Dina Abdel Razek Midan

Despite the intense research work since the beginning of the pandemic, the pathogenesis of COVID-19 is not yet clearly understood. The previous mechanism of COVID-19, based on ACE2 tropism and explained through a single receptor, is insufficient to explain the pathogenesis due to the absence of angiotensin-converting enzyme 2 (ACE2) receptors in most of the affected organs. In the current study, we used the PatchDock server to run a molecular docking study of both the gonadotropin-releasing hormone receptor (GnRHR) and G-protein-coupled-receptor (GPCR) with the SARS-CoV-2 spike protein. Molecular Dynamics (MD) simulations were run to analyze the stability of the complexes using the GROMACS package. The docking results showed a high affinity between the spike protein with the GnRHR (−1424.9 kcal/mol) and GPCR (−1451.8 kcal/mol). The results of the MD simulations revealed the significant stability of the spike protein with the GnRHR and GPCR up to 100 ns. The SARS-CoV-2 spike protein had strong binding interactions with the GPCRs and GnRHRs, which are highly expressed in the brain, endocrine organs, and olfactory neurons. This study paves the way towards understanding the complex mechanism of neuroendocrine involvement and peripheral organ involvement, may explain the changing symptoms in patients due to new variants, and may lead to the discovery of new drug targets for COVID-19. In vitro studies involving genetic engineering or gene knockdown of the GPCRs and GnRHRs are needed to further investigate the role of these receptors in COVID-19 pathogenesis.

Sepsis is a life-threatening condition associated with high morbidity and mortality rates among neonates. Clinical diagnosis is limited due to the neonates’ unspecific signs and symptoms as well as the long time required to obtain the blood culture results. Consequently, there is an urgent need for new biomarkers to early diagnose neonatal sepsis. We aimed to evaluate Neutrophil Gelatinase-Associated Lipocalin (NGAL) diagnostic performance to detect neonatal sepsis. We enrolled 30 neonates with sepsis admitted to the neonatal intensive care units and 30 age- and sex-matched healthy neonates recruited from the neonatal outpatient clinic during their routine follow-up visits. We measured NGAL levels by sandwich enzyme-linked immunosorbent assay, the C-reactive protein (CRP) with nephelometry technique using BN II nephelometer, and the complete blood count by Mindray BC-6800 analysers. NGAL, CRP, TLC, haemoglobin, and platelet levels showed significant differences between cases and control (all p < .001). Of the 30 neonates with sepsis, 17 neonates (56.7%) survived. At 0 h, the NGAL level showed no statistically significant difference between the non-survivors and survivors’ groups; however, after 96 h, NGAL was significantly higher in the non-survivors group (p ˂ .001). Our diagnostic analysis showed that NGAL levels have strong discrimination power to early differentiate neonates with sepsis; at the 475.00 pg/ml cut-off value, NGAL showed both sensitivity and specificity of 100% with an area under curve of 100%. Conclusion: Our study suggests that NGAL could be a promising biomarker for neonatal sepsis detection. Further studies with larger sample sizes and survival analysis are warranted to confirm this finding and to clarify the efficacy of NGAL in survival prediction.

Objective: To assess the oxidant and antioxidant status in neonates with and without hyperbilirubinemia and their association with early manifestations of acute bilirubin encephalopathy (ABE), in addition to eliciting the possible oxidative effects of phototherapy. Methods: This prospective observational study was conducted with 104 full-term newborns at Menoufia University Hospitals from January 2020 to January 2021 to help resolve the debate regarding whether bilirubin is an antioxidant. The cases group (Group I) included 52 full-term newborns (37–40 weeks) with hyperbilirubinemia during the neonatal period, while the control group (Group II) included 52 healthy, full-term age and sex-matched newborns who did not have hyperbilirubinemia. The cases group was further subdivided into Group Ia (n = 12), which included newborns who presented with neurological manifestations suggesting early ABE, and Group Ib (n = 40), which included newborns with no signs suggestive of ABE. All newborns were subjected to clinical and neurological examinations, as well as laboratory investigations. Results: Comparing the specific biological markers between the Group 1 subgroups before phototherapy, the mean plasma levels of prostaglandin-E_m, prostaglandin E₂, and TSB were significantly higher in Subgroup I(a) (all p < 0.05). After phototherapy, Subgroup I(a) patients had significantly higher levels of prostaglandin-E_m, DSB, and TSB (p < 0.05). The biological marker levels improved after phototherapy in terms of TAC (0.811 vs. 0.903), MDA (8.18 vs. 5.13), prostaglandin-E_m (37.47 vs. 27.23), prostaglandin E₂ (81.09 vs. 31.49), DSB (1.21 vs. 0.55), and TSB (16.63 vs. 8.26; p-value < 0.05). Conclusion: Our study showed that an elevated level of serum bilirubin increases oxidative stress and decreases antioxidant capacity. The reduction in bilirubin levels by phototherapy is associated with a decrease in oxidative stress markers (MDA, PGE_m, and PGE₂) and an upsurge in TAC, highlighting the absence of oxidative stress effects arising from phototherapy. Neonates with neurological manifestations suggesting ABE had higher levels of oxidative stress markers and lower levels of total antioxidant capacity than those without.

Background. There was a contradiction in the previous literature on whether the D/D genotype of angiotensin-converting enzyme (ACE) is a protective or risk factor for respiratory distress syndrome (RDS) in premature neonates. To solve this debate, we intended to examine the association between ACE gene polymorphism and RDS in premature neonates. Methods. We enrolled a total of 100 premature neonates with gestational age below 37 weeks. They were divided into 2 groups, the case group included 50 premature neonates diagnosed with RDS. While the control group included 50 premature neonates with no signs of RDS. We assessed ACE gene polymorphism using polymerase chain reaction. All neonates underwent chest x-ray, echocardiography, and routine laboratory investigations. Results. D/D and D/I genotypes were higher in the control group (48% and 50%) than in the case group (26% and 40%). Whereas, I/I genotype was lower in the control group (2%) than in the case group (34%) (p<0.001). By counting D alleles among members of both groups, D-alleles were significantly higher in the control group (73%) than in the case group (46%) (p <0.001). Conclusions. In premature neonates, D/D and D/I genotypes and D-alleles are protective factors for RDS. Whereas, I/I genotype and I-alleles are associated with the incidence of RDS with complications.

Background Hypoxic-ischaemic encephalopathy (HIE) is one of the most common causes of morbidity and mortality among neonates. There is a critical need for non-invasive novel biomarkers to detect HIE early, predict its outcomes and monitor its progression. We conducted this observational study to assess the relative expression of miRNA-376c and miRNA-1268a in cord blood as potential diagnostic and prognostic biomarkers for HIE. Methods A total of 100 neonates divided into two independent groups were included. The case group included 50 neonates with HIE, while the control group included 50 matched healthy neonates. Relative expressions of miRNA-376c and miRNA-1268a were measured in whole cord blood at birth using real-time PCR. Results Compared with the control group, patients with HIE had a significantly lower median level of miRNA-376c (0.168, IQR=0.011–0.411 vs 1, IQR=0.80–1.20) and a higher median level of miRNA-1268a (13.46, IQR=2.7–22.8 vs 1, IQR=0.4–1.6). Comparing neonates with HIE who survived versus those who did not survive, no statistically significant difference between the groups in terms of miRNA-376c and miRNA-1268a (p=0.124 and p=0.279) was elicited. Our diagnostic analysis showed that, at 0.90 points, miRNA-376c has a sensitivity and a specificity of 88% and 68.40%, with an area under the curve of 84%. At 2.70 points, miRNA-1268a has a sensitivity and a specificity of 76% and 100%, with an area under the curve of 96%. Conclusion The relative expression of miRNA-376c and miRNA-1268a was altered in the cord blood of neonates with HIE. In addition, they have moderate diagnostic accuracy in detecting HIE.