Metal–organic
frameworks (MOFs) can be applied in biology and medicine as drug delivery
systems by carrying drugs on their surfaces or releasing bioactive
ligands. To investigate the therapeutic potential of hydrogels that
contain MOFs, three MOFs containing glutarate and 1,2-bis(4-pyridyl)ethylene
ligands were synthesized by the previously reported hydrothermal or
solvothermal reactions: Cu-MOF 1, Co-MOF 2, and Zn-MOF 3. Bioactive MOF-embedded hydrogels (hydrogel@Cu-MOF 1, hydrogel@Co-MOF 2, and hydrogel@Zn-MOF 3) were prepared by UV light-mediated thiol–ene photopolymerization
using diacrylated polyethylene glycol (PEG), 4-arm-thiolated PEG,
and MOFs. The activities of the MOF-embedded hydrogels were tested
against the Gram-negative bacterium Escherichia coli and the Gram-positive bacterium Staphylococcus aureus. These MOF-embedded hydrogels were observed to be very stable, based
on the release test of MII ions, and both hydrogel@Cu-MOF 1 and hydrogel@Co-MOF 2 showed excellent antibacterial
activity. Although, in human dermal fibroblasts, hydrogel@Cu-MOF 1 showed no cytotoxic effects, it exhibited 99.9% antibacterial
effects at the minimum bactericidal concentration. Physical properties
such as the surface area and dimension of MOFs with different central
metals appeared to be more important than the chemical properties
of the ligands in determining the effects on bacteria. These MOF-embedded
hydrogels may be useful in antibacterial applications such as cosmetics,
treatment of skin diseases, and drug delivery owing to their low cytotoxicity
and high bactericidal activity.
Atmospheric-pressure non-thermal bio-compatible plasma is a partially ionized gas with electrically charged particles. Previous studies demonstrated that dielectric barrier discharge (DBD) plasma could induce apoptosis of various cancer cells, in particular demonstrating the selective cytotoxicity of cancer cells over normal cells. Therefore, DBD plasma can be considered as a potential cancer treatment method for clinical applications. We previously developed a microwave jet plasma system, producing nitric oxide called nitric oxide-plasma activated water (NO-PAW). In this study, we explored the effects of NO-PAW on a cervical cancer cell line, in comparison with DBD plasma. The cytotoxicity results showed that the treatment of HeLa cell with DBD for 4 minutes and 7 μM concentration of NO-PAW could reach almost IC60. For the apoptosis assay, 4 minutes treatment of DBD could induce 7% apoptotic effect, whereas 7 μM NO-PAW could induce 18% apoptotic effect. In addition, we assumed that both DBD plasma and NO-PAW could induce HeLa cell apoptosis by facilitating an accumulation of intracellular reactive oxygen and nitrogen species (RONS). Although further detail on the molecular signal pathway is still needed, DBD and NO-PAW could become promising applications for effective and safe clinical trials for cancer therapy.
IntroductionAlthough mesenchymal stem cells (MSCs) have antitumor potential in hepatocellular carcinoma and breast cancer cells, the antitumor mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in prostate cancer cells still remains unclear. Thus, in the present study, we elucidated the antitumor activity of hUCMSCs in PC-3 prostate cancer cells in vitro and in vivo.MethodshUCMSCs were isolated from Wharton jelly of umbilical cord and characterized via induction of differentiations, osteogenesis, and adipogenesis. Antitumor effects of UCMSCs on tumor growth were evaluated in a co-culture condition with PC-3 prostate cancer cells. PC-3 cells were subcutaneously (sc) injected into the left flank of nude mice, and UCMSCs were sc injected into the right flank of the same mouse.ResultsWe found that hUCMSCs inhibited the proliferation of PC-3 cells in the co-culture condition. Furthermore, co-culture of hUCMSCs induced the cleavage of caspase 9/3 and PARP, activated c-jun NH2-terminal kinase (JNK), and Bax, and attenuated the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/ AKT, extracellular signal-regulated kinase (ERK), and the expression of survival genes such as Bcl-2, Bcl-xL, Survivin, Mcl-1, and cIAP-1 in PC-3 cells in Western blotting assay. Conversely, we found that treatment of specific JNK inhibitor SP600125 suppressed the cleavages of caspase 9/3 and PARP induced by hUCMSCs in PC-3 cells by Western blotting and immunofluorescence assay. The homing of hUCMSCs to, and TUNEL-positive cells on, the K562 xenograft tumor region were detected in Nu/nu-BALB/c mouse.ConclusionsThese results suggest that UCMSCs inhibit tumor growth and have the antitumor potential for PC-3 prostate cancer treatment.
Nonthermal plasma is a promising novel therapy for the alteration of biological and clinical functions of cells and tissues, including apoptosis and inhibition of tumor progression. This therapy generates reactive oxygen and nitrogen species (RONS), which play a major role in anticancer effects. Previous research has verified that plasma jets can selectively induce apoptosis in various cancer cells, suggesting that it could be a potentially effective novel therapy in combination with or as an alternative to conventional therapeutic methods. In this study, we determined the effects of nonthermal air soft plasma jets on a U87 MG brain cancer cell line, including the dose- and time-dependent effects and the physicochemical and biological correlation between the RONS cascade and p38/mitogen-activated protein kinase (MAPK) signaling pathway, which contribute to apoptosis. The results indicated that soft plasma jets efficiently inhibit cell proliferation and induce apoptosis in U87 MG cells but have minimal effects on astrocytes. These findings revealed that soft plasma jets produce a potent cytotoxic effect via the initiation of cell cycle arrest and apoptosis. The production of reactive oxygen species (ROS) in cells was tested, and an intracellular ROS scavenger, N-acetyl cysteine (NAC), was examined. Our results suggested that soft plasma jets could potentially be used as an effective approach for anticancer therapy.
PurposeThe differentiation properties of stem cells are not yet fully understood due to their close association with multiple environmental and extrinsic factors. This study investigates the differentiation properties of mesenchymal stem cells (MSCs) and correlates them with their intrinsic mechanical properties.MethodsA total of 3 different types of MSCs, namely bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UCSCs), and adipose-derived MSCs (ADSCs) were evaluated. These 3 MSCs were individually differentiated into adipocytes and osteoblasts for 3 weeks. The mechanical properties of the MSCs and differentiated cells were determined by atomic force microscopy.ResultsADSCs showed the greatest ability to differentiate into adipocytes, followed by BMSCs and UCSCs. While UCSCs differentiated readily into osteoblasts, BMSCs and ADSCs were less likely to undergo this differentiation. UCSCs were the “hardest” cells, while ADSCs were the “softest.” The cells differentiated from “hard” MSCs were stiffer than the cells differentiated from “soft” MSCs, irrespective of lineage specification.ConclusionsThe differentiation ability of MSCs and the mechanical properties of the differentiated cells were closely linked. However, there were no significant correlations regarding changes in the mechanical properties between the nuclear region and the cytoplasm during differentiation.
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