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1.
Biodivers Data J ; 12: e125570, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39099603

RESUMEN

Background: Mycena (Pers.) Roussel (1806) is a large genus of Mycenaceae known for having small to medium-sized basidiomata. It is typified by the species Mycenagalericulata (Scop.) Gray. For years, many mycologists have made important contributions to understanding Mycena and several monographs have been published. Three specimens were collected from China that belonged to the genus Mycena. On the basis of morphological analysis and phylogenetic analyses employing DNA sequences, a new species is described. New information: Mycenabrunnescens sp. nov. is described as a new species from subtropical areas of China. It is characterised by its brown pileus, whitish lamellae that turns brown when bruised, orange to brown lamellae edges, the absence of pleurocystidia and cheilocystidia with simple or branched excrescences at the apex containing yellowish-brown contents. We performed phylogenetic analyses on a concatenated dataset comprising the internal transcribed spacer and large subunit regions of nuclear ribosomal RNA using Bayesian Inference and Maximum Likelihood methods. The result showed that the new taxon clustered in an independent group and is closely related to M.albiceps and M.flosoides.

2.
J Hazard Mater ; 476: 135103, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38972203

RESUMEN

An earlier study found that respiratory cadmium chloride (CdCl2) exposure caused COPD-like lung injury. This study aimed to explore whether mitochondrial dysfunction-mediated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury. Adult C57BL/6 mice were exposed to CdCl2 (10 mg/L) aerosol for six months. Beta-galactosidase-positive cells, p21 and p16 were increased in CdCl2-exposed mouse lungs. The in vitro experiments showed that γ-H2AX was elevated in CdCl2-exposed alveolar epithelial cells. The cGAS-STING pathway was activated in CdCl2-exposed alveolar epithelial cells and mouse lungs. Cxcl1, Cxcl9, Il-10, Il-1ß and Mmp2, several senescence-associated secretory phenotypes (SASP), were upregulated in CdCl2-exposed alveolar epithelial cells. Mechanistically, CdCl2 exposure caused SIRT3 reduction and mitochondrial dysfunction in mouse lungs and alveolar epithelial cells. The in vitro experiment found that Sirt3 overexpression attenuated CdCl2-induced alveolar epithelial senescence and SASP. The in vivo experiments showed that Sirt3 gene knockout exacerbated CdCl2-induced alveolar epithelial senescence, alveolar structure damage, airway inflammation and pulmonary function decline. NMN, an NAD+ precursor, attenuated CdCl2-induced alveolar epithelial senescence and SASP in mouse lungs. Moreover, NMN supplementation prevented CdCl2-induced COPD-like alveolar structure damage, epithelial-mesenchymal transition and pulmonary function decline. These results suggest that mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury.


Asunto(s)
Senescencia Celular , Ratones Endogámicos C57BL , Mitocondrias , Enfermedad Pulmonar Obstructiva Crónica , Animales , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Senescencia Celular/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/metabolismo , Masculino , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/patología , Sirtuina 3/metabolismo , Sirtuina 3/genética , Ratones , Ratones Noqueados
4.
Ecotoxicol Environ Saf ; 255: 114799, 2023 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-36933479

RESUMEN

Increasing evidence have demonstrated that early-life exposure to environmental toxicants elevates risk of allergic asthma. Cadmium (Cd) is widely present in the environment. The purposes of this study were to evaluate the impact of early-life Cd exposure on susceptibility to ovalbumin (OVA)-evoked allergic asthma. Newly weaned mice were subjected to a low concentration of CdCl2 (1 mg/L) by drinking water for 5 consecutive weeks. Penh value, an index of airway obstruction, was increased in OVA-stimulated and challenged pups. Abundant inflammatory cells were observed in the lung of OVA-exposed pups. Goblet cell hyperplasia and mucus secretion were shown in the airway of OVA-stimulated and challenged pups. Early-life Cd exposure exacerbated OVA-evoked airway hyperreactivity, Goblet cell hyperplasia and mucus secretion. The in vitro experiments showed that mucoprotein gene MUC5AC mRNA was upregulated in Cd-exposed bronchial epithelial cells. Mechanistically, endoplasmic reticulum (ER) stress-related molecules GRP78, p-eIF2α, CHOP, p-IRE1α and spliced XBP-1 (sXBP-1) were elevated in Cd-subjected bronchial epithelial cells. The blockade of ER stress, using chemical inhibitor 4-PBA or sXBP-1 siRNA interference, attenuated Cd-induced MUC5AC upregulation in bronchial epithelial cells. These results indicate that early-life Cd exposure aggravates OVA-induced allergic asthma partially through inducing ER stress in bronchial epithelial cells.


Asunto(s)
Asma , Cadmio , Ratones , Animales , Ovalbúmina , Cadmio/toxicidad , Endorribonucleasas , Hiperplasia/patología , Proteínas Serina-Treonina Quinasas , Asma/inducido químicamente , Asma/patología , Pulmón/patología , Ratones Endogámicos BALB C
5.
Sci Total Environ ; 879: 163073, 2023 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-36965727

RESUMEN

Accumulating evidences demonstrate that long-term exposure to atmospheric fine particles and air pollutants elevates the risk of chronic obstructive pulmonary disease (COPD). Cadmium (Cd) is one of the important toxic substances in atmospheric fine particles and air pollutants. In this study, we aimed to establish a mouse model to evaluate whether respiratory Cd exposure induces COPD-like lung injury. Adult male C57BL/6 mice were exposed to CdCl2 (10 mg/L, 4 h per day) by inhaling aerosol for either 10 weeks (short-term) or 6 months (long-term). The mean serum Cd concentration was 6.26 µg/L in Cd-exposed mice. Lung weight and coefficient were elevated in long-term Cd-exposed mice. Pathological scores and alveolar destructive indices were increased in long-term Cd-exposed mouse lungs. Mean linear intercept and airway wall thickness were accordingly elevated in Cd-exposed mice. Inflammatory cell infiltration was obvious and inflammatory cytokines, including TNF-α, IL-1ß, IL-6, IL-8, IL-10 and TGF-ß, were up-regulated in Cd-exposed mouse lungs. α-SMA, N-cadherin and vimentin, epithelial-mesenchymal transition markers, and extracellular matrix collagen deposition around small airway, determined by Masson's trichrome staining, were shown in Cd-exposed mouse lungs. COPD-characteristic lung function decline was observed in long-term Cd-exposed mice. These outcomes show that long-term respiratory exposure to Cd induces COPD-like lung lesions for the first time.


Asunto(s)
Contaminantes Atmosféricos , Enfermedad Pulmonar Obstructiva Crónica , Masculino , Ratones , Animales , Cadmio/toxicidad , Ratones Endogámicos C57BL , Pulmón , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente
6.
Environ Res ; 222: 115334, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36702192

RESUMEN

Accumulating data demonstrate that polycyclic aromatic hydrocarbons (PAH) exposure is linked to compromised respiratory diseases. This study aimed to analyze urinary PAH metabolites and their associations with chronic obstructive pulmonary disease (COPD) in a sample size of 3015 subjects from a total population of 50,588 from the National Health and Nutrition Examination Survey (NHANES) in 2007-2016. Results showed that the most predominant metabolite was 1-Hydroxynaphthalene (1-NAP, 84%) with a geometric mean concentration of 50,265 ng/L, followed by its homologue 2-NAP (10%), both of which arose from sources including road emission, smoking and cooking. Multiple logistic regression showed that seven of the ten major PAH metabolites were correlated with increased COPD risk: including 1-NAP (OR: 1.83, 95%CI: 1.25, 2.69), 2-Hydroxyfluorene (2-FLU, OR: 2.29, 95%CI: 1.42, 3.68) and 1-Hydroxyphenanthrene (1-PHE, OR: 2.79, 95%CI: 1.85, 4.21), when compared to the lowest tertile after adjusted for covariates. Total exposure burden per PAH congener sub-group demonstrated persistent positive correlation with COPD for ∑PHE (OR: 1.80, 95%CI: 1.34, 2.43) and ∑FLU (OR: 2.74, 95%CI: 1.77, 4.23) after adjusted for covariates. To address the contribution of PAH exposure as mixture towards COPD, weighted quantile sum (WQS) regression analyses revealed that 1-NAP, 9-Hydroxyfluorene (9-FLU), 3-Hydroxyfluorene (3-FLU) and 1-PHE were among the top contributors in the associations with COPD. Our results demonstrate the contemporary yet ongoing exposure burden of PAH exposure for over a decade, particularly towards NAPs and FLUs that contribute significantly to COPD risk, calling for more timely environmental regulation.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Hidrocarburos Policíclicos Aromáticos/metabolismo , Encuestas Nutricionales , Estudios Longitudinales , Modelos Logísticos , Biomarcadores/orina
7.
Ecotoxicol Environ Saf ; 251: 114548, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36652742

RESUMEN

BACKGROUND: Environmental cadmium (Cd) exposure is linked to pulmonary function injury in the general population. But, the association between blood Cd concentration and pulmonary function has not been investigated thoroughly in chronic obstructive pulmonary disease (COPD) patients, and the potential mechanisms are unclear. METHODS: All eligible 789 COPD patients were enrolled from Anhui COPD cohort. Blood specimens and clinical information were collected. Pulmonary function test was conducted. The subunit of telomerase, telomerase reverse transcriptase (TERT), was determined through enzyme linked immunosorbent assay (ELISA). Blood Cd was measured via inductively coupled-mass spectrometer (ICP-MS). RESULTS: Blood Cd was negatively and dose-dependently associated with pulmonary function. Each 1-unit increase of blood Cd was associated with 0.861 L decline in FVC, 0.648 L decline in FEV1, 5.938 % decline in FEV1/FVC %, and 22.098 % decline in FEV1 % among COPD patients, respectively. Age, current-smoking, self-cooking and higher smoking amount aggravated Cd-evoked pulmonary function decrease. Additionally, there was an inversely dose-response association between Cd concentration and TERT in COPD patients. Elevated TERT obviously mediated 29.53 %, 37.50 % and 19.48 % of Cd-evoked FVC, FEV1, and FEV1 % declines in COPD patients, respectively. CONCLUSION: Blood Cd concentration is strongly associated with the decline of pulmonary function and telomerase activity among COPD patients. Telomere attrition partially mediates Cd-induced pulmonary function decline, suggesting an underlying mechanistic role of telomere attrition in pulmonary function decline from Cd exposure in COPD patients.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Telomerasa , Humanos , Cadmio/toxicidad , Volumen Espiratorio Forzado , Pulmón
8.
Mycobiology ; 50(5): 294-301, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36404895

RESUMEN

Mycena subpiligera, a new taxon in sect. Fragilipedes that can strongly enhance the germination efficiency of Gastrodia elata seeds, was discovered in subtropical areas of China. As revealed by a morphological comparison with related Mycena species as well as maximum likelihood (ML) and Bayesian phylogenetic analyses based on sequences of the internal transcribed spacer (ITS) and the large subunit (LSU) regions of nuclear ribosomal RNA, the new taxon can be distinguished from phenotypically similar and phylogenetically related species. Optimal cultural conditions for M. subpiligera basidiomata are reported, and the germination rate of the new species is compared with that of M. citrinomarginata.

9.
Environ Pollut ; 315: 120462, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36270563

RESUMEN

Gestational arsenic (As) exposure has been associated with adverse developmental outcomes. The purpose of this study was to explore the impacts of As exposure in different periods on susceptibility to allergic asthma. In model 1, dams were administered with NaAsO2 (0.1 or 1 ppm) by drinking water throughout pregnancy and lactation. In model 2, newly weaned pups were exposed to NaAsO2 (1 ppm) through drinking water. Pups were sensitized and challenged with ovalbumin (OVA). Inflammatory cell infiltration and pulmonary T helper 2 (Th2) cytokine upregulation were shown in OVA-sensitized and challenged pups. Goblet cell hyperplasia and airway mucus secretion were observed in OVA-sensitized and challenged pups. Maternal As exposure throughout pregnancy and lactation did not aggravate inflammatory cell infiltration, airway mucus secretion and pulmonary Th2 cytokine upregulation in OVA-sensitized and challenged pups. Although airway hyperreactivity, inflammatory cell infiltration and Th2 cytokine weren't influenced, OVA-evoked Goblet cell hyperplasia and airway mucus secretion were aggravated in pups who were exposed to NaAsO2 after weaning. In conclusion, juvenile As exposure increases susceptibility to allergic asthma through aggravating Goblet cell hyperplasia and airway mucus secretion. The impacts of maternal As exposure during pregnancy and lactation on susceptibility to allergic asthma needs to be further evaluated in other animal experiments.


Asunto(s)
Arsénico , Asma , Agua Potable , Embarazo , Femenino , Ratones , Animales , Ovalbúmina , Células Caliciformes/patología , Arsénico/toxicidad , Hiperplasia/inducido químicamente , Hiperplasia/patología , Ratones Endogámicos BALB C , Modelos Animales de Enfermedad , Asma/inducido químicamente , Pulmón/patología , Citocinas , Moco , Líquido del Lavado Bronquioalveolar
10.
Int Immunopharmacol ; 113(Pt A): 109359, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36288647

RESUMEN

Numerous studies demonstrated that bleomycin (BLM) caused acute lung injury (ALI). This study explored the role of mitochondrial reactive oxygen species (ROS) on BLM-induced ALI and pulmonary epithelial ferroptosis. Male C57BL/6J mice were intratracheally injected with BLM (3.0 mg/kg). BEAS-2B cells, human bronchial epithelial cells, were cultured with BLM (10 µg/ml). Pulmonary MDA and 4-HNE, two markers of lipid peroxidation, were elevated in BLM-exposed mice. Oxidized lipids were upregulated in BLM-exposed BEAS-2B cells. Ferroptosis-characteristic ultrastructure, mainly disappearance of mitochondrial bilayer membrane structure and cristae, was observed in BLM-exposed pulmonary epithelium. Ferrostatin-1, a specific inhibitor of ferroptosis, attenuated BLM-evoked pulmonary lipid peroxidation, ferroptosis-characteristic mitochondrial ultrastructure and pulmonary epithelial death. The in vitro experiments showed that mitochondrial membrane potentials (MMPs) were decreased and mitochondrial ROS were increased in BLM-exposed BEAS-2B cells. Mitoquinone (MitoQ), a mitochondria-targeted antioxidant, prevented BLM-induced MMP reduction and mitochondrial ROS elevation in BEAS-2B cells. The in vivo experiment found that MitoQ attenuated BLM-evoked GSH depletion and lipid peroxidation in mouse lungs. Moreover, MitoQ prevented BLM-induced ferroptosis-characteristic mitochondrial changes, pulmonary epithelial death and ALI. In conclusion, mitochondrial ROS are an initiator of BLM-induced pulmonary epithelial ferroptosis. Mitochondria-targeted antioxidants may be used as potential therapeutic agents for BLM-induced ALI.


Asunto(s)
Lesión Pulmonar Aguda , Ferroptosis , Masculino , Ratones , Humanos , Animales , Bleomicina/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos C57BL , Pulmón , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Mitocondrias
11.
Environ Sci Pollut Res Int ; 29(3): 3474-3486, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34387821

RESUMEN

Benzo[a]pyrene (BaP), a representative polycyclic aromatic hydrocarbon, exists widely in automobile emissions and polluted atmosphere. The current study aimed to describe pulmonary inflammation during BaP-induced acute lung injury (ALI). All mice except controls were intratracheally instilled with a single dose of BaP (90 µg per mouse). The alveolar structure was damaged, accompanied by numerous inflammatory cell infiltration around pulmonary interstitium and small airway. Airway wall area and mean linear intercept were reduced in BaP-exposed mouse lungs. By contrast, airway wall thickness and destructive index were elevated in BaP-exposed mouse lungs. Several inflammatory genes, such as Tnf-α, Il-1ß, Il-6, Mip-2, Kc, and Mcp-1, were upregulated in mouse lungs. Phosphorylated IκBα was elevated in BaP-exposed mouse lungs. Nuclear translocation of NF-κB p65 and p50 was accordingly observed in BaP-exposed mouse lungs. Several molecules of the MAPK pathway, including JNK, ERK1/2, and p38, were activated in mouse lungs. Of interest, pretreatment with N-acetylcysteine (NAC), an antioxidant, alleviated BaP-induced ALI. Moreover, NAC attenuated BaP-induced inflammatory cell infiltration in mouse lungs and inflammatory gene upregulation in A549 cells. In addition, NAC attenuated BaP-induced NF-κB activation in A549 cells and mouse lungs. These results suggest that NAC alleviates pulmonary inflammatory response during BaP-evoked ALI.


Asunto(s)
Lesión Pulmonar Aguda , Neumonía , Acetilcisteína/farmacología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Animales , Benzo(a)pireno/toxicidad , Pulmón , Ratones , FN-kappa B
12.
Front Med (Lausanne) ; 8: 781596, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34917638

RESUMEN

Background: Cysteine-rich 61 (CYR61) and inflammation was upregulated in the lungs of patients with chronic obstructive pulmonary disease (COPD). However, the association between CYR61 and inflammation was unclear in COPD patients. This study aimed to analyze the association of serum CYR61 with pulmonary inflammation and lung function indexes in COPD patients. Methods: One hundred and fifty COPD patients and 150 control subjects were enrolled. Serum and pulmonary CYR61 was detected. Lung function indexes were evaluated in COPD patients. Results: Serum CYR61 level was elevated and pulmonary CYR61 expression was upregulated in COPD patients. An increased CYR61 was associated with decreased pulmonary function indexes in COPD patients. Further analyses showed that nuclear factor-kappa B (NF-κB) p65-positive nuclei was elevated in the lungs of COPD patients with high level of CYR61. Accordingly, serum monocyte chemotactic protein (MCP)-1 and tumor necrosis factor α (TNF-α), two downstream inflammatory cytokines of NF-κB pathway, were increased in parallel with CYR61, among which serum MCP-1 and TNF-α were the highest in COPD patients with high level of CYR61. Moreover, a positive correlation, determined by multivariate regression that excluded the influence of age, gender and smoking, was observed between serum CYR61 and inflammatory cytokines in COPD patients. Conclusion: These results provide evidence that an increased CYR61 is associated with pulmonary inflammation and COPD progression. Inflammatory cytokines may be the mediators between CYR61 elevation and COPD progression.

13.
Int J Med Sci ; 18(11): 2449-2456, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33967623

RESUMEN

Parkinson protein 7 (PARK7)/DJ-1 (DJ-1) is a redox sensitive molecular and stabilizer of nuclear factor erythroid 2-related factor 2 (Nrf-2). Nrf-2 regulates the downstream antioxidant defense system and exerts a significant function in patients with chronic obstructive pulmonary disease (COPD). Vitamin D receptor (VDR) is the nuclear receptor that regulates the downstream target genes. This study aimed to analyze the associations among pulmonary function, DJ-1, VDR and Nrf-2 in COPD patients. Serum was collected from 180 COPD patients and control subjects. Thirty-five lung tissues were obtained. DJ-1 was measured using ELISA and western blotting. Nrf-2 and VDR were detected by immunohistochemistry. Serum and pulmonary DJ-1 levels were lower in COPD patients than those in control subjects. Pulmonary VDR-positive nuclei were reduced in COPD patients. Nrf-2-positive nuclei were reduced in lung tissues of COPD patients. On the contrary, Nrf-2-related downstream target proteins were elevated in COPD patients. Further correlation analysis indicated that forced expiratory volume in 1 second (FEV1) was positively associated with pulmonary DJ-1, VDR and Nrf-2 in patients with COPD. In addition, there were positive correlations among DJ-1, VDR and Nrf-2 in lung tissues of COPD patients. In conclusion, DJ-1, VDR and Nrf-2 were decreased in COPD patients compared with control subjects. The reduction of DJ-1 and VDR associating with Nrf-2 downregulation may be involved in the process of COPD.


Asunto(s)
Pulmón/patología , Factor 2 Relacionado con NF-E2/metabolismo , Proteína Desglicasa DJ-1/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Receptores de Calcitriol/metabolismo , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Regulación hacia Abajo , Femenino , Humanos , Pulmón/fisiopatología , Pulmón/cirugía , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/cirugía , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad
14.
BMC Pulm Med ; 21(1): 149, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33952237

RESUMEN

BACKGROUND: Several studies demonstrate that endoplasmic reticulum (ER) stress-mediated epithelial-mesenchymal transition (EMT) is involved in the process of bleomycin (BLM)-induced pulmonary fibrosis. Tauroursodeoxycholic acid (TUDCA), a bile acid with chaperone properties, is an inhibitor of ER stress. This study aimed to investigate the preventive effects of TUDCA on BLM-induced EMT and lung fibrosis. METHODS: The model of lung fibrosis was established by intratracheal injection with a single dose of BLM (3.0 mg/kg). In TUDCA + BLM group, mice were intraperitoneally injected with TUDCA (250 mg/kg) daily. RESULTS: BLM-induced alveolar septal destruction and inflammatory cell infiltration were alleviated by TUDCA. BLM-induced interstitial collagen deposition, as determined by Sirius Red staining, was attenuated by TUDCA. BLM-induced elevation of pulmonary α-smooth muscle actin (α-SMA) and reduction of pulmonary E-cadherin were attenuated by TUDCA. BLM-induced pulmonary Smad2/3 phosphorylation was suppressed by TUDCA. BLM-induced elevation of Ki67 and PCNA was inhibited by TUDCA in mice lungs. In addition, BLM-induced elevation of HO-1 (heme oxygenase-1) and 3-NT (3-nitrotyrosine) was alleviated by TUDCA. Finally, BLM-induced upregulation of pulmonary GRP78 and CHOP was attenuated by TUDCA. CONCLUSIONS: These results provide evidence that TUDCA pretreatment inhibits Smad2/3-medited EMT and subsequent lung fibrosis partially through suppressing BLM-induced ER stress and oxidative stress.


Asunto(s)
Estrés del Retículo Endoplásmico/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Pulmón/efectos de los fármacos , Fibrosis Pulmonar/prevención & control , Ácido Tauroquenodesoxicólico/farmacología , Animales , Bleomicina , Modelos Animales de Enfermedad , Chaperón BiP del Retículo Endoplásmico , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Fosforilación , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba
15.
Environ Pollut ; 283: 117134, 2021 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-33866216

RESUMEN

1-Nitropyrene (1-NP) is one component of atmospheric fine particles. Previous report revealed that acute 1-NP exposure induced respiratory inflammation. This study aimed to investigate whether chronic 1-NP exposure induces pulmonary fibrosis. Male C57BL6/J mice were intratracheally instilled to 1-NP (20 µg/mouse/week) for 6 weeks. Diffuse interstitial inflammation, a-smooth muscle actin (a-SMA)-positive cells, a marker of epithelial-mesenchymal transition (EMT), and an extensive collagen deposition, measured by Masson staining, were observed in 1-NP-exposed mouse lungs. Pulmonary function showed that lung dynamic compliance (Cydn-min) was reduced in 1-NP-exposed mice. Conversely, inspiratory resistance (Ri) and expiratory resistance (Re) were elevated in 1-NP-exposed mice. Mechanistically, cell migration and invasion were accelerated in 1-NP-exposed pulmonary epithelial cells. In addition, E-cadherin, an epithelial marker, was downregulated, and vimentin, a-SMA and N-cadherin, three mesenchymal markers, were upregulated in 1-NP-exposed pulmonary epithelial cells. Although TGF-ß wasn't altered, phosphorylated Smad2/3 were enhanced in 1-NP-exposed pulmonary epithelial cells. Moreover, reactive oxygen species (ROS) were increased and endoplasmic reticulum (ER) stress was activated in 1-NP-exposed pulmonary epithelial cells. N-Acetylcysteine (NAC), an antioxidant, attenuated 1-NP-evoked excess ROS, ER stress and EMT in pulmonary epithelial cells. Similarly, pretreatment with NAC alleviated 1-NP-caused pulmonary EMT and lung fibrosis in mice. These results demonstrate that ROS-evoked ER stress contributes, at least partially, to 1-NP-induced EMT and pulmonary fibrosis.


Asunto(s)
Transición Epitelial-Mesenquimal , Fibrosis Pulmonar , Animales , Bleomicina , Estrés del Retículo Endoplásmico , Masculino , Ratones , Fibrosis Pulmonar/inducido químicamente , Pirenos , Especies Reactivas de Oxígeno
16.
Front Endocrinol (Lausanne) ; 12: 615446, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33927690

RESUMEN

Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses in rats consuming a high fat diet (HFD). However, the mechanisms by which asperuloside exerts its anti-obesity properties were not clarified. Here, we investigated homeostatic and nutrient-sensing mechanisms regulating food intake in mice consuming HFD. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Asperuloside reduced body weight and food intake in mice consuming HFD by 10.5 and 12.8% respectively, with no effect on mice eating a standard chow diet. Fasting glucose and plasma insulin were also significantly reduced. Mechanistically, asperuloside significantly reduced hypothalamic mRNA ghrelin, leptin, and pro-opiomelanocortin in mice consuming HFD. The expression of fat lingual receptors (CD36, FFAR1-4), CB1R and sweet lingual receptors (TAS1R2-3) was increased almost 2-fold by the administration of asperuloside. Our findings suggest that asperuloside might exert its therapeutic effects by altering nutrient-sensing receptors in the oral cavity as well as hypothalamic receptors involved in food intake when mice are exposed to obesogenic diets. This signaling pathway is known to influence the subtle hypothalamic equilibrium between energy homeostasis and reward-induced overeating responses. The present pre-clinical study demonstrated that targeting the gustatory system through asperuloside administration could represent a promising and effective new anti-obesity strategy.


Asunto(s)
Fármacos Antiobesidad/farmacología , Peso Corporal/efectos de los fármacos , Monoterpenos Ciclopentánicos/farmacología , Glucósidos/farmacología , Piranos/farmacología , Percepción del Gusto/efectos de los fármacos , Aumento de Peso/efectos de los fármacos , Animales , Glucemia , Dieta Alta en Grasa , Ingestión de Energía/efectos de los fármacos , Ghrelina/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Insulina/sangre , Leptina/metabolismo , Masculino , Ratones , Proopiomelanocortina/metabolismo
17.
J Immunol ; 206(3): 515-523, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33361208

RESUMEN

Vitamin D deficiency is associated with increased risks of chronic obstructive pulmonary disease (COPD). Nevertheless, the mechanisms remain unknown. This study analyzed the correlations between vitamin D levels and inflammation in COPD patients. One hundred and one patients with COPD and 202 control subjects were enrolled. Serum 25(OH)D level and inflammatory cytokines were detected. Serum 25(OH)D was decreased and inflammatory cytokines were increased in COPD patients. According to forced expiratory volume in 1 s, COPD patients were divided into three grades. Furthermore, serum 25(OH)D was gradually decreased in COPD patients ranging from grade 1-2 to 4. Serum 25(OH)D was inversely associated with inflammatory cytokines in COPD patients. Further analysis found that NF-κB and AP-1 signaling were activated in COPD patients. Besides, inflammatory signaling was gradually increased in parallel with the severity of COPD. By contrast, pulmonary nuclear vitamin D receptor was decreased in COPD patients. In vitro experiments showed that 1,25(OH)2D3 inhibited LPS-activated inflammatory signaling in A549 cells (human lung adenocarcinoma cell). Mechanically, 1,25(OH)2D3 reinforced physical interactions between vitamin D receptor with NF-κB p65 and c-Jun. Our results indicate that vitamin D is inversely correlated with inflammatory signaling in COPD patients. Inflammation may be a vital mediator of COPD progress in patients with low vitamin D levels.


Asunto(s)
Inflamación/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Receptores de Calcitriol/metabolismo , Deficiencia de Vitamina D/inmunología , Vitamina D/sangre , Células A549 , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Inflamación/metabolismo , Masculino , Persona de Mediana Edad , FN-kappa B/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Transducción de Señal , Factor de Transcripción AP-1/metabolismo , Deficiencia de Vitamina D/metabolismo
18.
J Infect ; 81(4): 567-574, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32768450

RESUMEN

OBJECTIVES: The aim of this study is to investigate the clinical usefulness of metagenomic Next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) samples to discriminate pulmonary tuberculosis (PTB) from Non-TB community-acquired pneumonia (CAP) in PTB suspects. METHODS: We investigate the performance of mNGS on BALF samples from 110 PTB suspects, in comparison with conventional microbiological testing (solid media culture, acid-fast bacilli staining (AFS), Xpert) of BALF or sputum samples and final clinical diagnosis. RESULTS: We finally clinically diagnosed 48 cases of pulmonary tuberculosis patients and 62 cases of non-tuberculosis patients. Comparing to the final clinical diagnosis, mNGS produced a sensitivity of 47.92%, which was similar to that of Xpert (45.83%) and culture (46.81%), but much higher than that of AFS (29.17%) for TB diagnosis in BALF samples. Apart from detecting Mycobacterium tuberculosis, mNGS also identified mixed infections in PTB patients, including 3 fungal cases and 1 bacteria case. Meanwhile, mNGS efficiently identified 14 of 22 (63.63%) cases of non-tuberculous mycobacteria (NTM), 7 cases of fungi, 1 case of viral infection, and other common bacterial pathogens in Non-PTB group. Finally, mNGS identified 67.23% infection cases within 3 days, while the conventional methods identified 49.58% infection cases for over 90 days. CONCLUSION: Our data show that mNGS of BALF represents a potentially effective tool for the rapid diagnosis of PTB suspects.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Pulmonar , Humanos , Metagenoma , Metagenómica , Mycobacterium tuberculosis/genética , Sensibilidad y Especificidad , Esputo , Tuberculosis Pulmonar/diagnóstico
19.
J Bone Miner Metab ; 38(6): 780-793, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32533328

RESUMEN

INTRODUCTION: Osteonecrosis of the femoral head (ONFH) is a disease in which the blood supply of the femoral head is interrupted or damaged, resulting in joint dysfunction. Hypoxic environments increase the expression of EPO, VEGF, and HIF causes vascular proliferation and increases the blood supply. It also causes the organism to be in a state of hypercoagulability and increases thrombosis. Therefore, the purpose of this study was to explore the occurrence of ONFH after the use of glucocorticoids (GCs) under conditions of hypoxia tolerance for a long time. MATERIALS AND METHODS: Sprague-Dawley rats were fed in a hypobaric hypoxic chamber at an altitude of 4000 m, the whole blood viscosity, and plasma viscosity were determined to analyze the blood flow and hemagglutination. Western blotting, polymerase chain reaction, and immunohistochemistry were used to detect EPO, VEGF, CD31, and osteogenesis related proteins. Femoral head angiography was used to examine the local blood supply and micro-CT scanning was used to detect the structure of the bone trabecula. RESULTS: Under hypoxic environments, the expression of EPO and VEGF increased, which increased the local blood supply of the femoral head, but due to more severe thrombosis, the local blood supply of the femoral head decreased. CONCLUSIONS: Hypoxic environments can aggravate ONFH in SD rats; this aggravation may be related to the hypercoagulable state of the blood. We suggest that long-term hypoxia should be regarded as one of the risk factors of ONFH and we need to conduct a more extensive epidemiological investigation on the occurrence of ONFH in hypoxic populations.


Asunto(s)
Necrosis de la Cabeza Femoral/patología , Hipoxia/patología , Fosfatasa Alcalina/metabolismo , Animales , Coagulación Sanguínea , Diferenciación Celular , Proliferación Celular , Eritropoyetina/metabolismo , Necrosis de la Cabeza Femoral/sangre , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Glucocorticoides/efectos adversos , Masculino , Osteogénesis , Oxígeno , Presión Parcial , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular/metabolismo , Microtomografía por Rayos X
20.
Reprod Toxicol ; 94: 40-47, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32330513

RESUMEN

Gestational vitamin D deficiency is associated with pulmonary diseases. This study aimed to investigate the effect of gestational vitamin D deficiency on fetal lung development in mice. Absolute and relative weights of fetal lungs were reduced in vitamin D deficient (VDD) group. Incrassate mesenchyme, measured by septal wall thickness, accompanied by lessened saccular space, was shown in VDD group. Numerous immature type II pneumocytes, as determined by PAS staining, were observed in VDD group. Moreover, increased Ki67-positive cells, a marker of cell proliferation, was detected in VDD group. The additional experiments showed that Sftpa, Sftpb, Sftpc and Sftpd, four surfactant genes, were downregulated and pro-surfactant protein B was reduced in VDD group. FoxA1, FoxA2 and TTF-1, three transcription factors that regulate surfactant genes, and VEGF, a key regulator for pulmonary maturation, were downregulated in VDD group. These results suggest that gestational vitamin D deficiency impairs fetal lung development partially through suppressing type II pneumocyte differentiation.


Asunto(s)
Células Epiteliales Alveolares/citología , Desarrollo Fetal , Pulmón/crecimiento & desarrollo , Deficiencia de Vitamina D/complicaciones , Células Epiteliales Alveolares/metabolismo , Animales , Diferenciación Celular , Citocinas/genética , Proteínas de Unión al ADN/genética , Femenino , Feto , Factor Nuclear 3-alfa del Hepatocito/genética , Factor Nuclear 3-beta del Hepatocito/genética , Humanos , Antígeno Ki-67/metabolismo , Masculino , Ratones , Embarazo , Proteínas Asociadas a Surfactante Pulmonar/genética , Proteínas Asociadas a Surfactante Pulmonar/metabolismo , Factores de Transcripción/genética , Factor A de Crecimiento Endotelial Vascular/genética , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/genética , Deficiencia de Vitamina D/metabolismo , Vitaminas/sangre
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