RESUMO
BACKGROUND: Platinum-based chemotherapy is the recommended adjuvant treatment for patients with resectable, ALK-positive non-small-cell lung cancer (NSCLC). Data on the efficacy and safety of adjuvant alectinib as compared with chemotherapy in patients with resected ALK-positive NSCLC are lacking. METHODS: We conducted a global, phase 3, open-label, randomized trial in which patients with completely resected, ALK-positive NSCLC of stage IB (tumors ≥4 cm), II, or IIIA (as classified according to the seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer and Union for International Cancer Control) were randomly assigned in a 1:1 ratio to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy in four 21-day cycles. The primary end point was disease-free survival, tested hierarchically among patients with stage II or IIIA disease and then in the intention-to-treat population. Other end points included central nervous system (CNS) disease-free survival, overall survival, and safety. RESULTS: In total, 257 patients were randomly assigned to receive alectinib (130 patients) or chemotherapy (127 patients). The percentage of patients alive and disease-free at 2 years was 93.8% in the alectinib group and 63.0% in the chemotherapy group among patients with stage II or IIIA disease (hazard ratio for disease recurrence or death, 0.24; 95% confidence interval [CI], 0.13 to 0.45; P<0.001) and 93.6% and 63.7%, respectively, in the intention-to-treat population (hazard ratio, 0.24; 95% CI, 0.13 to 0.43; P<0.001). Alectinib was associated with a clinically meaningful benefit with respect to CNS disease-free survival as compared with chemotherapy (hazard ratio for CNS disease recurrence or death, 0.22; 95% CI, 0.08 to 0.58). Data for overall survival were immature. No unexpected safety findings were observed. CONCLUSIONS: Among patients with resected ALK-positive NSCLC of stage IB, II, or IIIA, adjuvant alectinib significantly improved disease-free survival as compared with platinum-based chemotherapy. (Funded by F. Hoffmann-La Roche; ALINA ClinicalTrials.gov number, NCT03456076.).
Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Compostos de Platina , Humanos , Carbazóis/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Piperidinas/uso terapêutico , Receptores Proteína Tirosina Quinases , Resultado do Tratamento , Administração Oral , Administração Intravenosa , Compostos de Platina/uso terapêutico , Antineoplásicos/uso terapêuticoRESUMO
PURPOSE: Acute palliative care units (APCUs) are inpatient services in tertiary hospitals that provide intensive symptom management and assist in hospital discharge for transitions to hospice care. We aimed to analyze the clinical outcomes of operating an APCU at a comprehensive cancer center. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 1,440 consecutive patients admitted to the APCU and analyzed demographic and clinical information, discharge outcomes, symptom assessments using the Edmonton Symptom Assessment System, spiritual distress, and financial distress. RESULTS: The median age of patients was 67.0 (range, 23-97) years, and 41% were female. The most common primary cancer types were lung (21.9%), hepatopancreatobiliary (14.1%), and colorectal cancers (12.9%). The median length of stay was 8.0 days (range, 1-60 days), and 31.0% of patients died in the APCU. Death in the APCU showed a significant decrease over time, and overall inpatient death in oncology wards did not increase after APCU opening. In total, 44.7% of patients were discharged to government-certified hospice centers. The proportion of patients discharged to certified hospice centers increased from 32.2% in 2015 to 62.4% in 2018. Among 715 patients with a follow-up evaluation 1 week after admission, Edmonton Symptom Assessment System symptom scores, spiritual distress, and financial distress showed statistically significant improvements compared with the baseline symptom scores (P < .001). This improvement was limited to patients who did not die in the APCU. CONCLUSION: Patients with advanced cancer admitted to the APCU may experience significant improvements in distressing symptoms. The majority of patients requiring transition to hospice were successfully transferred to certified hospice centers. The percentage discharged alive improved over time.
Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Adulto , Idoso , Idoso de 80 Anos ou mais , Cuidados Críticos , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/terapia , Cuidados Paliativos , Estudos Retrospectivos , Adulto JovemRESUMO
CONTEXT: Pinus densiflora Siebold & Zucc. (Pinaceae) needle extracts ameliorate oxidative stress, but research into their anti-inflammatory effects is limited. OBJECTIVE: To investigate antioxidant and anti-inflammatory effects of a Pinus densiflora needles (PINE) ethanol extract in vitro and in vivo. MATERIALS AND METHODS: We measured levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at various PINE concentrations (25, 50 and 100 µg/mL; but 6.25, 12.5 and 25 µg/mL for interleukin-1ß and prostaglandin E2 (PGE2)). Thirty ICR mice were randomized to six groups: vehicle, control, PINE pre-treatment (0.1, 0.3 and 1 mg/left ear for 10 min followed by arachidonic acid treatment for 30 min) and dexamethasone. The posttreatment ear thickness and myeloperoxidase (MPO) activity were measured. RESULTS: PINE 100 µg/mL significantly decreased ROS (IC50, 70.93 µg/mL, p < 0.01), SOD (IC50, 30.99 µg/mL, p < 0.05), malondialdehyde (p < 0.01), nitric oxide (NO) (IC50, 27.44 µg/mL, p < 0.01) and tumour necrosis factor-alpha (p < 0.05) levels. Interleukin-1ß (p < 0.05) and PGE2 (p < 0.01) release decreased significantly with 25 µg/mL PINE. PINE 1 mg/ear inhibited LPS-stimulated expression of cyclooxygenase-2 and inducible NO synthase in RAW264.7 macrophages and significantly inhibited ear oedema (36.73-15.04% compared to the control, p < 0.01) and MPO activity (167.94-105.59%, p < 0.05). DISCUSSION AND CONCLUSIONS: PINE exerts antioxidant and anti-inflammatory effects by inhibiting the production of inflammatory mediators. Identified flavonoids such as taxifolin and quercetin glucoside can be attributed to effect of PINE.
Assuntos
Mediadores da Inflamação , Pinus , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Dinoprostona/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/uso terapêutico , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Activated astrocytes are involved in the progression of neurodegenerative diseases. Traditionally, Ailanthus altissima (Mill.) Swingle, widely distributed in East Asia, has been used as a medicine for the treatment of fever, gastric diseases, and inflammation. Although A. altissima has been reported to play an anti-inflammatory role in peripheral tissues or cells, its role in the central nervous system (CNS) remains unclear. AIM OF THE STUDY: In the present study, we investigated the anti-inflammatory effects and mechanism of action of A. altissima in primary astrocytes stimulated by lipopolysaccharide (LPS). MATERIALS AND METHODS: A nitrite assay was used to measure nitric oxide (NO) production, and the tetrazolium salt 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to determine cytotoxicity. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) were determined with western blotting. Reverse-transcription PCR was used to assess the expression of inflammatory cytokines. The levels of reactive oxygen species were measured using 2,7-dichlorodihydrofluorescein diacetate. Luciferase assay and immunocytochemistry were used for assessing nuclear factor-kappa B (NF-κB) transcription and p65 localization, respectively. Memory and social interaction were analyzed using the Y-maze and three-chamber tests, respectively. RESULTS: The ethanol extract of A. altissima leaves (AAE) inhibited iNOS and COX-2 expression in LPS-stimulated astrocytes. Moreover, AAE reduced the transcription of various proinflammatory mediators, hindered NF-κB activation, and suppressed extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activation without p38 activation. Ultra-high performance liquid chromatography with mass spectrometry analysis revealed that AAE comprised ethyl gallate, quercetin, and kaempferol, along with luteolin, which has anti-inflammatory properties, and repressed LPS-induced nitrite levels and the nuclear translocation of p65. Finally, oral administration of AAE attenuated LPS-induced memory and social impairment in mice and repressed LPS-induced ERK and JNK activation in the cortices of mice. CONCLUSION: AAE could have therapeutic uses in the treatment of neuroinflammatory diseases via suppression of astrocyte activation.
Assuntos
Ailanthus/química , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Citocinas/metabolismo , Inflamação/patologia , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias/tratamento farmacológico , Óxido Nítrico/metabolismo , Extratos Vegetais/isolamento & purificação , Folhas de PlantaRESUMO
Pinus thunbergii Parl. (PTP) has traditionally been used for edible and medicinal purposes to treat several disorders, including diabetes and neuralgia. Therefore, this study sought to evaluate the inhibitory effects of PTP leaf ethanol extracts on acute inflammation. Moreover, the reactive oxygen species (ROS) scavenging activity, superoxide dismutase (SOD) activity, lipopolysaccharide (LPS)-induced nitric oxide (NO) generation, and H2O2-induced lipid peroxidation capacity of PTP were assessed in vitro in RAW 264.7 macrophages. Our results suggest that PTP prevents cell damage caused by oxidative free radicals and downregulates the expression of LPS-induced inflammation-associated factors including inducible nitric oxidase synthetase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). PTP inhibited NO production by 53.5% (P < 0.05) and iNOS expression by 71.5% (P < 0.01) at 100 µg/mL. PTP at 100 µg/mL also inhibited ROS generation by 58.2% (P < 0.01) and SOD activity by 29.3%, as well as COX-2 expression by 83.3% (P < 0.01) and PGE2 expression by 98.6% (P < 0.01). The anti-inflammatory effects of PTP were confirmed in vivo using an arachidonic acid (AA)-induced ear edema mouse model. Ear thickness and myeloperoxidase (MPO) activity were evaluated as indicators of inflammation. PTP inhibited edema formation by 64.5% (P < 0.05) at 1.0 mg/ear. A total of 16 metabolites were identified in PTP extracts and categorized into subgroups, including two phenolic acids (mainly quinic acid), seven flavonoids, five lignans, one sesquiterpenoid, and one long-chain fatty acid. Therefore, our results suggest that PTP possesses anti-inflammatory properties.
RESUMO
BACKGROUND: Plants have been used as an important source of indispensable bioactive compounds in various cosmetics, foods, and medicines. However, the subsequent functional annotation of these compounds seems arduous because of the largely uncharacterized, vast metabolic repertoire of plant species with known biological phenotypes. Hence, a rapid multi-parallel screening and characterization approach is needed for plant functional metabolites. RESULTS: Fifty-one species representing three plant families, namely Asteraceae, Fabaceae, and Rosaceae, were subjected to metabolite profiling using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultrahigh-performance liquid chromatography quadrupole orbitrap ion trap tandem mass spectrometry (UHPLC-Q-orbitrap-MS/MS) as well as multivariate analyses. Partial least squares discriminant analysis (PLS-DA) of the metabolite profiling datasets indicated a distinct clustered pattern for 51 species depending on plant parts (leaves and stems) and relative phylogeny. Examination of their relative metabolite contents showed that the extracts from Fabaceae plants were abundant in amino acids, fatty acids, and genistein compounds. However, the extracts from Rosaceae had higher levels of catechin and ellagic acid derivatives, whereas those from Asteraceae were higher in kaempferol derivatives and organic acids. Regardless of the different families, aromatic amino acids, branch chain amino acids, chlorogenic acid, flavonoids, and phenylpropanoids related to the shikimate pathway were abundant in leaves. Alternatively, certain amino acids (proline, lysine, and arginine) as well as fatty acids levels were higher in stem extracts. Further, we investigated the associated phenotypes, i.e., antioxidant activities, affected by the observed spatial (leaves and stem) and intra-family metabolomic disparity in the plant extracts. Pearson's correlation analysis indicated that ellagic acid, mannitol, catechin, epicatechin, and quercetin derivatives were positively correlated with antioxidant phenotypes, whereas eriodictyol was positively correlated with tyrosinase inhibition activity. CONCLUSIONS: This work suggests that metabolite profiling, including multi-parallel approaches and integrated bioassays, may help the expeditious characterization of plant-derived metabolites while simultaneously unraveling their chemodiversity.
Assuntos
Metaboloma , Extratos Vegetais/química , Folhas de Planta/química , Caules de Planta/química , Aminoácidos/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Asteraceae/química , Asteraceae/metabolismo , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Fabaceae/química , Fabaceae/metabolismo , Ácidos Graxos/metabolismo , Flavonoides/química , Flavonoides/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Redes e Vias Metabólicas , Metabolômica/métodos , Monofenol Mono-Oxigenase/metabolismo , Extratos Vegetais/metabolismo , Folhas de Planta/metabolismo , Caules de Planta/metabolismo , Rosaceae/química , Rosaceae/metabolismo , Espectrometria de Massas em TandemRESUMO
Plant species have traditionally been revered for their unparalleled pharmacognostic applications. We outline a non-iterative multi-parallel metabolomic-cum-bioassay-guided methodology toward the functional characterization of ethanol extracts from the Betulaceae family plants (n = 10). We performed mass spectrometry (MS)-based multivariate analyses and bioassay-guided (ABTS antioxidant activity and cytoprotective effects against H2O2-induced cell damage) analyses of SPE fractions. A clearly distinct metabolomic pattern coupled with significantly higher bioactivities was observed for 40% methanol SPE eluate. Further, the 40% SPE eluate was subjected to preparative high-performance liquid chromatography (prep-HPLC) analysis, yielding 72 sub-fractions (1 min-1), with the highest antioxidant activities observed for the 15 min and 31 min sub-fractions. We simultaneously performed hyphenated-MS-based metabolite characterization of bioactive components for both the 40% methanol SPE fraction and its prep-HPLC sub-fraction (15 min and 31 min). Altogether, 19 candidate metabolites were mainly observed to contribute toward the observed bioactivities. In particular, ethyl gallate was mainly observed to affect the antioxidant activities of SPE and prep-HPLC fractions of Alnus firma extracts. We propose an integrated metabolomic-cum-bioassay-guided approach for the expeditious selection and characterization of discriminant metabolites with desired phenotypes or bioactivities.
RESUMO
Skin aging is associated with increased reactive oxygen species (ROS) produced by human cells. These radicals are the main causes of skin aging, and skin cells have developed antioxidant enzymes for protection against ROS-induced damage. Antioxidants play critical roles to prevent ROS-induced aging symptoms. In this study, the antioxidant properties of Pourthiaea villosa (Thunb.) Decne. extract (PVDE) were studied. Human dermal fibroblast (HDF) cells were treated with PVDE to evaluate its antioxidant and antiaging activities and to investigate the underlying mechanisms. The identified compounds were polyols, and phenolic and flavonoid compounds from PVDE by UHPLC-LTQ-IT-MS/MS. PVDE exhibited significant antioxidant effects, as evaluated with reducing power, and ABTS and DPPH radical scavenging activity. Furthermore, PVDE treatment significantly increased antioxidant enzyme expressions and effectively blocked H2O2-induced matrix metalloproteinase activity through MAPK signaling pathways in HDFs. Therefore, these results showed that PVDE affords an advantage of being a functional natural material with antioxidant and antiaging effects for the skin.
Assuntos
Fibroblastos/efeitos dos fármacos , Peróxido de Hidrogênio/efeitos adversos , Photinia/química , Extratos Vegetais/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Protetores Solares/farmacologia , Antioxidantes/farmacologia , Fibroblastos/metabolismo , Humanos , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Envelhecimento da Pele/efeitos da radiação , Protetores Solares/química , Raios Ultravioleta/efeitos adversosRESUMO
Liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics implies that annotated metabolites can serve as potential markers of the associated bioactivities of plant extracts. Firstly, we selected Aphananthe aspera and Zelkova serrata (Family: Ulmaceae) from 16 Korean plant species based on their distinct principal component analysis (PCA) patterns in LC-MS datasets and antioxidant activity assays. Further, we chose 40% solid-phase extraction (SPE) extracts of the two species displaying the highest antioxidant activities coupled with distinct PCA patterns. Examining the metabolite compositions of the 40% SPE extracts, we observed relatively higher abundances of quercetin, kaempferol, and isorhamnetin O-glucosides for A. aspera, whereas quercetin, isorhamnetin O-glucuronides, and procyanidin dimer were relatively higher in Z. serrata. These metabolites were clearly distinguished in pathway map and displayed strong positive correlations with antioxidant activity. Further, we performed preparative high-performance liquid chromatography (prep-HPLC) analysis coupled with the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) assay to validate their functional correlations. As a result, quercetin O-sophoroside was determined as the main antioxidant in A. aspera, while isorhamnetin O-glucuronide and procyanidin dimer were the primary antioxidants in Z. serrata. The current study suggests that the LC-MS-based untargeted metabolomics strategy can be used to illuminate subtle metabolic disparities as well as compounds associated with bioactivities.
Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ulmaceae/química , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Descoberta de Drogas , Metaboloma , Metabolômica/métodos , Estrutura Molecular , Espectrometria de Massas em Tandem , Ulmaceae/metabolismoRESUMO
Plants are an important and inexhaustible source of bioactive molecules in food, medicine, agriculture, and industry. In this study, we performed systematic liquid chromatography-mass spectrometry (LC-MS)-based metabolic profiling coupled with antioxidant assays for indigenous plant family extracts. Partial least-squares discriminant analysis of LC-MS datasets for the extracts of 34 plant species belonging to the families Aceraceae, Asteraceae, and Rosaceae showed that these species were clustered according to their respective phylogenies. In particular, seven Aceraceae species were clearly demarcated with higher average antioxidant activities, rationalizing their application for bioconversion studies. On the basis of further evaluation of the interspecies variability of metabolic profiles and antioxidant activities among Aceraceae family plants, we found that Acer tataricum (TA) extracts were clearly distinguished from those of other species, with a higher relative abundance of tannin derivatives. Further, we detected a strong positive correlation between most tannin derivatives and the observed higher antioxidant activities. Following Aspergillus oryzae-mediated fermentative bioconversion of Acer plant extracts, we observed a time-correlated (0-8 days) linear increase in antioxidant phenotypes for all species, with TA having the highest activity. Temporal analysis of the MS data revealed tannin bioconversion mechanisms with a relatively higher abundance of gallic acid (m/z 169) accumulated at the end of 8 days, particularly in TA. Similarly, quercetin precursor (glycoside) metabolites were also transformed to quercetin aglycones (m/z 301) in most Acer plant extracts. The present study underscores the efficacy of fermentative bioconversion strategies aimed at enhancing the quality and availability of bioactive metabolites from plant extracts.
Assuntos
Acer/química , Acer/metabolismo , Aspergillus oryzae/crescimento & desenvolvimento , Metaboloma , Extratos Vegetais/química , Antioxidantes/química , Antioxidantes/metabolismo , Cromatografia Líquida , Ácido Gálico/química , Ácido Gálico/metabolismo , Espectrometria de Massas , Metabolômica , Quercetina/química , Quercetina/metabolismo , Taninos/química , Taninos/metabolismoRESUMO
The purpose of the present study was to investigate the antioxidant activity and anti-adipogenic effect of extracts from Alnus firma (A. firma), which is an edible plant that grows in mountainous areas. The total phenolic, flavonoid and anthocyanin content as well as the antioxidant activity of a 70% ethanolic extract of A. firma (AFE) was assessed. Furthermore, the effects of AFE on lipid accumulation and reactive oxygen species (ROS) production during adipogenesis of 3T3-L1 cells were investigated. The results revealed that the total phenolic, flavonoid and pro-anthocyanidin content of AFE as 436.26±3.30 mg gallic acid equivalents/g, 73.82±0.54 mg quercetin equivalents/g and 149.25±6.06 mg catechin equivalents/g, respectively. In addition, AFE exerted significant antioxidant effects in terms of 1,1-diphenyl-2-picryl hydrazyl radical scavenging activity, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity, reducing power, oxygen radical absorbance capacity and nitric oxide radical scavenging activity. As for its anti-adipogenic activity, AFE significantly inhibited ROS production and lipid accumulation during adipogenesis of 3T3-L1 cells compared with those in control cells. In addition, AFE regulated adipogenic transcription factors including peroxisome proliferatoractivated receptor-γ, CCAAT/enhance-binding protein α and adipocyte protein 2. These results indicated that A. firma is a potential candidate for a functional food supplement.
Assuntos
Adipogenia/efeitos dos fármacos , Alnus/química , Sequestradores de Radicais Livres/administração & dosagem , Extratos Vegetais/administração & dosagem , Células 3T3-L1 , Adipogenia/genética , Animais , Antocianinas/genética , Antioxidantes/administração & dosagem , Antioxidantes/química , Fator de Ligação a CCAAT/genética , Proteínas de Ligação a Ácido Graxo/genética , Sequestradores de Radicais Livres/química , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Camundongos , Óxido Nítrico/biossíntese , PPAR gama/genética , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
PURPOSE: To determine the social and clinical characteristics of immigrants with tuberculosis (TB) in South Korea. MATERIALS AND METHODS: The registered adult TB patients who were diagnosed and treated in Korea Medical Centers from January 2013 to December 2015 were analyzed retrospectively. A total of 105 immigrants with TB were compared to 932 native Korean TB patients. RESULTS: Among these 105 immigrants with TB, 86 (82%) were Korean-Chinese. The rate of drug-susceptible TB were lower in the immigrants group than in the native Korean group [odds ratio (OR): 0.46; 95% confidence interval (CI): 0.22-0.96, p=0.035]. Cure rate was higher in the immigrant group than in the native Korean group (OR: 2.03; 95% CI: 1.26-3.28, p=0.003). Treatment completion rate was lower in the immigrant group than in the native Korean group (OR: 0.50; 95% CI: 0.33-0.74, p=0.001). However, treatment success rate showed no significant difference between two groups (p=0.141). Lost to follow up (default) rate was higher in the immigrant group than in the native Korean group after adjusting for age and drug resistance (OR: 3.61; 95% CI: 1.36-9.61, p=0.010). There was no difference between defaulter and non-defaulter in clinical characteristics or types of visa among these immigrants (null p value). However, 43 TB patients with recent immigration were diagnosed as TB even though they had been screened as normal at the time of immigration. CONCLUSION: Endeavor to reduce the default rate of immigrants with TB and reinforce TB screening during the immigration process must be performed for TB infection control in South Korea.
Assuntos
Antituberculosos/uso terapêutico , Emigrantes e Imigrantes , Adesão à Medicação , Tuberculose/tratamento farmacológico , Tuberculose/etnologia , Adulto , Idoso , Emigrantes e Imigrantes/psicologia , Emigrantes e Imigrantes/estatística & dados numéricos , Feminino , Humanos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Razão de Chances , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Tuberculose/diagnósticoRESUMO
KEY MESSAGE: A multi-parallel approach gauging the mass spectrometry-based metabolite fingerprinting coupled with bioactivity and pathway evaluations could serve as an efficacious tool for inferring plant taxonomic orders. Thirty-four species from three plant families, namely Cornaceae (7), Fabaceae (9), and Rosaceae (18) were subjected to metabolite profiling using gas chromatography-time-of-flight-mass spectrometry (GC-TOF-MS) and ultrahigh performance liquid chromatography-linear trap quadrupole-ion trap-mass spectrometry (UHPLC-LTQ-IT-MS/MS), followed by multivariate analyses to determine the metabolites characteristic of these families. The partial least squares discriminant analysis (PLS-DA) revealed the distinct clustering pattern of metabolites for each family. The pathway analysis further highlighted the relatively higher proportions of flavonols and ellagitannins in the Cornaceae family than in the other two families. Higher levels of phenolic acids and flavan-3-ols were observed among species from the Rosaceae family, while amino acids, flavones, and isoflavones were more abundant among the Fabaceae family members. The antioxidant activities of plant extracts were measured using ABTS, DPPH, and FRAP assays, and indicated that extracts from the Rosaceae family had the highest activity, followed by those from Cornaceae and Fabaceae. The correlation map analysis positively links the proportional concentration of metabolites with their relative antioxidant activities, particularly in Cornaceae and Rosaceae. This work highlights the pre-eminence of the multi-parallel approach involving metabolite profiling and bioactivity evaluations coupled with metabolic pathways as an efficient methodology for the evaluation of plant phylogenies.
Assuntos
Cornaceae/metabolismo , Fabaceae/metabolismo , Redes e Vias Metabólicas , Metabolômica/métodos , Rosaceae/metabolismo , Antioxidantes/metabolismo , Análise Discriminante , Análise dos Mínimos Quadrados , Metaboloma , Metabolismo Secundário , Especificidade da EspécieRESUMO
Korean red ginseng (KRG), a highly valuable medicinal herb in oriental societies, has biological activity similar to that of Panax ginseng. Recently, it has been discovered that the biological activities of red ginseng can vary according to heating and steaming processes under different conditions that change the principal components of KRG and result in changes in biological activity. This study evaluated and compared the effects of high temperature- and high pressure-treated red ginseng (HRG) and commercial red ginseng (RG) on ß-oxidation in C2C12 myotubes. HRG enhanced the phosphorylation levels of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), but RG did not affect the phosphorylation of AMPK in C2C12 myotubes. HRG also promoted the nuclear translocation of forkhead box protein O1 (FoxO1), and the translocation exerted an increase in the protein expression of adipose triglyceride lipase (ATGL). As a consequence, HRG increased the mRNA expression level of carnitine palmitoyltransferase 1 (CPT-1) compared to the control. Taken together, our results indicated that HRG promotes the lipolysis of triglycerides and mitochondrial ß-oxidation of fatty acids in C2C12 myotubes, suggesting that alterations to the principal components by high temperature and pressure may positively influence the nutraceutical functions of HRG.
Assuntos
Lipólise/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Panax/química , Extratos Vegetais/farmacologia , Animais , Química Farmacêutica , Ácidos Graxos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Oxirredução/efeitos dos fármacos , Extratos Vegetais/química , Triglicerídeos/metabolismoRESUMO
The antioxidant activity and chlorogenic acid and caffeic acid contents were investigated from different parts of Acanthopanax senticosus and A. koreanum. Antioxidant activity was assessed by various in vitro assays such as DPPH, ABTS, FRAP, reducing power assays and ORAC, and the chlorogenic acid and caffeic acid were validated by HPLC chromatography. Among the various extracts, the fruit extracts of A. senticosus and A. koreanum exhibited strongest antioxidant activities including ABTS, FRAP, reducing power and ORAC, however, strongest DPPH radical scavenging activity was observed from the leaf extract of A. senticosus. In addition, the antioxidant activities of various extracts were correlated with total phenolic and proanthocyanidin contents. The major phenolic contents from various parts of these plants observed that leaf extract of A. senticosus expressed higher levels of chlorogenic acid (14.86 mg/dry weigh g) and caffeic acid (3.09 mg/dry weigh g) than other parts. Therefore, these results suggest that the leaf of A. senticosus may be an excellent natural source for functional foods and pharmaceutical agents, and the validated method was useful for the quality control of A. senticosus.
Assuntos
Antioxidantes/química , Antioxidantes/isolamento & purificação , Eleutherococcus/química , Extratos Vegetais/químicaRESUMO
Codonopsis lanceolata is a perennial plant that has been used as a food and in traditional medicine for the treatment of cough, bronchitis, and inflammation in East Asia including Korea, Japan, and China. However, information regarding its toxicity is limited. Therefore, we performed a safety evaluation of aqueous C. lanceolata root extract (CLE) in Sprague-Dawley rats. Assessment of acute toxicity revealed that CLE did not influence mortality, clinical appearance, body weight gain, or necropsy findings at a dose of 5000 mg/kg body weight. In the subchronic oral toxicity, data revealed that several significant alteration in food consumption, water consumption, protein excretion, WBCs levels, TGs, BUN levels, and the absolute and relative weights in the liver, spleen and lungs. However, these changes were transient and were not considered treatment related because they showed no apparent dose dependent. These results suggest that CLE (1250, 2500, and 5000 mg/kg body weight/day) administered orally does not cause acute or subchronic toxicity to male or female rats. The 50% lethal dose (LD50) of CLE was determined to be greater than 5000 mg/kg.
Assuntos
Codonopsis , Extratos Vegetais/toxicidade , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Administração Oral , Animais , Biomarcadores/sangue , Biomarcadores/urina , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Dose Letal Mediana , Masculino , Tamanho do Órgão/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/administração & dosagem , Raízes de Plantas , Plantas Medicinais , Proteinúria/induzido quimicamente , Proteinúria/urina , Ratos Sprague-Dawley , Medição de Risco , Fatores de Tempo , Testes de Toxicidade Aguda/métodos , Testes de Toxicidade Crônica/métodosRESUMO
Ginseng has been used in humans for thousands of years but its effects on viral infection have not been well understood. We investigated the effects of red ginseng extract (RGE) on respiratory syncytial virus (RSV) infection using in vitro cell culture and in vivo mouse models. RGE partially protected human epithelial (HEp2) cells from RSV-induced cell death and viral replication. In addition, RGE significantly inhibited the production of RSV-induced pro-inflammatory cytokine (TNF-α) in murine dendritic and macrophage-like cells. More importantly, RGE intranasal pre-treatment prevented loss of mouse body weight after RSV infection. RGE treatment improved lung viral clearance and enhanced the production of interferon (IFN-γ) in bronchoalveolar lavage cells upon RSV infection of mice. Analysis of cellular phenotypes in bronchoalveolar lavage fluids showed that RGE treatment increased the populations of CD8+ T cells and CD11c+ dendritic cells upon RSV infection of mice. Taken together, these results provide evidence that ginseng has protective effects against RSV infection through multiple mechanisms, which include improving cell survival, partial inhibition of viral replication and modulation of cytokine production and types of immune cells migrating into the lung.
Assuntos
Antivirais/farmacologia , Células Epiteliais/virologia , Panax , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/administração & dosagem , Líquido da Lavagem Broncoalveolar/microbiologia , Antígeno CD11c/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/virologia , Feminino , Humanos , Interferon gama/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia , Mucosa Respiratória/virologia , Fator de Necrose Tumoral alfa/metabolismo , Carga Viral/efeitos dos fármacosRESUMO
The extract obtained from berries contains high amounts of anthocyanins, and this extract is used as a phytotherapeutic agent for different types of diseases. In this study, we examined the cytoprotective effects of cyanidin-3-glucoside (C3G) isolated from mulberry fruit against pancreatic ß-cell apoptosis caused by hydrogen peroxide (H2O2)-induced oxidative stress. The MIN6 pancreatic ß-cells were used to investigate the cytoprotective effects of C3G on the oxidative stress-induced apoptosis of cells. Cell viability was examined by MTT assay and lipid peroxidation was assayed by thiobarbituric acid (TBA) reaction. Immunofluorescence staining, flow cytometry and western blot analysis were also used to determine apoptosis and the expression of proteins associated with apoptosis. Our results revealed that H2O2 increased the rate of apoptosis by stimulating various pro-apoptotic processes, such as the generation of intracellular reactive oxygen species (ROS), lipid peroxidation, DNA fragmentation and caspase-3 activation. However, C3G reduced the H2O2-induced cell death in the MIN6N pancreatic ß-cells. In addition, we confirmed that H2O2 activated mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 MAPK. C3G inhibited the phosphorylation of ERK and p38 without inducing the phosphorylation of JNK. Furthermore, C3G regulated the intrinsic apoptotic pathway-associated proteins, such as proteins belonging to the Bcl-2 family, cytochrome c and caspase-3. Taken together, our results suggest that C3G isolated from mulberry fruit has potential for use as a phytotherapeutic agent for the prevention of diabetes by preventing oxidative stress-induced ß-cell apoptosis.
Assuntos
Antocianinas/farmacologia , Apoptose/efeitos dos fármacos , Frutas/química , Glucosídeos/farmacologia , Células Secretoras de Insulina/metabolismo , Morus/química , Estresse Oxidativo/efeitos dos fármacos , Animais , Antocianinas/química , Antocianinas/isolamento & purificação , Caspase 3/metabolismo , Linhagem Celular , Fragmentação do DNA/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glucosídeos/química , Glucosídeos/isolamento & purificação , Peróxido de Hidrogênio/farmacologia , Células Secretoras de Insulina/citologia , Peroxidação de Lipídeos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Oxidantes/farmacologiaRESUMO
The present study investigated the cytoprotective effects of cyanidin3glucoside (C3G), isolated from mulberry fruits, on the glucotoxicityinduced apoptosis of pancreatic ßcells to evaluate the antidiabetic effects of this compound. MIN6N pancreatic ßcells were used to investigate the cytoprotective effects of C3G. In addition, the effects of C3G on the glucotoxicityinduced apoptosis of pancreatic ßcells was evaluated using MTT assay, immunofluorescent staining, flow cytometric and western blot analyses. The pancreatic ßcells cultured under high glucose conditions exhibited distinct apoptotic features. C3G decreased the generation of intracellular reactive oxygen species, DNA fragmentation and the rate of apoptosis. C3G also prevented pancreatic ßcell apoptosis induced by high glucose conditions by interfering with the intrinsic apoptotic pathways. In addition, C3G treatment resulted in increased insulin secretion compared with treatment with high glucose only. In conclusion, the results of the present study suggested that C3G obtained from mulberry fruits may be a potential phytotherapeutic agent for the prevention of diabetes.
Assuntos
Antocianinas/farmacologia , Apoptose/efeitos dos fármacos , Glucose/metabolismo , Glucosídeos/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Substâncias Protetoras/farmacologia , Animais , Antocianinas/isolamento & purificação , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Frutas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Glucosídeos/isolamento & purificação , Insulina/metabolismo , Secreção de Insulina , Camundongos , Morus/química , NF-kappa B/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Substâncias Protetoras/isolamento & purificação , Transporte Proteico , Espécies Reativas de Oxigênio/metabolismoRESUMO
Codonopsis lanceolata extract (CLE) has been used in traditional medicine in the Asian-Pacific region for the treatment of bronchitis, cough, and inflammation. However, it is still unclear whether obesity in mice can be altered by diet supplementation with CLE. To investigate whether CLE could have preventative effects on high fat diet (HFD)-induced obesity, male C57BL/6 mice were placed on either a normal chow diet, 60% HFD, or a HFD supplemented with CLE (60, 180, and 360 mg/kg/day) for 12 weeks. CLE decreased body weight and subcutaneous and visceral fat weights in HFD-induced obese mice. CLE group mice showed lower fat accumulation and a smaller adipocyte area in the adipose tissue compared with the HFD group mice. CLE group mice exhibited lower serum levels of triglycerides, total cholesterol, low density lipoprotein (LDL), glucose, and insulin compared with the HFD group mice. In addition, CLE decreased liver weight and lowered the increase in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels in HFD-induced obese mice. These results indicate that CLE can inhibit the development of diet-induced obesity and hyperlipidemia in C57BL/6 mice.