AML patients with decreased TSGA10 expression, VEGF expression was high suggesting a TSGA10 mediated regulation of HIF-1 target genes. Altogether, the current study showed that TSGA10 could be considered as a tumor suppressor in AML patients.
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Biomarcadores de Tumor/análisis , Leucemia Mieloide Aguda/patología , Proteínas/metabolismo , Adolescente , Adulto , Anciano , Proteínas del Citoesqueleto , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Sensibilidad y Especificidad , Transcriptoma , Proteínas Supresoras de Tumor , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Adulto JovenRESUMEN
Gaucher disease (GD) is a rare inherited metabolic disorder and the most common lysosomal storage disorder, caused by a deficiency in glucocerebrosidase enzyme activity. It has been classified according to the neurological manifestations into three types: type 1, without neuropathic findings, type 2 with acute infantile neuropathic signs and type 3 or chronic neuropathic form. However, report of new variants has led to the expansion of phenotype as a clinical phenotype of GD considered as a continuum of phenotypes. Therefore, it seems that a new classification is needed to cover new forms of the disease.
RESUMEN
OBJECTIVE: Chitotriosidase (CT) activity is a useful biomarker for diagnosis and monitoring of Gaucher disease (GD). Its application is limited by some variants in the CT gene. Two main polymorphisms are 24 bp duplication and G102S led to reduce CT activity. The aim of this study was to determine these variants influencing on plasma CT activity. MATERIALS & METHODS: Blood samples were collected from 33 patients with GD, 15 sibling carriers and 105 healthy individuals serving as controls. CT activity was measured using 4-methylumbelliferyl-ß-D-N,N',Nâ³triacetylchitotrioside substrate in plasma samples. The CT genotypes of 24 bp duplication and G102S variants were determined using PCR and PCR-RFLP. RESULTS: Untreated GD patients had a significantly higher CT activity compared to treated patients (P = 0.021). In addition, chitotriosidase activity in carriers was higher rather than controls. Allele frequencies of 24 bp duplication in GD patients, sibling carriers and controls were 0.21, 0.266 and 0.29 and for G102S were 0.318, 0.366 and 0.219, respectively. Different G102S genotypes had not significant effect on CT activity. Chitotriosidase activity has a positive correlation with age in normal group, carriers, and negative correlation with hemoglobin in GD patients. Using cut-off level of 80.75 nmol/ml/h, sensitivity and specificity of CT activity were 93.9% and 100%, respectively. CONCLUSION: Chitotriosidase activity is a suitable biomarker for diagnosis and monitoring of GD. Determination of 24 bp duplication is helpful for more accurate monitoring the GD patient's therapy. However, it seems that, specifying of the G102S polymorphism is not required for Iranian GD patients.
RESUMEN
BACKGROUND: Biotinidase deficiency (BTD) is an autosomal recessive disorder of biotin metabolism. Biotin is a coenzyme that enhances the action of the four enzymes that play an important role in carbohydrates, amino acid, and fatty acid metabolism. Defects in these pathways cause severe metabolic disorder in the body. In general, biotinidase deficiency can be classified into two levels: partial and profound. The incidence of BTD is 1:40,000 to 1:60,000 births in the world, even though no convincing statistical data on the prevalence of this disorder exist in Iran. In this study, we aimed to set up a test for determining biotinidase activity among the Iranian population and report BTD mutations. PATIENTS AND METHODS: The quantitative method for the determination of biotinidase activity was set up in the National Biochemistry Reference Laboratory (NBRL) of Pasteur Institute of Iran in Tehran. To detect mutations in BTD, polymerase chain reaction (PCR) was performed followed by DNA sequencing. RESULTS: The biotinidase activity range values were 3.81 - 8.25 nmol/min/mL. We identified 8 BTD patients out of 47 cases with neurologic signs. We detected two mutations, c.98-104del7ins3 and p.Arg79Cys, in 5 patients with profound BTD, and one p.Asp444His mutation in 3 patients with partial BTD. CONCLUSION: Infants suffering from BTD seem healthy during their first months of life. At present, the screening program for metabolic disorders such as BTD is in progress. The patients that are BTD deficient benefit from the availability of the tests, and consequently receive the Biotin supplements before being clinically affected.
Asunto(s)
Deficiencia de Biotinidasa/diagnóstico , Deficiencia de Biotinidasa/genética , Biotinidasa/sangre , Pruebas Genéticas , Biotinidasa/genética , Deficiencia de Biotinidasa/sangre , Niño , Preescolar , Femenino , Humanos , Irán , Masculino , Mutación , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: The aim of the present study was to investigate the association between angiotensin converting enzyme (ACE) insertion/deletion (I/D) and angiotensin II type-1 receptor (AT1R) A1166C polymorphisms with the risk of preeclampsia and lipid peroxidation in preeclamptic women from Western Iran. METHODS: One hundred and ninety-eight preeclamptic women (128 women with mild and 70 with severe forms) and 100 age- and parity-matched controls were enrolled in this case-control study. RESULTS: The presence of D allele of ACE was associated with a 1.8-fold increased risk of preeclampsia (p=0.002) in total preeclamptic patients. The frequency of AT1R AC+CC genotypes was higher in mild preeclamptic women (32%) compared to controls (27.2%) (p>0.05). In mild preeclamptic women with ID genotype, the level of total antioxidant capacity (TAC) was significantly decreased compared to those with II genotype. Also, there was a trend toward increasing malondialdehyde (MDA) and decreasing TAC levels in mild and severe preeclamptic women with AT1R AA through CC genotypes. CONCLUSIONS: Our study indicates that lipid peroxidation and oxidative stress are involved in the development of preeclampsia that might be influenced by polymorphism in the renin-angiotensin-aldosterone system genes.