Several food-poisoning outbreaks have been attributed to Clostridium perfringens (C. perfringens) worldwide. Despite that, this crisis was discussed in a few studies, and additional studies are urgently needed in this field. Therefore, we sought to highlight the prevalence, antimicrobial resistance, toxin profiles, and toxinotypes of C. perfringens isolates. In this study, 50 C. perfringens isolates obtained from 450 different animal origin samples (beef, chicken meat, and raw milk) were identified by phenotypic and genotypic methods. The antimicrobial susceptibility results were surprising, as most of the isolates (74%) showed multidrug-resistant (MDR) patterns. The phenotypic resistance to tetracycline, lincomycin, enrofloxacin, cefoxitin/ampicillin, and erythromycin was confirmed by the PCR detections of tet, lnu, qnr, bla, and erm(B) genes, respectively. In contrast to the toxinotypes C and E, toxinotype A prevailed (54%) among our isolates. Additionally, we found that the genes for C. perfringens enterotoxin (cpe) and C. perfringens beta2 toxin (cpb2) were distributed among the tested isolates with high prevalence rates (70 and 64%, respectively). Our findings confirmed that the C. perfringens foodborne crisis has been worsened by the evolution of MDR strains, which became the prominent phenotypes. Furthermore, we were not able to obtain a fixed association between the toxinotypes and antimicrobial resistance patterns.

Widespread multidrug-resistant (MDR) and multi-virulent diarrheagenic E. coli create several crises among human and animal populations worldwide. For this reason, we looked forward to a breakthrough with this issue and tried to highlight these emerging threats. A total of 140 diarrheagenic E. coli isolates were recovered from animal and human sources. The O26 serotype, alongside the ampicillin/cefoxitin resistance phenotype, was predominant among both human and animal isolates. Of note, imipenem represented the most effective antibiotic against all the investigated isolates. Unfortunately, 90% and 57.9% of the tested isolates showed MDR and multi-virulent patterns, respectively. The animal isolates were more virulent and showed higher sensitivity to antimicrobial agents. Both animal and human isolates could not be arranged into related clusters. A strong negative correlation between the existence of virulence genes and antimicrobial resistance was clearly detected. A significant correlation between serotypes and antimicrobial resistance was not detected; meanwhile, a significant positive correlation between some serotypes and the presence of certain virulence genes was announced. Finally, our results confirmed the urgent need for restricted guidelines, in addition to new alternative therapies, due to the genetic diversity and wide spreading of MDR side by side with multi-virulent E. coli isolates.

CDK2 is a key player in cell cycle processes. It has a crucial role in the progression of various cancers. Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are two common cancers that affect humans worldwide. The available therapeutic options suffer from many drawbacks including high toxicity and decreased specificity. Therefore, there is a need for more effective and safer therapeutic agents. A series of new pyrazolo[3,4-d]pyrimidine analogs was designed, synthesized, and evaluated as anticancer agents against the CRC and HCC cells, HCT116, and HepG2, respectively. Pyrazolo[3,4-d]pyrimidinone derivatives bearing N⁵-2-(4-halophenyl) acetamide substituents were identified as the most potent amongst evaluated compounds. Further evaluation of CDK2 kinase inhibition of two potential cytotoxic compounds 4a and 4b confirmed their CDK2 inhibitory activity. Compound 4a was more potent than the reference roscovitine regarding the CDK2 inhibitory activity (IC₅₀ values: 0.21 and 0.25 µM, respectively). In silico molecular docking provided insights into the molecular interactions of compounds 4a and 4b with important amino acids within the ATP-binding site of CDK2 (Ile10, Leu83, and Leu134). Overall, compounds 4a and 4b were identified as interesting CDK2 inhibitors eliciting antiproliferative activity against the CRC and HCC cells, HCT116 and HepG2, respectively, for future further investigations and development.