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In-vacuum undulators (IVUs), which have become an essential tool in synchrotron radiation facilities, have two technical challenges toward further advancement: one is a strong attractive force between top and bottom magnetic arrays, and the other is a stringent requirement on magnetic materials to avoid demagnetization. The former imposes a complicated design on mechanical and vacuum structures, while the latter limits the possibility of using high-performance permanent magnets. To solve these issues, a number of technical developments have been made, such as force cancellation and modularization of magnetic arrays, and enhancement of resistance against demagnetization by means of a special magnetic circuit. The performance of a new IVU built upon these technologies has revealed their effectiveness for constructing high-performance IVUs in a cost-effective manner.
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Reducing recurrence following radical resection of colon cancer without over- or under-treatment remains a challenge. Postoperative adjuvant chemotherapy (Adj) is currently administered based solely on pathological tumor, node, and metastasis (TNM) stage. However, prognosis can vary significantly among patients with the same disease stage. Therefore, novel classification systems in addition to the TNM are necessary to inform decision-making regarding postoperative treatment strategies, especially stage II and III disease, and to minimize overtreatment and undertreatment with Adj. We developed a prognostic prediction system for colorectal cancer by using a combined convolutional neural network (CNN) and support vector machine (SVM) approach to extract features from hematoxyling and eosin staining (HE) images. We combined the TNM and our AI-based classification system into a TNM-AI (mTNM-AI) classification system with high discriminative power for recurrence-free survival (RFS). Furthermore, the cancer cell population recognized by this system as low risk of recurrence exhibited the mutational signature SBS87 as a genetic phenotype. The novel AI-based classification system developed here is expected to play an important role in prognostic prediction and personalized treatment selection in oncology.
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BACKGROUND AIMS: Haploidentical hematopoietic stem cell transplantation (haplo-HCT) is an appropriate option when an HLA-matched related or unrelated donor is not available. Haplo-HCT using post-transplant cyclophosphamide (PTCy) is being increasingly performed worldwide due to its effective suppression of GVHD and its safety. METHODS: We conducted a large nationwide cohort study to retrospectively analyze 366 patients with acute myeloid leukemia undergoing haplo-HCT with PTCy between 2010 and 2019 and to identify prognostic factors. RESULTS: A multivariate Cox analysis revealed that an older recipient age (≥60 years), a male donor to a male recipient, a cytomegalovirus IgG-negative donor to a cytomegalovirus IgG-positive recipient, a poor cytogenetic risk, a noncomplete remission status at the time of transplantation, and a history of HCT were independently associated with worse overall survival (OS). Based on each hazard ratio, these factors were scored (1-2 points) and stratified by their total score into three groups: favorable (0-1 points), intermediate (2-3 points), and poor (4 points or more) groups, and 2-year OS rates were 79.9%, 49.2%, and 25.1%, respectively (P < 0.001). CONCLUSIONS: The present study revealed significant prognostic factors in haplo-HCT with PTCy, and a scoring system based on these factors may be used to predict outcomes.
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Ciclofosfamida , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Transplante Haploidêntico , Humanos , Masculino , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidade , Feminino , Pessoa de Meia-Idade , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante Haploidêntico/métodos , Adulto , Prognóstico , Estudos Retrospectivos , Idoso , Adolescente , Doença Enxerto-Hospedeiro/etiologia , Adulto JovemRESUMO
BACKGROUND: Although many studies have explored the correlation between quality of life and survival, none have reported this relationship for specific cancers assessed at distinct time points. This meta-analysis aimed to investigate the impact of pretreatment Global Quality of Life (QOL) and functioning QOL, including physical, social, role, emotional, and cognitive QOLs, on mortality risk in patients with lung cancer. METHODS: A literature search was conducted across the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and PubMed databases for articles published between their inception and December 2022. Subsequently, 11 studies were selected based on predefined eligibility criteria to investigate the relationship between pretreatment QOLs and mortality risk in patients with lung cancer. RESULTS: Pretreatment global, physical, social, role, and emotional QOLs were significantly associated with mortality risk as follows: Global QOL (hazard ratio [HR] = 1.08 95% confidence interval [CI] = 1.03-1.13); Physical QOL (HR = 1.04 95% CI = 1.02-1.05); Social QOL (HR = 1.02 95% CI = 1.01-1.03; Role QOL (HR = 1.01 95% CI = 1.01-1.02); Emotional QOL (HR = 1.01 95% CI = 1.00-1.03). CONCLUSIONS: These findings underscore the importance of early QOL assessment after diagnosis as well as early provision of physical, social, and psychological support accommodating each patient's demands. TRIAL REGISTRATION: The International Prospective Register of Systematic Reviews registration number CRD42023398206, Registered on February 20, 2023.
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Neoplasias Pulmonares , Humanos , Qualidade de Vida , Ansiedade , Depressão , EmoçõesRESUMO
The lymphatic system (or lymphatics) consists of lymphoid organs and lymphatic vessels. Despite the numerous previously published studies describing conditions related to perirenal and intrarenal lymphoid organs in the radiology literature, the radiologic findings of conditions related to intrarenal and perirenal lymphatic vessels have been scarcely reported. In the renal cortex, interlobular lymphatic capillaries do not have valves; therefore, lymph can travel along the primary route toward the hilum, as well as toward the capsular lymphatic plexus. These two lymphatic pathways can be opacified by contrast medium via pyelolymphatic backflow at CT urography, which reflects urinary contrast agent leakage into perirenal lymphatic vessels via forniceal rupture. Pyelolymphatic backflow toward the renal hilum should be distinguished from urinary leakage due to urinary injury. Delayed subcapsular contrast material retention via pyelolymphatic backflow, appearing as hyperattenuating subcapsular foci on CT images, mimics other subcapsular cystic diseases. In contrast to renal parapelvic cysts originating from the renal parenchyma, renal peripelvic cysts are known to be of lymphatic origin. Congenital renal lymphangiectasia is mainly seen in children and assessed and followed up at imaging. Several lymphatic conditions, including lymphatic leakage as an early complication and acquired renal lymphangiectasia as a late complication, are sometimes identified at imaging follow-up of kidney transplant. Lymphangiographic contrast material accumulation in the renal hilar lymphatic vessels is characteristic of chylo-urinary fistula. Chyluria appears as a fat-layering fluid-fluid level in the urinary bladder or upper urinary tract. Recognition of the anatomic pathway of tumor spread via lymphatic vessels at imaging is of clinical importance for accurate management at oncologic imaging. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.
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Cistos , Neoplasias Renais , Vasos Linfáticos , Criança , Humanos , Meios de Contraste , Sistema Linfático , Vasos Linfáticos/diagnóstico por imagemRESUMO
PURPOSE: This systematic review and meta-analysis aimed to examine the impact of global quality of life (QOL) on mortality risk in patients with cancer, considering cancer type and timepoint of QOL assessment. METHODS: A systematic search was conducted using Cumulated Index to Nursing and Allied Health Literature, PubMed/MEDLINE, and Scopus databases from inception to December 2022. Observational studies that assessed QOL and examined mortality risk in patients with cancer were extracted. Subgroup analyses were performed for cancer types and timepoints of QOL assessment. RESULTS: Overall, global QOL was significantly associated with mortality risk (hazard ratio: 1.06, 95% confidence interval: 1.05-1.07; p < 0.00001). A subgroup analysis based on cancer type demonstrated that lung, head and neck, breast, esophagus, colon, prostate, hematologic, liver, gynecologic, stomach, brain, bladder, bone and soft tissue, and mixed type cancers were significantly associated with mortality risk; however, melanoma and pancreatic cancer were not significantly associated with mortality risk. Additionally, global QOL was associated with mortality risk at all timepoints (pretreatment, posttreatment, and palliative phase); pretreatment QOL had the largest impact, followed by posttreatment QOL. CONCLUSION: These findings provide evidence that QOL is associated with mortality risk in patients with cancer at any timepoint. These results indicate the importance of evaluating the QOL and supportive interventions to improve QOL in any phase.
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(-)-Epigallocatechin-3-gallate (EGCg), a major constituent of green tea extract, is well-known to exhibit many beneficial actions for human health by interacting with numerous proteins. In this study we identified synaptic vesicle membrane protein VAT-1 homolog (VAT1) as a novel EGCg-binding protein in human neuroglioma cell extracts using a magnetic pull-down assay and LC-tandem mass spectrometry. We prepared recombinant human VAT1 and analyzed its direct binding to EGCg and its alkylated derivatives using surface plasmon resonance. For EGCg and the derivative NUP-15, we measured an association constant of 0.02-0.85 ×103 M-1s-1 and a dissociation constant of nearly 8 × 10-4 s-1. The affinity Km(affinity) of their binding to VAT1 was in the 10-20 µM range and comparable with that of other EGCg-binding proteins reported previously. Based on the common structure of the compounds, VAT1 appeared to recognize a catechol or pyrogallol moiety around the B-, C- and G-rings of EGCg. Next, we examined whether VAT1 mediates the effects of EGCg and NUP-15 on expression of neprilysin (NEP). Treatments of mock cells with these compounds upregulated NEP, as observed previously, whereas no effect was observed in the VAT1-overexpressing cells, indicating that VAT1 prevented the effects of EGCg or NUP-15 by binding to and inactivating them in the cells overexpressing VAT1. Further investigation is required to determine the biological significance of the VAT1-EGCg interaction.
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Catequina , Proteínas de Transporte Vesicular , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Vesículas Sinápticas/metabolismo , Chá/química , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismoRESUMO
This retrospective study investigated whether necrotic lesions detected on a computed tomography (CT) scan are more regressive than non-necrotic lesions after methotrexate withdrawal in patients pathologically diagnosed with methotrexate-associated lymphoproliferative disorders (MTX-LPD). In total, 89 lesions extracted from 24 patients on CT scans were included in the analysis. All patients had been evaluated for the presence of necrosis within lesions via CT scan upon first suspicion of MTX-LPD (baseline CT scan). The percentage lesion size reduction between the baseline and initial follow-up CT scan was calculated. The association between necrosis within lesions and size changes was estimated via linear regression analyses using both crude and adjusted models. Necrosis was significantly more common in extranodal lesions (27 out of 30 lesions, 90%) than in nodal lesions (9 out of 59 lesions, 15%, p<0.001). In the crude model, the regression of necrotic lesions was 58.5% greater than that of non-necrotic lesions; the difference was statistically significant (p<0.001). Additionally, the longest diameter of necrotic lesions at the baseline CT scan was significantly greater than that of non-necrotic lesions (p<0.001). Based on the adjusted model, necrotic lesions showed 49.3% greater regression than non-necrotic lesions (p=0.017). Necrosis detected on a CT scan was found to be an independent predictor of regression after MTX withdrawal in patients with MTX-LPD.
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Artrite Reumatoide , Transtornos Linfoproliferativos , Humanos , Metotrexato/efeitos adversos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/diagnóstico , NecroseRESUMO
This systematic review and meta-analysis investigated the impact of quality of life (QoL) on mortality risk in patients with esophageal cancer. A literature search was conducted using the CINAHL, PubMed/MEDLINE, and Scopus databases for articles published from inception to December 2022. Observational studies that examined the association between QoL and mortality risk in patients with esophageal cancer were included. Subgroup analyses were performed for time points of QoL assessment and for types of treatment. Seven studies were included in the final analysis. Overall, global QoL was significantly associated with mortality risk (hazard ratio 1.02, 95% confidence interval 1.01-1.04; p < 0.00004). Among the QoL subscales of QoL, physical, emotional, role, cognitive, and social QoL were significantly associated with mortality risk. A subgroup analysis by timepoints of QoL assessment demonstrated that pre- and posttreatment global and physical, pretreatment role, and posttreatment cognitive QoL were significantly associated with mortality risk. Moreover, another subgroup analysis by types of treatment demonstrated that the role QoL in patients with surgery, and the global, physical, role, and social QoL in those with other treatments were significantly associated with mortality risk. These findings indicate that the assessment of QoL in patients with esophageal cancer before and after treatment not only provides information on patients' condition at the time of treatment but may also serve as an outcome for predicting life expectancy. Therefore, it is important to conduct regular QoL assessments and take a proactive approach to improve QoL based on the results of these assessments.
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Neoplasias Esofágicas , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , IdosoRESUMO
Tannins are a group of polyphenols that possess the ability to precipitate proteins, causing an undesirable astringent taste by interacting with salivary peptides. This interaction deactivates the digestive enzymes; therefore, tannins are considered as plant defense substances. The health benefits of tannins and related polyphenols in foods and beverages have been demonstrated by biological and epidemiological studies; however, their metabolism in living plants and the chemical changes observed during processing of foods and medicinal herbs raises some questions. This review summarizes our studies concerning dynamic changes observed in tannins. Ellagitannins present in the young leaves of Camellia japonica and Quercus glauca undergo oxidative degradation as the leaves mature. Similar oxidative degradation is also observed in whiskey when it is kept for aging in oak barrels, and in decaying wood caused by fungi in natural forests. In contrast, ellagitannins have been observed to undergo reduction in the leaves of Carpinus, Castanopsis, and Triadica species as the leaves mature. This phenomenon of reductive metabolism in leaves enabled us to propose a new biosynthetic pathway for the most fundamental ellagitannin acyl groups, which was also supported by biomimetic synthetic studies. Polyphenols undergo dynamic changes during the process of food processing. Catechin in tea leaves undergo oxidation upon mechanical crushing to generate black tea polyphenols. Though detailed production mechanisms of catechin dimers have been elucidated, structures of thearubigins (TRs), which are complex mixtures of oligomers, remain ambiguous. Our recent studies suggested that catechin B-ring quinones couple with catechin A-rings during the process of oligomerization.
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Catequina , Taninos , Taninos/química , Taninos/metabolismo , Taninos Hidrolisáveis/química , Taninos Hidrolisáveis/metabolismo , Catequina/química , Catequina/metabolismo , Polifenóis , Chá/química , OxirreduçãoRESUMO
Recent advances in wood treatment include the use of eco-friendly coatings to improve the wood's dimensional stability and appearance. Assessing coating performance during its service life is critical for establishing a knowledge base for product optimization. Numerous approaches, including microimaging, are available for analyzing coating behavior. In addition to conventional microscopic techniques, high-resolution X-ray microtomography is a tool that provides nondestructive imaging of coatings and their substrates. In this study, we performed two-dimensional (2D) and three-dimensional (3D) visualization of tomographic reconstruction images of two coating types, spray and brush, to observe and assess the distribution of several commercial Japanese coating materials in Fagus crenata. X-ray images and plot profiles were used to determine the penetration depths and thicknesses of coatings. Each coated sample was scanned using X-ray microtomography, which allowed successful visualization and quantification of the coating penetration depth. Chemical content and concentration of the coating materials influenced penetration depth and amount.
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Fagus , Madeira , Microtomografia por Raio-X , Microtomografia por Raio-X/métodos , Madeira/química , Fagus/química , Imageamento Tridimensional/métodosRESUMO
Crop growth monitoring is essential for both crop and supply chain management. Conventional manual sampling is not feasible for assessing the spatial variability of crop growth within an entire field or across all fields. Meanwhile, UAV-based remote sensing enables the efficient and nondestructive investigation of crop growth. A variety of crop-specific training image datasets are needed to detect crops from UAV imagery using a deep learning model. Specifically, the training dataset of cabbage is limited. This data article includes annotated cabbage images in the fields to recognize cabbages using machine learning models. This dataset contains 458 images with 17,621 annotated cabbages. Image sizes are approximately 500 to 1000 pixel squares. Since these cabbage images were collected from different cultivars during the whole growing season over the years, deep learning models trained with this dataset will be able to recognize a wide variety of cabbage shapes. In the future, this dataset can be used not only in UAVs but also in land-based robot applications for crop sensing or associated plant-specific management.
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The autoxidation of tea catechins by dissolved oxygen proceeds in pH-neutral aqueous solutions, and the major products are oligomers. However, the reaction mechanisms have not been clarified. In this study, the autoxidation of (-)-epigallocatechin-3-O-gallate (1) was examined. The autoxidation with ß-cyclodextrin, which includes the A-ring of 1, significantly suppressed oligomer production and increased the formation of products generated by the oxidative cleavage of the B-ring, indicating the participation of the A-ring in the oligomerization. Further, the autoxidation of 1 in the presence of phloroglucinol, a mimic of the catechin A-ring, yielded products via the nucleophilic addition of phloroglucinol to the B-ring quinone of 1. These results indicated that the oxidative A-B ring couplings accounted for the major oligomerization mechanism.
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Catequina , Catequina/análogos & derivados , Oxirredução , Catequina/química , Estrutura Molecular , Chá/químicaRESUMO
BACKGROUND: Patients with breast cancer present with various problems that have an adverse effect on the quality of life (QOL). However, the association between the QOL and mortality among patients with breast cancer remains controversial. Therefore, this systematic review and meta-analysis aimed to determine whether QOL impacts prognosis in patients with breast cancer. METHODS: The databases of CINAHL, Scopus, and PubMed databases were searched to retrieve observational studies that assessed the QOL and mortality risk in patients with breast cancer published before December 2022. RESULTS: Among the 119,061 articles retrieved, six observational studies were included in the meta-analysis. Physical QOL (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 1.01-1.07, p = 0.003), emotional QOL (HR: 1.01, 95% CI: 1.00-1.03, p = 0.05), and role QOL (HR: 1.01, 95% CI: 1.00-1.01, p = 0.007) showed significant associations with mortality risk. In contrast, global QOL, cognitive QOL, and social QOL showed no associations with mortality risk. Subgroup analysis performed according to treatment time points revealed that the post-treatment physical QOL was associated with mortality risk. CONCLUSIONS: Physical QOL, emotional QOL, and role QOL are associated with mortality risk in patients with breast cancer. Furthermore, post-treatment physical QOL showed a more significant association with prolonged survival than pre-treatment physical QOL.
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Neoplasias da Mama , Qualidade de Vida , Humanos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/psicologia , Feminino , Prognóstico , Estudos Observacionais como AssuntoRESUMO
Noonan syndrome (NS) is a dominantly inherited genetic disorder with mutations in genes encoding components or regulators of the Rat sarcoma virus/mitogen-activated protein kinase pathway. Its diagnosis is based on characteristic features, including typical facial features, a short stature, congenital heart disease, mild developmental delay, and cryptorchidism. Patients with NS sometimes develop autoimmune diseases, such as Hashimoto's thyroiditis and, rarely, systemic lupus erythematosus (SLE). We herein present a 29-year-old Japanese female with NS complicated by SLE and repeated severe hypoglycaemia. The patient was diagnosed with SLE based on thrombocytopenia, nephritis, a positive antinuclear antibody titre (1:640), and a positive anti-dsDNA antibody. The patient was treated with a glucocorticoid, mycophenolate mofetil, and tacrolimus, which attenuated both SLE and hypoglycaemia. Since insulin receptor antibody levels were higher to the upper normal range and decreased after treatment, hypoglycaemia probably appeared to be attributed to type B insulin resistance syndrome. We herein present the first case of SLE in NS complicated by type B insulin resistance syndrome. Although NS is a rare disease, we need to consider the complication of autoimmune diseases, including SLE.
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Hipoglicemia , Lúpus Eritematoso Sistêmico , Síndrome de Noonan , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Feminino , Adulto , Síndrome de Noonan/complicações , Síndrome de Noonan/diagnóstico , Hipoglicemia/etiologia , Hipoglicemia/diagnóstico , Resistência à Insulina , RecidivaRESUMO
Atezolizumab is an immune checkpoint inhibitor specific for the programmed death-1 (PD-1) receptor. In this case report, we describe two cases of oral mucositis that developed following the initiation of a systemic chemotherapy regimen comprising atezolizumab and bevacizumab for recurrent hepatocellular carcinoma. After 2 or 3 cycles of treatment, each patient presented with mucosal ulcers in the mouth, oral pain, difficulty in speech and oral intake, and both were admitted to our hospital for management. Following rule out of other conditions such as pharyngeal ulcers, herpetic mucositis, denture or oral trauma, or necrotizing mucositis, both patients were diagnosed with oral mucositis as a severe immune-related adverse event. Oral candidiasis was observed in both cases and should be considered a risk factor for the development of oral mucositis. Chemotherapy was discontinued and treatment with prednisolone was started, along with supportive care. The oral mucositis improved, and prednisolone was gradually reduced; however, in one patient, discontinuation of chemotherapy led to a recurrence of hepatocellular carcinoma. The other patient was lost to follow-up. In patients with risk factors, attention must be paid to the development of oral mucositis during immune checkpoint inhibitor treatment.
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Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Estomatite , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Estomatite/induzido quimicamente , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Bevacizumab/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Idoso , Feminino , Prednisolona/uso terapêutico , Prednisolona/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversosRESUMO
BACKGROUND/AIM: This study aimed to investigate the role of transient receptor potential vanilloid 2 (TRPV2) in a mouse model with non-alcoholic steatohepatitis (NASH) and to examine the effects of tranilast on TRPV2 and fibrosis-related cytokines. MATERIALS AND METHODS: C57BL/6N mice were fed a Gubra-Amylin NASH (GAN) diet for 20 weeks to induce NASH. The tranilast groups received oral administration of tranilast at doses of 300, 400 and 500 mg/kg/day, five days per week for 20 weeks, in addition to the GAN diet. The effects of tranilast were assessed based on the dosage of food intake, changes in body weight, liver weight, blood biochemical parameters, histopathological examination, and expression of TRPV2 and inflammatory cytokines. RESULTS: Hepatic expression of TRPV2 was observed in the GAN-fed NASH mouse model. The tranilast groups showed significantly suppressed increases in body and liver weights. The development of intrahepatic fat deposition and liver fibrosis, assessed histopathologically, was inhibited. Tranilast administration improved the expression of TRPV2 and inflammatory cytokines in the liver. Additionally, blood tests indicated a reduction in elevated liver enzyme levels. CONCLUSION: In GAN diet NASH models, TRPV2 was up-regulated in the liver and tranilast inhibited TRPV2 and suppressed fibrosis. Therefore, it might prevent the incidence of hepatocellular carcinoma associated with NASH.
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Modelos Animais de Doenças , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Canais de Cátion TRPV , Aumento de Peso , ortoaminobenzoatos , Animais , Canais de Cátion TRPV/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , ortoaminobenzoatos/farmacologia , Camundongos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/prevenção & controle , Aumento de Peso/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Progressão da Doença , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Citocinas/metabolismo , Canais de CálcioRESUMO
Abdominal vein replacement with synthetic tissue-engineered vascular grafts constructed from silk-based scaffold material has not been reported in middle-sized mammals. Fourteen canines that underwent caudal vena cava replacement with a silk fibroin (SF) vascular graft (15 mm long and 8 mm diameter) prepared with natural silk biocompatible thread were allocated to two groups, thin and thick SF groups, based on the graft wall thickness. The short-term patency rate and histologic reactions were compared. The patency rate at 2 weeks after replacement in the thin and thick SF groups was 50% and 88%, respectively (p = 0.04). CD31-positive endothelial cells covered the luminal surface of both groups at 4 weeks. The elastic modulus of the thick SF graft was significantly better than that of the thin SF graft (0.0210 and 0.0007 N/m2, p < 0.01). Roundness of thick SF groups (o = 0.8 mm) was better than thin SF (o = 2.0 mm). There was significant difference between the groups (p = 0.01). SF vascular grafts are a promising tissue-engineered scaffold material for abdominal venous system replacement in middle-sized mammals, with thick-walled grafts being superior to thin-walled grafts.
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Fibroínas , Animais , Cães , Células Endoteliais , Seda , Prótese Vascular , Alicerces Teciduais , MamíferosRESUMO
Cholera toxin (CT), a bacterial exotoxin composed of one A subunit (CTA) and five B subunits (CTB), functions as an immune adjuvant. CTB can induce production of interleukin-1ß (IL-1ß), a proinflammatory cytokine, in synergy with a lipopolysaccharide (LPS), from resident peritoneal macrophages (RPMs) through the pyrin and NLRP3 inflammasomes. However, how CTB or CT activates these inflammasomes in the macrophages has been unclear. Here, we clarify the roles of inositol-requiring enzyme 1 alpha (IRE1α), an endoplasmic reticulum (ER) stress sensor, in CT-induced IL-1ß production in RPMs. In RPMs, CTB is incorporated into the ER and induces ER stress responses, depending on GM1, a cell membrane ganglioside. IRE1α-deficient RPMs show a significant impairment of CT- or CTB-induced IL-1ß production, indicating that IRE1α is required for CT- or CTB-induced IL-1ß production in RPMs. This study demonstrates the critical roles of IRE1α in activation of both NLRP3 and pyrin inflammasomes in tissue-resident macrophages.