Acute myeloid leukemia (AML) is a cancer of the myeloid lineage of blood cells, and treatment for AML is lengthy and can be very expensive. Medicinal plants and their bioactive molecules are ...potential candidates for improving human health. In this work, we studied the effect of
(PV) essential oil and its derivatives, carvacrol and thymol, in AML cell lines. We demonstrated that a combination of carvacrol and thymol induced tumor cell death with low toxicity on normal cells. Mechanistically, we highlighted that different molecular pathways, including apoptosis, oxidative, reticular stress, autophagy, and necrosis, are implicated in this potential synergistic effect. Using quantitative RT-PCR, Western blotting, and apoptosis inhibitors, we showed that cell death induced by the carvacrol and thymol combination is caspase-dependent in the HL60 cell line and caspase-independent in the other cell lines tested. Further investigations should focus on improving the manufacturing of these compounds and understanding their anti-tumoral mechanisms of action. These efforts will lead to an increase in the efficiency of the oncotherapy strategy regarding AML.
Stem cells have been the focus of intense research opening up new possibilities for the treatment of various diseases. Mesenchymal stromal cells (MSCs) are multipotent cells with relevant ...immunomodulatory properties and are thus considered as a promising new strategy for immune disease management. To enhance their efficiency, several issues related to both MSC biology and functions are needed to be identified and, most importantly, well clarified. The sources from which MSCs are isolated are diverse and might affect their properties. Both clinicians and scientists need to handle a phenotypic-characterized population of MSCs, particularly regarding their immunological profile. Moreover, it is now recognized that the tissue-reparative effects of MSCs are based on their immunomodulatory functions that are activated following a priming/licensing step. Thus, finding the best ways to pre-conditionate MSCs before their injection will strengthen their activity potential. Finally, soluble elements derived from MSC-secretome, including extracellular vesicles (EVs), have been proposed as a cell-free alternative tool for therapeutic medicine. Collectively, these features have to be considered and developed to ensure the efficiency and safety of MSC-based therapy. By participating to this Special Issue "Mesenchymal Stem/Stromal Cells in Immunity and Disease", your valuable contribution will certainly enrich the content and discussion related to the thematic of MSCs.
Small molecules have been shown to be potent and selective probes to understand cell physiology. Here, we show that imidazo1,2-apyridines and imidazo1,2-apyrimidines compose a class of compounds that ...target essential, conserved cellular processes. Using validated chemogenomic assays in Saccharomyces cerevisiae, we discovered that two closely related compounds, an imidazo1,2-apyridine and -pyrimidine that differ by a single atom, have distinctly different mechanisms of action in vivo. 2-phenyl-3-nitroso-imidazo1,2-apyridine was toxic to yeast strains with defects in electron transport and mitochondrial functions and caused mitochondrial fragmentation, suggesting that compound 13 acts by disrupting mitochondria. By contrast, 2-phenyl-3-nitroso-imidazo1,2-apyrimidine acted as a DNA poison, causing damage to the nuclear DNA and inducing mutagenesis. We compared compound 15 to known chemotherapeutics and found resistance required intact DNA repair pathways. Thus, subtle changes in the structure of imidazo-pyridines and -pyrimidines dramatically alter both the intracellular targeting of these compounds and their effects in vivo. Of particular interest, these different modes of action were evident in experiments on human cells, suggesting that chemical-genetic profiles obtained in yeast are recapitulated in cultured cells, indicating that our observations in yeast can: (1) be leveraged to determine mechanism of action in mammalian cells and (2) suggest novel structure-activity relationships.
Mesenchymal stromal cells (MSCs) represent a progenitor cell population with several biological properties. MSCs are thus of therapeutic interest for cell-based therapy but great efforts are needed ...to enhance their efficiency and safety. Herbal remedies and in particular their bioactive molecules, are potential candidates for improving human health. The novelty and originality of this study is to develop an efficient cell-therapeutic product by combining MSCs with medicinal plant derived bioactive molecules. Thus, the impact of Essential Oil, Thymol and Carvacrol from Ptychotis verticillata on several BM-MSC biological features were studied. These compounds have shown positive effects on MSCs by preserving their morphology, sustaining their viability, promoting their proliferation, protecting them from cytotoxicity and oxidative stress. Accordingly, the combined administration of P. verticillata extract and MSCs may represent a new approach to enhance the therapeutic issue. Further investigations should greatly improve the manufacturing of these compounds as well as our understanding of the therapeutic effects of these bioactive molecules on the biology and functions of MSCs.
•Mesenchymal stromal cells (MSCs) are major therapeutic cell progenitors which efficiency needs to be improved.•Ptychotis verticillata derived bioactive molecules are tested as potential candidates for improving MSC efficacy.•MSC morphology, viability, proliferation and oxidative response are differentially influenced.•Combined administration of P. verticillata extract and MSCs may represent a new therapeutic approach.•Amelioration of compound manufacturing and characterization will increase their therapeutic value in combination with MSCs.
The budding yeast Saccharomyces cerevisiae is a valuable system to study cell-cycle regulation, which is defective in cancer cells. Due to the highly conserved nature of the cell-cycle machinery ...between yeast and humans, yeast studies are directly relevant to anticancer-drug discovery. The budding yeast is also an excellent model system for identifying and studying antifungal compounds because of the functional conservation of fungal genes. Moreover, yeast studies have also contributed greatly to our understanding of the biological targets and modes of action of bioactive compounds. Understanding the mechanism of action of clinically relevant compounds is essential for the design of improved second-generation molecules. Here we describe our methodology for screening a library of plant-derived natural products in yeast in order to identify and characterize new compounds with anti-proliferative properties.
When defatted jojoba meal is used as animal food, it causes food-intake reduction and growth retardation. Detoxification procedures by chemical, microbiological, and solvent extraction methods are ...reported by several authors. Here we report a successful detoxification of jojoba meal using enzymes. We establish reaction conditions that yield new meal which has the same nutritional qualities in proteins as the original meal. The enzymatic reaction gives rise to one major compound to which the structure of an amide is assigned on the basis of IR,
1
H and
13
C NMR spectra. The effect of the resulting jojoba meal on the food intake in rats is checked. In contrast, the detoxified meal containing the amide derivatives shows no toxicological activity since rats receiving oral administration of the obtained meal show normal growth. Thus, it is expected that this meal could be used as an animal feed ingredient.
Small molecules have been shown to be potent and selective probes to understand cell physiology. Here, we show that imidazo1,2-apyridines and imidazo1,2-apyrimidines compose a class of compounds that ...target essential, conserved cellular processes. Using validated chemogenomic assays in Saccharomyces cerevisiae, we discovered that two closely related compounds, an imidazo1,2-apyridine and -pyrimidine that differ by a single atom, have distinctly different mechanisms of action in vivo. 2-phenyl-3-nitroso-imidazo1,2-apyridine was toxic to yeast strains with defects in electron transport and mitochondrial functions and caused mitochondrial fragmentation, suggesting that compound 13 acts by disrupting mitochondria. By contrast, 2-phenyl-3-nitroso-imidazo1,2-apyrimidine acted as a DNA poison, causing damage to the nuclear DNA and inducing mutagenesis. We compared compound 15 to known chemotherapeutics and found resistance required intact DNA repair pathways. Thus, subtle changes in the structure of imidazo-pyridines and -pyrimidines dramatically alter both the intracellular targeting of these compounds and their effects in vivo. Of particular interest, these different modes of action were evident in experiments on human cells, suggesting that chemical-genetic profiles obtained in yeast are recapitulated in cultured cells, indicating that our observations in yeast can: (1) be leveraged to determine mechanism of action in mammalian cells and (2) suggest novel structure-activity relationships.
Various elements of the MAP kinase module have been isolated in plants. We describe here the characterisation of 14 new plant cDNAs and genes encoding putative MAP kinase kinase kinases (MAP3Ks) ...related to the MEKK/STE11 and RAF protein kinases. Plant MAP3Ks are characterised by a variety of primary structures conserved within closely related proteins. Southern blot analysis suggests that plant MAP3Ks are heterogenous in their genomic structure, existing either as single copy genes or as small gene families. An RT-PCR analysis showed that in
Arabidopsis thaliana, all organs studied contain detectable levels of transcripts of each of the
MAP3K genes identified; however, signals obtained with mature pollen were weak or non-existent except for
AtMAP3Kγ. None of the reported genes share a cell-cycle or a cold stress regulated expression.
We have isolated DNA polymerases and topoisomerases from two thermoacidophilic archaebacteria: Sulfolobus acidocaldarius and Thermoplasma acidophilum. The DNA polymerases are composed of a single ...polypeptide with molecular masses of 100 and 85 kDa, respectively. Antibodies against Sulfolobus DNA polymerase did not cross react with Thermoplasma DNA polymerase. Whereas the major DNA topoisomerase activity in S. acidocaldarius is an ATP-dependent type I DNA topoisomerase with a reverse gyrase activity, the major DNA topoisomerase activity in T. acidophilum is a ATP-independent relaxing activity. Both enzymes resemble more the eubacterial than the eukaryotic type I DNA topoisomerase. We have found that small plasmids from halobacteria are negatively supercoiled and that DNA topoisomerase II inhibitors modify their topology. This suggests the existence of an archaebacterial type II DNA topoisomerase related to its eubacterial and eukaryotic counterparts. As in eubacteria, novobiocin induces positive supercoiling of halobacterial plasmids, indicating the absence of a eukaryotic-like type I DNA topoisomerase that relaxes positive superturns.
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