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1.
Environ Sci Technol ; 58(9): 4368-4380, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38386007

RESUMO

Despite the increasing health risks shown by the continuous detection of organophosphate esters (OPEs) in biota in recent years, information on the occurrence and potential risks of OPEs in marine mammals remains limited. This study conducted the first investigation into the body burdens and potential risks of 10 traditional OPEs (tOPEs) and five emerging OPEs (eOPEs) in 10 cetacean species (n = 84) from the northern South China Sea (NSCS) during 2005-2021. All OPEs, except for 2-ethylhexyl diphenyl phosphate (EHDPHP), were detected in these cetaceans, indicating their widespread occurrence in the NSCS. Although the levels of the ∑10tOPEs in humpback dolphins remained stable from 2005 to 2021, the concentrations of the ∑5eOPEs showed a significant increase, suggesting a growing demand for these new-generation OPEs in South China. Dolphins in proximity to urban regions generally exhibited higher OPE concentrations than those from rural areas, mirroring the environmental trends of OPEs occurring in this area. All OPE congeners, except for EHDPHP, in humpback dolphins exhibited a maternal transfer ratio >1, indicating that the dolphin placenta may not be an efficient barrier for OPEs. The observed significant correlations between levels of OPEs and hormones (triiodothyronine, thyroxine, and testosterone) in humpback dolphins indicated that OPE exposures might have endocrine disruption effects on the dolphin population.


Assuntos
Golfinhos , Retardadores de Chama , Animais , Monitoramento Ambiental , Bioacumulação , Ésteres , China , Organofosfatos , Fosfatos , Retardadores de Chama/análise
2.
BMC Cardiovasc Disord ; 24(1): 305, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38880872

RESUMO

BACKGROUND: The role of circular RNAs (circRNAs) as biomarkers of coronary artery disease (CAD) remains poorly explored. This study aimed to identify and validate potential circulating circRNAs as biomarkers for the diagnosis of CAD. METHODS: The expression profile of circRNAs associated with CAD was obtained from Gene Expression Omnibus (GEO) database. Differential expression analysis, weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operation (LASSO) were employed to identify CAD-related hub circRNAs. The expression levels of these hub circRNAs were validated using qRT-PCR in blood samples from 100 CAD patients and 100 controls. The diagnostic performance of these circRNAs was evaluated through logistic regression analysis, receiver operator characteristic (ROC) analysis, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Functional enrichment analyses were performed to predict the possible mechanisms of circRNAs in CAD. RESULTS: A total of ten CAD-related hub circRNAs were identified through WGCNA and LASSO analysis. Among them, hsa_circ_0069972 and hsa_circ_0021509 were highly expressed in blood samples of CAD patients, and they were identified as independent predictors after adjustment for relevant confounders. The area under the ROC curve for hsa_circ_0069972 and hsa_circ_0021509 was 0.760 and 0.717, respectively. The classification of patients was improved with the incorporation of circRNAs into the clinical model composed of conventional cardiovascular risk factors, showing an IDI of 0.131 and NRI of 0.170 for hsa_circ_0069972, and an IDI of 0.111 and NRI of 0.150 for hsa_circ_0021509. Functional enrichment analyses revealed that the hsa_circ_0069972-miRNA-mRNA network was enriched in TGF-ß、FoxO and Hippo signaling pathways, while the hsa_circ_0021509-miRNA-mRNA network was enriched in PI3K/Akt and MAPK signaling pathways. CONCLUSION: Hsa_circ_0069972 and hsa_circ_0021509 were identified by integrated analysis, and they are highly expressed in CAD patients. They may serve as novel biomarkers for CAD.


Assuntos
Algoritmos , Doença da Artéria Coronariana , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Valor Preditivo dos Testes , RNA Circular , Humanos , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , RNA Circular/genética , RNA Circular/sangue , Estudos de Casos e Controles , Pessoa de Meia-Idade , Masculino , Feminino , Reprodutibilidade dos Testes , Marcadores Genéticos , Transcriptoma , Idoso , Biomarcadores/sangue
3.
Clin Exp Allergy ; 53(11): 1187-1197, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37794659

RESUMO

BACKGROUND: Similar immune responses in the nasal and bronchial mucosa implies that nasal allergen challenge (NAC) is a suitable early phase experimental model for drug development targeting allergic rhinitis (AR) and asthma. We assessed NAC reproducibility and the effects of intranasal corticosteroids (INCS) on symptoms, physiology, and inflammatory mediators. METHODS: 20 participants with mild atopic asthma and AR underwent three single blinded nasal challenges each separated by three weeks (NCT03431961). Cohort A (n = 10) underwent a control saline challenge, followed by two allergen challenges. Cohort B (n = 10) underwent a NAC with no treatment intervention, followed by NAC with 14 days pre-treatment with saline nasal spray (placebo), then NAC with 14 days pre-treatment with INCS (220 µg triamcinolone acetonide twice daily). Nasosorption, nasal lavage, blood samples, forced expiratory volume 1 (FEV1), total nasal symptom score (TNSS), peak nasal inspiratory flow (PNIF) were collected up to 24 h after NAC. Total and active tryptase were measured as early-phase allergy biomarkers (≤30 min) and IL-13 and eosinophil cell counts as late-phase allergy biomarkers (3-7 h) in serum and nasal samples. Period-period reproducibility was assessed by intraclass correlation coefficients (ICC), and sample size estimates were performed using effect sizes measured after INCS. RESULTS: NAC significantly induced acute increases in nasosorption tryptase and TNSS and reduced PNIF, and induced late increases in nasosorption IL-13 with sustained reductions in PNIF. Reproducibility across NACs varied for symptoms and biomarkers, with total tryptase 5 min post NAC having the highest reproducibility (ICC = 0.91). Treatment with INCS inhibited NAC-induced IL-13 while blunting changes in TNSS and PNIF. For a similar crossover study, 7 participants per treatment arm are needed to detect treatment effects comparable to INCS for TNSS. CONCLUSION: NAC-induced biomarkers and symptoms are reproducible and responsive to INCS. NAC is suitable for assessing pharmacodynamic activity and proof of mechanism for drugs targeting allergic inflammation.


Assuntos
Asma , Rinite Alérgica Sazonal , Rinite Alérgica , Humanos , Alérgenos , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/tratamento farmacológico , Interleucina-13 , Reprodutibilidade dos Testes , Triptases , Estudos Cross-Over , Rinite Alérgica/diagnóstico , Rinite Alérgica/tratamento farmacológico , Corticosteroides/uso terapêutico , Asma/tratamento farmacológico , Biomarcadores
4.
Environ Sci Technol ; 57(9): 3713-3721, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36812292

RESUMO

The potential risks of per- and polyfluoroalkyl substance (PFAS) accumulation in nearshore dolphins are not well understood. Here, transcriptional activities of 12 PFAS on peroxisome proliferator-activated receptors (PPAR-α, -ß/δ, and -γ) in Indo-Pacific humpback dolphins (Sousa chinensis) were evaluated. All PFAS activated scPPAR-α in a dose-dependent manner. PFHpA exhibited the highest induction equivalency factors (IEFs). The order of IEFs for other PFAS was as follows: PFOA > PFNA > PFHxA > PFPeA > PFHxS > PFBA > PFOS > PFBuS ≈ PFDA ≫ PFUnDA and PFDoDA (not activated). The total induction equivalents (∑IEQs, 5537 ng/g wet weight) indicated that more attention should be paid to investigating contamination levels in dolphins, especially in PFOS (82.8% contribution to the ∑IEQs). The scPPAR-ß/δ and -γ were not affected by any PFAS, except for PFOS, PFNA, and PFDA. Furthermore, PFNA and PFDA could induce higher PPAR-ß/δ and PPAR-γ-mediated transcriptional activities than PFOA. Compared to human beings, PFAS might be more potent PPAR-α activators in humpback dolphins, suggesting that the dolphins may be more susceptible to the adverse effects of PFAS. Our results may be instructive for understanding the impacts of PFAS on marine mammal health due to the identical PPAR ligand-binding domain.


Assuntos
Golfinhos , Fluorocarbonos , Animais , Ácidos Graxos , Receptores Ativados por Proliferador de Peroxissomo , Ativação Transcricional
5.
Clin Exp Hypertens ; 45(1): 2180020, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36843004

RESUMO

BACKGROUND: As one of the essential hypertension (EH)-mediated target organ damage, carotid plaque is a crucial subclinical precursor for cardiovascular events. Therefore, it is vital to identify the risk factors and pathogenesis for EH with carotid plaque. METHODS: Based on our previous microarray analysis, we selected four circRNAs as the candidate circRNAs and detected their expression levels in blood of 192 subjects (64 healthy controls, 64 EH patients, and 64 EH patients with carotid plaque) by qRT-PCR analysis. The regulatory mechanism of circRNAs involved in carotid plaque was predicted by bioinformatics analysis. RESULTS: The level of hsa_circ_0124782 increased significantly and the levels of hsa_circ_0131618 and hsa_circ_0127342 decreased significantly in the EH group and EH with carotid plaque group compared with the control group (P < .05). Functional enrichment analysis showed that three circRNAs might be implicated in pathogenesis for carotid plaque. CONCLUSION: Our study revealed the relationship between three circRNAs and carotid plaque, suggesting that they may serve as potential biomarkers for EH with carotid plaque.


Assuntos
RNA Circular , RNA , Humanos , RNA Circular/genética , RNA/genética , Biomarcadores , Fatores de Risco , Hipertensão Essencial/genética
6.
Respir Res ; 23(1): 11, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042537

RESUMO

BACKGROUND: Airway mucus hypersecretion is one of the important pathological features of chronic obstructive pulmonary disease (COPD). MUC5B is the main mucin expressed in the airways of COPD patients and has been indicated to play an important role in airway defense. However, the specific biological function of MUC5B in COPD and the possible mechanism are not clear. METHODS: We established a COPD model with 24-week-old MUC5B-/- mice exposed to cigarette smoke and tested our hypothesis through lung function tests, HE and PAS staining, immunohistochemistry (IHC), western blot, q-PCR and ELISA. RESULTS: Compared with MUC5B+/+ mice, MUC5B-/- mice had worse general condition and lung function, increased inflammatory infiltration, reduced goblet cell differentiation as indicated by decreased PAS staining (PAS grade: 1.8 ± 0.24 vs. 0.6 ± 0.16), reduced MUC5AC expression (ELISA: 0.30 ± 0.01 vs. 0.17 ± 0.01 mg/ml, q-PCR: 9.4 ± 1.7 vs. 4.1 ± 0.1 fold, IHC score: 3.1 ± 0.9 vs. 1.6 ± 0.7), increased macrophage secretion of inflammatory factors (TNF-α and IL-6) and expression of downstream pathway factors (ERK1/2 and NF-κB), decreased expression of SPDEF and STAT6, and increased expression of FOXA2. CONCLUSION: The protective effect of MUC5B in the development of COPD was mediated by the promotion of goblet cell differentiation and the inhibition of inflammation. The role of MUC5B in regulating inflammation was related to macrophage function, and goblet cell differentiation was promoted by the induced expression of STAT6 and SPDEF. This study describes a mechanism of mucus hypersecretion and identifies MUC5B as a new target for the treatment of mucus hypersecretion.


Assuntos
Regulação da Expressão Gênica , Inflamação/genética , Pulmão/patologia , Mucina-5B/genética , Doença Pulmonar Obstrutiva Crônica/genética , RNA/genética , Animais , Líquido da Lavagem Broncoalveolar/citologia , Diferenciação Celular , Modelos Animais de Doenças , Inflamação/metabolismo , Inflamação/patologia , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mucina-5B/biossíntese , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia
7.
Environ Sci Technol ; 56(18): 13046-13057, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36031938

RESUMO

Marine mammals often accumulate high levels of environmental contaminants, even those that are globally regulated regarding usage, raising concerns about their health status. Here, we conducted the first investigation of tissue distribution, spatiotemporal trends, and potential risks of six organotin compounds (OTs) in Indo-Pacific humpback dolphins (n = 101) from the northern South China Sea during 2003-2021. We detected the highest level of hepatic triphenyltin in these humpback dolphins compared with the results reported in cetaceans globally, and the liver accumulated the highest OT concentrations than other analyzed tissues. Despite the downward trend of butyltins in humpback dolphins after the global ban on the use of OTs as antifouling paints, levels of phenyltins have continued to increase over the past 20 years, suggesting that the other applications of phenyltins in South China remain prevalent. In vitro and in vivo analyses revealed that tissue-relevant doses of OTs could induce agonistic effects on the dolphin peroxisome proliferator-activated receptor γ as a master regulator of lipid homeostasis and altered the dolphin fatty acid profiles. Our results highlight the lipid-disrupting effects of current OT exposure in humpback dolphins and emphasize the need for further efforts to eliminate OT contamination in South China.


Assuntos
Golfinhos , Compostos Orgânicos de Estanho , Poluentes Químicos da Água , Animais , China , Estuários , Ácidos Graxos , Lipídeos , Compostos Orgânicos de Estanho/análise , PPAR gama , Rios , Poluentes Químicos da Água/análise
8.
Clin Exp Hypertens ; 44(7): 601-609, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-35787223

RESUMO

BACKGROUND: At present, no early diagnostic markers for essential hypertension (EH)-induced subclinical target organs damage (such as carotid plaque) are available. This study aimed to identify the circular RNAs (circRNAs) in EH with carotid plaques, and assess their utility as biomarkers. METHODS: First, circRNAs were identified through microarry analysis and database prediction. Second, a case-control study of EH patients with carotid plaque (n = 100) and healthy controls (n = 100) was performed to evaluate circRNAs expression in peripheral blood. Finally, receiver operating characteristic (ROC) curve was established to evaluate the diagnostic value. RESULTS: Five circRNAs (hsa_circ_0105130, hsa_circ_0109569, hsa_circ_0072659, hsa_circ_0079586 and hsa_circ_0064684) were identified as the candidate circRNAs. We found that circRNAs were increased in case group compared with controls (P < .05). The results of ROC shown that these five circRNAs, especially hsa_circ_0109569 (AUC = 0.741), all had the moderate predictive value. CONCLUSIONS: Our study revealed circulating circRNAs may act as promising noninvasive biomarkers for early detection and population screening of EH-induced subclinical target organ injury.


Assuntos
RNA Circular , Biomarcadores , Estudos de Casos e Controles , Hipertensão Essencial , Humanos , Curva ROC
9.
Molecules ; 27(11)2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35684541

RESUMO

Traditional Chinese Medicine is generally used as a decoction to guard health. Many active ingredients in the decoction are chemical ingredients that are not usually paid attention to in phytochemical research, such as polysaccharides, etc. Based on research interest in Chinese herbal decoction, crude polysaccharides from G. wilfordii (GCP) were purified to obtain two relatively homogeneous polysaccharides, a neutral polysaccharide (GNP), and an acid polysaccharide (GAP) by various chromatographic separation methods, which were initially characterized by GC-MS, NMR, IR, and methylation analysis. Studies on the hepatoprotective activity of GCP in vivo showed that GCP might be a potential agent for the prevention and treatment of acute liver injury by inhibiting the secretion levels of ALT, AST, IL-6, IL-1ß, TNF-α, and MDA expression levels, increasing SOD, and the GSH-Px activity value. Further, in vitro assays, GNP and GAP, decrease the inflammatory response by inhibiting the secretion of IL-6 and TNF-α, involved in the STAT1/T-bet signaling pathway.


Assuntos
Geranium , Polissacarídeos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Geranium/química , Humanos , Interleucina-6/metabolismo , Fígado/metabolismo , Polissacarídeos/química , Polissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
10.
Allergy ; 76(9): 2797-2808, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33784411

RESUMO

BACKGROUND: Allergic rhinitis is characterized by rhinorrhea, nasal congestion, sneezing and nasal pruritus. Group 2 innate lymphoid cells (ILC2s), CD4+ T cells and eosinophils in nasal mucosa are increased significantly after nasal allergen challenge (NAC). Effects of intranasal corticosteroids (INCS) on ILC2s remain to be investigated. METHODS: Subjects (n = 10) with allergic rhinitis and mild asthma were enrolled in a single-blind, placebo-controlled, sequential treatment study and treated twice daily with intranasal triamcinolone acetonide (220 µg) or placebo for 14 days, separated by a 7-day washout period. Following treatment, subjects underwent NAC and upper airway function was assessed. Cells from the nasal mucosa and blood, sampled 24 h post-NAC, underwent flow cytometric enumeration for ILC2s, CD4+ T and eosinophil progenitor (EoPs) levels. Cell differentials and cytokine levels were assessed in nasal lavage. RESULTS: Treatment with INCS significantly attenuated ILC2s, IL-5+ /IL-13+ ILC2s, HLA-DR+ ILC2s and CD4+ T cells in the nasal mucosa, 24 h post-NAC. EoP in nasal mucosa was significantly increased, while mature eosinophils were significantly decreased, 24 h post-NAC in INCS versus placebo treatment arm. Following INCS treatment, IL-2, IL-4, IL-5 and IL-13 were significantly attenuated 24 h post-NAC accompanied by significant improvement in upper airway function. CONCLUSION: Pre-treatment with INCS attenuates allergen-induced increases in ILC2s, CD4+ T cells and terminal differentiation of EoPs in the nasal mucosa of allergic rhinitis patients with mild asthma, with little systemic effect. Attenuation of HLA-DR expression by ILC2s may be an additional mechanism by which steroids modulate adaptive immune responses in the upper airways.


Assuntos
Asma , Rinite Alérgica , Corticosteroides/uso terapêutico , Alérgenos , Asma/tratamento farmacológico , Humanos , Imunidade Inata , Linfócitos , Mucosa Nasal , Método Simples-Cego
11.
Allergy Asthma Proc ; 42(5): e127-e134, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34474715

RESUMO

Background: The bronchial provocation test (BPT) performed by using the forced oscillation technique (FOT) is cooperated without forced expiratory effort. However, a comparison of the application value and safety of BPTs measured by using the FOT and the standardized dosimeter method is lacking, which limits its clinical practice. Objective: We aimed to analyze the diagnostic value and safety of the BPT as measured by the FOT in patients with asthma and in healthy subjects. Methods: This was a randomized cross-over clinical study. Airway responsiveness was measured by using the FOT and the aerosol provocation system (APS) dosimeter method in all the participants. The between-test interval was 24 hours. The diagnostic value and safety of the two tests were analyzed. Results: Asthma control status was assessed based on ACT scores, and patients with asthma (including 27 uncontrolled, 34 partially controlled, and 32 controlled) were collected, and 69 healthy subjects were recruited. Receiver operating characteristic curves revealed slightly superior screening capability of cumulative dose of methacholine causing a 20% decrease (PD20)-forced expiratory volume in the first second of expiration when measured by using the APS-dosimeter method (area under the curve [AUC] 0.981 [95% confidence interval {CI}, 0.952-1.000]) over that of cumulative dose of inhaled methacholine at the inflection point when respiratory resistance began to increase continuously (Dmin) by using the FOT (AUC 0.959 [95% CI, 0.924-0.994]). The sensitivity and specificity were 98.9% and 98.6%, respectively, with the APS-dosimeter method, and 100% and 87.0%, respectively, with the FOT. It took an average of 9.0 minutes (range, 6.0-11.0 minutes) when using the FOT and an average of 17.0 minutes (range, 14.0-25.0 minutes) when using APS-dosimeter method (p < 0.01) in all the participants. The measurement time for the FOT was reduced by 47.1% than the APS-dosimeter. The incidence rate of the adverse events with the FOT was slightly higher than that with the APS-dosimeter method (p < 0.05). Both tests were well tolerated. No serious adverse event was found. Conclusion: The FOT, characterized as being simple, safe, and time saving, could be used to assess airway hyperresponsiveness in patients with asthma and worthy of clinical application.


Assuntos
Asma , Testes de Provocação Brônquica , Asma/diagnóstico , Volume Expiratório Forçado , Humanos , Cloreto de Metacolina , Sistema Respiratório
12.
Clin Exp Hypertens ; 43(8): 715-722, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34392742

RESUMO

Background: The dysregulation of renin-angiotensin-aldosterone system (RAAS) is closely related to the development of essential hypertension (EH). MicroRNAs (miRNAs) are an important regulator of RAAS. The sponge effect of circular RNAs (circRNAs) on miRNAs makes the circRNA-miRNA-mRNA axis in EH possible, however, there is currently a lack of relevant evidence.Material and Methods: A circRNA-miRNA network was constructed based on the previous circRNAs microarray results. The expression of RAAS-related miRNAs and circRNAs were verified by qRT-PCR. Peripheral blood samples of 106 EH patients and 106 healthy volunteers were included in this study. GO and KEGG enrichment were performed to predict the role of candidate circRNAs in EH.Results: In EH patients, RAAS-related hsa-miR-483-3p and hsa-miR-27a-3p were down-regulated, and hsa_circ_0122153 and hsa_circ_0025088 were up-regulated. The relative expression of RAAS-related circRNAs and target miRNAs showed a negative correlation (hsa_circ_0122153-hsa-miR-483-3p and hsa_circ_0025088-hsa-miR-27a-3p). Hsa_circ_0122153 or hsa_circ_0025088 combined with corresponding miRNAs and environmental factors may support the early diagnosis of EH. Hsa_circ_0122153 and hsa_circ_0025088 may participate in the regulation of aldosterone and the secretion of renin through the circRNA-miRNA-mRNA network, respectively.Conclusion: Highly expressed hsa_circ_0122153 and hsa_circ_0025088 increase the risk of EH. The hsa_circ_0122153/hsa-miR-483-3p and hsa_circ_0025088/hsa-miR-27a-3p axis involving RAAS were potential EH pathways.


Assuntos
Hipertensão Essencial , MicroRNAs , Hipertensão Essencial/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular , RNA Mensageiro/metabolismo , Sistema Renina-Angiotensina/genética
15.
Acta Pharmacol Sin ; 37(5): 629-36, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26997568

RESUMO

AIM: We previously proven that carbocisteine, a conventional mucolytic drug, remarkably reduced the rate of acute exacerbations and improved the quality of life in the patients with chronic obstructive pulmonary disease. In this study we investigated the mechanisms underlying the anti-inflammatory effects of carbocisteine in human alveolar epithelial cells in vitro. METHODS: Human lung adenocarcinoma cell line A549 was treated with TNF-α (10 ng/mL). Carbocisteine was administered either 24 h prior to or after TNF-α exposure. The cytokine release and expression were measured using ELISA and qRT-PCR. Activation of NF-κB was analyzed with Western blotting, immunofluorescence assay and luciferase reporter gene assay. The expression of ERK1/2 MAPK signaling proteins was assessed with Western blotting. RESULTS: Carbocisteine (10, 100, 1000 µmol/L), administered either before or after TNF-α exposure, dose-dependently suppressed TNF-α-induced inflammation in A549 cells, as evidenced by diminished release of IL-6 and IL-8, and diminished mRNA expression of IL-6, IL-8, TNF-α, MCP-1 and MIP-1ß. Furthermore, pretreatment with carbocisteine significantly decreased TNF-α-induced phosphorylation of NF-κB p65 and ERK1/2 MAPK, and inhibited the nuclear translocation of p65 subunit in A549 cells. In an NF-κB luciferase reporter system, pretreatment with carbocisteine dose-dependently inhibited TNF-α-induced transcriptional activity of NF-κB. CONCLUSION: Carbocisteine effectively suppresses TNF-α-induced inflammation in A549 cells via suppressing NF-κB and ERK1/2 MAPK signaling pathways.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Carbocisteína/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Células A549 , Células Epiteliais Alveolares/metabolismo , Citocinas/metabolismo , Células HEK293 , Humanos , Inflamação/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
16.
Lung ; 192(5): 701-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24958577

RESUMO

BACKGROUND: Response-dose ratio (RDR) and cumulative provocative dosage (PD) are useful indices reflecting airway responsiveness in asthma. OBJECTIVES: To compare the diagnostic value of RDR and PD, by conducting leukotriene D4 (LTD4-BPT) and methacholine bronchial provocation test (MCh-BPT), in different asthma control levels. METHODS: Healthy subjects and asthmatic patients underwent LTD4-BPT and MCh-BPT, at 2-14-day interval. This entailed assessment of the distribution characteristics, correlation, and diagnostic value of PD inducing 20% fall in forced expiratory volume in one second (PD20FEV1) and the RDR, defined as FEV1 fall (%) at the final step divided by the corresponding provocative dosage. RESULTS: Twenty uncontrolled, 22 partly controlled, 20 controlled asthmatics, and 21 healthy subjects were enrolled. Log10RDR was positively correlated with log10PD20FEV1 in both BPTs (all P < 0.05). Poorer asthma control was associated with significantly lower PD20FEV1 and higher RDR (both P < 0.05). The differences in PD20FEV1 and RDR between partly controlled and controlled asthma were unremarkable (both P > 0.05). Compared with log10PD20FEV1, the log10RDR yielded similar diagnostic values in both BPTs. A lower percentile of RDR (≤ 25th percentile) was associated with higher baseline FEV1 (P < 0.05) and an increased proportion of well-controlled asthmatic patients. The combination of RDR and PD20FEV1 led to an increased diagnostic value compared with either parameter alone. CONCLUSIONS: RDR is a surrogate of PD20FEV1 for BPTs in asthma. This finding was not modified by different asthma control levels or the types of bronchoprovocants.


Assuntos
Asma/fisiopatologia , Testes de Provocação Brônquica/métodos , Broncoconstrição , Broncodilatadores , Leucotrieno D4 , Pulmão/fisiopatologia , Cloreto de Metacolina , Adulto , Antiasmáticos/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Broncoconstrição/efeitos dos fármacos , China , Estudos Cross-Over , Relação Dose-Resposta a Droga , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Capacidade Vital
17.
J Allergy Clin Immunol ; 131(2): 332-8.e1-4, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23040886

RESUMO

BACKGROUND: Both leukotriene D(4) (LTD(4)) and methacholine bronchial provocation tests are measurements of airway responsiveness; however, their correlation and distinction remain unexplored. OBJECTIVES: We sought to compare the 2 tests and classify leukotriene-responsiveness subtypes in asthmatic patients. METHODS: In this randomized cross-over study we enrolled healthy subjects and asthmatic patients with different control statuses. All subjects underwent both tests with a 2- to 14-day interval. Distribution and correlation of cumulative doses inducing a 20% decrease in FEV(1), LTD(4)/methacholine potency ratio, diagnostic value, and adverse events were recorded and analyzed. Asthmatic patients with a lower cumulative dose for LTD(4) and a higher leukotriene/methacholine potency ratio than geometric means were regarded as leukotriene responsive. RESULTS: Twenty patients with uncontrolled, 22 with partly controlled, and 20 with controlled asthma and 21 healthy subjects were enrolled. Geometric means of cumulative doses for LTD(4) and methacholine (0.272 nmol vs 0.945 µmol) were lowest in patients with uncontrolled asthma, followed by those with partly controlled (0.387 nmol vs 1.933 µmol) and controlled (1.484 nmol vs 3.946 µmol) asthma. The average potency ratio was highest in those with partly controlled asthma (5000.2), followed by those with uncontrolled (3477.7) and controlled (2702.6) asthma. Eighteen leukotriene-responsive asthmatic patients (29.03%) with a cumulative dose of LTD(4) of 0.533 nmol or less and a potency ratio of 3647 or greater were identified. Adverse events, including tachypnea and chest tightness, were similar and mild. No serious adverse event was reported. CONCLUSION: Diagnostic value and safety were ideal in both tests. The combination of cumulative dose for LTD(4) and potency ratio might be useful to identify leukotriene-responsive asthmatic patients.


Assuntos
Asma/diagnóstico , Brônquios/efeitos dos fármacos , Testes de Provocação Brônquica/métodos , Leucotrieno D4 , Cloreto de Metacolina , Administração por Inalação , Adulto , Estudos de Casos e Controles , Estudos Cross-Over , Humanos , Leucotrieno D4/administração & dosagem , Leucotrieno D4/efeitos adversos , Cloreto de Metacolina/administração & dosagem , Cloreto de Metacolina/efeitos adversos
18.
Chin Herb Med ; 16(1): 70-81, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38375047

RESUMO

The seco-prezizaane-type sesquiterpenes (SPS), as a special class of sesquiterpenes with a highly oxidative five-ring cage structure and seven consecutive chiral centers, are isolated from the genus Illicium, which have a variety of biological activities, including neurotoxicity and neurotrophic effects, etc. This review summarizes the chemical constituents and pharmacological effects of SPS, and discusses the potential trend and scope of future research.

19.
J Hazard Mater ; 465: 133389, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38185083

RESUMO

Plastic additives, such as organophosphate esters (OPEs) and phthalate esters (PAEs), are raising public concerns due to their widespread presence and potential health risks. Nonetheless, the occurrences and potential health risks of these additives in marine mammals remain limited. Here, we first investigated the accumulation patterns and potential risks of OPEs and metabolites of PAEs (mPAEs) in Indo-Pacific finless porpoises inhabiting the northern South China Sea (NSCS) during 2007-2020. The average hepatic concentrations of ∑15OPEs and ∑16mPAEs in the NSCS finless porpoises were 53.9 ± 40.7 and 98.6 ± 54.8 ng/g ww, respectively. The accumulation of mPAEs and OPEs in the finless porpoises is associated with the chemical structures of the compounds. ∑5halogenated-OPEs were the most dominant category (62.6%) of ∑15OPEs, followed by ∑6aryl-OPEs (25.9%) and ∑6nonhalogenated alkyl-OPEs (11.5%). The accumulation of mPAEs displayed a declining trend with increasing alkyl side chain length (C0-C10). Although the hepatic burden of mPAEs in finless porpoises was sex-independent, some OPEs, including TDCIPP, TBOEP, TCIPP, TCrP, TPHP, and TDBPP, exhibited significantly higher concentrations in adult males than in adult females. TDBPP, as a new-generation OPE, exhibited a gradual increase during the study period, suggesting that TDBPP should be prioritized for monitoring in the coastal regions of South China. The estimated hazard quotient indicated that almost all mPAEs and OPEs pose no hazard to finless porpoises, with only DEHP presenting potential health risks to both adult and juvenile finless porpoises.


Assuntos
Toninhas , Masculino , Animais , Feminino , Toninhas/metabolismo , Monitoramento Ambiental , China , Organofosfatos/análise , Oceanos e Mares , Ésteres/análise
20.
J Hazard Mater ; 467: 133720, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38335606

RESUMO

As long-lived apex predators, marine mammal adults often accumulate alarmingly levels of environmental contaminants. Nevertheless, the accumulation and risks of these contaminants in the critical calf stage of marine mammals remain largely unknown. Here, we investigated the exposure status and health risks of 74 organohalogen contaminants (OHCs) in Indo-Pacific humpback dolphin calves (Sousa chinensis) collected from the Pearl River Estuary (PRE), China, during 2005-2019. Our findings revealed moderate levels of polychlorinated biphenyls (PCBs), medium-high levels of dichlorodiphenyltrichloroethanes (DDTs) and hexachlorocyclohexanes (HCHs), and the highest levels of polybrominated diphenyl ethers (PBDEs) and alternative halogenated flame retardants (AHFRs) compared to those reported for cetaceans elsewhere. Traditional OHCs like DDTs, PCBs, and PBDEs did not exhibit significant decreasing trends in the dolphin calves despite global restrictions on these compounds, and AHFRs as emerging OHCs showed an increasing trend over the study period. Risk quotients of DDTs, HCHs, PBDEs, and PCBs in most of the dolphin samples were > 1, indicating that humpback dolphin calves may have suffered long-term threats from OHC exposure. The significant correlation observed between the traditional OHC levels and the stranding death number of the dolphin calves suggests these OHCs may impact the survival of this endangered species.


Assuntos
Golfinhos , Bifenilos Policlorados , Animais , Bifenilos Policlorados/análise , Éteres Difenil Halogenados/toxicidade , Monitoramento Ambiental , Hexaclorocicloexano , Ecossistema
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