Development of 2-oindolin-3-ylidene-indole-3-carbohydrazide derivatives as novel apoptotic and anti-proliferative agents towards colorectal cancer cells

Mitochondrial anti-apoptotic Bcl2 and BclxL proteins, are overexpressed in multiple tumour types, and has been involved in the progression and survival of malignant cells. Therefore, inhibition of such proteins has become a validated and attractive target for anticancer drug discovery. In this manner, the present studies developed a series of novel isatin–indole conjugates (7a-j and 9a-e) as potential anticancer Bcl2 and BclxL inhibitors. The progression of the two examined colorectal cancer cell lines was significantly inhibited by all of the prepared compounds with IC₅₀ ranges132–611 nM compared to IC₅₀ = 4.6 µM for 5FU, against HT-29 and IC₅₀ ranges 37–468 nM compared to IC₅₀ = 1.5 µM for 5FU, against SW-620. Thereafter, compounds 7c and 7g were selected for further investigations. Interestingly, both compounds exhibited selective cytotoxicity against both cell lines with high safety to normal fibroblast (HFF-1). In addition, both compounds 7c and 7g induced apoptosis and inhibited Bcl2 and BclxL expression in a dose-dependent manner. Collectively, the high potency and selective cytotoxicity suggested that conjugates 7c and 7g could be a starting point for further optimisation to develop novel pro-apoptotic and antitumor agents towards colon cancer.     

Detection of hypermethylation BRCA1/2 gene promoter in breast tumours among Moroccan women

Molecular Biology Reports - The promoter region is a key element of gene expression regulation. In mammals, most of the genes present, at the level of their promoter, a large number of islands CpG....     

Urinary exosomal microRNA-96-5p and microRNA-183-5p expression as potential biomarkers of bladder cancer

Molecular Biology Reports - Because of low sensitivity and specificity of the currently available urine biomarkers of bladder cancer (BC) detection and painful cystoscopy procedure. Our study aimed...     

Total Mercury Concentrations in Lake and Streams Sediments Related to Wet-Area Coverage and Geogenic Sources within Upslope Basins

Total mercury concentrations (THg) in lake and stream sediments generally decrease with wet-area coverage (A_W) per upslope basin area (A_B). This was determined by delineating the wet-area component of 12,653 basins above as many sediment-sampling locations of the Geological Survey of Canada. These locations represent four climate regions (maritime, boreal, arctic, alpine) comprising six stream and six lake study areas. The dependence of sediment THg on A_W/A_B was examined by dividing the 0 < A_W/A_B < 1 range into 40 equal segments, and obtaining the mean sediment THg value for each segment. The results were evaluated by way of regression analysis using the following equation: mean sediment THg = a (1 ? A_W/A_B)^b + c A_W/A_B, with a, b and c as area-specific coefficients. The “a” and “c” coefficients could – in part – be inferred from bedrock type, annual atmospheric Hg deposition, and mean monthly air temperatures, and mean annual precipitation. Both “a” and “c” increased with increasing atmospheric Hg deposition for lake sediments. For stream sediments, only “a” did so. The geogenic influence on the THg variations per study area was addressed through multiple regression analyses, using sediment concentrations of other heavy elements and organic matter as independent variables.     

Identification of Mx gene nucleotide dimorphism (G/A) as genetic marker for antiviral activity in Egyptian chickens

Egyptian chickens, representing 2 breeds and 7 strains, were genotyped using the PCR-RFLP and sequencing techniques for detection of a non-synonymous dimorphism (G/A) in exon 14 of chicken Myxovirus resistance (Mx) gene. This dimorphic position is responsible for altering Mx protein’s antiviral activity. Polymerase Chain reactions were performed using Egyptian chickens DNA and specific primer set to amplify Mx DNA fragments of 299 or 301?bp, containing the dimorphic position. Amplicons were cut with restriction enzyme Hpy81. Genotype and allele frequencies for the resistant allele A and sensitive allele G were calculated in all the tested chickens. Results of PCR-RFLP were confirmed by sequencing. The three genotypes AA, AG, GG at the target nucleotide position in Mx gene were represented in all the studied Egyptian chicken breeds and strains except Baladi strain which showed only one genotype AA. The average allele frequency of the resistant A allele in the tested birds (0.67) was higher than the sensitive G allele average frequency in the same birds (0.33). Appling PCR-RFLP technique in the breeding program can be used to select chickens carrying the A allele with high frequencies. This will help in improving poultry breeding in Egypt by producing infectious disease-resistant chickens.     

Buffalo species identification and delineation using genetic barcoding markers

Enrichment of barcode databases with mitochondrial cytochrome c oxidase subunit I (COI) barcode sequences in different animal taxa has become important for identification of animal source in food samples to prevent commercial fraud. In this study, COI barcode sequence in seventy one river buffalo samples were determined, analyzed and deposited in Genbank barcode database and barcode of life database (BOLD) to contribute for construction of public reference library for COI barcode sequence in river buffalo. Moreover COI barcode sequence was used to identify the closely related buffalo groups: river buffalo, swamp buffalo, lowland anoa and African buffalo. Results indicated the success of the COI barcode in the identification of each of the tested groups. Whereas a suggested sequence of other mitochondrial segment representing two successive transfer RNA (tRNA) genes; tRNA-Threonine (MT-TT) and tRNA-Proline (MT-TP) was failed to be used as a barcode marker for differentiation between the tested buffalo groups.     

A Natural Product with High Affinity to Sigma and 5-HT7 Receptors as Novel Therapeutic Drug for Negative and Cognitive Symptoms of Schizophrenia

Neurochemical Research - Dehydrocorybulbine (DHCB), an alkaloid from Corydalis yanhusuo. W.T, has been identified as a dopamine receptor antagonist. We extended our assessment of its...