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Unhealthy diet especially high-fat diet (HFD) is the major cause of hyperlipidemia leading to deterioration of chronic kidney diseases (CKD) in patients. Trimethylamine N-oxide (TMAO) is a gut-derived uremic toxin. Our previous clinical study demonstrated that the elevation of TMAO was positively correlated with CKD progression. Finasteride, a competitive and specific inhibitor of type II 5a-reductase, has been reported recently to be able to downregulate plasma TMAO level thus preventing the onset of atherosclerosis by our research group. In this study, we established a protein-overload nephropathy CKD mouse model by bovine serum albumin (BSA) injection to investigate whether hyperlipidemia could accelerate CKD progression and the underlying mechanisms. Finasteride was administrated to explore its potential therapeutic effects. The results of biochemical analyses and pathological examination showed that HFD-induced hyperlipidemia led to aggravated protein-overload nephropathy in mice along with an elevated level of circulating TMAO, which can be alleviated by finasteride treatment possibly through inhibition of Fmo3 in liver. The 16 S rRNA sequencing results indicated that HFD feeding altered the composition and distribution of gut microbiota in CKD mice contributing to the enhanced level of TMAO precursor TMA, while finasteride could exert beneficial effects via promoting the abundance of Alistipes_senegalensis and Akkermansia_muciniphila. Immunofluorescence staining (IF) and qRT-PCR results demonstrated the disruption of intestinal barrier by decreased expression of tight junction proteins including Claudin-1 and Zo-1 in HFD-fed CKD mice, which can be rescued by finasteride treatment. Cytokine arrays and redox status analyses revealed an upregulated inflammatory level and oxidative stress after HFD feeding in CKO mice, and finasteride-treatment could alleviate these lesions. To summarize, our study suggested that finasteride could alleviate HFD-associated deterioration of protein-overload nephropathy in mice by inhibition of TMAO synthesis and regulation of gut microbiota.

Pests not only attack field crops during the growing season, but also damage grains and other food products stored in granaries. Modified or controlled atmospheres (MAs or CAs) with higher or lower concentrations of atmospheric gases, mainly oxygen (O2), carbon dioxide (CO2), ozone (O3), and nitric oxide (NO), provide a cost-effective method to kill target pests and protect stored products. In this review, the most recent discoveries in the field of MAs are discussed, with a focus on pest control as well as current MA technologies. Although MAs have been used for more than 30 years in pest control and play a role in storage pest management, the specific mechanisms by which insects are affected by and adapt to low O2 (hypoxia) and high carbon CO2 (hypercapnia) are not completely understood. Insect tolerance to hypoxia/anoxia and hypercapnia involves a decrease in aerobic metabolism, including decreased NADPH enzyme activity, and subsequently, decreases in glutathione production and catalase, superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase activities, as well as increases in carboxyl esterase and phosphatase activities. In addition, hypoxia induces energy and nutrient production, and in adapted insects, glycolysis and pyruvate carboxylase fluxes are downregulated, accompanied with O2 consumption and acetate production. Consequently, genes encoding various signal transduction pathway components, including epidermal growth factor, insulin, Notch, and Toll/Imd signaling, are downregulated. We review the changes in insect energy and nutrient sources, metabolic enzymes, and molecular pathways in response to modified O2, CO2, NO, and O3 concentrations, as well as the role of MAs in pest control. This knowledge will be useful for applying MAs in combination with temperature control for pest control in stored food products.