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Metabolic dysfunction-associated steatotic liver disease and gallbladder polyp development : an observational study
No full textThe influence of metabolic dysfunction-associated steatotic liver disease (MASLD) on gallbladder polyp development in both sexes remains elusive. Therefore, to clarify the role of MASLD in gallbladder polyp development, we investigated the longitudinal association between MASLD and gallbladder polyps. In this observational study, we included 5,527 gallbladder polyp-free patients who underwent > 2 health check-ups over > 2 years. Generalized estimation equations were used to analyze associations between MASLD and gallbladder polyp development according to repeated measures at baseline and the most recent stage. Gallbladder polyp development rates in men and women were 7.5% and 5.6% (p < 0.01), respectively. MASLD was not significantly correlated with gallbladder polyp development. Regarding the association between gallbladder polyp development (men: ≥6 mm and women: ≥5 mm) and the number of MASLD components following lifestyle habits, men and women with ≥ 4 MASLD components had odds ratios of 3.397 (95% confidence interval: 1.096–10.53) and 5.338 (1.054–27.04), respectively. Higher nonalcoholic fatty liver disease fibrosis scores were associated with significant risk of gallbladder polyp development in women (1.991, 1.047–3.785). Although MASLD influence on gallbladder polyp development differs by sex, close monitoring of patients with an increasing number of MASLD components is essential to prevent gallbladder polyp development. Specifically, men with ≥ 4 MASLD components should be monitored for gallbladder polyps measuring ≥ 6 mm.journal articl
The binding selectivity of quercetin and its structure-related polyphenols to human serum albumin using a fluorescent dye cocktail for multiplex drug-site mapping
No full textHuman serum albumin (HSA) is a serum protein that carries flavonoids in blood circulation. In this report, the binding selectivity and strength of interactions to HSA-binding sites (sites I or II) by flavonoids were evaluated using competition experiments and the specific fluorescent dyes, dansylamide and BD140. Most tested flavonoids bound site I preferentially, with the binding strength dependent on the mother structure in the order flavonol > flavone > flavanone > flavan 3-ols. Glycosylation or glucuronidation reduced the binding of quercetin to site I of HSA, whereas sulfation increased binding. Quercetin 7-sulfate showed the strongest binding and molecular docking simulations supported this observation. Prenylation at any position or glucuronidation and sulfation at the C-4' or C-7 position of quercetin facilitated stronger binding to site II. The binding affinity of flavonoids toward site I correlated with the partition coefficient value (logP), whereas no corresponding correlation was observed for site II.journal articl
Creation of Dihedral Escher-like Tilings Based on As-Rigid-As-Possible Deformation
Get PDFAn Escher-like tiling is a tiling consisting of one or a few artistic shapes of tile. This article proposes a method for generating Escher-like tilings consisting of two distinct shapes (dihedral Escher-like tilings) that are as similar as possible to the two goal shapes specified by the user. This study is an extension of a previous study that successfully generated Escher-like tilings consisting of a single tile shape for a single goal shape. Building upon the previous study, our method attempts to exhaustively search for which parts of the discretized tile contours are adjacent to each other to form a tiling. For each configuration, two tile shapes are optimized to be similar to the given two goal shapes. By evaluating the similarity based on as-rigid-as possible deformation energy, the optimized tile shapes preserve the local structures of the goal shapes, even if substantial deformations are necessary to form a tiling. However, in the dihedral case, this approach is seemingly unrealistic because it suffers from the complexity of the energy function and the combinatorial explosion of the possible configurations. We developed a method to address these issues and show that the proposed algorithms can generate satisfactory dihedral Escher-like tilings in a realistic computation time, even for somewhat complex goal shapes.journal articl
GWAS of Folate Metabolism With Gene–environment Interaction Analysis Revealed the Possible Role of Lifestyles in the Control of Blood Folate Metabolites in Japanese : The J-MICC Study
Get PDFBackground: The present genome-wide association study (GWAS) aimed to reveal the genetic loci associated with folate metabolites, as well as to detect related gene–environment interactions in Japanese.
Methods: We conducted the GWAS of plasma homocysteine (Hcy), folic acid (FA), and vitamin B12 (VB12) levels in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study participants who joined from 2005 to 2012, and also estimated gene–environment interactions. In the replication phase, we used data from the Yakumo Study conducted in 2009. In the discovery phase, data of 2,263 participants from four independent study sites of the J-MICC Study were analyzed. In the replication phase, data of 573 participants from the Yakumo Study were analyzed.
Results: For Hcy, MTHFR locus on chr 1, NOX4 on chr 11, CHMP1A on chr 16, and DPEP1 on chr 16 reached genome-wide significance (P 33% on Hcy (β = 0.039, 0.038 and −0.054, P = 0.018, 0.021 and <0.001, respectively) and the interaction of MTHFR C677T with ever drinking on FA (β = 0.033, P = 0.048).
Conclusion: The present GWAS revealed the folate metabolism-associated genetic loci and gene–environment interactions with drinking and physical activity in Japanese, suggesting the possibility of future personalized cardiovascular disease prevention.journal articl
Drug combination of topical ripasudil and brimonidine enhances neuroprotection in a mouse model of optic nerve injury
Get PDFPurpose: To determine whether combination of topical ripasudil and brimonidine has more effective neuroprotection on retinal ganglion cells (RGCs) following injury to axons composing the optic nerve.
Methods: Topical ripasudil, brimonidine, or mixture of both drugs were administered to adult mice after optic nerve injury (ONI). The influence of drug conditions on RGC health were evaluated by the quantifications of surviving RGCs, phosphorylated p38 mitogen-activated protein kinase (phospho-p38), and expressions of trophic factors and proinflammatory mediators in the retina.
Results: Topical ripasudil and brimonidine suppressed ONI-induced RGC death respectively, and mixture of both drugs further stimulated RGC survival. Topical ripasudil and brimonidine suppressed ONI-induced phospho-p38 in the whole retina. In addition, topical ripasudil suppressed expression levels of TNFα, IL-1β and monocyte chemotactic protein-1 (MCP-1), whereas topical brimonidine increased the expression level of basic fibroblast growth factor (bFGF).
Conclusions: Combination of topical ripasudil and brimonidine may enhance RGC protection by modulating multiple signaling pathways in the retina.journal articl
Robotic-assisted minimally invasive repair surgery for progressive spondylolysis in a young athlete : a technical note
Get PDFPresently, the invasiveness of direct repair surgery for lumbar spondylolysis is relatively high. Thus, high school and junior high school students who play sports often cannot return to sports before graduation because of the invasiveness. The use of a robotic system enabled an accurate and minimally invasive procedure. Robotic-assisted minimally invasive direct pars repair surgery is useful for young patients with progressive spondylolysis.journal articl
Generation of Highly Functional Hepatocyte-like Organoids from Human Adipose-Derived Mesenchymal Stem Cells Cultured with Endothelial Cells
Get PDFPreviously, we successfully established a highly functional, three-dimensional hepatocyte-like cell (3D-HLC) model from adipose-derived mesenchymal stem cells (ADSCs) via a three-step differentiation protocol. The aim of the present study was to investigate whether generating hepatocyte-like organoids (H-organoids) by adding endothelial cells further improved the liver-like functionality of 3D-HLCs and to assess H-organoids’ immunogenicity properties. Genes representing liver maturation and function were detected by quantitative reverse transcription–PCR analysis. The expression of hepatic maturation proteins was measured using immunofluorescence staining. Cytochrome P (CYP)450 metabolism activity and ammonia metabolism tests were used to assess liver function. H-organoids were successfully established by adding human umbilical vein endothelial cells at the beginning of the definitive endoderm stage in our 3D differentiation protocol. The gene expression of alpha-1 antitrypsin, carbamoyl–phosphate synthase 1, and apolipoprotein E, which represent liver maturation state and function, was higher in H-organoids than non-organoid 3D-HLCs. H-organoids possessed higher CYP3A4 metabolism activity and comparable ammonia metabolism capacity than 3D-HLCs. Moreover, although H-organoids expressed human leukocyte antigen class I, they expressed little human leukocyte antigen class II, cluster of differentiation (CD)40, CD80, CD86, and programmed cell death ligand 1, suggesting their immunogenicity properties were not significantly upregulated during differentiation from ADSCs. In conclusion, we successfully established an H-organoid model with higher liver-like functionality than previously established 3D-HLCs and comparable immunogenicity to ADSCs.journal articl
Morphological Evaluation of Lumbar Facet Joints in Professional Baseball Players
Get PDFBackground: Many professional baseball players experience low back pain, a major cause of which is lumbar facet joint arthropathy.
Purpose: To evaluate the relationship between the dominant hand side and facet joint morphology in baseball movement.
Study Design: Cross-sectional study; Level of evidence, 3.
Methods: Participants were 25 Japanese professional baseball players (11 pitchers and 14 fielders) with low back pain and lower limb symptoms. Player age, hand dominance, and length of professional playing experience were recorded, and the lateral diameter of all lumbar facet joints was determined from the axial computed tomography scans. We defined the facet joints ipsilateral and contralateral to the dominant hand as dominant and nondominant, respectively. The nondominant-to-dominant (N/D) ratio of the lateral diameter was calculated, and differences between the pitchers and fielders were analyzed using the unpaired t test.
Results: The average player age and length of professional playing experience were 26.9 years (range, 19-37 years) and 7.2 years (range, 1-15 years), respectively. The right hand was dominant in 9 pitchers and 5 fielders, while the left hand was dominant in 2 pitchers and 9 fielders. In pitchers, the average lateral facet joint diameter on the nondominant side was significantly larger than on the dominant side at all vertebral levels except L1 to L2 (P < .05 for all). The N/D ratio for each facet joint was 1.06 (L1-L2), 1.11(L2-L3), 1.10 (L3-L4), 1.12 (L4-L5), and 1.12 (L5-S1). In fielders, the average lateral facet joint diameter on the dominant side was significantly larger than on the nondominant side at L3 to L4 (P < .05), with N/D ratios of 0.98 (L1-L2), 0.96 (L2-L3), 0.94 (L3-L4), 0.97 (L4-L5), and 0.98 (L5-S1). The N/D ratio was significantly larger in pitchers than in fielders at all levels (P < .05 for all).
Conclusion: The facet joints of professional baseball players were enlarged asymmetrically, with different tendencies observed between pitchers and fielders. Although pitching and batting are movements that transmit the rotation from the lower limbs to the upper limbs, the effects of rotation and lateral flexion were associated significantly with facet joint hypertrophy.journal articl