Niacin/ß-hydroxybutyrate regulates milk fat and milk protein synthesis via the GPR109A/Gi/mTORC1 pathway.

As a crucial receptor of BHBA and niacin, GPR109A is largely expressed in the mammary gland. However, the role of GPR109A in milk synthesis and its underlying mechanism is still largely unknown. In this study, we first investigated the effect of GPR109A agonists (niacin/BHBA) on milk fat and milk protein synthesis in a mouse mammary epithelial cell line (HC11) and PMECs (porcine mammary epithelial cells). The results showed that both niacin and BHBA promote milk fat and milk protein synthesis with the activation of mTORC1 signaling. Importantly, knockdown GPR109A attenuated the niacin-induced increase of milk fat and protein synthesis and the niacin-induced activation of mTORC1 signaling. Furthermore, we found that GPR109A downstream G protein-Gαi and -Gßγ participated in the regulation of milk synthesis and the activation of mTORC1 signaling. Consistent with the finding in vitro, dietary supplementation with niacin increases milk fat and protein synthesis in mice with the activation of GPR109A-mTORC1 signaling. Collectively, GPR109A agonists promote the synthesis of milk fat and milk protein through the GPR109A/Gi/mTORC1 signaling pathway.

Facile synthesis of biogenic palladium nanoparticles using biomass strategy and application as photocatalyst degradation for textile dye pollutants and their in-vitro antimicrobial activity.

Among biological applications, plant-mediated Pd NPs for multi-drug resistance (MDR) developed in pathogenic bacteria were synthesized with the help of biomass of lemon peel, a biological material, with a non-toxic, environmentally friendly, human-nature green synthesis method. Characterization of synthesized Pd NPs was carried out by UV-Vis spectrometry, Transmissive Electron Microscopy (TEM), X-ray diffraction (XRD), and Fourier Transform Infrared Spectroscopy (FTIR) techniques. According to TEM analysis, Pd NPs were confirmed to be in a spherical shape and the mean particle size was determined to be 4.11 nm. The crystal structure of Pd NPs was checked using XRD analysis and the mean particle size was observed to be 6.72 nm. Besides, the antibacterial activity of Pd NPs was determined against Escherichia coli (E. coli) (ATCC 8739), Bacillus subtilis (B. subtilis ATCC 6633), Staphylococcus aureus (S. aureus ATCC 6538), Klebsiella pneumoniae (K. pneumoniae ATCC 11296) and Serratia marcescens (S. marcescens ATCC) bacteria. Antibacterial activity was determined to be high in Pd NPs which is in conformance with the results acquired. The Pd NPs showed good photocatalytic activity, after 90 min illumination, about 81.55% and 68.45% of MB and MO respectively were catalysed by the Pd NPs catalyst, and 74.50% of RhB dyes were removed at 120 min of illumination. Within the scope of this project, it is recommended to use Pd NPs obtained by the green synthesis in the future as an antibacterial agent in biomedical use and for the cleaning of polluted waters.

Zuogui pills maintain the stemness of oogonial stem cells and alleviate cyclophosphamide-induced ovarian aging through Notch signaling pathway.

BACKGROUND: Zuogui pills (ZGP), a classical prescription of traditional Chinese medicine, have been widely used in the treatment of ovarian aging. Previous studies have demonstrated its efficacy on protecting ovarian aging, and the mechanisms were mostly relevant to inhibiting the apoptosis of follicles and activating the primordial follicles. However, whether ZGP could stimulate the oogonial stem cells (OSCs) to refresh the follicle pool remains poorly understood. PURPOSE: To investigate the effects of ZGP on the stemness of OSCs in cyclophosphamide (Cy)-induced ovarian aging. STUDY DESIGN AND METHODS: Female Sprague-Dawley (SD) rats were randomly divided into 8 groups: control group, model group, ZGP groups (low / high dose groups), estradiol valerate (EV) groups (low / high dose groups), DAPT group and DAPT+ZGP-L group. After modeling with Cy, the ZGP groups and EV groups were treated with ZGP and EV for 8 weeks respectively. Meanwhile, the DAPT groups were treated with DAPT twice a week. Additionally, OSCs were also isolated after modeling, and then treated with drug serum containing ZGP or EV. Ovarian volume and the ratio of weight of total ovaries to the body weight were measured. The serum hormones were measured by ELISA. Quantities and location of OSCs in ovaries were detected by flow cytometry and immunofluorescence. Cell viability was measured by CCK8. And OSCs were identified by immunofluorescence. Biomarkers of germ cells, stem cells and associated to differentiation and meiosis were detected by qPCR and western blot. Proteins in Notch signaling pathway were detected by western blot and immunofluorescence. RESULTS: After treating with ZGP, ovarian volume and the ratio of weight of total ovaries to the body weight increased. ZGP could increase serum AMH and E2 level and decrease serum FSH level. Quantities and cell viability of OSCs increased after ZGP treatment in vivo and in vitro. In addition, treatment with ZGP could increase not only the expression of MVH, Oct4 and DAZL, but also the expression of ZP1 and ZP2. Furthermore, ZGP could up-regulate the expression of Notch intracellular domain (NICD), HES1 and HES5. After blocking the Notch signaling pathway, ZGP could increase not only the expression of NICD, HES1 and HES5, but also the expression of MVH, Oct4, DAZL, ZP1 and ZP3. CONCLUSION: In conclusion, the mechanism of ZGP on treating ovarian aging may be relevant to maintain the stemness of OSCs by up-regulating Notch signaling pathway, which added the mechanism of ZGP on the perspective of OSCs at first time.