Protein kinases constitute a large group of enzymes catalysing protein phosphorylation and controlling multiple signalling events. The human protein kinase superfamily consists of 518 members and represents a complicated system with intricate internal and external interactions. Protein kinases are classified into two main families based on the ability to phosphorylate either tyrosine or serine and threonine residues. Among the 90 tyrosine kinase genes, 58 are receptor types classified into 20 groups and 32 are of the nonreceptor types distributed into 10 groups. Tyrosine kinases execute their biological functions by controlling a variety of cellular responses, such as cell division, metabolism, migration, cell–cell and cell matrix adhesion, cell survival and apoptosis. Over the last 30 years, a major focus of research has been directed towards cancer-associated tyrosine kinases owing to their critical contributions to the development and aggressiveness of human malignancies through the pathological effects on cell behaviour. Leukaemia represents a heterogeneous group of haematological malignancies, characterised by an uncontrolled proliferation of undifferentiated hematopoietic cells or leukaemia blasts, mostly derived from bone marrow. They are usually classified as chronic or acute, depending on the rates of their progression, as well as myeloid or lymphoblastic, according to the type of blood cells involved. Overall, these malignancies are relatively common amongst both children and adults. In malignant haematopoiesis, multiple tyrosine kinases of both receptor and nonreceptor types, including AXL receptor tyrosine kinase (AXL), Discoidin domain receptor 1 (DDR1), Vascular endothelial growth factor receptor (VEGFR), Fibroblast growth factor receptor (FGFR), Mesenchymal–epithelial transition factor (MET), proto-oncogene c-Src (SRC), Spleen tyrosine kinase (SYK) and pro-oncogenic Abelson tyrosine-protein kinase 1 (ABL1) mutants, are implicated in the pathogenesis and drug resistance of practically all types of leukaemia. The role of ABL1 kinase mutants and their therapeutic inhibitors have been extensively analysed in scientific literature, and therefore, in this review, we provide insights into the impact and mechanism of action of other tyrosine kinases involved in the development and progression of human leukaemia and discuss the currently available and emerging treatment options based on targeting these molecules.
Foodborne outbreaks associated with fresh fruits and vegetables are on the rise worldwide. Biofilm formation is one of the important traits of pathogens making them strongly attached to substrates as well as express virulence phenotypes. Present study investigates the biofilm forming ability of E. coli and Salmonella sp. isolated from fresh fruits and vegetables. A total of 53 strains, including 35 E. coli and 18 Salmonella sp. isolated from different fruit and vegetable samples were taken into account for the study. Initial screening for biofilm formation was done using Congo Red agar plate test. Results revealed that 22.8% E. coli and 22.2% Salmonella sp. were potential biofilm formers. However, the MTP (Micro-Titre Plate) assay suggested more isolates of both E. coli and Salmonella sp. were moderate to strong biofilm producers. Agar plate diffusion assay with Agrobacterium tumefaciens NTL-4 showed the production of quorum signaling molecules (AHLs) by three isolates of E. coli and one Salmonella sp. Two E. coli isolates showed a significant amount of EPS production indicating higher biofilm forming potential. The Presence of LUX R homologue gene (sdiA) in two of the Salmonella isolates were confirmed by PCR which demonstrated their potential pathogenicity. Results of the work underline the biofilm forming and potentially virulent capacities of isolates from the surface of fruits and vegetables.
Salmonella typhimurium (S. typhimurium) is one of the major food and waterborne bacteria that causes several health outbreaks in the world. Although there are few antibiotics against this bacterium, some of these drugs are challenged with resistance and toxicity. To mitigate this challenge, our group explored the ethnomedicinal/herbalism knowledge about a certain spice used in Northern Ghana in West Africa against bacterial and viral infection. This plant is Capsicum chinense (C. chinense). The plant is one of the commonest food spices consumed across the world. The seed of the plant contains both capsaicin and dihydrocapsaicin. Apart from capsaicin and dihydrocapsaicin, other major capsaicinoids in C. chinense include nordihydrocapsaicin, homodihydrocapsaicin, and homocapsaicin. In this pilot work, we investigated the antibacterial activity of pure capsaicin and capsaicin extract obtained from C. chinense against S. typhimurium in vitro. Capsaicin extract showed potent inhibition of S. typhimurium growth at concentrations as low as 100 ng/mL, whereas pure capsaicin comparatively showed poorer inhibition of bacteria growth at such a concentration. Interestingly, both capsaicin extract and pure capsaicin were found to potently block a S. typhimurium invasion of the Vero cell in vitro. Taken together, we believed that capsaicin might work synergistically with dihydrocapsaicin or the other capsaicinoids to inhibit S. typhimurium growth, whereas individually, capsaicin or dihydrocapsaicin could potently block the bacteria entry and invasion of Vero cells.
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