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1.
BMC Med Educ ; 24(1): 705, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943116

RESUMO

BACKGROUND: Entrustable Professional Activities (EPA)-based assessment is easily and intuitively used in evaluating the learning outcomes of competency-based medical education (CBME). This study aimed to develop an EPA for occupational therapy focused on providing health education and consultation (TP-EPA3) and examine its validity. METHODS: Nineteen occupational therapists who had completed online training on the EQual rubric evaluation participated in this study. An expert committee identified six core EPAs for pediatric occupational therapy. TP-EPA3 was developed following the EPA template and refined through consensus meetings. The EQual rubric, a 14-item, five-point criterion-based anchor system, encompassing discrete units of work (DU), entrustable, essential, and important tasks of the profession (EEIT), and curricular role (CR), was used to evaluate the quality of TP-EPA3. Overall scores below 4.07, or scores for DU, EEIT, and CR domains below 4.17. 4.00, and 4.00, respectively, indicate the need for modifications. RESULTS: The TP-EPA3 demonstrated good validity, surpassing the required cut-off score with an average overall EQual score of 4.21 (SD = 0.41). Specific domain scores for DU, EEIT, and CR were 3.90 (SD = 0.69), 4.46 (SD = 0.44), and 4.42 (SD = 0.45), respectively. Subsequent revisions clarified observation contexts, enhancing specificity and focus. Further validation of the revised TP-EPA3 and a thorough examination of its reliability and validity are needed. CONCLUSION: The successful validation of TP-EPA3 suggests its potential as a valid assessment tool in occupational therapy education, offering a structured approach for developing competency in providing health education and consultation. This process model for EPA development and validation can guide occupational therapists in creating tailored EPAs for diverse specialties and settings.


Assuntos
Competência Clínica , Educação Baseada em Competências , Terapia Ocupacional , Humanos , Terapia Ocupacional/educação , Competência Clínica/normas , Reprodutibilidade dos Testes , Avaliação Educacional , Educação em Saúde , Encaminhamento e Consulta/normas , Currículo , Masculino , Feminino
2.
BMC Public Health ; 23(1): 2346, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012695

RESUMO

BACKGROUND: Most studies have focused on the risk factors, treatment, and care of affective psychosis, and several have reported a relationship between ambient air quality and this psychosis. Although an association has been reported between psychosis and genes, studies mainly explored the associations between one type of psychosis and one gene; few have identified genes related to affective psychosis. This study investigates the genetic and environmental factors of affective psychosis. METHODS: In this retrospective longitudinal study, 27 604 participants aged 30-70 were selected from Taiwan Biobank. The participants' propensity scores were calculated based on their demographic information, and propensity score matching was performed to divide the participants into an experimental (i.e., affective psychosis) and control group at a 1:5 ratio. Plink was used to analyze the major and minor types of gene expression related to affective psychosis, and PM2.5 exposure was incorporated into the analyses. RESULTS: According to the generalized estimating equation analysis results, 8 single nucleotide polymorphisms (SNPs) belonging to the ANK3, BDNF, CACNA1C, and GRID1 genotypes were significantly correlated with depressive disorder (P < .001), with the majority belonging to the ANK3 and CACNA1C. A total of 5 SNPs belonging to the CACNA1C, GRID1, and SIRT1 genotypes were significantly correlated with bipolar disorder (P < .001), with the majority belonging to the CACNA1C. No significant correlation was identified between ambient air pollution and affective psychosis. CONCLUSIONS: CACNA1C and GRID1 are common SNP genotypes for depressive disorder and bipolar disorder and should be considered associated with affective psychosis.


Assuntos
Bancos de Espécimes Biológicos , Predisposição Genética para Doença , Humanos , Estudos Retrospectivos , Estudos Longitudinais , Taiwan/epidemiologia , Canais de Cálcio Tipo L/genética , Transtornos do Humor , Polimorfismo de Nucleotídeo Único , Material Particulado/efeitos adversos , Estudo de Associação Genômica Ampla
3.
BMC Pediatr ; 20(1): 398, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32838756

RESUMO

BACKGROUND: Kawasaki disease (KD) causes coronary artery lesions (CAL) and is the leading cause of acquired heart disease in children. The aim of this study is to evaluate the risk factors and set-up a scoring system for predicting CAL of KD. METHODS: We retrospectively reviewed a total of 478 patients diagnosed with KD. We compared age, gender, laboratory data, and treatment response in two groups and developed a scoring system for predicting CAL. RESULTS: During the study period, 365 of these patients had complete medical records of coronary surveys by echocardiography. Anemia, hypoalbuminemia, C reactive protein (CRP), alanine aminotransferase, neutrophil count, and neutrophil/lymphocyte ratio (NLR) showed significant differences with CAL formation. We determined the cut-off value using a receiver-operating-characteristic (ROC) curve, and following multivariate logistic regression analysis, four independent risk factors demonstrated a significant difference with CAL formation, including CRP > 103 mg/L, NLR > 3.5, male gender, and intravenous immunoglobulin (IVIG) resistance. We established a score system based on the above evaluation, for which a ROC curve was performed, and a total score of ≥ 2 points showed a sensitivity of 60.8% and a specificity of 70.6%, with an area under the ROC curve of 0.696. CONCLUSIONS: Identifying children at risk is important in order to prevent CAL from developing. Four independent risk factors that can predict CAL formation were CRP > 103 mg/L, NLR > 3.5, male gender, and IVIG resistance. This first report incorporated NLR into score systems to predict CAL reinforces previously well-known risk factors for the CAL formation among KD patients.


Assuntos
Doença da Artéria Coronariana , Síndrome de Linfonodos Mucocutâneos , Criança , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/etiologia , Vasos Coronários , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Linfócitos , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/diagnóstico por imagem , Neutrófilos , Estudos Retrospectivos
4.
Sci Rep ; 11(1): 1311, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446677

RESUMO

Fibromyalgia (FM) is a stress-related chronic pain disorder with common cognitive complaints. This study characterized cognitive dysfunction in patients with FM and explored whether these changes are linked to altered cortisol levels. Consecutive 44 patients with FM and 48 healthy controls were enrolled for the assessments of subjective and objective cognitive functions and diurnal levels of salivary cortisol (sampled at awakening, 30 min after awakening, 3 pm, and bedtime). All measurements were compared between the groups and evaluated for clinical correlation. The FM group had more subjective cognitive complaints and performed poorer in objective cognitive testing in memory (delayed recall in Chinese Version Verbal Learning Test and Taylor Complex Figure Test), language (Boston Naming Test), and executive domains (Wisconsin Card Sorting Test) after adjustments for education. The diurnal cortisol levels of patients with FM tended to be lower, especially at 30 min after awakening and bedtime. Moreover, moderate positive correlations existed between the Chinese Version Verbal Learning Test, Boston Naming Test and the morning cortisol levels within the FM group. We suggested the altered cognitive function in FM may be linked to stress maladaptation. Future studies are warranted to elucidate whether stress management improves cognitive performance in patients with FM.


Assuntos
Cognição , Fibromialgia/metabolismo , Hidrocortisona/metabolismo , Memória , Saliva/metabolismo , Adulto , Feminino , Fibromialgia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade
5.
Ther Innov Regul Sci ; 55(4): 872-880, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33904126

RESUMO

BACKGROUND: To promote the efficiency and quality of registration for medical products, the Asia-Pacific Economic Cooperation (APEC) Regulatory Harmonization Steering Committee (RHSC) has implemented a 2020 roadmap to promote the concept of GRM since 2011. Key outcomes of this roadmap are discussed in this article to provide recommendations for improved regulatory practices and accelerated regulatory convergence. METHODS: Adoption of relevant guidelines and delivery of training programs from the APEC Training Centers of Excellence for Regulatory Science (CoEs) have played a key role to promote capacity building, cooperation and convergence in good review practices (GRevPs) and good submission practices (GSubPs) for medical products among APEC economies. A key performance indicator (KPI) survey among the drug regulatory authorities (RAs) of APEC economies was conducted to understand the progress of this roadmap. RESULTS: The CoE programs have provided a unique opportunity to promote dialogues between regulatory authorities and industry and efficiently disseminated the concept of GRM among APEC economies. The results of the KPI survey indicated significant progress in the status of implementing GRevPs over the last ten years. CONCLUSIONS: To accelerate regulatory convergence among APEC economies, it is necessary to promote mutual trust and cooperation in approval of medical products over the time. Continuous training in GRevPs and GSubPs through the CoE platform would set the stage to achieve the goal in the next decade.


Assuntos
Inquéritos e Questionários , Ásia
6.
ANZ J Surg ; 91(11): 2459-2465, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34514684

RESUMO

BACKGROUND: Postoperative pancreatic fistula (POPF) remains a significant cause of morbidity in patients undergoing distal pancreatectomy (DP). The use of polyethylene glycol (PEG) and recombinant human albumin sealant gel applied to the transected pancreatic margin in DP may reduce POPF rates and was assessed. METHODS: A retrospective single centre cohort study of patient undergoing DP at an Australian high volume tertiary institution between January 2015 and January 2021. Rates of POPF in patients undergoing stapled pancreatic transection with PEG sealant were compared to other methods. RESULTS: A total of 54 cases were identified for analysis, with 16 undergoing stapled DP combined with staple line application of PEG (PEG group). Most patients in the control group had stapled DP 92% (35 of 38), with 47% (18 of 38) combined with a reinforcing buttress, with or without the use other glue types. Overall, 28 of 54 (52%) developed a POPF, with a significantly lower rate in the PEG group (3 of 16 vs. 25 of 38 in the Control group; p = 0.003). Clinically significant Grade B/C POPF was lower in the PEG group (0 of 16 vs. 9 of 28 in the Control group; p = 0.045), and patients in the PEG group had a shorter median (range) length of hospital stay (6 [4-14] days vs. 10 [6-41] days p = 0.04). CONCLUSION: Stapled DP with the application of PEG and recombinant human albumin sealant to the transection line appears to be associated with a lower rate of clinically significant POPF.


Assuntos
Pancreatectomia , Fístula Pancreática , Austrália , Estudos de Coortes , Humanos , Pancreatectomia/efeitos adversos , Fístula Pancreática/prevenção & controle , Polietilenoglicóis/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica Humana
7.
Opt Express ; 18(4): 3510-8, 2010 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-20389360

RESUMO

Enhanced surface plasmon resonances in a silvershell nanocylindrical pair connected by a different type of nanobar that interacts with incident plane wave of transverse magnetic polarization are simulated by use of the finite element method. Arrays of silver nanoshells connected by silver nanobars are also investigated. The proposed structure exhibits a red-shifted localized surface plasmon that can be tuned over an extended wavelength range by varying the width of the nanobar and the dielectric constant in dielectric holes (DHs). The increase in the scattering cross sections is attributed to the effects of surface plasmon on the nanobar surface and a larger effective size of DH that is filled with a higher refractive medium. The predictive character of these calculations allows one to tailor the shape of the nanoparticle to achieve excitation spectra on demand with a controlled field enhancement.


Assuntos
Modelos Químicos , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Prata/química , Ressonância de Plasmônio de Superfície/métodos , Simulação por Computador , Luz , Espalhamento de Radiação
8.
Front Pediatr ; 8: 221, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32432067

RESUMO

Background: Kawasaki disease (KD) is a form of vasculitis that primarily affects children under the age of 5 years old. Patients may be missed or diagnosis delayed when initial clinical symptoms do not fulfill the traditional criteria or a normal echocardiography was found. In this study, we aimed to analyze factors that clinicians could use to differentiate febrile children suspected of KD. Method: We retrospectively enrolled in this study a total of 50 febrile children who were initially suspected of KD, but they did not meet the American Heart Association (AHA) criteria for a diagnosis. However, some of these patients were diagnosed with KD during their second visit. We analyzed patients' characteristics, clinical symptoms, and laboratory data (initial data in the first visit). Results: In total, 50 patients were enrolled in the study. Of those, ten patients were diagnosed with KD on their second visit (group 1), while the other 40 patients still did not fit a KD diagnosis (group 2). A higher neutrophil-to-lymphocyte ratio (NLR, p = 0.037) and higher C-reactive protein levels (CRP, p = 0.02) were found in group 1 when compared to group 2. A patient with a NLR >1.33 combined with a CRP more than 33 mg/L was more likely to have KD (Sensitivity 90%, specificity 69.2%, p = 0.001; Odds ratio 20.25, 95% confident interval 2.3-178.25). Conclusion: Among patients suspected of KD that did not initially meet the criteria, clinicians should pay special attention to elevated neutrophil-to-lymphocyte ratios and CRP levels and closely follow up such patients.

9.
Curr Med Res Opin ; 35(1): 7-13, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29701487

RESUMO

Background: As the prevalence of diabetes mellitus (DM) continues to increase rapidly, there has been a rising need not only to assess the clinical outcomes but also the impact of DM on the health-related quality of life (HRQoL) of affected individuals. Most previous studies have found that having complications is strongly associated with decreased HRQoL in DM patients. As such, it is crucial to measure individuals' preferences for DM-related complications in order to assess the magnitude of complications' effect on overall HRQoL. In addition, preference scores are an essential component of cost-utility analyses (CUAs), which studies can incorporate healthcare costs, HRQoL and clinical outcomes of DM into one analysis.Objective: The aims of this study were to assess the preference scores of DM-related complications using both the standard gamble (SG), a choice-based method, and visual analogue scale (VAS), a scaling method. We also aimed to assess several possible factors that might be associated with the preference scores of the complications.Methods: This is a cross-sectional interview-administered survey, and 213 patients with type 2 DM were interviewed. The respondents' preference scores of eleven DM-related complications were obtained using VAS and SG techniques. Demographic information, clinical characteristics and risk attitudes were also collected to explore factors that may affect patients' preference scores.Results: Nearly one quarter of participants in Taiwan ranked at least one of the complications worse than death. The mean VAS scores ranged from 0.004 (amputation) to 0.47 (nocturnal hypoglycemia) while the mean adjusted SG scores ranged from 0.30 (blindness) to 0.66 (nocturnal hypoglycemia). There were significant differences in all of the complications' preference scores depending on risk attitudes.Conclusion: Both the VAS and SG methods were used to elicit the preference scores of DM-related complications, and the preference scores derived could be useful for future cost utility analyses.


Assuntos
Complicações do Diabetes/psicologia , Preferência do Paciente , Qualidade de Vida , Idoso , Análise Custo-Benefício , Estudos Transversais , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Taiwan
10.
Pediatr Rheumatol Online J ; 17(1): 46, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324255

RESUMO

BACKGROUND: The etiology of Kawasaki disease (KD) is still unknown; perinatal factors may have role with few studies. This study was aim to survey the perinatal factors and clinical outcome of KD, including coronary artery lesion (CAL) formation and intravenous immunoglobulin (IVIG) treatment response. METHODS: We enrolled a total of 185 KD patient-caregiver dyads in this study using questionnaires. The questionnaire included two categories: children's characteristics, which consisted of age at disease onset, gender, gestational age at delivery, birth body weight, delivery methods, and breastfeeding status, and caregivers' characteristics, which consisted of parents or not, education levels, maternal age at giving birth, total number of offspring, and family income. We analyzed the association of these factors with CAL formation and IVIG treatment response of KD. RESULTS: KD patients with CAL formation had a higher maternal age than non-CAL patients (32.49 ± 3.42 vs. 31.01 ± 3.92 years, p = 0.016). We also found that maternal age ≥ 32 years group had a higher rate of having KD patients with CAL (39/81 vs. 24/74, odds ratio 1.935, 95% confidence interval [1.007, 3.718], p = 0.047). The maternal age ≥ 35 years group had a higher rate of having KD patients with IVIG resistance (6/31 vs. 6/116, odds ratio 4.400, 95% confidence interval [1.309, 14.786], p = 0.01). There was no significant difference in either CAL formation or IVIG resistance in KD with regard to patient's age at disease onset, gestational age, birth body weight, delivery methods, breastfeeding, caregiver type, caregivers' education level, total number of offspring, or family income (p > 0.05). CONCLUSIONS: This study is the first to report that maternal age is significantly associated with CAL formation and IVIG resistance in KD. We hypothesize that a maternal age less than 32 years would benefit KD offspring.


Assuntos
Aneurisma Coronário/epidemiologia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Idade Materna , Síndrome de Linfonodos Mucocutâneos/terapia , Fístula Vascular/epidemiologia , Adulto , Pré-Escolar , Aneurisma Coronário/etiologia , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Dilatação Patológica , Feminino , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Razão de Chances , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Fístula Vascular/etiologia
11.
Steroids ; 73(6): 594-600, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18328519

RESUMO

Six new C(21) steroidal glycosides, named curassavosides A-F (3-8), were obtained from the aerial parts of Asclepias curassavica (Asclepiadaceae), along with two known oxypregnanes, 12-O-benzoyldeacylmetaplexigenin (1) and 12-O-benzoylsarcostin (2). By spectroscopic methods, the structures of the six new compounds were determined as 12-O-benzoyldeacylmetaplexigenin 3-O-beta-D-oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (3), 12-O-benzoylsarcostin 3-O-beta-D-oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (4), sarcostin 3-O-beta-D-oleandropyranosyl-(1-->4)-beta-D-canaropyranosyl-(1-->4)-beta-D-oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (5), sarcostin 3-O-beta-D-oleandropyranosyl-(1-->4)-beta-D-canaropyranosyl-(1-->4)-beta-D-canaropyranosyl-(1-->4)-beta-D-digitoxopyranoside (6), 12-O-benzoyldeacylmetaplexigenin 3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-oleandropyranosyl-(1-->4)-beta-D-canaropyranosyl-(1-->4)-beta-d-oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (7), and 12-O-benzoylsarcostin 3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-oleandropyranosyl-(1-->4)-beta-d-canaropyranosyl-(1-->4)-beta-D-oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (8), respectively. All compounds (1-8) were tested for in vitro cytotoxicity; only compound 3 showed weak inhibitory activity against Raji and AGZY cell lines.


Assuntos
Asclepias/química , Glicosídeos/isolamento & purificação , Esteroides/isolamento & purificação , Sequência de Carboidratos , Glicosídeos/química , Modelos Moleculares , Dados de Sequência Molecular , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria Infravermelho , Esteroides/química
12.
Patient Prefer Adherence ; 12: 667-672, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29750021

RESUMO

OBJECTIVE: The aim of this study was to translate, adapt, and validate the Satisfaction with Oral Anti-Diabetic Agent Scale (SOADAS) in type 2 diabetes mellitus (DM) patients taking oral antidiabetic drugs (OADs) in Taiwan. PATIENTS AND METHODS: The SOADAS was translated to Chinese and was modified based on reviews of two physicians, five diabetes educators, and two patient focus groups. A cross-sectional interviewer-administered survey was conducted in adult patients with type 2 DM who were taking OADs. The Chinese version of the SOADAS (C-SOADAS), the EuroQol 5 dimensions 3-level (EQ-5D-3L) questionnaire, and a demographic questionnaire were administered to participants. Instrument structure, internal consistency, convergent validity, and known-group validity were assessed. RESULTS: A total of 260 DM patients were recruited. The mean score of an individual item ranged from 3.6 to 3.9, while the mean total score (out of 25 possible points) was 18.7 points. Overall, floor and ceiling effects were negligible. The Cronbach's α value was 0.81. All the four predetermined hypotheses for known-group validity assessment were fulfilled. In convergent validity testing, the C-SOADAS total scores were found to be correlated with EuroQol-Visual Analog Scale (EQ-VAS) scores (r = 0.2; p < 0.01) but not with EuroQol 5 dimensions (EQ-5D) index scores (r = 0.02; p = 0.81). CONCLUSION: The 5-item C-SOADAS appears to be a psychometrically acceptable measure of OAD treatment satisfaction among type 2 DM patients in Taiwan. The tool may be incorporated into clinical practice to quickly assess treatment outcomes from patients' perspectives.

13.
Genetics ; 202(1): 77-92, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26564157

RESUMO

DNA double-strand breaks (DSBs) represent one of the most threatening lesions to the integrity of genomes. In yeast Saccharomyces cerevisiae, NuA4, a histone acetylation complex, is recruited to DSBs, wherein it acetylates histones H2A and H4, presumably relaxing the chromatin and allowing access to repair proteins. Two subunits of NuA4, Yng2 and Eaf3, can interact in vitro with methylated H3K4 and H3K36 via their plant homeodomain (PHD) and chromodomain. However, the roles of the two domains and how they interact in a combinatorial fashion are still poorly characterized. In this study, we generated mutations in the PHD and chromodomain that disrupt their interaction with methylated H3K4 and H3K36. We demonstrate that the combined mutations in both the PHD and chromodomain impair the NuA4 recruitment, reduce H4K12 acetylation at the DSB site, and confer sensitivity to bleomycin that induces DSBs. In addition, the double mutant cells are defective in DSB repair as judged by Southern blot and exhibit prolonged activation of phospho-S129 of H2A. Cells harboring the H3K4R, H3K4R, K36R, or set1Δ set2Δ mutant that disrupts H3K4 and H3K36 methylation also show very similar phenotypes to the PHD and chromodomain double mutant. Our results suggest that multivalent interactions between the PHD, chromodomain, and methylated H3K4 and H3K36 act in a combinatorial manner to recruit NuA4 and regulate the NuA4 activity at the DSB site.


Assuntos
DNA Fúngico/metabolismo , Histona Acetiltransferases/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Acetilação , Acetiltransferases/genética , Acetiltransferases/metabolismo , Sítios de Ligação , Bleomicina/farmacologia , Cromatina/metabolismo , Quebras de DNA de Cadeia Dupla , Farmacorresistência Fúngica/genética , Histona Acetiltransferases/química , Histona Acetiltransferases/genética , Histonas/metabolismo , Metilação , Mutação , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética
14.
Oncotarget ; 5(15): 6323-37, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25051366

RESUMO

Cisplatin can cause intrastrand and interstrand crosslinks between purine bases and is a chemotherapeutic drug widely used to treat cancer. However, the major barrier to the efficacy of the treatment is drug resistance. Homologous recombination (HR) plays a central role in restoring stalled forks caused by DNA lesions. Here, we report that chronic treatment with cisplatin induces HR to confer cisplatin resistance in nasopharyngeal carcinoma (NPC) cells. A high frequency of sister chromatid exchanges (SCE) occurs in the cisplatin-resistant NPC cells. In addition, several genes in the Fanconi anemia (FA) and template switching (TS) pathways show elevated expression. Significantly, depletion of HR gene BRCA1, TS gene UBC13, or FA gene FANCD2 suppresses SCE and causes cells to accumulate in the S phase, concomitantly with high γH2AX foci formation in the presence of low-dose cisplatin. Consistent with this result, depletion of several genes in the HR, TS, or FA pathway sensitizes the cisplatin-resistant NPC cells to cisplatin. Our results suggest that the enhanced HR, in coordination with the FA and TS pathways, underlies the cisplatin resistance. Targeting the HR, TS, or FA pathways could be a potential therapeutic strategy for treating cisplatin-resistant cancer.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Troca de Cromátide Irmã/efeitos dos fármacos , Carcinoma , Linhagem Celular Tumoral , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Fenótipo , Recombinação Genética/efeitos dos fármacos
15.
J Agric Food Chem ; 58(17): 9518-22, 2010 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-20687553

RESUMO

Phytoalexins t-resveratrol and t-piceatannol, the well-known health-promoting active components in plants, are secondary metabolites generated upon biotic or abiotic stresses. We have reported UV-irradiated peanut callus is a potent means to produce these compounds (J. Agric. Food Chem. 2005, 53, 3877). In this work, the effects of fungi and chemical elicitors on induction of t-resveratrol and t-piceatannol were examined. Results showed the investigated fungi Botryodiplodia theobromae and Reishi Ganoderma lucidum were generally more effective than chemical stress methyl jasmonate, salicylic acid, and sucrose. As high as 15.46+/-9.85 microg of t-resveratrol and 6.93+/-2.03 microg of t-piceatannol could be elicited in each gram of callus by sterilized G. lucidum mycelium (80 mg). Although much more sterilized G. ludicum mycelia was required to induce similar level of t-resveratrol and t-piceatannol in comparison to the sterilized B. theobromae mycelia (1 mg), uptake of the G. ludicum mycelium may provide a variety of health-promoting effects. Our findings suggest G. ludicum mycelium-treated peanut callus is a good source of bioactive components.


Assuntos
Arachis/metabolismo , Reishi/química , Estilbenos/metabolismo , Cromatografia Líquida de Alta Pressão , Resveratrol
16.
Phytochemistry ; 70(17-18): 2064-71, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19833361

RESUMO

Bioassay-guided fractionation of roots and stems of Ardisia virens Kurz (Myrsinaceae) led to isolation of fourteen compounds, (2'R)-6-(2'-acetoxypentadecyl)-5-hydroxy-2-methoxy-1,4-benzoquinone (1), (2'R)-6-(2'-acetoxytridecyl)-5-hydroxy-2-methoxy-1,4-benzoquinone (2), (2'R)-6-(2'-acetoxytridecyl)-2-methoxy-1,4-dihydroxybenzene (3), (2'R)-6-(2'-acetoxytridecyl)-5-formyl-2-methoxy-1,4-dihydroxybenzene (4), 1-(3,5-dihydroxyphenyl)nonan-1-one (5), 1-(3-hydroxy-5-methoxyphenyl)pentan-1-one (6), (2'S)-3-hydroxy-5-methoxyphenyl-2'-tridecanol (7), (2'S)-3-hydroxy-5-methoxyphenyl-2'-pentadecanol (8), (2'S)-5-acetoxy-3-hydroxyphenyl-2'-tetradecanol (9), 1-acetoxy-2-methoxy-6-pentadecyl-4-hydroxybenzene (10), 1-acetoxy-2-methoxy-6-tridecyl-4-hydroxybenzene (11), (2'R)-1-acetoxy-6-(2'-acetoxy-tridecyl)-2-methoxy-4-hydroxybenzene (12), (2'R)-1-acetoxy-6-(2'-acetoxypentadecyl)-2-methoxy-4-hydroxybenzene (13), and 1-acetoxy-6-(2'-ketopentadecyl)-2-methoxy-4-hydroxylbenzene (14), together with thirty-four other known compounds, of which three, 1-(3,5-dihydroxyphenyl)pentan-1-one (15), 1-(3,5-dihydroxyphenyl)heptan-1-one (16), and 1-(3,5-dihydroxyphenyl)pentadecan-1-one (17), were isolated for the first time from a natural source. Their structures were elucidated by analyses of spectroscopic data. Seven cytotoxic constituents were found to be 3, 10-12, ardisianone (18), cornudentanone (19), and ardisianol (31) with cytotoxic properties (IC(50) values < or =4 microg/mL) against MCF-7, NCI-H460 and SF-268 cancer cell lines in vitro.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Ardisia/química , Benzoquinonas/uso terapêutico , Neoplasias/tratamento farmacológico , Fenóis/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Alcanos/isolamento & purificação , Alquilação , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Benzoquinonas/isolamento & purificação , Benzoquinonas/farmacologia , Linhagem Celular Tumoral , Heptanos/isolamento & purificação , Humanos , Concentração Inibidora 50 , Fenóis/isolamento & purificação , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas , Caules de Planta
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