Search Results (56)

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease linked to fibrosis and hepatocellular carcinoma (HCC). Gut-derived lipopolysaccharide (LPS) promotes hepatic inflammation, fibrosis, and angiogenesis through toll-like receptor 4 (TLR4) signaling. This study examined the effects of rifaximin, a non-absorbable, gut-targeted antibiotic, on MASH-related liver fibrosis and early hepatocarcinogenesis, with a focus on the LPS–epiregulin–IL-8–angiogenesis axis.MASH was induced in Fischer 344 rats using a choline-deficient, L-amino acid-defined high-fat diet (CDAHFD). Rifaximin (30 mg/kg/day) was orally administered for 12 weeks. Liver histology, gene expression, intestinal permeability, LPS levels, and angiogenic markers were evaluated. Rifaximin reduced hepatic inflammation, fibrosis, hydroxyproline content, and fibrogenic gene expression. The number and size of GST-P-positive preneoplastic lesions and proliferation-related genes were decreased. Portal LPS levels and Kupffer cell activation declined, with downregulation of Lbp, Cd14, Tlr4, and inflammatory cytokines. Rifaximin decreased hepatic epiregulin and IL-8 expression, attenuated CD34-positive neovascularization, and suppressed proangiogenic gene expression, accompanied by improved intestinal barrier function and reduced gut permeability. Rifaximin mitigates MASH progression by restoring gut barrier integrity, limiting LPS translocation, and inhibiting fibrogenic and angiogenic pathways. These results suggest its potential as a chemopreventive agent in MASH-related hepatocarcinogenesis. Full article

Cisplatin (cis-diamminedichloro-platinum; CDDP) is a chemotherapeutic agent that frequently induces peripheral neuropathy characterized by mechanical allodynia. Herein, we aimed to determine the effects of valproic acid (VPA) on cisplatin-induced mechanical allodynia in rats and elucidate the underlying mechanisms. A single administration of VPA (150 mg/kg) transiently suppressed CDDP-induced mechanical allodynia, correlating with serum VPA concentrations. Repeated VPA administration before or after the onset of CDDP-induced mechanical allodynia significantly attenuated allodynia even after VPA discontinuation, suggesting fundamental treatment potential. Mechanistically, CDDP increased the expression of neurokinin 1 receptor (NK1R) mRNA in the dorsal horn of the spinal cord, and this increased expression was suppressed by repeated VPA administration. Treatment with an NK1R antagonist alleviated CDDP-induced mechanical allodynia, indicating the involvement of NK1R in allodynia. In vitro assays revealed that VPA did not affect the cytotoxicity of CDDP in Walker 256 cells, suggesting that VPA does not interfere with the antitumor activity of CDDP. Overall, repeated VPA administration may fundamentally ameliorate CDDP-induced peripheral neuropathy by suppressing the CDDP-induced increased NK1R expression without compromising the antitumor effects of CDDP. These findings provide insights into the potential use of VPA as a therapeutic agent for managing CDDP-induced peripheral neuropathy. Full article

Covert hepatic encephalopathy (CHE) can worsen the quality of life and prognosis of patients with cirrhosis. We analyzed the risk factors of CHE and identified patients at high risk for overt hepatic encephalopathy (HE) who would benefit from therapeutic interventions. We included 145 patients without a history of or treatment for overt HE. Patients were divided into the CHE and no-CHE groups (n = 91 and 54, respectively). CHE had a score above the age-based cutoff value of one of the neuropsychological tests, such as the Stroop and number connection tests. CHE prevalence was 62.8% (n = 91). Compared with the no-CHE group, the CHE group had significantly lower serum zinc and albumin levels. Multiple logistic regression analysis identified serum zinc levels at a cutoff value of 74 µg/dL. Subclinical zinc deficiency showed a diagnostic performance of 55.6% sensitivity and 81.5% specificity for CHE. Blood ammonia levels and liver functional reserves were not predictive of CHE. Compared with patients with zinc levels < 74 µg/dL (n = 102), those with ≥74 µg/dL (n = 43) had significantly lower CHE prevalence and better hepatic functional reserve. Subclinical zinc deficiency was associated with CHE occurrence in patients with cirrhosis without a history of or treatment for overt HE. Measurement of zinc levels facilitates early detection of CHE by neuropsychological testing. Full article

This review is focused on FC-BENTEN, an advanced synchrotron X-ray experimental database developed at SPring-8 with support from Japan’s New Energy and Industrial Technology Development Organization (NEDO). Designed to advance polymer electrolyte fuel cells (PEFCs) research, FC-BENTEN addresses challenges in improving efficiency, durability, and cost-effectiveness through data-driven approaches informed by materials informatics (MI). Through standardization of protocols for sample preparation, data acquisition, analysis, and formatting, the database ensures high-quality, reproducible data essential for reliable scientific outcomes. FC-BENTEN streamlines metadata creation using automated processes and template-based tools, enhancing data management, accessibility, and interoperability. Security measures include two-factor authentication, safeguarding sensitive information and maintaining controlled user access. Planned integration with MI platforms will broaden data cross-referencing capabilities, facilitate PEFC applications expansion, and guide future research. This review discusses FC-BENTEN’s architectural framework, metadata standardization efforts, and role in advancing PEFC research through a high-throughput experimental workflow. It illustrates how data-driven methods and standardized practices contribute to innovation, underscoring databases’ potential to accelerate next-generation PEFC technologies development. Full article

Fuchs endothelial corneal dystrophy (FECD) is a progressive disorder characterized by endothelial cell loss and excessive extracellular matrix (ECM) accumulation leading to corneal dysfunction. Emricasan, a pan-caspase inhibitor, was investigated for its therapeutic potential in suppressing these pathological changes. Patient-derived FECD cells and stress-induced cell models were treated with emricasan to assess its effects on apoptosis and ECM production. Caspase-specific knockdown experiments were performed to identify key mediators. Col8a2^Q455K/Q455K mice, model mice of early-onset FECD, received twice-daily administration of 0.1% emricasan eye drops from 8 to 28 weeks of age. Endothelial cell density, hexagonality, cell size variation, and guttae area were evaluated by contact specular microscopy, while transcriptomic changes were analyzed via RNA sequencing. Emricasan effectively reduced apoptosis and ECM production in vitro by selectively inhibiting caspase-7 without affecting canonical TGF-β signaling. In vivo, emricasan-treated mice exhibited significantly higher endothelial cell density, improved hexagonality, and reduced variation in cell size compared with controls. Transcriptome analysis revealed distinct gene expression changes in the corneal endothelium following emricasan treatment. These findings suggest that emricasan exerts dual protective effects by inhibiting caspase-7-mediated ECM accumulation and broadly suppressing apoptosis, highlighting its potential as a pharmacological therapy for FECD. Full article

Atopic dermatitis (AD) is characterized by chronic inflammation, barrier dysfunction, and pruritus, exacerbated by external stimuli, such as scratching. This study investigates the role of extracellular adenosine triphosphate (ATP) in the pathophysiology of AD and assesses the therapeutic potential of clodronate, an ATP release inhibitor. Our research demonstrates that extracellular ATP impairs skin barrier function by reducing the filaggrin expression in the keratinocytes, a critical protein for barrier integrity. Furthermore, ATP release, triggered by IL-4 and mechanical stimuli, amplifies inflammation by promoting cytokine and chemokine production by the immune cells. Clodronate, by inhibiting ATP release, restores the filaggrin levels in the keratinocytes, reduces TARC production in the dendritic cells, and alleviates AD symptoms in a mouse model. These findings suggest that targeting extracellular ATP could offer a novel therapeutic approach to improving skin barrier function and reducing inflammation in AD. Future studies should explore the long-term efficacy and safety of ATP-targeted therapies in clinical settings. Full article

Polystyrene (PS) is widely used because of its transparency, mechanical strength, and ease of production. With rising health concerns, antibacterial PS is increasingly sought after, but few polymer-based antibacterial agents have been prepared to date. In this study, polystyrene was synthesized using a cationic radical initiator, 2,2′-azobis-[2-(1,3-dimethyl-4,5-dihydro-1H-imidazol-3-ium-2-yl)] propane triflate (ADIP), and evaluated as an antibacterial additive. The PS polymerized with ADIP (ADIP-PS) was prepared with number-average molecular weights (M_n) from 15,000 to 40,000. Further, blending 5–10% ADIP-PS with an M_n of 23,000 into general-purpose polystyrene (GPPS) provided antibacterial activity against Staphylococcus aureus while maintaining the transparency and strength of GPPS. Surface analysis revealed hydrophilic properties and exposed cationic groups, as confirmed by contact angle measurement and anionic dye titration, respectively. In addition, the antibacterial activity increased with higher cationic group concentrations, particularly at lower molecular weights. This method presents a promising approach to introducing antibacterial properties to PS products. Full article

Vegetation coverage is a crucial parameter in agriculture, as it offers essential insight into crop growth and health conditions. The spatial resolution of spaceborne sensors is limited, hindering the precise measurement of vegetation coverage. Consequently, fine-resolution ground observation data are indispensable for establishing correlations between remotely sensed reflectance and plant coverage. We estimated rice plant coverage per pixel using time-series Sentinel-2 Multispectral Instrument (MSI) data, enabling the monitoring of rice growth conditions over a wide area. Coverage was calculated using unmanned aerial vehicle (UAV) data with a spatial resolution of 3 cm with the spectral unmixing method. Coverage maps were generated every 2–3 weeks throughout the rice-growing season. Subsequently, crop growth was estimated at 10 m resolution through multiple linear regression utilizing Sentinel-2 MSI reflectance data and coverage maps. In this process, a geometric registration of MSI and UAV data was conducted to improve their spatial agreement. The coefficients of determination (R²) of the multiple linear regression models were 0.92 and 0.94 for the Level-1C and Level-2A products of Sentinel-2 MSI, respectively. The root mean square errors of estimated rice plant coverage were 10.77% and 9.34%, respectively. This study highlights the promise of satellite time-series models for accurate estimation of rice plant coverage. Full article

Aim: Transarterial chemoembolization (TACE) combined with lenvatinib, employing a 4-day lenvatinib administration followed by TACE without an interval (short-term LEN-TACE), was performed for hepatocellular carcinoma (HCC). The aim was to assess tumor hemodynamics following the 4-day lenvatinib and to evaluate the treatment outcomes after the short-term LEN-TACE. Methods: 25 unresectable HCC patients received this combined therapy. Lenvatinib (4–12 mg) was administrated for 4 days prior to TACE. Perfusion CT scans were obtained before and after the lenvatinib administration. Either cTACE (76%) or DEB-TACE (24%) were performed. Results: intra-tumor blood flow significantly decreased after the 4-day lenvatinib (p < 0.05). The TACE procedure was successful with no severe adverse events in all patients. The overall complete response (CR) rate was 75% (cTACE 84%, DEB-TACE 40%). The lipiodol-washout ratio between 1 week and 4 months after cTACE correlated with the arterial flow reduction ratio by lenvatinib prior to TACE (r = −0.55). The 12-month progression-free survival (PFS) rate was 75.0%. Conclusions: The short-term LEN-TACE is feasible and safe, demonstrating promising outcomes with a high CR ratio, contributing to lipiodol retention in the tumor after cTACE, and extended PFS. To confirm the advantages of this treatment protocol, a prospective clinical trial is mandatory. Full article

DECIGO is a future Japanese project for the detection of gravitational waves in space. To conduct various scientific missions, including the verification of cosmic inflation through the detection of primordial gravitational waves as the main objective, DECIGO is designed to have high sensitivity in the frequency band from $0.1$ to 10 Hz, with arms of length 1000 km. Furthermore, the use of the Fabry-Perotcavity in these arms has been established for the DECIGO project. In this paper, we scrutinize the significance of the Fabry-Perot cavity for promoting this project, with a focus on the possibility of observing gravitational waves from cosmic inflation and binary compact star systems as indicators. The results show that using the Fabry-Perot cavity is extremely beneficial for detecting them, and it is anticipated to enable the opening of a new window in gravitational wave astronomy. Full article

Portal vein thrombosis (PVT), one of the most prevalent hepatic vascular conditions in patients with liver cirrhosis (LC), is associated with high mortality rates. An imbalance between a disintegrin-like metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS-13) enzyme and von Willebrand factor (VWF) is responsible for hypercoagulability, including spontaneous thrombus formation in blood vessels. Herein, we aimed to identify potential prognostic and diagnostic biomarkers in Japanese patients with LC and PVT. In total, 345 patients were divided into two groups: 40 patients who developed PVT (PVT group) and 305 who did not develop PVT (NPVT group). Among the 345 patients with LC, 81% (279/345) were deemed ineligible due to the presence of preventive comorbidities, active or recent malignancies, and organ dysfunction. The remaining 66 patients were divided into two groups: the PVT group (n = 33) and the NPVT group (n = 33). Plasma ADAMTS-13 activity (ADAMTS-13:AC) and the vWF antigen (VWF:Ag) were measured using enzyme-linked immunosorbent assays. Contrast-enhanced, three-dimensional helical computed tomography (CT) was used to detect and characterize PVT. ADAMTS-13:AC was significantly lower in the PVT group than in the NPVT group. No significant differences in plasma vWF:Ag or liver stiffness were observed between the two groups. ADAMTS-13:AC of <18.8 was an independent risk factor for PVT on multivariate analyses (odds ratio: 1.67, 95% confidence interval: 1.21–3.00, p < 0.002). The receiver operating characteristic analysis of ADAMTS-13:AC revealed an area under the curve of 0.913 in PVT detection. Patients with PVT having ADAMTS-13:AC ≥18.8 (n = 17) had higher albumin levels and better prognoses than those with ADAMTS-13:AC <18.8 (n = 16). No significant correlations of ADAMTS-13:AC levels with either fibrin degradation product or D-dimer levels were observed. ADAMTS-13:AC levels could be potential diagnostic and prognostic biomarkers for PVT in Japanese patients with LC. Full article

Foreign body reactions (FBRs) are inadvertently observed in invading or artificially embedded materials, triggering inflammation and subsequent fibrotic processes to occur in situ. Here, we assessed the spatiotemporal formation of connective tissue around implanted materials to establish a technique using connective tissue formed by FBRs as xenografts. An acrylic resin implant, comprising a columnar inner rod and a tubular outer cylinder (OC) with several slits, was embedded in adult dairy cows. Tissues formed in the inner rod and OC groups were histologically analyzed at weeks 2, 4, 8, and 12. Edematous tissues with non-collagenous fibers formed for 2 weeks and showed increased cellularity after 4 weeks. The weight, thickness, amounts of total protein, collagen, DNA, and quantitative scores of α-smooth muscle actin-positive myofibroblasts or elastic fibers notably increased after 8 weeks, with condensed collagen fibers showing orientation. Inflammatory cells were primarily localized in tissues close to the OC, and their numbers increased, with the count of CD204+ cells peaking at 8 weeks and declining at 12 weeks. The count of Ki67+ proliferating cells slightly increased in tissues close to the OC; however, the number and lumen of CD31+ vessels increased. These results may help understand FBR-related tissue remodeling. Full article

A total of 137 HCC patients treated with atezolizumab plus bevacizumab from October 2020 to September 2022 were enrolled. The median overall survival (OS) and progression-free survival (PFS) from the beginning of atezolizumab plus bevacizumab were 21.1 months (range, 18.8 months–not reached) and 10.5 months (range, 8.2–12.1 months), respectively. Fifty patients were diagnosed with progressive disease after atezolizumab plus bevacizumab. Of this group, 24 patients were administered lenvatinib, and the median OS and PFS from the beginning of lenvatinib were 15.3 months (range, 10.5 months–not reached) and 4.0 months (range, 2.5–6.4 months), respectively. The objective response rates based on the response evaluation criteria in solid tumors (RECISTs) criteria version 1.1 and modified RECISTs were 33.3% and 54.2%, respectively. There was no significant difference in the median serum alpha-fetoprotein level between before and after lenvatinib. In the multivariate analysis, Child–Pugh class A (hazard ratio 0.02, 95% confidence interval (CI) 0.02–0.76, p = 0.02) and intrahepatic tumor occupancy rate < 50% (hazard ratio < 0.01, 95% CI 0.003–0.35, p < 0.01) were the significant factors for OS. There were some frequent adverse events (AEs) in patients treated with lenvatinib such as hypertension, fatigue, anorexia, proteinuria, and so on, but none directly caused death. In conclusion, lenvatinib after atezolizumab plus bevacizumab for unresectable HCC should be considered an effective treatment option. Full article

Quantum locking using optical spring and homodyne detection has been devised to reduce the quantum noise that limits the sensitivity of the DECIGO, a space-based gravitational-wave antenna in the frequency band around 0.1 Hz for the detection of primordial gravitational waves. The reduction in the upper limit of energy density ${\mathsf{\Omega }}_{\mathrm{GW}}$ from $2\times {10}^{-15}$ to $1\times {10}^{-16}$, as inferred from recent observations, necessitates improved sensitivity in the DECIGO to meet its primary science goals. To accurately evaluate the effectiveness of this method, this paper considers a detection mechanism that takes into account the influence of vacuum fluctuations on homodyne detection. In addition, an advanced signal processing method is devised to efficiently utilize signals from each photodetector, and design parameters for this configuration are optimized for the quantum noise. Our results show that this method is effective in reducing quantum noise, despite the detrimental impact of vacuum fluctuations on its sensitivity. Full article

Compton scattering imaging with intense, high-energy synchrotron X-rays allows us to visualize a light element substance in an operating electrochemical device. In this paper, we report the first experiment of Compton scattering imaging (CSI) on an operating polymer electrolyte fuel cell (PEFC). The novelty of the CSI technique is a non-destructive direct observation of cross-sectional images with a sensitivity to light elements and a capability of simultaneous measurements with fluorescent X-rays of heavy elements. Analyses of the observed images provide the cross-sectional distribution of generated liquid water and its current density dependency. The results show that the amount of generated water increases in the vicinity of the cathode catalyst layer at current densities ranging from 100 to 500 mA/cm², while it remains constant or slightly decreases from 500 to 900 mA/cm². In both the gas diffusion layer and the channel, liquid water is observed near the channel and rib interface above 500 mA/cm², indicating the formation of a liquid water flow path. In addition, simultaneous measurements of fluorescent Pt-Ka X-rays reveal a significant correlation between the generated liquid water and Pt catalysts, using the Pearson correlation coefficient. The result shows that water is dispersed in the catalyst layer without any correlation with the amount of Pt catalysts at low current densities, but water tends to be distributed in the Pt-rich areas at high current densities. This study demonstrates that Compton scattering imaging is one of the unique techniques to characterize the behavior of generated liquid water in an operating PEFC. Full article