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1.
Nat Prod Res ; : 1-8, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35392742

RESUMO

A new 3,8''-flavanone-flavonol dimer gnidiflavanone-flavonol (1) and 10 known compounds (2-11), including four rare primula-type flavones 2-5, were isolated from the roots of Gnidia apiculata. Compounds 2-5 and 7 were reported for the first time from the plant family Thymelaeceae. Structures of the isolated compounds were established by spectroscopic data, including 1D and 2D NMR (COSY, HMBC, HSQC and ROESY) and mass spectrometry, as well as by the comparison with literature data. The crude roots extract and isolated compounds were evaluated for antimicrobial and antiplasmodial activities. Among isolated compounds, 6-hydroxyflavone (4) and 6-O-acetylflavone (4a) showed antiplasmodial activity against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum.

2.
Materials (Basel) ; 15(8)2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35454614

RESUMO

The UV durability of carbon fiber composites has been a concern. In this work, UV irradiation on carbon fiber-reinforced polymer (CFRP) materials was performed using an artificial accelerated UV aging chamber to investigate the effect of UV exposure on carbon fiber composites. UV aging caused some of the macromolecular chains on the surface resin to break, resulting in the loss of small molecules and loss of mass. After 80 days of UV irradiation exposure, a significant decline in the macroscopic mechanical properties occurred in the longitudinal direction, with the largest decrease of 23% in longitudinal compressive strength and a decreasing trend in the transverse mechanical properties at the later stage of aging. The microscopic mechanical properties of the CFRP specimens were characterized using nanoindentation, and it was found that UV aging had an embrittlement effect on the matrix, and its hardness/modulus values were higher than the initial values with UV exposure. The fibers were less affected by UV irradiation.

3.
J Healthc Eng ; 2022: 9148650, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35368930

RESUMO

Objective: To explore the effect of resveratrol (RES) combined with donepezil hydrochloride on inflammatory factor level and cognitive function level of patients with Alzheimer's disease (AD). Methods: A total of 90 AD patients treated in our hospital from June 2019 to June 2020 were selected as the study objects and divided into the control group (CG) and experimental group (EG) by the randomized and double-blind method, with 45 cases each. Patients in CG received donepezil hydrochloride treatment, and on this basis, those in EG received additional RES treatment, so as to compare the clinical indicators between the two groups. Results: Compared with CG after treatment, EG obtained significantly higher good rate, MMSE score, and FIM score (P < 0.05) and obviously lower clinical indicators and ADAS-cog score (P < 0.001), and between CG and EG, no obvious difference in total incidence rate of adverse reactions was observed after treatment (P > 0.05). Conclusion: Combining RES with donepezil hydrochloride has significant clinical efficacy in treating AD, which can effectively improve patients' inflammatory factor indicators, promote their cognitive function, and facilitate patient prognosis.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Cognição , Donepezila/farmacologia , Donepezila/uso terapêutico , Humanos , Indanos/farmacologia , Indanos/uso terapêutico , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico
4.
COPD ; 19(1): 118-124, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35385369

RESUMO

OBJECTIVE: We aimed to establish an easy-to-use screening questionnaire with risk factors and suspected symptoms of COPD for primary health care settings. METHODS: Based on a nationwide epidemiological study of pulmonary health among adults in mainland China (China Pulmonary Health, CPH study) between 2012 and 2015, participants ≥40 years who completed the questionnaire and spirometry tests were recruited and randomly divided into development set and validation set by the ratio of 2:1. Parameters including sex, age, BMI, residence, education, smoking status, smoking pack-years, biomass exposure, parental history of respiratory diseases and daily respiratory symptoms were initially selected for the development of scoring system. Receiver operating characteristic (ROC) curve, area under curve (AUC), positive and negative predictive values were calculated in development set and validation set. RESULTS: After random split by 2:1 ratio, 22443 individuals were assigned to development set and 11221 to validation set. Ten variables were significantly associated with COPD independently in development set after a stepwise selection by multivariable logistic model and used to develop scoring system. The scoring system yielded good discrimination, as measured by AUC of 0.7737, and in the validation set, the AUC was 0.7711. When applying a cutoff point of ≥16, the sensitivity in development set was 0.69 (0.67 - 0.71); specificity 0.72 (0.71 - 0.73), PPV 0.25 (0.24 - 0.26) and NPV 0.94 (0.94 - 0.95). CONCLUSION: We developed and validated a comprehensive screening questionnaire, COPD-CPHS, with good discrimination. The score system still needs to be validated by large cohort in the future.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2042504 .


Assuntos
Doença Pulmonar Obstrutiva Crônica , Adulto , Área Sob a Curva , China/epidemiologia , Estudos Epidemiológicos , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Curva ROC , Espirometria , Inquéritos e Questionários
5.
Front Mol Biosci ; 9: 839259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309511

RESUMO

Background: At present, few studies have reported the metabolic profiles of lung tissue in patients with COPD. Our study attempted to analyze the lung metabolome in male COPD patients and to screen the overlapping biomarkers of the lung and plasma metabolomes. Methods: We performed untargeted metabolomic analysis of normal lung tissue from two independent sets (the discovery set: 20 male COPD patients and 20 controls and the replication set: 47 male COPD patients and 27 controls) and of plasma samples from 80 male subjects containing 40 COPD patients and 40 controls. Results: We found glycerophospholipids (GPs) and Amino acids were the primary classes of differential metabolites between male COPD patients and controls. The disorders of GPs metabolism and the valine, leucine and isoleucine biosynthesis metabolism pathways were identified in lung discovery set and then also validated in the lung replication set. Combining lung tissue and plasma metabolome, Phytosphingosine and l-tryptophan were two overlapping metabolites biomarkers. Binary logistic regression suggested that phytosphingosine together with l-tryptophan was closely associated with male COPD and showed strong diagnostic power with an AUC of 0.911 (95% CI: 0.8460-0.9765). Conclusion: Our study revealed the metabolic perturbations of lung tissues from male COPD patients. The detected disorders of GPs and amino acids may provide an insight into the pathological mechanism of COPD. Phytosphingosine and l-tryptophan were two novel metabolic biomarkers for differentiating COPD patients and controls.

6.
Medicine (Baltimore) ; 101(11)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35356948

RESUMO

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) comprises about 50% of the cases of heart failure (HF), but so far there is no effective treatment strategy. This study used bibliometric methods to analyze the scientific literature on HFpEF in 2009 to 2020, and evaluate the global scientific output of HFpEF research, in order to explore the research status and trends in this field. METHODS: Documents about the HFpEF research published in 2009 to 2020 were retrieved from Science Citation Index Expanded (SCIE) in Web of Science. This study used bibliometrix R-package, VOSviewer, and CiteSpace to conduct the bibliometric analysis. RESULTS: A total of 1971 documents (1508 articles and 283 reviews) were retrieved to construct the local HFpEF literature collection for analysis. The number of annual documents had increased year by year in general, from 24 to 353. Relevant documents were mainly written in English, and mostly focused on the field of "Cardiovascular System Cardiology." USA ranked first in the relevant countries/regions with most documents, and the leading affiliation was Mayo Clin. Shah SJ was the most productive author, while Borlaug BA ranked highest among the local cited authors and G-index. Circulation was the most local cited source, while Eur J Heart Fail published the most documents and was rated as the top source in terms of G-index. "Paulus WJ, 2013, J Am Coll Cardiol" was the top local cited document within the local HFpEF literature collection, while "Owan TE, 2006, New Engl J Med" outside the local HFpEF literature collection was the most local cited reference. The keywords such as "mortality," "dysfunction," "diagnosis," "outcomes," and "diastolic dysfunction" were most frequent, while "hemodynamics," "comorbidity," "myocardial infarction," "inflammation," and "phenotype" indicated research frontiers or emerging trends. Furthermore, this study also found some deeper bibliometric relationships through bibliographic networks. CONCLUSIONS: Due to the multi-dimensional bibliometric analysis, this study shows a wide view of scientific productivity related to HFpEF, and provides valuable guidance for researchers interested in HFpEF, assisting them in understanding the research status, identifying potential collaborators, discovering research hotspots and frontiers, and conducting more in-depth research.


Assuntos
Insuficiência Cardíaca , Bibliometria , Eficiência , Insuficiência Cardíaca/terapia , Humanos , Publicações , Volume Sistólico
7.
Molecules ; 27(3)2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35163893

RESUMO

Aquilaria sinensis (Lour.) Spreng is known for its resinous secretion (agarwood), often secreted in defense against injuries. We investigated the effects of A. sinensis flower extract (AF) on peroxisome proliferator-activated receptors alpha and gamma (PPARα and PPARγ), liver X receptor (LXR), glucose uptake, and lipid accumulation (adipogenesis). Activation of PPARα, PPARγ and LXR was determined in hepatic (HepG2) cells by reporter gene assays. Glucose uptake was determined in differentiated muscle (C2C12) cells using 2-NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose). Adipogenesis was determined in adipocytes (3T3-L1 cells) by Oil red O staining. At a concentration of 50 µg/mL, AF caused 12.2-fold activation of PPARα and 5.7-fold activation of PPARγ, while the activation of LXR was only 1.7-fold. AF inhibited (28%) the adipogenic effect induced by rosiglitazone in adipocytes and increased glucose uptake (32.8%) in muscle cells at 50 µg/mL. It was concluded that AF acted as a PPARα/γ dual agonist without the undesired effect of adipogenesis and exhibited the property of enhancing glucose uptake. This is the first report to reveal the PPARα/γ dual agonistic action and glucose uptake enhancing property of AF along with its antiadipogenic effect, indicating its potential in ameliorating the symptoms of metabolic syndrome.


Assuntos
Síndrome Metabólica , Thymelaeaceae , Células 3T3-L1 , Adipogenia , Animais , Flores/metabolismo , Síndrome Metabólica/tratamento farmacológico , Camundongos , PPAR gama/metabolismo , Extratos Vegetais/farmacologia , Thymelaeaceae/metabolismo
9.
Environ Res ; 209: 112877, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35131324

RESUMO

BACKGROUND: Studies on the association of greenness with respiratory health are scarce in developing countries, and previous studies in China have focused on only one or two indicators of lung function. OBJECTIVE: The study aims to evaluate the associations of residential greenness with full-spectrum lung function indicators and prevalence of chronic obstructive pulmonary disease (COPD). METHODS: This nationwide cross-sectional survey included 50,991 participants from the China Pulmonary Health study. Lung function indicators included four categories: indicators of obstructive ventilatory dysfunction (FEV1, FVC and FEV1/FVC); an indicator of large-airway dysfunction (PEF); indicators of small-airway dysfunction (FEF25-75% and FEV3/FEV6); and other indicators. Residential greenness was assessed by the Normalized Difference Vegetation Index (NDVI). Multivariable linear regression models and logistic regression models were used to analyze associations of greenness with lung function and COPD prevalence. RESULTS: Within the 500 m buffer, an interquartile range (IQR) increase in NDVI was associated with higher FEV1 (24.76 mL), FVC (16.52 mL), FEV1/FVC (0.38), FEF50% (56.34 mL/s), FEF75% (33.43 mL/s), FEF25-75% (60.73 mL/s), FEV3 (18.59 mL), and FEV6 (21.85 mL). However, NDVI was associated with lower PEF. In addition, NDVI was significantly associated with 10% lower odds of COPD. The stratified analyses found that the associations were only significant in middle-young people, females, and nonsmokers. The associations were influenced by geographic regions. CONCLUSIONS: Residential greenness was associated with better lung function and lower odds of COPD in China. These findings provide a scientific basis for healthy community planning.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Adolescente , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Pulmão , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Testes de Função Respiratória
10.
Int J Infect Dis ; 117: 37-44, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35108608

RESUMO

OBJECTIVES: This study aimed to assess the current incidence and risk factors for polymyxin B-associated acute kidney injury (AKI) in Chinese hospitals for a more effective clinical use for polymyxin B. METHODS: This multicenter, retrospective cohort study included patients from 14 Chinese teaching hospitals who received polymyxin B therapy. Univariate and multivariate logistic regression models were used to determine the factors associated with polymyxin B-associated incident AKI. Furthermore, a multivariate logistic regression model was used to identify the independent risk factors for AKI. RESULTS: A total of 251 patients were included in the analysis. The overall incidence of AKI was 33.5%. A multivariate logistic regression model identified the loading dose (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.01-3.38; P = 0.0491) and the use of two or more nephrotoxic drugs (HR, 3.56; 95% CI, 1.55-8.18; P = 0.0029) as independent risk factors for the occurrence of AKI. Meanwhile, the estimated glomerular filtration rate had a protective effect (HR, 0.99; 95% CI, 0.98-0.99; P = 0.0006) on the occurrence of AKI. The daily dose, cumulative dose, and treatment duration of polymyxin B did not affect the occurrence of AKI. CONCLUSIONS: The use of polymyxin B loading doses and the combined use of multiple nephrotoxic drugs are independent risk factors for polymyxin B-associated AKI. The severity of AKI may be higher in patients with elevated baseline creatinine levels.


Assuntos
Injúria Renal Aguda , Polimixina B , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Antibacterianos/efeitos adversos , Humanos , Polimixina B/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
11.
J Asthma ; : 1-9, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35168451

RESUMO

Club cell 10-kDa protein (CC10) is a documented biomarker for airway obstructive diseases. Primarily produced by nonciliated club cells in the distal airway and in nasal epithelial cells, CC10 suppresses Th2 cell differentiation and Th2 cytokine production. In this study, we aimed to determine whether CC10 can also be used as an alternative biomarker for identifying Type 2 (T2) asthma.74 patients with asthma, and 24 healthy controls were enrolled in the study. T2-high asthma was defined as elevation in two or more biomarkers, such as sputum eosinophilia ≥ 3%, high blood eosinophils ≥ 300/µL, or high FeNO ≥ 30 ppb. T2-low asthma was defined as no elevation in biomarkers. Enzyme-linked immunosorbent assay (ELISA) was used to assess the CC10 levels in plasma.The plasma CC10 level in patients with T2-high asthma was lower than that of patients with T2-low asthma and healthy controls (P < 0.05). To distinguish between T2-high and T2-low phenotype in patients with asthma, a receiver-operating characteristic (ROC) analysis was performed. It showed a sensitivity of 58.1% and specificity of 78.0% when using 22.74 ng/ml of plasma CC10. Correlation analysis indicated that the plasma CC10 level was inversely correlated with sputum eosinophil, blood eosinophil, and FeNO, and positively correlated with log PD20. However, no correlation with sputum neutrophil percentages, macrophage percentages, IgE, or lung function was found.Plasma CC10 is potentially useful in predicting T2-high and T2-low asthma. Lower plasma CC10 was associated with enhanced airway hyperresponsiveness, and Type 2 inflammation.

12.
Oxid Med Cell Longev ; 2022: 9300269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35035670

RESUMO

Extensive inflammation and apoptosis in structural cells of the lung are responsible for the progression and pathogenesis of chronic obstructive pulmonary disease (COPD). Myotubularin-related protein 14 (MTMR14) has been shown to participate in various biological processes, including apoptosis, inflammation, and autophagy. Nonetheless, the role of MTMR14 in COPD remains elusive. In the present study, we explored the expression of MTMR14 in human lung tissues and investigated the effects of overexpressed MTMR14 on in vitro and in vivo COPD models. Moreover, one of the possible mechanisms of MTMR14 alleviating COPD was explored based on mitochondrial function and mitophagy homeostasis. The results showed that MTMR14 expression was reduced in COPD patients' lungs in comparison to control subjects. MTMR14 overexpression inhibited cigarette smoke extract-induced inflammation and apoptosis and improved mitochondrial function and mitophagy in vitro. Further verification was carried out in COPD model mice. MTMR14 overexpression inhibited lung inflammation and reduced levels of IL-6 and KC in bronchoalveolar lavage fluid, as well as prevented emphysema and a decline in lung function. Furthermore, MTMR14 overexpression improved mitochondrial function and mitophagy to a certain extent. Collectively, our data support the hypothesis that MTMR14 participates in the pathogenesis of COPD. Improving mitochondrial function and mitophagy homeostasis may be one of the mechanisms by which MTMR14 alleviates COPD and may potentially be a novel therapeutic target for COPD.


Assuntos
Inflamação/metabolismo , Pneumopatias/terapia , Monoéster Fosfórico Hidrolases/metabolismo , Doença Pulmonar Obstrutiva Crônica/urina , Enfisema Pulmonar/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Modelos Animais de Doenças , Humanos , Pneumopatias/genética , Pneumopatias/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/genética , Enfisema Pulmonar/genética , Enfisema Pulmonar/patologia
14.
Respir Res ; 23(1): 6, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35016680

RESUMO

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a chronic progressive advanced disorder pathologically characterized by pulmonary vascular remodeling. Notch4 as a cell surface receptor is critical for vascular development. However, little is known about the role and mechanism of Notch4 in the development of hypoxic vascular remodeling. METHODS: Lung tissue samples were collected to detect the expression of Notch4 from patients with HPH and matched controls. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic and normoxic conditions. Real-time quantitative PCR and western blotting were used to examine the mRNA and protein levels of Notch4. HPASMCs were transfected with small interference RNA (siRNA) against Notch4 or Notch4 overexpression plasmid, respectively. Cell viability, cell proliferation, apoptosis, and migration were assessed using Cell Counting Kit-8, Edu, Annexin-V/PI, and Transwell assay. The interaction between Notch4 and ERK, JNK, P38 MAPK were analyzed by co-immunoprecipitation. Adeno-associated virus 1-mediated siRNA against Notch4 (AAV1-si-Notch4) was injected into the airways of hypoxic rats. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular remodeling were evaluated. RESULTS: In this study, we demonstrate that Notch4 is highly expressed in the media of pulmonary vascular and is upregulated in lung tissues from patients with HPH and HPH rats compared with control groups. In vitro, hypoxia induces the high expression of Delta-4 and Notch4 in HPASMCs. The increased expression of Notch4 promotes HPASMCs proliferation and migration and inhibits cells apoptosis via ERK, JNK, P38 signaling pathways. Furthermore, co-immunoprecipitation result elucidates the interaction between Notch4 and ERK/JNK/P38. In vivo, silencing Notch4 partly abolished the increase in RVSP and pulmonary vascular remodeling caused by hypoxia in HPH rats. CONCLUSIONS: These findings reveal an important role of the Notch4-ERK/JNK/P38 MAPK axis in hypoxic pulmonary remodeling and provide a potential therapeutic target for patients with HPH.


Assuntos
Regulação da Expressão Gênica , Hipertensão Pulmonar/genética , Hipóxia/complicações , Miócitos de Músculo Liso/metabolismo , Receptor Notch4/genética , Remodelação Vascular/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Animais , Apoptose , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/patologia , Hipóxia/genética , Hipóxia/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Miócitos de Músculo Liso/patologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptor Notch4/biossíntese , Transdução de Sinais , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/biossíntese
15.
Eur Respir J ; 2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35086828

RESUMO

Although DNA methylation has been recognized in the pathogenesis of idiopathic pulmonary fibrosis (IPF), the exact mechanisms, however, are yet to be fully addressed. Herein, we demonstrated that lungs originated from IPF patients and mice after bleomycin (BLM)-induced pulmonary fibrosis are characterized by the altered DNA methylation along with overexpression of methyl-CpG-binding domain 2 (MBD2) in myofibroblasts, a reader responsible for interpreting DNA methylome-encoded information. Specifically, depletion of Mbd2 in fibroblasts or myofibroblasts protected mice from BLM-induced pulmonary fibrosis coupled with a significant reduction of fibroblast differentiation. Mechanistically, TGF-ß1 induced a positive feedback regulatory loop between transforming growth factor-ß receptor I (TßRI), Smad3 and Mbd2, and erythroid differentiation regulator 1 (Erdr1). TGF-ß1 induced fibroblasts to undergo a global DNA hypermethylation along with Mbd2 overexpression in a TßRI/Smad3 dependent manner, and Mbd2 selectively bound to the methylated CpG DNA within the Erdr1 promoter to repress its expression, through which it enhances TGF-ß/Smads signaling to promote fibroblast differentiating into myofibroblast and exacerbate pulmonary fibrosis. Therefore, enhancing Erdr1 expression strikingly reversed established pulmonary fibrosis. Collectively, our data support that strategies aimed at silencing Mbd2 or increasing Erdr1 could be viable therapeutic approaches for prevention and treatment of pulmonary fibrosis in clinical settings.

16.
Comput Intell Neurosci ; 2022: 9743123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35035470

RESUMO

Recent image captioning models based on the encoder-decoder framework have achieved remarkable success in humanlike sentence generation. However, an explicit separation between encoder and decoder brings out a disconnection between the image and sentence. It usually leads to a rough image description: the generated caption only contains main instances but neglects additional objects and scenes unexpectedly, which reduces the caption consistency of the image. To address this issue, we proposed an image captioning system within context-fused guidance in this paper. It incorporates regional and global image representation as the compositional visual features to learn the objects and attributes in images. To integrate image-level semantic information, the visual concept is employed. To avoid misleading decoding, a context fusion gate is introduced to calculate the textual context by selectively aggregating the information of visual concept and word embedding. Subsequently, the context-fused image guidance is formulated based on the compositional visual features and textual context. It provides the decoder with informative semantic knowledge. Finally, a captioner with a two-layer LSTM architecture is constructed to generate captions. Moreover, to overcome the exposure bias, we train the proposed model through sequence decision-making. The experiments conducted on the MS COCO dataset show the outstanding performance of our work. The linguistic analysis demonstrates that our model improves the caption consistency of the image.


Assuntos
Linguística , Semântica , Idioma , Aprendizagem
17.
Free Radic Biol Med ; 179: 213-228, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34808333

RESUMO

Chemoresistance is a major challenge for the treatment of cancer with metastasis. We investigated the mechanisms of lipid metabolites involved in drug resistance. Here, metastatic cancer cells isolated from mouse models were resistant to paclitaxel treatment in vitro and in vivo when compared with parental cancer cells. FOXM1, an oncogenic transcriptional factor, was highly expressed in metastatic cancer cells, and overexpression of FOXM1 conferred parental cancer cells resistance to paclitaxel. Lipidomic analysis showed that FOXM1 increased unsaturated triglyceride (TG) and phosphatidylcholine (PC) abundance, which are the main components of lipid droplet (LD). Inhibition of LD formation sensitized cells to paclitaxel. Mechanistically, the enzyme phospholipase D1 (PLD1) was identified as a potential effector target of FOXM1. PLD1 promoted LD accumulation, which reduced the level of reactive oxygen species (ROS) and maintained endoplasmic reticulum (ER) homeostasis in resistant cells with the treatment of paclitaxel. Moreover, inhibition of PLD1 reversed FOXM1-conferred paclitaxel resistance in vitro and in vivo. This study, for the first time, reveals the role of FOXM1-mediated PLD1 in LD accumulation and paclitaxel resistance. Targeting PLD1 or LD formation may help reverse chemoresistance in metastatic cancer cells. Generally, our results identified FOXM1 as a driver of paclitaxel resistance via activation of PLD1 to promote of LD accumulation, which contributes to the maintenace of ER homeostasis when metastatic cancer cells are confronted with ROS induced by paclitaxel.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Proteína Forkhead Box M1 , Neoplasias , Paclitaxel , Animais , Linhagem Celular Tumoral , Proteína Forkhead Box M1/genética , Gotículas Lipídicas , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Paclitaxel/farmacologia , Fosfolipase D , Espécies Reativas de Oxigênio
18.
Am J Respir Crit Care Med ; 205(4): 450-458, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34813411

RESUMO

Rationale: It remains unknown whether long-term ozone exposure can impair lung function. Objectives: To investigate the associations between long-term ozone exposure and adult lung function in China. Methods: Lung function results and diagnosis of small airway dysfunction (SAD) were collected from a cross-sectional study, the China Pulmonary Health Study (N = 50,991). We used multivariable linear and logistic regression models to examine the associations of long-term ozone exposure with lung function parameters and SAD, respectively, adjusting for demographic characteristics, individual risk factors, and longitudinal trends. We then performed a stratification analysis by chronic obstructive pulmonary disease (COPD). Measurements and Main Results: We observed that each 1 SD (4.9 ppb) increase in warm-season ozone concentrations was associated with a 14.2 ml/s (95% confidence interval [CI], 8.8-19.6 ml/s] decrease in forced expiratory flow at the 75th percentile of vital capacity and a 29.5 ml/s (95% CI, 19.6-39.5 ml/s) decrease in mean forced expiratory flow between the 25th and 75th percentile of vital capacity. The odds ratio of SAD was 1.09 (95% CI, 1.06-1.11) for a 1 SD increase in warm-season ozone concentrations. Meanwhile, we observed a significant association with decreased FEV1/FVC but not with FEV1 or FVC. The association estimates were greater in the COPD group than in the non-COPD group. Conclusions: We found independent associations of long-term ozone exposure with impaired small airway function and higher SAD risks, while the associations with airflow obstruction were weak. Patients with COPD appear to be more vulnerable.


Assuntos
Poluentes Atmosféricos/toxicidade , Exposição Ambiental/efeitos adversos , Pulmão/fisiopatologia , Ozônio/toxicidade , Adulto , Idoso , China , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória
19.
Nat Prod Res ; 36(1): 8-17, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32525748

RESUMO

Kadsura heteroclita Roxb. Craib. (Schisandraceae), is a vine plant mainly distributed in southwest part of China. A new dibenzocyclooctadiene lignan, kadsulignan W (1), along with eleven known lignans (2-12) were isolated from chloroform soluble fraction of stems of Kadsura heteroclita. The structure of new lignan was elucidated by extensive spectroscopic techniques, namely one- and two-dimensional NMR spectroscopy, and HRESI-MS analysis. The absolute configuration of the biphenyl ring in the new dibenzocyclooctadiene lignan was discerned by circular dichroism (CD) spectroscopy. Antioxidative effects of these compounds were evaluated on human isolated neutrophils, and compounds 5, 8, 9, and 10 were found to be strongly active with the IC50 of 36.68, 34.41, 35.97, and 33.65 µM, respectively. Furthermore, compound 8 was also found to be cytotoxic against human gastric cancer cells (BGC 823), and human cervical cancer cell lines (HeLa) with the IC50 values of 11.0, and 23.8 µM, respectively.


Assuntos
Kadsura , Lignanas , Ciclo-Octanos , Humanos , Estrutura Molecular , Caules de Planta
20.
J Pharm Biomed Anal ; 207: 114376, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34656935

RESUMO

Botanicals have played an important role in maintaining human health and well-being throughout history. During the past few decades in particular, the use of botanical health products has gained more popularity. Whereas, quality, safety and efficacy concerns have continuously been critical issues due to the intrinsic chemical complexity of botanicals. Chemical analytical technologies play an imperative role in addressing these issues. Nuclear magnetic resonance (NMR) spectroscopy has proven to be a powerful and useful tool for the investigation of botanical health products. In this review, NMR techniques and methodologies that have been successfully applied to the research and development of botanical health products in all stages, from plants to products, are discussed and summarized. Furthermore, applications of NMR together with other analytical techniques in a variety of domains of botanical health products investigation, such as plant species differentiation, adulteration detection, and bio-activity evaluation, are discussed and illustrated with typical examples. This article provides an overview of the potential uses of NMR techniques and methodologies in an attempt to further promote their recognition and utilization in the field of botanical health products analysis and quality control.


Assuntos
Contaminação de Medicamentos , Plantas , Humanos , Espectroscopia de Ressonância Magnética , Controle de Qualidade
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