Resveratrol (3,5,4′-trihydroxystilbene, RSV) is a natural potential anti-aging polyphenolic compound frequently used as a nutritional supplement against several diseases. However, the underlying mechanisms by which resveratrol regulates postovulatory aging of oocytes are still insufficiently known. In this study, we found that resveratrol could delay postovulatory aging and improve developmental competence of oocytes through activating selective mitophagy in the mouse. Resveratrol could maintain spindle morphology but it disturbed cortical granule (CG) distribution during oocyte aging. This might be due to upregulated mitophagy, since blocking mitophagy by cyclosporin A (CsA) treatment affected oocyte quality by damaging mitochondrial function and it decreased embryonic development. In addition, we also observed an involvement of FoxO3a in regulating mitophagy in aging oocytes following resveratrol treatment. Taken together, our results provide evidence that mitophagy induced by resveratrol is a potential mechanism to protect against postovulatory oocyte aging.

Apurinic/apyrimidinic endonuclease 1/redox effector-1 (Ape1/Ref-1) is the major apurinic/apyrimidinic (AP) endonuclease in mammalian cells. It functions mainly in the base excision repair pathway to create a suitable substrate for DNA polymerases. Human Ape1 protein can activate some transcription factors to varying degrees, dependent on its N-terminal, unstructured domain, and some of the cysteines within it, apparently via a redox mechanism in some cases. Many cancer studies also suggest that Ape1 has potential for prognosis in terms of the protein level or intracellular localization. While homozygous disruption of the Ape1 structural gene APEX1 in mice causes embryonic lethality, and most studies in cell culture indicate that the expression of Ape1 is essential, some recent studies reported the isolation of viable APEX1 knockout cells with only mild phenotypes. It has not been established by what mechanism the Ape1-null cell lines cope with the endogenous DNA damage that the enzyme normally handles. We review the enzymatic and other activities of Ape1 and the recent studies of the properties of the APEX1 knockout lines. The APEX1 deletions in CH12F3 and HEK293 FT provide an opportunity to test for possible off-target effects of Ape1 inhibition. For this work, we tested the Ape1 endonuclease inhibitor Compound 3 and the redox inhibitor APX2009. Our results confirmed that both APEX1 knockout cell lines are modestly more sensitive to killing by an alkylating agent than their Ape1-proficient cells. Surprisingly, the knockout lines showed equal sensitivity to direct killing by either inhibitor, despite the lack of the target protein. Moreover, the CH12F3 APEX1 knockout was even more sensitive to Compound 3 than its APEX1 + counterpart. Thus, it appears that both Compound 3 and APX2009 have off-target effects. In cases where this issue may be important, it is advisable that more specific endpoints than cell survival be tested for establishing mechanism.

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During NASA’s Apollo missions, inhalation of dust particles from lunar regolith was identified as a potential occupational hazard for astronauts. These fine particles adhered tightly to spacesuits and were brought accidentally into the living areas of the spacecraft. Apollo astronauts reported that exposure to the dust caused intense respiratory and ocular irritation. This problem is a potential challenge for the Artemis Program, which aims to return humans to the Moon for extended stays in this decade. Since lunar dust is “weathered” by space radiation, solar wind, and the incessant bombardment of micrometeorites, we investigated whether treatment of lunar regolith simulants to mimic space weathering enhanced their toxicity. Two such simulants were employed in this research, Lunar Mare Simulant-1 (LMS-1), and Lunar Highlands Simulant-1 (LHS-1), which were applied to human lung epithelial cells (A549). In addition to pulverization, previously shown to increase dust toxicity sharply, the simulants were exposed to hydrogen gas at high temperature as a proxy for solar wind exposure. This treatment further increased the toxicity of both simulants, as measured by the disruption of mitochondrial function, and damage to DNA both in mitochondria and in the nucleus. By testing the effects of supplementing the cells with an antioxidant (N-acetylcysteine), we showed that a substantial component of this toxicity arises from free radicals. It remains to be determined to what extent the radicals arise from the dust itself, as opposed to their active generation by inflammatory processes in the treated cells.

The thymus is a lobulated unique lymphoid immune organ that plays a critical role in the selection, development, proliferation, and differentiation of T cells. The thymus of developing chickens undergoes continued morphological alterations; however, the biomolecular and transcriptional dynamics of the postnatal thymus in avian species is not clear yet. Therefore, the thymuses from chickens at different stages of development (at weeks 0, 1, 5, 9, 18, and 27) were used in the present study. The RNA-seq method was used to study the gene expression patterns. On average, 24120819 clean reads were mapped, differentially expressed genes (DEGs) were identified on the basis of log values (fold change), including 744 upregulated and 425 downregulated genes. The expression pattern revealed by RNA-seq was validated by quantitative real-time PCR (qPCR) analysis of four important genes, which are PCNA, CCNA2, CCNB2, and CDK1. Thus, the current study revealed that during postnatal development, the thymus undergoes severe atrophy. Thymus structure was damaged and gene expression changed dramatically, especially at the 27th week of age. Moreover, we found significant changes of several signaling pathways such as the cytokine-cytokine receptor interaction and cell cycle signaling pathways. Hence, it may be inferred that those signaling pathways might be closely related to the postnatal chicken thymus development.