Clinical Assessment of Neuroinflammatory Markers and Antioxidants in Neonates with Hyperbilirubinemia and Their Association with Acute Bilirubin Encephalopathy.

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-Em, 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-Em, 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-Em (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, PGEm, 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.

Children with Down syndrome: association of Bcl-I polymorphism of nuclear receptor subfamily 3 group C member 1 gene with obesity.

BACKROUND: This study aimed to assess the possible association between rs41423247 (Bcl-I) polymorphism in the gene for the human glucocorticoid receptor (GR) called Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1) with obesity in Egyptian children with and without Down syndrome. METHODS: The Bcl-I polymorphism was assessed, using real-time PCR, in 300 children divided into four groups: Down-obese, Down-non obese, normal-obese, and normal non-obese. RESULTS: There was no significant difference between normal-obese and normal-non obese children regarding the Bcl-I genotypes and allele frequencies, while there was a significant difference between Down-obese and Down-non obese children regarding the Bcl-I GC genotype frequency. Again, there was a highly significant difference between Down-obese and normal-non obese children and between children with Down-syndrome (obese and non-obese) and normal children (obese and non-obese) regarding the Bcl-I genotypes and alleles frequencies. CONCLUSIONS: Our study found a weak association of the G allele of Bcl-I rs41423247 with the presence of obesity among normal Egyptian children, while there was a significant association of the mutant C allele of the Bcl-I rs41423247 with Down syndrome, suggesting a possible association with Down syndrome pathophysiology. IMPACT: Bcl-I polymorphism is not strikingly associated with obesity in normal children. The GG genotype is higher in obese normal children but without significant difference. The significant increase of the mutant C allele in Down-children than normal children. This may be relevant to Down syndrome's pathophysiology which disturbs the whole genome's balance.

Mir-142-5p as an indicator of autoimmune processes in childhood idiopathic nephrotic syndrome and as a part of MicroRNAs expression panels for its diagnosis and prediction of response to steroid treatment.

BACKGROUND: Nephrotic syndrome (NS) is the most frequent glomerular disease among children. Renal biopsy is the most precise procedure for diagnosing and following childhood NS; however, it is an invasive procedure with potential complications. As a result, early non-invasive diagnostic and prognostic indicators and new treatment targets are urgently needed for this disease. PURPOSE: To assess the miR-142-5p expression in peripheral blood as an indicator of the autoimmune processes in children with NS and the role of differential microRNAs (miR) expression and expression panels in diagnosing and predicting the response to steroid treatment in children with NS. METHODS: Eighty (80) children with NS and 100 subjects matched for age and gender used as controls constitute the study sample in this case-control study. MiR-142-5p, miR-191, miR-181-5p, miR-30a-5p and miR-50a-5p expression are measured in all enrolled children by real-time PCR. We assessed the sensitivity and accuracy of different MicroRNAs panels. RESULTS: miR-142-5p, miR-191, miR-181-5p, miR-30a-5p and miR-150a-5p expressions were significantly increased in the children with NS than controls. There was a significant difference in the five mRNAs differential expressions between steroid-resistant and steroid-sensitive children with NS. Of the selected five microRNAs, miR-142a-5p was the best to allow very good discrimination of the children with NS and predict steroid resistance (AUC = 0.965 and 1.00, respectively), suggesting the possible autoimmunity processes' role in the pathogenesis of NS and the resistance to steroids. The (miR-142a-5p with miR-181a-5p and miR-30a-5p) was the best expression panel to diagnose new NS cases and predict steroid resistance. CONCLUSIONS: microRNAs expressions, either differential or as a panel, are important for early diagnosing childhood NS and may provide a non-invasive clue for the response to steroid treatment in these patients. The (miR-142a-5p, miR-181-5p, and miR-30a-5p) panel was the best one to cover both the diagnosis of the new cases and prediction of response to steroid treatment. Autoimmunity has an important role in NS pathogenesis and resistance to steroid treatment.

The TM6SF2 variant as a risk factor for hepatocellular carcinoma development in chronic liver disease patients.

Introduction: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. A non-synonymous single nucleotide polymorphism (SNP) of the transmembrane 6 superfamily member 2 (TM6SF2) gene is associated with non-alcoholic fatty liver disease. SNPs of the TM6SF2 gene play an important role in the pathogenesis of HCC in alcoholic cirrhosis, but there are limited data regarding other possible etiologies. We aimed to evaluate the role of the rs58542926 polymorphism in the development of HCC in Egyptian chronic liver disease (CLD) patients. Material and methods: A total of 120 participants, including 40 HCC patients, 40 CLD patients, and 40 healthy controls, were selected. Real-time polymerase chain reaction (RT-PCR) was used to detect the TM6SF2 rs58542926 polymorphism. Results: There were no significant differences among the three studied groups regarding age (p = 0.06) and gender (p = 0.75). Frequencies of the CT, TT, CT + TT genotypes and the T allele were significantly higher in HCC patients than in the CLD and control groups (p < 0.001, p = 0.005, and p < 0.001, respectively). CLD patients with the CT genotype had a significantly increased risk of HCC development (OR = 4.67, 95% CI: 1.67-12.90). Patients with the TT genotype had a significantly increased risk of HCC (OR = 9.33, 95% CI: 1.72-50.61). Moreover, the T allele was correlated with an increased risk of HCC (OR = 5.44, 95% CI: 2.09-14.17) compared to the C allele. Conclusions: The TM6SF2 rs58542926 genotype is associated with an increased risk of HCC in the Egyptian population.

mRNA Expression of the CUB and Sushi Multiple Domains 1 (CSMD1) and Its Serum Protein Level as Predictors for Psychosis in the Familial High-Risk Children and Young Adults.

Background: Schizophrenia (SCZ) is still a challenging, refractory, and severe disorder. It is not a fully understood disease with genetic and epigenetic susceptibility and about 80% substantial heritability. The CUB and Sushi multiple domains 1 (CSMD1) gene is implicated in neurogenesis, memory, immunity, neuropsychology, and monoamine metabolism. Thus, it is one of the powerful genes involved in the pathogenesis of SCZ. Purpose: To evaluate the possible role of the CSMD1 gene's mRNA expression and its serum protein as markers for the early diagnosis of the first-episode SCZ in familial high-risk (FHR) Egyptian children and young adults. Subjects and methods: This case-control study included 80 first-episode drug-naïve SCZ patients from FHR Egyptian children and young adults and 80 healthy participants, as controls, from the FHR-susceptible children and young adults but did not develop SCZ. In this study, the CSMD1 gene's mRNA expression and CSMD1 serum levels were measured in the peripheral blood, and these levels were correlated with the lipid profile of the study populations. Results: The CSMD1 gene's mRNA expression and its' protein levels were significantly decreased in the SCZ patients compared to controls. The receiver operating characteristic (ROC) curve analysis succeeded in distinguishing SCZ patients from those not having SCZ using cutoff points of ≤0.711 and ≤4.83 ng/mL for the CSMD1 gene's mRNA expression and serum protein level, respectively. At these levels, the diagnostic sensitivities were 93.75 and 91.25%; specificity was 92.5%; positive predictive value (PPV) were 92.6 and 92.4%; and negative predictive values (NPVs) were 93.7 and 91.4%, respectively. Also, the ROC curve analysis succeeded in discriminating those with suicidal tendencies. Conclusion: CSMD1 gene's mRNA expression might be a reliable and early diagnostic predictor of first-episode SCZ in the FHR Egyptian children and young adults.

Role of oxidative stress and vascular endothelial growth factor expression in pterygium pathogenesis and prevention of pterygium recurrence after surgical excision.

PURPOSE: To assess the roles of oxidative stress and vascular endothelial growth factor (VEGF) in pterygium pathogenesis and prevention of pterygium recurrence after surgical excision. METHODS: Surgically removed pterygium tissue from 35 pterygium patients and normal conjunctival samples from 15 patients matched for age and sex (used as controls) constituted the study samples. The conjunctival samples were preserved at - 80 °C until analysis. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH) and total antioxidant (TAO) enzymatic activity and the levels of nitric oxide (NO), malondialdehyde (MDA) and VEGF were studied in both groups. To evaluate the recurrence rate after surgical excision, the pterygium patients were further subdivided into three groups according to the adjuvant therapy used to prevent recurrence. Group 1 consisted of 10 patients who were treated with 0.2 mg mitomycin-c (MMC) for 2 min. Group 2 consisted of 12 patients treated with subconjunctival bevacizumab injection after surgical removal of the pterygium. Group 3 consisted of 13 patients who underwent combined treatment with 0.2 mg of MMC for 2 min and subconjunctival bevacizumab injection. The follow-up of patients in the three groups ranged from 7 to 15 months. RESULTS: The activities of CAT, SOD, GSH and TAO were significantly lower in pterygium samples than in normal conjunctival samples (p < 0.0001 each). The levels of MDA (p = 0.046), NO (p < 0.0001) and VEGF (p < 0.0001) were significantly higher in pterygium patients than in controls. The lowest recurrence rate after surgical excision was that of the third group. CONCLUSIONS: Oxidative stress and VEGF could play a role in the pathogenesis of pterygium as indicated by decreased antioxidant enzymatic activity and increased levels of VEGF in the pterygium tissue and the role of MMC and anti-VEGF therapy in decreasing the recurrence rate after surgical excision.

Genetic Variants and Haplotypes of Tryptophan Hydroxylase 2 and Reelin Genes May Be Linked with Attention Deficit Hyperactivity Disorder in Egyptian Children.

Attention-deficit hyperactivity disorder (ADHD) has been proposed to stem from multiple etiologies, perhaps genetic in nature with biological and psychosocial motivates. Tryptophan hydroxylase 2 (TPH2) and Reelin (RELN) genes may play a key role in triggering ADHD. The purpose of this case-controlled study was to explore the linkage of the genetic variants of TPH2 and RELN genes with ADHD. One hundred Egyptian children with ADHD and 105 age and sex matched controls constituted the study samples. Genotyping was performed for TPH2 (rs11179027; rs1843809) and RELN (rs736707; rs362691) gene polymorphisms using real time PCR assay. The alleles and genotype frequencies of TPH2 and RELN gene polymorphisms were assessed in all study participants. The frequencies of the alleles of TPH2 rs11179027 (OR = 1.75, 95% CI = 1.08-2.85, p = 0.022), TPH2 rs1843809 (OR = 3.67, 95% CI = 1.82-7.43, p = <0.001), and RELN rs736707 (OR = 1.61, 95% CI = 1.03-2.51, p = 0.035) were significantly associated with ADHD, while there was no significant difference between ADHD patients and controls regarding the frequency of RELN rs362691 (OR = 1.34, 95% CI = 0.73-2.48, p = 0.34). The frequencies of CTAG, CTGG, CTAC, CTGC, and GTAC haplotypes were significantly higher in ADHD patients than in controls (p = 0.011, 0.005, 0.015, 0.001, and 0.027, respectively). In conclusion, TPH2 rs11179027, TPH2 rs1843809, and RELN rs736707 gene alleles and haplotypes might be significantly correlated with the genetic susceptibility to ADHD in Egyptian children.