Eman Toraih | Suez Canal University (original) (raw)

Papers by Eman Toraih

Research paper thumbnail of Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer

Biomedicines

Matrix metalloproteinase 9 (MMP9) and microRNA-145 (miR-145) have emerged as essential biomarkers... more Matrix metalloproteinase 9 (MMP9) and microRNA-145 (miR-145) have emerged as essential biomarkers in thyroid cancer progression and metastasis. However, their combined evaluation and clinical utility as a unified prognostic marker across diverse thyroid cancer subgroups remain unexplored. We investigated the diagnostic and prognostic value of the MMP9/miR-145 ratio in thyroid cancer, hypothesizing it may overcome inter-patient heterogeneity and serve as a versatile biomarker regardless of genetic mutations or autoimmune status. MMP9 and miR-145 expressions were analyzed in 175 paired papillary thyroid cancer (PTC) and normal tissues. Plasma levels were assessed perioperatively and longitudinally over 12–18 months in 86 matched PTC patients. The associations with clinicopathological parameters and patient outcomes were evaluated. MMP9 was upregulated, and miR-145 downregulated in cancer tissues, with a median MMP9/miR-145 ratio 17.6-fold higher versus controls. The tissue ratio accur...

Research paper thumbnail of Prognostic Value of BRAF, Programmed Cell Death 1 (PD1), and PD Ligand 1 (PDL1) Protein Expression in Colon Adenocarcinoma

Diagnostics, Jan 9, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of A Study of Plasma miR-23a Expression in Vitiligo Patients

Suez Canal University Medical Journal

Background: Vitiligo is a chronic autoimmune skin depigmentation disorder with multifactorial cau... more Background: Vitiligo is a chronic autoimmune skin depigmentation disorder with multifactorial causation, involving genetic susceptibility, immunological events, and environmental triggers. The exact molecular mechanisms of vitiligo development and progression are poorly understood. Recent studies reported microRNAs as promising biomarkers for disease detection and molecular targets for future treatment. Aim: Evaluating the expression level of circulating miR-23a in vitiligo patients and its association with the clinical features of vitiligo. Subjects and Methods: This is a case-control study comprising 50 vitiligo patients and 44 healthy controls. Plasma miR-23a expression levels were estimated by quantitative real-time PCR. Bioinformatic analysis for the miR-23a gene was performed. Results: Vitiligo patients displayed significantly lower circulating miR-23a expression levels compared to healthy controls. There was a significant negative correlation between miR-23a fold change and Vitiligo Area Severity Index (p= 0.003). Plasma miR-23a levels discriminated between vitiligo patients and controls with 60 % specificity and 64% sensitivity at the optimal cutoff value of 0.23 and likelihood ratio 1.61 (AUC=0.67). Conclusion: miR-23a along with its putative target genes could play a role in vitiligo pathogenesis.

Research paper thumbnail of Diagnostic and Prognostic Risk Assessment of Heat Shock Protein HSPA1B rs2763979 Gene Variant in Asthma

Genes

Given the significant role the heat shock protein Hsp70 plays in modulating cellular homeostasis ... more Given the significant role the heat shock protein Hsp70 plays in modulating cellular homeostasis in several chronic inflammatory disorders, the genetic variation of the inducible HSP70 (HSPA1B) gene may impact protein expression and disease phenotype. The HSPA1B rs2763979 variant has been associated with multiple inflammatory scenarios, but no previous studies have explored its association with asthma. In this sense, this cross-sectional study enrolled 90 children with asthma and 218 age-/sex-matched healthy volunteers for rs2763979 variant genotyping by TaqMan allelic discrimination analysis. The results were investigated under several genetic models and associated with disease susceptibility and clinicolaboratory data. Overall analysis, including the 308 participants, revealed a higher C allele frequency among patients relative to controls (43.0% vs. 33%, p = 0.006). Furthermore, patients with the C variant initially had a higher risk of asthma under heterozygous (OR = 2.75, 95%CI...

Research paper thumbnail of Thyroid Carcinoma: A Review for 25 Years of Environmental Risk Factors Studies

Cancers

Environmental factors are established contributors to thyroid carcinomas. Due to their known abil... more Environmental factors are established contributors to thyroid carcinomas. Due to their known ability to cause cancer, exposure to several organic and inorganic chemical toxicants and radiation from nuclear weapons, fallout, or medical radiation poses a threat to global public health. Halogenated substances like organochlorines and pesticides can interfere with thyroid function. Like phthalates and bisphenolates, polychlorinated biphenyls and their metabolites, along with polybrominated diethyl ethers, impact thyroid hormones biosynthesis, transport, binding to target organs, and impair thyroid function. A deeper understanding of environmental exposure is crucial for managing and preventing thyroid cancer. This review aims to investigate the relationship between environmental factors and the development of thyroid cancer.

Research paper thumbnail of Migration/Differentiation-Associated LncRNA SENCR rs12420823*C/T: A Novel Gene Variant Can Predict Survival and Recurrence in Patients with Breast Cancer

Genes

Long non-coding RNAs (lncRNAs) have key roles in tumor development and the progress of many cance... more Long non-coding RNAs (lncRNAs) have key roles in tumor development and the progress of many cancers, including breast cancer (BC). This study aimed to explore for the first time the association of the migration/differentiation-associated lncRNA SENCR rs12420823C/T variant with BC risk and prognosis. Genotyping was carried out for 203 participants (110 patients and 93 controls) using the TaqMan allelic discrimination technique. The corresponding clinicopathological data, including the recurrence/survival times, were analyzed with the different genotypes. After adjustment by age and risk factors, the T/T genotype carrier patients were more likely to develop BC under homozygote comparison (T/T vs. C/C: OR = 8.33, 95% CI = 2.44–25.0, p = 0.001), dominant (T/T-C/T vs. C/C: OR = 3.70, 95% CI = 1.72–8.33, p = 0.027), and recessive (T/T vs. C/T-C/C: OR = 2.17, 95% CI = 1.08–4.55, p < 0.001) models. Multivariate logistic regression analysis showed that the T/T genotype carriers were more ...

Research paper thumbnail of Component 1 Inhibitor Missense (Val480Met) Variant Is Associated With Gene Expression and Sepsis Development in Neonatal Lung Disease

Frontiers in Pediatrics, May 20, 2022

Background: Neonatal lung disease has a multifaceted etiopathology, including an explosive inflam... more Background: Neonatal lung disease has a multifaceted etiopathology, including an explosive inflammatory sequence in the immature lung. Complement component 1 Esterase INHibitor (C1INH) is implicated in controlling inflammation in response to infection/injury. Aim: To explore for the first time the association of the C1INH rs4926 (Val480Met) variant and circulatory transcript expression levels in the neonates that had evidence of lung disease and the clinic-laboratory data. Methods: A total of 139 unrelated neonates were enrolled in this case-control study. C1INH genotyping and expression analyses were done using TaqMan Genotyping and Real-Time qPCR, respectively.

Research paper thumbnail of Long Non-Coding RNAs ANRIL and HOTAIR Upregulation is Associated with Survival in Neonates with Sepsis in a Neonatal Intensive Care Unit

International Journal of General Medicine

Background: Recently, long non-coding RNAs (lncRNAs) have emerged as potential molecular biomarke... more Background: Recently, long non-coding RNAs (lncRNAs) have emerged as potential molecular biomarkers for sepsis. We aimed to profile the expression signature of three inflammation-related lncRNAs, MALAT1, ANRIL, and HHOTAIR, in the plasma of neonates with sepsis and correlate these signatures with the phenotype. Patients and Methods: This case-control study included 124 neonates with sepsis (88 survivors/36 non-survivors) admitted to the neonatal ICU and 17 healthy neonates. The relative expressions were quantified by real-time PCR and correlated to the cliniclaboratory data. Results: The three circulating lncRNAs were upregulated in the cases; the median levels were MALAT1 (median = 1.71, IQR: −0.5 to 3.27), ANRIL (median = 1.09, IQR: 0.89 to 1.30), and HOTAIR (median = 1.83, IQR: 1.44 to 2.41). Co-expression analysis showed that the three studied lncRNAs were directly correlated (all p-values <0.001). Overall and stratification by sex analyses revealed significantly higher levels of the three lncRNAs in non-survivors compared to the survivor group (all p-values <0.001). Principal component analysis showed a clear demarcation between the two study cohorts in males and females. Cohorts with upregulated ANRIL (hazard ratio; HR = 4.21, 95% CI = 1.15-10.4, p=0.030) and HOTAIR (HR = 2.49, 95% CI = 1.02-6.05, p=0.044) were at a higher risk of mortality. Conclusion: Circulatory MALAT1, ANRIL, and HOTAIR were upregulated in neonatal sepsis, and the latter two may have the potential as prognostic biomarkers for survival in neonatal sepsis.

Research paper thumbnail of GLUT1 and ASCT2 Protein Expression in Papillary Thyroid Carcinoma Patients and Relation to Hepatitis C Virus: A Propensity-Score Matched Analysis

International Journal of General Medicine, 2022

Recently, glucose and amino acid transporters have gradually become a hot topic in thyroid gland ... more Recently, glucose and amino acid transporters have gradually become a hot topic in thyroid gland biology and cancer research. We aimed to investigate the expressions of glucose transporter 1 (GLUT1) and glutamine transporter 2 (ASCT2) in papillary thyroid carcinoma (PTC) and their clinical significance and relation to HCV-related hepatitis. Patients and Methods: Screening 202 TC tissue samples against the selection criteria using a propensity-score matched analysis to adjust for age, sex, side of tumor, histopathological variants, TNM staging system, and the positivity for HCV yielded 51 matched (17 HCV positive and 34 HCV negative) PTC samples. The expressions of GLUT1 and ASCT2 expressions were detected by immunohistochemical staining. Kaplan-Meier survival curves were generated for disease-free and overall survival, and multivariate Cox regression analysis was applied to identify predictors for mortality. Results: Of 51 thyroid cancer tissues, 85% showed positive GLUT1 cytoplasmic staining, and 26% had a high expression score. All thyroid cancer specimens demonstrated ASCT2 cytoplasmic staining with membranous accentuation. Of these, 78% showed a high expression score, and 22% showed weak staining. On stratifying the study cohort based on the HCV status, HCV negative cohort showed a significantly higher immunoreactivity score for GLUT1 (p = 0.004) but not ASCT2 (p = 0.94) than HCV positive group. The expressions of the studied transporters showed no significant associations with the prognostic features of PTC nor the disease-free /overall survival. Conclusion: GLUT1 and ASCT2 immunohistochemical staining showed positive expression with variable intensity in nearly 85% and 100% of PTC tissue samples compared to normal ones, respectively. Furthermore, GLUT1 protein expression, not ASCT2, showed a higher immunoreactivity score in PTC patients who are negative for HCV than cancer patients with positive HCV. Meanwhile, the expression of both protein markers was not associated with the clinicopathological characteristics of the studied PTC patients. Further large-scale multicenter studies are recommended to validate the present findings.

Research paper thumbnail of MicroRNA-17-92a-1 Host Gene (MIR17HG) Expression Signature and rs4284505 Variant Association with Alopecia Areata: A Case–Control Study

Genes, 2022

Accumulating evidence indicates the implication of microRNAs (miRs) in cutaneous and hair follicl... more Accumulating evidence indicates the implication of microRNAs (miRs) in cutaneous and hair follicle immunobiology. We evaluated, for the first time, the miR-17-92a-1 cluster host gene (MIR17HG) expression in peripheral blood of 248 unrelated alopecia areata (AA) patients compared to 244 matched controls using Real-Time qPCR. We also tested its association with different rs4284505A>G genotypes (based on TaqMan allelic discrimination PCR) and the available clinical data. The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated for each genetic association model. The upregulation of miR-17 was observed in the serum of patients with alopecia compared to controls (p-value = 0.004). The ROC curve showed high diagnostic performance of miR-17 in differentiating between patients and controls (AUC = 0.85, p-value < 0.001). rs4284505*A/G heterozygotes were more susceptible to the disease (OR = 1.57, 95% CI = 1.01–2.45) under the over-dominant model. Interestingly, pat...

Research paper thumbnail of Association of Angio-LncRNAs MIAT rs1061540/MALAT1 rs3200401 Molecular Variants with Gensini Score in Coronary Artery Disease Patients Undergoing Angiography

Biomolecules, 2022

Long non-coding RNAs (lncRNAs) have emerged as essential biomolecules with variable diagnostic an... more Long non-coding RNAs (lncRNAs) have emerged as essential biomolecules with variable diagnostic and/or prognostic utility in several diseases, including coronary artery disease (CAD). We aimed for the first time to investigate the potential association of five angiogenesis-related lncRNAs (PUNISHER, SENCR, MIAT, MALAT1, and GATA6-AS) variants with CAD susceptibility and/or severity. TaqMan Real-Time genotyping for PUNISHER rs12318065A/C, SENCR rs12420823C/T, MIAT rs1061540C/T, MALAT1 rs3200401T/C, and GATA6-AS1 rs73390820A/G were run on the extracted genomic DNA from 100 unrelated patients with stable CAD undergoing diagnostic coronary angiography and from 100 controls. After adjusting covariates, the studied variants showed no association with disease susceptibility; however, MIAT*T/T genotype was associated with a more severe Gensini score. In contrast, MALAT1*T/C heterozygosity was associated with a lower score. The lipid profile, and to a lesser extent smoking status, male sex, w...

Research paper thumbnail of Differential Effect of Three Macrolide Antibiotics on Cardiac Pathology and Electrophysiology in a Myocardial Infarction Rat Model: Influence on Sodium Nav1.5 Channel Expression

Pharmaceuticals, 2021

Macrolides were reported to have cardiotoxic effects presented mainly by electrocardiogram (ECG) ... more Macrolides were reported to have cardiotoxic effects presented mainly by electrocardiogram (ECG) changes with increased risk in cardiac patients. We aimed to determine the impact of three macrolides, azithromycin, clarithromycin and erythromycin, on cardiac electrophysiology, cardiac enzyme activities, histopathological changes, and sodium voltage-gated alpha subunit 5 (Nav1.5) channel expression. We used eight experimental groups of male albino rats: vehicle, azithromycin (100 mg/kg), clarithromycin (100 mg/kg), erythromycin (100 mg/kg), MI + vehicle, MI + azithromycin (100 mg/kg), MI + clarithromycin (100 mg/kg) and MI + erythromycin (100 mg/kg); each group received chronic oral doses of the vehicle/drugs for seven weeks. ECG abnormalities and elevated serum cardiac enzymes were observed particularly in rats with AMI compared to healthy rats. Microscopic examination revealed elevated pathology scores for rats treated with clarithromycin in both experiments following treatment with...

Research paper thumbnail of Impact of cytotoxic T‐lymphocyte‐associated protein 4 codon 17 variant and expression on vitiligo risk

Journal of Clinical Laboratory Analysis, 2021

BackgroundCytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) is one of the essential brakes exp... more BackgroundCytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) is one of the essential brakes expressed on T cells that prevent T‐cell hyperactivation‐associated autoimmune disorders. Several CTLA4 polymorphisms were implicated in the regulation of gene expression. We aimed to explore the association of CTLA4 expression and rs231775 (c.49A>G) variant with vitiligo risk and severity of the disease in a sample of the Middle Eastern population.MethodsThe CTLA4 gene expression and genotyping for rs231775 (A/G) variant were assessed in 161 vitiligo patients and 165 controls using a real‐time polymerase chain reaction. Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity score (VIDA) were evaluated.ResultsA higher frequency of rs231775 G allele was observed in vitiligo cases than controls (45% vs. 33%, p = 0.002). After adjustment of age, sex, family history of vitiligo, and CTLA expression level, using multivariate analysis, G/G carriers were associated with a higher risk...

Research paper thumbnail of MicroRNA‑499a (rs3746444A/G) gene variant and susceptibility to type 2 diabetes‑associated end‑stage renal disease

Experimental and Therapeutic Medicine, 2021

Diabetic nephropathy (DN) is a major risk factor for end-stage renal disease (ESRD). MicroRNAs (m... more Diabetic nephropathy (DN) is a major risk factor for end-stage renal disease (ESRD). MicroRNAs (miRNAs/miRs) and their variants may be implicated in health and disease, including DN. The present study aimed to investigate the association of the miRNA-499a gene (MIR499A) A/G seed region variant (rs3746444) with DN-associated ESRD susceptibility in patients with diabetes mellitus, and to determine whether there was an association between the different genotypes and the patients' laboratory and clinical data. A case-control pilot study was conducted on 180 adult patients with type 2 diabetes mellitus. A total of 90 patients with ESRD on regular hemodialysis were considered as the cases, and 90 age-, sex-and ethnicity-matched diabetic patients with normo-albuminuria were considered as the controls. MIR499A genotyping was performed using a TaqMan Real-Time allele discrimination assay. Results demonstrated that the MIR499A rs3746444*G variant conferred susceptibility to the development of ESRD under co-dominant [(odds ratio (95% confidence interval): 2.49 (1.41-3.89) and 2.41 (1.61-6.68) for heterozygous and homozygous comparison, respectively], dominant [2.30 (1.18-3.90)] and allelic [1.82 (1.17-2.83)] models. Different genotypes of the specified variant did not exhibit significant associations with the clinic-laboratory data of the studied patients or the circulating miR-499a plasma levels. In conclusion, results of the present study suggested that MIR499A rs3746444 may be a susceptibility variant for DN-associated ESRD in the study population. However, larger sample size studies with different ethnicities are warranted to verify these findings.

Research paper thumbnail of MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis

Scientific Reports, 2021

Toll-like receptor (TLR) family signature has been implicated in sepsis etiopathology. We aimed t... more Toll-like receptor (TLR) family signature has been implicated in sepsis etiopathology. We aimed to evaluate the genetic profile of TLR pathway-related key genes; the myeloid differentiation protein 88 (MYD88), IL1 receptor-associated kinase 1 (IRAK1), the nuclear factor kappa-B1 (NFKB1), and interleukin 6 (IL6) in the blood of neonates with sepsis at the time of admission and post-treatment for the available paired-samples. This case–control study included 124 infants with sepsis admitted to the neonatal intensive care unit and 17 controls. The relative gene expressions were quantified by TaqMan Real-Time qPCR and correlated to the clinic-laboratory data. MYD88, NFKB1, and IL6 relative expressions were significantly higher in sepsis cases than controls. Higher levels of MYD88 and IL6 were found in male neonates and contributed to the sex-based separation of the cases by the principal component analysis. ROC analysis revealed MYD88 and NFKB1 transcripts to be good biomarkers for seps...

Research paper thumbnail of Antioxidants-Related Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPX), Glutathione-S-Transferase (GST), and Nitric Oxide Synthase (NOS) Gene Variants Analysis in an Obese Population: A Preliminary Case-Control Study

Antioxidants, 2021

Oxidative stress and antioxidants play an important role in obesity etiopathology. Genetic varian... more Oxidative stress and antioxidants play an important role in obesity etiopathology. Genetic variants, including single nucleotide polymorphisms (SNPs) of the antioxidant-related genes, may impact disease risk in several populations. This preliminary study aimed to explore the association of 12 SNPs related to superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST), and nitric oxide synthase (NOS) genes with obesity susceptibility in a Saudi population. A total of 384 unrelated participants, including 154 (40.1%) obese individuals, were enrolled. TaqMan OpenArray Genotyping assays were used. Six SNPs were significantly more prevalent in obese cohorts: (1) GSTM1 rs1056806*C/T; (2) SOD1 rs2234694*A; (3) SOD2 rs4880*G; (4) SOD3 rs2536512*A; (5) GPX1 rs1800668*A; (6) NOS3 rs1799983*G. Four SNPs were associated with higher obesity risk under heterozygote and dominant models for GSTM1 rs1056806 (C/T), homozygote model for SOD2 rs4880 (A/G), ...

Research paper thumbnail of Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients

PLOS ONE, 2020

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Research paper thumbnail of COVID‐19 and liver dysfunction: A systematic review and meta‐analysis of retrospective studies

Journal of Medical Virology, 2020

Recently, Coronavirus Disease 2019 (COVID‐19) pandemic is the most significant global health cris... more Recently, Coronavirus Disease 2019 (COVID‐19) pandemic is the most significant global health crisis. In this study, we conducted a meta‐analysis to find the association between liver injuries and the severity of COVID‐19 disease. Online databases, including PubMed, Web of Science, Scopus, and Science direct, were searched to detect relevant publications up to 16 April 2020. Depending on the heterogeneity between studies, a fixed‐ or random‐effects model was applied to pool data. Publication bias Egger's test was also performed. Meta‐analysis of 20 retrospective studies (3428 patients), identified that patients with a severe manifestation of COVID‐19 exhibited significantly higher levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin values with prolonged prothrombin time. Furthermore, lower albumin level was associated with a severe presentation of COVID‐19. Liver dysfunction was associated with a severe outcome of COVID‐19 disease. Close monitoring of th...

Research paper thumbnail of Association of VDBP rs4701 variant, but not VDR/RXR-α over-expression with bone mineral density in pediatric β-Thalassemia patients

Mediterranean Journal of Hematology and Infectious Diseases, 2020

Introduction: The reduced rate of bone formation despite the availability of vitamin D has been r... more Introduction: The reduced rate of bone formation despite the availability of vitamin D has been reported in β-thalassemia. This suggests genetic factors together with environmental one can be implicated in this condition. Since vitamin D binding protein (VDBP) maintains bioavailability of vitamin D which binds to vitamin D receptor (VDR)-retinoid X receptor alpha (RXRA) heterodimer to exert its molecular actions, we speculated that vitamin D metabolic-axis expression signature and variants could be potential molecular candidates for bone turnover/disease in thalassemia. To this end, this study aims to analyze VDR/RXRA expression signature, and two VDBP variants in a pilot sample of Egyptian β-thalassemia children in correlation with bone mineral density (BMD). Patients and methods: Forty-four β-thalassemia children and 40 unrelated controls were enrolled. The serum bone chemistry profile was measured. Peripheral blood mononuclear cells (PBMN) VDR/RXRA expression levels were quantif...

Research paper thumbnail of Circulating long noncoding RNAs H19 and GAS5 are associated with type 2 diabetes but not with diabetic retinopathy: A preliminary study

Bosnian Journal of Basic Medical Sciences, 2020

Recently, a wide range of biological and pathological roles of long noncoding RNAs (lncRNAs) have... more Recently, a wide range of biological and pathological roles of long noncoding RNAs (lncRNAs) have been discovered. However, the potential role of circulating lncRNAs H19 and GAS5 in type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) is not clear. Here, we assessed the plasma levels of H19 and GAS5 lncRNAs in T2DM patients with/without DR and evaluated if H19 and GAS5 pre-treatment plasma levels are a predictor of early response to a single aflibercept dose in DR subgroup. Plasma lncRNA expression profiles of 119 T2DM patients (66 with DR and 53 without DR) and 110 healthy controls were determined by quantitative reverse transcription PCR. The association of lncRNA expression profiles with clinical features and aflibercept early response in DR patients was investigated. Relative H19 expression levels were significantly increased in T2DM group (including DR and non-DR subgroups) vs. controls, while GAS5 levels were decreased in T2DM group (p < 0.001). There was no signif...

Research paper thumbnail of Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer

Biomedicines

Matrix metalloproteinase 9 (MMP9) and microRNA-145 (miR-145) have emerged as essential biomarkers... more Matrix metalloproteinase 9 (MMP9) and microRNA-145 (miR-145) have emerged as essential biomarkers in thyroid cancer progression and metastasis. However, their combined evaluation and clinical utility as a unified prognostic marker across diverse thyroid cancer subgroups remain unexplored. We investigated the diagnostic and prognostic value of the MMP9/miR-145 ratio in thyroid cancer, hypothesizing it may overcome inter-patient heterogeneity and serve as a versatile biomarker regardless of genetic mutations or autoimmune status. MMP9 and miR-145 expressions were analyzed in 175 paired papillary thyroid cancer (PTC) and normal tissues. Plasma levels were assessed perioperatively and longitudinally over 12–18 months in 86 matched PTC patients. The associations with clinicopathological parameters and patient outcomes were evaluated. MMP9 was upregulated, and miR-145 downregulated in cancer tissues, with a median MMP9/miR-145 ratio 17.6-fold higher versus controls. The tissue ratio accur...

Research paper thumbnail of Prognostic Value of BRAF, Programmed Cell Death 1 (PD1), and PD Ligand 1 (PDL1) Protein Expression in Colon Adenocarcinoma

Diagnostics, Jan 9, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of A Study of Plasma miR-23a Expression in Vitiligo Patients

Suez Canal University Medical Journal

Background: Vitiligo is a chronic autoimmune skin depigmentation disorder with multifactorial cau... more Background: Vitiligo is a chronic autoimmune skin depigmentation disorder with multifactorial causation, involving genetic susceptibility, immunological events, and environmental triggers. The exact molecular mechanisms of vitiligo development and progression are poorly understood. Recent studies reported microRNAs as promising biomarkers for disease detection and molecular targets for future treatment. Aim: Evaluating the expression level of circulating miR-23a in vitiligo patients and its association with the clinical features of vitiligo. Subjects and Methods: This is a case-control study comprising 50 vitiligo patients and 44 healthy controls. Plasma miR-23a expression levels were estimated by quantitative real-time PCR. Bioinformatic analysis for the miR-23a gene was performed. Results: Vitiligo patients displayed significantly lower circulating miR-23a expression levels compared to healthy controls. There was a significant negative correlation between miR-23a fold change and Vitiligo Area Severity Index (p= 0.003). Plasma miR-23a levels discriminated between vitiligo patients and controls with 60 % specificity and 64% sensitivity at the optimal cutoff value of 0.23 and likelihood ratio 1.61 (AUC=0.67). Conclusion: miR-23a along with its putative target genes could play a role in vitiligo pathogenesis.

Research paper thumbnail of Diagnostic and Prognostic Risk Assessment of Heat Shock Protein HSPA1B rs2763979 Gene Variant in Asthma

Genes

Given the significant role the heat shock protein Hsp70 plays in modulating cellular homeostasis ... more Given the significant role the heat shock protein Hsp70 plays in modulating cellular homeostasis in several chronic inflammatory disorders, the genetic variation of the inducible HSP70 (HSPA1B) gene may impact protein expression and disease phenotype. The HSPA1B rs2763979 variant has been associated with multiple inflammatory scenarios, but no previous studies have explored its association with asthma. In this sense, this cross-sectional study enrolled 90 children with asthma and 218 age-/sex-matched healthy volunteers for rs2763979 variant genotyping by TaqMan allelic discrimination analysis. The results were investigated under several genetic models and associated with disease susceptibility and clinicolaboratory data. Overall analysis, including the 308 participants, revealed a higher C allele frequency among patients relative to controls (43.0% vs. 33%, p = 0.006). Furthermore, patients with the C variant initially had a higher risk of asthma under heterozygous (OR = 2.75, 95%CI...

Research paper thumbnail of Thyroid Carcinoma: A Review for 25 Years of Environmental Risk Factors Studies

Cancers

Environmental factors are established contributors to thyroid carcinomas. Due to their known abil... more Environmental factors are established contributors to thyroid carcinomas. Due to their known ability to cause cancer, exposure to several organic and inorganic chemical toxicants and radiation from nuclear weapons, fallout, or medical radiation poses a threat to global public health. Halogenated substances like organochlorines and pesticides can interfere with thyroid function. Like phthalates and bisphenolates, polychlorinated biphenyls and their metabolites, along with polybrominated diethyl ethers, impact thyroid hormones biosynthesis, transport, binding to target organs, and impair thyroid function. A deeper understanding of environmental exposure is crucial for managing and preventing thyroid cancer. This review aims to investigate the relationship between environmental factors and the development of thyroid cancer.

Research paper thumbnail of Migration/Differentiation-Associated LncRNA SENCR rs12420823*C/T: A Novel Gene Variant Can Predict Survival and Recurrence in Patients with Breast Cancer

Genes

Long non-coding RNAs (lncRNAs) have key roles in tumor development and the progress of many cance... more Long non-coding RNAs (lncRNAs) have key roles in tumor development and the progress of many cancers, including breast cancer (BC). This study aimed to explore for the first time the association of the migration/differentiation-associated lncRNA SENCR rs12420823C/T variant with BC risk and prognosis. Genotyping was carried out for 203 participants (110 patients and 93 controls) using the TaqMan allelic discrimination technique. The corresponding clinicopathological data, including the recurrence/survival times, were analyzed with the different genotypes. After adjustment by age and risk factors, the T/T genotype carrier patients were more likely to develop BC under homozygote comparison (T/T vs. C/C: OR = 8.33, 95% CI = 2.44–25.0, p = 0.001), dominant (T/T-C/T vs. C/C: OR = 3.70, 95% CI = 1.72–8.33, p = 0.027), and recessive (T/T vs. C/T-C/C: OR = 2.17, 95% CI = 1.08–4.55, p < 0.001) models. Multivariate logistic regression analysis showed that the T/T genotype carriers were more ...

Research paper thumbnail of Component 1 Inhibitor Missense (Val480Met) Variant Is Associated With Gene Expression and Sepsis Development in Neonatal Lung Disease

Frontiers in Pediatrics, May 20, 2022

Background: Neonatal lung disease has a multifaceted etiopathology, including an explosive inflam... more Background: Neonatal lung disease has a multifaceted etiopathology, including an explosive inflammatory sequence in the immature lung. Complement component 1 Esterase INHibitor (C1INH) is implicated in controlling inflammation in response to infection/injury. Aim: To explore for the first time the association of the C1INH rs4926 (Val480Met) variant and circulatory transcript expression levels in the neonates that had evidence of lung disease and the clinic-laboratory data. Methods: A total of 139 unrelated neonates were enrolled in this case-control study. C1INH genotyping and expression analyses were done using TaqMan Genotyping and Real-Time qPCR, respectively.

Research paper thumbnail of Long Non-Coding RNAs ANRIL and HOTAIR Upregulation is Associated with Survival in Neonates with Sepsis in a Neonatal Intensive Care Unit

International Journal of General Medicine

Background: Recently, long non-coding RNAs (lncRNAs) have emerged as potential molecular biomarke... more Background: Recently, long non-coding RNAs (lncRNAs) have emerged as potential molecular biomarkers for sepsis. We aimed to profile the expression signature of three inflammation-related lncRNAs, MALAT1, ANRIL, and HHOTAIR, in the plasma of neonates with sepsis and correlate these signatures with the phenotype. Patients and Methods: This case-control study included 124 neonates with sepsis (88 survivors/36 non-survivors) admitted to the neonatal ICU and 17 healthy neonates. The relative expressions were quantified by real-time PCR and correlated to the cliniclaboratory data. Results: The three circulating lncRNAs were upregulated in the cases; the median levels were MALAT1 (median = 1.71, IQR: −0.5 to 3.27), ANRIL (median = 1.09, IQR: 0.89 to 1.30), and HOTAIR (median = 1.83, IQR: 1.44 to 2.41). Co-expression analysis showed that the three studied lncRNAs were directly correlated (all p-values <0.001). Overall and stratification by sex analyses revealed significantly higher levels of the three lncRNAs in non-survivors compared to the survivor group (all p-values <0.001). Principal component analysis showed a clear demarcation between the two study cohorts in males and females. Cohorts with upregulated ANRIL (hazard ratio; HR = 4.21, 95% CI = 1.15-10.4, p=0.030) and HOTAIR (HR = 2.49, 95% CI = 1.02-6.05, p=0.044) were at a higher risk of mortality. Conclusion: Circulatory MALAT1, ANRIL, and HOTAIR were upregulated in neonatal sepsis, and the latter two may have the potential as prognostic biomarkers for survival in neonatal sepsis.

Research paper thumbnail of GLUT1 and ASCT2 Protein Expression in Papillary Thyroid Carcinoma Patients and Relation to Hepatitis C Virus: A Propensity-Score Matched Analysis

International Journal of General Medicine, 2022

Recently, glucose and amino acid transporters have gradually become a hot topic in thyroid gland ... more Recently, glucose and amino acid transporters have gradually become a hot topic in thyroid gland biology and cancer research. We aimed to investigate the expressions of glucose transporter 1 (GLUT1) and glutamine transporter 2 (ASCT2) in papillary thyroid carcinoma (PTC) and their clinical significance and relation to HCV-related hepatitis. Patients and Methods: Screening 202 TC tissue samples against the selection criteria using a propensity-score matched analysis to adjust for age, sex, side of tumor, histopathological variants, TNM staging system, and the positivity for HCV yielded 51 matched (17 HCV positive and 34 HCV negative) PTC samples. The expressions of GLUT1 and ASCT2 expressions were detected by immunohistochemical staining. Kaplan-Meier survival curves were generated for disease-free and overall survival, and multivariate Cox regression analysis was applied to identify predictors for mortality. Results: Of 51 thyroid cancer tissues, 85% showed positive GLUT1 cytoplasmic staining, and 26% had a high expression score. All thyroid cancer specimens demonstrated ASCT2 cytoplasmic staining with membranous accentuation. Of these, 78% showed a high expression score, and 22% showed weak staining. On stratifying the study cohort based on the HCV status, HCV negative cohort showed a significantly higher immunoreactivity score for GLUT1 (p = 0.004) but not ASCT2 (p = 0.94) than HCV positive group. The expressions of the studied transporters showed no significant associations with the prognostic features of PTC nor the disease-free /overall survival. Conclusion: GLUT1 and ASCT2 immunohistochemical staining showed positive expression with variable intensity in nearly 85% and 100% of PTC tissue samples compared to normal ones, respectively. Furthermore, GLUT1 protein expression, not ASCT2, showed a higher immunoreactivity score in PTC patients who are negative for HCV than cancer patients with positive HCV. Meanwhile, the expression of both protein markers was not associated with the clinicopathological characteristics of the studied PTC patients. Further large-scale multicenter studies are recommended to validate the present findings.

Research paper thumbnail of MicroRNA-17-92a-1 Host Gene (MIR17HG) Expression Signature and rs4284505 Variant Association with Alopecia Areata: A Case–Control Study

Genes, 2022

Accumulating evidence indicates the implication of microRNAs (miRs) in cutaneous and hair follicl... more Accumulating evidence indicates the implication of microRNAs (miRs) in cutaneous and hair follicle immunobiology. We evaluated, for the first time, the miR-17-92a-1 cluster host gene (MIR17HG) expression in peripheral blood of 248 unrelated alopecia areata (AA) patients compared to 244 matched controls using Real-Time qPCR. We also tested its association with different rs4284505A>G genotypes (based on TaqMan allelic discrimination PCR) and the available clinical data. The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated for each genetic association model. The upregulation of miR-17 was observed in the serum of patients with alopecia compared to controls (p-value = 0.004). The ROC curve showed high diagnostic performance of miR-17 in differentiating between patients and controls (AUC = 0.85, p-value < 0.001). rs4284505*A/G heterozygotes were more susceptible to the disease (OR = 1.57, 95% CI = 1.01–2.45) under the over-dominant model. Interestingly, pat...

Research paper thumbnail of Association of Angio-LncRNAs MIAT rs1061540/MALAT1 rs3200401 Molecular Variants with Gensini Score in Coronary Artery Disease Patients Undergoing Angiography

Biomolecules, 2022

Long non-coding RNAs (lncRNAs) have emerged as essential biomolecules with variable diagnostic an... more Long non-coding RNAs (lncRNAs) have emerged as essential biomolecules with variable diagnostic and/or prognostic utility in several diseases, including coronary artery disease (CAD). We aimed for the first time to investigate the potential association of five angiogenesis-related lncRNAs (PUNISHER, SENCR, MIAT, MALAT1, and GATA6-AS) variants with CAD susceptibility and/or severity. TaqMan Real-Time genotyping for PUNISHER rs12318065A/C, SENCR rs12420823C/T, MIAT rs1061540C/T, MALAT1 rs3200401T/C, and GATA6-AS1 rs73390820A/G were run on the extracted genomic DNA from 100 unrelated patients with stable CAD undergoing diagnostic coronary angiography and from 100 controls. After adjusting covariates, the studied variants showed no association with disease susceptibility; however, MIAT*T/T genotype was associated with a more severe Gensini score. In contrast, MALAT1*T/C heterozygosity was associated with a lower score. The lipid profile, and to a lesser extent smoking status, male sex, w...

Research paper thumbnail of Differential Effect of Three Macrolide Antibiotics on Cardiac Pathology and Electrophysiology in a Myocardial Infarction Rat Model: Influence on Sodium Nav1.5 Channel Expression

Pharmaceuticals, 2021

Macrolides were reported to have cardiotoxic effects presented mainly by electrocardiogram (ECG) ... more Macrolides were reported to have cardiotoxic effects presented mainly by electrocardiogram (ECG) changes with increased risk in cardiac patients. We aimed to determine the impact of three macrolides, azithromycin, clarithromycin and erythromycin, on cardiac electrophysiology, cardiac enzyme activities, histopathological changes, and sodium voltage-gated alpha subunit 5 (Nav1.5) channel expression. We used eight experimental groups of male albino rats: vehicle, azithromycin (100 mg/kg), clarithromycin (100 mg/kg), erythromycin (100 mg/kg), MI + vehicle, MI + azithromycin (100 mg/kg), MI + clarithromycin (100 mg/kg) and MI + erythromycin (100 mg/kg); each group received chronic oral doses of the vehicle/drugs for seven weeks. ECG abnormalities and elevated serum cardiac enzymes were observed particularly in rats with AMI compared to healthy rats. Microscopic examination revealed elevated pathology scores for rats treated with clarithromycin in both experiments following treatment with...

Research paper thumbnail of Impact of cytotoxic T‐lymphocyte‐associated protein 4 codon 17 variant and expression on vitiligo risk

Journal of Clinical Laboratory Analysis, 2021

BackgroundCytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) is one of the essential brakes exp... more BackgroundCytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) is one of the essential brakes expressed on T cells that prevent T‐cell hyperactivation‐associated autoimmune disorders. Several CTLA4 polymorphisms were implicated in the regulation of gene expression. We aimed to explore the association of CTLA4 expression and rs231775 (c.49A>G) variant with vitiligo risk and severity of the disease in a sample of the Middle Eastern population.MethodsThe CTLA4 gene expression and genotyping for rs231775 (A/G) variant were assessed in 161 vitiligo patients and 165 controls using a real‐time polymerase chain reaction. Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity score (VIDA) were evaluated.ResultsA higher frequency of rs231775 G allele was observed in vitiligo cases than controls (45% vs. 33%, p = 0.002). After adjustment of age, sex, family history of vitiligo, and CTLA expression level, using multivariate analysis, G/G carriers were associated with a higher risk...

Research paper thumbnail of MicroRNA‑499a (rs3746444A/G) gene variant and susceptibility to type 2 diabetes‑associated end‑stage renal disease

Experimental and Therapeutic Medicine, 2021

Diabetic nephropathy (DN) is a major risk factor for end-stage renal disease (ESRD). MicroRNAs (m... more Diabetic nephropathy (DN) is a major risk factor for end-stage renal disease (ESRD). MicroRNAs (miRNAs/miRs) and their variants may be implicated in health and disease, including DN. The present study aimed to investigate the association of the miRNA-499a gene (MIR499A) A/G seed region variant (rs3746444) with DN-associated ESRD susceptibility in patients with diabetes mellitus, and to determine whether there was an association between the different genotypes and the patients' laboratory and clinical data. A case-control pilot study was conducted on 180 adult patients with type 2 diabetes mellitus. A total of 90 patients with ESRD on regular hemodialysis were considered as the cases, and 90 age-, sex-and ethnicity-matched diabetic patients with normo-albuminuria were considered as the controls. MIR499A genotyping was performed using a TaqMan Real-Time allele discrimination assay. Results demonstrated that the MIR499A rs3746444*G variant conferred susceptibility to the development of ESRD under co-dominant [(odds ratio (95% confidence interval): 2.49 (1.41-3.89) and 2.41 (1.61-6.68) for heterozygous and homozygous comparison, respectively], dominant [2.30 (1.18-3.90)] and allelic [1.82 (1.17-2.83)] models. Different genotypes of the specified variant did not exhibit significant associations with the clinic-laboratory data of the studied patients or the circulating miR-499a plasma levels. In conclusion, results of the present study suggested that MIR499A rs3746444 may be a susceptibility variant for DN-associated ESRD in the study population. However, larger sample size studies with different ethnicities are warranted to verify these findings.

Research paper thumbnail of MYD88, NFKB1, and IL6 transcripts overexpression are associated with poor outcomes and short survival in neonatal sepsis

Scientific Reports, 2021

Toll-like receptor (TLR) family signature has been implicated in sepsis etiopathology. We aimed t... more Toll-like receptor (TLR) family signature has been implicated in sepsis etiopathology. We aimed to evaluate the genetic profile of TLR pathway-related key genes; the myeloid differentiation protein 88 (MYD88), IL1 receptor-associated kinase 1 (IRAK1), the nuclear factor kappa-B1 (NFKB1), and interleukin 6 (IL6) in the blood of neonates with sepsis at the time of admission and post-treatment for the available paired-samples. This case–control study included 124 infants with sepsis admitted to the neonatal intensive care unit and 17 controls. The relative gene expressions were quantified by TaqMan Real-Time qPCR and correlated to the clinic-laboratory data. MYD88, NFKB1, and IL6 relative expressions were significantly higher in sepsis cases than controls. Higher levels of MYD88 and IL6 were found in male neonates and contributed to the sex-based separation of the cases by the principal component analysis. ROC analysis revealed MYD88 and NFKB1 transcripts to be good biomarkers for seps...

Research paper thumbnail of Antioxidants-Related Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPX), Glutathione-S-Transferase (GST), and Nitric Oxide Synthase (NOS) Gene Variants Analysis in an Obese Population: A Preliminary Case-Control Study

Antioxidants, 2021

Oxidative stress and antioxidants play an important role in obesity etiopathology. Genetic varian... more Oxidative stress and antioxidants play an important role in obesity etiopathology. Genetic variants, including single nucleotide polymorphisms (SNPs) of the antioxidant-related genes, may impact disease risk in several populations. This preliminary study aimed to explore the association of 12 SNPs related to superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST), and nitric oxide synthase (NOS) genes with obesity susceptibility in a Saudi population. A total of 384 unrelated participants, including 154 (40.1%) obese individuals, were enrolled. TaqMan OpenArray Genotyping assays were used. Six SNPs were significantly more prevalent in obese cohorts: (1) GSTM1 rs1056806*C/T; (2) SOD1 rs2234694*A; (3) SOD2 rs4880*G; (4) SOD3 rs2536512*A; (5) GPX1 rs1800668*A; (6) NOS3 rs1799983*G. Four SNPs were associated with higher obesity risk under heterozygote and dominant models for GSTM1 rs1056806 (C/T), homozygote model for SOD2 rs4880 (A/G), ...

Research paper thumbnail of Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients

PLOS ONE, 2020

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Research paper thumbnail of COVID‐19 and liver dysfunction: A systematic review and meta‐analysis of retrospective studies

Journal of Medical Virology, 2020

Recently, Coronavirus Disease 2019 (COVID‐19) pandemic is the most significant global health cris... more Recently, Coronavirus Disease 2019 (COVID‐19) pandemic is the most significant global health crisis. In this study, we conducted a meta‐analysis to find the association between liver injuries and the severity of COVID‐19 disease. Online databases, including PubMed, Web of Science, Scopus, and Science direct, were searched to detect relevant publications up to 16 April 2020. Depending on the heterogeneity between studies, a fixed‐ or random‐effects model was applied to pool data. Publication bias Egger's test was also performed. Meta‐analysis of 20 retrospective studies (3428 patients), identified that patients with a severe manifestation of COVID‐19 exhibited significantly higher levels of alanine aminotransferase, aspartate aminotransferase, and bilirubin values with prolonged prothrombin time. Furthermore, lower albumin level was associated with a severe presentation of COVID‐19. Liver dysfunction was associated with a severe outcome of COVID‐19 disease. Close monitoring of th...

Research paper thumbnail of Association of VDBP rs4701 variant, but not VDR/RXR-α over-expression with bone mineral density in pediatric β-Thalassemia patients

Mediterranean Journal of Hematology and Infectious Diseases, 2020

Introduction: The reduced rate of bone formation despite the availability of vitamin D has been r... more Introduction: The reduced rate of bone formation despite the availability of vitamin D has been reported in β-thalassemia. This suggests genetic factors together with environmental one can be implicated in this condition. Since vitamin D binding protein (VDBP) maintains bioavailability of vitamin D which binds to vitamin D receptor (VDR)-retinoid X receptor alpha (RXRA) heterodimer to exert its molecular actions, we speculated that vitamin D metabolic-axis expression signature and variants could be potential molecular candidates for bone turnover/disease in thalassemia. To this end, this study aims to analyze VDR/RXRA expression signature, and two VDBP variants in a pilot sample of Egyptian β-thalassemia children in correlation with bone mineral density (BMD). Patients and methods: Forty-four β-thalassemia children and 40 unrelated controls were enrolled. The serum bone chemistry profile was measured. Peripheral blood mononuclear cells (PBMN) VDR/RXRA expression levels were quantif...

Research paper thumbnail of Circulating long noncoding RNAs H19 and GAS5 are associated with type 2 diabetes but not with diabetic retinopathy: A preliminary study

Bosnian Journal of Basic Medical Sciences, 2020

Recently, a wide range of biological and pathological roles of long noncoding RNAs (lncRNAs) have... more Recently, a wide range of biological and pathological roles of long noncoding RNAs (lncRNAs) have been discovered. However, the potential role of circulating lncRNAs H19 and GAS5 in type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) is not clear. Here, we assessed the plasma levels of H19 and GAS5 lncRNAs in T2DM patients with/without DR and evaluated if H19 and GAS5 pre-treatment plasma levels are a predictor of early response to a single aflibercept dose in DR subgroup. Plasma lncRNA expression profiles of 119 T2DM patients (66 with DR and 53 without DR) and 110 healthy controls were determined by quantitative reverse transcription PCR. The association of lncRNA expression profiles with clinical features and aflibercept early response in DR patients was investigated. Relative H19 expression levels were significantly increased in T2DM group (including DR and non-DR subgroups) vs. controls, while GAS5 levels were decreased in T2DM group (p < 0.001). There was no signif...