Critical appraisal of metabolic dysfunction-associated steatotic liver disease: Implication of Janus-faced modernity

The existing term non-alcoholic fatty liver disease (NAFLD) has raised substantial concerns due to its inherent disadvantages of using exclusionary diagnostic criteria and the stigmatizing word ‘fatty.’ Three pan-national liver associations set out to explore a new nomenclature to replace both NAFLD and its suggested alternative, metabolic (dysfunction)-associated fatty liver disease (MAFLD). They surveyed if a change in nomenclature and/or definition is favored and which nomenclature best communicates disease characteristics and increases awareness. In lieu of NAFLD/MAFLD, metabolic dysfunction-associated steatotic liver disease (MASLD) has been chosen, and an umbrella term, steatotic liver disease (SLD), encompassing the whole spectrum of liver disease, has been proposed. It has been suggested that cardiometabolic risk factors should be considered when categorizing SLD patients. Furthermore, a new subcategory, MASLD with increased alcohol intake (MetALD), casts light on a neglected group of patients with moderate or more alcohol consumption. The importance of metabolic dysfunction was acknowledged in this new nomenclature, but the precise contribution of metabolic dysfunction and alcohol consumption to the development and progression of SLD remains unclear. Herein, we review hepatologists’ and endocrinologists’ perspectives on the new nomenclature, along with its possible impact on clinical practice. Although it is premature to predict the settlement of the new nomenclature, this review may help build more evidence for a soft landing of it in the future

Near-Infrared [Fe II] and H2 Line Observations of the Supernova Remnant 3C 396: Probing the Pre-supernova Circumstellar Materials

We present the results of near-infrared [Fe II] and H2 line imaging and spectroscopic observations of the supernova remnant 3C 396 using the Palomar 5 m Hale telescope. We detect long, filamentary [Fe II] emission delineating the inner edge of the radio emission in the western boundary of the remnant in imaging observations, together with a bright [Fe II] emission clump close to the remnant center. There appears to be faint, diffuse [Fe II] emission between the central clump and the western filamentary emission. The spectroscopic observations determine the expansion velocity of the central clump to be ~56 km/s. This is far smaller than the expansion velocity of 3C 396 obtained from X-ray observations, implying the inhomogeneity of the ambient medium. The electron number density of the [Fe II] emission gas is < 2,000 cm-3. The H2 line emission, on the other hand, lies slightly outside the filamentary [Fe II] emission in the western boundary, and forms a rather straight filament. We suggest that the [Fe II] emission represents dense clumps in the wind material from the red supergiant phase of a Type IIL/b progenitor of 3C 396 which have been swept up by the supernova remnant shocks. The H2 emission may represent either the boundary of a wind bubble produced during the main-sequence phase of the progenitor or molecular clumps left over inside the bubble. We propose that the near-infrared [Fe II] and H2 emission observed in several supernova remnants of Type IIL/b SNe likely has the same origin.Comment: 24 page including 8 figures; Accepted by Ap

Efficiency of Air Bubble Removal in Preparation of Low-Profile Angioplasty Balloon Catheter: Bench-Top Comparison of Six Methods

Purpose Complete removal of air bubbles from balloons for neurovascular angioplasty is cumbersome. We compared the preparation difficulty, air removal efficiency, and air collection pattern of six different balloon catheter preparation methods to propose a better preparation method for both initial and second balloon uses, especially for small-profile angioplasty balloon catheters.Materials and Methods A total of 18 neurovascular angioplasty balloon catheters with nominal diameters of 2 mm were prepared to test six different preparation methods: the instruction for use method (method A), simplified method using a syringe (method B) and four newly devised preparation methods using inflating devices (methods C–F). Serial radiographs were obtained while the balloons were gradually inflated. We measured the time for each preparation and the bubble number, analyzed their distribution in the balloon, and calculated the contrast filling ratio (contrast filling area/total balloon area) for initial and second ballooning. The whole process was repeated three times. Results The preparation time varied widely (11.5 seconds [method D] to 73.3 seconds [method A]). On initial inflation, the contrast filling ratio at 8 atm was the highest (100%) with methods A and F. On second inflation, the ratio was again highest with method A (99.5%), followed by method F (99.2%). Initial ballooning tended to show a uniform pattern of single bubble in the distal segment of the balloon; in contrast, second ballooning showed varying patterns in which the bubbles were multiple and randomly distributed. Conclusion None of the six methods were able to completely exclude air bubbles from the balloon catheters including the second ballooning; however, the method of repeating aspiration with high-volume inflating device (method F) could be a practical option considering the simplicity and efficiency of preparation

Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes.

Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH

Identification of protein functions using a machine-learning approach based on sequence-derived properties

<p>Abstract</p> <p>Background</p> <p>Predicting the function of an unknown protein is an essential goal in bioinformatics. Sequence similarity-based approaches are widely used for function prediction; however, they are often inadequate in the absence of similar sequences or when the sequence similarity among known protein sequences is statistically weak. This study aimed to develop an accurate prediction method for identifying protein function, irrespective of sequence and structural similarities.</p> <p>Results</p> <p>A highly accurate prediction method capable of identifying protein function, based solely on protein sequence properties, is described. This method analyses and identifies specific features of the protein sequence that are highly correlated with certain protein functions and determines the combination of protein sequence features that best characterises protein function. Thirty-three features that represent subtle differences in local regions and full regions of the protein sequences were introduced. On the basis of 484 features extracted solely from the protein sequence, models were built to predict the functions of 11 different proteins from a broad range of cellular components, molecular functions, and biological processes. The accuracy of protein function prediction using random forests with feature selection ranged from 94.23% to 100%. The local sequence information was found to have a broad range of applicability in predicting protein function.</p> <p>Conclusion</p> <p>We present an accurate prediction method using a machine-learning approach based solely on protein sequence properties. The primary contribution of this paper is to propose new <it>PNPRD </it>features representing global and/or local differences in sequences, based on positively and/or negatively charged residues, to assist in predicting protein function. In addition, we identified a compact and useful feature subset for predicting the function of various proteins. Our results indicate that sequence-based classifiers can provide good results among a broad range of proteins, that the proposed features are useful in predicting several functions, and that the combination of our and traditional features may support the creation of a discriminative feature set for specific protein functions.</p

The Risk of Type 2 Diabetes Mellitus according to Changes in Obesity Status in Late Middle-Aged Adults: A Nationwide Cohort Study of Korea

Background Although obesity is a well-known risk factor of type 2 diabetes mellitus (T2DM), there is scant data on discriminating the contribution of previous obesity and recent weight gain on developing T2DM. Methods We analyzed the Korean National Health Insurance Service-Health Screening Cohort data from 2002 to 2015 where Korean residents underwent biennial health checkups. Participants were classified into four groups according to their obesity status (body mass index [BMI] ≥25 kg/m2) before and after turning 50 years old: maintaining normal (MN), becoming obese (BO), becoming normal (BN), and maintaining obese (MO). Cox proportional hazards regression model was used to estimate the risk of T2DM factoring in the covariates age, sex, BMI, presence of impaired fasting glucose or hypertension, family history of diabetes, and smoking status. Results A total of 118,438 participants (mean age, 52.5±1.1 years; men, 45.2%) were prospectively evaluated for incident T2DM. A total of 7,339 (6.2%) participants were diagnosed with T2DM during a follow-up period of 4.8±2.6 years. Incidence rates of T2DM per 1,000 person-year were 9.20 in MN, 14.81 in BO, 14.42 in BN, 21.38 in MO. After factoring in covariates, participants in the groups BN (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.04 to 1.27) and MO (aHR, 1.14; 95% CI, 1.06 to 1.24) were at increased risk of developing T2DM compared to MN, whereas BO (hazard ratio, 1.06; 95% CI, 0.96 to 1.17) was not. Conclusion Having been obese before 50 years old increased the risk of developing T2DM in the future, but becoming obese after 50 did not. Therefore, it is important to maintain normal weight from early adulthood to prevent future metabolic perturbations

Change in gene expression of mouse embryonic stem cells derived from parthenogenetic activation

BACKGROUND We previously established parthenogenetic mouse embryonic stem cells (ESCs) and this study was subsequently conducted for elucidating the influence of oocyte parthenogenesis on gene expression profile of ESCs. METHODS Gene expression of parthenogenetic ESC (pESC)-1 or pESC-2 was separately compared with that of two normally fertilized ESC (nfESC) lines (B6D2F1 and R1 strains), and quantification of mRNA expression was conducted for validating microarray data. RESULTS In two sets of comparison, reaction of 11 347 and 15 454 gene probes were altered by parthenogenesis, while strain difference changed the expression of 15 750 and 14 944 probes. Level of correlation coefficient was higher in the comparisons between normal fertilization and parthenogenesis (0.974-0.985) than in the comparisons between strains of nfESCs (0.97-0.971). Overall, the expression of 3276-3329 genes was changed after parthenogenesis, and 88% (96/109) of major functional genes differentially (P < 0.01) expressed in one comparison set showed the same change in the other. When we monitored imprinted genes, expression of nine paternal and eight maternal genes were altered after parthenogenesis and 88% (14/16) of these was confirmed by mRNA quantification. CONCLUSIONS The change in gene expression after parthenogenesis was similar to, or less than, the change induced by a strain difference under a certain genetic background. These results may suggest the clinical feasibility of parthenogenesis-derived, pluripotent cell