GST T1, M1, and IRS-1 G972R Genetic Variants Association to Gestational Diabetes Mellitus (GDM) in Egyptian Women: Linkage to Maternal Hyperglycemia.

BACKGROUND: Gestational Diabetes Mellitus (GDM) shares in part the pathogenic mechanisms of multiple genetic interactions. Some of the T2D susceptibility genes are encountered in association with GDM. OBJECTIVE: We aimed to investigate GST T1, M1, and G972R IRS-I gene polymorphisms with the risk of developing GDM. METHODS: In this randomized case-control study, pregnant women with GDM were genotyped by PCR analysis for glutathione s-transferase-T1, M1 variant polymorphisms. RFLP was done for the G972R IRS 1 gene. Their newborns were additionally assayed for the whole of the clinical, laboratory, and genetic aspects. RESULTS: The T allele IRS-1rs1801278 TT genotype was more frequently detected in GDM mothers in comparison to healthy control ones [for TT homozygous variant; OR(CI 95%): 2.05(1.09-3.87, p: 0.025)]. Furthermore, GST T1 null was significantly presented in GDM mothers than those of control mothers [OR (CI95%: 0.29 (0.084-1.02), p:0.04]. Added to the significant correlation of glycemic indices to clinical parameters of infants born to GDM, the M1-null genotype of GST was significantly correlated (p<0.05) to abnormal values of respiratory rates and 1 minute-APGAR score noted for extra NICU care. CONCLUSION: Our results suggested that GST T1null and IRS-1 TT genotypic variants were claimed for GDM development among Egyptian women with a possible impact on their newly born infants.

Role of SCN2A c.56G/A Gene Polymorphism in Egyptian Children with Genetic Epilepsy with Febrile Seizure Plus.

BACKGROUND: Febrile Seizures (FS) are the most common seizures in children younger than 5 years. In the last decade, various coding and noncoding sequence variations of voltage-gated sodium channels SCN2A have been identified in patients with seizures, implying their genetic base. We aimed to evaluate the association between SCN2A c. G/A genetic polymorphism among Egyptian children with febrile seizure plus. METHODS: The present cross-sectional study was carried out on 100 epileptic infants and children, attendants of the Neurology Unit, pediatric department, Menoufia University Hospitals (Group Ι). The patients were sub-classified into two groups, according to response to anti-epileptic treatment; Group Ι a (drug responder) and Group Ι b (drug-resistant). Evenly divided number of apparently healthy, age and gender-matched children were selected as controls (Group II). A complete history, throughout the systemic examination and radiological & metabolic assessment, whenever needed was provided, all participants were genotyped for SCN2A rs17183814 polymorphism by Restriction Fragment Length Polymorphism (PCR-RFLP). RESULTS: Both of A allele and AA, GA genotypes of SCN2A c. 56 G/A were detected more in patients with febrile seizure plus comparison to the control group with a statistically significant difference at frequencies of 17% and 11% and 12% respectively; OR (CI95%): 10.04 (3.49-28.87) and p <0.001. On classifying epileptic patients into 2 subgroups, carriers of SCN2A rs17183814 AA genotype tended to respond poorly to Anti-epileptic Drugs (AEDs). Moreover, multivariate analysis revealed that rs17183814 A allele and positive family history of epilepsy were considered the highest predicted risk factors for the development of epilepsy; p<0.05. CONCLUSION: SCN2A rs17183814 (A) allele was specifically associated with developing febrile seizure plus and could modulate the patient's response to anti-epileptic medications.

Therapeutic strategies for Covid-19 based on molecular docking and dynamic studies to the ACE-2 receptors, Furin, and viral spike proteins.

SARS-CoV-2 is a pandemic virus that caused infections and deaths in many world countries, including the Middle East. The virus-infected human cells by binding via ACE-2 receptor through the Spike protein of the virus with Furin's help causing cell membrane fusion leading to Covid-19-cell entry. No registered drugs or vaccines are triggering this pandemic viral disease yet. Our present work is based on molecular docking and dynamics simulation that performed to spike protein-ACE-2 interface complex, ACE-2 receptor, Spike protein (RBD), and Furin as targets for new small molecules. These drugs target new potential therapies to show their probabilities toward the active sites of mentioned proteins, strongly causing inhibition and/or potential therapy for covid-19. All target proteins were estimated against new target compounds under clinical trials and repurposing drugs currently present. Possibilities of those molecules and potential therapeutics acting on a certain target were predicted. MD simulations over 200 ns with molecular mechanics-generalized Born surface area (MMGBSA) binding energy calculations were performed. The structural and energetic analyses demonstrated the stability of the ligands-MPros complex. Our present work will introduce new visions of some biologically active molecules for further studies in-vitro and in-vivo for Covid-19, repurposing of these molecules should be taking place under clinical works and offering different strategies for drugs repurposing against Covid-19 diseases.Communicated by Ramaswamy H. Sarma.

Genetic Variability of the Paired Box Transcription Factor; PAX8 Gene: Guidance Towards Treatment Strategies in a Cohort of Congenital Hypothyroidism.

The contribution of PAX8 genetic variants to congenital hypothyroidism (CH) is not well understood. We aimed to study the genetic variability of exons 3 and 5 of PAX8 gene among a cohort of children with congenital hypothyroidism in correspondence to their clinical aspect. Blood samples were collected from 117 children (63 girls and 54 boys) with CH and enrolled as cases (Group I). All cases underwent biochemical confirmation with low FT4 and high TSH levels and thyroid gland imaging, along with equal number of matched apparently healthy individuals who served as controls (Group II). Genomic materials for exons 3 and 5 of PAX8 gene were extracted, amplified by PCR, detected by electrophoresis, purified, and sequenced by the Sanger technique through the application of ABI 3730x1 DNA Sequencer. Out of 117 cases, eight different effective PAX8 mutations were detected in exon 3 (G23D, V35I, I34T, Q40P, p.R31C, p.R31H, p.R31A, and p.I47T) in 14 patients with their sonographic findings ranged from normal, hypoplastic to thyroid agenesis. Besides the reported mutations, one novel mutation; R31A was detected in 1 euotopic case. Exon 5 analysis revealed no detected mutations elsewhere. In contrast, all healthy control children showed no mutation and normal sonographic findings. Mutations in exon 3 of PAX8 gene, implies its important role in thyroid development and function, as a first estimate of PA8 mutation rate in Egyptian patients with CH having normal and dysgenetic gland. Using ultrasound is mandatory for diagnosis and guiding the treatment of children with CH.

IL-1ß-31/IL1-RA genetic markers association with idiopathic generalized epilepsy and treatment response in a cohort of Egyptian population.

Background: Neuroinflammation is an important feature of epileptogenesis.Objectives: To investigate the association of Interleukin-1beta-31 (IL-1ß-31) and Interleukin-1 receptor antagonist (IL1-RA) genetic polymorphisms with idiopathic generalized epilepsy and demonstrate their influence on drug resistance in children.Materials and Methods: One hundred children with idiopathic generalized epilepsy were age and gender-matched with apparently healthy controls. Both groups were genotyped for IL-1ß-31, and IL1-RA gene variants, analysis of these single nucleotide polymorphisms (SNPs) was done through restriction digestion of the corresponding polymerase chain reaction (PCR) products by restriction fragment length polymorphism (RFLP) assay.Results: Genotype frequency of rs1143627 TT of IL-1ß-31 and the homozygous IL1RN*I were found to be more prevalent in epileptic patients (p < .05, OR 0.12 and 5.27respectively). Also observed, T allele of IL-1ß-31 and IL1-RAI/I were substantially positively correlated with drug resistance against those who responded well to antiepileptic drugs (AEDs).Conclusions: The significant association with IL-1ß-31T and IL1-RAN*I alleles potentiated their useful role as predictive markers for the development of epilepsy and response to medical therapy.

Synthesis, in-vitro cytotoxicity of 1H-benzo[f]chromene derivatives and structure-activity relationships of the 1-aryl group and 9-position.

A series of 1H-benzo[f]chromene-2-carbonitriles was synthesized and evaluated for their cytotoxic activities against MCF-7, HCT-116, and HepG-2 cancer cells. The SAR studies reported that the substitution in the phenyl ring at 1-position of 1H-benzo[f]chromene nucleus with the specific group, H atom, or methoxy group at 9-position increases the ability of the molecule against the different cell lines.

Synthesis of 4H-chromene, coumarin, 12H-chromeno[2,3-d]pyrimidine derivatives and some of their antimicrobial and cytotoxicity activities.

Condensation of 3-N,N-diethylaminophenol (1) with α-cyanocinnamonitriles (2a-c) and ethyl α-cyanocinnamates (2d-f) provided compounds 3a-f and 4a-c. 12H-Chromeno[2,3-d]pyrimidine derivatives 6, 11-13 and 16 were obtained by treatment of 4H-chromene compounds (3) with different electrophiles followed by nucleophilic reagents. Structures of these compounds were established on the basis of IR, UV, 1H NMR, 13C NMR and MS data. Some of the new compounds were evaluated for antimicrobial and cytotoxicity activities.