Anti-Obesity Effect of Jeju Roasted Citrus Peel Extract in High-Fat Diet-Induced Obese Mice and 3T3-L1 Adipocytes Via Lipid Metabolism Regulation.

Lipid accumulation in adipocytes occurs through multifactorial effects such as overnutrition due to unbalanced eating habits, reduced physical activity, and genetic factors. In addition, obesity can be intensified by the dis-regulation of various metabolic systems such as differentiation, lipogenesis, lipolysis, and energy metabolism of adipocytes. In this study, the Jeju roasted peel extract from Citrus unshiu S.Markov. (JRC), which is discarded as opposed to the pulp of C. unshiu S.Markov., is commonly consumed to ameliorate obesity. To investigate the anti-obesity effect of JRC, these studies were conducted on differentiated 3T3-L1 cells and in high-fat diet-induced mice, and related methods were used to confirm whether it decreased lipid accumulation in adipocytes. The mechanism of inhibiting obesity by JRC was confirmed through mRNA expression studies. JRC suppressed lipid accumulation in adipocytes and adipose tissue, and significantly improved enzymes such as alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase and serum lipid profiles. In addition, it effectively modulated the expression of genes related to lipid and energy metabolism in adipose tissue. As a result, these findings suggest that JRC could be a therapeutic regulator of body fat accumulation by significantly alleviating the dis-regulation of intracellular lipid metabolism in adipocytes and by enhancement of energy metabolism (Approval No. CNU IACUC-YB-2023-98).

Effect of rice milling, washing, and cooking on reducing pesticide residues.

The effects of milling, washing, and cooking on etofenprox, flubendiamide, and tebufenozide levels in brown and polished rice were investigated by HPLC using a UV detector. The reduction rates of etofenprox, flubendiamide, and tebufenozide after milling were 68.74-93.16%, 64.49-90.25%, and 69.74-92.58%, respectively, 11.64-41.44%, 31.36-65.37%, and 31.61-73.79%, respectively, after washing brown rice, and 30.85-82.08%, 52.13-83.05%, and 43.04-83.89%, respectively, after washing polished rice. The residue levels of the three pesticides in brown rice decreased after electric and pressure cooking by 56.49 and 54.41%, 75.80 and 73.42%, and 70.01 and 71.27%, respectively, and the corresponding levels in polished rice decreased after electric and pressure cooking by 85.58 and 85.82%, 86.70 and 87.06%, and 89.89 and 89.68%, respectively. In conclusion, various processing methods decrease the residual levels of etofenprox, flubendiamide, and tebufenozide in rice.

Mitochondrial matrix RTN4IP1/OPA10 is an oxidoreductase for coenzyme Q synthesis.

Targeting proximity-labeling enzymes to specific cellular locations is a viable strategy for profiling subcellular proteomes. Here, we generated transgenic mice (MAX-Tg) expressing a mitochondrial matrix-targeted ascorbate peroxidase. Comparative analysis of matrix proteomes from the muscle tissues showed differential enrichment of mitochondrial proteins. We found that reticulon 4-interacting protein 1 (RTN4IP1), also known as optic atrophy-10, is enriched in the mitochondrial matrix of muscle tissues and is an NADPH oxidoreductase. Interactome analysis and in vitro enzymatic assays revealed an essential role for RTN4IP1 in coenzyme Q (CoQ) biosynthesis by regulating the O-methylation activity of COQ3. Rtn4ip1-knockout myoblasts had markedly decreased CoQ9 levels and impaired cellular respiration. Furthermore, muscle-specific knockdown of dRtn4ip1 in flies resulted in impaired muscle function, which was reversed by dietary supplementation with soluble CoQ. Collectively, these results demonstrate that RTN4IP1 is a mitochondrial NAD(P)H oxidoreductase essential for supporting mitochondrial respiration activity in the muscle tissue.

Salvia plebeia R. Br. Water Extract Ameliorates Hepatic Steatosis in a Non-Alcoholic Fatty Liver Disease Model by Regulating the AMPK Pathway.

Salvia plebeia R. Br. (SP), grown from autumn to spring, is used as a medicinal herb from roots to leaves. This herb exhibits antioxidant activities and various physiological effect, including anti-asthma, immune-promoting, anti-obesity, and anti-cholesterol effects. However, the effectiveness of SP against non-alcoholic fatty liver disease (NAFLD) and the associated mechanism have not been elucidated. In this study, alleviation of NAFLD by SP was confirmed in a mouse model of hepatic steatosis induced by a high-fat diet and in HepG2 cells administered free fatty acids (FFA). In the experimental model, intrahepatic lipid accumulation was investigated using the AdipoRedTM assay, Oil Red O staining, biomarker analysis, and hematoxylin and eosin staining. Furthermore, glucose tolerance was examined based on the fasting glucose levels and oral glucose tolerance. The molecular mechanisms related to hepatic steatosis were determined based on marker mRNA levels. Blood FFAs were found to flow into the liver via the action of fatty acid translocase, cluster of differentiation 36, and fatty acid transporter proteins 2 and 5. Salvia plebeia R. Br. water extract (SPW) suppressed the FFAs inflow by regulating the expression of the above-mentioned proteins. Notably, modulating the expression of AMP-activated protein kinase (AMPK) and liver X receptor, which are involved in the regulation of lipid metabolism, stimulated peroxisome proliferator activated receptor α in the nucleus to induce the expression genes involved in ß-oxidation and increase ß-oxidation in the mitochondria. AMPK modulation also increased the expression of sterol regulatory element binding protein-1c, which activated lipid synthesis enzymes. As a consequence of these events, triglyceride synthesis was reduced and lipid accumulation in hepatocytes was alleviated. Overall, our findings suggested that SPW could ameliorate NAFLD by inhibiting hepatic steatosis through AMPK modulation.

Deciphering Molecular Mechanism of Histone Assembly by DNA Curtain Technique.

Chromatin is a higher-order structure that packages eukaryotic DNA. Chromatin undergoes dynamic alterations according to the cell cycle phase and in response to environmental stimuli. These changes are essential for genomic integrity, epigenetic regulation, and DNA metabolic reactions such as replication, transcription, and repair. Chromatin assembly is crucial for chromatin dynamics and is catalyzed by histone chaperones. Despite extensive studies, the mechanisms by which histone chaperones enable chromatin assembly remains elusive. Moreover, the global features of nucleosomes organized by histone chaperones are poorly understood. To address these problems, this work describes a unique single-molecule imaging technique named DNA curtain, which facilitates the investigation of the molecular details of nucleosome assembly by histone chaperones. DNA curtain is a hybrid technique that combines lipid fluidity, microfluidics, and total internal reflection fluorescence microscopy (TIRFM) to provide a universal platform for real-time imaging of diverse protein-DNA interactions.Using DNA curtain, the histone chaperone function of Abo1, the Schizosaccharomyces pombe bromodomain-containing AAA+ ATPase, is investigated, and the molecular mechanism underlying histone assembly of Abo1 is revealed. DNA curtain provides a unique approach for studying chromatin dynamics.

Comprehensive Investigation of Stereoselective Food Drug Interaction Potential of Resveratrol on Nine P450 and Six UGT Isoforms in Human Liver Microsomes.

The stereoselectivity of the food drug inhibition potential of resveratrol on cytochrome P450s and uridine 5'-diphosphoglucuronosyl transferases was investigated in human liver microsomes. Resveratrol enantiomers showed stereoselective inhibition of CYP2C9, CYP3A, and UGT1A1. The inhibitions of CYP1A2, CYP2B6, and CYP2C19 by resveratrol were stereo-nonselective. The estimated Ki values determined for CYP1A2 were 13.8 and 9.2 µM for trans- and cis-resveratrol, respectively. Trans-resveratrol noncompetitively inhibited CYP3A and UGT1A1 activities with Ki values of 23.8 and 27.4 µM, respectively. Trans-resveratrol inhibited CYP1A2, CYP2C19, CYP2E1, and CYP3A in a time-dependent manner with Ki shift values >2.0, while cis-resveratrol time-dependently inhibited CYP2C19 and CYP2E1. The time-dependent inhibition of trans-resveratrol against CYP3A4, CYP2E1, CYP2C19, and CYP1A2 was elucidated using glutathione as a trapping reagent. This information helped the prediction of food drug interaction potentials between resveratrol and co-administered drugs which are mainly metabolized by UGT1A1, CYP1A2, CYP2C19, CYP2E1, and CYP3A.

Nontargeted Metabolomics by High-Resolution Mass Spectrometry to Study the In Vitro Metabolism of a Dual Inverse Agonist of Estrogen-Related Receptors ß and γ, DN203368.

DN203368 ((E)-3-[1-(4-[4-isopropylpiperazine-1-yl]phenyl) 3-methyl-2-phenylbut-1-en-1-yl] phenol) is a 4-hydroxy tamoxifen analog that is a dual inverse agonist of estrogen-related receptor ß/γ (ERRß/γ). ERRγ is an orphan nuclear receptor that plays an important role in development and homeostasis and holds potential as a novel therapeutic target in metabolic diseases such as diabetes mellitus, obesity, and cancer. ERRß is also one of the orphan nuclear receptors critical for many biological processes, such as development. We investigated the in vitro metabolism of DN203368 by conventional and metabolomic approaches using high-resolution mass spectrometry. The compound (100 µM) was incubated with rat and human liver microsomes in the presence of NADPH. In the metabolomic approach, the m/z value and retention time information obtained from the sample and heat-inactivated control group were statistically evaluated using principal component analysis and orthogonal partial least-squares discriminant analysis. Significant features responsible for group separation were then identified using tandem mass spectra. Seven metabolites of DN203368 were identified in rat liver microsomes and the metabolic pathways include hydroxylation (M1-3), N-oxidation (M4), N-deisopropylation (M5), N,N-dealkylation (M6), and oxidation and dehydrogenation (M7). Only five metabolites (M2, M3, and M5-M7) were detected in human liver microsomes. In the conventional approach using extracted ion monitoring for values of mass increase or decrease by known metabolic reactions, only five metabolites (M1-M5) were found in rat liver microsomes, whereas three metabolites (M2, M3, and M5) were found in human liver microsomes. This study revealed that nontargeted metabolomics combined with high-resolution mass spectrometry and multivariate analysis could be a more efficient tool for drug metabolite identification than the conventional approach. These results might also be useful for understanding the pharmacokinetics and metabolism of DN203368 in animals and humans.

Development of Temperature Monitoring System of Hospital Cold Storages Based on Wireless Network and its Database Management.

Storing bio-specimens in adequate temperatures is an important task in hospitals. Usually an assigned employee records manually the temperatures of the hospital cold storages such as refrigerators and freezers that keep them at regular intervals. In this research, a low power wireless Bluetooth Low Energy network is applied where the central monitoring personal computer, receives the temperature data and stores in a database. The system consists of many beacons which are wirelessly sending the measured temperature data, and the central monitoring computer which allows the user to monitor that data. In the case of wireless signals getting blocked due to obstacles, repeaters called bridges send the data to the central computer forming a so-called scatter net. Once the data is received by the Bluetooth module connected to the monitoring computer, an application saves the data into a database. This web application forms a website where the users holding the authentication information can log in and monitor the temperature data in the form of tables and graphs. The same information can be viewed by a smartphone and a person in charge receives a warning SMS message. This system also provides a scheduled backup system where the database is automatically backed up periodically. The suggested system has the advantage of managing reagent records with reduced manpower whilst coping for emergency situations automatically.