Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation in the absence of excess alcohol intake. NAFLD is the most common chronic liver disease, and ongoing research efforts are focused on understanding the underlying pathobiology of hepatic steatosis with the anticipation that these efforts will identify novel therapeutic targets. Under physiological conditions, the low steady-state triglyceride concentrations in the liver are attributable to a precise balance between acquisition by uptake of non-esterified fatty acids from the plasma and by de novo lipogenesis, versus triglyceride disposal by fatty acid oxidation and by the secretion of triglyceride-rich lipoproteins. In NAFLD patients, insulin resistance leads to hepatic steatosis by multiple mechanisms. Greater uptake rates of plasma non-esterified fatty acids are attributable to increased release from an expanded mass of adipose tissue as a consequence of diminished insulin responsiveness. Hyperinsulinemia promotes the transcriptional upregulation of genes that promote de novo lipogenesis in the liver. Increased hepatic lipid accumulation is not offset by fatty acid oxidation or by increased secretion rates of triglyceride-rich lipoproteins. This review discusses the molecular mechanisms by which hepatic triglyceride homeostasis is achieved under normal conditions, as well as the metabolic alterations that occur in the setting of insulin resistance and contribute to the pathogenesis of NAFLD

Enhancing Light-Absorption and Luminescent Properties of Non-Emissive 1,3,4,6,9b-Pentaazaphenalene through Perturbation of Forbidden Electronic Transition by Boron Complexation

We report an improvement of optical properties of the non‐emissive molecule through shuffling the molecular orbitals by boron complexation. The 1, 3, 4, 6, 9b‐pentaazaphenelene (5AP) derivative having a 2‐(dimesitylboryl)phenyl group was synthesized through a substitution reaction from a 2‐bromophenyl compound. The formation of the B−N dative bond was confirmed by ¹¹B{¹H} NMR spectroscopy and a single‐crystal X‐ray structure analysis. Most of the conventional 5AP derivatives hardly showed emission despite their planar and rigid molecular structures. The previous reports on 5AP derivatives ascribed the non‐luminescent behavior to the forbidden transition between frontier orbitals. On the other hand, the 5AP‐based boron complex in this work showed enhanced light absorption and luminescence from the HOMO−LUMO transition. Theoretical calculations suggested that the boron complexation should play a critical role in perturbing the forbidden character of the HOMO−LUMO transition. Because the nitrogen atom on the 5AP moiety formed the Lewis acid−base pair with the boron atom, the energy level of the HOMO of 5AP was downshifted. The character of the HOMO−LUMO transition of the boron complex was changed to afford the improved optical properties of the boron complex

Intestinal Diffuse Large B-Cell Lymphoma in a Patient with Systemic Lupus Erythematosus

A 44-year-old Japanese woman with systemic lupus erythematosus (SLE) presented to our hospital with abdominal pain. Radiological and endoscopic examinations led to the diagnosis of diffuse large B-cell lymphoma of the jejunum, which was subsequently resected. Patients with SLE reportedly have an increased risk of non-Hodgkin lymphoma, as demonstrated by our patient. Hence, lymphoma should be considered in the differential diagnosis of neoplastic lesions emerging in SLE patients. In addition, flow cytometry using endoscopically biopsied fragments is useful for the immediate diagnosis of lymphoma, leading to timely and accurate preoperative staging

A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis

In clinical studies, the next-generation anti-tumor necrosis factor-alpha (TNF-α) single domain antibody ozoralizumab showed high clinical efficacy shortly after the subcutaneous injection. To elucidate the mechanism underlying the rapid onset of the effects of ozoralizumab, we compared the biodistribution kinetics of ozoralizumab and adalimumab after subcutaneous injection in an animal model of arthritis. Alexa Fluor 680-labeled ozoralizumab and adalimumab were administered by subcutaneous injection once (2 mg/kg) at five weeks after induction of collagen-induced arthritis (CIA) in an animal arthritis model. The time-course of changes in the fluorescence intensities of the two compounds in the paws and serum were evaluated. The paws of the CIA mice were harvested at four and eight hours after the injection for fluorescence microscopy. Biofluorescence imaging revealed better distribution of ozoralizumab to the joint tissues than of adalimumab, as early as at four hours after the injection. Fluorescence microscopy revealed a greater fluorescence intensity of ozoralizumab in the joint tissues than that of adalimumab at eight hours after the injection. Ozoralizumab showed a significantly higher absorption rate constant as compared with adalimumab. These results indicate that ozoralizumab enters the systemic circulation more rapidly and is distributed to the target tissues earlier and at higher levels than conventional IgG antibodies. Our investigation provides new insight into the mechanism underlying the rapid onset of the effects of ozoralizumab in clinical practice.Oyama S., Ebina K., Etani Y., et al. A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis. Scientific Reports 12, 18102 (2022); https://doi.org/10.1038/s41598-022-23152-6

Development of fully automated and ultrasensitive assays for urinary adiponectin and their application as novel biomarkers for diabetic kidney disease

Glomerular filtration rate (GFR) and urinary albumin excretion rate (UAER) are used to diagnose and classify the severity of chronic kidney disease. Total adiponectin (T-AN) and high molecular weight adiponectin (H-AN) assays were developed using the fully automated immunoassay system, HI-1000 and their significance over conventional biomarkers were investigated. The T-AN and H-AN assays had high reproducibility, good linearity, and sufficient sensitivity to detect trace amounts of adiponectin in the urine. Urine samples after gel filtration were analyzed for the presence of different molecular isoforms. Low molecular weight (LMW) forms and monomers were the major components (93%) of adiponectin in the urine from a diabetic patient with normoalbuminuria. Urine from a microalbuminuria patient contained both high molecular weight (HMW) (11%) and middle molecular weight (MMW) (28%) adiponectin, although the LMW level was still high (52%). The amount of HMW (32%) and MMW (42%) were more abundant than that of LMW (24%) in a diabetic patient with macroalbuminuria. T-AN (r = − 0.43) and H-AN (r = − 0.38) levels showed higher correlation with estimated GFR (eGFR) than UAER (r = − 0.23). Urinary levels of both T-AN and H-AN negatively correlated with renal function in diabetic patients and they may serve as new biomarkers for diabetic kidney disease

Speaking Practices Designed to Improve Presentation Skills and Their Effect on High School Students’ Oral Performance

この研究は，口頭発表活動に必要な技術を身につける実践を通じて，発話力の伸びを検証することを目的とした実証的研究である。高校１年生の実験クラスを対象に，物語の紹介を目的とする，パターン化された構成で行うプレゼンテーション形式の活動を一定期間行い，ポストテストにおける発話を統制クラスと比較した結果，流暢さの面で向上が見られた。実験クラスの経験した発表活動では，パターン化された情報構造で発話内容を考えるため，活動時の発話過程において，概念化の段階で受ける認知的負荷が軽減され，言語化に向ける認知資源を増やすことができ，流暢さが高まったと考えられる。The present study takes an empirical approach to assessing the effect of speaking practice designed to improve presentation skills. First-year high-school students repeatedly engaged in book-talk activities for a certain period of time. During the activities, they were given a speaking format to facilitate their performance. At the end of the instruction period, students’ speaking fluency was measured, analyzed, and compared with that of a control group. The comparative analysis demonstrates that the students’ fluency improves substantially when they are provided with a speaking format. The result supports the hypothesis that this format helps to lessen the students’ cognitive load at the initial conceptualization stage and instead helps to save cognitive resources for successive stages of speech production, which consequently enhances the students’ speaking performance