Micro Rna 182-3-P, 519-D-5p, 378-3p As Non-Invasive Predictors Of Preeclampsia.

BACKGROUND: MicroRNAs (miRNAs) are an emerging field of interest in many diseases. Some of the miRNAs have been reported to be expressed differentially in diseased states of pregnancy. The current study was designed to measure and compare the levels of microRNA 182-3-p, 519-d-5p, and 378-3p and it was hypothesized that the microRNA 182-3-p, 519-d-5p, and 378-3p can be used as a non-invasive predictor of preeclampsia. METHODS: Expression level of the miRNAs 182-3-p, 519-d-5p, and 378-3p was measured in the serum of preeclamptic and normal pregnancies by real-time PCR. Data was entered and analysed by Statistical Package for the Social Sciences 22 (SPSS). RESULTS: Significantly high expression levels of MiRNA 182-3p, 519-d-5p and low levels of miR-378-3p were associated with preeclampsia (PE). CONCLUSIONS: The results revealed that miR-182-3p is a powerful predictor of PE with an Odds Ratio of 5.9 and can be used as a noninvasive, reliable predictor of PE to screen these patients at an early stage. Screening at early gestation with follow-up studies can emphasize the results.

Correlation of insulin resistance with neutrophil to lymphocyte ratio and serum ferritin in male patients of metabolic syndrome.

OBJECTIVE: To determine the correlation of insulin resistance with neutrophil-to-lymphocyte ratio and serum ferritin, and to evaluate whether NLR and serum ferritin can predict insulin resistance in metabolic syndrome. METHODS: The cross-sectional analytical study was conducted at the University of Health Sciences, Lahore, Pakistan, from July 2016 to 2019, and comprised male patients of metabolic syndrome and healthy controls. The correlation involving insulin resistance, serum ferritin and neutrophil-to-lymphocyte ratio was determined. Data was analysed using SPSS 22. RESULTS: Of the 210 subjects, 160(76.2%) were cases with a median age of 45 years (interquartile range: 39-50 years), and 50(23.8%) were controls with a median age of 41 years (interquartile range: 35-50 years). Serum ferritin, alanine aminotransferase, total neutrophil count, lymphocyte count and neutrophil-to-lymphocyte ratio were significantly higher among the cases than the controls (p<0.05). Significant positive correlation of insulin resistance was observed with serum ferritin and neutrophil-to-lymphocyte ratio (p<0.05)) among the cases. Neutrophil-to-lymphocyte ratio significantly predicted insulin resistance among the cases (p<0.05). Conclusion: Neutrophil-to-lymphocyte ratio was fund to be a significant predictor of insulin resistance in metabolic syndrome.

Expression levels of MiRNA-16, SURVIVIN and TP53 in Preeclamptic and Normotensive women.

OBJECTIVE: To measure and compare micro ribonucleic acid-16, survivin and tumour protein p53-regulated apoptosis-inducing protein 1 expression levels in preeclamptic and normotensive pregnancies, and to check the correlation of micro ribonucleic acid-16 with messenger ribonucleic acid expression of survivin and tumour protein p53. METHODS: The observational cross-sectional comparative study was conducted at the Department of Physiology and Cell Biology, University of Health Sciences, Lahore, Pakistan, from 2016 to 2018, and comprised preeclamptic women in group A and normotensive women in group B. The preeclamptic patients were further categorised into early-onset preeclampsia subgroup A1and late-onset preeclampsia group A2. Expression of micro ribonucleic acid-16, messenger ribonucleic acid expression of survivin and tumour protein p53 in preeclamptic and normotensive pregnancies were analysed using real time polymerase chain reaction. Data was analysed using SPSS 22. RESULTS: Of the 54 patients, 27(50%) were in each of the two groups. Within group A, 14(52%) patients were in group A1 and 13(48%) in group A2. The expression of micro ribonucleic acid 16 showed significant increase in group A compared to group B (p<0.05). The difference was not significant between the subgroups A1 and A2. The levels of messenger ribonucleic acid expression of survivin and tumour protein p53 were deregulated in group A, with a decrease in survivin and an increase in tumour protein p53. The messenger ribonucleic acid expression of survivin and tumour protein p53 showed statistically significant differences across subgroups A1 and A2 (p<0.05). The micro ribonucleic acid-16 expression correlated negatively with messenger ribonucleic acid expression of survivin, but exhibited a positive correlation with tumour protein p53. CONCLUSIONS: Deregulated micro ribonucleic acid-16 along with differentially expressed apoptotic genes, survivin and tumour protein p53 might result in altered apoptosis implicated in the pathogenesis of preeclampsia.

Association between hypoxia-inducible factor-1 alpha rs11549465 (1772 C>T) polymorphism and metabolic syndrome.

OBJECTIVE: To find the association of single nucleotide polymorphism of hypoxia-inducible factor-1 alpha, rs11549465 (1772 Cytosine > Thymine) with metabolic syndrome, and to compare the anthropometric and biochemical variables in different genotypes of hypoxia-inducible factor-1 alpha. METHODS: The cross-sectional comparative study was conducted at the University of Health Sciences, Lahore, Pakistan, from July 2016 to April 2019, and comprised patients of metabolic syndrome selected from the Sheikh Zayed Hospital, Lahore. Healthy controls were also enrolled. Fasting venous sample was taken for the determination of study parameters. The genetic variant of hypoxia-inducible factor-1 alpha was analysed by restriction fragment length polymorphism polymerase chain reaction. Data was analysed using SPSS 22. RESULTS: Out of 400 subjects, 200(50%) each were patients and controls. The frequency of CC genotype of hypoxia-inducible factor-1 alpha Cytosine > Thymine in patients was 166(83%) and in controls 147(73.5%); CT genotype was 34(17%) and 53(26.5%) respectively, while TT genotype was not observed. There was a significant association of the C allele and CC genotype (p=0.03) with the increased risk of metabolic syndrome (p=0.02). On comparison of study variables in the two genotypes, systolic blood pressure, anthropometric and lipid parameters were significantly higher in the wild CC genotype compared to CT in the control group (p<0.05), but there was no significant difference in the patients (p>0.05). CONCLUSIONS: Major allele C of hypoxia-inducible factor-1 alpha 1772 Cytosine > Thymine was found to be associated with increased risk of metabolic syndrome.

TCF7-L2 rs7903146 polymorphism in metabolic syndrome with and without acute coronary syndrome.

OBJECTIVE: To determine the frequency and association of single nucleotide polymorphism of transcription cell factor7-like2 rs7903146 (C>T) in metabolic syndrome patients with and without acute coronary syndrome. METHODS: The cross-sectional comparative study was conducted at the University of Health Sciences, Lahore, Pakistan, from July to December 2017. Patients of metabolic syndrome with and without acute coronary syndrome were selected from Sheikh Zayed Hospital, Lahore, and the Punjab Institute of Cardiology, Lahore. Healthy subjects were enrolled to act as controls. A fasting blood sample of 8ml was taken for deoxyribonucleic acid extraction and estimation of biochemical parameters. Single nucleotide polymorphism of transcription cell factor7-like2 rs7903146 C>T was determined using restriction fragment length polymorphism. SPSS 22 was used for data analysis. RESULTS: Of the 500 subjects, 200(40%) were group A patients without acute coronary syndrome, 100(20%) were in group B with acute coronary syndrome and 200(40%) were group C controls. Overall, 385(77%) were males and 115(23%) were females. The frequency of CC variant in group A was 35(17.5%) and in group C 22(11%), while CT was 32(16%) and 65(32.5%), and TT was 133(66.5%) and 113(56.5%), respectively. There was significant association of TT genotype with increased risk of metabolic syndrome (p=0.031), and CC genotype had no association (p=0.121). There was no significant difference of genotype frequency between groups A and B (p=0.246), but TT variant was significantly higher in group A compared to group B (p=0.009). CONCLUSIONS: TT genotype of transcription cell factor7-like2 rs7903146 C>T was found to be associated with increased risk of metabolic syndrome in patients without acute coronary syndrome compared to those with acute coronary syndrome and healthy controls.

Comparative gene expression analysis of Fas and related genes in preeclamptic and healthy women: A cross-sectional study.

BACKGROUND: Preeclampsia is a hypertensive disorder of pregnancy affecting about 2-10% pregnancies worldwide. mRNA expression of tumor necrosis factor alpha (TNF- α ), Fas, and FasL have been reported to be altered in placental bed in preeclamptic pregnancies. We hypothesized that the expression of these genes is also altered in peripheral blood mononuclear cells (PBMCs) in preeclampsia. OBJECTIVE: To compare the expression of Fas receptor and related genes in PBMCs of preeclamptic and normotensive pregnant women. MATERIALS AND METHODS: A cross-sectional comparative study comprising of 18 cases and 18 controls was designed. 5 ml of venous blood was drawn and collected considering aseptic measures. Buffy coat was separated by centrifugation and stored at -20°C. Favor Prep total RNA Isolation Kit (Favorgen, Taiwan) was used for RNA extraction. The mRNA expression of TNF- α , Fas, and FasL was measured by real-time polymerase chain reaction in PBMCs in preeclamptic and normal pregnancies. RESULTS: A significant increase in mRNA expression of TNF- α , Fas, and FasL (p ≤ 0.001) was observed in PBMCs of preeclamptic pregnancies compared to the control group (p ≤ 0.001). Moreover, a significant positive correlation was found between the TNF- α mRNA expression and Fas and FasL (p ≤ 0.001). CONCLUSION: The results lead to the conclusion that mRNA expression of TNF- α , Fas, and FasL in the maternal PBMCs is altered in preeclamptic pregnancies and might contribute to the pathogenesis of the disease.

Elevated Tumor Necrosis Factor (TNF)-α mRNA Expression Correlates with Nuclear Factor Kappa B Expression in Peripheral Blood Mononuclear Cells in Preeclampsia.

OBJECTIVE: To evaluate, compare and correlate the mRNA expression of nuclear factor kappa B (NF-kB) and tumor necrosis factor alpha (TNF-α) in peripheral blood mononuclear cells in preeclampsia and normotensive group. STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY: The study was done in the Department of Physiology and Cell Biology, University of Health Sciences, Lahore, from November 2016 to November 2018. METHODOLOGY: Blood samples were collected and mRNA expression of NF-kB and TNF-α was measured quantitatively by real-time polymerase chain reaction in peripheral blood mononuclear cells in 27 preeclamptic and 27 normal pregnancies. The preeclamptic group was further divided into early and late onset preeclampsia. Statistical analysis was done using SPSS (version 22). RESULTS: The peripheral blood mononuclear cells mRNA expression of NF-kB and TNF-α differed within the two groups with an increase in expression in the diseased group (p <0.001). There was an increase of 2.79 fold in mRNA expression of TNF-α while the result for NF-αB was 2.28 fold. The difference in the expression of both NF-kB and TNF-α was significant within the two subgroups of preeclampsia (p <0.001). TNF-α was found to be strongly correlated with NF-kB (p <0.01).

Emotional Intelligence: A predictor of undergraduate student's academic achievement in altered living conditions.

OBJECTIVE: To compare the impact of trait emotional intelligence between students of different faculties and associated factors. METHODS: The cross-sectional analytical study was conducted from August 2016 to March 2017 at the University of Faisalabad, Faisalabad, Pakistan, and comprised undergraduate students, both boarders and day scholars, from seven different faculties. Data was collected using the trait emotional intelligence questionnaire-short form. Student's yearly test scores were obtained as a measure of academic achievement. Data was analysed using SPSS 20. RESULTS: Of the 498 students, 109(21.9%) were studying medicine, 56(11.2%) dental sciences, 76(15.2%) optometry, 83(16.6%) nutrition and dietetics, 109(21.9%) physiotherapy, 35(7%) pharmacy, and 30(6%) social sciences. The overall mean age was 19.84±1.30 years. There were 210(42.2%) boarders compared to 288(57.8%) day scholars. There was significant difference in emotional intelligence based on student's faculty (p<0.0001). Significant impact was seen on test scores of faculty residing status (p<0.05). Significant relation of emotional quotient and residing status with student's test scores (p<0.05). CONCLUSIONS: Emotional intelligence was found to be an important factor in academic achievement and important variable in different faculties and different living conditions.

Adrenergic receptor beta-3 rs4994 (T>C) and liver X receptor alpha rs12221497 (G>A) polymorphism in Pakistanis with metabolic syndrome.

The present study aimed to determine the association of adrenergic receptor beta-3 (ADRB3) rs4994 T>C and liver X receptor alpha (LXR-α) rs12221497 G>A polymorphism with metabolic syndrome (Met S) and the related traits in Pakistanis. Patients of Met S were recruited from the Endocrinology and Diabetic Clinic of Sheikh Zayed Hospital Lahore, over the time span of 6 months from July to December 2016. Single-nucleotide polymorphism (SNP) of ADRB3 was determined by restriction fragment length polymorphism and of LXR-α by amplification refractory mutation system polymerase chain reaction. The frequency of TT variant of ADRB3 T>C in Met S was 69 (34.5%) and in controls 89 (44.5%), frequency of TC 103 (51.5%) and 96 (48%), and of CC 28 (14%) and 15 (7.5%), respectively. In the recessive model (CC: TT + TC), CC genotype was found to be associated with the increased risk of Met S (P = 0.027; odds ratio [OR] = 2.09; confidence interval [CI] =1.08-4.03) and the association remained significant after controlling for the confounders such as age and sex. The frequency of GG variant of LXR-α G>A in Met S was 35 (17.5%) and in controls 15 (7.5%), GA 129 (64.5%) and 137 (68.5%), and AA 36 (18%) and 48 (24%), respectively. In the recessive model (GG: GA + AA), GG genotype was found to be associated with the increased risk of Met S (P = 0.004; OR = 2.52; CI = 1.33-4.80) and the association remained significant after controlling for the confounders such as age and sex. It was concluded that SNP of ADRB3 (190 T>C) and LXR-α (-115 G>A) were associated with the risk of Met S and might increase the susceptibility to the obesity-related traits.

Role of Interleukin-10 and Abdominopelvic Ultrasound as a Potential Predictor of Disease Severity in Dengue Hemorrhagic Fever.

Introduction Dengue viral infections are a major cause of morbidity and mortality in tropical/subtropical countries. Early and prompt detection of dengue hemorrhagic fever (DHF), though challenging, is helpful to identify an individual that would benefit from intensive therapy. Objective The goal of this study was to determine the plasma interleukin-10 (IL-10) levels in DHF patients at four to seven days of disease onset and 24 hours after the first sample. We also aimed to determine the association of plasma IL-10 levels and abdominopelvic ultrasound findings. Methods A total of 50 registered DHF patients aged 15 to 50 years were recruited. Plasma IL-10 concentration measurements and abdominopelvic ultrasounds were performed. Patients were also categorized based on ultrasound grading I to IV (based on severity). Outcomes were described as recovery and shock. Platelet count and hematocrit percentages were also recorded. Results Plasma IL-10 levels were elevated in DHF patients and associated with fatal outcomes (p = 0.00). Binary regression-coefficient showed the direct effect of high levels of plasma IL-10 on the fatal outcome of patients 24 hours after the first sample (p = 0.04). Disease severity was predicted by a positive correlation between ultrasound grades and outcomes (p = 0.00). Spearman's correlation coefficient found a highly significant inverse relationship between plasma IL-10 levels and platelet count after 24 hours (p = 0.01). However, a significant positive relationship was observed between elevated plasma IL-10 levels and hematocrit percentage after 24 hours (p = 0.01). Conclusion Elevated plasma IL-10 levels and abdominopelvic ultrasonography are promising potential predictors of disease progression and fatal outcome in DHF patients.

Altered expression of vascular endothelial growth factor, vascular endothelial growth factor receptor-1, vascular endothelial growth factor receptor-2, and Soluble Fms-like Tyrosine Kinase-1 in peripheral blood mononuclear cells from normal and preeclamptic pregnancies.

Preeclampsia (PE) is the leading cause of maternal and fetal morbidity and mortality. It complicates around 2%-10% pregnancies worldwide due to imbalance between proangiogenic and anti-angiogenic factors, leading to incomplete placentation, ischemia, and endothelial dysfunction. The study was aimed to analyze the mRNA expression of vascular endothelial growth factor (VEGF) and its receptors, i.e., VEGF receptor-1 (VEGFR-1), VEGF receptor-2 (VEGFR-2), and soluble Fms-like tyrosine kinase-1 (sFlt-1) from maternal peripheral blood mononuclear cells (PBMCs) of PE patients. This was a cross-sectional comparative study comprising 18 normotensive and 18 PE patients; the patients were further divided as early-onset preeclampsia (EOP) and late-onset preeclampsia (LOP). The expression level of VEGF, its receptors (VEGFR-1 and VEGFR-2), and sFlt-1 was investigated using real-time polymerase chain reaction. There was a significant change in the mRNA expression with a decrease in VEGF, VEGFR-1, and VEGFR-2 and an increase in sFlt-1 in PBMCs of PE and normal pregnancies (P < 0.001). sFlt-1 mRNA expression was increased by 2.95-fold in the PE group with an inverse correlation with expression of VEGFR-2 (Spearman's rho = 0.68). Based on these findings, we conclude that PE is associated with decrease in the mRNA expression of VEGF, VEGFR-1, and VEGFR-2 as compared to an increase in sFlt-1 in PBMCs.

Differential Expression of Placental Growth Factor, Transforming Growth Factor-ß and Soluble Endoglin in Peripheral Mononuclear Cells in Preeclampsia.

OBJECTIVE: To measure the peripheral blood mononuclear cells (PBMCs) mRNA expression of placental growth factor (PlGF), Transforming growth factor beta (TGF-ß), and soluble Endoglin (sEng) in the blood of preeclamptic and normotensive pregnant women. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Department of Physiology and Cell Biology, University of Health Sciences, Lahore, from November 2016 to April 2018. METHODOLOGY: The study included 50 normotensive and 57 preeclamptic patients (18-40 years of age), all in the third trimester of pregnancy. The preeclamptic group was further divided into early-onset preeclampsia (EOP) and late-onset preeclampsia (LOP). Blood samples from patients and healthy controls were collected and mRNA expression was measured (18 patients and 18 controls) by real time PCR. Statistical analyses were done using SPSS (version 22). The values were considered significant at 0.05 level of significance. RESULTS: The PBMCs mRNA expression of PlGF, TGF- and sEng were significantly different between the preeclampsia and control group (p<0.001). A significant decrease in expression of TGF- was observed in LOP group compared to controls (p<0.001); whereas, the difference in the expression of EOP compared to controls was not significant (p=0.12). Similar to TGF-, the expression of PlGF was significantly decreased among EOP and LOP compared to controls. Detailed analysis of sEng showed significantly increased expression in both EOP and LOP as compared to healthy group (p<0.001). CONCLUSION: There is a significant difference in extra-placental expression of PlGF, and sEng in preeclampsia.

Correlation of CRP levels in third trimester with fetal birth weight in preeclamptic and normotensive pregnant women.

OBJECTIVE: To evaluate the levels of C-reactive protein, an inflammatory marker in preeclamptic and normotensive pregnant women and to determine its correlation with fetal birth weight. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Unit of Obstetrics and Gynaecology, Shaikh Zayed Hospital and Gynaecological Unit II of Jinnah Hospital, Lahore, from December 2011 to May 2012. METHODOLOGY: The participants included 60 cases with preeclampsia and 60 normotensive pregnant women, all in their third trimester. All the participants were in the age group of 20 - 40 years and had a BMI range of 18 - 25. High sensitive C-reactive protein (hsCRP) levels were measured by Enzyme Link Immunosorbent Assay. Statistical analysis was done using SPSS (version 15). The values were considered significant at 0.05 level of significance. RESULTS: C-reactive protein levels were significantly high (p < 0.001) in the preeclamptic group with a median value of 8.8 (0.3 - 25.5) as compared to 5.4 (0.24 - 9.8) mg/l in the normotensive women. The birth weight of babies was also significantly low in the preeclamptic group. The high CRP levels were negatively correlated with fetal birth weight in preeclamptic group. CONCLUSION: Elevated C-reactive protein levels in the preeclamptic pregnant women is a part of an exaggerated maternal systemic inflammatory response, and correlates with low fetal birth weight.