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1.
Mol Carcinog ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32914490

RESUMO

Despite considerable knowledge of viral pathogenesis, the pathophysiological changes related to the multifactorial, multistep process of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) development remains unclear. Longitudinal metabolomics study can reveal biological process for disease progression. We performed metabolite profiling with longitudinal prediagnostic plasma samples from two nested case-control studies of hepatitis B surface antigen carriers participating in ultrasound screening for HCC, one within a government employee cohort (870 samples from 109 HCC cases and 107 controls) and the other within a hospital-based cohort (266 samples from 63 HCC cases and 114 controls). Of the 34 measured metabolites, tyrosine, isoleucine, and glutamine were consistently associated with HCC. In analyses combining longitudinal data, a high metabolic risk score based on the three amino acids was robustly associated with increased risk of HCC (OR = 3.71, 95% confidence interval: 2.53-5.42), even after adjustment for clinical factors, or when assessed for different times up to ≥8 years before diagnosis. Similar association was observed in an independent, prospective analysis comprising 633 randomly selected individuals of the government employee cohort. More importantly, this metabolite signature was longitudinally influenced by HBV-infection phase and involved in gradual progression to liver fibrosis and cirrhosis. Furthermore, mediation analysis showed that the score mediated substantial proportions of the associations of key viral factors, insulin resistance, and diabetes status with HCC risk. Our results suggest that an amino-acid dysregulation metabotype may play a role in HBV-related HCC development, and may also be linked to common pathways that mediate increased HCC risks.

2.
J Formos Med Assoc ; 119 Suppl 1: S4-S12, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32482605

RESUMO

Nontuberculous mycobacteria (NTM) are critical emerging global infectious pathogens. Though NTM can be mere colonizers when isolated from human specimens, NTM are also responsible for diverse human infections. NTM-lung disease (NTM-LD) is the most common human disease entity. The present review aims to provide general insight into NTM-LD epidemiology in Taiwan. In reviewing NTM epidemiology in Taiwan, we discovered three distinguishing features. First, NTM disease incidence has increased in Taiwan over the past decade. Second, the distribution of NTM varies geographically in Taiwan. Mycobacterium avium-intracellulare complex (MAC) is the dominant species in northern Taiwan, whereas Mycobacterium abscessus complex and MAC may be equally dominant in southern Taiwan. Third, researchers in Taiwan have published valuable research investigating NTM among special patient populations, including patients in intensive care units, with ventilator dependency, with pulmonary tuberculosis, and who are infected with specific NTM species. The largest obstacle to clarifying NTM epidemiology in Taiwan may be the lack of routine NTM species identification in laboratories. Increased awareness of NTM diseases and acknowledgment that NTM species identification is crucial and guides clinical management are essential steps for facilitating the identification of NTM species in laboratories.

3.
J Formos Med Assoc ; 119 Suppl 1: S32-S41, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32423573

RESUMO

Great progress has recently been made in methodologies for identifying nontuberculous mycobacteria (NTM). Recommendations for drug susceptibility testing (DST) of NTM have been expanded and updated by the Clinical and Laboratory Standards Institute and are crucial in the management of NTM infections. This article summarizes the clinically relevant molecular methods used to discriminate NTM species and updates the information on DST. Furthermore, recent progress on new antimicrobials against NTM infections is reviewed.

4.
Sensors (Basel) ; 20(1)2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31948055

RESUMO

Numerous studies have addressed the use of perovskite materials for fabricating a wide range of optoelectronic devices. This study employs the deposition of an electron transport layer of C60 and an Ag electrode on CH3NH3PbBr3 perovskite crystals to complete a photodetector structure, which exhibits a metal-semiconductor-metal (MSM) type structure. First, CH3NH3PbBr3 perovskite crystals were grown by inverse temperature crystallization (ITC) in a pre-heated circulator oven. This oven was able to supply uniform heat for facilitating the growth of high-quality and large-area crystals. Second, the different growth temperatures for CH3NH3PbBr3 perovskite crystals were investigated. The electrical, optical, and morphological characteristics of the perovskite crystals were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), ultraviolet-visible spectroscopy, and photoluminescence (PL). Finally, the CH3NH3PbBr3 perovskite crystals were observed to form a contact with the Ag/C60 as the photodetector, which revealed a responsivity of 24.5 A/W.

5.
Methods Mol Biol ; 2102: 225-234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31989558

RESUMO

DNA methylation has been characterized as the representative example of epigenetic modifications and implicated in numerous biological processes, such as genomic imprinting and X chromosome inactivation. It primarily occurs at CpG dinucleotides in mammals and plays a critical role in transcriptional regulations. Examination of DNA methylation patterns in gene(s) or across a genome is vital to understand the role of epigenetic modulation in the progress of development and tumorigenesis. Currently, lots of approaches have been developed to investigate DNA methylation patterns for either limited regions or genome-scale studies, but some of them rely on using restriction enzymes. In this chapter, we describe two commonly used protocols to detect enrichment of methylated DNA regions, namely methylated immunoprecipitation (MeDIP) and capture of methylated DNA by methyl-CpG binding domain-based (MBD) proteins (MBDCap). They are the most economical and effective methods to study DNA methylation in either single locus or genome-wide scale.

6.
J Formos Med Assoc ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31932200

RESUMO

BACKGROUND: A nationwide program initiated by Taiwan CDC was conducted by the Taiwan Society of Tuberculosis and Lung Disease to improve the appropriateness of anti-TB prescriptions in Taiwan. METHODS: All anti-TB prescriptions from 12 hospitals across Taiwan were reviewed by experienced pulmonologists, according to the 2011 Taiwan TB treatment guidelines, between May and October 2013. The investigation period was divided into three stages: May to June, July to August, and September to October. The concordance rates between anti-TB prescriptions and the guidelines were compared among the three stages and between medical centers and regional hospitals. RESULTS: A total of 2574 new anti-TB prescriptions were reviewed. The appropriateness of anti-TB prescriptions was 82.0%. The most dominant error was inappropriate dosage of anti-TB medications. The appropriateness improved significantly with prescription review, and the concordance rates were 78.7%, 80.6%, and 87.6% in stages 1, 2, and 3, respectively (P < 0.001). The inappropriateness of medication dosage also improved significantly, with the rates of inappropriate dosage dropping from 10.2% in stage 1-5.4% in stage 3 (Odds ratio 0.491, P < 0.001). The appropriateness rates showed no significant difference between regional hospitals and medical centers (82.5% vs. 81.3%, Odds ratio 0.915, P = 0.393), but the improvement of prescription appropriateness was significant in regional hospitals but not in medical centers. CONCLUSION: Prescription review by TB experts is an effective approach to improve the appropriateness of anti-TB prescriptions.

7.
Micromachines (Basel) ; 10(11)2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31766172

RESUMO

In this work, the cascaded second-order spontaneous parametric down-conversion (SPDC) is considered to produce pure state photon triplets in periodically poled lithium niobite (PPLN) doped with 5% MgO. A set of parameters are optimized through calculating the Schmidt number of two-photon states generated by each down-conversion process with different pump durations and crystal lengths. We use a Gaussian filter in part and obtain three photons with 100% purity in spectrum. We provide a feasible and unprecedented scheme to manipulate the spectrum purity of photon triplets in the communication band (C-band).

8.
Int J Infect Dis ; 87: 21-29, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31301458

RESUMO

Asia has the highest burden of tuberculosis (TB) and latent TB infection (LTBI) in the world. Optimizing the diagnosis and treatment of LTBI is one of the key strategies for achieving the WHO 'End TB' targets. We report the discussions from the Asia Latent TubERculosis (ALTER) expert panel meeting held in 2018 in Singapore. In this meeting, a group of 13 TB experts from Bangladesh, Cambodia, Hong Kong, India, Indonesia, Malaysia, Myanmar, the Philippines, Singapore, Taiwan, Thailand and Vietnam convened to review the literature, discuss the barriers and propose strategies to improve the management of LTBI in Asia. Strategies for the optimization of risk group prioritization, diagnosis, treatment, and research of LTBI are reported. The perspectives presented herein, may help national programs and professional societies of the respective countries enhance the adoption of the WHO guidelines, scale-up the implementation of national guidelines based on the regional needs, and provide optimal guidance to clinicians for the programmatic management of LTBI.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Ásia/epidemiologia , Humanos , Tuberculose Latente/epidemiologia
9.
PLoS One ; 14(4): e0214792, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30939150

RESUMO

BACKGROUND: The treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients in the 1990s in Taiwan was not satisfactory. To strengthen programmatic management of drug-resistant tuberculosis (PMDT), Taiwan MDR-TB Consortium (TMTC) was established in 2007. We assess the performance and epidemiologic impact of TMTC. METHODOLOGY/PRINCIPLE FINDINGS: We analyzed the trends of proportion of TB cases with drug susceptibility testing, enrollment of MDR-TB patients into TMTC and outcomes of treatment of all MDR-TB patients in Taiwan from 2007-2016. We computed the trends of both incidence and prevalence of MDR-TB from 2007-2016. We assessed the trends of MDR-TB among both new and recurrent TB cases. The proportion of TB cases with drug susceptibility testing results increased from 24.2% in 2007 to 97.9% in 2016. Of the 1,452 MDR-TB patients who were eligible for TMTC care, 1,197 (82.4%) were enrolled in TMTC, in whom 82.9% had treatment success. MDR-TB incidence was 9.0 cases per million in 2007, which declined to 4.6 cases per million in 2016 (p<0.0001). MDR-TB prevalence decreased from 19.4 cases per million in 2007 to 8.4 cases per million in 2016 (p<0.0001). The proportion of MDR-TB among new TB cases decreased from 1.4% in 2010 to 1.0% in 2016 (p = 0.039); and that among recurrent TB cases from 9.0% in 2010 to 1.8% in 2016 (p<0.0001). CONCLUSIONS: We concluded that effective PMDT have had a significant impact on the epidemic of drug-resistant TB in Taiwan.


Assuntos
Antituberculosos/uso terapêutico , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Idoso , Terapia Diretamente Observada/métodos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologia , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto Jovem
10.
Biochimie ; 162: 8-14, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30935961

RESUMO

We previously reported that SOX4 is overexpressed in endometrial cancer and that it partially contributes to hypermethylation of miR-129-2 and miR-203. The current study seeks to identify methylation and expression levels of the SOX gene family in endometrial carcinomas. Methylation levels of the 16 SOX gene family members were measured by combining bisulfite restriction analysis (COBRA), MassARRAY, and pyrosequencing assays of cell lines and endometrial cancer samples. Gene expression was determined by RT-qPCR. The methylation level of the SOX11 locus was correlated with clinicopathologic factors in primary endometrial tumors and in TCGA endometrial cohort. It was also examined in DNA of serum and endometrial specimens from a longitudinal cohort of early stage endometrial cancer patients. COBRA assays indicated that hypermethylation of SOX1, SOX2, SOX11, SOX14, SOX15, SOX17, and SOX18 was present in endometrial cancer cell lines and not in the normal control. SOX11 expression was reactivated only by a DNA methylation inhibitor. Moreover, aberrant DNA methylation of SOX11 was detected in the majority of endometrioid endometrial carcinomas (n=114) and none of the 22 adjacent normal endometrial samples (P<0.0001). The methylation status of SOX11 associated significantly with microsatellite instability and MLH1 methylation in endometrial tumors (P<0.0001), and this finding was validated in TCGA endometrial cohort. Furthermore, SOX11 was not hypermethylated in serum DNA from early stage endometrial cancer patients. This study found that hypermethylation of SOX11 is common in endometrial carcinomas and strongly associates with microsatellite instability and MLH1 methylation.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Neoplasias do Endométrio/genética , Instabilidade de Microssatélites , Fatores de Transcrição SOXC/genética , Linhagem Celular Tumoral , Estudos de Coortes , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estudos Longitudinais , Proteína 1 Homóloga a MutL/genética
11.
Mol Nutr Food Res ; 63(12): e1900013, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30951235

RESUMO

SCOPE: The chemopreventive effects of black raspberries (BRBs) have not been studied in endometrial tumorigenesis. Here, they are examined in a mouse model of endometrial cancer. METHODS AND RESULTS: Wild-type and Pten heterozygous (+/-) female mice are weaned at 3 weeks and fed with four AIN-93G diets: 93G; 93G+5% BRBs powder; high-fat (HF); and HF+5% BRBs. Body weight and diet consumption are recorded weekly until the mice are euthanized at 28 weeks of age. Mice fed with HF diets are found to significantly gain body weight over time. BRBs are not found to affect the development of obesity. Mice in the HF+BRBs group consume less food than the HF-only mice. HF+BRBs diets suppress uterine tumor initiation and promotion more than the HF-only diet by inhibiting cell proliferation. It also reduces HF-induced levels of plasma leptin and 17ß-estradiol (E2). Urolithin A, a metabolite of BRBs, suppresses cell proliferation induced by leptin and E2. CONCLUSION: BRBs are preventive in HF-mediated uterine tumorigenesis because they suppress cell growth and plasma leptin and E2 levels.


Assuntos
Neoplasias do Endométrio/prevenção & controle , Rubus , Animais , Linhagem Celular Tumoral , Proliferação de Células , Dieta Hiperlipídica , Neoplasias do Endométrio/etiologia , Estradiol/sangue , Feminino , Leptina/sangue , Camundongos , PTEN Fosfo-Hidrolase/fisiologia
12.
Crit Rev Food Sci Nutr ; 59(6): 992-1007, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30795687

RESUMO

Cancer is considered a fetal disease caused by uncontrolled proliferation and progression of abnormal cells. The most efficient cancer therapies suppress tumor growth, prevent progression and metastasis, and are minimally toxic to normal cells. Natural compounds have shown a variety of chemo-protective effects alone or in combination with standard cancer therapies. Along with better understanding of the dynamic interactions between our immune system and cancer development, nutritional immunology-the use of natural compounds as immunomodulators in cancer patients-has begun to emerge. Cancer cells evolve strategies that target many aspects of the immune system to escape or even edit immune surveillance. Therefore, the immunesuppressive tumor microenvironment is a major obstacle in the development of cancer therapies. Because interaction between the tumor microenvironment and the immune system is a complex topic, this review focuses mainly on human clinical trials and animal studies, and it highlights specific immune cells and their cytokines that have been modulated by natural compounds, including carotenoids, curcumin, resveratrol, EGCG, and ß-glucans. These natural compounds have shown promising immune-modulating effects, such as inhibiting myeloid-derived suppressor cells and enhancing natural killer and cytolytic T cells, in tumor-bearing animal models, but their efficacy in cancer patients remains to be determined.


Assuntos
Fatores Imunológicos/imunologia , Fatores Imunológicos/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Animais , Carotenoides/farmacologia , Catequina/análogos & derivados , Catequina/farmacologia , Curcumina/farmacologia , Humanos , Sistema Imunitário , Células Matadoras Naturais/efeitos dos fármacos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Resveratrol/farmacologia , Linfócitos T/efeitos dos fármacos , Tretinoína/farmacologia , beta-Glucanas/farmacologia
13.
Genomics ; 111(1): 17-23, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-27453286

RESUMO

To develop accurate prognostic models is one of the biggest challenges in "omics"-based cancer research. Here, we propose a novel computational method for identifying dysregulated gene subnetworks as biomarkers to predict cancer recurrence. Applying our method to the DNA methylome of endometrial cancer patients, we identified a subnetwork consisting of differentially methylated (DM) genes, and non-differentially methylated genes, termed Epigenetic Connectors (EC), that are topologically important for connecting the DM genes in a protein-protein interaction network. The ECs are statistically significantly enriched in well-known tumorgenesis and metastasis pathways, and include known epigenetic regulators. Importantly, combining the DMs and ECs as features using a novel random walk procedure, we constructed a support vector machine classifier that significantly improved the prediction accuracy of cancer recurrence and outperformed several alternative methods, demonstrating the effectiveness of our network-based approach.


Assuntos
Algoritmos , Biomarcadores Tumorais , Metilação de DNA , Neoplasias do Endométrio , Recidiva Local de Neoplasia , Ilhas de CpG , DNA de Neoplasias , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Epigenômica , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Modelos Genéticos , Prognóstico , Domínios e Motivos de Interação entre Proteínas , Análise de Sequência de DNA
14.
Hepatology ; 69(4): 1412-1425, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30382583

RESUMO

Smoking interacts with hepatitis B virus (HBV) to increase the risk of hepatocellular carcinoma (HCC), which might be explained by its role in antiviral immunity. We evaluated the potential mediating role of viral load and/or alanine aminotransferase (ALT) in the relation of smoking with HBV-associated HCC risk. Using multiple mediation analyses to analyze data from 209 HCC cases and 1,256 controls nested within a cohort of 4,841 male HBV carriers, we found that the effect of smoking on the risk of subsequent HCC was substantially mediated through viral load (percent mediated, 31.7%; P = 0.0054), and a significant mediation effect by both viral load and ALT was also evidenced. Among the 1,143 subjects with repeated measures of viral load and ALT over periods of up to 16 years, we further observed that a higher number of pack-years of smoking was associated with higher viral load, maintenance of a high viral load (>4.39 log copies/mL), more severe hepatotoxicity grade, and increased likelihood of ALT ≥80 U/L (odds ratio, 3.14; 95% confidence interval, 1.03-9.64; odds ratio, 6.06; 95% confidence interval, 1.10-33.25, respectively, for 10-19 and ≥20 pack-years versus nonsmokers) during follow-up. Furthermore, plasma interferon-γ levels were reduced in smokers compared with nonsmokers (interferon-γ-positive rate, 14.9% versus 28.7%; P < 0.0001) at baseline. Smoking was also associated with a reduced natural killer (NK) cell frequency in peripheral blood, characterized by reduced NK function through a systems immunology approach, after long-term follow-up in a subsample (n = 171). The combination of smoking and reduced NK cell frequency further increased viral load and the likelihood of ALT ≥80 U/L. Conclusion: The data highlight a role of smoking in HBV viral load, underlining the importance of smoking prevention and cessation in hepatitis B management.

15.
Cancer Res ; 79(1): 196-208, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30389702

RESUMO

Emerging evidence indicates that adipose stromal cells (ASC) are recruited to enhance cancer development. In this study, we examined the role these adipocyte progenitors play relating to intercellular communication in obesity-associated endometrial cancer. This is particularly relevant given that gap junctions have been implicated in tumor suppression. Examining the effects of ASCs on the transcriptome of endometrial epithelial cells (EEC) in an in vitro coculture system revealed transcriptional repression of GJA1 (encoding the gap junction protein Cx43) and other genes related to intercellular communication. This repression was recapitulated in an obesity mouse model of endometrial cancer. Furthermore, inhibition of plasminogen activator inhibitor 1 (PAI-1), which was the most abundant ASC adipokine, led to reversal of cellular distribution associated with the GJA1 repression profile, suggesting that PAI-1 may mediate actions of ASC on transcriptional regulation in EEC. In an endometrial cancer cohort (n = 141), DNA hypermethylation of GJA1 and related loci TJP2 and PRKCA was observed in primary endometrial endometrioid tumors and was associated with obesity. Pharmacologic reversal of DNA methylation enhanced gap-junction intercellular communication and cell-cell interactions in vitro. Restoring Cx43 expression in endometrial cancer cells reduced cellular migration; conversely, depletion of Cx43 increased cell migration in immortalized normal EEC. Our data suggest that persistent repression by ASC adipokines leads to promoter hypermethylation of GJA1 and related genes in the endometrium, triggering long-term silencing of these loci in endometrial tumors of obese patients. SIGNIFICANCE: Studies reveal that adipose-derived stem cells in endometrial cancer pathogenesis influence epigenetic repression of gap junction loci, which suggests targeting of gap junction activity as a preventive strategy for obesity-associated endometrial cancer.


Assuntos
Adipocinas/farmacologia , Tecido Adiposo/patologia , Comunicação Celular , Conexina 43/genética , Neoplasias do Endométrio/patologia , Repressão Epigenética , Obesidade/complicações , Tecido Adiposo/metabolismo , Animais , Movimento Celular , Células Cultivadas , Conexina 43/metabolismo , Dieta Hiperlipídica/efeitos adversos , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Junções Comunicantes , Humanos , Masculino , Camundongos , Camundongos Knockout , Obesidade/fisiopatologia , Células Estromais/metabolismo , Células Estromais/patologia
16.
J Infect Dev Ctries ; 13(2): 123-129, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32036347

RESUMO

INTRODUCTION: Directly Observed Treatment Short course (DOTS) is one of the most cost-effective approaches for TB treatment. However, TB incidence rates remain high in the mountain areas of Taiwan. A lay health advisor (LHA) strategy is integrated into DOTS as an Enhanced-DOTS (E-DOTS) to provide trustworthy, culturally-specific services in mountain areas that consider the characteristics of local ethnic groups. METHODOLOGY: We recruited two Taiwanese indigenes as LHAs (one for each county) to screen close contacts in five townships of Hualien and Nantou counties from January 1, 2011 to December 31, 2013. Incidence and active finding rates of TB during the E-DOTS periods (2011-2013 for Hualien and 2012-2013 for Nantou) were compared with data when traditional DOTS was implemented (2006-2010 for Hualien and 2006-2011 for Nantou) to evaluate the effectiveness of E-DOTS using the before-and-after study design. RESULTS: Incidence rate in Hualien decreased from 393.3 in 2011 to 235.7 in 2013 per 100,000 population and from 338 in 2012 to 235.5 in 2013 in Nantou mountain area. Furthermore, the active case finding rate increased from 15.42% in 2012 to 27.38% in 2013 as compared to an average of 6.5% for CDC, Taiwan, for the specified years. TB treatment success rates were significantly improved from an average of less than 80% to an average of higher than 90% after E-DOTS was implemented. CONCLUSIONS: Our findings highlighted that the use of LHAs in E-DOTS is an effective and applicable strategy for controlling tuberculosis in the mountain areas of Taiwan.


Assuntos
Antituberculosos/uso terapêutico , Serviços de Saúde Comunitária/estatística & dados numéricos , Terapia Diretamente Observada/métodos , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , População Rural , Taiwan/epidemiologia , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-31892222

RESUMO

Weekly rifapentine and isoniazid therapy (3HP) is the most frequent treatment for latent tuberculosis infection (LTBI). However, the association between major adverse drug reactions (ADRs) and drug metabolic enzyme single-nucleotide polymorphisms (SNPs) remains unclear. In this study, 377 participants who received the 3HP regimen were recruited and examined for genotyping of CYP5A6, CYP2B6, CYP2C19, CYP2E1, and NAT2 SNPs. In our study, 184 participants (48.4%) developed ADRs. Moreover, CYP2C19 rs4986893 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 2.231 [1.015-4.906]), CYP2E1 rs2070676 (CC vs. CG+GG, OR [95% CI]: 1.563 [1.022-2.389]), and CYP2E1 rs2515641 (CC vs. CT+TT, OR [95% CI]: 1.903 [1.250-2.898]) were associated with ADR development. In conclusion, CYP2C19 and CYP2E1 SNPs may provide useful information regarding ADRs in LTBI patients receiving the 3HP regimen.


Assuntos
Antituberculosos/uso terapêutico , Arilamina N-Acetiltransferase/genética , Sistema Enzimático do Citocromo P-450/genética , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Rifampina/análogos & derivados , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Isoniazida/administração & dosagem , Isoniazida/efeitos adversos , Masculino , Razão de Chances , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Rifampina/uso terapêutico
18.
J Berry Res ; 8(3): 163-175, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30159104

RESUMO

Berries and their phytochemicals have well documented chemopreventive roles, but understanding their ability to regulate cancer immunology is only beginning to be explored. The literature, including human studies, suggests that berry components can modulate our immune system to delay cancer development. Moreover, their wide spectrum of phytochemicals suggests that they might influence the functions of multiple immune cells and different aspects of cancer immunity. Cancer immune-therapies are showing promise for some types of cancer because they boost T cells' ability to recognize tumor cells - an essential prelude to destruction. Recognition occurs after dendritic cells present antigen, such as tumor antigen, to T cells, generating an adaptive response. Therefore, the potential of berries to aid cancer immune-therapies by, for example, regulating dendritic cells, warrants further investigation in animal and human studies. More information is also needed about berries' effects on the entire spectrum of immunity so that a comprehensive view can inform efforts to use berries to enhance immune responses during cancer prevention and treatment. This review summarizes the effects of berries as anti-tumor agents from the immunological perspective in tumor-bearing animals and humans.

19.
J Berry Res ; 8(2): 137-146, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29977412

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of two subtypes of esophageal cancer, with high incidence and mortality rates in developing countries. OBJECTIVE: The current study investigated the potential chemoprotective effects of strawberries and aspirin against the development of rat esophageal papillomas, the precursors to ESCC. METHODS: Using a prevention model, we administered study diets to rats before, during, and after N-nitrosomethylbenzylamine (NMBA) treatment. The effects of the four diets were evaluated: the control diet, 5% strawberry powder in the control diet, 0.01% aspirin in the drinking water, and the combination of strawberries and aspirin. At week 25, we euthanized all the rats and collected their esophagi to quantify tumor incidence, multiplicity, and burden, as well as for molecular analysis. RESULTS: Both strawberries and aspirin significantly decreased esophageal tumor multiplicity, with the combination causing the most robust suppression. Aspirin alone and the combination decreased the total tumor burden in the esophagus. None of the diets had a significant effect on tumor incidence or the expression of COX-1 and COX-2. Strawberries and aspirin, alone and in combination, significantly suppressed squamous epithelial cell proliferation (PCNA). CONCLUSIONS: Strawberries, aspirin, and their combination exhibit chemoprotective effects against NMBA-induced esophageal tumors in rats.

20.
Tuberculosis (Edinb) ; 111: 121-126, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30029896

RESUMO

Treatment of latent tuberculosis (TB) infection (LTBI) effectively prevents its progression to active TB. However, long treatment duration and drug-related hepatotoxicity limit the effectiveness of the 9-month daily isoniazid (9H). Data on the 3-month weekly rifapentine plus isoniazid (3 HP) in Asian populations are currently unavailable. We prospectively randomised the LTBI contacts aged ≥12 years with positive tuberculin skin test into 9H and 3 HP groups in four hospitals between January 2014 and May 2016 in Taiwan. The primary and secondary outcomes were treatment completion rate and adverse drug reactions (ADRs), respectively. Overall, 263 participants with LTBI were randomised into the 3 HP (n = 132) and 9H groups (n = 131); 14 (10.6%) and 29 (22.1%) participants in the 3 HP and 9H groups, respectively, discontinued therapy (p = 0.011). Discontinuation rates owing to ADRs were 9.1% (3 HP) and 5.3% (9H) (p = 0.241). Clinically relevant hepatotoxicity was more common in the 9H than in the 3 HP group (5.3% vs. 1.5%; p = 0.103), whereas systemic drug reaction was more common in the 3 HP than in the 9H group (3.8% vs. 0%; p = 0.060). Women had a significantly higher rate of Grade II fever than men (13.7% vs. 1.2%; p = 0.003). Compared with the 9H regimen, the 3 HP regimen had a higher completion rate with lower hepatotoxicity and well-tolerated ADR. CLINICAL TRIALS REGISTRATION: number NCT02208427.


Assuntos
Antibióticos Antituberculose/administração & dosagem , Antituberculosos/administração & dosagem , Isoniazida/administração & dosagem , Tuberculose Latente/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Rifampina/análogos & derivados , Adolescente , Adulto , Idoso , Antibióticos Antituberculose/efeitos adversos , Antituberculosos/efeitos adversos , Criança , Quimioterapia Combinada , Feminino , Humanos , Isoniazida/efeitos adversos , Tuberculose Latente/diagnóstico , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Estudos Prospectivos , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Taiwan , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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