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1.
Molecules ; 26(24)2021 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-34946560

RESUMEN

Cr(VI) can be released into soil as a result of mining, electroplating, and smelting operations. Due to the high toxicity of Cr(VI), its removal is necessary in order to protect ecosystems. Vermiculite is applied in situations where there is a high degree of metal pollution, as it is helpful during the remediation process due to its high cation exchange capacity. The Cr(VI) contained in the vermiculite should be extracted in order to recover it and to reduce the impact on the environment. In this work, adsorption equilibrium data for Cr(VI) in a simulated sorbent for soil remediation (a mixture that included both humic acid (HA) and vermiculite) were a good fit with the Langmuir isotherm model. The simulated sorbent for soil remediation was a favorable sorbent for Cr(VI) when it was in the test soil. An ionic liquid, [C4mim]Cl (1-butyl-3-methylimidazolium chloride), was studied to determine its efficiency in extracting Cr(VI) from the Cr- contaminated simulated sorbent in soil remediation. At 298 K and within 30 min, approximately 33.48 ± 0.79% of Cr(VI) in the simulated sorbent in soil remediation was extracted into [C4mim]Cl. Using FTIR spectroscopy, the absorbance intensities of the bands at 1032 and 1010 cm-1, which were attributed to C-O bond stretching in the polysaccharides of HA, were used to detect the changes in HA in the Cr-contaminated simulated sorbent for soil remediation before and after extraction. The results showed that Cr(VI) that has been absorbed on HA can be extracted into [C4mim]Cl. Using 1H NMR, it was observed that the 1-methylimizadole of [C4mim] Cl played an important role in the extraction of Cr(VI), which bonded with HA on vermiculite and was able to be transformed into the [C4mim]Cl phase.

2.
J Cell Physiol ; 235(2): 1689-1699, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31298420

RESUMEN

Activated hepatic stellate cells promote hepatocellular carcinoma (HCC) progression. Hepatic stellate cells play a key role in retinoid metabolism, and activation of stellate cells increases retinoic acid (RA) in the liver. However, the role of RA in HCC proliferation remains unclear. We aimed to analyse the mechanism of RA in HCC proliferation. Thirty-eight patients who had undergone hepatic resection for HCCs were recruited. Paired non-tumour tissues, adjacent and distal to HCCs, were collected, and the RA levels in the tissues were analysed. The mechanisms of RA and HCC proliferation were assessed in liver cancer cell lines by protein and gene expression analyses. Early recurrence of HCC was significantly higher in patients with a higher RA concentration than in those with a lower RA concentration in tissues adjacent to HCCs (61.1% vs. 20%, p = .010). RA promoted HCC cell proliferation and activated the expression of Amphiregulin, a growth factor in hepatocarcinogenesis. The promoter of Amphiregulin contained the binding sites of the RA receptor, RXRα. Wnt signalling also activated the expression of Amphiregulin, and the RA and Wnt pathways acted synergistically to increase the expression of Amphiregulin. Furthermore, RXRα interacted with ß-catenin and then translocated to the nucleus to activate Amphiregulin. An increased RA concentration in the tissues adjacent to the tumour was associated with an early recurrence of HCC. RA activated the expression of Amphiregulin, and then promoted HCC proliferation, which might partly contribute to early recurrence of HCC after hepatic resection.


Asunto(s)
Anfirregulina/metabolismo , Carcinoma Hepatocelular/metabolismo , Proliferación Celular/efectos de los fármacos , Neoplasias Hepáticas/metabolismo , Tretinoina/farmacología , Proteínas Wnt/metabolismo , Anfirregulina/genética , Antineoplásicos/farmacología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , Receptor alfa X Retinoide/genética , Receptor alfa X Retinoide/metabolismo , Regulación hacia Arriba , Proteínas Wnt/genética , beta Catenina/genética , beta Catenina/metabolismo
3.
Asia Pac J Clin Nutr ; 29(2): 266-273, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32674234

RESUMEN

BACKGROUND AND OBJECTIVES: Aspiration pneumonia is a major cause of death in patients on nasogastric tube (NGT) feeding. This study aimed to evaluate the oropharyngeal dysphagia and stratify risk of pneumonia in patients undergoing NGT feeding. METHODS AND STUDY DESIGN: The study included patients on NGT feeding who underwent UGI endoscopy at Tri-Service General Hospital, Taiwan. Endoscopy was performed to examine the pharyngolaryngeal region. The severity of oropharyngeal dysphagia was evaluated according to the visualized amount and location of pooling of secretions in the pharyngolaryngeal region; 60 patients showed absent or minimal amount of secretions (control group), 14 patients showed moderate-to-large amounts of secretions filling the pyriform sinus (pharyngeal group), and 27 patients showed secretions entering the laryngeal vestibule (laryngeal group). Demographic data and occurrence of pneumonia were analyzed. RESULTS: The incidence of pneumonia was highest in the pharyngeal group (4.2±3.6 episodes/person-years), followed by the laryngeal (2.6±2.2 episodes/ person-years) and control groups (1.7±3.8 episodes/person-years) (p=0.042). Multivariable regression showed significantly higher risk of pneumonia in the pharyngeal (adjusted odds ratio=2.7, 95% CI, 2.4-2.8, p<0.001) and laryngeal (adjusted odds ratio=2.0, 95% CI, 1.7-2.4, p<0.001) groups. The cumulative incidence rate of pneumonia was significantly higher in the laryngeal and pharyngeal groups than in the control group (log rank test, p<0.001). CONCLUSIONS: Endoscopic pharyngolaryngeal observation can evaluate the oropharyngeal dysphagia. Visual evidence of oropharyngeal dysphagia increase the risk of pneumonia in patients on NGT feeding.


Asunto(s)
Trastornos de Deglución/terapia , Intubación Gastrointestinal/efectos adversos , Neumonía por Aspiración/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Trastornos de Deglución/complicaciones , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neumonía por Aspiración/etiología , Factores de Riesgo , Taiwán/epidemiología , Adulto Joven
4.
J Formos Med Assoc ; 118(5): 876-882, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30348493

RESUMEN

BACKGROUND: Colonic angiodysplasia (AGD) is a common cause of gastrointestinal bleeding. However, information on the characteristics and prevalence of colonic AGD is limited. We determined the clinical features of and risk factors for active bleeding in colonic AGD in a Taiwanese population. METHODS: From February 2007 to December 2016, 13,047 patients undergoing 16,760 colonoscopies at the Tri-Service General Hospital were included in this study. Eighty-four patients were diagnosed with AGD. We conducted a retrospective study by analyzing the medical records of these patients. The clinical features and endoscopic findings were evaluated. Furthermore, we distinguished colonic AGD into bleeding and non-bleeding types and identified the risk factors for bleeding in colonic AGD. RESULTS: In our study, the prevalence of colonic AGD was 0.6% among all patients who received colonoscopy. Among patients with colonic AGD, we found that many were aged; in all, 58.3% of patients with colonic AGD were older than 65 years. More than half of the patients had hypertensive cardiovascular disease (53.6%) and the AGD lesions were predominantly located in the left-sided colon (41.7%). We analyzed several factors to identify those associated with bleeding colonic AGD. Our results indicated that age (p < 0.001), hypertension (p = 0.020), atrial fibrillation (p = 0.027), and in-patient status (p = 0.006) were significant factors associated with active bleeding lesions. On multivariate analysis, old age was the only significant risk factor. CONCLUSION: Angiodysplastic lesions in Taiwanese patients were predominantly identified in the left-sided colon. Old age was an independent risk factor associated with active bleeding in colonic angiodysplasia.


Asunto(s)
Angiodisplasia/epidemiología , Colon/patología , Enfermedades del Colon/epidemiología , Colonoscopía , Hemorragia Gastrointestinal/etiología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Angiodisplasia/complicaciones , Pueblo Asiatico , Enfermedades del Colon/complicaciones , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiología , Adulto Joven
5.
Glycobiology ; 28(1): 9-20, 2018 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-29087466

RESUMEN

Despite well-recognized biological importance, mass spectrometry (MS)-based glycomic identification of sulfo-, sialylated terminal glyco-epitopes on the N-glycans of various immune cell types remains technically challenging and rarely reported. Previous studies with monoclonal antibody have implicated a regulated expression of 6-sulfo-α2-6-sialyl LacNAc on B cells in peripheral lymph nodes and the circulating peripheral blood lymphocytes but its occurrence on leukemia cells or lymphomas have not been critically addressed. In this study, we have extended our previously developed MS-based sulfoglycomic platform by incorporating additional complementary analytical approaches in order to achieve a high sensitivity mapping and relative quantification of the detected sulfated glycotopes down to the level of defining their sialyl linkages. We showed that discovery mode sulfoglycomics and precise location of sulfate were best achieved by multimode MS analyses of fractionated, permethylated sulfated N-glycans. On the other hand, the relative degree of sulfation on individual N-glycans could be more efficiently inferred from the respective extracted ion chromatograms of native, non-sulfated and sulfated target N-glycans in single LC-MS/MS runs. The GlcNAc-6-O-sulfated α2-6-sialyl LacNAc, which constitutes the higher affinity ligand for the human inhibitory co-receptor of B cells, CD22, was found to be commonly carried on a range of complex type N-glycans from human CD19+ and CD4+ lymphocytes. We further showed that its occurrence on the most abundant α2-6-disialylated biantennary structure from the peripheral blood mononuclear cells of patients diagnosed as B-cell chronic lymphocytic leukemia varied within ±2-fold abundance from the mean value determined for isolated CD19+ lymphocytes and cultured B-CLL cells.


Asunto(s)
Glicómica , Leucocitos Mononucleares/química , Linfocitos/química , Polisacáridos/química , Humanos , Espectrometría de Masas
6.
Am J Emerg Med ; 34(8): 1556-60, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27292601

RESUMEN

BACKGROUND: Although surgical intervention is the favorable treatment modality for perforated peptic ulcer, nonsurgical treatment is another option. The aim of this study is to analyze the results of conservative treatment for perforated peptic ulcer. METHODS: Between 2003 and 2014, 403 patients were admitted to our hospital for perforated peptic ulcer, and 383 patients underwent surgery, whereas 20 were allocated to conservative treatment. The results of nonsurgical intervention in these patients were analyzed retrospectively. RESULTS: The overall mortality rate of conservative treatment was 40%. Eleven patients remained hospitalized less than 2 weeks; among them, patients with a high (≥IV) American Society of Anesthesiologists class at admission had higher mortality than those with a low (

Asunto(s)
Tratamiento Conservador/métodos , Úlcera Duodenal/complicaciones , Úlcera Péptica Perforada/terapia , Adulto , Anciano , Anciano de 80 o más Años , Úlcera Duodenal/diagnóstico , Úlcera Duodenal/terapia , Endoscopía Gastrointestinal , Femenino , Humanos , Tiempo de Internación/tendencias , Masculino , Persona de Mediana Edad , Úlcera Péptica Perforada/diagnóstico , Úlcera Péptica Perforada/etiología , Radiografía Abdominal , Estudios Retrospectivos , Resultado del Tratamiento
7.
Liver Int ; 35(8): 2050-6, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25611851

RESUMEN

BACKGROUND & AIMS: Gilbert's syndrome causes pharmacological variation in drug glucuronidation and unexpected toxicity from therapeutic agents. The two common genotypes of Gilbert's syndrome are a dinucleotide polymorphism (TA)7 in TATA-Box as well as the 211G>A mutation in the coding exon 1, particularly in Asians, of human UGT1A1 gene. In this study, we aimed to establish an effective method to detect the 211G>A mutation. METHODS: The coding exon 1 sequence of human UGT1A1 gene was analysed by Vector NTI software. The 211G>A mutation in the coding exon 1 of UGT1A1 gene was determined by restriction fragment length polymorphism (RFLP) method. Serum total bilirubin level was measured as well. RESULTS: A newly identified BsmBI site was located in the coding exon 1 of UGT1A1 gene. The 211G>A mutation in the coding exon 1 of UGT1A1 gene was determined by DNA RFLP. Furthermore, we reported our present work on genetic analysis of mutations of UGT1A1 gene, and the correlation of UGT1A1 mutations with serum total bilirubin levels in Taiwanese population. The results showed that 15 subjects carried 211G>A mutation in 23 subjects related with Gilbert's syndrome. The homozygous 211G>A mutant as well as simultaneously heterozygous mutants both in TATA-Box and 211G>A significantly increased the risk of Gilbert's syndrome similar to subjects carrying homozygous TATA-Box mutant. CONCLUSIONS: BsmBI RFLP is an effective method to detect 211G>A mutation in the coding exon 1 of UGT1A1 gene. The common 211G>A mutation is one of the causes of Gilbert's syndrome in Taiwanese population.


Asunto(s)
Predisposición Genética a la Enfermedad/epidemiología , Enfermedad de Gilbert/genética , Glucuronosiltransferasa/genética , Polimorfismo de Longitud del Fragmento de Restricción/genética , Pueblo Asiatico/genética , Niño , Estudios de Cohortes , Exones/genética , Femenino , Genotipo , Enfermedad de Gilbert/diagnóstico , Enfermedad de Gilbert/epidemiología , Humanos , Incidencia , Masculino , Mutación , Regiones Promotoras Genéticas/genética , Estudios Retrospectivos , Taiwán/epidemiología
8.
Ann Hepatol ; 12(1): 78-84, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23293197

RESUMEN

BACKGROUND AND AIM: The aim of this study is to evaluate the role of hepatitis C virus (HCV) infection in patients with primary biliary cirrhosis (PBC). MATERIAL AND METHODS: On the basis of a retrospective review of medical records, all patients consecutively diagnosed with PBC or HCV infection between 1999 and 2011 and who had a regular follow-up of at least 3 years were included in the study. Clinical characteristics, especially the severity of cirrhosis, were analyzed in PBC patients with HCV infection (PBC-HCV), PBC patients without HCV infection (PBC-only), and patients with only HCV infection (HCV-only). RESULTS: A total of 76 patients with PBC, including 9 patients with HCV infection, were analyzed. Of the PBC-HCV patients, 7 (7/9, 77.8%) were women with a mean age of 55.11 ± 14.29 years. Age- and sex-matched PBC-only patients (n = 36) and HCV-only patients (n = 36) were used as control groups. In comparison to the PBC-only controls, PBC-HCV patients had a greater severity of cirrhosis based on Child-Pugh (p = 0.019) and Model for End-Stage Liver Disease (MELD) (p = 0.01) scores. However, no significant difference in the severity of cirrhosis was found between the PBC-HCV and HCV-only control patients (p = 0.94 in Child-Pugh scores; p = 0.64 in MELD scores). CONCLUSIONS: In PBC patients with concomitant HCV infection, aggressive management may be warranted in view of the associated more severe liver cirrhosis.


Asunto(s)
Hepatitis C/complicaciones , Cirrosis Hepática Biliar/complicaciones , Adulto , Anciano , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
9.
Biochim Biophys Acta ; 1810(12): 1262-71, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21782895

RESUMEN

BACKGROUND: There are two, largely autonomous antioxidant pathways in many organisms, one based on thioredoxin and one based on glutathione, with each pathway having a unique flavoprotein oxidoreductase to maintain them in a reduced state. A recently discovered protein, thioredoxin glutathione reductase (TGR) potentially connects these two pathways. In a large group of parasitic worms, responsible for hundreds of millions of infections in humans and animals, untold morbidity and significant mortality, TGR is the sole enzyme present to maintain redox balance. SCOPE OF REVIEW: In this review, the current understanding of the biochemical properties of TGR enzymes is compared to the related enzymes thioredoxin reductase and glutathione reductase. The role of the rare amino acid selenocysteine is discussed. An overview of the potential to target TGR for drug development against a range of parasitic worms and preliminary results to identify TGR inhibitors for schistosomiasis treatment is presented. MAJOR CONCLUSIONS: TGR has properties that are both unique and common to other flavoprotein oxidoreductases. TGR plays a fundamentally different and essential role in the redox biology of parasitic flatworms. Therefore, TGR is a promising target for drug development for schistosomiasis and other trematode and cestode infections. GENERAL SIGNIFICANCE: TGR may have differing functions in host organisms, but through analyses to understand its ability to reduce both glutathione and thioredoxin we can better understand the reaction mechanisms of an important class of enzymes. The unique properties of TGR in parasitic flatworms provide promising routes to develop new treatments for diseases.


Asunto(s)
Complejos Multienzimáticos/metabolismo , NADH NADPH Oxidorreductasas/metabolismo , Animales , Humanos , Oxidación-Reducción
10.
Org Biomol Chem ; 10(31): 6375-87, 2012 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-22777178

RESUMEN

Improving the solubility of polysubstituted 1,4-naphthoquinone derivatives was achieved by introducing nitrogen in two different positions of the naphthoquinone core, at C-5 and at C-8 of menadione through a two-step, straightforward synthesis based on the regioselective hetero-Diels-Alder reaction. The antimalarial and the antischistosomal activities of these polysubstituted aza-1,4-naphthoquinone derivatives were evaluated and led to the selection of distinct compounds for antimalarial versus antischistosomal action. The Ag(II)-assisted oxidative radical decarboxylation of the phenyl acetic acids using AgNO(3) and ammonium peroxodisulfate was modified to generate the 3-picolinyl-menadione with improved pharmacokinetic parameters, high antimalarial effects and capacity to inhibit the formation of ß-hematin.


Asunto(s)
Antimaláricos/química , Naftoquinonas/química , Plasmodium falciparum/efectos de los fármacos , Quinolinas/química , Schistosoma mansoni/efectos de los fármacos , Esquistosomicidas/química , Animales , Antimaláricos/síntesis química , Antimaláricos/farmacología , Hemina/antagonistas & inhibidores , Hemina/metabolismo , Humanos , Malaria Falciparum/tratamiento farmacológico , Metahemoglobina/metabolismo , Ratones , Naftoquinonas/síntesis química , Naftoquinonas/farmacología , Quinolinas/síntesis química , Quinolinas/farmacología , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomicidas/síntesis química , Esquistosomicidas/farmacología , Solubilidad
11.
Proc Natl Acad Sci U S A ; 106(34): 14581-6, 2009 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-19666478

RESUMEN

Infecting about one-half of the global human population, Helicobacter pylori is well established as the primary cause of gastritis, duodenal ulcer, and gastric cancer. Currently there is no clear information regarding if and how host cells interact with H. pylori, and if such interactions are dependent on the type of gastric disease. Using fluorescently labeled fucose-containing glycoconjugates, we provide evidence observing both the uptake of L-fucose from gastric cancer cells to H. pylori and that human alpha-L-fucosidase 2 (FUCA2) is secreted only under coculture conditions (i.e., host cells infected with H. pylori). Upon depletion of FUCA2 by RNA interference and detection of translocated CagA (a virulence factor of H. pylori) in host cells, FUCA2 was found to be essential for H. pylori adhesion, in particular to the gastric cancer- and duodenal ulcer-specific strains. Additionally FUCA2 was shown to significantly enhance the expression of Lewis x antigen in H. pylori, which is critical for bacterial cell adhesion in the pathogenesis and defense strategy to escape host surveillance. These findings not only demonstrate an important connection between FUCA2 and the adhesion, growth, and pathogenicity of H. pylori, but also support the idea that FUCA2 is a potential target for clinical diagnosis and therapeutic intervention of H. pylori-related diseases.


Asunto(s)
Fucosa/metabolismo , Helicobacter pylori/fisiología , alfa-L-Fucosidasa/metabolismo , Adenocarcinoma/enzimología , Adenocarcinoma/microbiología , Adenocarcinoma/patología , Secuencia de Aminoácidos , Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/metabolismo , Línea Celular , Línea Celular Tumoral , Electroforesis en Gel de Poliacrilamida , Fucosa/química , Helicobacter pylori/metabolismo , Interacciones Huésped-Patógeno , Humanos , Immunoblotting , Isoenzimas/genética , Isoenzimas/metabolismo , Cinética , Antígeno Lewis X/metabolismo , Espectrometría de Masas , Microscopía Confocal , Datos de Secuencia Molecular , Estructura Molecular , Interferencia de ARN , Homología de Secuencia de Aminoácido , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Especificidad por Sustrato , alfa-L-Fucosidasa/genética
12.
J Clin Med ; 11(13)2022 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-35807050

RESUMEN

Performing esophagogastroduodenoscopy (EGD) in recently occurring peri-coronary artery disease (CAD) accident settings is always a dilemma. This study used the Taiwan National Health Insurance Research Database to identify patients with CAD and gastrointestinal bleeding who had received EGD or not between 2000 and 2013.The final population included in this study was 15,147 individuals, with 3801 individuals having received EGD (study cohort group) and 11,346 individuals not having received EGD (comparison cohort group). We initially performed a sensitivity test for CAD recurrence-related factors using multivariable Cox regression during the tracking period. A relatively earlier EGD intervention within one week demonstrated a lower risk of CAD recurrence (adjusted HR = 0.712). Although there were no significant differences in the overall tracking period, the adjusted HR of CAD recurrence was still lower in patients in the EGD group. Furthermore, our findings revealed that there were no remarkably short intervals to CAD recurrence in the study group. The Kaplan-Meier survival curve demonstrated that individuals who underwent EGD were not associated with a significantly increased CAD recurrence rate compared with the control (Log-rank test, p = 0.255). CAD recurrence is always an issue in recent episodes of peri-CAD accident settings while receiving EGD. However, there is not a higher risk in comparison with the normal population in our study, and waiting periods may not be required.

13.
Biochemistry ; 50(26): 5870-82, 2011 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-21630672

RESUMEN

Thioredoxin glutathione reductase from Schistosoma mansoni (SmTGR) catalyzes the reduction of both thioredoxin and glutathione disulfides (GSSG), thus playing a crucial role in maintaining redox homeostasis in the parasite. In line with this role, previous studies have demonstrated that SmTGR is a promising drug target for schistosomiasis. To aid in the development of efficacious drugs that target SmTGR, it is essential to understand the catalytic mechanism of SmTGR. SmTGR is a dimeric flavoprotein in the glutathione reductase family and has a head-to-tail arrangement of its monomers; each subunit has the components of both a thioredoxin reductase (TrxR) domain and a glutaredoxin (Grx) domain. However, the active site of the TrxR domain is composed of residues from both subunits: FAD and a redox-active Cys-154/Cys-159 pair from one subunit and a redox-active Cys-596'/Sec-597' pair from the other; the active site of the Grx domain contains a redox-active Cys-28/Cys-31 pair. Via its Cys-28/Cys-31 dithiol and/or its Cys-596'/Sec-597' thiol-selenolate, SmTGR can catalyze the reduction of a variety of substrates by NADPH. It is presumed that SmTGR catalyzes deglutathionylation reactions via the Cys-28/Cys-31 dithiol. Our anaerobic titration data suggest that reducing equivalents from NADPH can indeed reach the Cys-28/Cys-31 disulfide in the Grx domain to facilitate reductions effected by this cysteine pair. To clarify the specific chemical roles of each redox-active residue with respect to its various reactivities, we generated variants of SmTGR. Cys-28 variants had no Grx deglutathionylation activity, whereas Cys-31 variants retained partial Grx deglutathionylation activity, indicating that the Cys-28 thiolate is the nucleophile initiating deglutathionylation. Lags in the steady-state kinetics, found when wild-type SmTGR was incubated at high concentrations of GSSG, were not present in Grx variants, indicating that this cysteine pair is in some way responsible for the lags. A Sec-597 variant was still able to reduce a variety of substrates, albeit slowly, showing that selenocysteine is important but is not the sole determinant for the broad substrate tolerance of the enzyme. Our data show that Cys-520 and Cys-574 are not likely to be involved in the catalytic mechanism.


Asunto(s)
Biocatálisis , Complejos Multienzimáticos/química , Complejos Multienzimáticos/metabolismo , NADH NADPH Oxidorreductasas/química , NADH NADPH Oxidorreductasas/metabolismo , Schistosoma mansoni/enzimología , Animales , Modelos Moleculares , Complejos Multienzimáticos/genética , Mutagénesis Sitio-Dirigida , NADH NADPH Oxidorreductasas/genética , Estructura Terciaria de Proteína , Selenocisteína
14.
BMC Gastroenterol ; 11: 12, 2011 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-21324124

RESUMEN

BACKGROUND: Unsedated esophagogastroduodenoscopy (EGD) is simpler and safer than sedated EGD; however, approximately 40% of patients cannot tolerate it. Early identification of patients likely to poorly tolerate unsedated EGD is valuable for improving compliance. The modified Mallampati classification (MMC) has been used to evaluate difficult tracheal intubation and laryngoscope insertion. We tried to assess the efficacy of MMC to predict the tolerance of EGD in unsedated patients. METHODS: Two hundred patients who underwent an unsedated diagnostic EGD were recruited. They were stratified according to the view of the oropharynx as either MMC class I + II (good view) or class III + IV (poor view). EGD tolerance was assessed in three ways: gag reflex by endoscopist assessment, patient satisfaction by interview, and the degree of change in vital signs. RESULTS: MMC was significantly correlated to gag reflex (P < 0.001), patient satisfaction (P = 0.028), and a change of vital signs (P = 0.024). Patients in the poor view group had a 3.87-fold increased risk of gag reflex (P < 0.001), a 1.78-fold increased risk of unsatisfaction (P = 0.067), and a 1.96-fold increased risk of a change in vital signs (P = 0.025) compared to those in the good view group. CONCLUSIONS: MMC appears to be a clinically useful predictor of EGD tolerance. Patients with poor view of oropharynx by MMC criteria may be candidates for sedated or transnasal EGD.


Asunto(s)
Endoscopía del Sistema Digestivo/efectos adversos , Atragantamiento , Glotis/anatomía & histología , Paladar Blando/anatomía & histología , Satisfacción del Paciente , Úvula/anatomía & histología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Presión Sanguínea/fisiología , Femenino , Reflujo Gastroesofágico/diagnóstico , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Úlcera Péptica/diagnóstico , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Adulto Joven
15.
Mol Cell Proteomics ; 8(9): 2034-50, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19505873

RESUMEN

Transcription factor activating enhancer-binding protein 4 (AP-4) is a basic helix-loop-helix protein that binds to E-box elements. AP-4 has received increasing attention for its regulatory role in cell growth and development, including transcriptional repression of the human homolog of murine double minute 2 (HDM2), an important oncoprotein controlling cell growth and survival, by an unknown mechanism. Here we demonstrate that AP-4 binds to an E-box located in the HDM2-P2 promoter and represses HDM2 transcription in a p53-independent manner. Incremental truncations of AP-4 revealed that the C-terminal Gln/Pro-rich domain was essential for transcriptional repression of HDM2. To further delineate the molecular mechanism(s) of AP-4 transcriptional control and its potential implications, we used DNA-affinity purification followed by complementary quantitative proteomics, cICAT and iTRAQ labeling methods, to identify a previously unknown E-box-bound AP-4 protein complex containing 75 putative components. The two labeling methods complementarily quantified differentially AP-4-enriched proteins, including the most significant recruitment of DNA damage response proteins, followed by transcription factors, transcriptional repressors/corepressors, and histone-modifying proteins. Specific interaction of AP-4 with CCCTC binding factor, stimulatory protein 1, and histone deacetylase 1 (an AP-4 corepressor) was validated using AP-4 truncation mutants. Importantly, inclusion of trichostatin A did not alleviate AP-4-mediated repression of HDM2 transcription, suggesting a previously unidentified histone deacetylase-independent repression mechanism. In contrast, the complementary quantitative proteomics study suggested that transcription repression occurs via coordination of AP-4 with other transcription factors, histone methyltransferases, and/or a nucleosome remodeling SWI.SNF complex. In addition to previously known functions of AP-4, our data suggest that AP-4 participates in a transcriptional-regulating complex at the HDM2-P2 promoter in response to DNA damage.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Elementos E-Box/genética , Proteómica , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteínas Represoras/metabolismo , Factores de Transcripción/metabolismo , Transcripción Genética , Secuencia de Bases , Sitios de Unión , Línea Celular Tumoral , Proteínas de Unión al ADN/química , Histona Desacetilasas/metabolismo , Humanos , Ácidos Hidroxámicos/farmacología , Modelos Biológicos , Datos de Secuencia Molecular , Proteínas Mutantes/metabolismo , Proteínas Nucleares/metabolismo , Regiones Promotoras Genéticas/genética , Unión Proteica/efectos de los fármacos , Estructura Terciaria de Proteína , Reproducibilidad de los Resultados , Factores de Transcripción/química , Transcripción Genética/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo
16.
Curr Med Imaging ; 17(10): 1243-1247, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34170809

RESUMEN

OBJECTIVE: Not all endoscopic clips are compatible with magnetic resonance imaging (MRI). The aim of this study is to investigate the safety of MRI-incompatible endoscopic clips in patients undergoing MRI scans. METHODS: We retrospectively reviewed the medical records of patients who had received endoscopic clip placement of Olympus Long Clip MRI-incompatible clips and then had undergone MRI scans within two weeks in our hospital between 2014 and 2019. RESULTS: A total of 44,292 patients had undergone an MRI examination at our hospital. Only 15 patients had MRI scans within two weeks after the endoscopic clip placement. Their median age was 65.5 years, and 12 of the 15 patients were men. At the time of the clip placement and MRI scan, four patients were taking anti-coagulation or anti-platelet agents. The indication for endoscopic clip placement of the 15 patients was mucosal/submucosal defect or hemorrhage and colonic perforation. Endoscopic clips were placed in the colon of 14 patients and in the stomach of only one patient for gastric hemorrhage. One patient experienced clip migration and three displayed artifacts in abdominal images. No patient complications of mortality, hemorrhage, or organ perforation occurred. CONCLUSION: No serious adverse event occurred during MRI scans of patients with MRI-incompatible clips in this study, suggesting that MRI-incompatible clips may be safe to use in MRI scans. However, this does not guarantee the safety of the Long Clip for MRI scans, as further tests are needed to verify that this clip is safe for use during MRI.


Asunto(s)
Imagen por Resonancia Magnética , Instrumentos Quirúrgicos , Anciano , Colon , Hemorragia Gastrointestinal , Humanos , Masculino , Estudios Retrospectivos
17.
Life Sci ; 284: 119708, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34153299

RESUMEN

AIMS: Hepatocellular carcinoma (HCC) is a primary malignancy of the hepatocyte. Interleukin enhancer binding factor 2 (ILF2) plays a role in the development of HCC. However, the regulatory mechanisms of ILF2 expression in HCC remain unclear. In this study, we aimed to identify ILF2-targeting microRNAs (miRNAs) and to explore how they affect ILF2 expression in HCC. MAIN METHODS: The tissue specimens were collected from 25 HCC patients. The underlying regulatory mechanism of ILF2 expression in HCC progression was determined using luciferase reporter assay, quantitative real-time PCR, Western blotting, and BrdU incorporation assay. KEY FINDINGS: Of predicted miRNA candidates (miR-122-5p, miR-425-5p, miR-136-5p, miR-7-5p, miR-421 and miR-543), a statistically significant inverse correlation by linear correlation analysis was observed between miR-136-5p and ILF2 mRNA expressions in patients with HCC (r = -0.627, P < 0.001). Further analysis demonstrated that ILF2 was directly regulated by miR-136-5p. In addition, we showed that long noncoding RNA colorectal neoplasia differentially expressed-h (lncRNA CRNDE-h) transcript expression was significantly up-regulated in HCC, and a miR-136-5p binding site was newly found in the lncRNA CRNDE-h transcript sequence using IntaRNA tool. In terms of mechanism, highly-expressed lncRNA CRNDE-h transcript can sponge miR-136-5p, thereby preventing it from interacting with target ILF2 mRNA while promoting the proliferation of HCC cells. SIGNIFICANCE: The lncRNA CRNDE-h/miR-136-5p/ILF2 axis plays a significant regulatory role in HCC progression, which may partly explain the pathogenic mechanisms of HCC and may provide promising potential targets for the diagnosis, treatment, and prognosis of HCC.


Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , MicroARNs/metabolismo , Proteína del Factor Nuclear 45/genética , ARN Largo no Codificante/metabolismo , Secuencia de Bases , Línea Celular Tumoral , Proliferación Celular/genética , Humanos , MicroARNs/genética , Proteína del Factor Nuclear 45/metabolismo , ARN Largo no Codificante/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo
18.
JPEN J Parenter Enteral Nutr ; 44(2): 239-245, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-30983013

RESUMEN

BACKGROUND: Aspiration pneumonia is the most common cause of death in patients who undergo percutaneous endoscopic gastrostomy (PEG). This study aims to evaluate the severity of oropharyngeal dysphagia and predict the risk of pneumonia in such patients, using upper gastrointestinal endoscopy. METHODS: Endoscope examined the pharyngolaryngeal region in patients who underwent PEG. The severity of oropharyngeal dysphagia was evaluated according to the amount and location of pooling of secretions in the pharyngolaryngeal region. Overall, 55 patients showed absent or minimal amount of secretions (control group), 10 patients showed moderate-to-large amounts of secretions filling the pyriform sinus (pharyngeal group), and 23 patients showed secretions entering the laryngeal vestibule (laryngeal group). Demographic data, swallowing level scale, and occurrence of pneumonia were recorded. RESULTS: The incidence of pneumonia was the highest in the pharyngeal group (70.0%), followed by that in the laryngeal (60.9%) and control groups (30.9%; P = 0.010). Multivariable regression showed that risk of pneumonia was significantly higher in the pharyngeal and laryngeal groups. Cumulative incidence rate of pneumonia was significantly higher in the laryngeal and pharyngeal groups than in the control group (log-rank test, P = 0.001). Mortality rate was significantly higher in patients with suboptimal protective cough reflex than in others (50.0% vs 5.9%, P = 0.034). CONCLUSION: Accumulation of abnormal amounts of secretions in the pyriform sinus or in the laryngeal vestibule increased the risk of the hospital admission following pneumonia in patients who underwent PEG. The mortality rate was higher in patients with suboptimal protective cough reflex.


Asunto(s)
Trastornos de Deglución , Gastrostomía , Neumonía por Aspiración , Neumonía , Deglución , Trastornos de Deglución/etiología , Gastrostomía/efectos adversos , Humanos , Neumonía/etiología , Neumonía por Aspiración/etiología
19.
World J Gastroenterol ; 26(26): 3767-3779, 2020 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-32774056

RESUMEN

BACKGROUND: Patient-ready duodenoscopes were designed with an assumed contamination rate of less than 0.4%; however, it has been reported that 5.4% of clinically used duodenoscopes remain contaminated with viable high-concern organisms despite following the manufacturer's instructions. Visual inspection of working channels has been proposed as a quality control measure for endoscope reprocessing. There are few studies related to this issue. AIM: To investigate the types, severity rate, and locations of abnormal visual inspection findings inside patient-ready duodenoscopes and their microbiological significance. METHODS: Visual inspections of channels were performed in 19 patient-ready duodenoscopes using the SpyGlass visualization system in two endoscopy units of tertiary care teaching hospitals (Tri-Service General Hospital and National Taiwan University Hospital) in Taiwan. Inspections were recorded and reviewed to evaluate the presence of channel scratches, buckling, stains, debris, and fluids. These findings were used to analyze the relevance of microbiological surveillance. RESULTS: Seventy-two abnormal visual inspection findings in the 19 duodenoscopes were found, including scratches (n = 10, 52.6%), buckling (n = 15, 78.9%), stains (n = 14, 73.7%), debris (n = 14, 73.7%), and fluids (n = 6, 31.6%). Duodenoscopes > 12 mo old had a significantly higher number of abnormal visual inspection findings than those ≤ 12 mo old (46 findings vs 26 findings, P < 0.001). Multivariable regression analyses demonstrated that the bending section had a significantly higher risk of being scratched, buckled, and stained, and accumulating debris than the insertion tube. Debris and fluids showed a significant positive correlation with microbiological contamination (P < 0.05). There was no significant positive Spearman's correlation coefficient between negative bacterial cultures and debris, between that and fluids, and the concomitance of debris and fluids. This result demonstrated that the presence of fluid and debris was associated with positive cultures, but not negative cultures. Further multivariate analysis demonstrated that fluids, but not debris, is an independent factor for bacterial culture positivity. CONCLUSION: In patient-ready duodenoscopes, scratches, buckling, stains, debris, and fluids inside the working channel are common, which increase the microbiological contamination susceptibility. The SpyGlass visualization system may be recommended to identify suboptimal reprocessing.


Asunto(s)
Duodenoscopios , Contaminación de Equipos , Desinfección , Endoscopios , Humanos , Taiwán
20.
Am J Med Sci ; 360(2): 161-165, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32448495

RESUMEN

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is regarded as a feature of metabolic syndrome in the liver. Metabolic syndrome is associated with a higher risk of bladder cancer. However, the association between NAFLD and bladder cancer is unclear. We aimed to investigate the association between NAFLD and bladder cancer. MATERIALS AND METHODS: The records of all patients (n = 251) diagnosed with the bladder cancer in our hospital between 2009 and 2013 were reviewed. We also randomly collected the records of adults without cancer (n = 266) as the control group. Clinical characteristics, biochemical tests for liver and metabolic function and abdominal computed tomography were assessed. RESULTS: The incidence of NAFLD was 12.0% in the bladder cancer group and 4.9% in the control group. By multiple logistic regression analysis, NAFLD (P = 0.007; odds ratio [OR]: 2.61; 95% confidence interval [CI]: 1.30-5.22), male sex (P < 0.001; OR: 2.34; 95% CI: 1.61-3.41) and use of lipid lowering drugs (P = 0.001; OR: 0.43; 95% CI: 0.26-0.72) showed significant associations with bladder cancer. In bladder cancer patients, the median survival time was significantly longer in patients without NAFLD than in these with NAFLD (40 months versus 21.5 months, P = 0.022). CONCLUSIONS: NAFLD was positively associated with bladder cancer and was a poor prognostic factor of bladder cancer. Further studies are needed to confirm whether NAFLD is a factor for the development of bladder cancer.


Asunto(s)
Carcinoma de Células Transicionales/epidemiología , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Neoplasias de la Vejiga Urinaria/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hipolipemiantes/uso terapéutico , Modelos Logísticos , Masculino , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Tasa de Supervivencia , Taiwán/epidemiología
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