Nicotinamide mononucleotide ameliorates the depression-like behaviors and is associated with attenuating the disruption of mitochondrial bioenergetics in depressed mice.

BACKGROUND: Nicotinamide mononucleotide (NMN) has been shown to stimulate oxidative phosphorylation in mitochondria and to improve various pathologies in patients and mouse disease models. However, whether NMN mediates mitochondrial energy production and its mechanism of action in depressed animals remain unclear. METHODS: Mice were subcutaneously injected with corticosterone (CORT; 20 mg/kg) each day for 6 weeks, while another group was given an additional dose of NMN (300 mg/kg) by oral gavage in the last 2 weeks. Then, transcriptome analyses, metabolome analyses and transient gene knockdown in primary mouse cells were performed. RESULTS: NMN administration alleviated depression-like behavior and the liver weight to body weight ratio in a mouse model of CORT-induced depression. Transcriptome and metabolome analyses revealed that in depressed mice, NMN reduced the mRNA expression of genes involved in fatty acid synthesis, stimulation of ß-oxidation and glycolysis, and increased production of acetyl-coenzyme A for the tricarboxylic acid cycle. Importantly, NMN supplementation increased NAD+ levels to enhance sirtuin (SIRT)3 activity, thereby improving mitochondrial energy metabolism in the hippocampus and liver of CORT-treated mice. Sirt3knockdown in primary mouse astrocytes reversed the effect of NMN by inhibiting energy production, although it did not affect NAD+ synthesis LIMITATIONS: Group sample sizes were small, and only one type of primary mouse cell was used CONCLUSION: These results provide evidence for the beneficial role of NMN in energy production and suggest that therapeutic strategies that increase the level of NMN can be an effective treatment for depression.

Crocin-I ameliorates the disruption of lipid metabolism and dysbiosis of the gut microbiota induced by chronic corticosterone in mice.

Glucocorticoids (GCs) are widely used as anti-inflammatory and immunosuppressive drugs. However, chronic treatment with GCs in clinical settings has a series of side effects, such as metabolic disorders, gut microbiota dysbiosis and neurological impairment. Therefore, searching for a functional substance that can alleviate these side effects is greatly meaningful to clinical patients. Crocin is the main active ingredient of saffron, which has been reported to have numerous pharmacological activities. However, the action of crocin-I, one major member of the crocin family, on the physiological mediation in the individuals receiving GC treatment remains unclear. In this study, we aimed to evaluate the efficacy of crocin-I on lipid metabolism and the gut microbiota in a mouse model of chronic corticosterone (CORT) treatment. Our findings showed that crocin-I reduced the levels of triglycerides and total cholesterol and the ratio of low density lipoprotein to high density lipoprotein in the serum of CORT-treated mice. In addition, transcriptome analysis revealed that crocin-I was effective in mediating the amelioration of lipid metabolism, mainly in fatty acid metabolism and steroid biosynthesis in CORT-treated mice. Moreover, metabolome analysis demonstrated that crocin-I could restore the disturbed metabolites in the liver of CORT-treated mice, most of which are long-chain fatty acids. Furthermore, high-throughput sequencing of 16s rRNA revealed that crocin-I could mitigate the dysbiosis of the gut microbiota caused by CORT at a dose of 40 mg kg-1, by resulting in a significant increase in the alpha diversity of the microbes in the cecal contents and a significant reduction in the abundance of Firmicutes, whereas by increasing the abundance of Bacteroidetes. These results indicated that oral administration of crocin-I could modify the composition of the gut microbiota and alleviate hepatic lipid disorder in mice treated with a high dose of GCs.

A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy.

To integrate photothermal ablation (PTA) with radiotherapy (RT) for improved cancer therapy, we constructed a novel multifunctional core/satellite nanotheranostic (CSNT) by decorating ultrasmall CuS nanoparticles onto the surface of a silica-coated rare earth upconversion nanoparticle. These CSNTs could not only convert near-infrared light into heat for effective thermal ablation but also induce a highly localized radiation dose boost to trigger substantially enhanced radiation damage both in vitro and in vivo. With the synergistic interaction between PTA and the enhanced RT, the tumor could be eradicated without visible recurrence in 120 days. Notably, hematological analysis and histological examination unambiguously revealed their negligible toxicity to the mice within a month. Moreover, the novel CSNTs facilitate excellent upconversion luminescence/magnetic resonance/computer tomography trimodal imagings. This multifunctional nanocomposite is believed to be capable of playing a vital role in future oncotherapy by the synergistic effects between enhanced RT and PTA under the potential trimodal imaging guidance.