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1.
Sci Rep ; 10(1): 9180, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513953

RESUMO

Data regarding the efficacy and tolerability of elbasvir/grazoprevir (EBR/GZR) for East-Asian hepatitis C virus genotype 1b (HCV GT1b) patients receiving hemodialysis were limited. We prospectively recruited 40 HCV GT1b hemodialysis patients who received EBR/GZR for 12 weeks at 6 academic centers in Taiwan. The efficacy endpoints were sustained virologic response 12 weeks off-therapy (SVR12) by intention-to-treat (ITT) modified ITT (mITT) analyses. Patients' baseline characteristics, early viral kinetics and HCV resistance-associated substitutions (RASs) at HCV non-structural 3 and 5 A (NS3 and NS5A) regions potentially affecting SVR12 were analyzed. The tolerability for EBR/GZR was also assessed. The SVR12 rates by ITT and mITT analyses were 95% (38 of 40 patients; 95% confidence interval (CI): 83.5-98.6%) and 100% (38 of 38 patients; 95% CI: 90.8-100%), respectively. Patients' baseline characteristics, on-treatment viral decline, and baseline HCV RASs did not affect SVR12. All patients tolerated treatment well. Among 5 patients who had serious adverse events (AEs) including one death due to on-treatment suicide and the other death due to off-therapy acute myocardial infarction, none of these events were judged related to EBR/GZR. The common AEs included upper respiratory tract infection (7.5%), fatigue (5.0%) and anorexia (5.0%). Nine (22.5%) and 8 (20.0%) patients had on-treatment hemoglobin levels of 9.0-10.0 g/dL and 7.0-9.0 g/dL. Three (7.5%) patients had on-treatment elevated alanine aminotransferase (ALT) quotient > 2.5, in whom one (2.5%) had EBR/GZR-induced late ALT elevation. No patients developed hyperbilirubinemia or hepatic decompensation. In conclusion, treatment with EBR/GZR is effective and well-tolerated for East-Asian HCV GT1b patients receiving hemodialysis.


Assuntos
Amidas/uso terapêutico , Antivirais/uso terapêutico , Benzofuranos/uso terapêutico , Carbamatos/uso terapêutico , Ciclopropanos/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Quinoxalinas/uso terapêutico , Sulfonamidas/uso terapêutico , Povo Asiático , Farmacorresistência Viral/efeitos dos fármacos , Quimioterapia Combinada/métodos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Resposta Viral Sustentada
2.
Obes Surg ; 30(4): 1249-1257, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31953745

RESUMO

BACKGROUND: The prevalence rate of nonalcoholic fatty liver disease (NAFLD) has been reported in 74 to 90% of morbidly obese patients. This study aims to develop a scoring system that predicts significant liver fibrosis in morbidly obese patients. METHODS: This prospective cohort study involved 123 morbidly obese patients who underwent metabolic surgery at Taipei Medical University Hospital between October 2016 and June 2018. Wedge liver biopsy was performed during surgery, and significant liver fibrosis was defined as a fibrosis score â‰§ 2. Ultrasonography and transient elastography were performed prior to surgery to assess the risk factors associated with significant liver fibrosis. RESULTS: Mean patient age was 35.5 years, mean body mass index (BMI) was 40.6 kg/m2, and 87 (70.7%) were female. Fibrosis staging revealed 28 (22.8%) at stage 2, 14 (11.4%) at stage 3, and 2 (1.6%) at stage 4. Patients were then separated into training (n = 73) and validation (n = 50) cohorts. Multivariate analysis revealed a liver stiffness measurement (LSM) > 7 kPa and aspartate aminotransferase/platelet ratio index (APRI) > 0.40 as independent factors associated with significant liver fibrosis among the training cohort. Fibroscan-base score weighted sum of (1 for presence of APRI > 0.40) + (2 for presence of LSM > 7 kPa) yielded the highest area under receiver operating curve (0.854, P = 0.0001; 0.785, P = 0.0002) compared with other non-invasive markers in the training and validation cohorts, respectively. CONCLUSION: We developed a simple, clinical scoring system incorporating Fibroscan and APRI to predict significant liver fibrosis in morbidly obese patients.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Adulto , Biópsia , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/cirurgia , Estudos Prospectivos
3.
Nutrients ; 10(8)2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127325

RESUMO

Red blood cell (RBC) aggregation and iron status are interrelated and strongly influenced by dietary factors, and their alterations pose a great risk of dyslipidemia and metabolic syndrome (MetS). Currently, RBC aggregation-related dietary patterns remain unclear. This study investigated the dietary patterns that were associated with RBC aggregation and their predictive effects on hyperlipidemia and MetS. Anthropometric and blood biochemical data and food frequency questionnaires were collected from 212 adults. Dietary patterns were derived using reduced rank regression from 32 food groups. Adjusted linear regression showed that hepcidin, soluble CD163, and serum transferrin saturation (%TS) independently predicted RBC aggregation (all p < 0.01). Age-, sex-, and log-transformed body mass index (BMI)-adjusted prevalence rate ratio (PRR) showed a significant positive correlation between RBC aggregation and hyperlipidemia (p-trend < 0.05). RBC aggregation and iron-related dietary pattern scores (high consumption of noodles and deep-fried foods and low intake of steamed, boiled, and raw food, dairy products, orange, red, and purple vegetables, white and light-green vegetables, seafood, and rice) were also significantly associated with hyperlipidemia (p-trend < 0.05) and MetS (p-trend = 0.01) after adjusting for age, sex, and log-transformed BMI. Our results may help dieticians develop dietary strategies for preventing dyslipidemia and MetS.


Assuntos
Agregação Celular , Dieta , Eritrócitos/citologia , Hiperlipidemias/sangue , Síndrome Metabólica/sangue , Adulto , Antropometria , Povo Asiático , Biomarcadores/sangue , Índice de Massa Corporal , Colesterol/sangue , Feminino , Hematócrito , Hemoglobinas/metabolismo , Hepcidinas/sangue , Humanos , Ferro/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Taiwan , Transferrina/metabolismo , Triglicerídeos/sangue , Adulto Jovem
4.
Sci Rep ; 8(1): 6316, 2018 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-29679033

RESUMO

Many human diseases are inflammation-related, such as cancer and those associated with aging. Previous studies demonstrated that plasmon-induced activated (PIA) water with electron-doping character, created from hot electron transfer via decay of excited Au nanoparticles (NPs) under resonant illumination, owns reduced hydrogen-bonded networks and physchemically antioxidative properties. In this study, it is demonstrated PIA water dramatically induced a major antioxidative Nrf2 gene in human gingival fibroblasts which further confirms its cellular antioxidative and anti-inflammatory properties. Furthermore, mice implanted with mouse Lewis lung carcinoma (LLC-1) cells drinking PIA water alone or together with cisplatin treatment showed improved survival time compared to mice which consumed only deionized (DI) water. With the combination of PIA water and cisplatin administration, the survival time of LLC-1-implanted mice markedly increased to 8.01 ± 0.77 days compared to 6.38 ± 0.61 days of mice given cisplatin and normal drinking DI water. This survival time of 8.01 ± 0.77 days compared to 4.62 ± 0.71 days of mice just given normal drinking water is statistically significant (p = 0.009). Also, the gross observations and eosin staining results suggested that LLC-1-implanted mice drinking PIA water tended to exhibit less metastasis than mice given only DI water.


Assuntos
Antioxidantes/uso terapêutico , Neoplasias Pulmonares/terapia , Água/farmacologia , Animais , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Linhagem Celular Tumoral , China , Cisplatino/farmacologia , Ouro/uso terapêutico , Neoplasias Pulmonares/patologia , Masculino , Nanopartículas Metálicas/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Ressonância de Plasmônio de Superfície/métodos
5.
ACS Omega ; 3(5): 4743-4751, 2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31458693

RESUMO

Conventionally, reactions in aqueous solutions are prepared using deionized (DI) water, the properties of which are related to inert "bulk water" comprising a tetrahedral hydrogen-bonded network. In this work, we demonstrate the distinguished benefits of using in situ plasmon-activated water (PAW) with reduced hydrogen bonds instead of DI water in electrochemical reactions, which generally are governed by diffusion and kinetic controls. Compared with DI water-based systems, the diffusion coefficient and the electron-transfer rate constant of K3Fe(CN)6 in PAW in situ can be increased by ca. 35 and 15%, respectively. These advantages are responsible for the improved performance of surface-enhanced Raman scattering (SERS). On the basis of PAW in situ, the SERS enhancement of twofold higher intensity of rhodamine 6G and the corresponding low relative standard deviation of 5%, which is comparable to and even better than those based on complicated processes shown in the literature, are encouraging.

6.
J Agric Food Chem ; 65(12): 2521-2529, 2017 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-28285527

RESUMO

In this study, hot-water extracts (HW) from roots of Vitis thunbergii var. taiwaniana (VTT-R) were shown to lower levels of lipid accumulation significantly (P < 0.01 or 0.001) compared to the control in 3T3-L1 adipocytes. The VTT-R-HW (40 mg/kg) interventions concurrent with a high-fat (HF) diet in C57BL/6 mice over a 5 eek period were shown to reduce body weights significantly (P < 0.05) compared to those of mice fed a HF diet under the same food-intake regimen. The (+)-ε-viniferin isolated from VTT-R-HW was shown to reduce the size of lipid deposits significantly compared to the control (P < 0.05 or 0.001) in 3T3-L1 adipocytes, and dose-dependent 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitions showed that the 50% inhibitory concentration was calculated to be 96 µM. The two-stage (+)-ε-viniferin interventions (10 mg/kg, day 1 to day 38; 25 mg/kg, day 39 to day 58) were shown to lower mice body weights significantly (P < 0.05 or 0.001), the weight ratio of mesenteric fat, blood glucose, total cholesterol, and low-density lipoprotein compared to that of the HF group under the same food-intake regimen but without concurrent VTT-R-HW interventions. It might be possible to use VTT-R-HW or (+)-ε-viniferin as an ingredient in the development of functional foods for weight management, and this will need to be investigated further.


Assuntos
Benzofuranos/administração & dosagem , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Raízes de Plantas/química , Estilbenos/administração & dosagem , Vitis/química , Animais , Benzofuranos/química , Benzofuranos/isolamento & purificação , Glicemia/metabolismo , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Obesidade/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Estilbenos/química , Estilbenos/isolamento & purificação
7.
J Agric Food Chem ; 64(18): 3598-608, 2016 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-27094403

RESUMO

Hydrogen peroxide, one of the reactive oxygen species (ROS), can cause intracellular oxidative stress associated with skin aging and/or photoaging. Curcumin, a polyphenol in turmeric, has been reported to exhibit biological activity. In this study, five naturally occurring curcuminoids [curcumin, demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), monohydroxy-DMC, and monohydroxy-BDMC] were used to investigate their protective roles against hydrogen peroxide-induced oxidative stress in the immortalized human keratinocyte cell lines (HaCaT cells). These five curcuminoids at 10 µM, but not at 5 µM, were shown to exhibit cytotoxicities toward HaCaT keratinocytes. Therefore, a 5 µM concentration of the five curcuminoids was selected for further investigations. Cells were pretreated with or without curcuminoids for 2.5 h before 24-h hydrogen peroxide (150 µM) treatments. Pretreatments with the minor components monohydroxy-DMC or monohydroxy-BDMC, but not curcumin, DMC, and BDMC, showed protective activity, elevating cell viability compared to cells with direct hydrogen peroxide treatments. Pretreatments with monohydroxy-DMC and monohydroxy-BDMC showed the best protective effects, reducing apoptotic cell populations and intracellular ROS, as demonstrated by flow cytometry, as well as reducing the changes of the mitochondrial membrane potential compared to cells with direct hydrogen peroxide treatments. The pretreatments with monohydroxy-DMC and monohydroxy-BDMC reduced c-jun and c-fos mRNA expression and p53 tumor suppressor protein expression and increased HO-1 protein expression and glutathione peroxidase (GPx) activity, respectively, compared to cells with direct hydrogen peroxide treatments. The five curcuminoids exhibited similar hydrogen peroxide-scavenging activity in vitro. It was proposed that monohydroxy-DMC and monohydroxy-BDMC could induce antioxidant defense systems better than curcumin, DMC, or BDMC could against hydrogen peroxide-induced oxidative stress and apoptosis of HaCaT keratinocytes and that they may have potential as ingredients in antiaging cosmetics for skin care.


Assuntos
Curcuma/química , Curcumina/farmacologia , Peróxido de Hidrogênio/toxicidade , Queratinócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Estresse Oxidativo , Extratos Vegetais/química , Substâncias Protetoras/química , Espécies Reativas de Oxigênio/metabolismo
8.
Oncotarget ; 6(28): 25988-6001, 2015 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-26317903

RESUMO

Bortezomib (Velcal) was the first proteasome inhibitor to be approved by the US Food and Drug Administration to treat patients with relapsed/refractory multiple myelomas. Previous studies have demonstrated that bortezomib inhibits tumor cell proliferation and induces apoptosis by blocking the nuclear factor (NF)-κB pathway. However, the exact mechanism by which bortezomib induces cancer cell apoptosis is still not well understood. In this study, we found that bortezomib significantly inhibited cell proliferation in both human Burkitt's lymphoma CA46 and Daudi cells. Through proteomic analysis, we found that bortezomib treatment changed the expression of various proteins in distinct functional categories including unfolding protein response (UPS), RNA processing, protein targeting and biosynthesis, apoptosis, and signal transduction. Among the proteins with altered expression, hnRNP K, hnRNP H, Hsp90α, Grp78, and Hsp7C were common to both Daudi and CA46 cells. Interestingly, bortezomib treatment downregulated the expression of high-molecular-weight (HMw) hnRNP K and c-Myc but upregulated the expression of low-molecular-weight (LMw) hnRNP K. Moreover, cell proliferation was significantly correlated with high expression of HMw hnRNP K and c-Myc. HMw and LMw hnRNP K were identified as sumoylated and desumoylated hnRNP K, respectively. Using transient transfection, we found that sumoylated hnRNP K increased c-Myc expression at the translational level and contributed to cell proliferation, and that Lys422 of hnRNP K is the candidate sumoylated residue. Our results suggest that besides inhibiting the ubiquitin-proteasome pathway, bortezomib may inhibit cell proliferation by downregulating sumoylated hnRNP K and c-Myc expression in Burkitt's lymphoma cells.


Assuntos
Bortezomib/farmacologia , Proliferação de Células/efeitos dos fármacos , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Antineoplásicos/farmacologia , Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Eletroforese em Gel Bidimensional , Chaperona BiP do Retículo Endoplasmático , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/genética , Humanos , Immunoblotting , Lisina/genética , Lisina/metabolismo , Mutação , Proteômica/métodos , Proteínas Proto-Oncogênicas c-myc/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Sumoilação
9.
Urol Oncol ; 32(1): 29.e1-11, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23428538

RESUMO

OBJECTIVE: Glucose-regulated protein 78 (Grp78) is an endoplasmic reticulum chaperone; it maintains endoplasmic reticulum homeostasis and modulates unfolded protein response. The protein is overexpressed in various cancer types, including renal cell carcinoma (RCC). Increased Grp78 expression in patients with RCC is correlated with more aggressive tumors and poorer prognoses. This study investigated the role of Grp78 in regulating tumorigenesis and evaluated the potential of Grp78-targeted therapy for RCC. METHODS: The expression level of Grp78 was examined in von Hippel-Lindau (VHL)-intact or VHL-null RCC cell lines by reverse transcription polymerase chain reaction and Western blot. Specific Grp78 ribonucleic acid interference was applied as a molecularly Grp78-targeted therapeutic approach. This method enabled us to assess the effects of manipulating Grp78 expression to regulate RCC cell growth. RESULTS: The Grp78 messenger ribonucleic acid and protein were expressed in both VHL-intact and VHL-null RCC cell lines. The specific inhibition of Grp78 expression suppressed RCC cell growth and colony formation significantly, and induced G1 cell-cycle arrest. We also showed that inhibiting Grp78 expression increased the cells' resistance to the cytotoxicity of the S-phase-specific anticancer drug 5-fluorouracil. This effect was regulated by the unfolded protein response-induced suppression of G1/S transition-related cyclins (D1, E1, and E2) and cyclin-dependent kinase (CDK4 and CDK6) protein expression. CONCLUSION: Overall, our findings indicate the regulatory function of Grp78 in RCC cell proliferation, and provide a molecular-based mechanism of Grp78 positivity in the progression of RCC.


Assuntos
Antineoplásicos/química , Carcinoma de Células Renais/genética , Resistencia a Medicamentos Antineoplásicos , Inativação Gênica , Proteínas de Choque Térmico/genética , Neoplasias Renais/genética , Carcinogênese , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Fluoruracila/química , Fase G1 , Humanos , Neoplasias Renais/metabolismo , RNA Interferente Pequeno/metabolismo , Resposta a Proteínas não Dobradas
10.
Food Chem ; 138(2-3): 923-30, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23411197

RESUMO

Our previous report showed that yam dioscorin and its peptic hydrolysates exhibit radical scavenging activities; however, the functions of these peptic hydrolases are still under investigation. In this study, the thiol-containing peptides derived from computer-aided simulation of pepsin hydrolysis of dioscorin, namely, KTCGNGME (diotide1), PPCSE (diotide2), CDDRVIRTPLT (diotide3), KTCGY (diotide4), and PPCTE (diotide5) were synthesized to compare their antioxidant activities with GSH and/or carnosine by examining hydroxyl radical scavenging activity by electron spin resonance spectrometry, anti-low-density lipoprotein peroxidation, anti-AAPH-induced hemolysis, and oxygen radical absorbance capacity activity. We found that while all the synthesized diotides showed antioxidant activity, diotide4 exhibited the highest levels. Moreover, all diotides (100 µM) showed protective effects against methylglyoxal-induced human umbilical vein endothelial cell death. These results suggest that thiol-containing diotides derived from dioscorin hydrolysis exhibit antioxidant activities and reveal the benefits of yam tuber as an antioxidant-rich food.


Assuntos
Antioxidantes/química , Dioscorea/química , Peptídeos/química , Proteínas de Plantas/química , Antioxidantes/síntese química , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Hidrólise , Pepsina A/química , Peptídeos/síntese química , Peptídeos/farmacologia , Tubérculos/química
12.
Hepat Mon ; 11(10): 843-6, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22224084

RESUMO

BACKGROUND: Itraconazole is believed to carry a low risk of hepatic toxicity owing to its low affinity for the human P-450 enzyme. Therefore, hepatic failure caused by itraconazole is exceedingly rare. OBJECTIVES: We report the case of a 46-year-old woman who developed hepatic failure related to itraconazole that was administered for the treatment of onychomycosis. Her condition deteriorated after withdrawal of the drug, followed solely by supportive care initially. CASE REPORT: Treatment with corticosteroids was started 10 days after her admission, and her condition gradually improved. Unfortunately, her condition worsened when the dosage of corticosteroids was abruptly decreased. Ultimately, her condition improved with appropriate adjustments of corticosteroid dosage. DISCUSSION: We conclude that corticosteroid therapy may be effective for itraconazole-induced hepatitis, especially in those patients who do not respond to conservative treatment. Notably, any decrease in the dosage should be performed with caution. We also recommend that close monitoring of liver function is mandatory during the use of itraconazole.

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