Perspectives on folate with special reference to epigenetics and neural tube defects.

Folate is a micronutrient essential for DNA synthesis, cell division, fetal growth and development. Folate deficiency leads to genomic instability. Inadequate intake of folate during conception may lead to neural tube defects (NTDs) in the offspring. Folate influences the DNA methylation, histone methylation and homocysteine mediated gene methylation. DNA methylation influences the expression of microRNAs (miRNAs). Folate deficiency may be associated with miRNAs misregulation leading to NTDs. Mitochondrial epigenetics and folate metabolism has proved to be involved in embryogenesis and neural tube development. Folate related genetic variants also cause the occurrence of NTDs. Unmetabolized excessive folate may affect health adversely. Hence estimation of folate levels in the blood plays an important role in high-risk cases.

Coronavirus Disease 2019 Infection among Children: Pathogenesis, Treatment, and Outcome.

Coronavirus disease 2019 (COVID-19) is a contagious disease that may lead to respiratory distress syndrome and even death. Neonates and children are most vulnerable population to COVID-19 infection; however, the infection is usually milder and has a better prognosis in pediatric patients compared with adults. It remains unclear why pediatric population is less symptomatic than adults. Children frequently experience respiratory infections and their immune system is in developing stage. However, large proportion of the asymptomatic pediatric population may contribute to transmission. This review explored several aspects of COVID-19 infection such as its epidemiology, its molecular pathogenesis with respect to angiotensin-converting enzyme 2 receptor and inflammatory mediators, intrauterine vertical transmission, imaging findings, and complications like cytokine release syndrome (multisystem inflammatory syndrome in children). We also looked at prognostic factors and treatment modalities like corticosteroids, RNA replicate inhibitors, protease inhibitors, Bruton tyrosine kinase inhibitor, that is, acalabrutinib and convalescent plasma therapy. Since there is no strong evidence for the intrauterine transmission, early isolation should be performed to protect a neonate from a COVID-19 infected mother. Development of vaccine and an effective antiviral drug are the need of the hour.

Are Global DNA methylation and telomere length useful biomarkers for identifying intrauterine growth restricted neonates?

Background: Intrauterine growth restriction (IUGR) is manifested by decreased growth rate of fetus than its normal genetic growth potential. Global DNA methylation is a crucial investigation for identification of epigenetic changes. Epigenetic change regulates Gene transcription, maintenance of genomic stability, and telomere length.Objectives: To investigate whether the global DNA methylation and telomere length are useful for identifying intrauterine growth restriction.Methods: This cohort study was conducted in the Neonatology Department of JIPMER during the period of November 2016 to December 2017. Forty (40) IUGR and forty (40) AGA neonates were recruited. Umbilical cord blood samples were collected at birth. DNA has been separated from the blood samples and using 5-mC DNA ELISA method, the percentage of genomic DNA methylated in these neonates was established. Telomere length (T/S ratio) was measured by using quantitative real time PCR. Data were expressed as a mean ± standard deviation.Results: Genomic DNA methylation varied significantly between IUGR and AGA neonates (IUGR: 3.12 ± 1.24; AGA: 4.40 ± 2.03; p: < .01). There was significant DNA hypo methylation in IUGR neonates. However, telomere length (T/S ratio) was (IUGR: 1.25 ± 0.13; AGA: 1.26 ± 0.22; p: 0.228 (NS)) similar in both groups.Conclusion: Although there is no significant difference in telomere length between IUGR and AGA neonates, global DNA methylation of 3.45 would identify IUGR with a sensitivity and specificity of 69 and 65% respectively.

Angiotensin-converting enzyme 2 (ACE2): COVID 19 gate way to multiple organ failure syndromes.

BACKGROUND: Globally, the current medical emergency for novel coronavirus 2019 (COVID-19) leads to respiratory distress syndrome and death. PURPOSE: This review highlighted the effect of COVID-19 on systemic multiple organ failure syndromes. This review is intended to fill a gap in information about human physiological response to COVID-19 infections. This review may shed some light on other potential mechanisms and approaches in COVID -19 infections towards systemic multiorgan failure syndromes. FINDING: SARS-CoV-2 intervened mainly in the lung with progression to pneumonia and acute respiratory distress syndrome (ARDS) via the angiotensin-converting enzyme 2(ACE2) receptor. Depending on the viral load, infection spread through the ACE2 receptor further to various organs such as heart, liver, kidney, brain, endothelium, GIT, immune cell, and RBC (thromboembolism). This may be aggravated by cytokine storm with the extensive release of proinflammatory cytokines from the deregulating immune system. CONCLUSION: The widespread and vicious combinations of cytokines with organ crosstalk contribute to systemic hyper inflammation and ultimately lead to multiple organ dysfunction (Fig. 1). This comprehensive study comprises various manifestations of different organs in COVID-19 and may assist the clinicians and scientists pertaining to a broad approach to fight COVID 19.

Global DNA Methylation in Cord Blood and Neurodevelopmental Outcome at 18 Months of Age among Intrauterine Growth Restricted and Appropriate for Gestational Age Infants.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with faltered growth and development later in life. Alteration in DNA methylation may occur among IUGR babies and it can have bearing on the outcome. OBJECTIVES: To compare the DNA methylation in the cord blood among IUGR and appropriate for gestational age (AGA) babies and find it is association with their neurodevelopmental outcome at 18 months of age. METHODOLOGY: Genomic DNA methylation among 40 IUGR and equal number of AGA neonates was estimated by using 5-mC ELISA kit in the cord blood. Infants were assessed at birth and their anthropometric measurements were taken. They were regularly followed up and assessed for neurodevelopment outcome till 18 months of age using DASII (Developmental Assessment Scale for Indian Infants). DNA methylation was correlated with neurodevelopmental outcome. Numbers and percentages were used for categorical data. Mean and SD were used for continuous variables. The significant mean difference between IUGR and AGA was determined by independent Student t-test. To study the association between the DNA methylation and outcome, Spearman correlation was used. A p < 0.05 was considered as statistically significant. RESULTS: Significant difference in DNA methylation was observed between IUGR and AGA infants (IUGR: 3.12 ± 1.24; AGA: 4.40 ± 2.03; p < 0.001). Anthropometry (weight, length and head circumference) at birth was significantly decreased among IUGR infants. Hospital stay was significantly longer for IUGR infants. Motor (IUGR: 89.98 ± 18.77; AGA: 101.75 ± 9.62; p < 0.001), and mental (IUGR: 90.81 ± 11.13; AGA: 105.71 ± 7.20; p < 0.001) scores were significantly decreased among IUGR compared with AGA neonates at 18 months of follow-up. Global DNA methylation had a significant positive correlation with mental score but not with motor developmental score. CONCLUSION: IUGR babies had lower motor and mental score compared with AGA babies. Cord blood global DNA methylation significantly correlated with mental development score but not with motor development at 18 months of age.

Molecular mechanisms of intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is a pregnancy specific disease characterized by decreased growth rate of fetus than the normal growth potential at particular gestational age. In the current scenario it is a leading cause of fetal and neonatal morbidity and mortality. In the last decade exhilarating experimental studies from several laboratories have provided fascinating proof for comprehension of molecular basis of IUGR. Atypical expression of enzymes governed by TGFß causes the placental apoptosis and altered expression of TGFß due to hyper alimentation causes impairment of lung function. Crosstalk of cAMP with protein kinases plays a prominent role in the regulation of cortisol levels. Increasing levels of NOD1 proteins leads to development of IUGR by increasing the levels of inflammatory mediators. Increase in leptin synthesis in placental trophoblast cells is associated with IUGR. In this review, we emphasize on the regulatory mechanisms of IUGR and its associated diseases. They may help improve the in-utero fetal growth and provide a better therapeutic intervention for prevention and treatment of IUGR.