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1.
BMC Cardiovasc Disord ; 22(1): 286, 2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35751015

RESUMO

BACKGROUND: Circulating microRNAs (miRNAs) are considered a hot spot of research that can be employed for monitoring and/or diagnostic purposes in coronary artery disease (CAD). Since different disease features might be reflected on altered profiles or plasma miRNAs concentrations, a combination of miRNAs can provide more reliable non-invasive biomarkers for CAD. SUBJECTS AND METHODS: We investigated a panel of 14-miRNAs selected using bioinformatics databases and current literature searching for miRNAs involved in CAD using quantitative real-time PCR technique in 73 CAD patients compared to 73 controls followed by function and pathway enrichment analysis for the 14-miRNAs. RESULTS: Our results revealed three out of the 14 circulating miRNAs understudy; miRNAs miR133a, miR155 and miR208a were downregulated. While 11 miRNAs were up-regulated in a descending order from highest fold change to lowest: miR-182, miR-145, miR-21, miR-126, miR-200b, miR-146A, miR-205, miR-135b, miR-196b, miR-140b and, miR-223. The ROC curve analysis indicated that miR-145, miR-182, miR-133a and, miR-205 were excellent biomarkers with the highest AUCs as biomarkers in CAD. All miRNAs under study except miR-208 revealed a statistically significant relation with dyslipidemia. MiR-126 and miR-155 showed significance with BMI grade, while only miR-133a showed significance with the obese patients in general. MiR-135b and miR-140b showed a significant correlation with the Wall Motion Severity Index. Pathway enrichment analysis for the miRNAS understudy revealed pathways relevant to the fatty acid biosynthesis, ECM-receptor interaction, proteoglycans in cancer, and adherens junction. CONCLUSION: The results of this study identified a differentially expressed circulating miRNAs signature that can discriminate CAD patients from normal subjects. These results provide new insights into the significant role of miRNAs expression associated with CAD pathogenesis.


Assuntos
MicroRNA Circulante , Doença da Artéria Coronariana , MicroRNAs , Biomarcadores , Estudos de Casos e Controles , MicroRNA Circulante/genética , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/genética , Humanos
2.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802633

RESUMO

The current study was designed to investigate the protective role of diosmin against cyclophosphamide-induced premature ovarian insufficiency (POI). Female Swiss albino rats received a single intraperitoneal dose of cyclophosphamide (200 mg/kg) followed by 8 mg/kg/day for the next 15 consecutive days either alone or in combination with oral diosmin at 50 or 100 mg/kg. Histopathological examination of ovarian tissues, hormonal assays for follicle stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH), assessment of the oxidative stress status, as well as measurement of the relative expression of miRNA-145 and its target genes [vascular endothelial growth factor B (VEGF-B) and regulator of cell cycle (RGC32)] were performed. Diosmin treatment ameliorated the levels of E2, AMH, and oxidative stress markers. Additionally, both low and high diosmin doses significantly reduced the histopathological alterations and nearly preserved the normal ovarian reserve. MiRNA-145 expression was upregulated after treatment with diosmin high dose. miRNA-145 target genes were over-expressed after both low and high diosmin administration. Based on our findings, diosmin has a dose-dependent protective effect against cyclophosphamide-induced ovarian toxicity in rats.


Assuntos
Diosmina/uso terapêutico , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/tratamento farmacológico , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Caspase 3/metabolismo , Catalase/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Colágeno/metabolismo , Ciclofosfamida , Diosmina/farmacologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônios/sangue , Malondialdeído/sangue , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/patologia , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Ovariana Primária/sangue , Insuficiência Ovariana Primária/patologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
3.
Cancer Control ; 26(1): 1073274819847226, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31046428

RESUMO

Glioblastoma (GBM), the most common and aggressive brain tumor in adults, shows resistance to treatment, particularly radiotherapy. One method for effective treatment is using a group of radiosensitizers that make tumor cells responsive to radiotherapy. A class of molecules whose expression is affected by radiotherapy is the microRNAs (miRNAs) that present promising regulators of the radioresponse. Eighteen miRNAs (miR-26a, -124, -128, -135b, -145, -153, -181a/b, -203, -21, -210, -212, -221/222, -223, -224, -320, and -590), involved in the pathogenesis of GBM and its radioresponsive state, were reviewed to identify their role in GBM and their potential as radiosensitizing agents. MicroRNAs-26a, -124, -128, -145, -153, -181a/b, -203, -221/222, -223, -224, -320, and -590 promoted GBM radiosensitivity, while microRNAs-135b, -21, -210, and -212 encouraged radioresistance. Ectopic overexpression of the radiosensitivity promoting miRNAs and knockdown of the radioresistant miRNAs represent a prospective radiotherapy enhancement opportunity. This offers a glimmer of hope for a group of the most unfortunate patients known to medicine.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Glioblastoma/genética , Glioblastoma/radioterapia , MicroRNAs/genética , Humanos , Radiossensibilizantes/uso terapêutico
4.
Tumour Biol ; 39(11): 1010428317726842, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29110584

RESUMO

The role of microRNAs in brain cancer is still naive. Some act as oncogene and others as tumor suppressors. Discovery of efficient biomarkers is mandatory to debate that aggressive disease. Bioinformatically selected microRNAs and their targets were investigated to evaluate their putative signature as diagnostic and prognostic biomarkers in primary glioblastoma multiforme. Expression of a panel of seven microRNAs (hsa-miR-34a, hsa-miR-16, hsa-miR-17, hsa-miR-21, hsa-miR-221, hsa-miR-326, and hsa-miR-375) and seven target genes ( E2F3, PI3KCA, TOM34, WNT5A, PDCD4, DFFA, and EGFR) in 43 glioblastoma multiforme specimens were profiled compared to non-cancer tissues via quantitative reverse transcription-polymerase chain reaction. Immunohistochemistry staining for three proteins (VEGFA, BAX, and BCL2) was performed. Gene enrichment analysis identified the biological regulatory functions of the gene panel in glioma pathway. MGMT ( O-6-methylguanine-DNA methyltransferase) promoter methylation was analyzed for molecular subtyping of tumor specimens. Our data demonstrated a significant upregulation of five microRNAs (hsa-miR-16, hsa-miR-17, hsa-miR-21, hsa-miR-221, and hsa-miR-375), three genes ( E2F3, PI3KCA, and Wnt5a), two proteins (VEGFA and BCL2), and downregulation of hsa-miR-34a and three other genes ( DFFA, PDCD4, and EGFR) in brain cancer tissues. Receiver operating characteristic analysis revealed that miR-34a (area under the curve = 0.927) and miR-17 (area under the curve = 0.900) had the highest diagnostic performance, followed by miR-221 (area under the curve = 0.845), miR-21 (area under the curve = 0.836), WNT5A (area under the curve = 0.809), PDCD4 (area under the curve = 0.809), and PI3KCA (area under the curve = 0.800). MGMT promoter methylation status was associated with high miR-221 levels. Moreover, patients with VEGFA overexpression and downregulation of TOM34 and BAX had poor overall survival. Nevertheless, miR-17, miR-221, and miR-326 downregulation were significantly associated with high recurrence rate. Multivariate analysis by hierarchical clustering classified patients into four distinct groups based on gene panel signature. In conclusion, the explored microRNA-target dysregulation could pave the road toward developing potential therapeutic strategies for glioblastoma multiforme. Future translational and functional studies are highly recommended to better understand the complex bio-molecular signature of this difficult-to-treat tumor.


Assuntos
Neoplasias Encefálicas/genética , Glioblastoma/genética , MicroRNAs/genética , Adulto , Área Sob a Curva , Análise por Conglomerados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Transcriptoma
5.
Mol Diagn Ther ; 27(3): 405-423, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37016095

RESUMO

BACKGROUND: Psoriasis and vitiligo are both chronic, skin-specific diseases classified as autoimmune diseases due to the involvement of several biochemical pathways in their pathogenesis, similar to those altered in other autoimmune diseases. The role of miRNAs in regulating skin autoimmune function has yet to be fully characterized. AIM: The aim of this study was to assess the expression profile of a panel of 11 circulating immune-related miRNAs in patients with autoimmune skin diseases, specifically psoriasis and vitiligo, and correlate their expression signature with the clinicopathological features of the diseases. SUBJECTS AND METHODS: Relative gene expression quantification for 11 immune-related circulating miRNAs in plasma was done for 300 subjects-100 patients with psoriasis, 100 patients with vitiligo and 100 normal healthy volunteers-followed by different modalities of bioinformatics analysis for the results. RESULTS: The expression levels of all the studied immune-related miRNAs were elevated in both autoimmune skin disorders, with much higher levels of expression in psoriasis than in vitiligo patients. There was a significant correlation between most of the studied miRNAs, suggesting shared target genes and/or pathways. Moreover, all the studied miRNAs showed significant results as biomarkers for autoimmune skin disease, with miRNA-145 being the best candidate. Regarding the clinicopathological data, miRNA-7, miRNA-9, miRNA-145, miRNA-148a, and miRNA-148b were positively correlated with age. All the miRNAs were inversely correlated with obesity and disease duration. CONCLUSION: This study highlights the critical role of miRNAs in skin-specific autoimmune diseases that proved to be potential biomarkers for autoimmune skin disorders, warranting their exploration as therapeutic targets.


Assuntos
Doenças Autoimunes , MicroRNAs , Psoríase , Vitiligo , Humanos , Vitiligo/genética , Vitiligo/patologia , Pele/patologia , Psoríase/metabolismo , MicroRNAs/genética , Doenças Autoimunes/genética , Doenças Autoimunes/patologia , Biomarcadores/metabolismo
6.
Mol Diagn Ther ; 27(2): 243-259, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36538237

RESUMO

BACKGROUND: Atherosclerotic plaque is considered the hallmark of atherosclerotic lesions in coronary atherosclerosis (CAS), the primary pathogenesis in coronary artery disease (CAD), which develops and progresses through a complex interplay between immune cells, vascular cells, and endothelial shear stresses. Early diagnosis of CAS is critical for avoiding plaque rupture and sudden death. Therefore, identifying new CAD biomarkers linked to vessel wall functions, such as RNA molecules with their distinct signature, is a promising development for these patients. With this rationale, the present study investigated the expression level of the vascular-related RNA transcripts (lncRNA ANRIL, miRNA-126-5p, CDK4, CDK6, TGF-ß, E-cadherin, and TNF-α) implicated in the cellular vascular function, proliferation, and inflammatory processes. METHODS: A case-control study design with a total of 180 subjects classified participants into two groups; CAD and control groups. The relative expression levels of the seven transcripts under study-selected using online bioinformatics tools and current literature-were assessed in the plasma of all study participants using RT-qPCR. Their predictive significance testing, scoring of disease prioritization, enrichment analysis, and the miRNA-mRNA regulatory network was investigated. RESULTS: The relative expression levels of all seven of the circulating vascular-related transcripts under study were statistically significant between CAD patients and controls. Receiver operating characteristic (ROC) analysis results indicated the statistical significance of all the transcripts under study with CDK4 showing the highest area under the curve (AUC) equivalent to 0.91, followed by E-cadherin (0.90), miRNA-126-5p (0.83), ANRIL (0.82), TNF-α (0.63), TGF-ß (0.62), and CDK6 (0.59), in descending order. A strong association was detected between most of the transcripts studied in CAD patients with a significant Spearman's correlation coefficient with a two-tailed significance of p < 0.001. Network analysis revealed a strong relationship between the five circulating vasculature transcripts studied and their target miRNAs and miR-126-5p, but not for ANRIL. CONCLUSION: The seven circulating vascular-related RNA transcripts under study could serve as potential CAD biomarkers, reflecting the cellular vascular function, proliferation, and inflammatory processes in CAD patients. Therefore, blood transcriptome analysis opens new frontiers for the non-invasive diagnosis of CAD.


Assuntos
Doença da Artéria Coronariana , MicroRNAs , Placa Aterosclerótica , Humanos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/genética , Fator de Necrose Tumoral alfa , Estudos de Casos e Controles , MicroRNAs/genética , Biomarcadores , Fator de Crescimento Transformador beta
7.
Front Med (Lausanne) ; 10: 1340703, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38404462

RESUMO

Introduction: Psoriasis and vitiligo are inflammatory autoimmune skin disorders with remarkable genetic involvement. Mannose-binding lectin (MBL) represents a significant immune molecule with one of its gene variants strongly linked to autoimmune diseases. Therefore, in this study, we investigated the role of the MBL variant, rs1800450, in psoriasis and vitiligo disease susceptibility. Methods: The study comprised performing in silico analysis, performing an observational study regarding psoriasis patients, and performing an observational study regarding vitiligo patients. Various in silico tools were used to investigate the impact of the selected mutation on the function, stability, post-translational modifications (PTMs), and secondary structures of the protein. In addition, a total of 489 subjects were enrolled in this study, including their demographic and clinicopathological data. Genotyping analysis was performed using real-time PCR for the single nucleotide polymorphism (SNP) rs1800450 on codon 54 of the MBL gene, utilizing TaqMan genotyping technology. In addition, implications of the studied variant on disease susceptibility and various clinicopathological data were analyzed. Results: Computational analysis demonstrated the anticipated effects of the mutation on MBL protein. Furthermore, regarding the observational studies, rs1800450 SNP on codon 54 displayed comparable results in our population relative to global frequencies reported via the 1,000 Genomes Project. This SNP showed no significant association with either psoriasis or vitiligo disease risk in all genetic association models. Furthermore, rs1800450 SNP did not significantly correlate with any of the demographic or clinicopathological features of both psoriasis and vitiligo. Discussion: Our findings highlighted that the rs1800450 SNP on the MBL2 gene has no role in the disease susceptibility to autoimmune skin diseases, such as psoriasis and vitiligo, among Egyptian patients. In addition, our analysis advocated the notion of the redundancy of MBL and revealed the lack of significant impact on both psoriasis and vitiligo disorders.

8.
Mol Diagn Ther ; 26(4): 451-465, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35761165

RESUMO

BACKGROUND: The interaction between genes and the environment in psoriasis is firmly coupled by epigenetic modification. Epigenetic modifications are inherited variations in gene expression devoid of DNA sequence alterations. Non-coding RNAs are regarded as one of the epigenetic modifications that lead eventually to enduring heritable variations in gene expression. In the present study, we chose the lncRNA, Psoriasis-susceptibility-Related RNA Gene Induced by Stress (PRINS) known to have a regulatory role in psoriasis and deduced its axis of lncRNA-miRNA-mRNA through an in silico data analysis. We aimed to assess the expression levels of this lncRNA-miRNA-mRNA in patients with psoriasis to elucidate their possible roles in psoriasis management. METHODS: We investigated the lncRNA-PRINS and its target microRNAs (miRNA124-3p, miRNA203a-5p, miRNA129-5p, miRNA146a-5p, miRNA9-5p) and partner genes (NPM, G1P3) expression levels in the plasma of 120 patients with psoriasis compared to 120 healthy volunteers using quantitative real-time polymerase chain reaction and correlated the results with the patients' clinicopathological data. Finally, we performed a function, disease, and pathway enrichment analysis for the LncRNA-miRNA-mRNA axis under study. RESULTS: The lncRNA PRINS, G1P3, and NPM genes showed significantly under-expressed levels while all miRNAs included in the study showed significant over-expression in patients with psoriasis relative to controls. The lncRNA PRINS, G1P3, and NPM genes showed a significant direct correlation with each other and inverse significant correlations with all miRNAs under study. All the study biomarkers showed significant results for discriminating between patients with psoriasis and controls using a receiver operating curve analysis with sensitivity over 90% except for PRINS, which was 74.2%. The G1P3 gene showed a direct significant correlation with body mass index in patients with psoriasis (p = 0.009) and an inverse significant correlation with age (p = 0.034). The NPM gene showed a significant correlation with body mass index in patients with psoriasis (p = 0.002). CONCLUSIONS: Based on our results, we suggest that restoring the altered PRINS-miRNA-mRNA axis gene expression levels might represent a tool to prevent psoriasis worsening, along with standard therapy. Thus, on the clinical practice level, the PRINS-miRNA-mRNA axis expression profile can be utilized in designing specific targeted therapy aimed at applying a personalized medicine approach among patients with psoriasis.


Assuntos
MicroRNAs , Psoríase , RNA Longo não Codificante , Biomarcadores , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Marcação in Situ com Primers , Psoríase/diagnóstico , Psoríase/genética , Psoríase/metabolismo , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Transcriptoma
9.
Diagnostics (Basel) ; 12(5)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35626191

RESUMO

(1) Background: The psoriasis susceptibility 1 (PSORS1) locus, located within the major histocompatibility complex, is one of the main genetic determinants for psoriasis, the genotyping profile for three single-nucleotide polymorphisms (SNPs) comprising the PSORS1 locus: rs1062470 within PSORS1C1/CDSN genes, rs887466 within PSORS1C3 gene, rs10484554 within LOC105375015 gene, were investigated and correlated with psoriasis risk and severity. (2) Methods: This pilot case-controlled study involved 100 psoriatic patients and 100 healthy individuals. We investigated three SNPs and assessed the relative gene expression profile for the PSORS1C1 gene. We then correlated the results with both disease risk and severity. (3) Results: The most significantly associated SNP in PSORS1 locus with psoriasis was rs10484554 with its C/T genotype 5.63 times more likely to develop psoriasis under codominant comparison. Furthermore, C/T and T/T genotypes were 5 times more likely to develop psoriasis. The T allele was 3 times more likely to develop psoriasis under allelic comparison. The relative gene expression of PSORS1C1 for psoriatic patients showed to be under-expressed compared to normal controls. (4) Conclusions: Our study revealed the association of the three studied SNPs with psoriasis risk and severity in an Egyptian cohort, indicating that rs10484554 could be the major key player in the PSORS1 locus.

10.
Front Genet ; 13: 797465, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664315

RESUMO

Egypt is the third most densely inhabited African country. Due to the economic burden and healthcare costs of overpopulation, genomic and genetic testing is a huge challenge. However, in the era of precision medicine, Egypt is taking a shift in approach from "one-size-fits all" to more personalized healthcare via advancing the practice of medical genetics and genomics across the country. This shift necessitates concrete knowledge of the Egyptian genome and related diseases to direct effective preventive, diagnostic and counseling services of prevalent genetic diseases in Egypt. Understanding disease molecular mechanisms will enhance the capacity for personalized interventions. From this perspective, we highlight research efforts and available services for rare genetic diseases, communicable diseases including the coronavirus 2019 disease (COVID19), and cancer. The current state of genetic services in Egypt including availability and access to genetic services is described. Drivers for applying genomics in Egypt are illustrated with a SWOT analysis of the current genetic/genomic services. Barriers to genetic service development in Egypt, whether economic, geographic, cultural or educational are discussed as well. The sensitive topic of communicating genomic results and its ethical considerations is also tackled. To understand disease pathogenesis, much can be gained through the advancement and integration of genomic technologies via clinical applications and research efforts in Egypt. Three main pillars of multidisciplinary collaboration for advancing genomics in Egypt are envisaged: resources, infrastructure and training. Finally, we highlight the recent national plan to establish a genome center that will aim to prepare a map of the Egyptian human genome to discover and accurately determine the genetic characteristics of various diseases. The Reference Genome Project for Egyptians and Ancient Egyptians will initialize a new genomics era in Egypt. We propose a multidisciplinary governance system in Egypt to support genomic medicine research efforts and integrate into the healthcare system whilst ensuring ethical conduct of data.

11.
Diagnostics (Basel) ; 12(7)2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35885466

RESUMO

Background: Methotrexate (MTX) is one of the most common medications used for rheumatoid arthritis (RA) treatment. Single-nucleotide polymorphisms (SNPs) could potentially predict variability in therapeutic outcomes. Aim: This study aims to assess the impact of SNPs in genes encoding for the MTX pathway for predicting clinical and therapeutic responses to MTX in a cohort of Egyptian patients with RA. Subjects and Methods: Data from 107 Egyptian RA patients (aged 44.4 ± 11.4 years) treated with MTX monotherapy, for a duration of 3.7 ± 3.3 years, were collected. Genotypes of 10 SNPs from four different genes were analyzed using the allelic discrimination PCR technique. Results: The ATIC rs3821353 G/T (p = 0.034) and the C/T and C/C of SLC19A1 rs7279445 (p = 0.0018) were associated with a non-response to MTX, while DHFR rs10072026 C/T and C/C were associated with a good response (p < 0.001). Carriers of the ATIC rs382135 3 G (p = 0.001) and ATIC rs4673990 G (p < 0.001) alleles were more likely to develop RA, while the SLC19A1 rs11702425 T (p < 0.001) and GGH rs12681874 T (p = 0.003) allele carriers were more likely to be protected against RA. Carriers of the ATIC rs4673990 A/G genotype (p < 0.001) were at risk of developing RA, while carriers of the following genotypes were mostly protected against RA: ATIC rs3821353 T/T (p < 0.001), ATIC rs3821353 G/G (p = 0.004), SLC19A1 rs11702425 T/T (p = 0.001), SLC19A1 rs11702425 C/T (p = 0.003), GGH rs12681874 C/T (p = 0.004) and GGH rs12681874 T/T (0.002). Conclusion: The genotyping of genes involved in the MTX pathway may be helpful to predict which RA patients will/will not benefit from MTX, and thus, may help to apply a personalized medicine approach in RA.

12.
Diagnostics (Basel) ; 12(2)2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35204551

RESUMO

Sepsis is a serious infection-induced syndrome with serious ramifications, especially in intensive care units. Global concern motivated the investigation of the role of related genes' polymorphism in predicting the liability to infection, sepsis, septic shock and survival. Among these genes is the gene encoding mannose-binding lectin (MBL), with its remarkable importance in the immune system. However, the previous studies showed conflicting results and ambiguity that urged us to engage with this issue in the Egyptian population. Prediction of functional and structural impacts of single nucleotide polymorphisms (SNPs) was done using in silico methods. A prospective observational study was conducted in intensive care units; one hundred and thirty patients were followed up. Genotyping was performed using real-time polymerase chain reaction (RT-PCR) technology. MBL SNPs showed a remarkable high frequency in our population, as well. No significant association was found between MBL2 genotypes and any of our analyses (sepsis, septic shock and survival). Only septic shock and age were independently associated with time of survival by Cox regression analysis. Our study may confirm the redundancy of MBL and the absence of significant impact on sepsis liability and mortality in adult patients.

13.
J Taibah Univ Med Sci ; 17(6): 1074-1082, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36212588

RESUMO

Objectives: C1q is a key activator of the classical pathway of the complement system and exerts consequences relating to opsonization and phagocytosis. The C1qA gene is one of three genes encoding the C1q molecule. Defects in C1q, and especially in C1qA, have been linked to an increased susceptibility to infection, sepsis, and systemic lupus erythematosus. These defects could arise from missense single nucleotide polymorphisms (SNPs) and their deleterious impacts on protein structure and function. Thus, identifying high-risk missense SNPs in C1qA has become a necessity if we are to identify appropriate measures for prevention and management of affected patients. Methods: A comprehensive in silico study was conducted to screen the 184 missense SNPs in the C1qA gene using different tools with different algorithms and approaches. We investigated the impact of SNPs on protein function, stability, and structure. In addition, we identified the location of the SNPs on protein domains, secondary structure alignment, and the phylogenetic conservation of their positions. Results: Of the 184 missense SNPs, 10 SNPs were predicted to be the most damaging to protein function and structure. Conclusion: Ten missense SNPs were predicted to have the highest risk of damaging protein function and structure, thus leading to infection, sepsis, and systemic lupus erythematosus. These 10 SNPs constitute the best candidates for further experimental investigations.

14.
Front Med (Lausanne) ; 9: 988962, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341243

RESUMO

Numerous microRNAs (miRNAs) have been found to have an aberrant expression in the peripheral blood or psoriasis patients' lesions. Psoriasis was shown to have the abnormal expression of microRNA-203 (miR-203). It is a skin-specific signal that governs cellular proliferation in a protein kinase C-dependent manner and is mostly generated by keratinocytes. This work evaluated the expression levels of the circulating miR-203 target genes SOCS3, SOCS6, TP63, TNF-, IL8, and IL24 in psoriasis patients. Using a relative quantitation PCR technique, we determined the expression levels of miR-203 and its target genes (SOCS3, SOCS6, TP63, TNF-, IL8, and IL24) in the plasma of 120 psoriatic patients and matched healthy controls. The disease characteristics of the patients were then correlated with the expression results. We also conducted numerous enrichment analyses for the diseases, functions, and pathways connected to the under-researched biomarkers. Compared to healthy controls, psoriatic patients had significantly increased levels of miR-203 expression; 7.1 (4.4-9.9). In contrast, psoriatic patients had significantly lower expression of all the examined genes compared to healthy controls. Regarding all the study biomarkers, the receiver operating characteristic (ROC) curve analysis demonstrated significant sensitivity and specificity for differentiating between psoriatic patients and healthy controls. According to the results of the disease matching score generated by miR-203 and its target genes, psoriasis was ranked first with a score of 4.45. The third-place finisher with a value of 3.98, it also demonstrated that miR-203 and its target genes are connected to various skin disorders. Our results show that miR-203 contributes to psoriasis pathogenesis not only locally in skin lesions but also in circulation, indicating that it may contribute to the systemic symptoms of the illness. MiR-203 overexpression in psoriasis suggests that miR-203 may be involved in an anti-inflammatory response because it targets both SOCS gene family members and pro-inflammatory cytokines.

15.
Sci Rep ; 12(1): 13526, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941163

RESUMO

Vitiligo is considered a disabling disease that affects physical, social, psychological, and occupational aspects of an individual's quality of life. The search for non-invasive and reliable biomarkers for vitiligo's early diagnosis, prognosis, and treatment prediction is under intensive investigation. There is currently an emerging interest in employing miRNAs as biomarkers to predict vitiligo diagnosis and prognosis, inspired by the well-preserved nature of miRNAs in serum or plasma. In the current study, we assessed a panel of 20 melanogenesis pathway-related microRNAs (miRNAs) using quantitative real-time PCR technique in 85 non-segmental vitiligo (NSV) patients compared to 85 normal controls followed by function and pathway enrichment analysis for the miRNAs with significant results. Twelve out of the 20 circulating miRNAs showed significantly higher expression levels in vitiligo patients relative to controls where miR-423 show the highest expression level followed by miR-182, miR-106a, miR-23b, miR-9, miR-124, miR-130a, miR-203a, miR-181, miR-152, and miR-320a. While six miRNAs (miR-224, miR-148a, miR-137, and miR-7, miR-148b, miR-145, miR-374b, and miR-196b) didn't show significant expression level. The analysis of the receiver operating curve indicated that miR-423, miR-106a, and miR-182 were outstanding biomarkers with the highest areas under the curve in vitiligo. This study is the first Egyptian study to investigate a panel of miRNAs expression profile in the plasma of patients with NSV. Our results suggest that specific circulating miRNAs signature might be implicated in vitiligo pathogenesis and could potentially be used as biomarkers in vitiligo.


Assuntos
MicroRNA Circulante , MicroRNAs , Vitiligo , Biomarcadores , Biomarcadores Tumorais , Perfilação da Expressão Gênica/métodos , Humanos , MicroRNAs/genética , Qualidade de Vida , Vitiligo/diagnóstico , Vitiligo/genética
16.
Epigenomics ; 11(4): 367-380, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30793921

RESUMO

AIM: Glioblastoma (GB) is one notable example of miRNA-modulated neoplasms. Given its unique expression signature, proper miRNA profiling can help discriminate between GB and other types of brain tumors. The current work aimed to develop a more GB-specific and applicable custom designed quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) miRNA assay. MATERIALS & METHODS: A comprehensive data analysis of bioinformatics databases, previous literature and commercially available pre-designed miRNA PCR arrays within the market. RESULTS: A highly enriched panel of 84 deregulated and GB-specific miRNAs has been developed. CONCLUSION: After validation of this newly developed array, it can not only save the researcher's time and effort, but can also have a potential diagnostic and/or prognostic role in GB, paving the road toward personalized medicine.


Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas/genética , Perfilação da Expressão Gênica , Glioblastoma/genética , MicroRNAs/genética , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Encefálicas/diagnóstico , Biologia Computacional/métodos , Análise de Dados , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Glioblastoma/diagnóstico , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/normas , Reprodutibilidade dos Testes
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