In recent years, the study of oxidative stress (OS) has become increasingly popular. In particular, the role of OS on female fertility is very important and has been focused on closely. The occurrence of OS is due to the excessive production of reactive oxygen species (ROS). ROS are a double-edged sword; they not only play an important role as secondary messengers in many intracellular signaling cascades, but they also exert indispensable effects on pathological processes involving the female genital tract. ROS and antioxidants join in the regulation of reproductive processes in both animals and humans. Imbalances between pro-oxidants and antioxidants could lead to a number of female reproductive diseases. This review focuses on the mechanism of OS and a series of female reproductive processes, explaining the role of OS in female reproduction and female reproductive diseases caused by OS, including polycystic ovary syndrome (PCOS), endometriosis, preeclampsia and so on. Many signaling pathways involved in female reproduction, including the Keap1-Nrf2, NF-κB, FOXO and MAPK pathways, which are affected by OS, are described, providing new ideas for the mechanism of reproductive diseases.

Obesity and its complications have become a prominent global public health problem that severely threatens human health. Melatonin, originally known as an effective antioxidant, is an endogenous hormone found throughout the body that serves various physiological functions. In recent decades, increasing attention has been paid to its unique function in regulating energy metabolism, especially in glucose and lipid metabolism. Accumulating evidence has established the relationship between melatonin and obesity; nevertheless, not all preclinical and clinical evidence indicates the anti-obesity effect of melatonin, which makes it remain to conclude the clinical effect of melatonin in the fight against obesity. In this review, we have summarized the current knowledge of melatonin in regulating obesity-related symptoms, with emphasis on its underlying mechanisms. The role of melatonin in regulating the lipid profile, adipose tissue, oxidative stress, and inflammation, as well as the interactions of melatonin with the circadian rhythm, gut microbiota, sleep disorder, as well as the α7nAChR, the opioidergic system, and exosomes, make melatonin a promising agent to open new avenues in the intervention of obesity.

Light pollution is one of the most serious public problems, especially the night light. However, the effect of dim blue light at night (dLAN-BL) on cognitive function is unclear. In this study, we evaluated the effects of exposure to dLAN-BL in C57BL/6J mice for 4 consecutive weeks. Our results showed dLAN-BL significantly impaired spatial learning and memory and increased plasma corticosterone level in mice. Consistent with these changes, we observed dLAN-BL significantly increased the numbers and activation of microglia and the levels of oxidative stress product MDA in the hippocampus, decreased the levels of antioxidant enzymes Glutathione peroxidase (GSH-Px), Superoxide dismutase (SOD), Gluathione reductase (Gsr), total antioxidants (T-AOC) and the number of neurons in the hippocampus, up-regulated the mRNA expression levels of IL6, TNF-α and the protein expression levels of iNOS, COX2, TLR4, p-p65, Cleaved-Caspase3 and BAX, and down-regulated the mRNA expression levels of IL4, IL10, Psd95, Snap25, Sirt1, Dcx and the protein expression level of BCL2. In vitro results further showed corticosterone (10uM)-induced BV2 cell activation and up-regulated content of IL6, TNF-α in the cell supernatant and the protein expression levels of iNOS, COX2, p-p65 in BV2 cells. Our findings suggested dLAN-BL up-regulated plasma corticosterone level and hippocampal microglia activation, which in turn caused oxidative stress and neuroinflammation, leading to neuronal loss and synaptic dysfunction, ultimately leading to spatial learning and memory dysfunction in mice.

Ferroptosis is a newly recognized type of cell death that is different from traditional forms of cell death, such as apoptosis, autophagy, and necrosis. It is caused by the accumulation of intracellular iron, promoting lipid peroxidation and leading to cell death. Iron is essential as a redox metal in several physiological functions. The brain is one of the organs known to be affected by iron homeostatic balance disruption. An increased concentration of iron in the central nervous system has been associated with oxidative stress, lipid peroxidation of proteins, and cell death. The hippocampus is an important brain region for learning, memory, and emotional responses, and is also a sensitive part of the brain to the dysfunctional homeostasis of transition metals. Damage of hippocampal structure and function are intimately involved in the pathogenic mechanisms underlying neurodegenerative diseases. Currently, ferroptosis is playing an increasingly important role in treatment areas of central nervous system diseases. Thus, we provide an overview of ferroptosis regulatory mechanisms, such as lipid metabolism, glutathione metabolism, and iron metabolism in this review. We also highlight the role of ferroptosis in hippocampal-related diseases and investigate a theoretical basis for further research on the role of ferroptosis in nervous system disease treatment.

Radical cure colitis is a severe public health threat worldwide. Our previous studies have confirmed that melatonin can effectively improve gut microbiota disorder and mucosal injury caused by sleep deprivation (SD). The present study further explored the mechanism whereby exogenous melatonin prevented SD-induced colitis. 16S rRNA high-throughput sequencing and metabolomics analysis were used to explore the correlation between SD-induced colitis and intestinal microbiota and metabolite composition in mice. Fecal microbiota transplantation (FMT) and melatonin or butyrate supplementation tests verified the core role of gut microbiota in melatonin-alleviating SD-induced colitis. Further, in vitro tests studied the modulatory mechanism of metabolite butyrate. The results demonstrated that SD leads to reductions in plasma melatonin levels and colonic Card9 expression and consequent occurrence of colitis and gut microbiota disorder, especially the downregulation of Faecalibacterium and butyrate levels. The FMT from SD-mice to normal mice could restore SD-like colitis, while butyrate supplementation to SD-mice inhibited the occurrence of colitis, but with no change in the plasma melatonin level in both treatments. However, melatonin supplementation reversed all inductions in SD-mice. In intestinal epithelial cells, the inflammatory ameliorative effect of butyrate was blocked with pretreatments of HDAC3 agonist and HIF-1α antagonist but was mimicked by GSK-3β and p-P65 antagonists. Therefore, the administration of MLT may be a better therapy for SD-induced colitis relative to butyrate. A feasible mechanism would involve that melatonin up-regulated the Faecalibacterium population and production of its metabolite butyrate and MCT1 expression and inhibited HDAC3 in the colon, which would allow p-GSK-3β/β-catenin/HIF-1α activation and NF-κB/NLRP3 suppression to up-regulate Card9 expression and suppress inflammation response.

Alzheimer’s disease (AD) is a global concern and has become a major public health event affecting human health. Insulin is a metabolic hormone secreted mainly by the peripheral tissue pancreas. In recent years, more and more evidence has proved that insulin regulates various functions of the brain. The hippocampus, one of the earliest brain regions affected by AD, is widely distributed with insulin receptors. Studies have shown that type 2 diabetes mellitus, characterized by insulin resistance, is closely related to AD, which has drawn extensive attention to the relationship between hippocampal insulin signaling and AD. Therefore, we provide an overview of intranasal insulin administration on memory and its underlying mechanism. We also highlight the molecular link between hippocampal insulin resistance and AD and provide a theoretical basis for finding new therapeutic targets for AD in clinical practice.