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BACKGROUND: Hepatocellular Carcinoma (HCC) is a universal health problem responsible for 8.2% of all cancer deaths. Numerous risk factors were documented to be contributed to HCC development with viral hepatitis C ranking as the major predisposing factor in Egypt. The presence of a detectable amount of long noncoding RNAs (lncRNAs) in the circulation is linked to the development and spread of tumors. LncRNAs NBAT-1 and FOXCUT expression levels were used as genetic markers for the detection of gastrointestinal tract cancers. We hypothesized that serum expression levels of NBAT-1 and FOXCUT are new biomarkers for HCC that are related to laboratory and pathological markers. PATIENTS AND METHODS: This study included 165 hepatitis C virus (HCV)-related HCC Egyptian patients, 180 HCV-infected noncancer patients, and 180 healthy controls, the serum expression levels of NBAT-1 and FOXCUT were measured by using quantitative real-time polymerase chain reaction. RESULTS: This study's results include that medians (inter-quartile range [IQRs]) of NBAT-1 in HCC and HCV patients were (1.9 [0.87-4.94], 10.01 [7.34-13.29] respectively) which exhibited significantly higher expression than controls, while the medians (IQRs) of FOXCUT in HCC and HCV patients were (0.15 [0.04-0.52], 6.42 [2.49-10.10], respectively) that exhibited significantly lower expression than controls regarding HCC patients but significantly higher expression than controls regarding HCV patients. In comparing serum fold changes of NBAT-1 and FOXCUT between HCC patients and HCV patients; we obtained significantly higher levels of target genes in HCV patients (p < 0.001) than in HCC patients. Also, a positive correlation was detected between NBAT-1 and FOXCUT in HCC group (r = 0.262, p = 0.001) and in HCV group (r = 0.937, p < 0.001). Higher serum NBAT-1 and FOXCUT were significantly associated with better clinical and laboratory data of the disease. Multivariate regression analysis showed that FOXCUT was an independent predictor for HCC among HCV patients (p < 0.001). CONCLUSION: Our study cited that NBAT-1 and FOXCUT could be considered new diagnostic serum biomarkers for HCC on top of HCV.
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Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , ARN Largo no Codificante , Humanos , Biomarcadores , Carcinoma Hepatocelular/patología , Hepatitis C/complicaciones , Hepatitis C/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/genética , Neoplasias Hepáticas/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease which affects various tissues and organs mainly joints. Serum microRNAs are considered a new class of non-coding RNA which plays a vital role in pathogenesis of RA. METHODS: The current study was conducted on 80 RA patients and 80 healthy participants. Serum expression levels of miR-224, miR-760, miR-483-5p, miR-378 and miR-375 were evaluated via real-time quantitative polymerase chain reaction (PCR). RESULTS: Significant upregulation of miR-224, miR-760, miR-483-5p, miR-378 and miR-375 was reported in the present study with respect to the control group (P = .031, P = .017, P = .026, P = .036 and P = .05, respectively). Furthermore, significant positive correlation between the abovementioned microRNAs with DAS28 score (P < .001, each) was demonstrated. CONCLUSION: Early detection of RA could be achieved through evaluation of serum expression of miR-224, miR-760, miR-483-5p, miR-378 and miR-375 which also may be used as targets for treatment of patients with RA.
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Artritis Reumatoide , MicroARNs , Artritis Reumatoide/genética , Biomarcadores , Humanos , MicroARNs/genéticaRESUMEN
Noncoding RNAs are emerging biomarkers for many diseases including diabetic retinopathy (DR). This study aimed to measure the expression levels of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 in DR patients. A total of 80 patients diagnosed as type 2 diabetes (T2D) and 81 healthy subjects were recruited in this study. T2D patients were divided into three groups: nondiabetic retinopathy (NDR) group (30 patients), nonproliferative diabetic retinopathy (NPDR) group (30 patients), and proliferative diabetic retinopathy (PDR) group (20 patients). Quantitative real-time polymerase chain reaction (PCR) was used to assess the expression of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1. We found a significant decrease in serum miR-20b and a significant increase in serum HOTAIR and MALAT1 in NDR patients compared to healthy subjects. Also, we revealed a significant decrease in serum miR-20b and miR-17-3p and a significant increase in serum HOTAIR and MALAT1 in each of NPDR and PDR groups when compared with healthy subjects. Furthermore, we reported a significant decrease in miR-20b and miR-17-3p and a significant increase in HOTAIR and MALAT1in DR as well as in PDR patients when compared with NDR patients. However, on comparing NPDR with NDR patients, no significant difference was observed regarding the expression levels of miR-20b and miR-17-3p, in contrast, significant elevation of serum HOTAIR and MALAT1 was found in NPDR. Moreover, we observed a significant decrease in serum miR-20b and miR-17-3p and a significant increase in serum HOTAIR and MALAT1 in PDR group relative to NPDR group. Receiver operating characteristic (ROC) curve was used for evaluating the diagnostic value of the examined serum noncoding RNAs as novel biochemical indicators detecting severity of DR. Our analyses suggested that the examined serum noncoding RNAs may discriminate DR (PDR and NPDR) from NDR. Furthermore, these noncoding RNAs (less importantly miR-17) can be used as promising novel biomarkers for prediction DR severity, distinguishing PDR from NPDR patients. We can conclude that serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 may be used as noninvasive biomarkers for screening of DR and early diagnosis of PDR. © 2018 IUBMB Life, 71(3):310-320, 2019.
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Diabetes Mellitus Tipo 2/genética , Retinopatía Diabética/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/patología , Retinopatía Diabética/sangre , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/patología , Diagnóstico Precoz , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , MicroARNs/sangre , Persona de Mediana Edad , Pronóstico , ARN Largo no Codificante/sangre , Curva ROC , Índice de Severidad de la EnfermedadRESUMEN
The effects of epigallocatechin-3-gallate (EGCG) and metformin single treatment have been tested against hepatocellular carcinoma (HCC). This study aimed to assess the combination effects of EGCG and metformin on proliferation and apoptosis of HepG2cells and identified new potential molecular targets. The effect of EGCG and metformin against cell proliferation in HepG2 was determined using MTT assay. Reverse transcription polymerase chain reaction was applied to examine the gene expression of cyclin D1, lncRNA-AF085935, caspase-3, survivin and VEGF. The level of protein expression of glypican-3 was assessed by western blot. In HepG2 cells, EGCG and metformin combination treatment exhibited high significant effect against tumor proliferation. It significantly reduced cyclin D1, lncRNA-AF085935, glypican-3 and promoted apoptosis through increasing caspase3 and decreasing survivin compared to control cells. Moreover, EGCG and metformin treated cells showed decreased expression levels of VEGF. Our study provided new insights of the anticarcinogenic effects of EGCG and metformin on HCC through their effects on glypican-3 and lncRNA-AF085935.
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Carcinoma Hepatocelular/tratamiento farmacológico , Catequina/análogos & derivados , Metformina/farmacología , Anticarcinógenos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Caspasa 3/efectos de los fármacos , Catequina/metabolismo , Catequina/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclina D1/efectos de los fármacos , Glipicanos/metabolismo , Células Hep G2/efectos de los fármacos , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Metformina/metabolismo , ARN Largo no Codificante/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Survivin/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacosRESUMEN
BACKGROUND: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) are immune inhibitory factors that provide inhibitory signals to T cells. METHODS: A case-controlled genetic association study was conducted in478 patients (160 patients with chronic Hepatitis C virus (HCV) and diabetes mellitus (DM) and156 patients with chronic HCV without DM) and162healthy controls. We genotyped selected single nucleotide polymorphisms (SNPs) of rs10204525 and rs231775using real-time-polymerase chain reaction (RT-PCR). RESULTS: Our study revealed thatthers10204525 CT genotype was significantly associated with a high susceptibility to chronic HCV infection and to HCV+DM (adjusted odds ratio (OR)7.531, 95% confidence interval (CI):4.099-13.836, P < 0.0001 and adjusted OR 7.791, 95% CI:4.244-14.303, P < 0.0001, respectively).In addition, the frequency of CT+TT genotypes versus the CC genotype and the T allele versus the C allele were elevated in non-responder patients to antiviral therapy compared with responder patients (P < 0.0001) in HCV group. For rs231775,the AG genotype was significantly associated with a high susceptibility to chronic HCV infection and HCV infection with DM (adjusted OR 5.124,95% CI:3.150-8.334, P < 0.0001 and adjusted OR 20.594, 95% CI:11.026-38.467, P < 0.0001, respectively).Furthermore, the frequency of AG+GG genotypes versus the CC genotype and the G allele versus the A allele was elevated in non-responder patients to antiviral therapy when compared with responder patients in the HCV and HCV+DM groups(P < 0.05). CONCLUSIONS: Both rs10204525 and rs231775 are associated with a risk of chronic HCV, with or without DM.
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Antígeno CTLA-4/genética , Hepatitis C Crónica , Hepatitis C , Receptor de Muerte Celular Programada 1/genética , Antivirales/uso terapéutico , Apoptosis , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Hepacivirus , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/genética , Humanos , Polimorfismo de Nucleótido Simple , Linfocitos T CitotóxicosRESUMEN
BACKGROUND: Neonatal sepsis is a serious condition. Recent clinical studies have indicated that microRNAs (miRNAs) are key players in the pathogenesis of sepsis, which could be used as biomarkers for this condition. PATIENTS AND METHODS: A total of 90 neonates with sepsis and 90 healthy neonates were enrolled in this study. qRT-PCR was performed to measure the expression levels of serum miR-34a-5p and miR-199a-3p. RESULTS: miR-34a-5p and miR-199a-3p serum levels were significantly reduced in neonates with sepsis compared with those in healthy neonates (P = 0.006 and P = 0.001, respectively). Significant correlations of miR-34a-5p and miR-199a-3p with each of TLC, RDW, RBS, and C-reactive protein (CRP) as well as SNAPII were observed, indicating their associations with the severity of neonatal sepsis. CONCLUSION: miR-34a-5p and miR-199a-3p may be useful as novel biomarkers in neonatal sepsis and may provide a new direction for its treatment.
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Biomarcadores/sangre , MicroARNs/sangre , Sepsis Neonatal/sangre , Proteína C-Reactiva/metabolismo , Femenino , Humanos , Recién Nacido , Masculino , Sepsis Neonatal/metabolismoRESUMEN
Introduction: The current study was designed to analyze whether polymorphisms of miR-146a and miR-155 are related to Behçet's disease (BD) in the Egyptian population. Material and methods: A total of 96 unrelated BD patients and 100 healthy subjects were genotyped for miR-146a (rs2910164) and miR-155 (rs767649) using real-time polymerase chain reaction. Results: The results showed significant elevation in the frequency of rs2910164 GG and CC genotypes in BD patients compared with controls (adjusted OR = 22.156, 95% CI: 4.728-103.818; p < 0.001 and adjusted OR = 40.358, 95% CI: 8.928-182.440; p < 0.001, respectively). Also, the rs2910164 G allele conferred a higher risk of developing BD (adjusted OR = 3.665, 95% CI: 2.013-6.671; p < 0.001). MiR-146a (rs2910164) polymorphism was a risk factor for susceptibility to BD in dominant, recessive and additive models of inheritance (all p < 0.001), while the miR-155 (rs767649) polymorphism was a risk factor in the recessive model only (p = 0.021). GG and CG genotypes of rs2910164 were associated with higher Behcet's disease current activity index (BDCAI) and ocular involvement compared with CC genotype (p = 0.005 and p = 0.004, respectively). Genotype AT of rs767649 was related to higher BDCAI (p = 0.026) compared with TT and AA genotypes. Conclusions: miR-146a (rs2910164) and miR-155 (rs767649) are likely to play an important role in the Egyptian population in development of BD and also influence disease severity.
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BACKGROUND: The role of the long non-coding RNAs (lncRNAs) in the pathogenesis of systemic lupus erythematosus (SLE) is mostly unknown, despite increasing evidence that lncRNAs extensively participate in physiological and pathological conditions. AIM: To detect the level of lncRNA-Cox2, HOTAIR, IL-6, and MMP-9 in the serum of SLE patients and to correlate these levels with disease activity and patients' clinical and laboratory data to evaluate the value of these biomarkers for SLE diagnosis and assessment of disease activity. METHODS: Blood samples from 58 SLE patients, and 60 healthy controls (HCs) were used for detection of lncRNAs-Cox2 and HOTAIR expression levels by real-time polymerase chain reaction. Both IL-6 and MMP-9 serum levels were assayed by enzyme-linked immunosorbent assay. Lupus activity was assessed with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS: The serum expression levels of lncRNA-Cox2 and HOTAIR were significantly up-regulated in SLE patients vs HCs (fold change [median (IQR) was 1.29(0.81-1.71, P<0.0001) and 2.68(0.95-3.67), P = 0.038) for lncRNA-Cox2 and HOTAIR, respectively. Serum levels of both IL-6 and MMP-9 were significantly high in SLE patients compared with HCs (P≤0.001 for each). The up-regulated lncRNA-Cox2 was positively associated with the presence of neurological manifestations in SLE patients (P = 0.007). Furthermore, HOTAIR expression level had significantly positive correlation with IL-6 (r = 0.578, P<0.0001), MMP-9 level (r = 0.762, P<0.0001), nephritis grades (r = 0.296, P = 0.024) and proteinuria (r = 0.287, P = 0.035). LncRNA-Cox2 showed sensitivity and specificity 72.4%, and 100.0% respectively. HOTAIR sensitivity was 60.3%, and specificity was 100.0%. By multiple logistic regression analysis, lncRNA-Cox2 and HOTAIR were found as SLE independent predictors. CONCLUSION: LncRNA-COX2 and HOTAIR can be used as new non-invasive biomarkers for the diagnosis of SLE.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , ARN Largo no Codificante , Biomarcadores , Humanos , Interleucina-6/sangre , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/genética , Metaloproteinasa 9 de la Matriz/sangre , ARN Largo no Codificante/genéticaRESUMEN
Hepatitis B virus (HBV) infection is a significant health issue worldwide.. We attempted to fulfill the molecular mechanisms of epigenetic and genetic factors associated with chronic HBV (CHBV). Expression levels of the lncRNA growth arrest-specific 5 (GAS5) and miR-137 and their corresponding SNPs, rs2067079 (C/T) and rs1625579 (G/T) were analyzed in 117 CHBV patients and 120 controls to investigate the probable association between these biomarkers and CHBV pathogenesis in the Egyptian population. Serum expression levels of GAS5 and miR-137 were significantly down-regulated in cases vs controls. Regarding GAS5 (rs2067079), the mutant TT genotype showed an increased risk of CHBV (p < 0.001), while the dominant CC was a protective factor (p = 0.004). Regarding miR-137 rs1625579, the mutant genotype TT was reported as a risk factor for CHBV (p < 0.001) and the normal GG genotype was a protective factor, p < 0.001. The serum GAS5 was significantly higher in the mutant TT genotype of GAS5 SNP as compared to the other genotypes (p = 0.007). Concerning miR-137 rs1625579, the mutant TT genotype was significantly associated with a lower serum expression level of miR-137 (p = 0.018). We revealed the dysregulated expression levels of GAS5 and miR-137 linked to their functioning SNPs were associated with CHBV risk and might act as potential therapeutic targets.
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Hepatitis B Crónica , MicroARNs , ARN Largo no Codificante , Adulto , Biomarcadores/análisis , Egipto/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Hepatitis B/epidemiología , Hepatitis B/genética , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/genética , Humanos , Masculino , MicroARNs/análisis , MicroARNs/genética , Polimorfismo de Nucleótido Simple , ARN Largo no Codificante/análisis , ARN Largo no Codificante/genéticaRESUMEN
Background: Behçet's disease (BD) is a chronic autoimmune disease. The early diagnosis of BD is very important to avoid serious and/or fatal complications such as eye damage, severe neurological involvement, and large vessel occlusion. New, sensitive biomarkers would aid in rapid diagnosis, the monitoring of disease activity, and the response to treatment. Methods: This study's aim is to identify two immune system-related BD biomarkers. We measured long non-coding RNAs (lncRNAs) NEAT1 (nuclear-enriched abundant transcript 1), and lnc-DC (lncRNA in dendritic cells) in serum by real-time polymerase chain reaction (RT-PCR) in 52 BD patients and 52 controls. We analyzed the association between NEAT1 and lnc-DC and the clinical parameters of BD. Receiver operating characteristic (ROC) curve analysis was performed to explore the diagnostic performance of the studied genes. Results: Compared to controls, the significant upregulation of NEAT1 {median [interquartile range (IQR)] = 1.68 (0.38-7.7), p < 0.0001} and downregulation of lnc-DC [median (IQR) = 0.2 (0.12-1.39), p = 0.03] were detected in the sera collected from BD patients. Higher serum expression levels of NEAT1 and lnc-DC were significantly associated with the following clinical presentations: cutaneous lesions, vascular manifestations, articular manifestations, neurological manifestations, and higher disease activity score. Also, high NEAT1 levels were significantly associated with a negative pathergy test, while higher lnc-DC was significantly associated with a positive family history. ROC curves showed that NEAT1 and lnc-DC levels in serum could be used as predictors of BD with high specificity and fair sensitivity. NEAT1 had an area under the curve (AUC) of 0.692 (95% CI: 0.591-0.794, p = 0.001), and lnc-DC had an AUC of 0.615 (95% CI: 0.508-0.723, p = 0.043). Conclusion: Serum lncRNAs NEAT1 and lnc-DC are biomarkers for BD.
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Background: Ischemic stroke is one of the serious complications of diabetes. Non-coding RNAs are established as promising biomarkers for diabetes and its complications. The present research investigated the expression profiles of serum TUG1, LINC00657, miR-9, and miR-106a in diabetic patients with and without stroke. Methods: A total of 75 diabetic patients without stroke, 77 patients with stroke, and 71 healthy controls were recruited in the current study. The serum expression levels of TUG1, LINC00657, miR-9, and miR-106a were assessed using quantitative real-time polymerase chain reaction assays. Results: We observed significant high expression levels of LINC00657 and miR-9 in the serum of diabetic patients without stroke compared to control participants. At the same time, we found marked increases of serum TUG1, LINC00657, and miR-9 and a marked decrease of serum miR-106a in diabetic patients who had stroke relative to those without stroke. Also, we revealed positive correlations between each of TUG1, LINC00657, and miR-9 and the National Institutes of Health Stroke Scale (NIHSS). However, there was a negative correlation between miR-106a and NIHSS. Finally, we demonstrated a negative correlation between LINC00657 and miR-106a in diabetic patients with stroke. Conclusion: Serum non-coding RNAs, TUG1, LINC00657, miR-9, and miR-106a displayed potential as novel molecular biomarkers for diabetes complicated with stroke, suggesting that they might be new therapeutic targets for the treatment of diabetic patients with stroke.
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BACKGROUND: Polymorphisms of long noncoding RNAs are lately documented as hazardous factors for the development of numerous tumors. Furthermore, the evaluation of noncoding RNAs has emerged as a novel detector of breast cancer patients. We aimed to genotype the HOXA transcript at the distal tip (HOTTIP) rs1859168 and assess its relationship with the levels of the serum HOTTIP and its target miR-615-3p in patients with breast cancer (BC). METHODS: One hundred and fifty-one patients with BC, 139 patients with fibroadenoma (FA), and 143 healthy participants were incorporated into the current study. The genotyping of rs1859168 and the measurements of the HOTTIP and miR-615-3p levels were assessed using quantitative real-time PCR. RESULTS: We revealed a significant association between each of the CC genotypes, C allele, dominant and recessive models, and the increased risk of BC (p = 0.013, p < 0.001, p < 0.001, and p < 0.001, respectively) relative to the healthy controls. Similarly, the CC genotype, C allele, and recessive model were observed to be related to the increased incidence of BC with respect to FA (p < 0.001 for all). A significant upregulation of HOTTIP and a marked decrease of miR-615-3p were verified in patients with BC compared to each of the healthy individuals, patients with FA, and the non-BC group (healthy subjects + FA) (p < 0.001 for all). A significant negative correlation was demonstrated between the expression of HOTTIP and miR-615-3p in the serum of patients with BC. The HOTTIP expression was upregulated, while that of miR-615-3p was downregulated in patients with BC who carried the CC genotype with respect to those who carried the AA or AC genotypes (p < 0.05 for all). CONCLUSIONS: The genetic variants of rs1859168 are linked to an increased susceptibility to BC. Moreover, HOTTIP and miR-615-3p may be used as novel indicators and targets for the treatment of patients with BC.
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Neoplasias de la Mama/patología , MicroARNs/sangre , ARN Largo no Codificante/sangre , ARN Largo no Codificante/genética , Alelos , Neoplasias de la Mama/sangre , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Estudios de Casos y Controles , Egipto , Femenino , Humanos , MicroARNs/genética , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Curva ROCRESUMEN
Despite the increased proof that long noncoding RNAs (lncRNAs) can control gene expression and broadly affect the normal physiological and disease conditions, the part of lncRNAs in rheumatoid arthritis (RA) is not well known. This study aimed to assess the serum expression levels of lnc-Cox2 and HOTAIR in RA and to investigate their role as novel noninvasive biomarkers in diagnosis of RA. Also, their relations with the levels of interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 and with other clinicolaboratory data in RA patients were analyzed. LncRNAs-Cox2 and HOTAIR expression levels were detected in serum by real-time quantitative polymerase chain reaction. Both IL-6 and MMP-9 levels in serum were measured by enzyme-linked immunosorbent assay. The mRNA expression of lncRNA-Cox2 and HOTAIR was significantly upregulated in RA patients compared with healthy controls. Serum levels of both IL-6 and MMP-9 were significantly higher in RA patients than in healthy subjects (P < 0.001 each). Receiver operating characteristic (ROC) curve demonstrated that lncRNA-Cox2 and HOTAIR could discriminate RA patients from healthy controls. HOTAIR (not lnc-Cox2) was observed to be an independent predictor for RA using multiple logistic regression analysis. We concluded that lnc-Cox2 and HOTAIR serum expression levels can be used as novel noninvasive biomarkers for the diagnosis of RA.
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Artritis Reumatoide/genética , Ciclooxigenasa 2/genética , ARN Largo no Codificante/genética , Adulto , Artritis Reumatoide/sangre , Biomarcadores/sangre , Ciclooxigenasa 2/sangre , Femenino , Perfilación de la Expresión Génica , Humanos , Interleucina-6/sangre , Masculino , Metaloproteinasa 9 de la Matriz/sangre , ARN Largo no Codificante/sangreRESUMEN
Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease. We aimed to measure the level of miR-155 and its genetic variant rs767649 in patients with RA and to evaluate their relationship with ischemia-modified albumin (IMA). The study was performed on 79 patients with RA (group I) and 78 healthy control participants (group II). Quantitative real-time polymerase chain reaction was used to assess the expression of serum miR-155 in addition to its functional variant rs767649. IMA levels were measured by enzyme-linked immunosorbent assay. Significant overexpression of miR-155 and higher levels of IMA were detected in patients with RA compared with those in controls (P < 0.0001). The fold change in miR-155 was significantly positively associated with IMA (r = 0.362, P = 0.001) in patients with RA. Significant differences in the frequency of miR-155 (rs767649) genotypes and alleles were noted between patients with RA and controls. MiR-155 and IMA levels were significantly associated with the genotype distribution of miR-155 (rs767649) in patients with RA and were higher in patients with the TT genotype. MiR-155 and its functional variant rs767649 might play an important role in susceptibility to the increased risk of RA, stressing the role of miR-155 as a therapeutic target in the treatment of RA. In addition, IMA levels were increased and correlated with miR-155 and its single nucleotide polymorphism rs767649 in Egyptian patients with RA.
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Artritis Reumatoide/inmunología , MicroARNs/inmunología , Polimorfismo de Nucleótido Simple/inmunología , Albúmina Sérica Humana/inmunología , Adulto , Artritis Reumatoide/sangre , Artritis Reumatoide/genética , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Masculino , MicroARNs/sangre , MicroARNs/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Long non-coding RNAs (lncRNAs) play an important role in gene regulation and show greater tissue specificity and complexity of biological functions. There is on-going research in their contribution in autoimmune diseases like multiple sclerosis (MS). Our study aimed at the evaluation of serum levels of lncRNAs, MALAT1 and lnc-DC in MS patients and the investigation of the association between these lncRNAs and the disease activity. Serum from 45 MS patients and 45 healthy controls was separated. MALAT1 and lnc-DC expression levels were assayed by qRT-PCR. MALAT1 and lnc-DC were significantly increased in MS patients (P=0.004 and P=0.006, respectively) in comparison with controls. There was a significant increase in expression of MALAT1 in secondary progressive MS (SPMS) subgroup compared with controls (P<0.0001); however, significant elevation of lnc-DC was demonstrated in relapsing remitting MS (RRMS) subtype (P=0.003) compared with normal controls. A positive association between the expression levels of MALAT1 and lnc-DC (r = 0.513, P < 0.0001) in MS patients was detected. Moreover, positive correlation was observed between MALAT1and lnc-DC in RRMS (r = 0.569, P = 0.001). Serum levels of MALAT1 and lnc-DC may serve as potential novel molecular biomarkers for MS diagnosis and may provide a new direction for its treatment.
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Esclerosis Múltiple Crónica Progresiva/genética , Esclerosis Múltiple Recurrente-Remitente/genética , ARN Largo no Codificante/genética , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Esclerosis Múltiple Crónica Progresiva/sangre , Esclerosis Múltiple Crónica Progresiva/diagnóstico , Esclerosis Múltiple Crónica Progresiva/patología , Esclerosis Múltiple Recurrente-Remitente/sangre , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/patología , ARN Largo no Codificante/sangre , Índice de Severidad de la EnfermedadRESUMEN
Helicobacter pylori is a ubiquitous Gram-negative bacterium, that is responsible for gastric mucosal inflammation. It is the most common risk factor for gastric cancer (GC). The current study aimed to investigate the association between interleukin-11 (IL-11) and leukemia inhibitory factor (LIF) levels among H. pylori-infected Egyptian patients with gastritis and GC. One hundred forty-seven patients with gastric lesions were endoscopically biopsied and assessed using rapid urease test and immunohistochemistry. Quantitative real-time polymerase chain reaction was done for the detection of H. pylori load in gastric biopsies and detection of LIF as well as IL-11 relative gene expression. The mean values of H. pylori load, LIF, and IL-11 were significantly elevated in GC patients compared to gastritis group (P < 0.0001). A positive significant correlation was detected between mucosal levels of LIF, IL-11, and H. pylori load in both groups. Both LIF and IL-11 had the same pattern of expression in gastric tissues with different types of gastritis and different types and grades of gastric carcinoma. This report could clarify the molecular events associated with the immune response against H. pylori infection and H. pylori-associated pathology. Therefore, development of immunotherapy strategies against H. pylori-induced cytokines becomes inevitable.