Synthesis and Biological Evaluation of 2-Oxo/Thioxoquinoxaline and 2-Oxo/Thioxoquinoxaline-Based Nucleoside Analogues

Several O- and S-quinoxaline glycosides have been prepared by glycosidation of 3-methyl-2-oxo(thioxo)-1,2-dihydroquinoxalines 1a,b with α-D-glucopyranosyl, α-D-galactopyranosyl, and α-D-lactosyl bromide in the presence of K₂CO₃ followed by deacetylation with Et₃N/H₂O. Furthermore, alkylation of 1a,b with 4-bromobutyl acetate, 2-acetoxyethoxymethyl bromide, and 3-chloropropanol afforded the corresponding O- and S-acycloquinoxaline nucleosides. Reaction of 1b with chloroacetic acid followed by condensation with sulfacetamide and sulfadiazine in the presence of Et₃N/THF and ethyl chloroformate gave the corresponding sulfonamide derivatives 14 and 15, respectively. The structures of new compounds were confirmed by using IR, ¹H, ¹³C NMR spectra and microanalysis. Some of these compounds were screened in vitro for antitumor and antifungal activities.     

Serum levels of TNF-α and antioxidant enzymes and placental TNF-α expression in unexplained recurrent spontaneous miscarriage

It has been proposed that many factors have been implicated in the pathogenesis of unexplained recurrent spontaneous miscarriage (URSM). The objective of this study was to evaluate the levels of some antioxidants, tumor necrosis factor-α (TNF-α), luteinizing (LH) and follicle-stimulating hormone (FSH) in URSM. Serum levels of superoxide dismutase (SOD), catalase (CAT), LH, FSH as well as TNF-α in serum and the expression of TNF-α positive cells in placental tissues, were assayed in women suffering from unexplained first trimester miscarriage. Two groups were included, the first was represented by 16 women with URSM (number of abortions: 3–5) and the second one included 24 women with URSM (number of abortions > 5). The control groups included 20 women within their first trimester of pregnancy and 20 non pregnant healthy females within their follicular phase. The obtained results showed a highly significant decrease in serum levels of SOD and CAT, in the URSM groups compared to control groups (p< 0.05 for each comparison). Higher serum levels of TNF-α were detected in URSM groups compared to control groups (p< 0.05 for each comparison). A significant increase in serum levels of LH was encountered between URSM groups compared to control groups; on the other hand the mean levels of FSH expressed no significant changes among URSM groups as compared to first trimester pregnancies control group. A positive correlation was noticed between serum levels of TNF-α and the levels of LH (p< 0.05). We conclude that antioxidant enzymes (CAT, SOD), TNF-α, LH and FSH may play a major role in the pathogenesis of URSM. Much more work is required before the mechanisms, which lead to RSM, can be fully understood.     

The Knoevenagel reactions of pregnenolone with cyanomethylene reagents: Synthesis of thiophene,thieno[2,3-b]pyridine,thieno[3,2-d]isoxazole derivatives of pregnenolone and their in vitro cytotoxicity towards tumor and normal cell lines

The reaction of pregnenolone with either 2-aminoprop-1-ene-1,1,3-tricarbonitrile or 3-oxo-3-phenylpropanenitrile gave the Knoevenagel condensation products 3 and 6, respectively. Separation of the E and Z isomeric compounds of 3 and 6 together with their structure elucidation were carried out. Some chemical transformations of the latter products were carried out and the cytotoxicity of the newly obtained products was evaluated against some cancer cell lines and a human normal cell line. The results indicated that compounds 15, 17a, 18 and 20e among the tested compounds showed the highest cytotoxicity against the cancer cell lines.     

Synthesis and anti-H5N1 virus activity of triazole- and oxadiazole-pyrimidine hybrids and their nucleoside analogs

Abstract

New 1,2,3-triazole glycosides and 1,2,4-thioglycosides incorporating a substituted pyrimidinedione ring system were synthesized via click dipolar cycloaddition and heterocyclization of hydrazine-1-carbodithioate derivatives, respectively. The sugar hydrazine derivatives linked aminodimethyluracil were also prepared. In addition, the oxadiazoline substituted with acyclic sugar moieties linked to the pyrimidinedione as acyclic nucleoside analogs were synthesized. The antiviral activity of the synthesized compounds against avian influenza H5N1 virus was investigated and compounds 18, 13 and 19 showed good activities against the virus strains.     

Bacterial classification with convolutional neural networks based on different data reduction layers

Abstract

For high accuracy classification of DNA sequences through Convolutional Neural Networks (CNNs), it is essential to use an efficient sequence representation that can accelerate similarity comparison between DNA sequences. In addition, CNN networks can be improved by avoiding the dimensionality problem associated with multi-layer CNN features. This paper presents a new approach for classification of bacterial DNA sequences based on a custom layer. A CNN is used with Frequency Chaos Game Representation (FCGR) of DNA. The FCGR is adopted as a sequence representation method with a suitable choice of the frequency k-lengthen words occurrence in DNA sequences. The DNA sequence is mapped using FCGR that produces an image of a gene sequence. This sequence displays both local and global patterns. A pre-trained CNN is built for image classification. First, the image is converted to feature maps through convolutional layers. This is sometimes followed by a down-sampling operation that reduces the spatial size of the feature map and removes redundant spatial information using the pooling layers. The Random Projection (RP) with an activation function, which carries data with a decent variety with some randomness, is suggested instead of the pooling layers. The feature reduction is achieved while keeping the high accuracy for classifying bacteria into taxonomic levels. The simulation results show that the proposed CNN based on RP has a trade-off between accuracy score and processing time.     

Dietary Supplementation of Chromium Can Alleviate Negative Impacts of Heat Stress on Performance,Carcass Yield,and Some Blood Hematology and Chemistry Indices of Growing Japanese Quail

Ideal coatings for orthopedic implants should be able to induce excellent osseointegration with host bone tissue, which requires good osteogenic responses and limited inflammatory reactions. Cerium oxide (CeO₂) ceramics have anti-oxidative properties and can be used to decrease mediators of inflammation, making them attractive for biomedical application. In this study, two kinds of CeO₂ incorporated calcium silicate coatings (CS-10Ce and CS-30Ce) were prepared via plasma spraying technique, and the effects of CeO₂ addition on the responses of bone mesenchymal stem cells (BMSCs) and RAW264.7 macrophages were evaluated. The CS-10Ce and CS-30Ce coatings were characterized by X-ray diffraction, scanning electron microscopy, and X-ray photoelectron spectroscopy. An increase in CeO₂ content in the coatings resulted in enhanced chemical stability and better BMSCs osteogenic behaviors in terms of cell adhesion, proliferation, ALP activity, and mineralized nodule formation. With respect to either ZrO₂-added or unmodified CS coating, the CS-30Ce coating elicited higher effects on the macrophages, suppressing the gene expressions of pro-inflammatory (M1) markers (CCR7, IL-6, and TNF-α), while upregulating the expressions of anti-inflammatory (M2) markers (CD206, IL-1ra, and IL-10); moreover, it could also increase the expression of osteoinductive molecules (BMP2 and TGF-β1) by the macrophages. The results suggested that the regulation of BMSCs behaviors and macrophage-mediated responses at the coating’s surface was related to CeO₂ incorporation. The incorporation of CeO₂ in CS coatings can be a valuable strategy to promote osteogenic responses and mitigate inflammatory reactions.