scholarly journals Association of Circulating miRNA Expression with Preeclampsia, Its Onset, and Severity

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 476
Author(s):  
Zuzana Kolkova ◽  
Veronika Holubekova ◽  
Marian Grendar ◽  
Marcela Nachajova ◽  
Pavol Zubor ◽  
...  

MicroRNAs (miRNAs) are one of the important regulators of cellular functions fundamental for healthy pregnancy processes, including angiogenesis and differentiation of trophoblast cells, and their deregulation could be implicated in the pathogenesis of pregnancy complications, including preeclampsia (PE). The aim of this study was to assess the association of miRNA expression in plasma samples with PE, its onset, and severity. Our study enrolled 59 pregnant women, 27 in the preeclamptic study group and 32 in the control group with physiological pregnancy. Preeclamptic pregnancies were divided into subgroups based on the severity and onset of disease. Relative expression of miR-21-5p, miR-155-5p, miR-210-5p, miR-16-5p, and miR-650 isolated from plasma samples was analysed by quantitative real-time PCR and normalised to experimentally established reference genes. Our results revealed upregulation of miR-21-5p (1.16-fold change, p = 0.0015), miR-155-5p (1.62-fold change, p = 0.0005) in preeclamptic pregnancies, compared to controls. Overexpression of these two miRNAs was observed, especially in subgroups of severe and late-onset PE compared to healthy pregnancies. Although we hypothesised that the expression level of studied miRNAs could vary between PE subtypes (mild vs. severe, early onset vs. late-onset), no obvious differences were detected. In conclusion, our study could contribute to the large-scale studies for the identification of non-invasive biomarkers for PE detection to improve outcomes for women and their new-borns.

Folia Medica ◽  
2021 ◽  
Vol 63 (3) ◽  
pp. 355-364
Author(s):  
Silva Garo Kyurkchiyan ◽  
Todor Miroslavov Popov ◽  
Felitsiya Shakola ◽  
Julian Rangachev ◽  
Vanyo Ivanov Mitev ◽  
...  

Introduction: Recently, miRNAs have become popular molecules used as non-invasive biomarkers in cancer diseases. Aim: The aim of the study was to explore the expression of four miRNAs isoforms: miR-31-3p, miR-196a-5p, miR-210-3p and miR-424-5p in plasma and tissue samples from patients with advanced laryngeal squamous cell carcinoma (LSCC) and healthy controls. Materials and methods: Fresh-frozen tumour and normal laryngeal tissue as well as plasma samples were obtained from 22 patients diagnosed with advanced LSCC. The control group included plasma samples from 21 cancer-free volunteers. Total RNA (including miRNAs) extraction, reverse transcription and real time qPCR were the laboratory techniques used in the study. The obtained results were analyzed using SPSS software v. 23. Results: We found that miR-31-3p, miR-196a-5p, and miR-210-3p levels were significantly elevated in laryngeal tumour tissue, but only the levels of miR-31-3p and miR-196a-5p were significantly upregulated in the plasma LSCC target group. Positive correlation was obtained for miR-31-3p (rs=0.443, p=0.039) and miR-196a-5p (rs=0.548; p=0.008) between plasma and adjacent tumour tissue LSCC samples. ROC analyses were used to evaluate the discriminative power of both miRNAs alone and in combination. The combination of miR-31-3p and miR-196a-5p showed best results with AUC=0.978 (95% CI: 0.945&ndash;1.000, p<0.001) with 100% sensitivity and 81% specificity at cut-off: RQ=2.99. Conclusions: Based on this miR-31-3p and miR-196a-5p are proposed as potential biomarkers for validation in larger LSCC group and could be included in a non-invasive miRNAs set for detection of advanced LSCC.


Biomolecules ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 24 ◽  
Author(s):  
Esra Demir ◽  
Hanise Ozkan ◽  
Kerem Doga Seckin ◽  
Berrak Sahtiyancı ◽  
Bulent Demir ◽  
...  

Objective: We aimed to compare the levels of plasma zonulin, a non-invasive biomarker of increased intestinal permeability, between pregnant subjects, with and without gestational diabetes mellitus (GDM), at 24–28 gestational weeks. The eighty-five consecutive pregnant subjects that presented to our hospital’s obstetrics outpatient clinic and were diagnosed with GDM, for the first time by an oral glucose tolerance test (OGTT), formed the GDM group; 90 consecutive subjects that were not diagnosed with GDM by OGTT, formed the control group. The diagnosis of GDM was made by an OGTT performed between the 24th and 28th weeks of gestation, and in compliance with the American Diabetes Association (ADA) criteria. Plasma zonulin levels were measured by the enzyme-linked immunosorbent assay (ELISA) methods. The Plasma zonulin level was significantly higher in the GDM group than the control group (p < 0.001). A correlation analysis showed that plasma zonulin level was positively correlated to body mass index (BMI), creatinine, fasting plasma glucose, baseline, first hour, and two hours glucose levels and the OGTT, hemoglobin A1C (HbA1C), homeostatic model assessment for insulin resistance (HOMA-IR), and alanine aminotransferase (ALT) levels. Our findings suggest that zonulin may be a non-invasive biomarker involved in the pathogenesis of GDM. Further large-scale studies are needed on this subject.


2021 ◽  
Author(s):  
Hanan Sakr Sherbiny ◽  
Hanaa Mostafa ◽  
Mahmoud Abdel-el Halm ◽  
Amal El Shal ◽  
Naglaa Kamal ◽  
...  

Abstract Background: Sepsis remains one of the leading causes of neonatal morbidity and mortality particularly among premature infants. Blood culture is the “gold standard” for diagnosis of neonatal sepsis but is associated with several pitfalls. Adjunctive diagnostic tests, including biological markers should be used to aid in antibiotic -starting decision in presumed septic preemies until culture results are availableAim of the work: We aim to evaluate the validity of measuring serum hepcidin concentration as diagnostic biomarker for late-onset sepsis in preemies and to quantify its cut-off value that differentiate truly septic from non-septic symptomatic premature infants. In addition, to examine the correlation between serum hepcidin (Hep-S) and urinary hepcidin (Hep-U) and to find out if measuring Hep-U can be used as an alternative safe, non-invasive biomarker for late-onset sepsis diagnosis, without exposure to frequent phlebotomy and its risks.Patients and Methods: The current case-control study included seventy-three (73) cases of clinically and laboratory confirmed late-onset sepsis as "case group" and fifty (50) non-septic premature infants of comparable age and gender as "control group". All participants were evaluated as per unit protocol to rule out sepsis by complete blood count, CRP, blood, urine, CSF and other cultures as indicated, plus different radiologic modalities as needed. Acute serum and urinary hepcidin concentration were evaluated by ELISA for all participants at enrollment "acute sample". After one week of treatment, convalescent samples for serum and urine hepcidin were collected and compared with the acute samples.Results: Statistically significant higher concentration of both serum and urinary hepcidin were recorded among cases as compared with non-septic peers (t=44.2&p=0.0001, t=23.8 &p=0.0001 for serum and urine hepcidin respectively). Similarly, Significant reduction of hepcidin at different body fluids was recoded after one week of treatment as compared with acute samples (paired t =18.1&p=0.001, paired t =14.1&p=0.001 for serum and urine hepcidin respectively). Significant direct correlations were reported between acute serum hepcidin levels and CRP, urinary hepcidin, and total leucocyte count. While significant negative correlation was recorded with platelets count. AUC of serum hepcidin ROC is 0.93, A cut off value of ≥94.8ng/ml of S. hepcidin showed sensitivity (88%), specificity (94%), PPV (95%) and NPV (84%) respectively with accurately diagnosing 90.2% of presenting cases as septic or not. While urinary hepcidin showed slightly less discriminating ability with AUC of 0.87. At cut-off value of ≥ 264 ng/mg of urinary hepcidin/urinary creatinine showed sensitivity (85%), specificity (90%), PPV (92.5%) and NPV (81%) respectively with accurately diagnosing 84.5% of presenting cases as septic or not.Conclusions: Hepcidin concentration in different body fluid can function as promising accurate and rapid surrogate test, with blood culture, that guide empiric antibiotics –starting decision or withholding it safely until the culture results is ready in symptomatic presumed septic preemies. Urinary hepcidin has advantages over serum hepcidin as; it is non-invasive, no hazards of phlebotomy, and less variable throughout the day.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Felipe Martins Elias ◽  
Nathalia Lisboa Gomes ◽  
Mirian Yumie Nishi ◽  
Rafael Loch Batista ◽  
Debora Delmonte Bissegatto ◽  
...  

Abstract Introduction: Despite the use of robust techniques for diagnosis, such as arrays and large-scale sequencing of patients with differences of sex development (DSD), the etiology of a great number of DSD patients remains unclear. Investigation of alternative signaling pathways and epigenetic factors is scarce in 46,XY DSD patients. The ZEB proteins have been related to the occurrence of hypospadias in humans, a feature often observed in the atypical genitalia of patients with 46,XY DSD. Additionally, miR-200c has been reported to regulate ZEB. Objective: To evaluate the expression of miR-200c in plasma samples of 46,XY DSD patients with unknown etiology. Methods: Plasma miR-200c of six adult 46,XY DSD patients with unknown etiology (age 18-33, mean 19±8) and 15 adult male controls (age 18-55, mean 29±10 yo) were analyzed. External Masculinization Score (EMS) was used to describe the undervirilization degree of patients’ external genitalia and to classify them in two groups with low EMS (LEMS: 0-4.9 points) and high EMS (HEMS: 5-10 points). All patients presented atypical genitalia with hypospadias. miR-200c was selected based on its targeting to ZEB1 and in silico analysis; miR-23a was used as internal normalization control. RNA was extracted from plasma samples with Magmax Mirvana Total RNA isolation kit. cDNA was synthesized using TaqMan Advanced miRNA cDNA Synthesis Kit and qPCR was performed using TaqMan Advanced miRNA. The data analysis of qPCR results of patients, of each individualized patient and also the EMS groups were compared with the control group by statistical test. Results: LEMS group presented lower expression values of miR-200c when compared to HEMS group (P=0.0001) and control group (p=0.0009), but no difference was observed when comparing HEMS group and controls, the two patients with lower miR-200c expression presented the lowest EMS (EMS- 3 and 3.5). Altogether, patients presented lower values of miR-200c, although not significantly (p=0.09). Discussion: These findings corroborate with previous literature data correlating miR200-c, ZEB1 and hypospadias. The regulatory loop of miR-200c/Zeb1 was previously demonstrated in rats with hypospadias, confirming that low expression of miR-200c induce a higher Zeb1 expression. The ZEB1 upregulation in penile tissue is positively correlated with the severity of hypospadias in animal models and humans. In the present study, 46,XY DSD patients with severe genital undervirilization had lower miR-200c expression in plasma. Conclusion: Plasma miRNA expression patterns may be a new strategy research in 46,XY DSD, contributing for understanding the processes involved in the external genitalia development.


2020 ◽  
Vol 20 (3) ◽  
pp. 1283-1291
Author(s):  
Mona Salah ◽  
Iman Shaheen ◽  
Pakinam El-Shanawany ◽  
Nagwa Eid Saad ◽  
Rasha Saad ◽  
...  

Background: Colorectal cancer (CRC) has high morbidity and mortality rates. Invasive techniques and other laboratory tests with variable sensitivity and specificity are currently used in diagnosis. Micro ribonucleic acids (miRNAs) have bio vital roles in cell proliferation and apoptosis. Dys-regulation of miRNAs is linked to tumour genesis. The objective of this study was to evaluate the specificity and sensitivity of serum non-invasive biomarkers (micro-RNAs), miR-1246, miR-23a, and miR-451in CRC patients. Methods: Peripheral expression of three miRNAs (miR-1246, miR-23a and miR-451) was investigated in sera of 37 CRC Egyptian patients and 30 healthy controls, using quantitative real-time polymerase chain reaction trying to reach the optimal non-invasive combination of miRNAs. Results: Serum miR-1246 was up-regulated in sera of CRC patients compared to normal controls (fold change = 3.55; P< 0.001) and showed 100% sensitivity and 80% specificity in diagnosis of CRC. Serum miR-451 was significantly down-reg- ulated in CRC patients (fold change = -4.86; p= 0.014), whereas, miR-23a was down-regulated but this was not statistically significant. Conclusion: Up-regulation of miR-1246 and down-regulation of miR-451 in the sera of primary CRC Egyptian patients were confirmed with high sensitivity and specificity. Large-scale studies on a wider spectrum of miRNAs in Egyptian CRC patients are needed. Keywords: miR-1246; miR-451; miR-23a.


2020 ◽  
Vol 41 (2) ◽  
pp. 134-140
Author(s):  
Yuriy Bisyuk ◽  
Andrew Dubovyi ◽  
Ilona DuBuske ◽  
Viktor Litus ◽  
Lawrence M. DuBuske

Background: This study assessed gene polymorphisms of the CD14 receptor (C-159T) and Toll-like receptor 4 (Asp299Gly) in a patient population in Crimea, Ukraine, stratified by clinical (early versus late onset; frequent versus occasional relapses; fixed versus reversible obstruction) and immunologic (atopic versus nonatopic; eosinophilic; neutrophilic or paucigranulocytic inflammation) subtype. Methods: Two polymorphisms, CD14 C-159T and TLR4 Asp299Gly, were assessed in 331 patients with asthma. The control group included 285 volunteers who were nonatopic. The single nucleotide polymorphisms were studied by using polymerase chain reaction with electrophoretic detection. Results: There were increased odds of asthma development in patients with the Asp299Gly TLR4 mutation compared with the general population underdominant odds ratio (OR) 1.52 [95% confidence interval (CI), 1.00‐2.32] and overdominant (OR 1.55 [95% CI, 1.01‐2.38]) models after adjustment for gender and age. In addition, mutations in this gene decreased the odds of nonatopic asthma in underdominant (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.027), overdominant (OR 0.27 [95% CI, 0.07‐0.96]; p = 0.033), and log-additive models (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.026) compared with the atopic subgroup after adjustment for gender, age, number of exacerbations, and type of airway inflammation. Allele frequencies for CD14 and TLR4 polymorphisms did not show statistical differences between the patients with asthma and the control subjects. Conclusion: CD14 C-159T polymorphisms were not associated with asthma in the adult population in Crimea. TLR4 Asp299Gly polymorphisms were associated with asthma and with decreased odds of nonatopic asthma compared with atopic asthma in the adult population in Crimea.


2020 ◽  
Vol 17 (2) ◽  
pp. 105-111
Author(s):  
Haitao Liu ◽  
Wei Ge ◽  
Wei Chen ◽  
Xue Kong ◽  
Weiming Jian ◽  
...  

Objectives: Previous case-control studies have focused on the relationship between ALDH2 gene polymorphism and late-onset Alzheimer's Disease (LOAD), but no definite unified conclusion has been reached. Therefore, the correlation between ALDH2 Glu504Lys polymorphism and LOAD remains controversial. To analyze the correlation between ALDH2 polymorphism and the risk of LOAD, we implemented this up-to-date meta-analysis to assess the probable association. Methods: Studies were searched through China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, China Biology Medicine, PubMed, Cochrane Library, Clinical- Trials.gov, Embase, and MEDLINE from January 1, 1994 to December 31, 2018, without any restrictions on language and ethnicity. Results: Five studies of 1057 LOAD patients and 1136 healthy controls met our criteria for the analysis. Statistically, the ALDH2 GA/AA genotype was not linked with raising LOAD risk (odds ratio (OR) = 1.48, 95% confidence interval (CI) = 0.96-2.28, p = 0.07). In subgroup analysis, the phenomenon that men with ALDH2*2 had higher risk for LOAD (OR = 1.72, 95%CI = 1.10-2.67, p = 0.02) was observed. Conclusions: This study comprehends only five existing case-control studies and the result is negative. The positive trend might appear when the sample size is enlarged. In the future, more large-scale casecontrol or cohort studies should be done to enhance the association between ALDH2 polymorphism and AD or other neurodegenerative diseases.


2020 ◽  
Vol 16 (1) ◽  
pp. 47-53
Author(s):  
Vicente Benavides-Córdoba ◽  
Mauricio Palacios Gómez

Introduction: Animal models have been used to understand the pathophysiology of pulmonary hypertension, to describe the mechanisms of action and to evaluate promising active ingredients. The monocrotaline-induced pulmonary hypertension model is the most used animal model. In this model, invasive and non-invasive hemodynamic variables that resemble human measurements have been used. Aim: To define if non-invasive variables can predict hemodynamic measures in the monocrotaline-induced pulmonary hypertension model. Materials and Methods: Twenty 6-week old male Wistar rats weighing between 250-300g from the bioterium of the Universidad del Valle (Cali - Colombia) were used in order to establish that the relationships between invasive and non-invasive variables are sustained in different conditions (healthy, hypertrophy and treated). The animals were organized into three groups, a control group who was given 0.9% saline solution subcutaneously (sc), a group with pulmonary hypertension induced with a single subcutaneous dose of Monocrotaline 30 mg/kg, and a group with pulmonary hypertension with 30 mg/kg of monocrotaline treated with Sildenafil. Right ventricle ejection fraction, heart rate, right ventricle systolic pressure and the extent of hypertrophy were measured. The functional relation between any two variables was evaluated by the Pearson correlation coefficient. Results: It was found that all correlations were statistically significant (p <0.01). The strongest correlation was the inverse one between the RVEF and the Fulton index (r = -0.82). The Fulton index also had a strong correlation with the RVSP (r = 0.79). The Pearson correlation coefficient between the RVEF and the RVSP was -0.81, meaning that the higher the systolic pressure in the right ventricle, the lower the ejection fraction value. Heart rate was significantly correlated to the other three variables studied, although with relatively low correlation. Conclusion: The correlations obtained in this study indicate that the parameters evaluated in the research related to experimental pulmonary hypertension correlate adequately and that the measurements that are currently made are adequate and consistent with each other, that is, they have good predictive capacity.


Author(s):  
Aysegul Altunkeser ◽  
Zeynep Ozturk Inal ◽  
Nahide Baran

Background: Shear wave electrography (SWE) is a novel non-invasive imaging technique which demonstrate tissue elasticity. Recent research evaluating the elasticity properties of normal and pathological tissues emphasize the diagnostic importance of this technique. Aims: Polycystic ovarian syndrome (PCOS), which is characterized by menstrual irregularity, hyperandrogenism, and polycystic overgrowth, may cause infertility. The aim of this study was to evaluate the elasticity of ovaries in patients with PCOS using SWE. Methods: 66 patients diagnosed with PCOS according to the Rotterdam criteria (PCOS = group I) and 72 patients with non-PCOS (Control = group II), were included in the study. Demographic and clinical characteristics of the participants were recorded. Ovarian elasticity was assessed in all patients with SWE, and speed values were obtained from the ovaries. The elasticity of the ovaries was compared between the two groups. Results: While there were statistically significant differences between the groups in body mass index (BMI), right and left ovarian volumes, luteinizing hormone and testosterone levels (p<0.05), no significant differences were found between groups I and II in the velocity (for the right ovary 3.89±1.81 vs. 2.93±0.72, p=0.301; for the left ovary 2.88±0.65 vs. 2.95±0.80, p=0.577) and elastography (for the right ovary 36.62±17.78 vs. 36.79±14.32, p=0.3952; for the left ovary 36.56±14.15 vs. 36.26±15.10, p=0.903) values, respectively. Conclusion: We could not obtain different velocity and elastography values from the ovaries of the patients with PCOS using SWE. Therefore, further large-scale studies are needed to elucidate this issue.


Author(s):  
Adel Hagag ◽  
Mohamed S Elfarargy ◽  
Reham Lyonis ◽  
Ghada M Al-Ashmawy

Background: Neonatal sepsis is a clinical syndrome characterized by symptoms and signs of infection in the first twenty eight days of life. Serum thyroid, cortisol and hepcidin are affected by neonatal sepsis. Aim of the work: The aim of this study was to assess the predictive value of serum thyroid hormones including free triiodothyronine (free TT3) and free tetraiodothyronine (free TT4), serum cortisol and hepcidin levels through comparison of their concentrations between normal neonates and neonates with high probable late onset sepsis. Patients and Methods: This case control study was carried out on 40 neonates with suspected high probable late onset neonatal sepsis based on clinical and laboratory finding who were admitted to NICU of Pediatric Department, Tanta University, Egypt in the period from April 2017 to May 2019 (group I) and 40 healthy neonates matched in age and sex as a control group (group II). For patients and controls; blood culture, highly sensitive C‑reactive protein (H-s CRP), serum hepcidin, serum cortisol and thyroid hormones levels including free TT3 and free TT4 were assessed. Results: There were no significant differences between studied groups as regard weight, gestational age, sex and mode of delivery. H-s CRP, serum cortisol and hepcidin were significantly higher in group I than group II while serum free TT3 and free TT4 were significantly lower in group I compared with controls. There was significantly lower H-s CRP, serum hepcidin and cortisol and significantly higher serum free TT3 and free TT4 in group I after antibiotic therapy compared to the same group before treatment while there were no significant differences between group I after antibiotic therapy and control group as regard the same parameters. There were significant positive correlation between H-s CRP and serum hepcidin and cortisol in group I while there was significant negative correlation between H-s CRP and free TT3 and free TT4. ROC curve of specificity and sensitivity of H-s CRP, serum hepcidin, cortisol, free TT3 and free TT4 in prediction of neonatal sepsis shows that serum hepcidin had the highest sensitivity and specificity with 95% and 90% respectively followed by serum cortisol, H-s CRP, free TT3 and lastly free TT4. Conclusion and recommendations: Neonates with high probable sepsis had significantly higher serum cortisol and hepcidin and significantly lower free TT3 and free TT4 compared with healthy neonates. These findings may arouse our attention about the use of these markers in diagnosis of in neonatal sepsis which can lead to early treatment and subsequently better prognosis.


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