Although oocytes from prepubertal animals are found less competent than oocytes from adults, the underlying mechanisms are poorly understood. Using the mouse oocyte model, this paper has tested the hypothesis that the developmental potential of prepubertal oocytes is compromised due mainly to their impaired potential for glutathione synthesis. Oocytes from prepubertal and adult mice, primed with or without eCG, were matured in vitro and assessed for glutathione synthesis potential, oxidative stress, Ca2+ reserves, fertilization and in vitro development potential. In unprimed mice, abilities for glutathione synthesis, activation, male pronuclear formation, blastocyst formation, cortical granule migration and polyspermic block were all compromised significantly in prepubertal compared to adult oocytes. Cysteamine and cystine supplementation to maturation medium significantly promoted oocyte glutathione synthesis and blastocyst development but difference due to maternal age remained. Whereas reactive oxygen species (ROS) levels increased, Ca2+ storage decreased significantly in prepubertal oocytes. Levels of both catalytic and modifier subunits of the γ-glutamylcysteine ligase were significantly lower in prepubertal than in adult oocytes. Maternal eCG priming improved all the parameters and eliminated the age difference. Together, the results have confirmed our hypothesis by showing that prepubertal oocytes have a decreased ability to synthesize glutathione leading to an impaired potential to reduce ROS and to form male pronuclei and blastocysts. The resulting oxidative stress decreases the intracellular Ca2+ store resulting in impaired activation at fertilization, and damages the microfilament network, which affects cortical granule redistribution leading to polyspermy.

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Objective:Recent studies have shown that activation of the immune system, inflammatory cell infiltration, and activation of inflammatory mediators play an important role in the development of heart failure. The purpose of this study was to investigate whether cardiac function can be improved by regulating the balance of lymphocyte subsets and cytokines.Methods:Ninety-six patients with chronic heart failure (CHF) who were older than 60 years were randomly divided into two groups: CHF testing group (CHFT) received regular therapy and thymopentin (2 mg thymopentin per day, 15th as a course, three courses in total). CHF control group (CHFC) received regular therapy. Forty-five healthy individuals older than 60 years were used as normal controls. The ejection fraction of left ventricle (LVEF), inner diameter of left ventricular end-diastole (LVEDD), inner diameter of left ventricular end-systole (LVESD), plasma high sensitive C-reactive protein (hsCRP), plasma brain natriuretic peptide (BNP), 6-min walking distance (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) assessment, lymphocyte subsets, and inflammatory cytokines were tested.Results:The levels of LVEF, 6MWT, CD 3+, CD4+T cells, natural killer cells, CD4+/CD8+ and IL-10 in CHFT were increased (p<0.01) compared with CHFC, while BNP, hsCRP, MLHFQ, CD8+, TNF-a, IL-1b, and TNF-a/IL-10 ratio in CHFT were decreased (p<0.01). LVEDD and LVESD were decreased, even though there was no significant difference between the two CHF groups.Conclusion:These data suggest that immune modulation therapy improve cardiac function and regulate cytokines and lymphocyte subsets in older patients with CHF.

Ferroptosis is a novel iron-dependent form of cell death implicated in brain pathology. However, whether arsenite is an inducer of ferroptosis in the neuron remains completely unknown. In this study, the seven-week-old healthy C57BL/6 J male mice were treated with environmental related doses (0.5, 5 and 50 mg/L) of arsenite for 6 months via drinking water, and the ferroptosis-related indicators were further determined. Our results demonstrated for the first time that, arsenite exposure significantly reduced the number of neuron and caused the pathological changes of mitochondria in the cerebral cortex of mice. We further revealed that arsenite induced ferroptotic cell death in neuron by accumulation of reactive oxygen species and lipid peroxidation products, disruption of Fe homeostasis, depletion of glutathione and adenosine triphosphate, inhibition of cysteine/glutamate antiporter, activation of mitogen-activated protein kinases and mitochondrial voltage-dependent anion channels pathways, up-regulation of endoplasmic reticulum stress, all of which were involved in the process of ferroptosis. These findings were also verified in the cultured PC-12 cells by using ferropotosis inhibitor, desferoxamine. Taken together, our results not only reveal a novel mechanism that chronic arsenite exposure may trigger the new form of cell death, ferroptosis, but also shed a new light on a potential clue for the intervention and prevention against arsenite-related neurodegenerative diseases.