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Photodynamic therapy (PDT) is an innovative and perspective antineoplastic therapy. Tetra-α-(4-carboxyphenoxy) phthalocyanine zinc (TαPcZn)-mediated PDT (TαPcZn-PDT) has shown antitumor activity in some tumor cells, but the manner in which caspase-1 is involved in the regulation of apoptosis and pyroptosis in the TαPcZn-PDT-treated breast cancer MCF-7 cells is unclear. Therefore, effects of TαPcZn-PDT on cytotoxicity, cell viability, apoptosis, pyroptosis, cellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), caspase-1, caspase-3, and nuclear transcription factor-κB (NFκB) in MCF-7 cells was firstly examined in the present study. The findings demonstrated that TαPcZn-PDT resulted in the increase in cytotoxicity and the percentage of apoptotic and pyroptotic cells, the reduction in cell viability and ΔΨm, the production of ROS and the activation of caspase-1, caspase-3 and NFκB in MCF-7 cells. Furthermore, the results also revealed that siRNA-targeting caspase-1 (siRNA-caspase-1) attenuated the effect of TαPcZn-PDT on apoptosis, pyroptosis and the activation of caspase-1, caspase-3 and NFκB in MCF-7 cells. Taken together, we conclude that caspase-1 regulates the apoptosis and pyroptosis induced by TαPcZn-PDT in MCF-7 cells.

To investigate the role of mitoxantrone in regulating gastric cancer cell phenotypes and the underlying mechanism. To reveal mitoxantrone-induced effects on gastric cancer cell malignancy, AGS cells were divided into different groups according to various study purposes, including negative control, 5 µmol/l mitoxantrone, 10 µmol/l mitoxantrone, 20 µmol/l mitoxantrone, anti-microRNA-negative control, anti-microRNA-211-5p, 20 µmol/l mitoxantrone+microRNA-negative control, and 20 µmol/l mitoxantrone+microRNA-211-5p groups. AGS cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide, while apoptotic rate was quantified via flow cytometry. Bcl-2 associated X-protein, activated caspase-3, phosphorylated-p65 and phosphorylated-IκBα was detected by Western blot for protein expression. Malondialdehyde was detected via colorimetry, nicotinamide adenine dinucleotide phosphate oxidase activity was detected by chemiluminescence, superoxide dismutase activity was measured via colorimetry, and microRNA-211-5p was quantified by reverse transcription-quantitative polymerase chain reaction. AGS cell proliferation, superoxide dismutase activity, as well as microRNA-211-5p expression in mitoxantrone groups (5, 10 and 20 µmol/l) were decreased compared with the negative control group, while the apoptotic rate, Bcl-2-associated X-protein and activated caspase-3 protein expression, malondialdehyde content, and nicotinamide adenine dinucleotide phosphate oxidase activity were increased. Protein expression of phosphorylated-p65 and phosphorylated-IκBα (inhibitor of nuclear factor kappa B) was decreased in the 20 µmol/l mitoxantrone group. The microRNA-211-5p expression, cell proliferation, superoxide dismutase activity, and phosphorylated-p65 and phosphorylated-IκBα protein expression in anti-microRNA-211-5p group were significantly decreased in relative to anti-microRNA-negative control group, while cell apoptosis, Bcl-2-associated X-protein and activated caspase-3 protein expression, malondialdehyde content, and nicotinamide adenine dinucleotide phosphate oxidase activity were increased. The microRNA-211-5p expression, cell proliferation, superoxide dismutase activity, and phosphorylated-p65 and phosphorylated-IκBα protein expression in the 20 µmol/l mitoxantrone+microRNA-211-5p group were higher than in 20 µmol/l mitoxantrone+microRNA-negative control group, while apoptotic, Bcl-2-associated X-protein and activated caspase-3 protein expression, malondialdehyde content, and nicotinamide adenine dinucleotide phosphate oxidase activity were lower than those in the 20 µmol/l mitoxantrone+microRNA-negative control group. Mitoxantrone repressed gastric cancer cell tumor property by downregulating the microRNA-211-5p/nuclear factor kappa B pathway. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is a common and harmful chronic inflammatory oral disease, characterized by the destruction of periodontal soft and hard tissues. The NLRP3 inflammasome-related pyroptosis and human periodontal ligament fibroblasts (hPDLFs) osteogenic dysfunction are involved in its pathogenesis. Studies have shown that lipoxin A4 is an endogenous anti-inflammatory mediator and BML-111 is a lipoxin A4 analog, which was found to have potent and durable anti-inflammatory effects in inflammatory diseases, but the mechanism remains unclear. The purpose of this study was to investigate whether BML-111 inhibits H2O2-induced dysfunction of hPDLFs, attenuates inflammatory responses, and identifies the underlying mechanisms. Methods: The oxidative stress model was established with H2O2, and the cell proliferation activity was measured by CCK-8. ALP staining and alizarin red staining were used to detect the osteogenic differentiation capacity of cells; flow cytometry and ELISA were used to detect cell pyroptosis; we explored the effect of BML-111 on hPDLFs under oxidative stress by analyzing the results of PCR and Western blotting. The Nrf2 inhibitor ML385 was added to further identify the target of BML-111 and clarify its mechanism. Results: BML-111 can alleviate the impaired cell proliferation viability induced by H2O2. H2O2 treatment can induce NLRP3 inflammasome-related pyroptosis, impairing the osteogenic differentiation capacity of hPDLFs. BML-111 can effectively alleviate H2O2-induced cellular dysfunction by activating the Nrf2/HO-1 signaling pathway. Conclusion: The results of this study confirmed the beneficial effects of BML-111 on H2O2-induced NLRP3 inflammasome-related pyroptosis in hPDLFs, and BML-111 could effectively attenuate the impaired osteogenic differentiation function. This beneficial effect is achieved by activating the Nrf2/HO-1 signaling pathway, therefore, our results suggest that BML-111 is a potential drug for the treatment of periodontitis. [ABSTRACT FROM AUTHOR]

Portunus trituberculatus , or the swimming crab, is tolerant of reduced salinity; however, the molecular mechanism of this tolerance is not clear. Cells can be damaged by hyperosmotic salinity. The protein p53, sometimes referred to as "the guardian of the genome," displays versatile and important functions under changing environmental conditions. Herein, the P. trituberculatus p53 gene (designated as Ptp53) was cloned and studied. The full-length Ptp53 cDNA comprised 1,544bp, with a 1,314bp open reading frame, which encodes a putative polypeptide of 437 amino acids. Quantitative real-time reverse transcription PCR assays revealed ubiquitous expression of Ptp53 in all tissues examined, with the gills showing the highest expression level. Extensive apoptosis was detected under low salinity conditions using terminal deoxynucleotidyl transferase nick-end-labeling staining. Oxidative stress was induced under low salinity conditions, consequently leading to apoptosis. Low salinity stress caused significant upregulation of Ptp53 mRNA and protein levels in the gills. Moreover, compared with that in the control group, the mortality of Ptp53 -silenced crabs under low salinity stress was enhanced significantly. Taken together, our findings suggest that Ptp53, via regulation of apoptosis and antioxidant defense, played important functions in the low salinity stress response of the swimming crab. [ABSTRACT FROM AUTHOR]

Oocyte quality is critical for fertilization and early embryo development. Fumonisin B1 (FB1) is a Fusarium mycotoxin and it is commonly found in contaminated food and feedstuff, posing a potential health hazard to both animals and human. FB1 is reported to have hepatotoxicity, neurotoxicity, nephrotoxicity, immunotoxicity and embryotoxicity. However, the effects of FB1 on mouse oocyte quality are still unknown. Here, we explored the toxic effects and potential mechanisms of FB1 on oocyte maturation quality in mice. FB1 exposure inhibited the first polar body extrusion at concentrations of 30 μM and 50 μM, which further induced oocyte meiotic arrest. Besides, disrupted spindle structure was found in oocytes after FB1 exposure. Our results also showed that FB1 exposure impaired mitochondria dysfunction, which further induced oxidative stress and early apoptosis. In addition, we reported that FB1 exposure induced the accumulation of lysosome and occurrence of autophagy. Aberrant ER distribution and ER stress were also found in FB1-exposed oocytes. Moreover, DNA damage was also observed. These results together suggested that FB1 exposure affected oocyte quality by destroying spindle structure, leading to mitochondria, lysosome and ER dysfunction, which further induced oxidative stress, apoptosis, autophagy and DNA damage in mouse oocytes. [Display omitted] • FB1 exposure deteriorates spindle formation and polar body extrusion in oocytes. • FB1 exposure altered mitochondria function for ROS level and apoptosis in oocytes. • FB1 exposure induced lysosome dysfunction and autophagy in oocytes. • FB1 exposure disrupted ER distribution and induced ER stress in oocytes. • FB1 exposure caused DNA damage in oocytes. [ABSTRACT FROM AUTHOR]