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BackgroundMouse mammary tumor virus (MMTV) is thought to have a role in human breast cancer (BC) pathogenesis. BRCA1 and 2 genes mutations are well-established risk factors for BC. The purpose of this study was to evaluate the presence of MMTV in familial and non-familial Egyptian breast cancer patients. We also aimed to establish a correlation between BRCAs genes mutations and MMTV infection in those patients.Patients and methodsThe study was included 80 BC patients and 10 healthy women were included as a control group. We used PCR to amplify a 250-bp MMTV-like env sequence. We also used PCR followed by direct sequencing to identify the genetic variation of exons 2, 13, 19 of BRCA1 gene and exon 9 and region f of exon 11 of BRCA2 gene. High resolution melting (HRM) analysis was used to screen the selected exons of BRCA1/2 genes in order to detect different variants.ResultsMMTV DNA-like env sequences were detected in 70%, 76% of familial and non-familial BC patients, respectively, and it was not detected in any of the control subjects. The presence of viral sequences was associated with larger tumor size in the sporadic patients. Seventy BC patients showed variations in BRCA1/2 genes according to HRM analysis and sequencing analysis showed two different sequences of polymorphism among 22 familial and non-familial BC patients.ConclusionMMTV DNA was present among BC patients and it was associated with increased tumor growth. This indicates a potential role for MMTV in BC patients with and without deleterious mutation in BRCA1/2 genes.

Thiazole derivatives (7a-f and 9a-i) were synthesized in good yields (up to 98%). The synthetic protocol is achieved through a two-step reaction. The synthesized candidates were then evaluated for their antimicrobial efficacies against gram-positive and gram-negative bacteria. 4-methyl-2-(2-(3-(pentyloxy)benzylidene)hydrazinyl)-5-(p-tolyldiazenyl)thiazole showed significant antimicrobial activity against Staphylococcus aureus (ATCC: 13565) compared to ampicillin. On the other hand, 2-(2-(3-(hexyloxy)benzylidene)hydrazinyl)-4-(4-methoxyphenyl)thiazole shows potent activity against Klebsiella pneumonia (ATCC: 10031) compared to gentamicin as a standard antibiotic. The ADME profile of the prepared compounds indicated favorable pharmacological behaviors. Additionally, docking and in-silico ADMET analyses were performed for the promising derivatives and the results revealed strong antimicrobial activity. DFT calculations were performed, which provided additional insight into the thiazoles' structure and formation. [ABSTRACT FROM AUTHOR]

Two series of bis-thiazole derivatives (7a–f and 9a–j) were synthesized efficiently via two steps. First, the condensation of 3,3'-(alkane-diylbis(oxy)) dibenzaldehyde (3a,b) with hydrazinecarbothioamide (4) affording 2,2'-(((alkane-1,2-diylbis(oxy))bis(3,1-phenylene))bis(methaneylylidene))bis(hydrazine-1-carbothioamide) (5a,b). The formed 5a,b were then mixed with 2-bromo-1-arylethan-1-one 6a–c affording the corresponding thiazole derivatives 7a–f. Similarly, bis-thiazole derivatives 9a–j were synthesized through heating bis(hydrazine-1-carbothioamides) 5a,b with 2-oxo-N-arylpropanehydrazonoyl chloride 8a–i. Afterwards the synthesized bis-thiazoles 7a–f and 9a–j were evaluated for their in vitro-antibacterial activity against gram-positive and gram-negative bacterial strains. Among the tested candidates, compounds 7a, 7c, and 7d exhibited the highest antibacterial activity. Furthermore, a docking analysis showed that the most promising biologically active candidates under investigation are joined to the same amino acid (acids) as references supporting the biological activity of the tested compounds toward both gram-positive bacteria-protein and gram-negative bacteria-protein. DFT calculations were carried out to gain a better understanding of the target bis-thiazole-structures and their assembly mechanism. [ABSTRACT FROM AUTHOR]

Introduction: Use of sodium glucose cotransporter 2 inhibitors (SGLT2i) was associated with a reduction in atrial fibrillation hospitalizations. Therefore, we aim to evaluate the effects of SGLT2i on atrial tachy‐arrhythmias (ATA) in patients with cardiac implantable electronic devices (CIEDs). Methods: All 13 888 consecutive patients implanted with a CIED in two tertiary medical centers were enrolled. Treatment with SGLT2i was assessed as a time dependent variable. The primary endpoint was the total number of ATA. Secondary endpoints included total number of ventricular tachy‐arrhythmias (VTA), ATA and VTA, and death. All events were independently adjudicated blinded to the treatment. Multivariable propensity score modeling was performed. Results: During a total follow‐up of 24 442 patient years there were 62 725 ATA and 10 324 VTA events. Use of SGLT2i (N = 696) was independently associated with a significant 22% reduction in the risk of ATA (hazard ratio [HR] = 0.78 [95% confidence interval {CI} = 0.70–0.87]; p <.001); 22% reduction in the risk of ATA/VTA (HR = 0.78 [95% CI = 0.71–0.85]; p <.001); and with a 35% reduction in the risk of all‐cause mortality (HR = 0.65 [95% CI = 0.45–0.92]; p =.015), but was not significantly associated with VTA risk (HR = 0.92 [95% CI = 0.80–1.06]; p =.26). SGLT2i were associated with a lower ATA burden in heart failure (HF) patients but not among diabetes patients (HF: HR = 0.68, 95% CI = 0.58–0.80, p <.001 vs. Diabetes: HR = 0.95, 95% CI = 0.86–1.05, p =.29; p <.001 for interaction between SGLT2i indication and ATA burden). Conclusion: Our real world findings suggest that in CIED HF patients, those with SGLT2i had a pronounced reduction in ATA burden and all‐cause mortality when compared with those not on SGLT2i. [ABSTRACT FROM AUTHOR]

Inhibition of the cyclin dependent kinase 2 (CDK2) is a well-known cancer treatment approach. Based on the molecular docking simulation analysis, two new series of 2-(1-(4-methoxyphenyl)-2-(phenylsulfonyl)ethylidene)hydrazineylidene)-2,5-dihydrothiazole as CDK-2 inhibitors were designed. The lead compound IV (5-benzoyl-N2-phenyl-1,3-thiazole-2,4-diamine) was modified and optimized prior to this analysis. In contrast to Roniciclib (−8.6 kcal/mol), docking results of CDK2 hits showed high affinity and docking scores ranging from −9.1 to −10.3 kcal/mol. All of the compounds studied were evaluated in vitro for CDK2 inhibitory activity. In comparison to Roscovitine's IC50 of 0.432 µM, compound 11b had a maximum IC50 of 0.416 µM. Additionally, all hits were tested for antiproliferative activities against PC-3 human prostate cancer cells, HEPG-2 human hepatocellular carcinoma, and MCF-7 breast adenocarcinoma cell lines. The arylhydrazine moiety of the tested compounds 11a–e demonstrated high potency against HEPG-2, with 11b (IC50 = 0.11 µM) being more active than doxorubicin (IC50 = 0.12 µM). In addition, compound 11b (IC50 = 0.245 µM) was nearly as effective as doxorubicin (IC50 = 0.246 µM) against MCF-7 cancer cells. 11d showed superior antiproliferative activity against PC-3 cell line (IC50= 0.23 µM) relative to doxorubicin (IC50 = 0.29 µM). [ABSTRACT FROM AUTHOR]

Background: Inborn errors of metabolism (IEM) are single gene disorders responsible for abnormalities in the synthesis or catabolism of proteins, carbohydrates and fats by means of defective enzymes or transport proteins which results in a block of the metabolic pathway and accumulation of metabolites in different tissues. This study shows the most common diagnosed inherited inborn errors of metabolism among the Egyptian population. Prior to 1995, the diagnosis of inherited metabolic disorders in Egypt was very limited and diagnosed mainly on clinical suspicion. In 1995, The Biochemical Genetics Unit at The National Research Centre has been established as a part of The Human Genetics Department and later on in 2003 it was developed into The Biochemical Genetics Department by applying advanced techniques and equipments and providing early diagnosis for the metabolic disorders which led to better outcome in our patients. Material and methods: We have retrospectively reviewed a total of 12,148 cases suspected to have inborn errors of metabolism (IEM) with different age groups. They had been referred from several diagnostic centers and hospitals in Egypt to The Department of Biochemical Genetics at The National Research Centre. The diagnosis of these disorders was confirmed by qualitative determination of amino acid profile, quantitative determination of phenylalanine and galactose levels using dried blood spots (DBSs), quantitative determination of urinary glycosaminoglycans (GAGs), two-dimensional electrophoretic separation of GAGs in urine and the assay for lysosomal enzymes activities in plasma and leukocytes. Results: Out of the total number of cases; 1041 (8.6%) patients were proved to have metabolic disorders. Those patients were classified as: 722 patients (69.4%) with lysosomal storage disorders, 302 patients (29%) with amino acid disorders and 17 patients (1.6%) with galactosemia. Conclusion: This study illustrates the experience of the reference metabolic lab in Egypt over 15 years. The lab began metabolic disorder screening by using simple diagnostic techniques like thin layer chromatography and colored tests in urine which by time updated and upgraded the methods to diagnose a wide range of disorders. This study shows the most common diagnosed inherited inborn errors of metabolism among the Egyptian population. [ABSTRACT FROM AUTHOR]

Background: Graphene nanosheets have a broad spectrum of biomedical applications. Hepatocellular cancer (HCC) is a major health problem in the Egyptian population. Currently, treatment strategies are invasive and have several adverse side effects. Thus, other approaches are required for managing this aggressive type of cancer. Our objective here was to prepare and characterize graphene oxide nanosheets and evaluate cytotoxic effect at the molecular level in an in vitro human liver cancer cell model (HepG2). Methods: Graphene oxide nanosheets were generated by chemical oxidation and characterized by transmission electron microscopy and X-ray diffraction. Cytotoxic effects in HepG2 cells were monitored by sulforhodamine B (SRB) colorimetric assay followed by flow cytometric analysis. Molecular investigations of DNA fragmentation and expression of some apoptotic genes at the transcriptional RNA level were also performed. Results: Treatment of HepG2 cells with 400μg/ml graphene oxide nanosheets showed alteration in cell morphology after 24 h. Flow cytometry revealed accumulation of cells in S phase of cell cycle followed by dramatic effects on cellular DNA. Extensive evaluation of the cytotoxic effects of graphene oxide showed increased mRNA Bax apoptotic gene expression with not of P53 and caspase-3 mRNA after 24h, suggesting involvement of an intrinsic apoptotic caspase-independent pathway. Conclusion. Graphene oxide can mediate apoptotic gene signaling in human liver cancer cells opening a novel approach to cancer management. Further analyses at the molecular level are now required to confirm our results and facilitate biomedical applications in vivo., (Creative Commons Attribution License)