Melatonin Administration Accelerates Puberty Onset in Mice by Promoting FSH Synthesis.

Although melatonin has been extensively studied in animal reproduction, the mechanism of melatonin in puberty remains elusive. This study was designed to explore the effect of intraperitoneal administration of melatonin on puberty onset in female mice. The injection of melatonin into postnatal days 10 mice at a dose of 15 mg/kg accelerated the puberty onset in mice. Mechanistically, there was no difference in physical growth and serum Leptin levels after melatonin administration. Meanwhile, the serum levels of reproductive hormones involved in hypothalamic-pituitary-ovarian axis, such as FSH and estrogen level in serum were increased. The mRNA levels of GnRH and GnRHr were not affected by melatonin, while the expressions of FSHß in pituitary and Cyp19a1 in ovary were significantly up-regulated. In addition, melatonin still promoted FSH synthesis after ovariectomy. Furthermore, the enhanced activity of ERK1/2 signaling verified that the expression of FSHß increased in pituitary. We confirmed that melatonin promoted the FSH synthesis in pituitary, thereby increased serum estrogen levels and ultimately accelerated puberty onset. However, these effects of melatonin may be pharmacological due to the high dose. This study would help us to understand the functions of melatonin in pubertal regulation comprehensively.

Octopod PtCu Nanoframe for Dual-Modal Imaging-Guided Synergistic Photothermal Radiotherapy.

Heavy atom nanoparticles have high X-ray absorption capacity and near infrared (NIR) photothermal conversion efficiency, which could be used as radio-sensitizers. We hypothesized that concave PtCu octopod nanoframes (OPCNs) would be an efficient nanoplatform for synergistic radio-photothermal tumor ablation. Methods: In this study, we newly exploited a folic acid-receptor (FR) mediated photothermal radiotherapy nanoagent base on OPCNs. OPCNs were synthesized with a hydrothermal method and then modified with polyethylene glycol (PEG) and folic acid (FA). A series of physical and chemical characterizations, cytotoxicity, targeting potential, endocytosis mechanism, biodistribution, systematic toxicological evaluation, pharmacokinetics, applications of OPCNs-PEG-FA for in vitro and in vivo infrared thermal imaging (ITI)/photoacoustic imaging (PAI) dual-modal imaging and synergistic photothermal radiotherapy against tumor were carried out. Results: The OPCNs-PEG-FA demonstrated good biocompatibility, strong NIR absorption and X-ray radio-sensitization, which enabling it to track and visualize tumor in vivo via ITI/PAI dual-modal imaging. Moreover, the as-synthesized OPCNs-PEG-FA exhibited remarkable photothermal therapy (PTT) and radiotherapy (RT) synergistic tumor inhibition when treated with NIR laser and X-ray. Conclusion: A novel multifunctional theranostic nanoplatform based on OPCNs was designed and developed for dual-modal image-guided synergistic tumor photothermal radiotherapy.

Anti-Inflammatory Effects and Mechanisms of Fatsia polycarpa Hayata and Its Constituents.

Fatsia polycarpa, a plant endemic to Taiwan, is an herbal medicine known for treating several inflammation-related diseases, but its biological function needs scientific support. Thus, the anti-inflammatory effects and mechanisms of the methanolic crude extract (MCE) of F. polycarpa and its feature constituents, that is, brassicasterol (a phytosterol), triterpenoids 3 α -hydroxyolean-11,13(18)-dien-28-oic acid (HODA), 3 α -hydroxyolean-11-en-28,13 ß -olide (HOEO), fatsicarpain D, and fatsicarpain F, were investigated. MCE and HOEO, but not brassicasterol, dose-dependently inhibited lipopolysaccharide- (LPS-)induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophage line, whereas HODA, fatsicarpain D and fatsicarpain F were toxic to RAW cells. Additionally, MCE and HOEO suppressed LPS-induced production of nitric oxide, prostaglandin E2, and interleukin-1 ß and interfered with LPS-promoted activation of the inhibitor kappa B kinase (IKK)/nuclear factor- κ B (NF- κ B) pathway, and that of the mitogen-activated protein kinases (MAPKs) extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In animal tests, MCE and HOEO effectively ameliorated 12-O-tetradecanoylphorobol-13 acetate- (TPA-)induced ear edema of mice. Thus, MCE of F. polycarpa exhibited an obvious anti-inflammatory activity in vivo and in vitro that likely involved the inhibition of the IKK/NF- κ B pathway and the MAPKs, which may be attributed by triterpenoids such as HOEO.