Protocatechuic acid induces apoptosis in human osteosarcoma cells by regulating P13K/AKT/ROS pathway

Previous investigations have demonstrated that protocatechuic acid (PCA) provides anti-tumour properties in different tumour cell types. It does, however, have an unknown cause on osteosarcoma cells. In this investigation, the underlying mechanism of the effect of PCA on osteosarcoma cells (MNNG or HOS) was investigated and established. The viability of the cell was assessed with the MTT test. Acridine orange/ethidium bromide staining and Western blot analysis were conducted for assessment of cell apoptosis. Western blot analysis was identified for cell cycle progression. In addition to establishing the above findings, the Western blot analysis demonstrated that PCA mediated osteosarcoma cellular apoptosis by triggering the apoptotic pathway of Caspase-9. Additionally, we found that PCA considerably stimulated osteosarcoma cell apoptosis and arrest of cell cycle proliferation by controlling a pathway involving P13K/Akt/ROS signalling. In short, we observed that PCA prevented the advancement of osteosarcoma through the stimulation of apoptosis in osteosarcoma cells. The mechanism underlying this study also showed that PCA generated effective anti-tumour activity on osteosarcoma cells by controlling the signalling pathways of P13K/Akt/ROS

Dietary alpha-ketoglutarate promotes beige adipogenesis and prevents obesity in middle-aged mice

Aging usually involves the progressive development of certain illnesses, including diabetes and obesity. Due to incapacity to form new white adipocytes, adipose expansion in aged mice primarily depends on adipocyte hypertrophy, which induces metabolic dysfunction. On the other hand, brown adipose tissue burns fatty acids, preventing ectopic lipid accumulation and metabolic diseases. However, the capacity of brown/beige adipogenesis declines inevitably during the aging process. Previously, we reported that DNA demethylation in the Prdm16 promoter is required for beige adipogenesis. DNA methylation is mediated by ten-eleven family proteins (TET) using alpha-ketoglutarate (AKG) as a cofactor. Here, we demonstrated that the circulatory AKG concentration was reduced in middle-aged mice (10-month-old) compared with young mice (2-month-old). Through AKG administration replenishing the AKG pool, aged mice were associated with the lower body weight gain and fat mass, and improved glucose tolerance after challenged with high-fat diet (HFD). These metabolic changes are accompanied by increased expression of brown adipose genes and proteins in inguinal adipose tissue. Cold-induced brown/beige adipogenesis was impeded in HFD mice, whereas AKG rescued the impairment of beige adipocyte functionality in middle-aged mice. Besides, AKG administration up-regulated Prdm16 expression, which was correlated with an increase of DNA demethylation in the Prdm16 promoter. In summary, AKG supplementation promotes beige adipogenesis and alleviates HFD-induced obesity in middle-aged mice, which is associated with enhanced DNA demethylation of the Prdm16 gene

The Sihailongwan Maar Lake, northeastern China as a candidate Global Boundary Stratotype Section and Point for the Anthropocene Series

Sihailongwan Maar Lake, located in Northeast China, is a candidate Global boundary Stratotype Section and Point (GSSP) for demarcation of the Anthropocene. The lake’s varved sediments are formed by alternating allogenic atmospheric inputs and authigenic lake processes and store a record of environmental and human impacts at a continental-global scale. Varve counting and radiometric dating provided a precise annual-resolution sediment chronology for the site. Time series records of radioactive (239,240Pu, 129I and soot 14C), chemical (spheroidal carbonaceous particles, polycyclic aromatic hydrocarbons, soot, heavy metals, δ13C, etc), physical (magnetic susceptibility and grayscale) and biological (environmental DNA) indicators all show rapid changes in the mid-20th century, coincident with clear lithological changes of the sediments. Statistical analyses of these proxies show a tipping point in 1954 CE. 239,240Pu activities follow a typical unimodal globally-distributed profile, and are proposed as the primary marker for the Anthropocene. A rapid increase in 239,240Pu activities at 88 mm depth in core SHLW21-Fr-13 (1953 CE) is synchronous with rapid changes of other anthropogenic proxies and the Great Acceleration, marking the onset of the Anthropocene. The results indicate that Sihailongwan Maar Lake is an ideal site for the Anthropocene GSSP

The Community Anchor Institutions of Champaign-Urbana, Illinois Technology Use by Non-Profit and Public Organizations in the Broadband Moment

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Fetal programming in meat production

Nutrient fluctuations during the fetal stage affects fetal development, which has long-term impacts on the production efficiency and quality of meat. During the early development, a pool of mesenchymal progenitor cells proliferate and then diverge into either myogenic or adipogenic/fibrogenic lineages. Myogenic progenitor cells further develop into muscle fibers and satellite cells, while adipogenic/fibrogenic lineage cells develop into adipocytes, fibroblasts and resident fibro-adipogenic progenitor cells. Enhancing the proliferation and myogenic commitment of progenitor cells during fetal development enhances muscle growth and lean production in offspring. On the other hand, promoting the adipogenic differentiation of adipogenic/fibrogenic progenitor cells inside the muscle increases intramuscular adipocytes and reduces connective tissue, which improves meat marbling and tenderness. Available studies in mammalian livestock, including cattle, sheep and pigs, clearly show the link between maternal nutrition and the quantity and quality of meat production. Similarly, chicken muscle fibers develop before hatching and, thus, egg and yolk sizes and hatching temperature affect long-term growth performance and meat production of chicken. On the contrary, because fishes are able to generate new muscle fibers lifelong, the impact of early nutrition on fish growth performance is expected to be minor, which requires further studies.•Brief review of fetal programming and adipose and connective tissue development•Brief review of fetal programming and muscle development•Overview of fetal programming and meat qualit

Maternal high-fat diet during lactation impairs thermogenic function of brown adipose tissue in offspring mice

Maternal obesity and high-fat diet (HFD) predisposes offspring to obesity and metabolic diseases. Due to uncoupling, brown adipose tissue (BAT) dissipates energy via heat generation, mitigating obesity and diabetes. The lactation stage is a manageable period for improving the health of offspring of obese mothers, but the impact of maternal HFD during lactation on offspring BAT function is unknown. To determine, female mice were fed either a control or HFD during lactation. At weaning, HFD offspring gained more body weight and had greater body fat mass compared to the control, and these differences maintained into adulthood, which correlated with glucose intolerance and insulin resistance in HFD offspring. Adaptive thermogenesis of BAT was impaired in HFD offspring at weaning. In adulthood, HFD offspring BAT had lower Ucp1 expression and thermogenic activity. Mechanistically, maternal HFD feeding during lactation elevated peripheral serotonin, which decreased the sensitivity of BAT to sympathetic β3-adrenergic signaling. Importantly, early postnatal metformin administration decreased serotonin concentration and ameliorated the impairment of offspring BAT due to maternal HFD. Our data suggest that attenuation of BAT thermogenic function may be a key mechanism linking maternal HFD during lactation to persisted metabolic disorder in the offspring

Maternal obesity epigenetically alters visceral fat progenitor cell properties in male offspring mice

Maternal obesity reduces adipogenic progenitor density in offspring adipose tissue. The ability of adipose tissue expansion in the offspring of obese mothers is limited and is associated with metabolic dysfunction of adipose tissue when challenged with a high-fat diet. Maternal obesity induces DNA demethylation in the promoter of zinc finger protein 423, which renders progenitor cells with a high adipogenic capacity. Maternal obesity demonstrates long-term effects on the adipogenic capacity of progenitor cells in offspring adipose tissue, demonstrating a developmental programming effect. Maternal obesity (MO) programs offspring obesity and metabolic disorders, although the underlying mechanisms remain poorly defined. Progenitor cells are the source of new adipocytes. The present study aimed to test whether MO epigenetically predisposes adipocyte progenitors in the fat of offspring to adipogenic differentiation and subsequent depletion, which leads to a failure of adipose tissue plasticity under positive energy balance, contributing to adipose tissue metabolic dysfunction. C57BL/6 female mice were fed either a control diet (10% energy from fat) or a high-fat diet (45% energy from fat) for 8 weeks before mating. Male offspring of control (Con) and obese (OB) dams were weaned onto a regular (Reg) or obesogenic (Obe) diet until 3 months of age. At weaning, male OB offspring had a higher expression of Zinc finger protein 423 (zfp423), a key transcription factor in adipogenesis, as well as lower DNA methylation of its promoter in progenitors of epididymal fat compared to Con offspring, which was correlated with enhanced adipogenic differentiation. At 3 months of age, progenitor density was 30.9 ± 9.7% lower in OB/Obe compared to Con/Obe mice, accompanied by a limited expansion of the adipocyte number when challenged with a high-energy diet. This difference was associated with lower DNA methylation in the zfp423 promoter in the epididymal fat of OB/Obe offspring, which was correlated with greater macrophage chemotactic protein-1 and hypoxia-inducible factor 1α expression. In summary, MO epigenetically limits the expansion capacity of offspring adipose tissue, providing an explanation for the adipose metabolic dysfunction of male offspring in the setting of MO

Maternal Retinoids Increase PDGFRα\u3csup\u3e+\u3c/sup\u3e Progenitor Population and Beige Adipogenesis in Progeny by Stimulating Vascular Development

© 2017 The Authors Maternal vitamin A intake varies but its impact on offspring metabolic health is unknown. Here we found that maternal vitamin A or retinoic acid (RA) administration expanded PDGFRα+ adipose progenitor population in progeny, accompanied by increased blood vessel density and enhanced brown-like (beige) phenotype in adipose tissue, protecting offspring from obesity. Blockage of retinoic acid signaling by either BMS493 or negative RA receptor (RARαDN) over-expression abolished the increase in blood vessel density, adipose progenitor population, and beige adipogenesis stimulated by RA. Furthermore, RA-induced beige adipogenesis was blocked following vascular endothelial growth factor receptor (VEGFR) 2 knock out in PDGFRα+ cells, suggesting its mediatory role. Our data reveal an intrinsic link between maternal retinoid level and offspring health via promoting beige adipogenesis. Thus, enhancing maternal retinoids is an amiable therapeutic strategy to prevent obesity in offspring, especially for those born to obese mothers which account for one third of all pregnancies