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This corrects the article on p. e308 in vol. 37, PMID: 36345254.
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BACKGROUND: Preventive measures are needed to reduce the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers (HCWs). Notably, hospital staff are usually exposed when they are unmasked. There are limited data on the risk of transmission during mealtimes at hospital staff cafeterias. We aimed to evaluate the risk of transmission in cafeterias. METHODS: From January 2020 through September 2021, we analyzed the risk of SARS-CoV-2 transmission through closed-circuit television and radio-frequency identification tracking and follow-up testing when 33 HCWs, who were eventually diagnosed as coronavirus disease 2019 (COVID-19), ate in staff cafeterias during the infectious period. The seats were arranged so the HCWs would sit on either side without facing each other. There were no plastic barriers installed, and HCWs were encouraged not to talk during meals. RESULTS: Three of the 119 individuals who ate at seats next (about 30 cm) to index during the period of transmission and underwent follow-up SARS-CoV-2 polymerase chain reaction tests were diagnosed with COVID-19 (2.5%; 95% confidence interval, 0.5-7.4%). Among the 98 HCWs who were investigated about talking during meals, there was a higher attack rate among those who spoke with each other than among those who did not (12.5% [3/24] vs. 0% [0/74], P = 0.013). CONCLUSION: The risk of transmission in a hospital's employee cafeterias is not high with side-by-side seating, especially in the absence of conversation.
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COVID-19/epidemiologia , COVID-19/transmissão , Busca de Comunicante/métodos , Pessoal de Saúde/estatística & dados numéricos , Restaurantes/estatística & dados numéricos , Teste para COVID-19 , Hospitais/estatística & dados numéricos , Humanos , Refeições , Distanciamento Físico , SARS-CoV-2 , Vacinação/estatística & dados numéricosRESUMO
BACKGROUND: To evaluate the effects of isolating coronavirus disease 2019 (COVID-19) patients in general wards, we compared the rates of COVID-19 infection in nurses and nursing assistants working in COVID-19 designated wards and in general wards of our hospital from 1 October 2021 to 21 April 2022. METHODS: This study was conducted in a 2,700-bed tertiary care hospital in Seoul, Korea. Designated wards comprised single, negative pressure rooms and a 100% outdoor air system. RESULTS: During the study period, a total of 2,698 nurses and nursing assistants were employed at our hospital, of whom 310 (11%) were working in the designated wards, and the remaining 2,388 (89%) in the general wards, and among whom 1,158 (43%) were diagnosed with COVID-19. The healthcare workers (HCWs) in the designated wards were less frequently diagnosed with COVID-19 than those in the general wards (31% vs. 45%, P < 0.001). During the period before patients with COVID-19 were isolated in general wards, and during the period after these cases were isolated in general ward, HCWs in designated wards were less frequently infected with the virus than those in general wards (7% vs. 11%, P = 0.039; and 23% vs. 33%, P < 0.001, respectively). CONCLUSION: HCWs in designated wards have a lower rate of contracting COVID-19 than those in general wards. A lack of exposure to undiagnosed cases and their caregivers, greater care with social distancing outside the hospital, higher rates of 3-dose vaccinations, and the use of isolation rooms with negative pressure may be associated with this finding.
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COVID-19 , Humanos , COVID-19/epidemiologia , Quartos de Pacientes , SARS-CoV-2 , Pessoal de Saúde , HospitaisRESUMO
BACKGROUND: The potential for a nosocomial outbreak of coronavirus disease 2019 (COVID-19) from a fully vaccinated individual is largely unknown. METHODS: In October 2021, during the time when the delta variant was dominant, a nosocomial outbreak of COVID-19 occurred in two wards in a tertiary care hospital in Seoul, Korea. We performed airflow investigations and whole-genome sequencing (WGS) of the virus. RESULTS: The index patient developed symptoms 1 day after admission, and was diagnosed with COVID-19 on day 4 post-admission. He was fully vaccinated (ChAdOx1 nCoV-19) 2 months before the diagnosis. Three inpatients and a caregiver in the same room, two inpatients in an adjacent room, two inpatients in rooms remote from the index room, and one nurse on the ward tested positive. Also, two resident doctors who stayed in an on-call room located on the same ward tested positive (although they had no close contact), as well as a caregiver who stayed on an adjacent ward, and a healthcare worker who had casual contact with this caregiver. Samples from five individuals were available for WGS, and all showed ≤ 1 single-nucleotide polymorphism difference. CCTV footage showed that the index case walked frequently in the corridors of two wards. An airflow study showed that the air from the corridor flowed into the resident on-call room, driven by an air circulator that was always turned on. CONCLUSION: Transmission of severe acute respiratory syndrome coronavirus 2 from a fully vaccinated index occurred rapidly via the wards and on-call room. Care must be taken to not use equipment that can change the airflow.
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COVID-19 , Infecção Hospitalar , COVID-19/epidemiologia , ChAdOx1 nCoV-19 , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Surtos de Doenças , Humanos , Masculino , SARS-CoV-2/genéticaRESUMO
BACKGROUND: Patients with hematologic malignancies may produce replication-competent virus beyond 20 days of SARS-CoV-2 infection. However, data regarding the transmission of SARS-CoV-2 from patients with prolonged viral shedding is limited. METHODS: In May 2022, four additional cases of COVID-19 were reported in a hematologic ward at a tertiary care hospital in South Korea, after an 8-week isolation of a patient with prolonged viral shedding. We performed whole-genome sequencing (WGS) of SARS-CoV-2 to evaluate the possibility of post-isolation transmission from this prolonged viral shedding. RESULTS: A patient (case 1) with acute myeloid leukemia was released from isolation 54 days after the diagnosis of COVID-19 based on rising Ct value of up to 29.3, and moved to a six-patient room. On days 10 and 11 post-isolation, his doctor (case 2) and 2 patients who were his roommates (case 3, 4) had positive SARS-CoV-2 PCR results. Additionally, 16 days post-isolation, another patient (case 5) in a remote room had positive SARS-CoV-2 PCR result. All the three patients were hospitalized for ≥ 14 days when they were diagnosed with SARS-CoV-2 infection. Except for case 3, the remaining 4 cases were available for WGS, which revealed that case 1 exhibited a 7 nucleotides difference in comparison to cases 4 and 5 and case 2 displayed a 20 nucleotides difference compared with case 1, while sequences of cases 4 and 5 were identical. CONCLUSIONS: Despite the possibility of transmission from the patient with prolonged viral shedding, no evidence of the transmission of SARS-CoV-2 from the patient with prolonged positive RT-PCR using WGS was found.
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COVID-19 , COVID-19/diagnóstico , Hospitais , Humanos , Nucleotídeos , RNA Viral/genética , SARS-CoV-2/genética , Eliminação de Partículas ViraisRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission among non-close contacts is not infrequent. We evaluated the proportion and circumstances of individuals to whom SARS-CoV-2 was transmitted without close contact with the index patient in a nosocomial outbreak in a tertiary care hospital in Korea. From March 2020 to March 2021, there were 36 secondary cases from 14 SARS-CoV-2 infected individuals. Of the 36 secondary cases, 26 (72%) had been classified as close contact and the remaining 10 (28%) were classified as non-close contact. Of the 10 non-close contact, 4 had short conversations with both individuals masked, 4 shared a space without any conversation with both masked, and the remaining 2 entered the space after the index had left. At least one quarter of SARS-CoV-2 transmissions occurred among non-close contacts. The definition of close contact for SARS-CoV-2 exposure based on the mode of droplet transmission should be revised to reflect the airborne nature of SARS-CoV-2 transmission.
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COVID-19/transmissão , SARS-CoV-2 , COVID-19/epidemiologia , Busca de Comunicante , Humanos , República da Coreia/epidemiologiaRESUMO
We conducted a prospective, mobile-based survey on the self-reported adverse reactions in healthcare workers (HCWs) who received both doses of the BNT162b2 mRNA vaccine. Of the 342 HCWs who completed the two-dose vaccination, 265 (77.5%) responded to the survey at least once. Overall, the rates of adverse reactions were higher after the second dose compared with the first dose (89.1% vs. 80.1%, P = 0.006). The most common systemic reactions were muscle ache (69.1%), fatigue (65.7%), headache (48.7%), chills (44.2%), and fever (32.1%), and were notably more common after the second dose vaccine as well. We also noted a sex difference in which the frequency of adverse reactions after the second dose of the vaccine was significantly higher in females, which was not observed after the first dose. The rates of adverse reactions were lower in older age groups, and the rates and severities of the adverse reactions decreased during the 3-day period following vaccination.
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Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Pessoal de Saúde , SARS-CoV-2/imunologia , Vacinação/efeitos adversos , Adulto , Idoso , Vacina BNT162 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: We performed a prospective survey on the adverse reactions following the first dose of two types of vaccines against coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs) in South Korea. METHODS: HCWs at a tertiary referral hospital in Seoul, South Korea, received a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) or an mRNA-based vaccine (BNT162b2) between March 5 and March 26, 2021. The HCWs were asked to report adverse reactions through a mobile self-report questionnaire for three days after vaccination. RESULTS: A total of 7,625 HCWs received the first dose of ChAdOx1 or BNT162b2 vaccine during the study period. Of them, 5,866 (76.9%) HCWs (ChAdOx1, n = 5,589 [95.3%]; BNT162b2, n = 277 [4.7%]) participated at least once in the survey, of whom 77% were female and 86% were younger than 50 years. The overall adverse reaction rate was 93% in the ChAdOx1 group and 80% in the BNT162b2 group (P < 0.001). Both local and systemic reactions were more commonly reported in the ChAdOx1 group, and the difference was larger in systemic reactions such as fever and fatigue. In the ChAdOx1 group, the incidence of adverse reactions was significantly higher in females and those in the younger age groups, while the BNT162b2 group showed such difference according to age. CONCLUSION: In our prospective survey, vaccine-associated adverse reactions were more commonly reported in the ChAdOx1 group than in the BNT162b2 group. Females and younger age groups experienced vaccine-associated adverse reactions more frequently.
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Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Adulto , Fatores Etários , Idoso , Vacina BNT162 , ChAdOx1 nCoV-19 , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Caracteres Sexuais , Adulto JovemRESUMO
Hemistepta lyrata (Bunge) Bunge is a biennial medicinal plant possessing beneficial effects including anti-inflammation, and hemistepsin A (HsA) isolated from H. lyrata has been known as a hepatoprotective sesquiterpene lactone. In this report, we explored the cytotoxic effects of H. lyrata on hepatocellular carcinoma (HCC) cells and investigated the associated bioactive compounds and their relevant mechanisms. From the viability results of HCC cells treated with various H. lyrata extracts, HsA was identified as the major compound contributing to the H. lyrata-mediated cytotoxicity. HsA increased expression of cleaved PARP and cells with Sub-G1 phase, Annexin V binding, and TUNEL staining, which imply HsA induces apoptosis. In addition, HsA provoked oxidative stress by decreasing the reduced glutathione/oxidized glutathione ratio and accumulating reactive oxygen species and glutathione-protein adducts. Moreover, HsA inhibited the transactivation of signal transducer and activator of transcription 3 (STAT3) by its dephosphorylation at Y705 and glutathione conjugation. Stable expression of a constitutive active mutant of STAT3 prevented the reduction of cell viability by HsA. Finally, HsA enhanced the sensitivity of sorafenib-mediated cytotoxicity by exaggerating oxidative stress and Y705 dephosphorylation of STAT3. Therefore, HsA will be a promising candidate to induce apoptosis of HCC cells via downregulating STAT3 and sensitizing conventional chemotherapeutic agents.
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Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Lactonas/farmacologia , Neoplasias Hepáticas/patologia , Proteínas de Neoplasias/biossíntese , Fator de Transcrição STAT3/biossíntese , Sesquiterpenos/farmacologia , Ativação Transcricional/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Genes Reporter , Humanos , Proteínas de Neoplasias/genética , Estresse Oxidativo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Recombinantes/metabolismo , Fator de Transcrição STAT3/genética , Sorafenibe/farmacologiaRESUMO
Endoplasmic reticulum (ER) stress designates a cellular response to the accumulation of misfolded proteins, which is related to disease progression in the liver. Luteolin (3',4',5,7-tetrahydroxyflavone) is a phytochemical found frequently in medicinal herbs. Although luteolin has been reported to possess the therapeutic potential to prevent diverse stage of liver diseases, its role in hepatic ER stress has not been established. Thus, the present study aimed to determine the role of luteolin in tunicamycin (Tm)-induced ER stress, and to identify the relevant mechanisms involved in its hepatoprotective effects. In hepatocyte-derived cells and primary hepatocytes, luteolin significantly decreased Tm- or thapsigargin-mediated C/EBP homologous protein (CHOP) expression. In addition, luteolin reduced the activation of three canonical signaling pathways related to the unfolded protein response, and decreased mRNA levels of glucose-regulated protein 78, ER DNA J domain-containing protein 4, and asparagine synthetase. Luteolin also significantly upregulated sestrin 2 (SESN2), and luteolin-mediated CHOP inhibition was blocked in SESN2 (+/-) cells. Moreover, luteolin resulted in phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), as well as increased nuclear Nrf2 expression. Deletion of the antioxidant response element in the human SESN2 promoter inhibited increased luciferase activation by luteolin, suggesting that Nrf2 is a critical transcription factor for luteolin-dependent SESN2 expression. In a Tm-mediated liver injury model, luteolin decreased serum alanine aminotransferase and aspartate aminotransferase activities, prevented degenerative changes and apoptosis of hepatocytes, and inhibited CHOP and glucose-regulated protein 78 expression in hepatic tissues. Therefore, luteolin may be an effective phytochemical to manage ER stress-related liver injury.
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Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fígado/efeitos dos fármacos , Luteolina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Nucleares/metabolismo , Tunicamicina/farmacologia , Animais , Elementos de Resposta Antioxidante/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Células HEK293 , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fosforilação/efeitos dos fármacos , Fator de Transcrição CHOP/metabolismo , Resposta a Proteínas não Dobradas/efeitos dos fármacosRESUMO
There were two rallies of medical students and trainee doctors, where 9,000 participants gathered. We performed polymerase chain reaction (PCR)-based universal screening for the participants using pooling at a tertiary care hospital. Around 609 (94%) of 646 participants underwent PCR tests for severe acute respiratory syndrome coronavirus 2; all of them tested negative. Our data suggested low transmission rates in open air mass gatherings when appropriate personal protective practices were followed.
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Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico , Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Reação em Cadeia da Polimerase , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/epidemiologia , Higiene das Mãos , Humanos , Internato e Residência , Máscaras , Programas de Rastreamento , Pandemias , Médicos , Pneumonia Viral/epidemiologia , República da Coreia/epidemiologia , SARS-CoV-2 , Isolamento Social , Estudantes de Medicina , Centros de Atenção TerciáriaRESUMO
Between August 31st and September 4th 2020 in a tertiary care hospital in Seoul, the fever detection rate by infrared thermoscanning camera at the gates was 0.002% (95% confidence interval [CI], 0.001%-0.006%) and that by manual fever check at the outpatient clinics was 0.02% (95% CI, 0.01%-0.03%) (P < 0.001). The difference strongly suggests that sensitivity of the thermoscanning camera in the market must be upgraded.
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Betacoronavirus , Infecções por Coronavirus/epidemiologia , Febre/diagnóstico , Pneumonia Viral/epidemiologia , COVID-19 , Hospitais , Humanos , Raios Infravermelhos , Pandemias , SARS-CoV-2 , Sensibilidade e EspecificidadeRESUMO
From January to September 2020, we conducted contact-tracing for confirmed coronavirus disease 2019 (COVID-19) patients who visited our outpatient clinic to evaluate the risk of COVID-19 transmission from infected patients to healthcare workers (HCWs). COVID-19 was diagnosed in 8 outpatients. Per the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction test results, none of the 317 HCWs who came in contact had a confirmed COVID-19 diagnosis (0.00%; 95% confidence interval, 0.00%-0.01%). This low rate of transmission from infected outpatients to HCWs suggests that standard precaution such as using surgical mask and hand hygiene protects HCWs from SARS-CoV-2 in a low-risk, outpatient clinic setting.
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COVID-19/transmissão , Pessoal de Saúde , Transmissão de Doença Infecciosa do Paciente para o Profissional , SARS-CoV-2 , COVID-19/prevenção & controle , Humanos , Pacientes Ambulatoriais , Equipamento de Proteção IndividualRESUMO
BACKGROUND: Papaver nudicaule belongs to the Papaveraceae family, which is planted as an annual herbaceous species generally for ornamental purpose. Papaver rhoeas in the same family has been reported to have various pharmacological activities such as antioxidant and analgesic effects. In contrast, little is known about the pharmacological activity of Papaver nudicaule. In this study, the anti-inflammatory activity of Papaver nudicaule extracts and the action mechanisms were investigated in RAW264.7 macrophage cells. METHODS: To investigate the anti-inflammatory activity of five cultivars of Papaver nudicaule with different flower color, samples were collected from their aerial parts at two growth stages (60 and 90 days) and their ethanol extracts were evaluated in the lipopolysaccharide (LPS)-treated RAW264.7 cells by measuring nitric oxide (NO) and prostaglandin E2 (PGE2) levels. Interleukin 1-beta (IL-1ß), Interleukin-6 (IL-6) and Tumor necrosis factor alpha (TNF-α) production were also analyzed by RT-PCR and multiplex assays. Nuclear Factor-kappa-light-chain-enhancer of activated B cells (NF-κB) and Signal transducer and activator of transcription 3 (STAT3) signaling pathways were examined using western blotting and luciferase reporter assays to reveal the action mechanism of Papaver nudicaule extracts in their anti-inflammatory activity. RESULTS: All of the Papaver nudicaule extracts were effective in reducing the LPS-induced NO, which is an important inflammatory mediator, and the extract of Papaver nudicaule with white flower collected at 90 days (NW90) was selected for further experiments because of the best effect on reducing the LPS-induced NO as well as no toxicity. NW90 lowered the LPS-induced PGE2 level and decreased the LPS-induced Nitric oxide synthase 2 (NOS2) and Cyclooxygenase 2 (COX2). In addition, NW90 reduced the LPS-induced inflammatory cytokines, IL-1ß and IL-6. Furthermore, NW90 inhibited the LPS-induced activation of NF-κB and STAT3. CONCLUSIONS: These results indicate that NW90 may restrain inflammation by inhibiting NF-κB and STAT3, suggesting the potential therapeutic properties of Papaver nudicaule against inflammatory disease.
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Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismo , Papaver/química , Extratos Vegetais/farmacologia , Fator de Transcrição STAT3/metabolismo , Animais , Anti-Inflamatórios/química , Sobrevivência Celular/efeitos dos fármacos , Inflamação/induzido quimicamente , Lipopolissacarídeos/efeitos adversos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacosRESUMO
Nurses implement structured documentation using standardized nursing terminologies in computerized healthcare settings. Nurses' perceptions, shaped by their experiences of implementing such documentation, are an important indicator for the documentation system's optimal maintenance and improvement. The purpose of this study was to describe perceptions of nurses using SYSTEM featuring standard nursing statements and structured documentation. A quantitative cross-sectional study design was used. A total of 42 nurses from a tertiary teaching hospital participated in this study. A researcher-developed survey questionnaire included seven questions asking nurses' perceptions of nursing process phases and SYSTEM's usefulness, effectiveness, necessity, assistance in decision making, and suggestions for SYSTEM improvement. As results, the assessment phase was perceived to be the most necessary, while the planning phase was perceived to be the most unnecessary. Perceived disadvantages were decreased patient care time, increased charting time, and standard nursing statements not covering diverse patients' conditions. These disadvantages conflicted with perceived advantages. For successful implementation of electronic nursing records, stakeholders at clinical, information technology, and administrative levels should cooperate closely to address adverse consequences from implementation of structured documentation and standardized nursing terminologies.
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Documentação/métodos , Enfermeiras e Enfermeiros/psicologia , Cuidados de Enfermagem/métodos , Percepção , Padrões de Referência , Adulto , Atitude do Pessoal de Saúde , Estudos Transversais , Documentação/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros/normas , Inquéritos e QuestionáriosRESUMO
Papaver plants can produce diverse bioactive alkaloids. Papaver rhoeas Linnaeus (common poppy or corn poppy) is an annual flowering medicinal plant used for treating cough, sleep disorder, and as a sedative, pain reliever, and food. It contains various powerful alkaloids like rhoeadine, benzylisoquinoline, and proaporphine. To investigate and identify alkaloids in the aerial parts of P. rhoeas, samples were collected at different growth stages and analyzed using liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. A liquid chromatography with mass spectrometry method was developed for the identification and metabolite profiling of alkaloids for P. rhoeas by comparing with Papaver somniferum. Eighteen alkaloids involved in benzylisoquinoline alkaloid biosynthesis were used to optimize the liquid chromatography gradient and mass spectrometry conditions. Fifty-five alkaloids, including protoberberine, benzylisoquinoline, aporphine, benzophenanthridine, and rhoeadine-type alkaloids, were identified authentically or tentatively by liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry in samples taken during various growth stages. Rhoeadine alkaloids were observed only in P. rhoeas samples, and codeine and morphine were tentatively identified in P. somniferum. The liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry method can be a powerful tool for the identification of diverse metabolites in the genus Papaver. These results may help understand the biosynthesis of alkaloids in P. rhoeas and evaluate the quality of this plant for possible medicinal applications.
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Alcaloides/química , Cromatografia Líquida/métodos , Papaver/química , Extratos Vegetais/química , Espectrometria de Massas em Tandem/métodos , Componentes Aéreos da Planta/química , Plantas Medicinais/químicaRESUMO
BACKGROUND/AIMS: Our group reported that cinnamaldehyde derivative, (E)-4-((2-(3-oxopop-1-enyl)phenoxy)methyl)pyridinium malonic acid (CB-PIC) induced apoptosis in hypoxic SW620 colorectal cancer cells via activation of AMP-activated protein kinase (AMPK) and extracellular signal regulated kinase (ERK). Herein, sensitizing effect of CB-PIC was investigated in resistant cancer cells such as paclitaxel (PT) resistant lung cancer cells (H460/PT), and Adriamycin (Adr) resistant breast cancer (MCF7/Adr) and colon cancer (HCT15/cos) cells. METHODS: Various drug resistant cell lines were treated with CB-PIC, and the signalling pathway and functional assay were explored by Western blot, Rhodamine assay, FACS, RT-PCR and MTT assay. RESULTS: We found that CB-PIC effectively exerted cytotoxicity, increased sub G1 population and the cleaved form of poly (ADP-ribose) polymerase (PARP) and caspase 9 in drug resistant cancer cells. Furthermore, CB-PIC sensitized resistant cancer cells to adriamycin via downregulation of survival proteins such as survivin, Bcl-xL and Bcl-2, along with MDR1 suppression leading to accumulation of drug in the intracellular region. Of note, CB-PIC transcriptionally decreased MDR1 expression via suppression of STAT3 and AKT signalling in three resistant cancer cells with highly expressed P-glycoprotein. Nonetheless, CB-PIC did not affect transport activity of P-glycoprotein in a short time efflux assay, while epigallocatechin gallate (EGCG) accumulated Rhodamine 123 into intracellular region of cell by direct inhibition of MDR1 transport activity. CONCLUSIONS: These data demonstrate that CB-PIC suppresses the P-glycoprotein expression through inhibition of STAT3 and AKT signalling to overcome drug resistance in chemo-resistant cancer cells as a potent chemotherapeutic sensitizer.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Acroleína/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Acroleína/química , Acroleína/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 9/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Células MCF-7 , Fosforilação/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Piridinas/química , Survivina , Proteína bcl-X/genética , Proteína bcl-X/metabolismoRESUMO
BACKGROUND/AIMS: The use of tyrosine kinase inhibitors (TKIs) to target active epidermal growth factor receptor (EGFR)-harbouring mutations has been effective in patients with advanced non-small-cell lung cancer (NSCLC). However, the use of TKIs in NSCLS patients with somatic EGFR mutations, particularly T790M, causes drug resistance. Thus, in the present study, we investigated overcoming resistance against the TKI gefitinib by combination treatment with melatonin in H1975 NSCLC cells harbouring the T790M somatic mutation. METHODS: H1975 and HCC827 cells were treated with melatonin in combination with gefitinib, and cell viability, cell cycle progression, apoptosis, and EGFR, AKT, p38, Bcl-2, Bcl-xL, caspase 3 and Bad protein levels were examined. RESULTS: Treatment with melatonin dose-dependently decreased the viability of H1975 cells harbouring the T790M somatic mutation compared to HCC827 cells with an EGFR active mutation. Melatonin-mediated cell death resulted in decreased phosphorylation of EGFR and Akt, leading to attenuated expression of survival proteins, such as Bcl-2, Bcl-xL and survivin, and activated caspase 3 in H1975 cells, but not in HCC827 cells. However, we did not observe a significant change in expression of cell cycle proteins, such as cyclin D, cyclin A, p21 and CDK4 in H1975 cells. Surprisingly, co-treatment of gefitinib with melatonin effectively decreased the viability of H1975 cells, but not HCC827 cells. Moreover, co-treatment of H1975 cells caused consistent down-regulation of EGFR phosphorylation and induced apoptosis compared to treatment with gefitinib or melatonin alone. CONCLUSIONS: Our findings demonstrate that melatonin acts as a potent chemotherapeutic agent by sensitising to gefitinib TKI-resistant H1975 cells that harbour a EGFR T790M mutation.
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Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Neoplasias Pulmonares/patologia , Melatonina/farmacologia , Mutação , Quinazolinas/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Citometria de Fluxo , Gefitinibe , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , FosforilaçãoRESUMO
Porcine circular single-stranded DNA viruses have been just identified from swine feces in Korea. This virus was mentioned as bovine stool-associated circular DNA virus (BoSCV)-like virus discovered from porcine stools. However, the thorough characteristics of the virus were not identified. Therefore, this research focuses on finding a full genome sequence and analyzing the genetic features of the virus. The virus, now called porcine stool-associated circular DNA virus in Korea (PoSCV Kor), consists of 2,589 bases forming circular structure. It has two major ORFs inversely encoding replicase and capsid protein, with each stem-loop structure between 5' ends and 3' ends of the two putative ORFs. This characteristics is the same as PoSCV in New Zealand, but different from chimpanzee stool-associated circular virus (ChiSCVs) and BoSCV, which have one stem-loop structure. Therefore, it would be sure that PoSCV Kor is very similar to PoSCV in respect to the genetic aspect; the same number of nucleotide bases and the amino acid identity of replicase and capsid protein (96 and 93 %, respectively). This fact could be certified through the finding that PoSCV Kor and PoSCV are in the same cluster by phylogenetic analysis based on the comparison with full-sequences of other circular ssDNA viruses.
Assuntos
Infecções por Vírus de DNA/veterinária , Vírus de DNA/genética , DNA Viral/química , DNA Viral/genética , Fezes/virologia , Genoma Viral , Proteínas do Capsídeo/genética , Análise por Conglomerados , Vírus de DNA/isolamento & purificação , DNA de Cadeia Simples/química , DNA de Cadeia Simples/genética , DNA Polimerase Dirigida por DNA/genética , Coreia (Geográfico) , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Fases de Leitura Aberta , Filogenia , Análise de Sequência de DNA , Homologia de SequênciaRESUMO
BACKGROUND: We aimed at evaluating the diagnostic performance of rapid antigen test (RAT) compared to polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 and the possible transmission of infection to close contacts from patients with negative RAT and positive PCR results. MATERIALS AND METHODS: Patients/guardians urgently requiring admission to the ward on the same day had been hospitalized with RAT-negative result before the PCR results were available. We performed an epidemiologic investigation of the close contacts of those with negative RAT but positive PCR results after hospitalization. RESULTS: A total of 4,237 RATs were performed from March to August 2022. When the PCR test was used as the reference, RAT had a sensitivity of 28.8% (17/59; 95% confidence interval [CI], 17.8 - 42.1), a specificity of 100% (4,220/4,220; 95% CI, 99.9 - 100.0), a positive predictive value of 100.0% (17/17; 95% CI, 100.0 - 100.0), and a negative predictive value of 99.0% (4,178/4,220; 95% CI, 99.3 - 99.8). The epidemiologic investigation revealed that among the 32 patients with negative RAT and subsequent positive PCR results after admission into multi-patient room, two (6.3%) showed secondary coronavirus disease 2019. CONCLUSION: The secondary transmission rate from patients with negative RAT and positive PCR results was low. Our data suggest that RAT may be useful for rapid exclusion of high transmissible cases. However, further evaluation using whole genome sequencing is needed to determine the potential for transmissibility in cases showing a negative RAT but a positive PCR result.