Background: Doxorubicin, by aggregating in bone marrow, causes genotoxic effects, and thus reduces the repair ability of cells.
The present study was conducted as an in vitro evaluation of age effects on the cytotoxicity induced by doxorubicin in mesenchymal
stem cells (MSCs).
Methods: The MSCs of female BALB/c mice aged 1, 8, and 16 months were separated, characterized, and subsequently evaluated in
cellular growth media. After 24 hours, exposure of the MSCs of the 3 groups of mice to doxorubicin (25, 50, 100, 200, 400, 800, 1200
nM) and cytotoxicity were assessed, and the sublethal dose was determined using flow cytometry technique and lactate dehydrogenase
(LDH) release assay.
Results: The IC50 values determined by flow cytometry for the separated MSCs of 1 young, 8 middle- aged, and 16 old mice were
and respectively. Interestingly, the results of these 2 methods in determining cytotoxicity were in agreement, and a concentration of
approximately 25 nM was considered to be the shared sublethal dose for different ages.
Conclusion: The results indicated that MSCs of middle-aged mice were more resistant to the toxic effects of the drug. Besides,
MSCs separated from the old mice were the most sensitive to chemotherapy and its side effects such as disruptions of cell proliferation
and viability. These disruptions can be ascribed to the alteration of function and physiological processes with age. Determining proper
concentration of doxorubicin drug to destruct cancerous cells based on age and individual sensitivity can minimize the amount of toxicity
Quorum quenching (QQ), the enzymatic degradation of N-acyl homoserine lactones (AHLs), has been suggested as a promising strategy to control bacterial diseases. In this study, 10 AHL-degrading bacteria isolated from the intestine of barramundi were identified by 16S rDNA sequencing. They were able to degrade both short and long-chain AHLs associated with several pathogenic Vibrio species (spp.) in fish, including N-[(RS)-3-Hydroxybutyryl]-l-homoserine lactone (3-oh-C4-HSL), N-Hexanoyl-l-homoserine lactone (C6-HSL), N-(β-Ketocaproyl)-l-homoserine lactone (3-oxo-C6-HSL), N-(3-Oxodecanoyl)-l-homoserine lactone (3-oxo-C10-HSL), N-(3-Oxotetradecanoyl)-l-homoserine lactone (3-oxo-C14-HSL). Five QQ isolates (QQIs) belonging to the Bacillus and Shewanella genera, showed high capacity to degrade both synthetic AHLs as well as natural AHLs produced by Vibrio harveyi and Vibrio alginolyticus using the well-diffusion method and thin-layer chromatography (TLC). The genes responsible for QQ activity, including aiiA, ytnP, and aaC were also detected. Analysis of the amino acid sequences from the predicted lactonases revealed the presence of the conserved motif HxHxDH. The selected isolates were further characterized in terms of their probiotic potentials in vitro. Based on our scoring system, Bacillus thuringiensis QQ1 and Bacillus cereus QQ2 exhibited suitable probiotic characteristics, including the production of spore and exoenzymes, resistance to bile salts and pH, high potential to adhere on mucus, appropriate growth abilities, safety to barramundi, and sensitivity to antibiotics. These isolates, therefore, constitute new QQ probiotics that could be used to control vibriosis in Lates calcalifer.
In recent years, cell-based immunotherapies have demonstrated promising results in the treatment of cancer. Chimeric antigen receptors (CARs) arm effector cells with a weapon for targeting tumor antigens, licensing engineered cells to recognize and kill cancer cells. The quality of the CAR-antigen interaction strongly depends on the selected tumor antigen and its expression density on cancer cells. CD19 CAR-engineered T cells approved by the Food and Drug Administration have been most frequently applied in the treatment of hematological malignancies. Clinical challenges in their application primarily include cytokine release syndrome, neurological symptoms, severe inflammatory responses, and/or other off-target effects most likely mediated by cytotoxic T cells. As a consequence, there remains a significant medical need for more potent technology platforms leveraging cell-based approaches with enhanced safety profiles. A promising population that has been advanced is the natural killer (NK) cell, which can also be engineered with CARs. NK cells which belong to the innate arm of the immune system recognize and kill virally infected cells as well as (stressed) cancer cells in a major histocompatibility complex I independent manner. NK cells play an important role in the host’s immune defense against cancer due to their specialized lytic mechanisms which include death receptor (i.e., Fas)/death receptor ligand (i.e., Fas ligand) and granzyme B/perforin-mediated apoptosis, and antibody-dependent cellular cytotoxicity, as well as their immunoregulatory potential via cytokine/chemokine release. To develop and implement a highly effective CAR NK cell-based therapy with low side effects, the following three principles which are specifically addressed in this review have to be considered: unique target selection, well-designed CAR, and optimized gene delivery.
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