Aging is a complicated multifactorial process in which a progressive decline in the physiologic function of organisms occurs. Oxidative stress and reactive oxygen species (ROS) have been proposed to be major cause of aging and other aging-related neurodegenerative conditions such as Alzheimer's disease.1,2) Aging-related oxidative damage in the brain and memory impairment mainly result from an imbalance between ROS generation and antioxidant enzyme activities. The overproduction of ROS or decrease in antioxidants in the brain can cause lipid peroxidation, nuclear and mitochondrial DNA damage, and protein oxidation and finally affect the normal functions of organisms. [3][4][5][6] D-Galactose (D-gal) is a reducing sugar normally present in the body. When present at levels greater than its normal content, it can be oxidized into aldehydes and hydrogen peroxide (H 2 O 2 ) by galactose oxidase. 7,8) It has been shown that D-galtreated animal models show aging-related changes including the impairment of spatial learning and memory, object novelty preference, and locomotor activity, 9,10) and increased production of ROS and lowered activities of antioxidant enzymes. 11,12) Other studies demonstrated that long-term subcutaneous injection of D-gal in mice induced decreased immune responses and increased cell karyopyknosis, apoptosis, and caspase-3 protein levels in hippocampal neurons.11,13) Therefore mice continuously injected with D-gal have been extensively used for pharmacologic research on brain aging.(Ϫ)-Epigallocatechin-3-gallate (EGCG) is a member of the catechin family and a major polyphenolic constituent of green tea.14) It was reported that EGCG has potent ironchelating, antioxidant, antiinflammatory, anticancer, and neuroprotective activities. [15][16][17][18][19] In particular, EGCG has been shown to have neuroprotective effects by elevating the a-secretase activity of amyloid precursor protein (APP) and conversion to soluble APP-alpha (sAPP-a) and reducing amyloid beta (Ab)-induced neurotoxicity in a 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) mouse model, the "Swedish" APP transgenic (Tg2576) mouse model of Alzheimer's disease, and N2a cells stably transfected with "Swedish" mutant human APP. 20,21) Furthermore, some studies have recently demonstrated that the neuroprotective mechanisms of EGCG are partly due to increasing activities of antioxidant enzymes and decreasing advanced glycation endproduct (AGE)-induced damage in aged rat brain or neuronal cells. 22,23) However, no study has been performed to evaluate whether EGCG has protective effects on aging mice induced by D-gal and its mechanisms of action. In the present study, we induced the aging mice model with D-gal (150 mg/kg/d, 6 weeks subcutaneously (s.c.)) and observed whether EGCG (2 mg/kg/d or 6 mg/kg/d, 4 weeks intragastrically (i.g.)) had potent antioxidant and antiapoptotic neuroprotective effects using behavioral testing and measurements of the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px), con...

Isoflavonoids isolated from plants have been confirmed to fight osteoporosis and promote bone health. However, few studies have been conducted to describe the anti-osteoporosis activity of botanical flavonone. Based on the experimental outcomes, we demonstrated the ability of naringin to fight osteoporosis in vitro. We developed a retinoic acid-induced osteoporosis model of rats to assess whether naringin has similar bioactivity against osteoporosis in vitro. After a 14-day supplement of retinoic acid to induce osteoporosis, SD rats were administered naringin. A blood test showed that naringin-treated rats experienced significantly lower activity of serum alkaline phosphatase and had higher femur bone mineral density, compared to untreated rats. All three dosages of naringin improved the decrease in bone weight coefficient, the length and the diameter of the bone, the content of bone ash, calcium, and phosphorus content induced by retinoic acid. The data of histomorphological metrology of naringin groups showed no difference as compared to normal control rats. These outcomes suggest that naringin offer a potential in the management of osteoporosis in vitro.

Retinal organoids (ROs) derived from human induced pluripotent stem cells (hiPSCs) provide potential opportunities for studying human retinal development and disorders; however, to what extent ROs recapitulate the epigenetic features of human retinal development is unknown. In this study, we systematically profiled chromatin accessibility and transcriptional dynamics over long-term human retinal and RO development. Our results showed that ROs recapitulated the human retinogenesis to a great extent, but divergent chromatin features were also discovered. We further reconstructed the transcriptional regulatory network governing human and RO retinogenesis in vivo. Notably, NFIB and THRA were identified as regulators in human retinal development. The chromatin modifications between developing human and mouse retina were also cross-analyzed. Notably, we revealed an enriched bivalent modification of H3K4me3 and H3K27me3 in human but not in murine retinogenesis, suggesting a more dedicated epigenetic regulation on human genome.