RESUMO
The objective of this study was to evaluate the effectiveness of common antibiotics against different microorganisms in apparently healthy cattle in Shandong province and its suburb. A total of 220 nasal swab samples were collected and cultured for bacteriological evaluation. All the bacteria isolates after preliminary identification were subjected to antibiogram studies following disc diffusion method. It was found in the study that E. coli is the most commonly associated isolate (21%), followed by Klebsiella spp. (18%), Pseudomonas aeruginosa (13%), Salmonella spp. (15%), Shigella spp (12%), and Proteus spp (11%). While the antibiogram studies reveled that highest number of bacterial isolates showed resistance to Ampicillin (95%), followed by Augmentin (91%), Cefuroxime (85%) and Tetracycline (95%) of (Escherichia coli and Klebsiella spp). In the case of pseudomonas spp. and Salmonella the highest resistance was showed by Ampicillin (90%) followed by Amoxicillin + Clavulanic Acid (80%), Cefixime (90%), and Erythromycin (80%). In Shigella spp and Salmonella spp highest resistance was showed by Amoxicillin, Ceftazidime, Augmentin (60%), and Amoxicillin + Clavulanic Acid (50%). It is concluded that in vitro antibiogram studies of bacterial isolates revealed higher resistance for Ampicillin, Augmentin, Cefuroxime, Cefixime, Tetracycline, Erythromycin, and Amoxicillin + Clavulanic Acid. The high multiple Antibiotics resistance indexes (MARI) observed in all the isolates in this study ranging from 0.6 to 0.9. MARI value of >0.2 is suggests multiple antibiotic resistant bacteria and indicate presence of highly resistant bacteria.
O objetivo deste estudo foi avaliar a eficácia dos antibióticos comuns contra diferentes microrganismos em bovinos aparentemente saudáveis na província de Shandong e seus subúrbios. Um total de 220 amostras de esfregaço nasal foi coletado e cultivado para avaliação bacteriológica. Todos os isolados de bactérias após identificação preliminar foram submetidos a estudos de antibiograma seguindo o método de difusão em disco. Verificou-se no estudo que E. coli é o isolado mais comumente associado (21%), seguido por Klebsiella spp. (18%), Pseudomonas aeruginosa (13%), Salmonella spp. (15%), Shigella spp (12%) e Proteus spp (11%). Enquanto os estudos de antibiograma revelaram que o maior número de isolados bacterianos apresentou resistência à Ampicilina (95%), seguido por Augmentin (91%), Cefuroxima (85%) e Tetraciclina (95%) de (Escherichia coli e Klebsiella spp). No caso de Pseudomonas spp. e Salmonella, a maior resistência foi apresentada pela Ampicilina (90%) seguida pela Amoxicilina + Ácido Clavulânico (80%), Cefixima (90%) e Eritromicina (80%). Em Shigella spp e Salmonella spp, a maior resistência foi demonstrada por Amoxicilina, Ceftazidima, Augmentina (60%) e Amoxicilina + Ácido Clavulânico (50%). Conclui-se que estudos de antibiograma in vitro de isolados bacterianos revelaram maior resistência para Ampicilina, Augmentina, Cefuroxima, Cefixima, Tetraciclina, Eritromicina e Amoxicilina + Ácido Clavulânico. Os altos índices de resistência a antibióticos múltiplos (MARI) observados em todos os isolados neste estudo variaram de 0,6 a 0,9. O valor MARI de > 0,2 sugere várias bactérias resistentes a antibióticos e indica a presença de bactérias altamente resistentes.
Assuntos
Animais , Bovinos , Farmacorresistência Bacteriana , Resistência a Múltiplos Medicamentos , Resistência beta-Lactâmica/efeitos dos fármacosRESUMO
Abstract The objective of this study was to evaluate the effectiveness of common antibiotics against different microorganisms in apparently healthy cattle in Shandong province and its suburb. A total of 220 nasal swab samples were collected and cultured for bacteriological evaluation. All the bacteria isolates after preliminary identification were subjected to antibiogram studies following disc diffusion method. It was found in the study that E. coli is the most commonly associated isolate (21%), followed by Klebsiella spp. (18%), Pseudomonas aeruginosa (13%), Salmonella spp. (15%), Shigella spp (12%), and Proteus spp (11%). While the antibiogram studies reveled that highest number of bacterial isolates showed resistance to Ampicillin (95%), followed by Augmentin (91%), Cefuroxime (85%) and Tetracycline (95%) of (Escherichia coli and Klebsiella spp). In the case of pseudomonas spp. and Salmonella the highest resistance was showed by Ampicillin (90%) followed by Amoxicillin + Clavulanic Acid (80%), Cefixime (90%), and Erythromycin (80%). In Shigella spp and Salmonella spp highest resistance was showed by Amoxicillin, Ceftazidime, Augmentin (60%), and Amoxicillin + Clavulanic Acid (50%). It is concluded that in vitro antibiogram studies of bacterial isolates revealed higher resistance for Ampicillin, Augmentin, Cefuroxime, Cefixime, Tetracycline, Erythromycin, and Amoxicillin + Clavulanic Acid. The high multiple Antibiotics resistance indexes (MARI) observed in all the isolates in this study ranging from 0.6 to 0.9. MARI value of >0.2 is suggests multiple antibiotic resistant bacteria and indicate presence of highly resistant bacteria.
Resumo O objetivo deste estudo foi avaliar a eficácia dos antibióticos comuns contra diferentes microrganismos em bovinos aparentemente saudáveis na província de Shandong e seus subúrbios. Um total de 220 amostras de esfregaço nasal foi coletado e cultivado para avaliação bacteriológica. Todos os isolados de bactérias após identificação preliminar foram submetidos a estudos de antibiograma seguindo o método de difusão em disco. Verificou-se no estudo que E. coli é o isolado mais comumente associado (21%), seguido por Klebsiella spp. (18%), Pseudomonas aeruginosa (13%), Salmonella spp. (15%), Shigella spp (12%) e Proteus spp (11%). Enquanto os estudos de antibiograma revelaram que o maior número de isolados bacterianos apresentou resistência à Ampicilina (95%), seguido por Augmentin (91%), Cefuroxima (85%) e Tetraciclina (95%) de (Escherichia coli e Klebsiella spp). No caso de Pseudomonas spp. e Salmonella, a maior resistência foi apresentada pela Ampicilina (90%) seguida pela Amoxicilina + Ácido Clavulânico (80%), Cefixima (90%) e Eritromicina (80%). Em Shigella spp e Salmonella spp, a maior resistência foi demonstrada por Amoxicilina, Ceftazidima, Augmentina (60%) e Amoxicilina + Ácido Clavulânico (50%). Conclui-se que estudos de antibiograma in vitro de isolados bacterianos revelaram maior resistência para Ampicilina, Augmentina, Cefuroxima, Cefixima, Tetraciclina, Eritromicina e Amoxicilina + Ácido Clavulânico. Os altos índices de resistência a antibióticos múltiplos (MARI) observados em todos os isolados neste estudo variaram de 0,6 a 0,9. O valor MARI de > 0,2 sugere várias bactérias resistentes a antibióticos e indica a presença de bactérias altamente resistentes.
RESUMO
The objective of this study was to evaluate the effectiveness of common antibiotics against different microorganisms in apparently healthy cattle in Shandong province and its suburb. A total of 220 nasal swab samples were collected and cultured for bacteriological evaluation. All the bacteria isolates after preliminary identification were subjected to antibiogram studies following disc diffusion method. It was found in the study that E. coli is the most commonly associated isolate (21%), followed by Klebsiella spp. (18%), Pseudomonas aeruginosa (13%), Salmonella spp. (15%), Shigella spp (12%), and Proteus spp (11%). While the antibiogram studies reveled that highest number of bacterial isolates showed resistance to Ampicillin (95%), followed by Augmentin (91%), Cefuroxime (85%) and Tetracycline (95%) of (Escherichia coli and Klebsiella spp). In the case of pseudomonas spp. and Salmonella the highest resistance was showed by Ampicillin (90%) followed by Amoxicillin + Clavulanic Acid (80%), Cefixime (90%), and Erythromycin (80%). In Shigella spp and Salmonella spp highest resistance was showed by Amoxicillin, Ceftazidime, Augmentin (60%), and Amoxicillin + Clavulanic Acid (50%). It is concluded that in vitro antibiogram studies of bacterial isolates revealed higher resistance for Ampicillin, Augmentin, Cefuroxime, Cefixime, Tetracycline, Erythromycin, and Amoxicillin + Clavulanic Acid. The high multiple Antibiotics resistance indexes (MARI) observed in all the isolates in this study ranging from 0.6 to 0.9. MARI value of >0.2 is suggests multiple antibiotic resistant bacteria and indicate presence of highly resistant bacteria.(AU)
O objetivo deste estudo foi avaliar a eficácia dos antibióticos comuns contra diferentes microrganismos em bovinos aparentemente saudáveis na província de Shandong e seus subúrbios. Um total de 220 amostras de esfregaço nasal foi coletado e cultivado para avaliação bacteriológica. Todos os isolados de bactérias após identificação preliminar foram submetidos a estudos de antibiograma seguindo o método de difusão em disco. Verificou-se no estudo que E. coli é o isolado mais comumente associado (21%), seguido por Klebsiella spp. (18%), Pseudomonas aeruginosa (13%), Salmonella spp. (15%), Shigella spp (12%) e Proteus spp (11%). Enquanto os estudos de antibiograma revelaram que o maior número de isolados bacterianos apresentou resistência à Ampicilina (95%), seguido por Augmentin (91%), Cefuroxima (85%) e Tetraciclina (95%) de (Escherichia coli e Klebsiella spp). No caso de Pseudomonas spp. e Salmonella, a maior resistência foi apresentada pela Ampicilina (90%) seguida pela Amoxicilina + Ácido Clavulânico (80%), Cefixima (90%) e Eritromicina (80%). Em Shigella spp e Salmonella spp, a maior resistência foi demonstrada por Amoxicilina, Ceftazidima, Augmentina (60%) e Amoxicilina + Ácido Clavulânico (50%). Conclui-se que estudos de antibiograma in vitro de isolados bacterianos revelaram maior resistência para Ampicilina, Augmentina, Cefuroxima, Cefixima, Tetraciclina, Eritromicina e Amoxicilina + Ácido Clavulânico. Os altos índices de resistência a antibióticos múltiplos (MARI) observados em todos os isolados neste estudo variaram de 0,6 a 0,9. O valor MARI de > 0,2 sugere várias bactérias resistentes a antibióticos e indica a presença de bactérias altamente resistentes.(AU)
Assuntos
Animais , Bovinos , Resistência a Múltiplos Medicamentos , Resistência beta-Lactâmica/efeitos dos fármacos , Farmacorresistência BacterianaRESUMO
A infecção por parvovírus de ganso (GPV) é uma doença infecciosa altamente patogênica em gansinhos e patinhos de Muscovy. Para detectar o antígeno GPV, desenvolvemos um novo ensaio imunoenzimático (ELISA) sanduíche usando um anticorpo de domínio único de cadeia pesada específico contra a proteína GPV NS1 como anticorpo de detecção. Os limites de detecção da proteína GST-NS1 e do título do vírus da cepa GPV H1 foram 5 ng/mL e 102,9 TCID50/mL, respectivamente. O ELISA sanduíche foi específico para GPV sem reatividade cruzada com outros vírus comuns de ganso, incluindo vírus Tembusu, circovírus de ganso, adenovírus de aves, vírus Newcastle ou vírus H9 da gripe aviária. Um total de 118 amostras de swab cloacal foram usadas para detectar o antígeno GPV usando o ELISA sanduíche e reação em cadeia da polimerase com uma taxa de coincidência de 91,5%. A sensibilidade e especificidade do ELISA sanduíche foram de 91,6% e 91,4%, respectivamente. Esses resultados sugerem que este ELISA sanduíche pode ser aplicado para detectar GPV.
Assuntos
Animais , Proteínas Recombinantes/análise , Parvovirus/isolamento & purificação , Gansos/virologia , Ensaio de Imunoadsorção Enzimática/veterinária , Reação em Cadeia da Polimerase/veterináriaRESUMO
Tibetan pigs are characterized by significant phenotypic differences relative to lowland pigs. Our previous study demonstrated that the genes CRYAB and CTGF were differentially expressed in heart tissues between Tibetan (highland breed) and Yorkshire (lowland breed) pigs, indicating that they might participate in hypoxia adaptation. CRYAB (ÉB-crystallin) and CTGF (connective tissue growth factor) have also been reported to be associated with lung development. However, the expression patterns of CRYAB and CTGF in lung tissues at different altitudes and their genetic characterization are not well understood. In this study, qRT-PCR and western blot of lung tissue revealed higher CRYAB expression levels in highland and middle-highland Tibetan and Yorkshire pigs than in their lowland counterparts. With an increase in altitude, the expression level of CTGF increased in Tibetan pigs, whereas it decreased in Yorkshire pigs. Furthermore, two novel single-nucleotide polymorphism were identified in the 5' flanking region of CRYAB (g.39644482C>T and g.39644132T>C) and CTGF (g.31671748A>G and g.31671773T>G). The polymorphism may partially contribute to the differences in expression levels between groups at the same altitude. These findings provide novel insights into the high-altitude hypoxia adaptations of Tibetan pigs.
Porcos tibetanos são caracterizados por diferenças fenotípicas significativas em relação aos porcos de planície. Nosso estudo anterior demonstrou que os genes CRYAB e CTGF eram expressos diferentemente nos tecidos do coração entre os porcos tibetanos (raça das terras altas) e Yorkshire (raça das terras baixas), indicando que eles poderiam participar da adaptação à hipoxia. CRYAB (ÉB-crystallin) e CTGF (fator de crescimento do tecido conjuntivo) também foram relatados como estando associados ao desenvolvimento pulmonar. Entretanto, os padrões de expressão do CRYAB e CTGF nos tecidos pulmonares em diferentes altitudes e sua caracterização genética não são bem compreendidos. Neste estudo, o qRT-PCR e a mancha ocidental de tecido pulmonar revelou níveis de expressão de CRYAB mais elevados em porcos tibetanos e Yorkshire de altitude e média altitude do que em seus pares de planície. Com um aumento na altitude, o nível de expressão do CTGF aumentou nos porcos tibetanos, enquanto diminuiu nos porcos Yorkshire. Além disso, foram identificados dois novos polimorfismos de um único nucleotídeo na região flanqueadora de CRYAB (g.39644482C>T e g.39644132T>C) e CTGF (g.31671748A>G e g.31671773T>G). O polimorfismo pode contribuir parcialmente com as diferenças nos níveis de expressão entre grupos a uma mesma altitude. Estas descobertas proporcionam novos conhecimentos sobre as adaptações de hipoxia a alta altitude dos porcos tibetanos.
Assuntos
Animais , Polimorfismo Genético , Adaptação Biológica/genética , Expressão Gênica , Sus scrofa , Doença da Altitude/veterinária , Hipóxia/veterinária , TibetRESUMO
Chemotherapy is one of the most commonly used clinical treatments among the currently available cancer therapies. However, the phenomenon of Multidrug resistance (MDR) has become a challenge in the treatment process, weakening the impact of chemotherapy. Extensive research on elucidating the development of cancer MDR has identified the following mechanisms that play a critical role in the development of several MDR reversal agents: abnormal expression of cell membrane transporters, adaptation of cancer cells to the microenvironment, regulation of hypoxia, repair of DNA damage and reduction of apoptosis, the enhancement of the EMT process, the existence of cancer stem cells (CSCs), and the abnormal activation of key signaling pathways. However, they failed to demonstrate significant efficacy due to severe side effects during their clinical trials. Traditional Chinese medicines (TCMs) are known to play an important anti-cancer role since they have low toxicity, high efficacy, and safety and can reverse MDR. TCMs reversal agents can be divided into Chinese medicine monomers, synthetic monomers, analogs, or derivatives. Several studies have shown that TCMs can effectively overcome cancer MDR and can be effectively used for treating cancer patients.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Medicina Tradicional Chinesa , Neoplasias/tratamento farmacológico , HumanosRESUMO
This study investigated the effect of calcium (Ca) and phytase interaction on growth performance and bone quality in 1-42-day-old broiler chickens. A total of 624 female one-day-old Ross 308 broilers were allotted to 13 treatments with four replicates and 12 birds per replicate. A 2 × 6 factorial experiment was designed to test the combinations of 0.50% and 1.00% Ca with 0, 500, 1,000, 2,500, 5,000, and 10,000 FTU/kg phytase in the basal diet (0.25% non-phytate phosphorus, NPP). The control diet contained adequate Ca and phosphorus (P). Dietary Ca, phytase, and their interaction affected growth performance and bone mineralization of broilers at 1-42 days of age (p<0.05). The broilers fed with 1.00% Ca had lower body weight gain (BWG) and feed intake (FI) compared with the birds fed with 0.50% Ca (p<0.05). The BWG, FI, leg bone weight, and ash weight of the broilers fed with 0.25% NPP were lower than those of birds fed with the control diet (p<0.05). The addition of 500-10,000 FTU/kg phytase improved growth rate and leg bone quality, especially at 1.00% Ca (p<0.05). No differences were observed in growth performance and bone quality of 42-day-old broilers fed with 1.00% Ca + 2,500-10,000 FTU/kg phytase and the control diet (p>0.05). These data indicated that high doses of phytase (2,500-10,000 FTU/kg) alleviate the negative effects of Ca and P imbalance (Ca-to-NPP ratio = 4.0) on growth performance and bone mineralization of broiler chickens.(AU)
Assuntos
Animais , Feminino , Calcificação Fisiológica/efeitos dos fármacos , Galinhas/fisiologia , Fósforo/análise , Cálcio da Dieta/análise , Fenômenos Fisiológicos da Nutrição AnimalRESUMO
As an essential trace element for animals, copper significantly contributes to the growth and health of animals. Compared to inorganic trace elements, organic trace elements are better supplements; notably, they are acquired through microbial transformation. Therefore, we screened for copper-enriched microorganisms from high copper content soil to obtain organic copper. Sodium diethyldithio carbamate trihydrate was applied as a chromogenic agent for determining micro amounts of intracellular copper through spectrophotometry. In total, 50 fungi were isolated after the successful application of the screening platform for copper-rich microbes. Following morphological and molecular biology analyses, the N-2 strain, identified as Aspergillus niger sp. demonstrated showed better copper enrichment potential than others. Notably, the strain tolerance to copper was nearly thrice that of Saccharomyces cerevisiae, up to 1600mg/L. The content of the organic bound copper was 22.84mg Cu/g dry cell. Using the Central Composite Design (CCD) response surface method, we optimized the fermentation condition (inoculation amount, 13%; temperature, 28(C; pH, 5.0). Compared to the original strain results under the single factor fermentation condition, we reported an increase by 24.18% under the optimized conditions. Collectively, these findings provide a reference for uncovering new and low-cost organic copper additives.(AU)
Como elemento traço essencial para os animais, o cobre contribui significativamente para o crescimento e saúde dos animais. Comparado aos oligoelementos inorgânicos, os oligoelementos orgânicos são melhores suplementos; notavelmente, eles são adquiridos através de transformação microbiana. Portanto, nós selecionamos microorganismos enriquecidos com cobre de solos com alto teor de cobre para obter cobre orgânico. O carbamato de sódio diethyldithio trihidratado foi aplicado como agente cromogênico para a determinação de micro quantidades de cobre intracelular através da espectrofotometria. No total, 50 fungos foram isolados após a aplicação bem sucedida da plataforma de triagem para micróbios ricos em cobre. Após análises morfológicas e de biologia molecular, a cepa N-2, identificada como Aspergillus niger sp. demonstrou um melhor potencial de enriquecimento de cobre do que outras. Notavelmente, a tolerância da estirpe ao cobre foi quase três vezes maior que a da Saccharomyces cerevisiae, até 1600mg/L. O conteúdo de cobre ligado orgânico era de 22,84mg Cu/g de célula seca. Usando o método de superfície de resposta Central Composite Design (CCD), nós otimizamos a condição de fermentação (quantidade de inoculação, 13%; temperatura, 28C; pH, 5,0). Em comparação com os resultados da deformação original sob a condição de fermentação de fator único, relatamos um aumento de 24,18% sob as condições otimizadas. Coletivamente, estas descobertas fornecem uma referência para descobrir novos aditivos de cobre orgânico de baixo custo.(AU)
Assuntos
Animais , Análise do Solo , Cobre , Aditivos Alimentares , Aspergillus , Microbiologia do Solo , Tratamento do Solo , Sus scrofaRESUMO
The objective of this study was to evaluate the effectiveness of common antibiotics against different microorganisms in apparently healthy cattle in Shandong province and its suburb. A total of 220 nasal swab samples were collected and cultured for bacteriological evaluation. All the bacteria isolates after preliminary identification were subjected to antibiogram studies following disc diffusion method. It was found in the study that E. coli is the most commonly associated isolate (21%), followed by Klebsiella spp. (18%), Pseudomonas aeruginosa (13%), Salmonella spp. (15%), Shigella spp (12%), and Proteus spp (11%). While the antibiogram studies reveled that highest number of bacterial isolates showed resistance to Ampicillin (95%), followed by Augmentin (91%), Cefuroxime (85%) and Tetracycline (95%) of (Escherichia coli and Klebsiella spp). In the case of pseudomonas spp. and Salmonella the highest resistance was showed by Ampicillin (90%) followed by Amoxicillin + Clavulanic Acid (80%), Cefixime (90%), and Erythromycin (80%). In Shigella spp and Salmonella spp highest resistance was showed by Amoxicillin, Ceftazidime, Augmentin (60%), and Amoxicillin + Clavulanic Acid (50%). It is concluded that in vitro antibiogram studies of bacterial isolates revealed higher resistance for Ampicillin, Augmentin, Cefuroxime, Cefixime, Tetracycline, Erythromycin, and Amoxicillin + Clavulanic Acid. The high multiple Antibiotics resistance indexes (MARI) observed in all the isolates in this study ranging from 0.6 to 0.9. MARI value of >0.2 is suggests multiple antibiotic resistant bacteria and indicate presence of highly resistant bacteria.
Assuntos
Escherichia coli , Bactérias Gram-Negativas , Animais , Bovinos , Resistência a Medicamentos , Lactamas , FenótipoRESUMO
Fluorescence imaging in the near-infrared II (NIR-II, 1000-1700 nm) region opens up new avenues for biological systems due to suppressed scattering and low autofluorescence at longer-wavelength photons. Nonetheless, the development of organic NIR-II fluorophores is still limited mainly due to the shortage of efficient molecular design strategy. Herein, we propose an approach of designing Janus NIR-II fluorophores by introducing electronic donors with distinct properties into one molecule. As a proof-of-concept, fluorescent dye 2 TT-m, oC6B with both twisted and planar electronic donors displayed balanced absorption and emission which were absent in its parent compound. The key design strategy for Janus molecule is that it combines the merits of intense absorption from planar architecture and high fluorescence quantum yield from twisted motif. The resulting 2 TT-m, oC6B nanoparticles exhibit a high molar absorptivity of 1.12 ⨯104 M-1 cm-1 at 808 nm and a NIR-II quantum yield of 3.7%, displaying a typical aggregation-induced emission (AIE) attribute. The highly bright and stable 2 TT-m, oC6B nanoparticles assured NIR-II image-guided cancer surgery to resect submillimeter tumor nodules. The present study may inspire further development of molecular design philosophy for highly bright NIR-II fluorophores for biomedical applications.
RESUMO
BACKGROUND: Poly-(ADP-Ribose)-Polymerase inhibitors (PARPi) were reported as radiosensitizers in non-small cell lung cancer (NSCLC) with wide-type epidermal growth factor receptor (EGFR), but the effects of radiation combined with PARPi were not investigated in EGFR-mutated NSCLC. Moreover, the underlying mechanisms were not well examined. This study aimed to study the efficacy of radiation combined with niraparib in EGFR-mutated NSCLC and explore their influence on the immune system. METHODS: Clone formation and apoptosis assay were conducted to explore the effects of niraparib and radiation. Immunofluorescence was conducted to detect the double-strand DNA breaks. Real-time PCR and immunoblotting were employed to evaluate the activation of STING/TBK1/TRF3 pathway and the expression levels of interferon ß, CCL5 and CXCL10. Immunocompetent mice model bearing with subcutaneous Lewis lung cancer was established to confirm the results in vivo. RESULTS: Niraparib and radiation were synergistic to inhibit tumor both in vitro and in vivo. Radiation plus niraparib could activate anti-tumor immunity, which appeared as increased CD8+ T lymphocytes and activated STING/TBK1/IRF3 pathway. CONCLUSION: PARPi not only as a radiosensitizer inhibited EGFR-mutated NSCLC tumor growth, but also cooperated with radiation to promote anti-tumor immune responses.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Genes erbB-1 , Indazóis/farmacologia , Neoplasias Pulmonares/terapia , Mutação , Piperidinas/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Radiossensibilizantes/farmacologia , Animais , Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Lewis/imunologia , Carcinoma Pulmonar de Lewis/terapia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linhagem Celular Tumoral , Quimiocina CCL5/metabolismo , Quimiocina CXCL10/metabolismo , Quebras de DNA de Cadeia Dupla , Feminino , Imunofluorescência , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/efeitos da radiação , Imunocompetência , Fator Regulador 3 de Interferon/metabolismo , Interferon beta/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Linfócitos do Interstício Tumoral , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Semelhantes à Proteína de Ligação a TATA-Box/metabolismo , Ensaio Tumoral de Célula-TroncoRESUMO
PURPOSE: Paeonol is a natural chemical medicine derived from the bark of peony root, which has been found to inhibit tumor activity in various tumor cell lines, and can play a synergistic anti-tumor effect with chemotherapy or radiotherapy. METHODS: We used paeonol to act on human bladder cancer T24 and 5637 cells, and established xenograft tumor in nude mice by subcutaneous injection of T24 cells. RESULTS: CCK-8 assay and plate cloning experiments showed that paeonol could inhibit the proliferation of T24 and 5637 cells in vitro. The results of flow cytometry and the detection of BAX, Bcl-2 and Caspase-3 proteins suggested that paeonol can induce apoptosis of T24 and 5637 cells in vitro. Tumor formation, TUNEL detection and immunohistochemical results of Ki67, BAX, Bcl-2 and Caspase-3 in nude mice showed that paeonol could inhibit T24 cell proliferation and induce apoptosis in vivo, thus inhibiting tumor growth. Further research revealed that paeonol could reduce phosphorylation expression of PI3K and AKT in T24 and 5637 cells. CONCLUSION: We confirmed that paeonol could inhibit proliferation and induce apoptosis of human bladder cancer T24 and 5637 cells in vitro and in vivo, inhibit the growth of T24 tumor-forming nude mice, and possibly play a role by inhibiting the PI3K/AKT signaling pathway, so as to provide a potential therapeutic drug for bladder cancer.
Assuntos
Acetofenonas/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias da Bexiga Urinária/patologia , Animais , Caspase 3/análise , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Marcação In Situ das Extremidades Cortadas , Técnicas In Vitro , Antígeno Ki-67/análise , Camundongos , Camundongos Nus , Transplante de Neoplasias , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/análise , Neoplasias da Bexiga Urinária/química , Neoplasias da Bexiga Urinária/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/análiseRESUMO
OBJECTIVE: Recently, numerous studies have yielded inconsistent results regarding the effect of metformin on esophageal cancer risk in type 2 diabetes mellitus patients. The purpose of this study is to systematically assess this effect using meta-analysis. METHODS: We searched clinical studies on metformin and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. After literature screening, a series of meta-analyses were conducted using RevMan 5.3 software. The pooled hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the effect size. RESULTS: Five eligible studies (four cohort studies and one case-control study) were included for our meta-analysis using a random-effect model. The analysis showed that metformin could not reduce esophageal cancer risk in type 2 diabetes mellitus patients (HR 0.88, 95% CI 0.60-1.28, P > 0.05). Subgroup analyses by geographic location showed that metformin significantly reduced esophageal cancer risk in Asian patients with type 2 diabetes mellitus (HR 0.59, 95% CI 0.39-0.91, P = 0.02), without heterogeneity between studies (P = 0.80 and I2 = 0%). CONCLUSIONS: Overall, our systematic review and meta-analysis demonstrate that metformin does not reduce esophageal cancer risk in type 2 diabetes mellitus patients. However, a significant reduction in esophageal cancer risk in Asian populations remains to be clarified.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Neoplasias Esofágicas/prevenção & controle , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Povo Asiático , Estudos de Casos e Controles , Intervalos de Confiança , Diabetes Mellitus Tipo 2/etnologia , Neoplasias Esofágicas/etnologia , Humanos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Viés de Publicação , Estudos Retrospectivos , RiscoRESUMO
PURPOSE: The present study aimed to investigate the efficacy and severity of adverse effects of HCAG and CAG re-induction chemotherapy in elderly low- and intermediate-risk group patients diagnosed with acute myeloid leukemia (AML) following induction failure. METHODS: A total of 94 AML patients were enrolled in the study, of whom 46 were treated with HCAG chemotherapy, while 48 were treated with CAG chemotherapy. RESULT: The complete remission (CR) was 39.6% in the patients with HCAG, while the CR was 33.3% in the CAG group. The overall remission (ORR) was 63.0% and 43.5% in patients of the HCAG and CAG groups, respectively (P = 0.038). The median survival time of progression free survival (PFS) was 8.0 (95% CI 3.843-10.157) months in the HCAG group and 7.0 (95% CI 2.682-13.318) months in the CAG group (P = 0.032). A total of 31 patients in the HCAG group suffered from grade 4 hematological toxicity, whereas 29 patients were treated with CAG (P = 0.622). A total of 27 (58.7%) cases indicated apparent pulmonary infection in the HCAG group, while 25 (52.1%) were noted with this complication in the CAG group (P = 0.519). Oral cavity toxicity was evident for 13 (28.3%) and 11 (23.0%) cases in the HCAG and CAG groups, respectively (P = 0.216). CONCLUSION: The HCAG regimen was more effective than the CAG regimen in elderly low- and intermediate-risk group patients diagnosed with acute myeloid leukemia although the HCAG regimen exhibited similar toxicity with that of the CAG group.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mepesuccinato de Omacetaxina/uso terapêutico , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Aclarubicina/efeitos adversos , Aclarubicina/uso terapêutico , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/efeitos adversos , Citarabina/uso terapêutico , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mepesuccinato de Omacetaxina/efeitos adversos , Humanos , Quimioterapia de Indução/efeitos adversos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Indução de Remissão , Retratamento/métodos , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação , Método Simples-Cego , Fatores de Tempo , Falha de TratamentoRESUMO
PURPOSE: Cytokines are vital pro-inflammatory factors and involved in tumor immune infiltration, and immune infiltration is closely related to PD-1/PD-L1 blockades immunotherapy. This study aims to explore the associations between cytokines and prognosis and also PD-1/PD-L1 expression in early lung adenocarcinoma, which is seldom reported. METHODS: 324 early lung adenocarcinoma patients with prior surgical resection were included and the associations between overall survival time and clinical factors and also cytokines including IL-1ß, IL-6 and TNF-α were analyzed by multivariate cox regression and Kaplan-Meier curve (log-rank test). Resected tumor samples were randomly obtained to detect the PD-1/PD-L1 expression by immunohistochemistry, and Chi square test was used for relations between cytokines and PD-1/PD-L1 expression. RESULTS: In this study group, 26.2% patients showed a high level of IL-1ß and patients with high IL-1ß level showed 19 months shortened mOS than those with normal IL-1 ß expression (mOS: 24.00, 95%CI 11.98-36.02 vs 43.00, 95% CI 37.37-48.63, p = 0.017). Among detected samples, the positive rate of PD-1 was 25.0% (13/52), and the positive rate of PD-L1 was 37.3% (19/52). The positive rate of PD-1 was 36.1% higher in high-IL-1 ß-level group as compared to normal-IL-1ß-level group (50.0% vs 13.9%, p = 0.012). No significant association was found between IL-1 ß and PD-L1 expression. CONCLUSION: High expression level of IL-1ß was correlated with poor prognosis and higher positive rate of PD-1 expression, which gave us insights into biomarkers of survival prediction and immunotherapy in lung adenocarcinoma. Further studies were still needed.
Assuntos
Adenocarcinoma de Pulmão/metabolismo , Antígeno B7-H1/metabolismo , Interleucina-1beta/metabolismo , Neoplasias Pulmonares/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Distribuição de Qui-Quadrado , Feminino , Humanos , Interleucina-6/metabolismo , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Prognóstico , Análise de Regressão , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Reduction of surgeries in axillary has been proved feasible in breast cancer with negative and limited involved axillary lymph nodes. However, for women with a heavy axillary burden, the extent of dissection is still arguable. PATIENTS AND METHODS: From a total of 7042 patients with breast cancer who underwent surgical treatments between 2008 and 2014, 692 (9.85%) patients with the axillary staging of N2-3M0 were classified into Level I-II dissection group and Level I-III dissection group. 203 pairs of patients were matched by the propensity score. RESULTS: The positive rate of level-III lymph nodes is 62.4% in patients who underwent Level I-III dissection. There are 67 (22.1%) patients who experienced rise in staging from N2 to N3 due to level-III dissection. With a median follow-up of 62.4 months, no significant difference was observed in RFS (P = 0.897), MFS (P = 0.610) and OS (P = 0.755) between level I-II group and level I-III group. The same results were observed in the independent analysis of neoadjuvant and non-neoadjuvant subgroups. The binary regression model showed the positivity of level-III is only associated with involved lymph nodes in level-II. CONCLUSION: Additional level-III dissection has a limited impact on survival but still valuable in an accurate stage. The reduction of surgeries in axillary should be treated with discretion in breast cancer patients with a heavy axillary burden.
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Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Adulto , Idoso , Axila , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante/mortalidade , Progressão da Doença , Feminino , Humanos , Excisão de Linfonodo/classificação , Excisão de Linfonodo/mortalidade , Linfonodos/cirurgia , Pessoa de Meia-Idade , Terapia Neoadjuvante/mortalidade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Pontuação de Propensão , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
PURPOSE: Clinically, hypoxia is associated with increased distant metastasis and poor survival in gastric cancer (GC). In this study, we set out from the cellular interaction to further explain the molecular mechanism of invasion in GC cells under hypoxic conditions. METHODS: Gastric cancer cells were cultured under 1% O2 (hypoxia-cultured gastric cancer cells, HGC) and 20% O2 condition (normoxic-cultured gastric cancer cells, NGC). NGC was co-cultured with HGC-medium. Scrape and Transwell were used to evaluate invasion and migration. Exosomes from GC were extracted by ultracentrifugation. Electron microscopy images, western-blot used to analyze the size distributions and the number of exosomes. RESULTS: HGC-medium induced NGC dissociated. Long non-coding RNA (lncRNA) prostate cancer gene expression marker 1 (PCGEM1) was specifically expressed in HGC exosomes. HGC-derived PCGEM1-riched exosomes could promote the invasion and migration of NGC. On the mechanism, PCGEM1 maintained stability and reduced the degradation of SNAI1, which could induce the epithelial-mesenchymal transition of GC. CONCLUSION: LncRNA PCGEM1 was overexpressed in GC cells. And part of the PCGEM1 can be encapsulated into exosomes. These exosomes promoted invasion and migration of other GC cells. We considered PCGEM1 might act as a "scaffold" combined with SNAI1 and prompt the invasion and migration of GC.
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Exossomos/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Hipóxia Tumoral , Comunicação Celular , Movimento Celular/genética , Técnicas de Cocultura/métodos , Meios de Cultura/farmacologia , Transição Epitelial-Mesenquimal/fisiologia , Exossomos/ultraestrutura , Humanos , Invasividade Neoplásica , Metástase Neoplásica , RNA Mensageiro/metabolismo , Fatores de Transcrição da Família Snail/genética , Microambiente Tumoral , Regulação para CimaRESUMO
Evidence from previous voxel-based morphometry (VBM) studies indicates that widespread brain regions are involved in Parkinson's disease with mild cognitive impairment (PD-MCI). However, the spatial localization reported for gray matter (GM) abnormalities is heterogeneous. The aim of the present study was to quantitatively integrate studies on GM abnormalities observed in PD-MCI in order to determine whether a pattern exists. Eligible whole-brain VBM studies were identified by a systematic search of articles in PubMed and EMBASE databases spanning from 1995 to January 1, 2019. A meta-analysis was performed to investigate regional GM abnormalities in PD-MCI. The anisotropic effect size version of seed-based d mapping (AES-SDM) meta-analysis was conducted to explore the GMV differences of PD-MCI compared with PD patients with normal cognitive function (PD-NC). A total of 12 studies comprising 243 PD-MCI patients and 326 PD-NC were included in the meta-analysis. PD-MCI patients showed a robust GM decrease in the left insula and left superior temporal gyrus. Moreover, meta-regression analysis demonstrated that age, PD duration and stage, and Unified Parkinson's Disease Rating Scale III and Mini-Mental State Examination scores might be partly correlated with the GM abnormalities observed in PD-MCI patients. The convergent findings of this quantitative meta-analysis revealed a characteristic neuroanatomical pattern in PD-MCI. The findings provide some evidence that MCI in PD may result in the breakdown of the insula and temporal gyrus, which may serve as specific regions of interest for further investigations.
Assuntos
Disfunção Cognitiva/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Feminino , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologiaRESUMO
Macrophages play an important role in the immune system as a key host defense against pathogens. Non-polarized macrophages can differentiate into pro-inflammatory classical pathway-activated macrophages or anti-inflammatory alternative pathway-activated macrophages, both of which play central roles in breast cancer growth and progression in a process called polarization of macrophages. Classical pathway-activated and alternative pathway-activated macrophages can transform into each other and their transformational properties and orientation are determined by cytokines in the tumor microenvironment. Tumor-associated macrophages display many functions, such as tissue reforming, participating in inflammation and tumor growth in breast cancer progression. Some cytokines, such as interleukins and transcriptional activators, reside in the tumor microenvironment and influence tumor-associated macrophages. Chemotherapy is a common treatment for breast cancer and macrophages play an important role in mammary tumor cell migration, cancer invasion, and angiogenesis. This review summarizes the activities of tumor-associated macrophages in the mammary tumor, chemotherapeutic processes and some potential strategies for breast cancer therapy.
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Neoplasias da Mama/etiologia , Macrófagos Associados a Tumor/fisiologia , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Polaridade Celular , Feminino , Humanos , Ativação de Macrófagos , Microambiente TumoralRESUMO
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a kind of cancer with heterogeneous biological characteristics, which is affected by a complex network of gene interactions. Identification of molecular biomarkers paves the way for individualized therapy based on gene expression profiles, which can overcome the heterogeneity of ESCC. METHODS: In this study, GSE20347, GSE23400 and GSE45670 datasets were retrieved from Gene Expression Omnibus (GEO) database, and the overlapping differentially expressed genes (DEGs) in three datasets were screened. Then the overlapping DEGs function was annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis. The prognostic value of the top five KEGG pathway-related genes were further validated in The Cancer Genome Atlas (TCGA) database. After extensive statistical analysis, four genes (CDC25B, CXCL8, FZD6 and MCM4) were identified as potential prognostic markers. Among the four candidate genes, the prognostic value of FZD6 in ESCC patients has not been evaluated. Therefore, we finally used immunohistochemistry method to evaluate the effect of FZD6 on the prognosis of patients with ESCC. Additionally, we detected the expression level of FZD6 in ESCC cell line and normal esophageal epithelial cell line, and observed the cell viability of ESCC cell line after FZD6 knockdown. RESULTS: The results showed that the overexpression of FZD6 predicted poor overall survival (OS) (P = 0.005) and progression-free survival (PFS) (P = 0.004) in ESCC patients. COX regression analysis showed that N stage (P = 0.026) and FZD6 expression level (P = 0.001) were independent prognostic factors of OS for ESCC patients. Furthermore, compared with normal esophageal epithelial cell line, the up-regulation of FZD6 was detected in ESCC cell line. Knockdown of FZD6 could significantly inhibit the proliferation of ESCC cells (P < 0.001). CONCLUSION: CDC25B, CXCL8, FZD6 and MCM4 were screened as candidate genes for prognosis assessment of patients with ESCC. The prognostic role of FZD6 in ESCC patients was confirmed in current study.