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In order to study the alkaloids from branches and leaves of Ervatamia hainanensis, silica gel, ODS, Sephadex LH-20 and HPLC chromatography were used to obtain six alkaloids from the branches and leaves of E. hainanensis with use of. Based on the physicochemical properties and spectral data, their structures were identified as 10-hydroxydemethylhirsuteine(1), 3R-hydroxycoronaridine(2), 3-(2-oxopropyl)coronaridine(3), pandine(4), 16-epi-vobasine(5), and 16-epi-vobasinic acid(6). Among them, compound 1 was a new monoterpenoid indole alkaloid, and compounds 5 and 6 were obtained from this plant for the first time.
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Alcaloides , Tabernaemontana , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Folhas de PlantaRESUMO
Five novel bisindole alkaloids, hunzeylanines A-E (1-5), with an unprecedented skeleton were isolated from the roots of Hunteria zeylanica. Compounds 1-5 represent the first examples of akuammine-pleioarpamine-type bisindole alkaloids fused with a dihydropyran unit. Their structures including absolute configurations were established through comprehensive spectroscopic data analyses and computational calculation methods. The plausible biogenetic pathway of 1 was also proposed. Alkaloids 1 and 2 displayed moderate cytotoxicity toward three human cancer cell lines (MDA-MB-231, AV3, and Huh7).
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Alcaloides , Apocynaceae , Humanos , Alcaloides Indólicos/farmacologia , Estrutura Molecular , Raízes de Plantas , Análise EspectralRESUMO
Numerous studies have demonstrated that serum high-density lipoprotein cholesterol (HDL-C) levels correlate strongly with cancer patient survival. However, other studies have had the opposite results. We therefore conducted a systematic review and meta-analysis to assess the prognostic value of HDL-C levels in people with cancer. We searched PubMed, Embase, and the Cochrane Library (last update by December 28, 2017) for studies evaluating the effect of serum HDL-C levels on cancer patient prognosis. Data from 25 studies covering13,140 patients were included. Combined hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were assessed using fixed-effects and random-effects models. High serum HDL-C levels were associated with better OS (pooled HR = 0.70; 95% confidence interval (CI) (0.60-0.82). In the subgroup, the relative high level of HDL-C yielded a favorable outcome in most of tumor types. However, in the nasopharyngeal carcinoma subgroup, the correlation was not significant (combined HR = 1.31; 95% CI (0.91-1.90)). High serum HDL-C levels were associated with better DFS (pooled HR = 0.64; 95% confidence interval (CI) (0.50-0.81)). This meta-analysis demonstrates that high serum HDL-C levels are associated with better OS in patients with solid tumors, but not nasopharyngeal carcinoma; and high serum HDL-C levels are associated with better DFS.
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Biomarcadores Tumorais/sangue , HDL-Colesterol/sangue , Neoplasias/sangue , Neoplasias/mortalidade , Intervalo Livre de Doença , Humanos , Carcinoma Nasofaríngeo/sangue , Neoplasias Nasofaríngeas/sangue , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Numerous studies reported that dyslipidemia was associated with cancer risk. However, few studies investigated the associations between dyslipidemia and non-small cell lung cancer (NSCLC). METHODS: Four hundred twenty-four histologically confirmed NSCLC cases and 414 controls, matched for age and sex, were enrolled to examine the relationship between dyslipidemia and NSCLC. Demographic and clinical data were obtained from patients' medical records and telephone interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. RESULTS: Abnormal triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels showed statistically significant coexistence with NSCLC compared with controls. Higher levels of TG were associated with a higher risk of NSCLC (OR = 1.541, 95% CI, (1.072-2.215)). The odds ratios (ORs) for NSCLC for normal and high levels of HDL-C versus those with a low level of HDL-C were 0.337(95% CI, (0.242-0.468)) and 0.288(95% CI, (0.185-0.448)), respectively. After adjustment for age, sex, smoking status, hypertension, body mass index, diabetes and lipid profiles, the adjusted OR for normal and high levels of HDL-C were 0.320(95% CI, (0.218-0.470)) and 0.233(95% CI, (0.134-0.407)), respectively. However, after adjustment, high levels of TG increased the risk of NSCLC but not significantly (OR = 1.052, 95% CI (0.671-1.649)). CONCLUSIONS: This study provided evidence that dyslipidemia increased the risk of NSCLC in Chinese population.
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Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Dislipidemias/epidemiologia , Hipertensão/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , China/epidemiologia , HDL-Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/complicações , Dislipidemias/fisiopatologia , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar , Triglicerídeos/sangueRESUMO
PURPOSE: Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant and fatal liver tumor with increasing incidence worldwide. Lactate metabolism has been recently reported as a crucial contributor to tumor progression and immune regulation in the tumor microenvironment. However, it remains poorly identified about the biological functions of lactate metabolism in iCCA, which hinders the development of prognostic tools and therapeutic interventions. METHODS: The univariate Cox regression analysis and Boruta algorithm were utilized to identify key lactate metabolism-related genes (LMRGs), and a prognostic signature was constructed based on LMRG scores. Genomic variations and immune cell infiltration were evaluated in the high and low LMRG score groups. Finally, the biological functions of key LMRGs were verified with in vitro and in vivo experiments. RESULTS: Patients in the high LMRG score group exhibit a poor prognosis compared to those in the low LMRG score group, with a high frequency of TP53 and KRAS mutations. Moreover, the infiltration and function of NK cells were compromised in the high LMRG score group, consistent with the results from two independent single-cell RNA sequencing datasets and immunohistochemistry of tissue microarrays. Experimental data revealed that lactate dehydrogenase A (LDHA) knockdown inhibited proliferation and migration in iCCA cell lines and tumor growth in immunocompetent mice. CONCLUSION: Our study revealed the biological roles of LDHA in iCCA and developed a reliable lactate metabolism-related prognostic signature for iCCA, offering promising therapeutic targets for iCCA in the clinic.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Animais , Camundongos , Prognóstico , Colangiocarcinoma/genética , Lactato Desidrogenase 5 , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , Lactatos , Microambiente Tumoral/genéticaRESUMO
Pneumonia stands as the leading infectious cause of childhood mortality annually, underscoring its significant impact on pediatric health. Although dexamethasone (DXMS) is effective for treating pulmonary inflammation, its therapeutic potential is compromised by systemic side effects and suboptimal carrier systems. To address this issue, the current study introduces solid lipid nanoparticles encapsulating hydrophobic dexamethasone palmitate (DXMS-Pal-SLNs) as an anti-inflammatory nanoplatform to treat pneumonia. The specialized nanoparticle formulation is characterized by high drug loading efficiency, low drug leakage and excellent colloidal stability in particular during nebulization and is proficiently designed to target alveolar macrophages in deep lung regions via local delivery with the nebulization administration. In vitro analyses revealed substantial reductions in the secretions of tumor necrosis factor-α and interleukin-6 from alveolar macrophages, highlighting the potential efficacy of DXMS-Pal-SLNs in alleviating pneumonia-related inflammation. Similarly, in vivo experiments showed a significant reduction in the levels of these cytokines in the lungs of mice experiencing lipopolysaccharide-induced pulmonary inflammation after the administration of DXMS-Pal-SLNs via nebulization. Furthermore, the study demonstrated that DXMS-Pal-SLNs effectively control acute infections without causing pulmonary infiltration or excessive recruitment of immunocytes in lung tissues. These findings highlight the potential of nebulized DXMS-Pal-SLNs as a promising therapeutic strategy for mitigating pneumonia-related inflammations.
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Digital holography has been employed for in situ observation of dynamic processes occurring at the electrode|electrolyte interface during the anodic dissolution of Alloy 690 in solutions containing SO4 2- + SCN- with or without magnetic field (MF). It was found that MF increased the anodic current of Alloy 690 in 0.5 M Na2SO4 + 5 mM KSCN solution but showed a decreased value when evaluated in 0.5 M H2SO4 + 5 mM KSCN solution. For each solution, as a result of the stirring effect due to Lorentz force, MF showed a decreased localized damage further preventing pitting corrosion. The content of nickel and iron at grain boundaries is higher than that on the grain body, in accordance with the Cr-depletion theory. MF increased the anodic dissolution of nickel and iron, which in turn increased the anodic dissolution at grain boundaries. In situ inline digital holography revealed that IGC begins at one grain boundary and progresses to adjacent grain boundaries with or without MF.
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ABSTRACT: Estrogen impacts neural development; meanwhile, it has a protective effect on the brain. Bisphenols, primarily bisphenol A (BPA), can exert estrogen-like or estrogen-interfering effects by binding with estrogen receptors. Extensive studies have suggested that neurobehavioral problems, such as anxiety and depression, can be caused by exposure to BPA during neural development. Increasing attention has been paid to the effects on learning and memory of BPA exposure at different developmental stages and in adulthood. Further research is required to elucidate whether BPA increases the risk of neurodegenerative diseases and the underlying mechanisms, as well as to assess whether BPA analogs, such as bisphenol S and bisphenol F, influence the nervous system.
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Estrogênios , Receptores de Estrogênio , Receptores de Estrogênio/metabolismo , Compostos Benzidrílicos/farmacologia , Sistema Nervoso/metabolismoRESUMO
KRAS mutations are causally linked to protumor inflammation and are identified as driving factors in tumorigenesis. Here, using multiomics data gathered from a large set of patients, we showed that KRAS mutation was associated with a specific landscape of alternative mRNA splicing that connected to myeloid inflammation in intrahepatic cholangiocarcinoma (iCCA). Then, we identified a negative feedback mechanism in which the upregulation of interleukin 1 receptor antagonist (IL1RN)-201/203 due to alternative splicing confers vital anti-inflammatory effects in KRAS-mutant iCCA. In KRAS-mutant iCCA mice, both IL1RN-201/203 upregulation and anakinra treatment ignited a significant antitumor immune response by altering neutrophil recruitment and phenotypes. Furthermore, anakinra treatment synergistically enhanced anti-PD-1 therapy to activate intratumoral GZMB+ CD8+ T cells in KRAS-mutant iCCA mice. Clinically, we found that high IL1RN-201/203 levels in patients with KRAS-mutant iCCA were significantly associated with superior response to anti-PD-1 immunotherapy. SIGNIFICANCE: This work describes a novel inflammatory checkpoint mediated by IL1RN alternative splicing variants that may serve as a promising basis to develop therapeutic options for KRAS-mutant iCCA and other cancers. This article is featured in Selected Articles from This Issue, p. 2109.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Animais , Camundongos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Inflamação/tratamento farmacológico , Inflamação/genéticaRESUMO
Organoid models have the potential to recapitulate the biological and pharmacotypic features of parental tumors. Nevertheless, integrative pharmaco-proteogenomics analysis for drug response features and biomarker investigation for precision therapy of patients with liver cancer are still lacking. We established a patient-derived liver cancer organoid biobank (LICOB) that comprehensively represents the histological and molecular characteristics of various liver cancer types as determined by multiomics profiling, including genomic, epigenomic, transcriptomic, and proteomic analysis. Proteogenomic profiling of LICOB identified proliferative and metabolic organoid subtypes linked to patient prognosis. High-throughput drug screening revealed distinct response patterns of each subtype that were associated with specific multiomics signatures. Through integrative analyses of LICOB pharmaco-proteogenomics data, we identified the molecular features associated with drug responses and predicted potential drug combinations for personalized patient treatment. The synergistic inhibition effect of mTOR inhibitor temsirolimus and the multitargeted tyrosine kinase inhibitor lenvatinib was validated in organoids and patient-derived xenografts models. We also provide a user-friendly web portal to help serve the biomedical research community. Our study is a rich resource for investigation of liver cancer biology and pharmacological dependencies and may help enable functional precision medicine.
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Neoplasias Hepáticas , Proteogenômica , Humanos , Proteômica , Medicina de Precisão , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , OrganoidesRESUMO
In our study we aimed to identify rapidly reacting gravity-responsive mechanisms in mammalian cells in order to understand if and how altered gravity is translated into a cellular response. In a combination of experiments using "functional weightlessness" provided by 2D-clinostats and real microgravity provided by several parabolic flight campaigns and compared to in-flight-1g-controls, we identified rapid gravity-responsive reactions inside the cell cycle regulatory machinery of human T lymphocytes. In response to 2D clinorotation, we detected an enhanced expression of p21 Waf1/Cip1 protein within minutes, less cdc25C protein expression and enhanced Ser147-phosphorylation of cyclinB1 after CD3/CD28 stimulation. Additionally, during 2D clinorotation, Tyr-15-phosphorylation occurred later and was shorter than in the 1 g controls. In CD3/CD28-stimulated primary human T cells, mRNA expression of the cell cycle arrest protein p21 increased 4.1-fold after 20s real microgravity in primary CD4+ T cells and 2.9-fold in Jurkat T cells, compared to 1 g in-flight controls after CD3/CD28 stimulation. The histone acetyltransferase (HAT) inhibitor curcumin was able to abrogate microgravity-induced p21 mRNA expression, whereas expression was enhanced by a histone deacetylase (HDAC) inhibitor. Therefore, we suppose that cell cycle progression in human T lymphocytes requires Earth gravity and that the disturbed expression of cell cycle regulatory proteins could contribute to the breakdown of the human immune system in space.
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Heat-shock protein 90 (Hsp90) functions as part of a multichaperone complex that folds, activates and assembles its client proteins. Androgen receptor (AR), a pathogenic gene product in spinal and bulbar muscular atrophy (SBMA), is one of the Hsp90 client proteins. We examined the therapeutic effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG), a potent Hsp90 inhibitor, and its ability to degrade polyglutamine-expanded mutant AR. Administration of 17-AAG markedly ameliorated motor impairments in the SBMA transgenic mouse model without detectable toxicity, by reducing amounts of monomeric and aggregated mutant AR. The mutant AR showed a higher affinity for Hsp90-p23 and preferentially formed an Hsp90 chaperone complex as compared to wild-type AR; mutant AR was preferentially degraded in the presence of 17-AAG in both cells and transgenic mice as compared to wild-type AR. 17-AAG also mildly induced Hsp70 and Hsp40. 17-AAG would thus provide a new therapeutic approach to SBMA and probably to other related neurodegenerative diseases.
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Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/patologia , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/patologia , Peptídeos/genética , Rifabutina/análogos & derivados , Animais , Benzoquinonas , Linhagem Celular , Células Cultivadas , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/metabolismo , Lactamas Macrocíclicas , Masculino , Camundongos , Camundongos Transgênicos , Atrofia Muscular Espinal/tratamento farmacológico , Mutação , Fenótipo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Rifabutina/farmacologia , Rifabutina/uso terapêutico , Expansão das Repetições de Trinucleotídeos/genéticaRESUMO
Objective: To analyze the incidences of long-term complications and revision surgery associated with diced cartilage grafts in dorsal augmentation rhinoplasty. Methods: The PubMed, MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for clinical studies on the use of diced cartilage for dorsal augmentation published. A meta-analysis was conducted to pool the estimated rates of infection, overcorrection, visible irregularity, absorption, and revision surgery. Result: A total of 14 studies involving 2380 patients were included in the systematic review. The combined rates were 11.5% for overall complications and 5.3% for revision surgery. The rates of the most frequently reported complications were 4.5% for infection, 5.3% for visible irregularity, 0.7% for overcorrection, and 0.5% for absorption. There was no significant difference in the rates of visible irregularity (p = 0.23) and revision surgery (p = 0.71) among the wrapped diced cartilage, glued diced cartilage, and free diced cartilage groups. Conclusion: This meta-analysis presents the first comprehensive and quantitative report of long-term complications associated with diced cartilage in dorsal augmentation rhinoplasty. Infection and visible irregularity were the most frequently reported complications. The rates of irregularity and revision surgery were not correlated with the diced cartilage packing methods.
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Rinoplastia , Cartilagem/transplante , Fáscia/transplante , Humanos , Reoperação , Rinoplastia/efeitos adversos , Rinoplastia/métodosRESUMO
Colorectal cancer (CRC) is the fourth leading cause of cancer-related mortality globally. Therefore, a better understanding of the early molecular events of this disease is needed. Long noncoding RNAs (lncRNAs) play a critical role in the regulation of tumorigenesis and cancer progression. In this study, we investigated the characteristics of ZFAS1 in CRC. We analyzed three independent microarray datasets of CRC tissues from GEO and found that ZFAS1 expression was remarkably upregulated in all three datasets. Moreover, we validated the overexpression of ZFAS1 in CRC tissues compared with normal tissues and found that ZFAS1 was positively correlated with tumor size and metastasis in CRC. Knockdown of ZFAS1 significantly suppressed the malignant phenotype and lipogenesis of CRC cells. Mechanistically, ZFAS1 binds polyadenylate-binding protein 2 (PABP2) to stabilize SREBP1 mRNA, thereby increasing the expression of SREBP1 and its target genes stearoyl-CoA desaturase (SCD1) and fatty acid synthase (FASN), thus promoting CRC lipid accumulation. These data demonstrated that ZFAS1 could act as an oncogene for CRC and that ZFAS1 reprograms lipid metabolism by binding with PABP2 to stabilize SREBP1 mRNA accumulation, implicating it as a novel and potent target for the treatment of CRC.
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BACKGROUND: Immune microenvironment is well recognized as a critical regulator across cancer types, despite its complex roles in different disease conditions. Intrahepatic cholangiocarcinoma (iCCA) is characterized by a tumor-reactive milieu, emphasizing a deep insight into its immunogenomic profile to provide prognostic and therapeutic implications. METHODS: We performed genomic, transcriptomic, and proteomic characterization of 255 paired iCCA and adjacent liver tissues. We validated our findings through H&E staining (n=177), multiplex immunostaining (n=188), single-cell RNA sequencing (scRNA-seq) (n=10), in vitro functional studies, and in vivo transposon-based mouse models. RESULTS: Integrated multimodule data identified three immune subgroups with distinct clinical, genetic, and molecular features, designated as IG1 (immune-suppressive, 25.1%), IG2 (immune-exclusion, 42.7%), and IG3 (immune-activated, 32.2%). IG1 was characterized by excessive infiltration of neutrophils and immature dendritic cells (DCs). The hallmark of IG2 was the relatively higher tumor-proliferative activity and tumor purity. IG3 exhibited an enrichment of adaptive immune cells, natural killer cells, and activated DCs. These immune subgroups were significantly associated with prognosis and validated in two independent cohorts. Tumors with KRAS mutations were enriched in IG1 and associated with myeloid inflammation-dominated immunosuppression. Although tumor mutation burden was relatively higher in IG2, loss of heterozygosity in human leucocyte antigen and defects in antigen presentation undermined the recognition of neoantigens, contributing to immune-exclusion behavior. Pathological analysis confirmed that tumor-infiltrating lymphocytes and tertiary lymphoid structures were both predominant in IG3. Hepatitis B virus (HBV)-related samples tended to be under-represented in IG1, and scRNA-seq analyses implied that HBV infection indeed alleviated myeloid inflammation and reinvigorated antitumor immunity. CONCLUSIONS: Our study elucidates that the immunogenomic traits of iCCA are intrinsically heterogeneous among patients, posing great challenge and opportunity for the application of personalized immunotherapy.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Animais , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Vírus da Hepatite B , Humanos , Inflamação , Camundongos , Proteômica , Microambiente TumoralRESUMO
Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease that affects males. It is caused by the expansion of a polyglutamine (polyQ) tract in androgen receptors. Female carriers are usually asymptomatic. No specific treatment has been established. Our transgenic mouse model carrying a full-length human androgen receptor with expanded polyQ has considerable gender-related motor impairment. This phenotype was abrogated by castration, which prevented nuclear translocation of mutant androgen receptors. We examined the effect of androgen-blockade drugs on our mouse model. Leuprorelin, a lutenizing hormone-releasing hormone (LHRH) agonist that reduces testosterone release from the testis, rescued motor dysfunction and nuclear accumulation of mutant androgen receptors in male transgenic mice. Moreover, leuprorelin treatment reversed the behavioral and histopathological phenotypes that were once caused by transient increases in serum testosterone. Flutamide, an androgen antagonist promoting nuclear translocation of androgen receptors, yielded no therapeutic effect. Leuprorelin thus seems to be a promising candidate for the treatment of SBMA.
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Leuprolida/uso terapêutico , Transtornos Musculares Atróficos/tratamento farmacológico , Peptídeos/metabolismo , Antagonistas de Androgênios/uso terapêutico , Animais , Modelos Animais de Doenças , Feminino , Flutamida/uso terapêutico , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Atividade Motora/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Transtornos Musculares Atróficos/metabolismo , Tamanho do Órgão , Fenótipo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Medula Espinal/metabolismo , Medula Espinal/patologia , Testosterona/metabolismo , Testosterona/farmacologiaRESUMO
BACKGROUND: With the knowledge of oligometastases, primary surgery plays an increasingly vital role in metastatic non-small cell lung cancer. We aimed to evaluate the survival benefit of primary surgery based on metastatic patterns. MATERIALS AND METHODS: The selected patients with stage IV extrathoracic metastatic (m1b) non-small cell lung cancer between 2010 and 2015 were included in a retrospective cohort study from the Surveillance, Epidemiology, and End Results (SEER) database. Multiple imputation was used for the missing data. Patients were divided into 2 groups depending on whether surgery was performed. After covariate balancing propensity score (CBPS) weighting, multivariate Cox regression models and Kaplan-Meier survival curve were built to identify the survival benefit of different metastatic patterns. RESULTS: Surgery can potentially increase the overall survival (OS) (adjusted HR: 0.68, P < 0.001) of non-small cell lung cancer. The weighted 3-year OS in the surgical group was 16.9%, compared with 7.8% in the nonsurgical group. For single organ metastasis, surgery could improve the survival of metastatic non-small cell lung cancer. Meanwhile, no significant survival improvements in surgical group were observed in patients with multiple organ metastases. CONCLUSION: The surgical survival benefits for extrathoracic metastatic non-small cell lung cancer could be divided by metastatic pattern.
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Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Tomada de Decisão Clínica , Gerenciamento Clínico , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Programa de SEER , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Infection and severe trauma can result in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and eventually pulmonary fibrosis. Epithelial-to-mesenchymal transition (EMT) is related to pulmonary fibrosis. Our study found that pyocyanin (PCN) could promote apoptosis and EMT in alveolar type II epithelial A549 cells. We hypothesized that there might be a common mechanism related to both apoptosis and EMT in A549 cells. The aim of this study was to determine whether reactive oxygen species (ROS) induced by PCN is the common stimulus upstream of apoptosis and EMT as well as the relevant signalling pathways. A549 cells were challenged with PCN; ROS was then detected by immunofluorescence, and apoptosis was measured by flow cytometry. Caspases, EMT markers and the TGF-ß/Smad pathway were assessed by Western blot, qPCR or ELISA. The results showed that PCN promoted ROS production, and the apoptosis rate was clearly increased. E-cadherin downregulation, vimentin and α-SMA upregulation in A549 cells, cleaved caspase-9 and caspase-3, TGF-ß1 and activated Smad2/3 were also detected. Interestingly, the protein expression of cleaved caspase-3 and vimentin was highly positively correlated. Inhibition of ROS could partially reverse PCN-induced EMT and apoptosis in A549 cells, and EMT could also be reversed by TGF-ß1 inhibitors. In conclusion, ROS may be a common activating mechanism of apoptosis and EMT in alveolar epithelial cells, during which the degree of apoptosis is positively related to EMT. ROS may induce alveolar epithelial cell apoptosis through the mitochondrial pathway or endoplasmic reticulum pathway. ROS activates TGF-ß1, followed by SMADs, eventually inducing EMT.
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Células Epiteliais Alveolares/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Piocianina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Células A549/efeitos dos fármacos , Lesão Pulmonar Aguda/metabolismo , Humanos , Síndrome do Desconforto Respiratório/metabolismoRESUMO
Bisphenol A (BPA) is a widely used raw material that can be detected both in the environment and in the human body. Due to its estrogen-like effects, wide concerns have been raised about the potential role of BPA in the initiation and development of hormone-dependent cancers. Ovarian cancer is the most common reproductive system cancer and has a high mortality rate in women. Despite recent investigations into BPA's carcinogenic effects, studies on its role in ovarian cancer development remain limited. In this study, we aimed to assess the effect of BPA at various environmentally relevant concentrations on proliferation and metastasis of ovarian cancer cells. We discovered that BPA can stimulate proliferation of OVCAR-3 ovarian cancer cells after exposure for up to 5 days. Strikingly, BPA enhanced ovarian cancer cell migration, invasion, and adhesion (to vascular endothelial cells) through upregulation of matrix metalloproteinase-2 (MMP-2), MMP-9, and intercellular cell adhesion molecule-1 (IMAC-1). The stimulatory effects of BPA on cancer cell proliferation and metastasis were reversed by treatment with an ERα inhibitor, but not by treatment with an ERß inhibitor. Together, these results suggest that BPA induces proliferation and metastasis of ovarian cancer cells through ERα signaling pathways. This study provides new insights into the carcinogenic effects of BPA with regard to ovarian cancer.
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Receptor alfa de Estrogênio , Neoplasias Ovarianas , Apoptose , Compostos Benzidrílicos/toxicidade , Linhagem Celular Tumoral , Proliferação de Células , Células Endoteliais , Feminino , Humanos , Metaloproteinase 2 da Matriz , Fenóis , Receptores de EstrogênioRESUMO
Escherichia coli has been known to cause a variety of infectious diseases. The conventional enzyme-linked immunosorbent assay (ELISA) is a well-known method widely used to diagnose a variety of infectious diseases. This method is expensive and requires considerable time and effort to conduct and complete multiple integral steps. We previously proposed the use of paper-based ELISA to rapidly detect the presence of E. coli. This approach has demonstrated utility for point-of-care (POC) urinary tract infection diagnoses. Paper-based ELISA, while advantageous, still requires the execution of several procedural steps. Here, we discuss the design and experimental implementation of a turntable paper-based device to simplify the paper-based ELISA protocols for the detection of E. coli. In this process, antibodies or reagents are preloaded onto zones of a paper-based device and allowed to dry before use. We successfully used this device to detect E. coli with a detection limit of 105 colony-forming units (colony-forming unit [CFU])/mL.