RESUMO
Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug. Here, we use a combination of two well-established anticancer DNA intercalators, actinomycin D (ActD) and echinomycin (Echi), to screen their binding capabilities with DNA duplexes containing different mismatches embedded within Watson-Crick base-pairs. We have found that combining ActD and Echi preferentially stabilised thymine-related T:T mismatches. The enhanced stability of the DNA duplex-drug complexes is mainly due to the cooperative binding of the two drugs to the mismatch duplex, with many stacking interactions between the two different drug molecules. Since the repair of thymine-related mismatches is less efficient in mismatch repair (MMR)-deficient cancer cells, we have also demonstrated that the combination of ActD and Echi exhibits enhanced synergistic effects against MMR-deficient HCT116 cells and synergy is maintained in a MMR-related MLH1 gene knockdown in SW620 cells. We further accessed the clinical potential of the two-drug combination approach with a xenograft mouse model of a colorectal MMR-deficient cancer, which has resulted in a significant synergistic anti-tumour effect. The current study provides a novel approach for the development of combination chemotherapy for the treatment of cancers related to DNA-mismatches.
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Neoplasias Colorretais , Equinomicina , Humanos , Animais , Camundongos , Dactinomicina/química , Equinomicina/química , Timina , Sequência de Bases , Sítios de Ligação , Conformação de Ácido Nucleico , DNA/químicaRESUMO
BACKGROUND: Adult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity. METHODS: Environmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM2.5) and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case-control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables. FINDINGS: In the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM2.5 and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28-3.48) and its severity, correlating with the level of oxidative stress markers, notably Nε-(hexanoyl)-lysine (r=0.108-0.311, p<0.05), but not with the accumulated levels of PM2.5 exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (p<0.001 and p<0.05, respectively), correlating with the levels of PAH (r=0.196, p<0.01) and metal exposure (r=0.202-0.323, p<0.05), respectively, and both correlating with circulating inflammatory markers (r=0.186-0.427, p<0.01). Analysis of six phenotypic clusters and those cases with comorbid type 2 diabetes mellitus (T2DM) revealed cluster-selective environmental risks and biosignatures. INTERPRETATION: These results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity.
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Poluentes Atmosféricos , Poluição do Ar , Asma , Diabetes Mellitus Tipo 2 , Hidrocarbonetos Policíclicos Aromáticos , Adulto , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Esfingolipídeos , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Material Particulado/toxicidade , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Monitoramento Ambiental/métodosRESUMO
Realizing high-precise and adjustable regulation of engineering nanozyme is important in nanotechnology. Here, Ag@Pt nanozymes with excellent peroxidase-like and antibacterial effects are designed and synthesized by nucleic acid and metal ions coordination-driven one-step rapid self-assembly. The adjustable NA-Ag@Pt nanozyme is synthesized within 4 min using single-stranded nucleic acid as templates, and peroxidase-like enhancing FNA-Ag@Pt nanozyme is received by regulating functional nucleic acids (FNA) based on NA-Ag@Pt nanozyme. Both Ag@Pt nanozymes that are developed not only has simple and general synthesis approaches, but also can produce artificial precise adjustment and possess dual-functional. Moreover, when lead ion-specific aptamers as FNA are introduced to NA-Ag@Pt nanozyme, the Pb2+ aptasensor is successfully constructed by increasing electron conversion efficiency and improving the specificity of nanozyme. In addition, both nanozyme has good antibacterial properties, with ~100% and ~85% antibacterial efficiency against Escherichia coli and Staphylococcus aureus, respectively. This work provides a synthesis method of novelty dual-functional Ag@Pt nanozymes and successful application in metal ions detection and antibacterial agents.
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Ácidos Nucleicos , Peroxidase , Peroxidases , Antibacterianos/farmacologia , ÍonsRESUMO
Since Salmonella can cause foodborne disease and public health safety issues and requires a robust, rapid, on-site detection method, a novel visual qualitative method with nano-gold-enhanced loop-mediated isothermal amplification (LAMP) reaction was established for detecting Salmonella in an integrated tube. During the experiment, nano-gold were used to enhance LAMP amplification, improving amplification efficiency and shortening the reaction time to within 30 min. Visual qualitative detection is achieved via negative staining, involving the addition of CuSO4 to the final products of the LAMP reaction. Ring-like white accumulation occurs in the absence of Salmonella targets but not when they are present. After completing the LAMP reaction, the integration tube was shaken gently for 1 min to observe the liquid phase system changes, realizing the closed tube detection of Salmonella. The process resolved the challenge presented by cross-contamination, false positives, and nonspecific amplification during the LAMP reaction. This method was used to detect Salmonella in milk, further highlighting its prospects in the field of rapid food safety detection.
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Microbiologia de Alimentos , Leite , Animais , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico/métodos , Salmonella/genéticaRESUMO
Chronic obstructive pulmonary disease (COPD) has significant contributions to morbidity and mortality world-wide. Early symptoms of COPD are not readily distinguishable, resulting in a low rate of diagnosis and intervention. Different guidelines and recommendatations for the diagnosis and treatment of COPD exist globally. The first edition of clinical practice guidelines for COPD was published in 2016 by the Ministry of Health and Welfare in Taiwan in collaboration with the Taiwan evidence-based medicine association and Cochrane Taiwan, and was revised in 2019 in order to update recent diagnostic and therapeutic modalities for COPD and its acute exacerbation. This revised guideline covered a range of topics highlighted in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report, including strategies for the diagnosis, assessment, monitoring, and management of stable COPD and exacerbations, with particular focus on evidence from Taiwan. The recommendations included in the revised guideline were formed based on a comprehensive systematic review or meta-analysis of specific clinical issues identified by an expert panel that surveyed relevant scientific evidence in the literature and guidelines published by the clinical communities and organizations nationally and internationally. The guidelines and recommendations are applicable to the clinical settings in Taiwan. We expect this revised guideline to facilitate the diagnosis, treatment and management of patients with COPD by physicians and health care professionals in Taiwan. Adaptations of the materials included herein for educational and training purposes is encouraged.
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Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Inquéritos e Questionários , TaiwanRESUMO
BACKGROUND: Epidemiologic evidence suggests that exposure to particulate matter of 2.5 µm or less in diameter (PM2.5) aggravates asthma. OBJECTIVE: We sought to investigate the underlying mechanisms between PM2.5 exposure and asthma severity. METHODS: The relationship between PM2.5 exposure and asthma severity was investigated in an asthma model with CD4+ T cell-specific aryl hydrocarbon receptor (AhR)-null mice. Effects of PM2.5 and polycyclic aromatic hydrocarbons (PAHs) on differentiation of TH17/regulatory T (Treg) cells were investigated by using flow cytometry and quantitative RT-PCR. Mechanisms were investigated by using mRNA sequencing, chromatin immunoprecipitation, bisulfite sequencing, and glycolysis rates. RESULTS: PM2.5 impaired differentiation of Treg cells, promoted differentiation of TH17 cells, and aggravated asthma in an AhR-dependent manner. PM2.5 and one of its prominent PAHs, indeno[1,2,3-cd]pyrene (IP), promoted differentiation of TH17 cells by upregulating hypoxia-inducible factor 1α expression and enhancing glycolysis through AhRs. Exposure to PM2.5 and IP enhanced glutamate oxaloacetate transaminase 1 (Got1) expression through AhRs and accumulation of 2-hydroxyglutarate, which inhibited ten-eleven translocation methylcytosine dioxygenase 2 activity, resulting in hypermethylation in the forkhead box P3 locus and impaired differentiation of Treg cells. A GOT1 inhibitor, (aminooxy)acetic acid, ameliorated asthma by shifting differentiation of TH17 cells to Treg cells. Similar regulatory effects of exposure to PM2.5 or IP on TH17/Treg cell imbalance were noted in human T cells, and in a case-control design PAH exposure appeared to be a potential risk factor for asthma. CONCLUSIONS: The AhR-hypoxia-inducible factor 1α and AhR-GOT1 molecular pathways mediate pulmonary responses on exposure to PM2.5 through their ability to disturb the balance of TH17/Treg cells.
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Aspartato Aminotransferase Citoplasmática/imunologia , Asma/imunologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , Material Particulado/toxicidade , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Animais , Aspartato Aminotransferase Citoplasmática/genética , Asma/induzido quimicamente , Asma/genética , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Modelos Animais de Doenças , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Camundongos , Camundongos Mutantes , Tamanho da Partícula , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/imunologia , Linfócitos T Reguladores/patologia , Células Th17/patologiaRESUMO
Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic change in alveolar epithelial cells and leads to the irreversible deterioration of pulmonary function. Transforming growth factor-beta 1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells contributes to excessive collagen deposition and plays an important role in IPF. Atractylodin (ATL) is a kind of herbal medicine that has been proven to protect intestinal inflammation and attenuate acute lung injury. Our study aimed to determine whether EMT played a crucial role in the pathogenesis of pulmonary fibrosis and whether EMT can be utilized as a therapeutic target by ATL treatment to mitigate IPF. To address this topic, we took two steps to investigate: 1. Utilization of anin vitro EMT model by treating alveolar epithelial cells (A549 cells) with TGF-ß1 followed by ATL treatment for elucidating the underlying pathways, including Smad2/3 hyperphosphorylation, mitogen-activated protein kinase (MAPK) pathway overexpression, Snail and Slug upregulation, and loss of E-cadherin. Utilization of an in vivo lung injury model by treating bleomycin on mice followed by ATL treatment to demonstrate the therapeutic effectiveness, such as, less collagen deposition and lower E-cadherin expression. In conclusion, ATL attenuates TGF-ß1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in mice.
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Células Epiteliais Alveolares/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Furanos/farmacologia , Fibrose Pulmonar Idiopática/prevenção & controle , Células A549 , Células Epiteliais Alveolares/fisiologia , Animais , Bleomicina/efeitos adversos , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Furanos/uso terapêutico , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/fisiologiaRESUMO
BACKGROUND: The therapeutic strategies for clinical stage T1-3N2 (cT1-3N2) lung cancer are controversial. For operable tumors, treatment can vary by center, region, and continent. This study aimed to identify the optimal therapeutic method and type of surgical strategy for cT1-3N2 lung cancer. METHODS: This retrospective evaluation analyzed the records of 17,954 patients with cT1-3N2 lung cancer treated in 2010 through 2015 from the SEER database. The effects of different therapeutic methods and types of surgical strategies on overall survival (OS) were assessed. Univariate and multivariate analyses were performed using a Cox proportional hazards model. RESULTS: The 5-year OS rates were 27.7% for patients with T1N2 disease, 21.8% for those with T2N2 disease, and 19.9% for T3N2 disease. Neoadjuvant therapy plus operation (OP) plus adjuvant therapy, and OP plus adjuvant therapy, provided better 5-year OS rates than OP alone or concurrent chemoradiotherapy (34.1%, 37.7%, 29.3%, and 16.1%, respectively). In the T1N2, T2N2, and T3N2 groups, lobectomy provided better 5-year OS than pneumonectomy, sublobectomy, and no surgery. Both univariate and multivariate analyses showed that young age, female sex, well-differentiated histologic grade, adenocarcinoma cell type, neoadjuvant and adjuvant therapy, lobectomy, and T1 stage were statistically associated with better 5-year OS rates. CONCLUSIONS: In cT1-3N2 lung cancer, multimodal treatments tended to provide better 5-year OS than OP alone or concurrent chemoradiotherapy. In addition, lobectomy was associated with better survival than other operative methods.
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Quimiorradioterapia Adjuvante/estatística & dados numéricos , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante/estatística & dados numéricos , Pneumonectomia/estatística & dados numéricos , Idoso , Quimioterapia Adjuvante/estatística & dados numéricos , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia/métodos , Estudos Retrospectivos , Programa de SEER/estatística & dados numéricos , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
The present study was carried out to explore the effect of sinensetin in human T-cell lymphoma Jurkat cells and to reveal the underlying molecular mechanisms. We found that sinensetin significantly impeded Jurkat cell proliferation in a dose-dependent and time-dependent manner. Additionally, sinensetin treatment triggered apoptosis and autophagy in Jurkat cells. The apoptosis induction was related to a loss of mitochondrial membrane potential and to increased caspase-3/-8/-9 and poly(ADP-ribose) polymerase (PARP) cleavage. Sinensetin also induced autophagy, as evidenced by the formation of acidic vacuoles, the upregulation of LC3-II and beclin-1, and the downregulation of p62. In addition, the inhibition of autophagy by 3-methyladenine significantly enhanced the apoptosis rate and improved the sensitivity of the Jurkat cells to sinensetin. Moreover, sinensetin induced cell death, apoptosis, and autophagy through the activation of the reactive oxygen species/ c-Jun N-terminal kinase signaling pathway and the inhibition of the Akt/mTOR signaling pathways. In summary, our results revealed that sinensetin induced apoptosis and autophagy in human T-cell lymphoma Jurkat cells by activating reactive oxygen species/ c-Jun N-terminal kinase and blocking the Akt/mTOR signaling pathways. Thus, sinensetin might be a potential candidate in the development of antitumor drugs targeting T-cell leukemia.
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Antineoplásicos/farmacologia , Apoptose , Autofagia , Flavonoides/farmacologia , Linfoma de Células T/patologia , Animais , Proliferação de Células , Humanos , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/metabolismo , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
24-methyl-cholesta-5,24(28)-diene-3ß,19-diol-7ß-monoacetate (MeCDDA) is a natural steroid compound isolated from a wild-type soft coral (Nephthea erecta). The present study aimed to investigate the anti-small cell lung cancer (SCLC) effects of MeCDDA in vitro and in vivo, as well as to elucidate its underlying mechanism. Our results indicated that H1688 and H146 cells show relevant sensitivity to MeCDDA, and the exposure to MeCDDA in SCLC cells caused dose-dependent growth inhibitory responses. In addition, MeCDDA treatment promoted cell apoptosis and increased the activities of caspases in H1688 cells, reducing the mitochondrial membrane potential and stimulating the release of cytochrome c into the cytosol. Along with the increase in Bax expression and reduction in Bcl-2, the MeCDDA treatment also significantly decreased Akt and mTOR phosphorylation. Finally, MeCDDA treatment in the mouse xenograft model of H1688 cells exhibited significant inhibition of tumor growth, corroborating MeCDDA as a potential pre-clinical candidate for the treatment of SCLC. Overall, our results demonstrate that the cytotoxic effects of MeCDDA towards H1688 and H146 cells, possibly through the activation of the mitochondrial apoptotic pathway and inhibition of the PI3K/Akt/mTOR pathway, merit further studies for its possible clinical application in chemotherapy.
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Antozoários/química , Antineoplásicos/farmacologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Esteroides/farmacologia , Animais , Antozoários/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Caspases/genética , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Esteroides/química , Esteroides/metabolismoRESUMO
Transforming growth factor-ß (TGF-ß)-induced epithelial-mesenchymal transition is a critical process in the initiation of metastasis of various types of cancer. Chidamide is a class I histone deacetylase inhibitor with anti-tumor activity. This study investigated the effects of chidamide on TGF-ß-mediated suppression of E-cadherin expression in adenocarcinomic lung epithelial cells and the molecular mechanisms involved in these effects. Western blot analysis, confocal microscopy, Quantitative methyl-specific PCR and bisulfite sequencing were used to evaluate the effects of different treatments on chidamide ameliorating TGF-ß induced-E-cadherin loss. H3 acetylation binding to the promoter of E-cadherin was detected by chromatin immunoprecipitations (CHIP). We found that chidamide reduced the level of lung cancer cell migration observed using a Boyden chamber assay (as an indicator of metastatic potential). Chidamide inhibited TGF-ß-induced SMAD2 phosphorylation and attenuated TGF-ß-induced loss of E-cadherin expression in lung cancer cells by Western blotting and confocal microscopy, respectively. Quantitative methyl-specific PCR and bisulfite sequencing revealed that TGF-ß-enhanced E-cadherin promoter methylation was ameliorated in cells treated with chidamide. We demonstrated that histone H3 deacetylation within the E-cadherin promoter was required for TGF-ß-induced E-cadherin loss; cell treatment with chidamide increased the H3 acetylation detected by CHIP. Taken together, our results demonstrate that TGF-ß suppressed E-cadherin expression by regulating promoter methylation and histone H3 acetylation. Chidamide significantly enhanced E-cadherin expression in TGF-ß-treated cells and inhibited lung cancer cell migration. These findings indicate that chidamide has a potential therapeutic use due to its capacity to prevent cancer cell metastasis.
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Aminopiridinas/farmacologia , Antineoplásicos/farmacologia , Benzamidas/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Fator de Crescimento Transformador beta/fisiologia , Células A549 , Antígenos CD , Caderinas/genética , Caderinas/metabolismo , Metilação de DNA , Ensaios de Seleção de Medicamentos Antitumorais , Epigênese Genética , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Fosforilação , Regiões Promotoras Genéticas , Processamento de Proteína Pós-TraducionalRESUMO
Drug resistance is one of the major causes of cancer chemotherapy failure. In the current study, we used a pair of lung adenocarcinoma cell lines, A549 and the pemetrexed-resistant A549/PEM cells, as a model to monitor resistance-dependent cellular responses and identify potential therapeutic targets. By means of 2D differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), we investigated the global protein expression alterations induced by pemetrexed treatment and resistance. The proteomic result revealed that pemetrexed exposure obviously altered the expression of 81 proteins in the A549 cells, whereas no significant response was observed in the similarly treated A549/PEM cells, hence implying an association between these proteins and the drug-specific response. Moreover, 72 proteins including flavin reductase and calreticulin demonstrated differential expression between the A549 and A549/PEM cells, indicating baseline resistance. Additional tests employed siRNA silencing, protein overexpression, cell viability analysis, and analysis of apoptosis to examine and confirm the potency of flavin reductase and calreticulin proteins in the development of pemetrexed resistance. In summary, by using a proteomic approach, we identified numerous proteins, including flavin reductase and calreticulin, involved in pemetrexed drug resistance-developing mechanisms. Our results provide useful diagnostic markers and therapeutic candidates for pemetrexed-resistant lung cancer treatment.
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Antineoplásicos/farmacologia , Calreticulina/isolamento & purificação , FMN Redutase/isolamento & purificação , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Pemetrexede/farmacologia , Proteoma/isolamento & purificação , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Apoptose/efeitos dos fármacos , Calreticulina/genética , Calreticulina/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Eletroforese em Gel Bidimensional , FMN Redutase/genética , FMN Redutase/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Proteoma/genética , Proteoma/metabolismo , Proteômica/métodos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Introduction: Impaired lung function has been observed in patients following COVID-19 infection, with studies reporting persistent lung volume and diffusing capacity impairments. Some studies have demonstrated significantly higher small airway resistance in COVID-19 positive cases. This retrospective study aims to examine impulse oscillometry (IOS) data of patients with persistent symptoms after COVID-19 infection, focusing on the relationship between time and symptoms. Material and Method: The study analyzed data from adult patients with persistent symptoms who underwent IOS testing within and after 84 days from the diagnosis date. Result: The results showed that patients within 84 days and those between 31 and 84 days had higher small airway resistance values, indicating peripheral airway disease. Patients with dyspnea exhibited higher IOS values compared to those with cough symptoms, suggesting more significant impairment in the peripheral airways. Conclusion: The study highlights the importance of using comprehensive diagnostic tools like IOS to assess respiratory impairments in post-COVID-19 patients, particularly in the small airways. Understanding the relationship between time and symptoms can provide valuable insights for the treatment of peripheral airway dysfunction in post-COVID-19 patients.
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Early detection of Toxoplasma gondii (T. gondii) is critical due to a lack of effective treatment for toxoplasmosis.This study established a simple, cost-effective, and rapid colorimetric detection method for T. gondii. The entire testing process, from sample collection to results, takes only 0.5 h. These characteristics fulfill the demands of researchers seeking rapid target detection with minimal equipment reliance. For genomic extraction, this study evaluated the ability of two filter papers to capture genomes. A rapid genomic extraction device combined with the two filter papers was designed to simplify the genomic extraction process, which was completed within 10 min and increased the detection sensitivity tenfold. The method utilized a simplified primer design for isothermal amplification, namely allosteric strand displacement (ASD), and employed an underutilized commercial color indicator, Bromothymol Blue (BTB), for signal output. Compared with other reported indicators, BTB exhibited a more pronounced color change, shifting from blue to yellow in positive samples, facilitating easier visual differentiation. The reaction was completed in 20 min with a limit of detection (LOD) as low as 0.014 T. gondii per microliter.
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Técnicas Biossensoriais , Toxoplasma , Toxoplasma/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Sensibilidade e Especificidade , DNA de Protozoário/genética , Azul de BromotimolRESUMO
Background: The application of positron emission tomography/computed tomography (PET/CT) helps provide accurate clinical staging for lung cancer patients. However, the effects and trends in early-stage lung cancer remain unclear. The aim of this study was to compare differences between clinical stage I lung cancer patients who received PET/CT for staging and those who did not. Methods: Data were obtained from the Taiwan Society of Cancer Registry. There were 6587 clinical stage I lung cancer patients between 2009 and 2014 analyzed in this study. We compared the characteristics of the PET/CT and no PET/CT groups. After propensity score matching, it resulted in both groups having 2649 patients. We measured the overall survival rates of all clinical stage I lung cancer patients and the overall survival rates of patients with PET/CT and without PET/CT. Results: The 1-, 3-, and 5-year survival rates of all clinical stage I lung cancer patients were 97.2%, 88.2%, and 79.0%, respectively. Patients with a larger tumor size tended to receive PET/CT for staging (stage Ib: 38.25% vs. 27.82%, p < 0.0001) and a larger resection (lobectomy: 74.62% vs. 66.61%, p < 0.0001). The 5-year survival rates were 79.8% in the PET/CT group and 78.2% in the no PET/CT group after propensity score matching (p = 0.6528). Conclusions: For clinical stage I lung cancer in Taiwan, patients with larger tumor sizes tend to have PET/CT for staging. Although PET/CT provided more precise clinical staging, these patients still received larger resections and had more pathological migration. However, there was no overall survival rate benefit after PET/CT.
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BACKGROUND: Type 2 diabetes mellitus (DM) is a common medical disorder and a leading cause of morbidity and mortality worldwide. We investigated whether chronic obstructive pulmonary disease (COPD) was the risk factor for type 2 diabetes in an Asian population. MATERIALS AND METHODS: From Taiwan's National Health Insurance Research Database, we collected data from 16,088 patients, including 8044 COPD patients and 8044 age- and gender- matched control subjects. Cox proportional hazard regression was performed to evaluate independent risk factors for type 2 diabetes in all patients and identify risk factors in patients with COPD. RESULTS: During the 5.5-year follow-up, patients with COPD were found to have a significantly higher rate of incident type 2 diabetes than the control group (P < 0.001). COPD was significantly associated with type 2 diabetes hazard ratio (HR : 1.41, 1.23-1.63, P < 0.001) after adjusting sex, age, residential area, insurance premium, steroid use, hypertriglycemia, hypertension, coronary artery disease (CAD) and cerebrovascular disease. Cox regression analysis showed that hypertension (HR : 1.55, 1.33-1.80, P < 0.001) and hypertriglycemia (HR : 1.48, 1.15-1.90, P = 0.002) were important risk factors for type 2 diabetes in patients with COPD. CONCLUSIONS: Patients with COPD have a higher risk of type 2 diabetes compared with control subjects after adjusting for confounding factors such as sex, age, residential area, insurance premium, steroid use, hypertriglycemia, hypertension, CAD and cerebrovascular disease. Continuous surveillance of signals of dysglycemia may be incorporated into care programmes for patients with COPD.
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Diabetes Mellitus Tipo 2/etiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/mortalidade , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/mortalidade , Distribuição por Sexo , Taiwan/epidemiologia , Adulto JovemRESUMO
Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN- γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF- κ B translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases.
Assuntos
Antitussígenos/farmacologia , Células Dendríticas/efeitos dos fármacos , Dextrometorfano/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Animais , Antígenos CD/genética , Antígenos CD/imunologia , Células Cultivadas , Células Dendríticas/citologia , Células Dendríticas/imunologia , Feminino , Expressão Gênica , Antígenos HLA-DR/genética , Antígenos HLA-DR/imunologia , Humanos , Interferon gama/genética , Interferon gama/imunologia , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/imunologia , NF-kappa B/genética , NF-kappa B/imunologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
Toehold-mediated strand displacement (TMSD) reactions between double-stranded DNA and single-stranded oligonucleotides, which use a toehold structure as a switch, enable DNA rehybridization in a fast, base-to-base, programmable and controlled manner. TMSD offers numerous advantages, as reactions are enzyme-free, highly efficient, isothermal and cost-effective. Consequently, TMSD-based reaction systems have attracted great interest from researchers in the last two decades as they become increasingly diverse, versatile and robust, and have been widely used in biochemical sensing and medical diagnosis. In this review, we provide a comprehensive overview of TMSD reactions and their applications in biosensors. The six current TMSD reaction types are generalized according to their various modes of action and nucleic acid conformations. Reaction mechanisms via three major thermodynamic driving forces are explained, along with their dynamic affecting factors, and seven toehold-mediated biosensing strategies are summarized. Furthermore, TMSD-reaction biodetection and bioimaging applications are discussed and, finally, several current challenges and perspectives in the field are considered.
Assuntos
Técnicas Biossensoriais , Conformação de Ácido Nucleico , Oligonucleotídeos , TermodinâmicaRESUMO
Cadmium is a heavy metal that is exceedingly hazardous to humans and can enter the body through tainted food or drink, causing severe harm. It is critical to develop a technology for detecting cadmium in food and water that is sensitive and accurate. One such approach, which employs nucleases, is uncommon. A cadmium(II) turn-on biosensor was successfully created in this work using repetitive cleavage of certain specific nucleases for signal conversion and sophisticated stem-loop qPCR (quantitative polymerase chain reaction) for quick signal amplification and output. The method has strong selectivity and sensitivity for precise quantification, with a detection limit of 6 nmol L-1, i.e. 0.948 g L-1, which is far lower than the 5.0 g L-1 set by the United States Environmental Protection Agency, and it also operates well in retail rice samples.