Comparative Lipidomics and Metabolomics Reveal the Underlying Mechanisms of Taurine in the Alleviation of Nonalcoholic Fatty Liver Disease Using the Aged Laying Hen Model.

SCOPE: Aged laying hen is recently suggested as a more attractive animal model than rodent for studying nonalcoholic fatty liver disease (NAFLD) of humans. This study aims to reveal effects and metabolic regulation mechanisms of taurine alleviating NAFLD by using the aged laying hen model. METHODS AND RESULTS: Liver histomorphology and biochemical indices show 0.02% taurine effectively alleviated fat deposition and liver damage. Comparative liver lipidomics and gene expressions analyses reveal taurine promoted lipolysis, fatty acids oxidation, lipids transport, and reduced oxidative stress in liver. Furthermore, comparative serum metabolomics screen six core metabolites negatively correlated with NAFLD, including linoleic acid, gamma-linolenic acid, pantothenate, L-methionine, 2-methylbutyroylcarnitine, L-carnitine; and two core metabolites positively correlated with NAFLD, including lysophosphatidylcholine (14:0/0:0) and lysophosphatidylcholine (16:0/0:0). Metabolic pathway analysis reveals taurine mainly regulated linoleic acid metabolism, cysteine and methionine metabolism, carnitine metabolism, pantothenic acid and coenzyme A biosynthesis metabolism, and glycerophospholipid metabolism to up-adjust levels of six negatively correlated metabolites and down-adjust two positively correlated metabolites for alleviating NAFLD of aged hens. CONCLUSION: This study firstly reveals underlying metabolic mechanisms of taurine alleviating NAFLD using the aged hen model, thereby laying the foundation for taurine's application in the prevention of NAFLD in both human and poultry.

How iron-bearing minerals affect the biological reduction of Sb(V): A newly discovered function of nitrate reductase.

As a toxic element of global concern, the elevated concentration of antimony (Sb) in the environment has attracted increasing attention. Microorganisms have been reported as important driving forces for Sb transformation. Iron (Fe) is the most important metal associated element of Sb, however, how Fe-bearing minerals affect the biological transformation of Sb is still unclear. In this study, the effects of Fe-bearing minerals on biological Sb(V) reduction were investigated by employing a marine Shewanella sp. CNZ-1 (CNZ-1). Our results showed that the presence of hematite, magnetite and ferrihydrite (1 g/L) resulted in a decrease in Sb(III) concentration of ~19-31 % compared to the Fe(III)-minerals free system. The calculated Sb(V) reduction rates are 0.0256 (R2 0.71), 0.0389 (R2 0.87), 0.0299 (R2 0.96) and 0.0428 (R2 0.95) h-1 in the hematite-, magnetite-, ferrihydrite-supplemented and Fe(III)-minerals free systems, respectively. The cube-shaped Sb2O3 was characterized as a reductive product by using XRD, XPS, FTIR, TG and SEM approaches. Differential proteomic analysis showed that flagellar protein, cytochrome c, electron transfer flavoprotein, nitrate reductase and polysulfide reductase (up-regulation >1.5-fold, p value <0.05) were supposed to be included in the electron transport pathway of Sb(V) reduction by strain CNZ-1, and the key role of nitrate reductases was further highlighted during this reaction process based on the RT-qPCR and confirmatory experiments. Overall, these findings are beneficial to understand the environmental fate of Sb in the presence of Fe-bearing minerals and provide guidance in developing the bacteria/enzyme-mediated control strategy for Sb pollution.

1α,25-Dihydroxyvitamin D3 Improves Follicular Development and Steroid Hormone Biosynthesis by Regulating Vitamin D Receptor in the Layers Model.

1α,25-Dihydroxyvitamin D3 (VitD3) is the active form of vitamin D, and it regulates gene expression and protein synthesis in mammalian follicle development. However, the function of VitD3 in the follicular development of layers remains unclear. This study investigated, through in vivo and in vitro experiments, the effects of VitD3 on follicle development and steroid hormone biosynthesis in young layers. In vivo, ninety 18-week-old Hy-Line Brown laying hens were randomly divided into three groups for different treatments of VitD3 (0, 10, and 100 µg/kg). VitD3 supplementation promoted follicle development, increasing the number of small yellow follicles (SYFs) and large yellow follicles (LYFs) and the thickness of the granulosa layer (GL) of SYFs. Transcriptome analysis revealed that VitD3 supplementation altered gene expression in the ovarian steroidogenesis, cholesterol metabolism, and glycerolipid metabolism signaling pathways. Steroid hormone-targeted metabolomics profiling identified 20 steroid hormones altered by VitD3 treatment, with 5 being significantly different among the groups. In vitro, it was found that VitD3 increased cell proliferation, promoted cell-cycle progression, regulated the expression of cell-cycle-related genes, and inhibited the apoptosis of granulosa cells from pre-hierarchical follicles (phGCs) and theca cells from prehierarchical follicles (phTCs). In addition, the steroid hormone biosynthesis-related genes, estradiol (E2) and progesterone (P4) concentrations, and vitamin D receptor (VDR) expression level was significantly altered by VitD3. Our findings identified that VitD3 altered the gene expression related to steroid metabolism and the production of testosterone, estradiol, and progesterone in the pre-hierarchical follicles (PHFs), resulting in positive effects on poultry follicular development.

Doxorubicin delivered by redox-responsive Hyaluronic Acid-Ibuprofen prodrug micelles for treatment of metastatic breast cancer.

During the process of cancer metastasis, various enzymes, cytokines, and factors were involved, and upregulated cyclooxygenase-2(COX-2) in tumor cells led to proliferation and invasion of various tumors. Many nonsteroidal anti-inflammatory drugs (NSAIDs) were used as an anticancer adjuvant in chemotherapy, such as ibuprofen (BF) and celecoxib. NSAIDs could effectively inhibit local inflammation and decreased COX-2 expression. However, most of them have serious toxicity issues due to their limit selectivity against cancer and poor water solubility. Thus hyaluronic acid-ibuprofen (HA-ss-BF), which was sensitive to the reducing environment, was prepared by binding ibuprofen (BF) to the hyaluronic acid backbone through a disulfide bond, and the HA-ss-BF polymer could self-assemble into micelles and serve as carriers to delivery doxorubicin. These redox-sensitive prodrug polymeric micelles hold multiple therapeutic advantages, including on-demand BF release and disassembling micelles responding to redox stimuli, as well as desirable cellular uptake and favorable biodistribution. These advantages indicated the redox-responsive hyaluronic acid-ibuprofen prodrug could be a promising delivery system for metastatic breast cancer treatment.