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1.
Appetite ; 192: 107078, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37898406

RESUMEN

This study aimed to investigate the influence of smooth texture preference on smoothness perception. An online questionnaire (Study 1, n = 464) and a sensory evaluation test (Study 2, n = 65) were administered to Japanese elderly participants (65-74 years), with common Japanese confectionery (Daifuku) as test foods. Through the online questionnaire, four distinct texture preference groups were formed based on the factors of preference for smoothness and firmness of the inner bean paste layer. Analysis of the food preference scale for imbalanced diet (FPSID) revealed that smooth-texture likers were more likely to be picky eaters than firm-texture likers. Furthermore, high (HiSm) and low smoothness preference groups (LoSm) were selected for the food sensory evaluation test to compare perceived textures (smoothness and firmness). Only the HiSm group exhibited a positive association between perceived smoothness and overall texture liking, perceiving smoothness significantly more intense than the LoSm group in situations where overall texture liking was high. This finding indicates that smooth texture preference does not act independently but rather interacts with food texture matching to affect perception. Our findings suggest that when food texture aligns with individuals' preferences, it elicits hedonic emotions and dynamically enhances food texture perception. This preference-involved perceptual process may contribute to the development of more explicit texture preferences.


Asunto(s)
Gusto , Percepción del Tacto , Humanos , Anciano , Alimentos , Preferencias Alimentarias/psicología , Dieta
2.
Biochem Biophys Res Commun ; 642: 192-200, 2023 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-36586187

RESUMEN

Transforming growth factor (TGF)-ß/Smad pathway is implicated in the pathogenesis of liver fibrosis, a condition characterized by excessive deposition of extracellular matrix (ECM) proteins such as collagen in response to chronic inflammation. It has been reported that ceramide regulates collagen production through TGF-ß/Smad pathway activation. In this study, we examined whether miglustat, an inhibitor of glucosylceramide synthase, can suppress liver fibrosis by reducing TGF-ß/Smad pathway activity. Human hepatic stellate cells (HHSteCs) were cultured with TGF-ß and multiple miglustat concentrations to examine dose-dependent effects on the expression levels of ECM-related genes and Smad proteins. To evaluate the efficacy of miglustat for fibrosis mitigation, C57BL/6 mice were treated with carbon tetrachloride (CCl4) for 4 weeks to induce liver fibrosis, followed by combined CCl4 plus miglustat for a further 2 weeks. To examine if miglustat can also prevent fibrosis, mice were treated with CCl4 for 2 weeks, followed by CCl4 plus miglustat for 2 weeks. Miglustat dose-dependently downregulated expression of α-smooth muscle actin and ECM components in TGF-ß-treated HHSteCs. Both phosphorylation and nuclear translocation of Smad2 and Smad3 were also suppressed by miglustat treatment. Sirius-Red staining and hydroxyproline assays of model mouse liver samples revealed that miglustat reduced fibrosis, an effect accompanied by decreased expression of ECM. Our findings suggest that miglustat can both prevent and reverse liver fibrosis by inhibiting TGF-ß/Smad pathway.


Asunto(s)
Factor de Crecimiento Transformador beta1 , Factor de Crecimiento Transformador beta , Animales , Humanos , Ratones , Tetracloruro de Carbono/farmacología , Células Estrelladas Hepáticas/metabolismo , Hígado/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Ratones Endogámicos C57BL , Transducción de Señal , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo
3.
Medicina (Kaunas) ; 59(4)2023 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-37109751

RESUMEN

Background and objectives: The safety of electrohydraulic lithotripsy (EHL) in older adults remains unclear. We aimed to investigate the efficacy and safety of EHL using peroral cholangioscopy (POCS) under endoscopic retrograde cholangiopancreatography (ERCP) guidance in older adults aged ≥80 years. Materials and Methods: This retrospective clinical study was conducted at a single center. Fifty patients with common bile duct stones who underwent EHL using POCS under ERCP guidance at our institution, between April 2017 and September 2022, were enrolled in this study. The eligible patients were divided into an elderly group (n = 21, age ≥80 years) and a non-elderly group (n = 29, age ≤79 years), and were analyzed. Results: A total of 33 and 40 EHL procedures were performed in the elderly and non-elderly groups, respectively. After excluding cases in which stone removal was performed at other institutions, complete removal of common bile duct stones was confirmed in 93.8% and 100% of the elderly and non-elderly groups, respectively (p = 0.20). The mean number of ERCPs required for complete removal of bile duct stones was 2.9 and 4.3 in the elderly and non-elderly groups, respectively (p = 0.17). In the EHL session, the overall occurrence of adverse events was eight and seven in the elderly (24.2%) and non-elderly (17.5%) groups, respectively; however, the difference was insignificant (p = 0.48). Conclusions: EHL using POCS under ERCP guidance is effective in patients aged ≥80 years and there was no significant increase in adverse event rates compared to those aged ≤79 years.


Asunto(s)
Cálculos Biliares , Litotricia , Humanos , Anciano , Persona de Mediana Edad , Colangiopancreatografia Retrógrada Endoscópica/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Cálculos Biliares/cirugía
4.
Chem Senses ; 472022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36374622

RESUMEN

Flavor compounds provide aroma and sensations in the oral cavity. They are not present alone in the oral cavity, but rather in combination with several other food ingredients. This study aimed to clarify the relationship between the mixing of pungent flavor compounds and the response of pungent receptors, TRPV1 and TRPA1 channels. We focused on lactones that activate TRPV1 despite their presence in bland foods, such as dairy products and fruits, and analyzed their interaction with receptors using TRPV1- and TRPA1-expressing HEK293 cells. We found that γ-octalactone, γ-nonalactone, and δ-nonalactone activated TRPA1. When mixed with pungent components, some γ- and δ-lactones inhibited capsaicin-mediated TRPV1 responses, and δ-dodecalactone inhibited allyl isothiocyanate-mediated TRPA1 responses. Furthermore, the dose-response relationship of capsaicin and γ-nonalactone to TRPV1 suggests that γ-nonalactone acts as an agonist or antagonist of TRPV1, depending on its concentration. Conversely, γ-nonalactone and δ-dodecalactone were found to act only as agonists and antagonists, respectively, against TRPA1. These results suggest that lactones in foods may not only endow food with aroma, but also play a role in modulating food pungency by acting on TRPV1 and TRPA1. The dose-response relationships of a mixture of flavor compounds with TRPV1 and TRPA1 provide insights into the molecular physiological basis of pungency that may be the cornerstone for developing new spice mix recipes.


Asunto(s)
Capsaicina , Canal Catiónico TRPA1 , Canales Catiónicos TRPV , Gusto , Canales de Potencial de Receptor Transitorio , Humanos , Capsaicina/farmacología , Células HEK293 , Lactonas/farmacología , Canal Catiónico TRPA1/metabolismo , Canales Catiónicos TRPV/metabolismo
5.
Surg Endosc ; 36(5): 3408-3417, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34370123

RESUMEN

BACKGROUND: Peroral cholangioscopy (POCS) has been used to overcome the difficulty in diagnosing indeterminate biliary stricture or tumor spread. However, the value of adding POCS to computed tomography (CT) remains unclear. Our aim was to evaluate the diagnostic value of adding POCS to CT for indeterminate biliary stricture and tumor spread by interpretation of images focusing on the high diagnostic accuracy of visual findings in POCS. METHODS: We retrospectively identified 52 patients with biliary stricture who underwent endoscopic retrograde cholangiography (ERC) at our institution between January 2013 and December 2018. Two teams, each composed of an expert endoscopist and surgeon, performed the interpretation independently, referring to the CT findings of the radiologist. The CT + ERC + POCS images (POCS group) were evaluated 4 weeks after the evaluation of CT + ERC images (CT group). A 5-point scale (1: definitely benign to 5: definitely malignant) was used to determine the confident diagnosis rate, which was defined as an evaluation value of 1 or 5. Tumor spread was also evaluated. RESULTS: In the evaluation of 45 malignant diagnoses, the score was significantly closer to 5 in the POCS group than in the CT group in both teams (P < 0.001). The confident diagnosis rate was significantly higher for the POCS group (92% and 73%) than for the CT group (25% and 12%) in teams 1 and 2, respectively (P < 0.001). We found no significant difference in diagnostic accuracy for tumor spread between the groups. CONCLUSION: Visual POCS findings confirmed the diagnosis of biliary strictures. POCS was useful in cases of indefinite diagnosis of biliary strictures by CT.


Asunto(s)
Neoplasias de los Conductos Biliares , Colestasis , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Colestasis/diagnóstico por imagen , Colestasis/etiología , Colestasis/cirugía , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/etiología , Endoscopía del Sistema Digestivo/métodos , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
6.
Ann Hepatol ; 27(3): 100696, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35257932

RESUMEN

INTRODUCTION AND OBJECTIVES: Acute cholangitis, which is characterized by biliary infection and acute liver injury, may impact cirrhosis prognosis. However, the prognosis itself remains unclear. MATERIALS AND METHODS: This multicenter retrospective cohort study compared the mortality and liver function change between patients with and without cirrhosis who underwent endoscopic treatment for acute cholangitis caused by choledocholithiasis between January 2004 and December 2019. RESULTS: We analyzed 699 patients, 44 of whom had cirrhosis. The cirrhotic group had a significantly higher 30-day mortality rate than the noncirrhotic group (14% vs. 1%; P < 0.001). The cirrhotic group also had significantly lower total bilirubin and albumin recovery. However, all patients with cirrhosis who survived achieved total-bilirubin recovery, and 91% achieved albumin recovery within 90 days. In multivariable Cox regression analysis, the independent risk factors for total-bilirubin recovery included cirrhosis (hazard ratio, 0.37; 95%CI, 0.24‒0.58; P < 0.001) and high total-bilirubin level (0.46; 95%CI, 0.34‒0.60; P < 0.001), whereas those for albumin recovery were cirrhosis (0.51; 95%CI, 0.33‒0.79; P = 0.002), high age (0.62; 95%CI, 0.47‒0.82; P < 0.001), organ dysfunction (0.62; 95%CI, 0.39‒0.96; P = 0.03), low albumin level (0.57; 95%CI, 0.36‒0.91; P = 0.02), and high C-reactive protein level (0.73; 95%CI, 0.56‒0.95; P = 0.02). CONCLUSIONS: Patients with cirrhosis complicated with acute cholangitis had poor prognosis. Recovery of liver function after endoscopic treatment was slow; nevertheless, most patients who survived could recover within 90 days.


Asunto(s)
Colangitis , Coledocolitiasis , Enfermedad Aguda , Albúminas , Bilirrubina , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangitis/etiología , Colangitis/terapia , Coledocolitiasis/complicaciones , Coledocolitiasis/cirugía , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
7.
Biochem Biophys Res Commun ; 549: 171-178, 2021 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-33676186

RESUMEN

Lenvatinib is one of the first-line drugs for patients with advanced hepatocellular carcinoma (HCC) and widely used around the world. However, the mechanisms underlying resistance to lenvatinib remain unclear. In this study, we conducted characteristic analyses of lenvatinib-resistant HCC cells. Lenvatinib-resistant HCC cell lines were established by exposure to serially escalated doses of lenvatinib over 2 months. The biological characteristics of these cells were examined by in vitro assays. To investigate the cytokine profile of lenvatinib-resistant HCC cells, the supernatant derived from lenvatinib-resistant Huh7 cells was subjected to nitrocellulose membrane-based sandwich immunoassay. Both activation of the MAPK/MEK/ERK signaling pathway and upregulation of epithelial mesenchymal transition markers were observed in lenvatinib-resistant cells. Concordant with these findings, proliferation and invasion abilities were enhanced in these cells compared with control cells. Screening of a cytokine array spotted with 105 different antibodies to human cytokines enabled us to identify 16 upregulated cytokines in lenvatinib-resistant cells. Among them, 3 angiogenic cytokines: vascular endothelial growth factor (VEGF), platelet-derived growth factor-AA (PDGF-AA), and angiogenin, were increased significantly. Conditioned medium from lenvatinib-resistant cells accelerated tube formation of human umbilical vein cells. In conclusion, lenvatinib-resistant HCC cells were characterized by enhanced proliferation and invasion abilities. These findings might contribute to the establishment of new combination therapies with lenvatinib.


Asunto(s)
Inductores de la Angiogénesis/metabolismo , Carcinoma Hepatocelular/patología , Resistencia a Antineoplásicos , Neoplasias Hepáticas/patología , Mesodermo/patología , Compuestos de Fenilurea/farmacología , Quinolinas/farmacología , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Citocinas/biosíntesis , Resistencia a Antineoplásicos/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neovascularización Fisiológica/efectos de los fármacos , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo
8.
Pancreatology ; 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33865724

RESUMEN

BACKGROUND/OBJECTIVES: Recently, increase in cell-free DNA (cfDNA) concentration or newly detected KRAS mutation after endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy were reported to be related to the occurrence of new distant metastasis. In this study, we investigated whether cfDNA concentration increased with the release of tumor components into the blood after EUS-FNA and whether its increase was related to prognosis. METHODS: Sixty-eight patients underwent EUS-FNA and were pathologically confirmed as having pancreatic ductal adenocarcinoma (PDAC). We measured plasma cfDNA concentration and the copy number of KRAS mutation in 68 patients and circulating tumor cells in 8 before and after EUS-FNA. RESULTS: The average cfDNA concentration after EUS-FNA (672.5 ± 919.6 ng/mL) was significantly higher than that before EUS-FNA (527.7 ± 827.3 ng/mL) (P < 0.001). KRAS mutation in plasma was detected in 8 patients (11.8%), however a significant increase in cfDNA concentration after EUS-FNA was not related to the change in KRAS-mutant copy number. Minimal increase in circulating tumor cells was observed in 3 of 8 patients. New distant metastasis was observed within 286 days to initial metastasis detection in 6 of 12 patients with ≥2-fold increase in cfDNA concentration and 26 of 56 patients with <2-fold increase within 185 days. In 32 patients who underwent surgery, ≥2-fold increase in cfDNA did not affect early recurrence. CONCLUSIONS: The increase in cfDNA concentration after EUS-FNA was not caused by tumor cell components released into blood vessels. Hence, the risk of seeding via the blood stream after EUS-FNA may need not be considered.

9.
Invest New Drugs ; 38(1): 172-180, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31172442

RESUMEN

Background Conversion from sorafenib to regorafenib is primarily an evidence-based treatment strategy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the safety and efficacy of sequential therapy with sorafenib and regorafenib in patients with advanced HCC by analysis of outcomes in clinical practice with the aim to complement phase III findings. Methods The medical records of patients with advanced HCC receiving regorafenib were retrieved to collect data on sorafenib administration at seven Japanese institutions. Radiological responses and adverse events were evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Common Terminology Criteria for Adverse Events version 4.0, respectively. Results Before March 2018, 44 patients were administered regorafenib for advanced HCC. The median sorafenib treatment duration was 8.4 months. The most common adverse events were similar to those reported by the RESORCE trial. The median overall survival (OS) was 17.3 months (95% confidence interval [CI] 11.4-22.9), and 17 of 37 patients (45.9%) discontinued regorafenib and received sequential systemic therapy after regorafenib. These patients had significantly longer OS than those who were treated by the best supportive care or sub-optimal therapy (not reached versus 8.7 months [95% CI 5.8-11.7]; P < 0.001). Conclusion The results based on Japanese clinical practices verified the tolerability of regorafenib in advanced HCC. Major regorafenib-associated adverse events were similar to those related to sorafenib. OS was significantly longer than expected, which might be associated with the sequential systemic therapies after regorafenib, mainly lenvatinib.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Compuestos de Fenilurea/administración & dosificación , Pronóstico , Piridinas/administración & dosificación , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios Retrospectivos , Sorafenib/administración & dosificación , Tasa de Supervivencia
10.
Jpn J Clin Oncol ; 50(12): 1403-1411, 2020 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-32761096

RESUMEN

OBJECTIVE: Pancreatic cancer and diabetes status have complex bilateral interactions; therefore, understanding their clinical features is essential for the clinical management of pancreatic cancer patients. We aimed to evaluate the diabetes status before diagnosis, after resection and until the time of recurrence in patients with resectable pancreatic cancer and to clarify the correlations among the clinical course of pancreatic cancer, operative procedure and diabetes status. METHODS: Between 2011 and 2016, we retrospectively identified 189 pancreatic cancer patients who underwent pancreatoduodenectomy or distal pancreatectomy at our institution. The entire clinical course of each patient was retrieved from the medical records, and the diabetes status in the longest possible duration was assessed. RESULTS: Among 115 pancreatic cancer patients who had normal glucose tolerance at the time of resection, 22 (19.1%) developed type 2 diabetes after resection. In a multivariate analysis, distal pancreatectomy was strongly associated with the development of postoperative diabetes. On the other hand, 74 pancreatic cancer patients had already been diagnosed with type 2 diabetes at the time of resection. During the follow-up period, 15 patients were noted to have diabetes resolution after resection; interestingly, the majority of these patients had newly diagnosed diabetes, which was defined as the diagnosis of diabetes within 3 months before resection. Moreover, newly diagnosed diabetes was an independent factor for diabetes resolution after resection. CONCLUSIONS: In pancreatic cancer patients who underwent pancreatectomy, distal pancreatectomy was correlated with postoperative diabetes, and newly diagnosed diabetes had a high probability of resolution after resection.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Neoplasias Pancreáticas/complicaciones , Anciano , Glucemia/análisis , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/cirugía , Femenino , Humanos , Masculino , Pancreatectomía/efectos adversos , Pancreatectomía/métodos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Periodo Preoperatorio , Estudios Retrospectivos , Factores de Riesgo
11.
Int J Med Sci ; 17(7): 874-880, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32308540

RESUMEN

Aim: Tolvaptan, an oral vasopressin-2 antagonist, sometimes improves hepatic edema including ascites in patients with decompensated cirrhosis. In this study, we examined the effectiveness and survival advantage in patients with the long-term administration of tolvaptan. Methods: A total of 115 patients with refractory ascites who were treated with tolvaptan were retrospectively analyzed based on their clinical records. Patients with a decrease in body weight of ≥1.5 kg from the baseline on day 7 were determined as responders. Re-exacerbation was defined as a return to the baseline BW, dose escalation of conventional diuretics, or abdominal drainage. Results: Of the 115 patients, 84 were included in this analysis. Response to tolvaptan treatment was observed in 55 out of the 84 patients (65.5%), with a mean weight reduction of 2.52 kg. Multivariate analyses demonstrated that body mass index (≥24) and urinary specific gravity (≥1.018) were significant predictors of the response to tolvaptan. However, cumulative re-exacerbation rates in responders at 6 and 12 months were 42.4 and 60.1%, respectively. Child-Pugh (classification C), HCC complication, and serum sodium levels (≥133 mEq/L) were determined as independent prognostic factors impacting overall survival (OS). Although there were no significant differences in OS between tolvaptan responders and non-responders, the responders without re-exacerbation within 3 months showed significantly longer OS than those with re-exacerbation within 3 months. Conclusion: A persistent therapeutic response, but not early response to tolvaptan, was associated with favorable survival of decompensated cirrhotic patients.


Asunto(s)
Antagonistas de los Receptores de Hormonas Antidiuréticas/administración & dosificación , Cirrosis Hepática/tratamiento farmacológico , Tolvaptán/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antagonistas de los Receptores de Hormonas Antidiuréticas/efectos adversos , Antagonistas de los Receptores de Hormonas Antidiuréticas/uso terapéutico , Ascitis/tratamiento farmacológico , Ascitis/etiología , Ascitis/mortalidad , Biomarcadores Farmacológicos/sangre , Biomarcadores Farmacológicos/orina , Índice de Masa Corporal , Femenino , Humanos , Estimación de Kaplan-Meier , Cirrosis Hepática/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Sodio/sangre , Tolvaptán/efectos adversos , Tolvaptán/uso terapéutico , Resultado del Tratamiento
12.
BMC Cancer ; 19(1): 1088, 2019 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-31718608

RESUMEN

BACKGROUND: Abnormal autocrine fibroblast growth factor 19 (FGF19) production has been observed in several types of cancers, including hepatocellular carcinoma (HCC). In this study, we investigated the potential of serum FGF19 as a novel tumor marker of HCC based on a sandwich enzyme-linked immunosorbent assay (ELISA). METHODS: The serum FGF19 levels of 304 patients with HCC was measured by ELISA. The serum levels of existing markers, including alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) were determined by chemiluminescence enzyme immunoassay. Both diagnostic value of FGF19 and its changes after curative ablation therapy was further examined. RESULTS: The median FGF19 levels in controls, chronic liver disease patients, and primary HCC patients, were 78.8 pg/mL, 100.1 pg/mL, and 214.5 pg/mL, respectively. The subsequent receiver operating characteristic curves (ROC) successfully determined an optimal cut-off value of 200.0 pg/mL. The area under the ROC curve (AUC) of FGF19 for HCC detection was comparable to those of AFP and DCP. Of importance, FGF19 showed higher sensitivity for the detection of small HCC (solitary cancer with diameter < 20 mm) than those of existing markers. In addition, 43 out of 79 cases (54.4%) with normal AFP and DCP (so-called "double negative HCC") exhibited serum FGF19 level ≥ 200 pg/mL. In 45 HCC patients treated with curative ablation therapy, serum FGF19 levels changed from 257.4 pg/mL to 112.0 pg/mL after the treatment. CONCLUSION: Our findings reveal that FGF19 can be a potential novel biomarker for HCC. Although FGF19 is not necessarily a substitute for existing markers, it may help improve the prognosis in HCC patients owing to its resourceful use in various aspects of HCC management and treatment.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Hepatocelular/sangre , Factores de Crecimiento de Fibroblastos/sangre , Neoplasias Hepáticas/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores , Carcinoma Hepatocelular/diagnóstico , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Recurrencia , alfa-Fetoproteínas
13.
Hepatol Res ; 49(1): 3-13, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30238570

RESUMEN

Due to the advances made in research based on next generation sequencers, it is now possible to detect and analyze epigenetic abnormalities associated with cancer. DNA methylation, various histone modifications, chromatin remodeling, and non-coding RNA-associated gene silencing are considered to be transcriptional regulatory mechanisms associated with gene expression changes. The breakdown of this precise regulatory system is involved in the transition to cancer. The important role of epigenetic regulation can be observed from the high rate of genetic mutations and abnormal gene expression leading to a breakdown in epigenetic gene expression regulation seen in hepatocellular carcinoma (HCC). Based on an understanding of epigenomic abnormalities associated with pathological conditions, these findings will lead the way to diagnosis and treatment. In particular, in addition to the fact that there are few choices in terms of extant drug therapies aimed at HCC, there are limits to their antitumor effects. The clinical application of epigenetic therapeutic agents for HCC has only just begun, and future developments are expected.

14.
Pancreatology ; 18(2): 176-183, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29305088

RESUMEN

BACKGROUND: Insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3) is a valuable marker that distinguishes malignant from benign lesions and predicts prognosis. METHODS: First, we evaluated IMP3 expression in 77 resected specimens of pancreatic ductal adenocarcinoma (PDAC), intraductal papillary mucinous neoplasm (IPMN), and chronic pancreatitis (CP). Eleven PDAC patients preoperatively underwent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Survival analysis of IMP3 and clinicopathological factors was performed. IMP3 and p53 expression was evaluated in another 127 EUS-FNA samples of solid pancreatic masses to compare the diagnostic value of routine and immunohistochemical staining. RESULTS: IMP3 expression was detected in 72.3%, 50%, 20%, and 0% of PDAC, malignant IPMN, benign IPMN, and CP, respectively. Evaluation of IMP3 expression in EUS-FNA specimens coincided with that in resected specimens in 10 of 11. IMP3 expression correlated with tumor differentiation in PDAC samples (p = .006) and with poor prognosis through univariate analysis (p = .045). Tumor differentiation and lymph node metastasis were significantly associated with poor prognosis through multivariate analysis. In EUS-FNA specimens, the sensitivity, specificity, and accuracy of cytohistological analysis were 80.8%, 100%, and 85.0%, respectively. IMP3 and p53 expression were detected in 80.8% and 44.9% of malignant and 0% and 5% of benign lesions. Combined with IMP3 immunostaining, the sensitivity, specificity and accuracy of cytohistological analysis significantly increased to 87.9%, 100%, and 90.8% (p = .016), respectively. Meanwhile, p53 staining had no impact on the results. CONCLUSIONS: IMP3 immunohistochemical staining can improve the diagnostic accuracy of EUS-FNA for malignant pancreatic tumors.


Asunto(s)
Regulación Neoplásica de la Expresión Génica/fisiología , Enfermedades Pancreáticas/diagnóstico , Enfermedades Pancreáticas/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Biopsia con Aguja , Endosonografía , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Enfermedades Pancreáticas/patología , Enfermedades Pancreáticas/cirugía , Proteínas de Unión al ARN/genética , Proteína p53 Supresora de Tumor/genética
15.
Pathobiology ; 83(6): 287-94, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27251053

RESUMEN

OBJECTIVE: The decrease in female hormone levels at menopause affects whole-body homeostasis. Various therapies including hormone therapy and treatment with herbal supplements are available to improve menopausal symptoms. However, a method for evaluating their effectiveness has not been established. We sought to identify useful biomarkers to assess therapy efficacy. METHODS: We searched for salivary proteins affected by changes in female hormone levels in mouse submandibular glands. RESULTS: The expression of submandibular gland protein C (Smgc) was decreased following ovariectomy, while the expression of the alternative splicing transcript t-Smgc was increased. Notably, Smgc expression increased following ß-estradiol administration, and was barely detectable in the submandibular glands of male mice. CONCLUSION: The results suggest that Smgc expression may be estrogen dependent. Moreover, changes in the SMGC protein amount in the saliva were in accordance with those in mRNA expression in the submandibular gland. Our findings suggest that salivary proteins have potential as markers for evaluating therapies for menopausal symptoms.


Asunto(s)
Estrógenos/metabolismo , Mucinas/metabolismo , Proteínas y Péptidos Salivales/metabolismo , Glándula Submandibular/metabolismo , Animales , Femenino , Humanos , Masculino , Menopausia/metabolismo , Ratones , Ratones Endogámicos C57BL , Ovariectomía , Caracteres Sexuales
16.
J Biol Chem ; 289(37): 25711-20, 2014 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-25056955

RESUMEN

Gymnemic acids are triterpene glycosides that selectively suppress taste responses to various sweet substances in humans but not in mice. This sweet-suppressing effect of gymnemic acids is diminished by rinsing the tongue with γ-cyclodextrin (γ-CD). However, little is known about the molecular mechanisms underlying the sweet-suppressing effect of gymnemic acids and the interaction between gymnemic acids versus sweet taste receptor and/or γ-CD. To investigate whether gymnemic acids directly interact with human (h) sweet receptor hT1R2 + hT1R3, we used the sweet receptor T1R2 + T1R3 assay in transiently transfected HEK293 cells. Similar to previous studies in humans and mice, gymnemic acids (100 µg/ml) inhibited the [Ca(2+)]i responses to sweet compounds in HEK293 cells heterologously expressing hT1R2 + hT1R3 but not in those expressing the mouse (m) sweet receptor mT1R2 + mT1R3. The effect of gymnemic acids rapidly disappeared after rinsing the HEK293 cells with γ-CD. Using mixed species pairings of human and mouse sweet receptor subunits and chimeras, we determined that the transmembrane domain of hT1R3 was mainly required for the sweet-suppressing effect of gymnemic acids. Directed mutagenesis in the transmembrane domain of hT1R3 revealed that the interaction site for gymnemic acids shared the amino acid residues that determined the sensitivity to another sweet antagonist, lactisole. Glucuronic acid, which is the common structure of gymnemic acids, also reduced sensitivity to sweet compounds. In our models, gymnemic acids were predicted to dock to a binding pocket within the transmembrane domain of hT1R3.


Asunto(s)
Saponinas/administración & dosificación , Edulcorantes/administración & dosificación , Papilas Gustativas/efectos de los fármacos , Gusto/genética , Triterpenos/administración & dosificación , Secuencia de Aminoácidos , Animales , Derivados del Benceno/administración & dosificación , Sitios de Unión , Células HEK293 , Humanos , Ratones , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Gusto/efectos de los fármacos , Papilas Gustativas/metabolismo
17.
Front Nutr ; 11: 1356210, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863584

RESUMEN

Introduction: Food neophobia (FN) is a psychological trait that inhibits one's willingness to eat unfamiliar foods. It is related to the acceptance of insect foods and cultured meat, which are major protein alternatives to conventional meat, and is an important personality trait for understanding the near-future food industry. However, the factor structure of Pliner and Hobden's FN scale (FNS) is unstable due to respondents' cultural backgrounds. Thus, we aimed to develop a Japanese version based on the alternative FNS (FNS-A), the most recent revised version, and to examine its validity. Methods: Four online surveys (preliminary 1: n = 202; preliminary 2: n = 207; main: n = 1,079; follow-up: n = 500) were conducted on the FNS-A. For the main survey, Japanese respondents (aged 20-69 years) answered the Japanese version of the FNS-A (J-FNS-A), their willingness to eat (WTE), and their familiarity with hamburgers containing regular protein foods (ground beef, tofu) and alternative protein foods (soy meat, cultured meat, cricket powder, algae powder, and mealworm powder). Results: Consistent with the FNS-A, confirmatory factor analysis assuming a two-dimensional structure (approach and avoidance) showed satisfactory model fit indices. The mean J-FNS-A score (Cronbach's α for 8 items = 0.83) was 4.15 [standard deviation (SD) = 0.93]. J-FNS-A scores were not associated with age and gender, whereas a greater than moderate association was found with WTE hamburgers containing alternative protein foods (rs = -0.42 to -0.33). The strength of these negative associations increased as food familiarity decreased (r = 0.94). The test-retest reliability at 1 month was also satisfactory (r = 0.79). Discussion: The validity of the J-FNS-A was confirmed. Higher J-FNS-A scores (mean = 41.51, SD = 9.25, converted to Pliner and Hobden's FNS score) of the respondents suggest that Japanese people prefer conservative foods. This scale could predict the negative attitudes toward foods with low familiarity, such as alternative proteins. The J-FNS-A appears to be a useful psychological tool for assessing Japanese food neophobia tendencies and predicting novel food choices of Japanese individuals.

18.
ACG Case Rep J ; 10(3): e01016, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36968126

RESUMEN

A 64-year-old woman was diagnosed with emphysematous cholecystitis. An open cholecystectomy was performed immediately. After the cholecystectomy, jaundice and multiple bile duct strictures that were not present preoperatively appeared. The patient was diagnosed with sclerosing cholangitis secondary to emphysematous cholecystitis. Endoscopic biliary stenting and endoscopic biliary balloon dilatation were performed. However, jaundice did not improve. She developed candidemia 75 days after cholecystectomy. The patient died of multiple organ failures 92 days after cholecystectomy. Although rare, secondary sclerosing cholangitis occurred after emphysematous cholecystitis, and endoscopic treatment was ineffective in this case.

19.
Sci Rep ; 13(1): 1265, 2023 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-36690708

RESUMEN

Nasal pressure signal is commonly used to evaluate obstructive sleep apnea. This study aimed to assess its safety for respiratory monitoring during sedation. A total of 45 adult patients undergoing sedation with propofol and fentanyl for invasive endoscopic procedures were enrolled. While both nasal pressure and capnograph signals were continuously recorded, only the nasal pressure signal was displayed. The primary outcome was the incidence of oxygen desaturation below 90%. The secondary outcomes were the ability to predict the desaturation and incidence of harmful events and false alarms, defined as an apnea waveform lasting more than 3 min without desaturation. Of the 45 participants, 43 completed the study. At least one desaturation event occurred in 12 patients (27.9%; 95% confidence interval 15.3-43.7%). In these 12 patients, more than half of the desaturation events were predictable in 9 patients by capnography and 11 patients by nasal pressure monitoring (p = 0.59). In the 43 patients, false alarms were detected in 7 patients with capnography and 11 patients with nasal pressure monitoring (p = 0.427). Harmful events unrelated to nasal pressure monitoring occurred in 2 patients. Nasal pressure monitoring is safe and possibly useful for respiratory monitoring despite false alarms during sedation.


Asunto(s)
Propofol , Apnea Obstructiva del Sueño , Adulto , Humanos , Capnografía/métodos , Propofol/efectos adversos , Monitoreo Fisiológico/métodos , Endoscopía , Apnea Obstructiva del Sueño/inducido químicamente
20.
Geriatr Gerontol Int ; 23(11): 836-841, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37752034

RESUMEN

AIM: There are few reports on the safety of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the elderly. In this study, we investigated the safety of EUS-FNA for pancreatic solid masses in patients aged ≥80 years. METHODS: This is a single-center retrospective study. A total of 600 patients with pancreatic solid masses who underwent EUS-FNA under midazolam-based sedation at our institution between September 2016 and December 2022 were enrolled in this study. Eligible patients were divided into two groups: an elderly group aged ≥80 (n = 84), as well as a nonelderly group aged ≤79 (n = 516). These two groups were compared. RESULTS: The elderly group required significantly fewer midazolam doses for sedation (P < 0.001). Adverse events occurred in eight patients (1.3%), including one (1.2%) and seven (1.4%) in the elderly and nonelderly groups, respectively (P = 0.90). There were no cases of early adverse events in the elderly group and six cases (1.2%) in the nonelderly group (P = 0.32). There was one case of late adverse events in both the elderly and nonelderly groups (P = 0.14), and both were needle tract seeding. There was no significant difference between the two groups in the proportion of cases in which percutaneous oxygen saturation decreased to ≤90% during the EUS-FNA. CONCLUSIONS: Our analysis suggests that EUS-FNA for pancreatic solid masses can be safely performed in patients aged >80 years without increasing the adverse event rate compared to nonelderly patients aged <80 years. Geriatr Gerontol Int 2023; 23: 836-841.


Asunto(s)
Anestesia , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Anciano , Humanos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/efectos adversos , Páncreas/diagnóstico por imagen , Estudios Retrospectivos , Midazolam
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