RESUMEN

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology. Several studies have suggested that interleukin-18 (IL-18) is associated with SLE pathogenesis. The genotype distribution of IL-18 promoter polymorphisms differs among ethnic populations. The present study aimed to investigate the correlation between IL-18 polymorphisms at positions -137 and -607 in patients situated in Northeastern Iran. METHODS: This case-control study examined the prevalence of IL-18 -137C/G and -607C/A polymorphic variants among 95 SLE patients referred to the Department of Rheumatology, who were referred to the general clinics of Ghaem Hospital and Imam Reza Hospital in Mashhad, Iran, were included in the study. In addition, 100 healthy individuals were included in the control group. DNA from whole blood was extracted by the salting-out method using a commercial kit (Biogene, US). Allelic and genotypic frequencies of polymorphisms (-137G/C, -607C/A) in the IL-18 promoter gene were analyzed using a polymerase chain reaction (PCR)-based amplification refractory mutation system (ARMS) method. RESULTS: The results of this study demonstrated that the frequency of SLE patients with the homozygous C/C genotype of the IL-18 promoter gene at position -137 was significantly higher than that of the homozygous G/G genotype (P < 0.001) in normal controls. Furthermore, the polymorphism analysis performed illustrated a significant association between (-137G/C) and (-607C/A) polymorphisms in the IL-18 promoter gene and SLE (P < 0.005). CONCLUSION: These results indicated that the 607A/A and 137C/C polymorphisms are more prevalent in SLE. Further research involving larger sample sizes from various populations is necessary to elucidate the role of these polymorphisms and the distribution of alleles in SLE patients.

RESUMEN

BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) has a high recurrence rate and muscle-invasive bladder cancer (MIBC) has unfavorable outcomes in urothelial bladder cancer (UBC) patients. Complex UBC-related protein biomarkers for outcome prediction may provide a more efficient management approach with an improved clinical outcome. The aim of this study is to recognize tumor-associated proteins, which are differentially expressed in different stages of UBC patients compared non-cancerous tissues. METHODS: The proteome of tissue samples of 42 UBC patients (NMIBC n = 25 and MIBC n = 17) was subjected to two-dimensional electrophoresis (2-DE) combined with Liquid chromatography-mass spectrometry (LC-MS) system to identify differentially expressed proteins. The intensity of protein spots was quantified and compared with Prodigy SameSpots software. Functional, pathway, and interaction analyses of identified proteins were performed using geneontology (GO), PANTHER, Reactome, Gene MANIA, and STRING databases. RESULTS: Twelve proteins identified by LC-MS showed differential expression (over 1.5-fold, p < 0.05) by LC-MS, including 9 up-regulated in NMIBC and 3 up-regulated in MIBC patients. Proteins involved in the detoxification of reactive oxygen species and cellular responses to oxidative stress showed the most significant changes in UBC patients. Additionally, the most potential functions related to these detected proteins were associated with peroxidase, oxidoreductase, and antioxidant activity. CONCLUSION: We identified several alterations in protein expression involved in canonical pathways which were correlated with the clinical outcomes suggested might be useful as promising biomarkers for early detection, monitoring, and prognosis of UBC.

RESUMEN

Urothelial bladder cancer (UBC) is a heterogeneous multifactorial malignancy with a high recurrence rate. Current procedures for UBC diagnosis suffering from the lack of clinical sensitivity and specificity screening tests. Therefore, biomarkers have promising values to predict pathological conditions and can be considered as effective targets for early diagnosis, prognosis and antitumor immunotherapy. Recently, researchers have been interested for tumor proteins as biomarkers for different diseases. At present, proteomics methods have rapidly progressive that has potential identified biomarkers of UBC. Specifically, there has been several studies on the potential application of proteomics for the identification, quantification, and profiling of proteins for UBC in different sources. Based on these studies, using the panel of biomarkers as proteomic patterns may achieve higher sensitivity and specificity than single proteins in the diagnosis of UBC. In the present review, we evaluate recent literature related to the UBC proteome focusing especially on new proteomics techniques. Moreover, we classify UBC tumor biomarkers as diagnostic, prognostic, and therapeutic targets based on their sources (urine, serum/plasm, cell line, and tumor tissue) and we also discuss the advantages and limitations of each source. In this manner, this review article provides a critical assessment presentation of the advances in proteomics for all aspects of UBC diagnosis, prognosis, and treatment based on sources.

Asunto(s)

Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Biomarcadores de Tumor/metabolismo , Proteómica , Neoplasias de la Vejiga Urinaria/diagnóstico , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/patología , Pronóstico

RESUMEN

A systematic review and meta-analysis were conducted to find out if there was association between Plasminogen Activator Inhibitor-1 (PAI-1) gene polymorphisms (- 844 G > A and - 675 4G > 5G) and susceptibility to coronary artery disease (CAD). Search of electronic databases was performed and the pooled odds ratio (OR) and 95% confidence interval (CI) were exerted to evaluate the pooled association between the single-nucleotide polymorphisms (SNPs) and risk of CAD. For - 675 4G > 5G SNP, dominant (OR = 0.90), recessive (OR = 0.90), allelic (OR = 0.91), homozygous (OR = 0.84), and heterozygous (OR = 0.96) models were significantly associated with decreased risk of CAD. Moreover, all five genetic models were associated significantly with decreased CAD risk in the Causation and Arab populations. The results in Asians were marginally significant in recessive, allelic, and homozygote models. The male gender was found to be a risk factor in individuals with PAI-1 4G > 5G SNP in the dominant model (OR = 0.89), recessive model (OR = 0.91), allelic model (OR = 0.92), homozygous model (OR = 0.86), and heterozygous model (OR = 0.91). The results of pooled ORs for overall populations and subgroup analysis by ethnicity reject any association between PAI-1 gene - 844 G > A polymorphism and CAD risk under all genetic comparisons. The results of this meta-analysis indicated that PAI-1 4G > 5G SNP was associated with decreased risk of CAD in the overall population as well as in the Asians, Caucasians, and Arab populations. However, the PAI-1 gene - 844 G > A polymorphism had no significant association with susceptibility to CAD.

Asunto(s)

Enfermedad de la Arteria Coronaria , Inhibidor 1 de Activador Plasminogénico , Pueblo Asiatico , Enfermedad de la Arteria Coronaria/genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Oportunidad Relativa , Inhibidor 1 de Activador Plasminogénico/genética , Polimorfismo de Nucleótido Simple , Factores de Riesgo

RESUMEN

Several studies have noted that vitamin D receptor (VDR) gene polymorphisms are involved in the susceptibility to Coronary artery disease (CAD). Nonetheless, the results have been inconclusive. Here, we performed the most up-to-date analysis of the association between VDR gene polymorphisms and risk of CAD. We conducted a comprehensive systematic search in the major electronic database, including Scopus and PubMed to look up for relevant studies evaluating the association between the VDR gene FokI (rs2228570), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232) polymorphisms and susceptibility to CAD published before December 2019. The level of association between VDR gene polymorphisms and susceptibility to CAD in the polled analysis was calculated by odds ratio (OR) and the corresponding 95% confidence interval (CI). We found 14 articles containing 20,398 cases and 9371 controls. The analysis revealed that all genetic models in the FokI SNP were associated with increased risk of CAD. Furthermore, for the ApaI SNP, except recessive model, all other genetic models significantly increased the risk of CAD in the overall analysis. In addition, it was divulged that both FokI and ApaI SNPs were involved in increasing the risk of CAD in Asians and Europeans in a number of models. FokI and ApaI polymorphisms may confer a susceptibility genetic risk factor for development of CAD, particularly in the Asian population.

Asunto(s)

Enfermedad de la Arteria Coronaria/genética , Predisposición Genética a la Enfermedad , Receptores de Calcitriol/genética , Humanos , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Factores de Riesgo

RESUMEN

MicroRNAs (miRNAs) are important molecules which implicated in various processes, such as differentiation, development, cell survival, cell apoptosis and also cell metabolism. Investigations over decades have revealed that various genes and signaling pathways are implicated in beginning and development of atherosclerosis, several miRNAs being involved in these dysregulated genes and pathways. miRNAs have provided new molecular vision in the context of atherosclerosis. miRNAs are considered as important regulators of cellular migration, differentiation, proliferation, lipid uptake and efflux, as well as cytokine production. Application of miRNAs as a biomarker in diagnosis, prognosis and even therapy is quiet exciting. Although animal researches showed promising results, still some practical difficulties and technical challenges need to be addressed before translation from researches into clinical practices. In this review, we present important data about three critical cells endothelial cell (EC), vascular smooth muscle cell (VSMC), and monocyte/macrophage and regulation of these cells through miRNAs. Furthermore, we discuss about the potential of miRNAs as a prognostic and diagnostic biomarkers, therapeutic opportunities and challenges, and also future perspective.

Asunto(s)

Aterosclerosis/diagnóstico , Aterosclerosis/metabolismo , MicroARNs/metabolismo , Animales , Aterosclerosis/terapia , Biomarcadores/metabolismo , Movimiento Celular , Proliferación Celular , Células Endoteliales/metabolismo , Regulación de la Expresión Génica , Humanos , Inflamación , Lípidos/sangre , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Pronóstico , Transducción de Señal

RESUMEN

BACKGROUND: It has comprehensively been acknowledged that a genetic contribution, especially in immune inflammatory players, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, are critically involved in the pathophysiology of coronary artery disease (CAD). This meta-analysis study aimed to reach a conclusive understanding of the role of genetic polymorphisms, including IL6 gene C572G (rs1800796) and G174C (rs1800795) as well as TNFA gene G238A (rs361525) and G308A (rs1800629) in susceptibility to CAD. METHODS: Two major databases, namely MEDLINE and Scopus, were searched to find the studies surveying the mentioned polymorphisms and CAD susceptibility up to July 2020. Association comparison between the polymorphisms and CAD susceptibility were assessed using pooled odds ratio (OR) and their corresponding 95% confidence interval (CI). RESULTS: This meta-analysis study was conducted on 69 papers (73 population studies), comprising 5062 patients and 8446 controls for IL6 gene rs1800796 (17 studies), 13801 patients and 16215 controls for IL6 gene rs1800795 (38 studies), 1439 patients and 2850 controls for TNFA gene rs361525 (5 studies), and 5051 patients and 3958 controls for TNFA gene rs1800629 (13 studies), according to inclusion and exclusion criteria. There were statistically positive association between all genetic comparisons of IL6 gene rs1800795 polymorphism and the CAD risk. Moreover, the recessive model (CC vs. CG + GG) in IL6 gene rs1800796 polymorphism had marginally significant association with decreased risk of CAD. None of the TNFA gene polymorphisms were associated with CAD risk. CONCLUSIONS: The meta-analysis revealed the positive association of IL6 gene rs1800795 polymorphism in susceptibility to CAD.

Asunto(s)

Enfermedad de la Arteria Coronaria/genética , Citocinas/genética , Predisposición Genética a la Enfermedad , Humanos , Inflamación/genética , Polimorfismo de Nucleótido Simple

RESUMEN

Epstein-Barr virus (EBV) associated with several diseases such as contagious mononucleosis chronic active EBV infection, and diverse sorts of malignant tumors. Therefore, using applicable vaccines could be advantageous for public health. Yet, the vaccine has been unavailable to protect from EBV so far. In the current study, to develop a multi-peptide vaccine for EBV and assess its expression in Pichia pastoris yeast system, three immunodominant sequences in glycoprotein (gp) 85, gp350 and latent membrane protein 1 (LMP1) were chosen. To construct fusion peptide, -GGGGS- liker was applied. After cloning the fusion peptide in the pPICZαA expression vector, this recombinant vector processed and transfected into Pichia pastoris host cells. The expression of high level of EBV fusion peptide was confirmed by dot blot and SDS-PAGE procedures. The Pichia pastoris is capable of supporting EBV fusion peptide expression. The application of this fusion peptide as a peptide vaccine to fight EBV is suggested.

Asunto(s)

Herpesvirus Humano 4/inmunología , Fragmentos Fc de Inmunoglobulinas/genética , Glicoproteínas de Membrana/genética , Proteínas del Envoltorio Viral/genética , Proteínas de la Matriz Viral/genética , Vacunas Virales/biosíntesis , Secuencia de Aminoácidos , Linfoma de Burkitt/inmunología , Linfoma de Burkitt/prevención & control , Linfoma de Burkitt/virología , Clonación Molecular , Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Herpesvirus Humano 4/genética , Humanos , Fragmentos Fc de Inmunoglobulinas/inmunología , Mononucleosis Infecciosa/inmunología , Mononucleosis Infecciosa/prevención & control , Mononucleosis Infecciosa/virología , Glicoproteínas de Membrana/inmunología , Péptidos/genética , Péptidos/inmunología , Pichia/genética , Pichia/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Vacunas de Subunidad , Proteínas del Envoltorio Viral/inmunología , Proteínas de la Matriz Viral/inmunología

RESUMEN

Atherosclerosis is a complex disease with involvement of intermediate-, large-sized arteries. Atherosclerosis is characterized by the accumulation of vascular lipids, immune system activation, inflammation, oxidative stress and oxidized low-density lipoproteins (LDLs), endothelial cell (EC) activation, arterial smooth muscle cell (SMC) proliferation, macrophage activation and foam cell formation that cause endothelial dysfunction. DNA methylation is one of important epigenetic mechanisms which changes gene expression. It has been evident that this mechanism plays an important role in the initiation and propagation of atherosclerosis. Furthermore, DNA methylation is a crucial and distinct mechanism that modulates genes governing cell proliferation, thereby connecting environmental insults with gene expression. This study represents many atherosclerosis-related genes which are regulated through DNA methylation mechanism. Although the role of epigenetics in atherosclerosis is at their infancy. Nevertheless, various studies demonstrated that DNA methylation involvement in this disease is undeniable. DNA methyltransferases are the main player of the smooth muscle cell proliferation, endothelial cell integrity, as well as arteriosclerosis formation. In this review, we focus on recent achievements in the functional and description interpretation of the DNA methylation pattern of cells and tissues implicated in atherosclerosis. Besides, we discuss the association of DNA methylation with oxidative stress, hyperhomocysteinemia (HHcy), ageing, and inflammation in the development and pathogenesis of atherosclerosis.

Asunto(s)

Aterosclerosis/genética , Metilación de ADN , Envejecimiento/genética , Animales , Aterosclerosis/complicaciones , Aterosclerosis/metabolismo , Aterosclerosis/patología , Humanos , Hiperhomocisteinemia/complicaciones , Miocitos del Músculo Liso/patología , Estrés Oxidativo/genética

RESUMEN

Background: Coronary heart disease (CHD) is a chronic inflammatory disease, which is still regarded as a major cause of morbidity and mortality worldwide. Several studies have suggested that polymorphisms in cytokine genes are associated with the pathogenesis of CHD. The genotype distribution of Tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) genes polymorphisms have been shown to be different in various ethnic populations. This study was aimed to investigate the association of TNF-α-308 G/A and IFN-γ + 874T/A polymorphisms with risk of CHD in an Iranian population. Methods: A total of 187 unrelated subjects comprised 96 CHD patients and 91 healthy controls were enrolled in this cross-sectional study. The TNF-α-308 G/A and IFN-γ + 874T/A polymorphisms were genotyped using amplification refractory mutation system-PCR (ARMS-PCR). The chi-square and logistic regression tests were used to calculate the odds ratios (ORs) as a measure of differences in genotype frequencies. Results: A significant differences in the allelic and genotypic distribution of TNF-α-308 G/A and IFN-γ + 874T/A polymorphisms was found between CHD patients and healthy controls (P = 0.017, P = 0.011, P = 0.006 and P = 0.002, respectively). Logistic regression analyses were also revealed statistically significant risk for CHD with respect to TNF-α-308 A and IFN-γ + 874 T carriers either in crude or after adjustment for potential confounders (P = 0.003 and P = 0.006, respectively). Conclusion: This study provides strong evidence supporting the association of TNF-α-308G/A and IFN-γ + 874T/A polymorphisms with the increased risk of CHD. Therefore, these two cytokine polymorphisms may play a role in predisposition to coronary heart disease.

Asunto(s)

Enfermedad Coronaria/genética , Interferón gamma/genética , Factor de Necrosis Tumoral alfa/genética , Adulto , Estudios de Casos y Controles , Estudios Transversales , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mutación , Polimorfismo Genético

RESUMEN

Opium is considered as the second most abused addictive compound in worldwide. It seems that one of the causes for common consumption of opium in many countries is a traditional belief, even among medical personnel, through which opium might have advantageous influences on cardiovascular events and be beneficial in controlling hypertension, dyslipidemia, and diabetes. According to several investigations, it is thought that opium not only has no beneficial effects on cardiovascular events, but it might have deleterious influences on these settings. As a result, people need to be trained with regard to the adverse effects of opium on cardiovascular events. In this review, we try to go through the understanding of the effects of opium cardiovascular disorders and related complications such as blood pressure, blood sugar, lipid circumstances, and finally atherosclerosis.

Asunto(s)

Enfermedades Cardiovasculares/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Opio/efectos adversos , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/patología , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/patología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Dislipidemias/complicaciones , Dislipidemias/tratamiento farmacológico , Dislipidemias/patología , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hipertensión/patología , Opio/uso terapéutico , Factores de Riesgo

RESUMEN

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is one of the most common chronic rheumatic diseases in children. The complex nature of this immune-mediated disease owes itself to several predisposing genes and environmental factors affecting its pathogenesis. Conducted in Iran, this study was originally intended to investigate every possible association between HLA DRB1 alleles and a susceptibility to JIA. MATERIALS AND METHODS: In this case-control study, 45 patients with a definite diagnosis of JIA based on International League against Rheumatism (ILAR) criteria were compared against 46 healthy controls. DNA samples taken from both groups were analyzed using PCR-sequence specific primers (PCR-SSP) method. Data analysis including parametric and nonparametric test and multivariate analysis was undertaken using the SPSS 11.5 software. A P-value< 0.05 was regarded as statistically significant. RESULTS: Mean ages in case group and healthy controls were 14.64±6.21 and 13.73±6.39, respectively with no significant difference between the two groups (P=0.515). Sex difference between JIA group and healthy controls was also not significant (P=0.068). The frequency of HLA-DRB1*01 was found the most frequent HLA-RB1 in our patients (33.3%). No significant statistical correlation between various HLA-DRB1 alleles and clinical subtypes of the disease could be established from the data. HLA-DRB1*11 was shown to raise protection to JIA (P=0.035, OR=2.755, 95% CI=0.963-8.055) in northeastern Iran. In addition, we found that HLA-RB1*09 is nominally associated with an increased risk of JIA (P=0.56, OR=2, 05, 95% CI=0.18-23.63). CONCLUSION: HLA-DRB1*11 was shown to raise protection to JIA in northeastern Iran. The disparity of findings in other ethnicities prompts further investigations with larger sample sizes.

RESUMEN

BACKGROUND: The vitamin D receptor (VDR) gene polymorphisms have been reported to be related to the development of Behcet's disease (BD). However, the results have been inconsistent among diverse populations. Therefore, this comprehensive meta-analysis has been designed to assess a more accurate association between VDR polymorphisms and BD susceptibility. METHODS: An electronic literature search was conducted to identify eligible studies. Pooled odds ratios (OR) with corresponding 95% confidence interval (CI) were calculated in different genetic models to assess this association. RESULTS: A total of six separate comparisons comprised of 468 cases and 516 controls were included in the meta-analysis model. The meta-result demonstrated that A allele of ApaI (A vs. a: 1.54 95% CI = 1.04-2.26, P = 0.029), and F allele of FokI (F vs. f: OR = 0.58, 95% CI = 0.45-0.76, P = 0.007) polymorphisms were associated with the risk of BD in total and African populations, respectively. This significant association was also found in recessive and homozygotes models. Subgroup analysis indicated that FokI variant among Africans and ApaI variant among Caucasian were significantly associated with the risk of BD. No relationship was found between Bsmi and TaqI polymorphisms and BD risk. CONCLUSION: This meta-analysis demonstrated the association between FokI and ApaI polymorphisms in VDR gene with the risk of BD, providing insights into the potential role of vitamin D receptor in the pathogenesis of BD.

Asunto(s)

Síndrome de Behçet/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Receptores de Calcitriol/genética , Humanos , Oportunidad Relativa , Polimorfismo de Longitud del Fragmento de Restricción , Sesgo de Publicación

RESUMEN

Several studies have estimated breast cancer risk in patients with systemic lupus erythematosus (SLE) relative to the general population. However, the results have been inconclusive. Therefore, we conducted a meta-analysis to ascertain a more comprehensive conclusion. A systematic literature search of electronic databases including PubMed, Web of Science, Embase, Cochrane Library, and Scopus was conducted to identify eligible studies using multiple search strategies. Based on the degree of heterogeneity, a random-effect model was chosen to calculate the pooled standardized incidence rate (SIR) with 95% confidence interval (CI), to estimate the strength of association between SLE and breast cancer incidence risk. A total of 18 eligible studies including 110,720 patients with SLE were enrolled in this meta-analysis. The combined results showed no significant association between SLE and breast cancer incidence (SIRs = 1.012 (95% CI, 0.797-1.284)). Subgroup analysis by study type, ethnicity, follow-up years, sample size, and SLE diagnostic criteria also showed no altered risk for breast cancer incidence (the summary risk estimate of each subgroup ranged from 0.82 to 1.40 with no statistical significance). This meta-analysis suggests no direct association between SLE and risk of breast cancer incidence.

Asunto(s)

Neoplasias de la Mama/epidemiología , Lupus Eritematoso Sistémico/epidemiología , Femenino , Humanos , Incidencia , Medición de Riesgo

RESUMEN

OBJECTIVES: Human Cytomegalovirus (HCMV) remains a major morbidity and mortality cause in immuno suppressed patients. Therefore, significant effort has been made towards the development of a vaccine. In this study, the expression of the pp65 and gB fusion peptides and Fc domain of mouse IgG2a as a novel delivery system for selective uptake of antigens by antigen-presenting cells (APCs) in Pichia pastoris yeast system were studied. MATERIALS AND METHOD: In this study, four immune dominant sequences in pp65 protein and 3 immuno dominant sequences in gB protein were selected according to literature review. Peptide linker -GGGGS- was used for construction of fusion peptide. This fusion peptide was cloned in the pPICZαA expression vector and transfected into P. pastoris host cells. RESULTS: Dot blot and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) techniques showed that a high level of pp65-gB-Fc fusion peptide was expressed. CONCLUSION: This CMV pp65-gB-Fc fusion peptide could be a promising candidate for the development of a novel peptide vaccine.