RESUMEN
The link between neonatal jaundice and urinary tract infection (UTI) remains debated, with congenital kidney and urinary tract anomalies (CAKUT) potentially playing a role. This population-based study aimed to analyze the correlations between neonatal jaundice, CAKUT, and concomitant UTI. The study cohort consisted of 2,078,122 live births from 2004 to 2014. We linked several population-based datasets in Taiwan to identify infants with unexplained neonatal jaundice and their mothers. The primary outcome was the rate of CAKUT occurring within 3 years after delivery, and the presence of concomitant UTI during neonatal jaundice hospitalization. Infants with neonatal jaundice had a significantly higher risk of CAKUT (adjusted odds ratio [aOR] 1.24, 95% confidence interval [CI] 1.11-1.39) during early childhood. Among the subtypes of CAKUT, obstructive uropathy, vesicoureteral reflux and other CAKUT were associated with an increased risk of neonatal jaundice. Infants who underwent intensive phototherapy, had a late diagnosis (> 14 days of postnatal age) or underwent a prolonged duration of phototherapy (> 3 days) exhibited a higher risk of concomitant UTI compared to other infants with jaundice. Our findings indicate a notable association between neonatal jaundice and increased risks of UTIs in the context of CAKUT. This study underscore the importance of vigilant monitoring and timely interventions for neonates presenting with jaundice, while acknowledging the complexity and variability in the progression of CAKUT and its potential connection to UTIs.
Asunto(s)
Ictericia Neonatal , Infecciones Urinarias , Reflujo Vesicoureteral , Humanos , Infecciones Urinarias/complicaciones , Infecciones Urinarias/epidemiología , Ictericia Neonatal/epidemiología , Ictericia Neonatal/complicaciones , Ictericia Neonatal/etiología , Femenino , Recién Nacido , Masculino , Taiwán/epidemiología , Factores de Riesgo , Riñón/anomalías , Lactante , Sistema Urinario/anomalías , Anomalías Urogenitales/complicaciones , Anomalías Urogenitales/epidemiologíaRESUMEN
PURPOSE: Lack of control over Internet gaming habits may result in negative consequences. This study aimed to evaluate the emotional regulation of adults with Internet gaming disorder (IGD) and the association of emotion regulation, depression, and hostility. METHODS: Advertisements were used to recruit 69 young adults with IGD, 69 sex- and age-matched controls, and 69 sex- and age-matched regular gamers. The diagnosis of IGD was according to diagnostic interviews based on DSM-5 IGD research criteria. Participants completed the Affective Style Questionnaire, the center of epidemiological studies depression scale and the short-form Chinese version of Buss-Durkee Hostility Inventory. RESULTS: In the IGD group, the emotion adjustment score was significantly lower, whereas the scores for depression, and hostility were significantly higher than in the other two groups. In addition, emotion adjustment is the most associated emotion regulation behavior of IGD, followed by emotion concealment. In IGD group, emotion adjustment had a negative correlation with depression and hostility. CONCLUSIONS: Our study demonstrate that emotion adjustment is significantly associated with IGD. The depression and hostility mediated the association. Knowing that emotion adjustment plays a critical role in IGD, future interventions should focus on this subscale of emotion regulation.
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Regulación Emocional/fisiología , Trastorno de Adicción a Internet/diagnóstico , Trastorno de Adicción a Internet/psicología , Encuestas y Cuestionarios , Juegos de Video/psicología , Adulto , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Hostilidad , Humanos , Trastorno de Adicción a Internet/epidemiología , Masculino , Adulto JovenRESUMEN
Circulating tumor cells (CTC) play important roles in various cancers; however, few studies have assessed their clinical utility in neuroendocrine tumors. This study aimed to prospectively evaluate the prognostic value of CTC counts in Asian patients with neuroendocrine tumors before and during anti-cancer therapy. Patients who were diagnosed with unresectable histological neuroendocrine tumors between September 2011 and September 2017 were enrolled. CTC testing was performed before and during anti-cancer therapy using a negative selection protocol. Chromogranin A levels were also assessed. Univariate and multivariate Cox's proportional hazard model with forward LR model was performed to investigate the impact of independent factors on overall survival and progression-free survival. Kaplan-Meier method with log-rank tests were used to determine the difference among different clinicopathological signatures and CTC cutoff. The baseline CTC detection rate was 94.3% (33/35). CTC counts were associated with cancer stages (I-III vs. IV, P = 0.015), liver metastasis (P = 0.026), and neuroendocrine tumor grading (P = 0.03). The median progression-free survival and overall survivals were 12.3 and 30.4 months, respectively. In multivariate Cox regression model, neuroendocrine tumors grading and baseline CTC counts were both independent prognostic factors for progression-free survival (PFS, P = 0.005 and 0.015, respectively) and overall survival (OS, P = 0.018 and 0.023, respectively). In Kaplan-Meier analysis, lower baseline chromogranin A levels were associated with longer PFS (P = 0.024). Baseline CTC counts are associated with the clinicopathologic features of neuroendocrine tumors and are an independent prognostic factor for this malignancy.
Asunto(s)
Células Neoplásicas Circulantes/patología , Tumores Neuroendocrinos/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Adulto JovenRESUMEN
BACKGROUND: This study aimed to evaluate the role of baseline circulating tumor cells (CTCs) before and during concurrent chemoradiotherapy and attempted to determine the impacts of CTCs on the outcomes in patients with head and neck squamous cell carcinoma. METHODS: CTCs were detected using a negative selection strategy and flow cytometry protocol. RESULTS: We observed a significant correlation between baseline CTCs and staging (P = 0.001). The CTC counts were significantly reduced within 2-4 weeks in 47 concurrent chemoradiotherapy responders (P < 0.001). Change of CTC counts correlates with progression-free survival (PFS, P = 0.01) and overall survival (OS, P = 0.01). CTC decline status was an independent prognostic factor in PFS (P = 0.03) and OS (P = 0.05) in multivariate analyses. CONCLUSION: In chemoradiotherapy responders, CTCs are significantly reduced. CTC decline within the first month indicates a longer PFS and OS, suggesting that the dynamics of CTCs could be more important than CTC number alone.
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Quimioradioterapia , Neoplasias de Cabeza y Cuello/patología , Células Neoplásicas Circulantes , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Adulto , Anciano , Biomarcadores de Tumor/sangre , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/terapia , Humanos , Análisis de Intención de Tratar , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Análisis de SupervivenciaRESUMEN
OBJECTIVE OF STUDY: Alcohol use disorder is one of the most important factors contributing to dementia. This study examined the protective effect of thiamine administration on the incidence of dementia among patients with alcohol use disorder in Taiwan by evaluating a nationwide database. METHODS: We retrieved data for this retrospective cohort study from the Longitudinal Health Insurance Database 1995-2000. Patients receiving thiamine therapy after the diagnosis of alcohol use disorder were recruited as the thiamine therapy (TT) group, and the comparison group without TT (NTT group) included randomly assigned and age-, sex-, and index year-matched individuals with alcohol use disorder. Demographic data, comorbid medical disorders, and psychotropic medication use were evaluated and controlled. The cumulative defined daily dose (DDD) was analyzed to demonstrate the dose effect. RESULTS: Each group had 5059 patients. The TT group had a lower crude hazard ratio (0.76; 95% confidence interval: 0.60-0.96) of dementia than the NTT group. After adjusting for demographic data, comorbidity, and psychotropic medication use, the adjusted hazard ratio was 0.54 (95% confidence interval: 0.43-0.69). The significance existed among TT subjects with cumulative DDD higher than 23. The Kaplan-Meier analysis demonstrated a lower cumulative incidence of dementia in the TT group than in the NTT group. CONCLUSION: The results indicated that thiamine therapy could be a protective factor for dementia development in patients with alcohol use disorder. Thiamine therapy should be a crucial part of the treatment plan and health policies to prevent dementia development or progression among patients with alcohol use disorder.
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Alcoholismo , Demencia , Sustancias Protectoras/uso terapéutico , Tiamina/uso terapéutico , Adulto , Anciano , Alcoholismo/complicaciones , Alcoholismo/epidemiología , Comorbilidad , Demencia/tratamiento farmacológico , Demencia/etiología , Demencia/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Bioelectrical impedance analysis (BIA) is commonly used to assess body composition. Cross-mode (left hand to right foot, Z(CR)) BIA presumably uses the longest current path in the human body, which may generate better results when estimating fat-free mass (FFM). We compared the cross-mode with the hand-to-foot mode (right hand to right foot, Z(HF)) using dual-energy x-ray absorptiometry (DXA) as the reference. We hypothesized that when comparing anthropometric parameters using stepwise regression analysis, the impedance value from the cross-mode analysis would have better prediction accuracy than that from the hand-to-foot mode analysis. We studied 264 men and 232 women (mean ages, 32.19 ± 14.95 and 34.51 ± 14.96 years, respectively; mean body mass indexes, 24.54 ± 3.74 and 23.44 ± 4.61 kg/m2, respectively). The DXA-measured FFMs in men and women were 58.85 ± 8.15 and 40.48 ± 5.64 kg, respectively. Multiple stepwise linear regression analyses were performed to construct sex-specific FFM equations. The correlations of FFM measured by DXA vs. FFM from hand-to-foot mode and estimated FFM by cross-mode were 0.85 and 0.86 in women, with standard errors of estimate of 2.96 and 2.92 kg, respectively. In men, they were 0.91 and 0.91, with standard errors of the estimates of 3.34 and 3.48 kg, respectively. Bland-Altman plots showed limits of agreement of -6.78 to 6.78 kg for FFM from hand-to-foot mode and -7.06 to 7.06 kg for estimated FFM by cross-mode for men, and -5.91 to 5.91 and -5.84 to 5.84 kg, respectively, for women. Paired t tests showed no significant differences between the 2 modes (P > .05). Hence, cross-mode BIA appears to represent a reasonable and practical application for assessing FFM in Chinese populations.
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Absorciometría de Fotón/estadística & datos numéricos , Composición Corporal , Índice de Masa Corporal , Postura , Adolescente , Adulto , Anciano , Impedancia Eléctrica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Cancer stem cells (CSCs) represent a unique sub-population of tumor cells with the ability to initiate tumor growth and sustain self-renewal. Although CSC biomarkers have been described for various tumors, only a few markers have been identified for nasopharyngeal carcinoma (NPC). In this study, we show that CD24+ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/ß-catenin signaling pathway. CD24+ cells possess typical CSC characteristics that include enhanced cell proliferation, increased colony and sphere formation, maintenance of cell differentiation potential in prolonged culture, and enhanced resistance to chemotherapeutic drugs. Notably, CD24+ cells produce tumors following inoculation of as few as 500 cells in immunodeficient NOD/SCID mice. CD24+ cells further show increased invasion ability in vitro, which correlates with enhanced expression of matrix metalloproteinase 2 and 9. In summary, our results suggest that CD24 represents a novel CSC biomarker in NPC.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Antígeno CD24/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Células Madre Neoplásicas/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Carcinoma , Recuento de Células , Diferenciación Celular , Línea Celular Tumoral , Proliferación Celular , Separación Celular , Células Clonales , Resistencia a Antineoplásicos , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica , Humanos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos NOD , Ratones SCID , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/enzimología , Neoplasias Nasofaríngeas/genética , Invasividad Neoplásica , Proteínas de Neoplasias/metabolismo , Esferoides Celulares/patología , Vía de Señalización WntRESUMEN
We conducted an extensive study in Taiwan of Orientia tsutsugamushi (OT) infection in small wild mammals. Field trapping was carried out at six districts in eastern and western Taiwan as well as various offshore islands during the period 2006-2010. A total of 1061 specimens representing 11 rodent species were captured. The presence of OT infection was assessed by indirect immunofluorescence assay and polymerase chain reaction assays of 56-kDa type-specific antigen gene. The chigger infestation rate among the animals was 35% (371/1061). Among these, OT was detected in 64% (238/371) of the chiggers from the infested animals and in the spleens from 273 (34.3%) of 797 animals. Excluding animals in the Suncus murinus group, the antibody positive rate of scrub typhus was 69.1% (477 of 690 of serum samples). The prevalence of OT infection in animals from areas with a low incidence of human cases of scrub typhus was significantly lower than that in rodents obtained from regions with a high incidence of human cases of the disease (44.4%±4.0% vs. 71.2%±9.7%, p<0.001). In Taiwan, the prevalence of OT infection in wild rodents is considerably high and appears to correlate positively with the occurrence of scrub typhus in humans.
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Anticuerpos Antibacterianos/sangre , Infestaciones por Ácaros/veterinaria , Orientia tsutsugamushi/aislamiento & purificación , Enfermedades de los Roedores , Roedores/microbiología , Tifus por Ácaros/veterinaria , Animales , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Masculino , Infestaciones por Ácaros/epidemiología , Infestaciones por Ácaros/microbiología , Orientia tsutsugamushi/genética , Reacción en Cadena de la Polimerasa/veterinaria , Prevalencia , Tifus por Ácaros/epidemiología , Tifus por Ácaros/microbiología , Bazo/microbiología , Taiwán/epidemiología , Trombiculidae/microbiologíaRESUMEN
Rapid identification of single and multiple infectious agents is vital in clinical settings and during biothreat attack. This study assesses the assay of single-stranded multiplex polymerase chain reaction (PCR) amplicons by suspension bead array (SSMP-SBA) for multiple pathogens identification in a single-tube reaction. A 15-plex assay for identification of 11 highly infectious pathogens was developed to evaluate the performance of SSMP-SBA. Pathogen-specific amplicons were obtained by sequential amplification of genomic DNAs using gene-specific primers tagged with artificial unique sequences and unique primers of which the reverse primer was modified by biotin and phosphorothioate. The SSMP products generated by T7 exonuclease-mediated DNA hydrolysis were hybridized to 15 sets of beads coupled with gene-specific and control oligonucleotide probes for pathogen identification and quantification by flow cytometry. This method was validated via assessment of 57 reference strains and one clinical bacterial isolate. All 11 pathogens can be detected by the 15-plex SSMP-SBA assay, and this design significantly enhanced the signal-to-noise ratio and improved the assay performance. This assay achieves similar sensitivity to our in-house real-time PCR system with the limit of detection equivalent to 5-100 genome copies and a linear dynamic range crossing three to five logs. In the validation assay, a 100% accuracy rate was achieved when the pathogens were among the target species. Notably, the species of pathogens were accurately identified from the samples with multiple infections. SSMP-SBA presents superior performance with multiplexing capability in a single-tube reaction and provides a new approach for detection and species identification of multiple pathogen infections.
Asunto(s)
Patógenos Transmitidos por la Sangre/aislamiento & purificación , Brucella/genética , ADN Bacteriano/análisis , Reacción en Cadena de la Polimerasa Multiplex/métodos , Patógenos Transmitidos por la Sangre/clasificación , Brucella/aislamiento & purificación , Brucelosis/diagnóstico , Brucelosis/genética , ADN Bacteriano/genética , Femenino , Humanos , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Relación Señal-RuidoRESUMEN
BACKGROUND: Lethal toxin (LT) is a major virulence factor of Bacillus anthracis. Sprague Dawley rats manifest pronounced lung edema and shock after LT treatments, resulting in high mortality. The heart failure that is induced by LT has been suggested to be a principal mechanism of lung edema and mortality in rodents. Since LT-induced death occurs more rapidly in rats than in mice, suggesting that other mechanisms in addition to the heart dysfunction may be contributed to the fast progression of LT-induced pathogenesis in rats. Coagulopathy may contribute to circulatory failure and lung injury. However, the effect of LT on coagulation-induced lung dysfunction is unclear. METHODS: To investigate the involvement of coagulopathy in LT-mediated pathogenesis, the mortality, lung histology and coagulant levels of LT-treated rats were examined. The effects of activated protein C (aPC) on LT-mediated pathogenesis were also evaluated. RESULTS: Fibrin depositions were detected in the lungs of LT-treated rats, indicating that coagulation was activated. Increased levels of plasma D-dimer and thrombomodulin, and the ameliorative effect of aPC further suggested that the activation of coagulation-fibrinolysis pathways plays a role in LT-mediated pathogenesis in rats. Reduced mortality was associated with decreased plasma levels of D-dimer and thrombomodulin following aPC treatments in rats with LT-mediated pathogenesis. CONCLUSIONS: These findings suggest that the activation of coagulation in lung tissue contributes to mortality in LT-mediated pathogenesis in rats. In addition, anticoagulant aPC may help to develop a feasible therapeutic strategy.
Asunto(s)
Carbunco , Bacillus anthracis , Insuficiencia Cardíaca/inducido químicamente , Proteína C , Animales , Carbunco/tratamiento farmacológico , Carbunco/microbiología , Carbunco/fisiopatología , Antígenos Bacterianos/efectos de los fármacos , Antígenos Bacterianos/toxicidad , Bacillus anthracis/efectos de los fármacos , Bacillus anthracis/patogenicidad , Toxinas Bacterianas/antagonistas & inhibidores , Toxinas Bacterianas/toxicidad , Coagulación Sanguínea/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Humanos , Inyecciones Intraventriculares , Pulmón/irrigación sanguínea , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/fisiopatología , Proteína C/administración & dosificación , Proteína C/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
ß-Amyloid peptides (Aß) are neurotoxic and contribute to the development of Alzheimer's disease (AD). Ergothioneine (EGT) has been shown to protect against loss of memory and learning abilities in mice. In this study, mice were orally fed EGT (0.5 or 2 mg/kg body weight) for 16 days before treatment (i.c.v) with a single dose of Aß1-40 in the hippocampus. After resting for 12 days to restore the body weight, the mice were again fed EGT for additional 39 days. Active avoidance tests were conducted on days 37-39 (short-memory avoidance) and on days 37, 44 and 51 (long-memory avoidance). Water maze task was used to evaluate learning and memory abilities by acquisition test and retention test. In both long-memory avoidance and water maze tests, EGT significantly decreased the escape latency and increased the frequency of successful avoidance. Furthermore, EGT significantly prevented Aß accumulation in the hippocampus and brain lipid peroxidation, restored acetylcholinesterase (AChE) activity, maintained glutathione/glutathione disulfide ratio and superoxide dismutase activity in brain tissues of Aß1-40-teated mice. Thus, EGT can protect against Aß-induced loss of memory and learning abilities in mice. Further studies are required to confirm the protective effects of EGT on the development or progression of AD.
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Péptidos beta-Amiloides/toxicidad , Encéfalo/efectos de los fármacos , Ergotioneína/farmacología , Neuronas/efectos de los fármacos , Fragmentos de Péptidos/toxicidad , Acetilcolinesterasa/metabolismo , Administración Oral , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Animales , Reacción de Prevención/efectos de los fármacos , Encéfalo/metabolismo , Ergotioneína/administración & dosificación , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/prevención & control , Ratones , Ratones Endogámicos C57BL , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Fragmentos de Péptidos/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
S-Adenosylhomocysteine (SAH) is a risk factor for neurodegenerative diseases such as Alzheimer's disease, for which ß-Amyliod (Aß) formation is a major risk factor. We recently showed that SAH increases Aß formation in mouse microglial BV2 cells. Here, we show that incubation of BV2 cells with SAH (0-500nM) for 6-24h sequentially increased Aß formation, ROS and DNA damage measured as 8-oxo-deoxyguanosine (8-oxo-dG) levels. Pre-incubation of BV2 cells with 20µM ß-secretase inhibitor IV for 30min followed by incubation with SAH (500nM) markedly decreased Aß formation and 8-oxo-dG levels. Treatment with SAH for 24h concentration-dependently inhibited DNA methyltransferase (DNMT1) activity and inhibited DNMT1 binding to Sp1 site of 8-oxoG-DNA glycosylases I (OGG1) promoter and OGG1 protein and mRNA expression at 24h; the latter effect was attributed to hypomethylation of the OGG1 gene promoter, because pre-incubation of cells with betaine (1.0mM for 30 min) markedly prevented the inhibition of OGG1 protein expression induced by SAH. Overall, we demonstrate that SAH increases DNA damage in BV-2 cells possible by increased Aß formation leading to increased formation of ROS. Furthermore, the DNA damage is enhanced by SAH through inhibition of DNMT1 activity and hypomethylation of OGG1 gene promoter.
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Péptidos beta-Amiloides/efectos de los fármacos , Daño del ADN/efectos de los fármacos , ADN Glicosilasas/antagonistas & inhibidores , Microglía/efectos de los fármacos , S-Adenosilhomocisteína/toxicidad , Péptidos beta-Amiloides/metabolismo , Animales , Células Cultivadas , ADN (Citosina-5-)-Metiltransferasa 1 , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , Reparación del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ratones , Microglía/metabolismo , Regiones Promotoras Genéticas , Especies Reactivas de Oxígeno/metabolismo , S-Adenosilhomocisteína/administración & dosificación , S-Adenosilhomocisteína/metabolismo , Factores de TiempoRESUMEN
Osajin is a prenylated isoflavone showing antitumor activity in different tumor cell lines. The underlying mechanism of osajin-induced cancer cell death is not clearly understood. In the present study, the mechanisms of osajin-induced cell death of human nasopharyngeal carcinoma (NPC) cells were explored. Osajin was found to significantly induce apoptosis of NPC cells in a dose- and time-dependent manner. Multiple molecular effects were observed during osajin treatment including a significant loss of mitochondrial transmembrane potential, release of cytochrome c into the cytosol, enhanced expression of Fas ligand (FasL), suppression of glucose-regulated protein 78 kDa (GRP78), and activation of caspases-9, -8, -4 and -3. In addition, up-regulation of proapoptotic Bax protein and down-regulation of antiapoptotic Bcl-2 protein were also observed. Taken together, osajin induces apoptosis in human NPC cells through multiple apoptotic pathways, including the extrinsic death receptor pathway, and intrinsic pathways relying on mitochondria and endoplasmic reticulum stress. Thus, osajin could be developed as a new effective and chemopreventive compound for human NPC.
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Apoptosis , Isoflavonas/farmacología , Neoplasias Nasofaríngeas/patología , Extractos Vegetales/farmacología , Línea Celular Tumoral , Chaperón BiP del Retículo Endoplásmico , Humanos , Potenciales de la Membrana/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Neoplasias Nasofaríngeas/metabolismoRESUMEN
Orientia tsutsugamushi is the etiological agent of scrub typhus, a mite-borne, febrile illness that occurs in the Asia-Pacific region. We conducted strain characterization of O. tsutsugamushi isolates from chiggers obtained from rodents based the nucleotide sequence of the 56-kDa outer membrane protein gene. With the use of PCR, a total of 68 DNA sequences of 56-kDa antigen genes were amplified. Phylogenetic analysis revealed that there were at least six definable clusters among the 68 isolates: 37% Karp-related strains (25/68), 27% TA763 strains (18/68), 12% JG-related strains (8/68), 19% Kato-related strains (13/68), 4% divergent strains (3/68), and 1% representing a Gilliam prototype strain (1/68). Overall, the O. tsutsugamushi genotypes exhibited a high degree of diversity, similar to that seen in strains from the rest of the areas where scrub typhus is endemic. Moreover, the 56-kDa protein sequence similarity between O. tsutsugamushi isolates from mites and those from human patients (H. Y. Lu et al., Am. J. Trop. Med. Hyg. 83:658-663, 2010) were striking, thus highlighting potential risk factors for this emerging zoonotic disease.
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Antígenos Bacterianos/genética , Proteínas de la Membrana Bacteriana Externa/genética , Técnicas de Tipificación Bacteriana , Tipificación Molecular , Orientia tsutsugamushi/clasificación , Roedores/parasitología , Trombiculidae/microbiología , Animales , Análisis por Conglomerados , ADN Bacteriano/química , ADN Bacteriano/genética , Variación Genética , Genotipo , Datos de Secuencia Molecular , Orientia tsutsugamushi/genética , Filogenia , Análisis de Secuencia de ADN , TaiwánRESUMEN
Resveratrol, a naturally occurring dietary compound with chemopreventive properties has been reported to trigger a variety of cancer cell types to apoptosis. Whether resveratrol shows any activity on human nasopharyngeal carcinoma (NPC) cells remained to be determined. The aim of this study was to investigate the effect and mechanism of resveratrol on human NPC cells. Treatment of resveratrol resulted in significant decrease in cell viability of NPC cell lines in a dose- and time-dependent manner. A dose-dependent apoptotic cell death was also measured by flow cytometery analysis. Molecular mechanistic studies of apoptosis unraveled resveratrol treatment resulted in a significant loss of mitochondrial transmembrane potential, release of cytochrome c, enhanced expression of Fas ligand (FasL), and suppression of glucose-regulated protein 78 kDa (GRP78). These were followed by activation of caspases-9, -8, -4, and -3, subsequently leading to DNA fragmentation and cell apoptosis. Furthermore, up-regulation of proapoptotic Bax and down-regulation of antiapoptotic Bcl-2 protein were also observed. Taken together, resveratrol induces apoptosis in human NPC cells through regulation of multiple apoptotic pathways, including death receptor, mitochondria, and endoplasmic reticulum (ER) stress. Resveratrol can be developed as an effective compound for human NPC treatment.
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Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Estilbenos/farmacología , Carcinoma , Caspasas/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Chaperón BiP del Retículo Endoplásmico , Proteína Ligando Fas/genética , Proteína Ligando Fas/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Modelos Biológicos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/enzimología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Resveratrol , Factor de Transcripción CHOP/genética , Factor de Transcripción CHOP/metabolismoRESUMEN
BACKGROUND: Lethal toxin (LT), the major virulence factor produced by Bacillus anthracis, has been shown to suppress the immune system, which is beneficial to the establishment of B. anthracis infections. It has been suggested that the suppression of MEK/MAPK signaling pathways of leukocytes contributes to LT-mediated immunosuppressive effects. However, the involvement of MAPK independent pathways has not been clearly elucidated; nor has the crucial role played by LT in the early stages of infection. Determining whether LT exerts any pathological effects before being enriched to an MEK inhibitory level is an important next step in the furtherance of this field. METHODOLOGY/PRINCIPAL FINDINGS: Using a cell culture model, we determined that low doses of LT inhibited phagocytosis of macrophages, without influencing MAPK pathways. Consistent low doses of LT significantly suppressed bacterial clearance and enhanced the mortality of mice with bacteremia, without suppressing the MEK1 of splenic and peripheral blood mononuclear cells. CONCLUSION/SIGNIFICANCE: These results suggest that LT suppresses the phagocytes in a dose range lower than that required to suppress MEK1 in the early stages of infection.
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Antígenos Bacterianos/metabolismo , Toxinas Bacterianas/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Animales , Bacillus anthracis/inmunología , Citometría de Flujo/métodos , Inmunosupresores/metabolismo , Leucocitos/citología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/microbiología , MAP Quinasa Quinasa 1/metabolismo , Macrófagos/microbiología , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Biológicos , Fagocitosis , Sepsis/microbiologíaRESUMEN
S-Adenosylhomocysteine (SAH) is a risk factor for many diseases, including tumor progression and neurodegenerative disease. In this study, we examined the hypothesis that SAH may indirectly enhance the invasion of C6 glioma cells by induction of matrix metalloproteinase-2 (MMP-2) secreted from the murine microglia BV2 cells. We obtained conditioned medium (CM) by incubating BV2 cells with SAH (1-50nM) for 24 h. We found that the SAH-containing CM (SAH-BV2-CM) strongly enhanced the invasiveness of C6 glioma cells and that this effect increased with increasing concentrations of SAH in the SAH-BV2-CM. The effect of CM could be attributed to its MMP-2 activity, as a result of increased protein and messenger RNA expression of MMP-2 in BV2 cells induced by SAH. In BV2 cells treated with SAH, the binding abilities of nuclear factor-kappa B (NF-kappaB) and stimulatory protein-1 (Sp1) to the MMP-2 promoter were increased, whereas the level of NF-kappaB inhibitor was decreased. In addition, SAH significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase/serine/threonine protein kinase (or protein kinase B) (PI3K/Akt) proteins but did not affect that of c-Jun NH2-terminal kinase or p38. Pretreatment of BV2 cells with an inhibitor specific for ERK (U0126) markedly abated the expression of ERK and MMP-2. Furthermore, SAH significantly and dose dependently decreased tissue inhibitor of metalloproteinase-2 (TIMP-2) in BV2 cells. Thus, SAH may induce the invasiveness of C6 glioma cells by decreased TIMP-2 expression and increased MMP-2 expression in BV2 cells. The latter effect is likely mediated through the ERK and PI3K/Akt pathways, with increased binding activities of NF-kappaB and Sp1 to the MMP-2 gene promoter.
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Glioma/patología , Metaloproteinasa 2 de la Matriz/metabolismo , Microglía/enzimología , S-Adenosilhomocisteína/toxicidad , Animales , Secuencia de Bases , Línea Celular , Línea Celular Tumoral , Inmunoprecipitación de Cromatina , Medios de Cultivo Condicionados , Cartilla de ADN , Ratones , FN-kappa B/metabolismo , Invasividad Neoplásica , Proteínas Quinasas/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Factores de Transcripción/metabolismoRESUMEN
S-Adenosylhomocysteine (SAH) has been implicated as a risk factor for neurodegenerative diseases such as Alzheimer's disease. As SAH is a potent inhibitor of all cellular methyltransferases, we herein examined the hypothesis that SAH may increase the formation of amyloid beta-peptide (Abeta) in BV-2 mouse microglial cells through hypomethylation of presenilin 1 protein (PS1) and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), both of which cleave Abeta precursor protein (APP) to form Abeta. The results showed that SAH increased Abeta protein formation in a concentration-dependent manner (10-500 nM), and this effect of SAH was accompanied by significantly increased expression of APP and PS1 proteins, although SAH only significantly increased the expression of BACE1 at the highest concentration used (500 nM). SAH (500 nM) markedly induced hypomethylation of APP and PS1 gene promoters. Incubation of cells with 5'-azc (20 microM), also an inhibitor of DNA methyltransferases enhanced Abeta protein expression and APP and PS1 gene promoters hypomethylation. By contrast, pre-incubation of cells with betaine (1.0 mM), 30 min followed by incubation with SAH (500 nM) or 5'-azc (20 microM) for 24h markedly prevented the expression of Abeta protein (by 50%, P<0.05) and the gene promoter hypomethylation of APP and PS1. Taken together, this study demonstrates that SAH increases the production of Abeta in BV-2 cells possibly by increased expression of APP and induction of hypomethylation of APP and PS1 gene promoters.
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Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Microglía/metabolismo , Presenilina-1/metabolismo , S-Adenosilhomocisteína/farmacología , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genética , Análisis de Varianza , Animales , Ácido Aspártico Endopeptidasas/metabolismo , Betaína/farmacología , Línea Celular Transformada , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Lipotrópicos/farmacología , Metilación/efectos de los fármacos , Ratones , Microglía/efectos de los fármacos , Presenilina-1/genética , Regiones Promotoras Genéticas/efectos de los fármacos , Factores de TiempoRESUMEN
BACKGROUND: Photocatalysis of titanium dioxide (TiO(2)) substrates is primarily induced by ultraviolet light irradiation. Anion-doped TiO(2) substrates were shown to exhibit photocatalytic activities under visible-light illumination, relative environmentally-friendly materials. Their anti-spore activity against Bacillus anthracis, however, remains to be investigated. We evaluated these visible-light activated photocatalysts on the reduction of anthrax spore-induced pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Standard plating method was used to determine the inactivation of anthrax spore by visible light-induced photocatalysis. Mouse models were further employed to investigate the suppressive effects of the photocatalysis on anthrax toxin- and spore-mediated mortality. We found that anti-spore activities of visible light illuminated nitrogen- or carbon-doped titania thin films significantly reduced viability of anthrax spores. Even though the spore-killing efficiency is only approximately 25%, our data indicate that spores from photocatalyzed groups but not untreated groups have a less survival rate after macrophage clearance. In addition, the photocatalysis could directly inactivate lethal toxin, the major virulence factor of B. anthracis. In agreement with these results, we found that the photocatalyzed spores have tenfold less potency to induce mortality in mice. These data suggest that the photocatalysis might injury the spores through inactivating spore components. CONCLUSION/SIGNIFICANCE: Photocatalysis induced injuries of the spores might be more important than direct killing of spores to reduce pathogenicity in the host.
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Bacillus anthracis/efectos de la radiación , Toxinas Bacterianas/antagonistas & inhibidores , Luz , Fármacos Fotosensibilizantes/farmacología , Titanio/farmacología , Animales , Antibacterianos/farmacología , Antígenos Bacterianos/metabolismo , Bacillus anthracis/patogenicidad , Bacillus subtilis/metabolismo , Toxinas Bacterianas/metabolismo , Ratones , Ratones Endogámicos C57BL , Esporas Bacterianas/patogenicidad , Esporas Bacterianas/efectos de la radiaciónRESUMEN
AIM OF THIS STUDY: Phellinus igniarius (Linnearus: Fries) Quelet (Phellinus igniarius) has been used in oriental countries for treatment of various diseases including cancer. However, it is unclear how Phellinus igniarius exerts anticancer effects. MATERIALS AND METHODS: In this study the ethanolic extract from the fruiting body of Phellinus igniarius (EEPI) was used to evaluate the antiproliferative and antimetastatic effects in human hepatocarcinoma SK-Hep-1 cells and rat heart vascular endothelial cells (RHE cells). RESULTS: We found that EEPI inhibited the proliferation of both cell lines in a dose-dependent manner, and the IC50 values at 48 h were 72 and 103 microg/ml for SK-Hep-1 cells and RHE cells, respectively. EEPI at non- or sub-cytotoxic concentrations (25-100 microg/ml) markedly inhibited the migration and invasion of SK-Hep-1 cells. EEPI added at 25 microg/ml significantly decreased the secretion of matrix metalloproteinase-2 (MMP-2) (49%, p<0.01) and vascular endothelial growth factor (VEGF) (13%, p<0.05) in SK-Hep-1 cells. EEPI at 25 microg/ml completely inhibited matrigel-induced tube formation in RHE cells. Importantly, EEPI (25 or 50 microg/ml) in combination with oxaliplatin (Oxa) or 5-flurouracil (5-FU) synergistically inhibited the proliferation of SK-Hep-1 cells. CONCLUSION: These results demonstrate the antiproliferative and antimetastatic effects of EEPI in vitro and the potential of EEPI as an adjuvant for chemotherapy.