Caloric restriction of db/db mice reverts hepatic steatosis and body weight with divergent hepatic metabolism

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver disease and its prevalence is a serious and growing clinical problem. Caloric restriction (CR) is commonly recommended for improvement of obesity-related diseases such as NAFLD. However, the effects of CR on hepatic metabolism remain unknown. We investigated the effects of CR on metabolic dysfunction in the liver of obese diabetic db/db mice. We found that CR of db/db mice reverted insulin resistance, hepatic steatosis, body weight and adiposity to those of db/m mice. H-NMR- and UPLC-QTOF-MS-based metabolite profiling data showed significant metabolic alterations related to lipogenesis, ketogenesis, and inflammation in db/db mice. Moreover, western blot analysis showed that lipogenesis pathway enzymes in the liver of db/db mice were reduced by CR. In addition, CR reversed ketogenesis pathway enzymes and the enhanced autophagy, mitochondrial biogenesis, collagen deposition and endoplasmic reticulum stress in db/db mice. In particular, hepatic inflammation-related proteins including lipocalin-2 in db/db mice were attenuated by CR. Hepatic metabolomic studies yielded multiple pathological mechanisms of NAFLD. Also, these findings showed that CR has a therapeutic effect by attenuating the deleterious effects of obesity and diabetes-induced multiple complications

Photometric Selection of Unobscured QSOs in the Ecliptic Poles: KMTNet in the South Field and Pan-STARRS in the North Field

We search for quasi-stellar objects (QSOs) in a wide area of the south ecliptic pole (SEP) field, which has been and will continue to be intensively explored through various space missions. For this purpose, we obtain deep broadband optical images of the SEP field covering an area of $\sim$$14.5\times14.5$ deg$^2$ with the Korea Microlensing Telescope Network. The 5$\sigma$ detection limits for point sources in the $BVRI$ bands are estimated to be $\sim$22.59, 22.60, 22.98, and 21.85 mag, respectively. Utilizing data from Wide-field Infrared Survey Explorer, unobscured QSO candidates are selected among the optically point-like sources using the mid-infrared (MIR) and optical-MIR colors. To further refine our selection and eliminate any contamination not adequately removed by the color-based selection, we perform the spectral energy distribution fitting with archival photometric data ranging from optical to MIR. As a result, we identify a total of 2,383 unobscured QSO candidates in the SEP field. We also apply a similar method to the north ecliptic pole field using the Pan-STARRS data and obtain a similar result of identifying 2,427 candidates. The differential number count per area of our QSO candidates is in good agreement with those measured from spectroscopically confirmed ones in other fields. Finally, we compare the results with the literature and discuss how this work will be implicated in future studies, especially with the upcoming space missions.Comment: 14 pages, 9 figures, accepted for publication in ApJ

Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the cause of a present pandemic, infects human lung alveolar type 2 (hAT2) cells. Characterizing pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hAT2 cells limits the study. Here, we develop a feeder-free, long-term, three-dimensional (3D) culture technique for hAT2 cells derived from primary human lung tissue and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and proinflammatory genes in infected hAT2 cells, indicating a robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2 and the application of defined 3D hAT2 cultures as models for respiratory diseases

Factors affecting porcine in vitro oocyte maturation, fertilization, and early embryo development

The thesis investigated the various factors influencing porcine in vitro maturation of an oocyte (IVM), fertilization (IVF), and early embryo culture (IVC). The study revealed that (1) the addition of cysteine during IVM was beneficial to early embryo development; (2) application of gradient Percoll and glutathione during sperm conditioning for IVF also improved the outcome of early embryo development; (3) when two common porcine embryo culture media, NCSU23 and BECM3 were tested for their ability to support porcine zygotes in vitro, the NCSU23 medium consistently showed an equal or better rate of embryo development; (4) the efficacy of two-step embryo culture using these two media was no better in supporting the development of embryos when compared to the single-step NCSU23 medium; (5) the developmental competence of the IVM-produced oocyte was maintained for at least 16h; (6) the oocyte activation by a combination treatment, calcium ionophore followed by 6-dimethylaminopurine, was the most effective among three common activation protocols evaluated; (7) the developmental competence of porcine oocytes was significantly affected by an interaction among the age of the donor animal, ovarian follicle size, and exogenous gonadotropic stimulation. In conclusion, this study provided a valuable assessment of the factors involved in porcine in vitro oocyte and embryo culture system.

Synthesis of Pyridoxine-Derived Dimethylpyridinols Fused with Aminooxazole, Aminoimidazole, and Aminopyrrole

Described in this paper are studies on the preparation of three classes of dimethylpyridinols derived from pyridoxine fused with aminooxazole, aminoimidazole, and aminopyrrole. The key feature of this synthetic strategy is the manipulation of hydroxymethyl moiety of C(5)-position of the pyridoxine starting material along with the installation of an amino group at C(6)-position. Efficient and practical synthesis for the oxazole- and imidazole-fused targets was accomplished, while the instability of the pyrrole-fused one was observed

The Aminopyridinol Derivative BJ-1201 Protects Murine Hippocampal Cells against Glutamate-Induced Neurotoxicity via Heme Oxygenase-1

Glutamate is the major excitatory neurotransmitter in the brain. It can cause neuronal cell damage in the context of oxidative stress. BJ-1201 is a derivative of the compound aminopyridinol, which is known for its antioxidant activity. In this study, we examined the effect of BJ-1201, a 6-(diphenylamino)-2,4,5-trimethylpyridin-3-ol compound, on neuroprotection in HT22 cells. Our data showed that BJ-1201 can protect HT22 cells against glutamate-induced cell cytotoxicity. In addition, BJ-1201 upregulated heme oxygenase-1 (HO-1) to levels comparable to those of the CoPP-treated group. BJ-1201 treatment induced phosphorylation of JNK, but not p38-MAPK or ERK. It also increased the signal in the reporter assay based on β-galactosidase activity driven by the nuclear transcription factor erythroid-2 related factor 2 (Nrf2) promoter harboring antioxidant response elements (AREs) and induced the translocation of Nrf2. These results demonstrate that BJ-1201 may be a good therapeutic platform against neurodegenerative diseases induced by oxidative stress

Retraction: Lee, D.-S. et al. The Aminopyridinol Derivative BJ-1201 Protects Murine Hippocampal Cells against Glutamate-Induced Neurotoxicity via Heme Oxygenase-1. Molecules 2016, 21, 594.

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