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1.
Lab Anim Res ; 40(1): 13, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38582857

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a biphasic type of skin inflammation characterized by a predominance of type-2 (TH2) and type-1 (TH1) helper T cell-biased immune responses at the acute and persistent chronic phases, respectively. The present study was aimed to evaluate the efficacy of Artemisia dubia folium extract (ADFE) on AD-like skin lesions through developing a murine model for acute and chronic stages of AD. To induce acute phase AD, the dorsal skin of BALB/c mice was sensitized twice a week with 1% 2, 4-dinitrochlorobenzene (DNCB), followed by challenge (twice) in the following week with 0.2% DNCB. To induce persistent chronic AD, some mice were challenged twice a week for 4 more weeks. After the second challenge, the dorsal skin was exposed to 3% ADFE (five times per week) for 2 weeks (acute phase) or 4 weeks (persistent chronic phase). RESULTS: The paradigm of TH2 or TH1 predominance at the acute and chronic phase, respectively, was observed in this mouse model. During the acute phase, we observed an increased IL-4/IFN-γ ratio in splenic culture supernatants, an increased IgG1/IgG2a ratio in serum, and elevated serum IgE levels; however, the skew toward TH2 responses was diminished during the chronic stage. Compared with vehicle controls, ADFE reduced the IL-4/IFN-γ and IgG1/IgG2a ratios in acute AD, but both ratios increased during the chronic stage. CONCLUSIONS: Our results suggest that ADFE concomitantly suppresses the TH2 predominant response in acute AD, as well as the TH1 predominant response in chronic AD. Thus, ADFE is a candidate therapeutic for AD.

2.
PLoS One ; 19(1): e0293974, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38241326

RESUMO

Radiotherapy is commonly used to treat solid cancers located in the pelvis. A considerable number of patients experience proctitis of varying severity, even for a considerable period after radiotherapy. These side effects are often long-lasting or progressively worsen despite multiple therapeutic efforts and are a primary cause of an unexpectedly low quality of life, even after successful cancer treatment. Therefore, this study evaluated the individual and combined efficacy of ginsenoside, curcumin, butyric acid, and sucralfate compounds in treating radiation-induced proctitis. While the candidate compounds did not affect the proliferation and migration of cancer cells, they promoted the recovery of cell activity, including motility. They exhibited anti-inflammatory effects on human dermal fibroblasts or human umbilical vein endothelial cells within in vitro disease models. When each compound was tested, curcumin and ginsenoside were the most effective in cell recovery and promoted the migration of human dermal fibroblasts and cell restoration of human umbilical vein endothelial cells. The combination of ginsenoside and curcumin resulted in cell migration recovery of approximately 54%. In addition, there was a significant improvement in the length of the endothelial tube, with an increase of approximately 25%, suggesting that the ginsenoside-curcumin-containing combination was the most effective against radiation-induced damage. Furthermore, studies evaluating the effects of combined treatments on activated macrophages indicated that the compounds effectively reduced the secretion of inflammatory cytokines, including chemokines, and alleviated radiation-induced inflammation. In conclusion, our study provides valuable insights into using curcumin and ginsenoside as potential compounds for the effective treatment of radiation-induced injuries and highlights the promising therapeutic benefits of combining these two compounds.


Assuntos
Curcumina , Ginsenosídeos , Proctite , Humanos , Curcumina/farmacologia , Ginsenosídeos/farmacologia , Qualidade de Vida , Proctite/terapia , Células Endoteliais da Veia Umbilical Humana , Compostos Fitoquímicos
3.
Sci Rep ; 12(1): 12968, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902671

RESUMO

Hyperhomocysteinemia was reported to enhance endoplasmic reticulum (ER) stress and subsequent apoptosis in several cells. However, the precise mechanisms of smoking susceptibility associated with hyperhomocysteinemia has not been fully elucidated. This study included 7- to 9-week-old C57BL6 male mice induced with hyperhomocysteinemia and were exposed to cigarette smoke (CS). A549 cells (human alveolar epithelial cell line) were cultured with homocysteine and were exposed to cigarette smoke extract (CSE) to observe cell viability and expression of proteins related to the ER stress. After 6 months of CS exposure, pulmonary emphysema was more severely induced in the group under the condition of hyperhomocysteinemia compared to that in the control group. The apoptotic A549 cells increased as homocysteine concentration increased and that was enhanced by CSE. Protein expression levels of ER stress markers were significantly increased after simultaneous stimulation. Notably, vitamin B12 and folate supplementation improved ER stress after simultaneous stimulation of A549 cells. In this study, we showed that hyperhomocysteinemia exacerbates CS exposure-induced emphysema in mice, suggesting that hyperhomocysteinemia and CS stimulation enhance ER stress and subsequent induced apoptosis in alveolar epithelial cells. It was suggested that there is a synergistic effect between homocysteine and CS.


Assuntos
Enfisema , Hiper-Homocisteinemia , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Animais , Apoptose , Modelos Animais de Doenças , Enfisema/etiologia , Homocisteína , Humanos , Hiper-Homocisteinemia/complicações , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doença Pulmonar Obstrutiva Crônica/metabolismo , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/metabolismo , Nicotiana/efeitos adversos
4.
Am J Respir Cell Mol Biol ; 66(4): 428-438, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35081017

RESUMO

Lung function deterioration is significantly associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). We previously reported that CC chemokine ligand 17/thymus and activation-regulated chemokine (CCL17/TARC) could be a predictive factor of lung function decline in patients with COPD. However, the role of CCL17 in the pathogenesis of COPD is unclear. Here we examined the role of CCL17 in lung inflammation using mouse COPD models. Exposure to cigarette smoking induced CCL17 production in bronchial epithelial cells and accumulation of alveolar macrophages in the lungs. Intranasal administration of recombinant CCL17 further enhanced cigarette smoke-induced macrophage accumulation and also aggravated elastase-induced pulmonary emphysema. We confirmed that cigarette smoke (CS) extract as well as hydrogen peroxide upregulated CCL17 in BAES-2B cells. Of note, macrophages of both M1 and M2 surface markers were accumulated by cigarette smoke. Both alveolar macrophage accumulation via exposure to cigarette smoking and emphysematous changes induced by elastase administration were significantly reduced in CCL17-deficient mice. We further demonstrated that CCL17 strongly induced the expression of CC chemokine ligand 2 (CCL2), a chemoattractant for macrophages, in RAW264.7 cells, and its production was inhibited by knockdown of CCR4, the receptor of CCL17. Collectively, the present results demonstrate that CCL17 is produced by lung epithelial cells upon CS exposure. Furthermore, CCL17 is involved in CS-induced accumulation of alveolar macrophages and development of elastase-induced pulmonary emphysema, possibly through CCL17-induced production of CCL2 by macrophages. Our findings may provide a new insight into the pathogenesis of COPD.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Animais , Modelos Animais de Doenças , Humanos , Ligantes , Pulmão/patologia , Camundongos , Doença Pulmonar Obstrutiva Crônica/patologia , Enfisema Pulmonar/metabolismo
5.
Mol Psychiatry ; 26(10): 5658-5668, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34272488

RESUMO

Perineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. We first confirmed that aged mice (20-months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated. We then explored the role of C6S in memory and neuroplasticity. Transgenic deletion of chondroitin 6-sulfotransferase (chst3) led to a reduction of permissive C6S, simulating aged brains. These animals showed very early memory loss at 11 weeks old. Importantly, restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment.


Assuntos
Sulfatos de Condroitina , Plasticidade Neuronal , Envelhecimento , Animais , Encéfalo , Matriz Extracelular , Camundongos
6.
Sci Adv ; 7(14)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33789891

RESUMO

Gene replacement approaches are leading to a revolution in the treatment of previously debilitating monogenic neurological conditions. However, the application of gene therapy to complex polygenic conditions has been limited. Down-regulation or dysfunction of receptor expression in the disease state or in the presence of excess ligand has been shown to compromise therapeutic efficacy. Here, we offer evidence that combined overexpression of both brain-derived neurotrophic factor and its receptor, tropomyosin receptor kinase B, is more effective in stimulating axonal transport than either receptor administration or ligand administration alone. We also show efficacy in experimental glaucoma and humanized tauopathy models. Simultaneous administration of a ligand and its receptor by a single gene therapy vector overcomes several problems relating to ligand deficiency and receptor down-regulation that may be relevant to multiple neurodegenerative diseases. This approach shows promise as a strategy to target intrinsic mechanisms to improve neuronal function and facilitate repair.


Assuntos
Transporte Axonal , Neurônios , Suplementos Nutricionais , Terapia Genética , Ligantes , Neurônios/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-33790550

RESUMO

PURPOSE: Lung cancer is a serious complication in patients with chronic obstructive pulmonary disease (COPD) and accounts for approximately 15% of deaths in patients with COPD. However, with the exception of emphysema, few reports to date have been published on the factors that predict lung cancer development in COPD patients. It has been reported that patients with COPD develop lung cancer at a rate of 0.8% - 1.7%/year, but the incidence may be higher in the Japanese population. Therefore, we investigated the incidence of lung cancer and the lung cancer mortality rate in Japanese COPD patients, as well as factors that are associated with the development of lung cancer in COPD patients. PATIENTS AND METHODS: We followed up 224 patients with stable COPD and performed CT examinations at least once per year. The incidence of lung cancer was recorded and data at enrollment were compared with data of the group that did not develop lung cancer. RESULTS: Over a median follow-up period of 4.58 years, lung cancer was newly diagnosed in 19 patients; the incidence of lung cancer in this population was 1.85%/year. Patients who developed lung cancer had more severe emphysema assessed by CT and GOLD classification and were more likely to be current smokers than those who did not develop lung cancer. No other significant differences were observed between these two groups. Mortality was significantly increased in patients who developed lung cancer compared with those who did not. CONCLUSION: In COPD patients, the incidence of lung cancer is higher and the development of lung cancer worsens the prognosis; however, lung cancer development is unpredictable and attention should be paid to all patients. Annual CT screening is important for early detection of lung cancer.


Assuntos
Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Detecção Precoce de Câncer , Humanos , Incidência , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Medição de Risco , Tomografia Computadorizada por Raios X
8.
Toxicol Ind Health ; 37(4): 219-228, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33663293

RESUMO

Animal husbandry workers are exposed to various malodorous compounds in the workplace. Although these compounds cause severe nuisance, no systemic investigation of their effects on the immune system has been conducted. To address this issue, we evaluated the effects of inhalational exposure to ammonia, dimethyl disulfide, 3-methylindole (3-MI), and propionic acid (PA), representing four major groups of malodorous compounds, on humoral and cellular immunity in mice. Mice were exposed to the substances (low dose: 10 µL and high dose: 200 µL) for 10 min/day for 4 weeks in a modified standard mouse cage. Neutrophil% and splenic cytotoxic T cell% were significantly lower in the high-dose ammonia group than in the vehicle control. Exposure to ammonia and 3-MI increased immature thymic T lymphocyte% relative to control and concomitantly decreased both mature helper and cytotoxic T-cell populations in the thymus. In the ammonia exposure group, levels of serum immunoglobulin E and immunoglobulin A were elevated, and the IgG2a:IgG1 ratio in the serum was reduced in a dose-dependent manner. Splenic natural killer cell activity was significantly less in the PA exposure group than in the control. Overall, our findings suggest that inhalational exposure to these malodorous substances disturbs immune homeostasis in vivo.


Assuntos
Amônia/imunologia , Dissulfetos/imunologia , Propionatos/imunologia , Escatol/imunologia , Criação de Animais Domésticos , Animais , Humanos , Imunoglobulina A/efeitos dos fármacos , Imunoglobulina E/efeitos dos fármacos , Exposição por Inalação , Células Matadoras Naturais/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Exposição Ocupacional/efeitos adversos , Linfócitos T/efeitos dos fármacos
9.
Respir Investig ; 59(4): 498-504, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33642232

RESUMO

BACKGROUND: Several studies have demonstrated the association between mean corpuscular hemoglobin concentration (MCHC), a hematological index used for the assessment of anemia, and the prognosis of patients with heart disease. While the red cell distribution width (RDW) is known to be related to the prognosis of patients with chronic obstructive pulmonary disease (COPD), few studies have focused on the association between the MCHC and COPD. Therefore, we examined the association between the MCHC and prognosis in patients with exacerbation of COPD. METHODS: We examined the association between the 30-day mortality and clinical findings in patients with COPD exacerbation who were hospitalized between October 2008 and December 2018. RESULTS: We enrolled 195 patients with COPD exacerbation (average age: 76.4 years; 181 men, 14 women). The MCHC was significantly lower, while the RDW was significantly higher in the 27 patients (13.8%) who died during the 30-day observation period compared to those in the patients who survived. Multivariate logistic regression analysis revealed that the MCHC was independently associated with 30-day mortality. The area under the curve calculated from the MCHC obtained from peripheral blood was 0.688 and the cutoff value was 31.6 g/dL, with a sensitivity of 0.593 and specificity of 0.810 (p = 0.0001). CONCLUSION: The MCHC might be a valuable biomarker for evaluating the prognosis of patients with COPD exacerbation.


Assuntos
Anemia , Doença Pulmonar Obstrutiva Crônica , Idoso , Biomarcadores , Índices de Eritrócitos , Feminino , Humanos , Masculino , Prognóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico
10.
ACS Appl Mater Interfaces ; 13(1): 955-961, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33379863

RESUMO

Development of two-dimensional (2D) semiconductor devices with good Ohmic contact is essential to utilize their full potential for nanoelectronics applications. Among the methods that have been introduced to reduce the Schottky barrier in 2D material-based electronic devices, charge transfer doping has attracted significant interest because of its efficiency, simplicity, and compatibility with the microelectronic fabrication process. In this study, 2D WSe2-based field-effect transistors (FETs) were subjected to selective UV/ozone treatment to improve the Ohmic contact by forming WOX with a high work function, which induced hole doping in the neighboring WSe2 via electron transfer. The atomic force microscopy, cross-sectional transmission electron microscopy, and micro-Raman spectroscopy analyses confirmed the self-limiting formation of WOX while maintaining the crystallinity of the underlying WSe2. The channel layer of the back-gated 2D WSe2 FETs was encapsulated using 2D hexagonal boron nitride to prevent the UV/ozone-induced oxidation. By contrast, the regions that were in contact with the underlying metal electrodes were open, which allowed area-selective p-doping in the 2D WSe2. Our study demonstrated that the Ohmic-like behaviors obtained after area-selective UV/ozone treatment improved the electrical properties of the 2D WSe2-based FETs such as the field-effect mobility (improvement of 3-4 orders of magnitude) and current on/off ratio (improvement of five orders of magnitude), while maintaining the p-type normally-off characteristics. These results provide useful insights into an effective and facile method to reduce contact resistance in 2D semiconductor materials, thereby enhancing the electrical performances of 2D material-based electronic devices.

11.
Allergol Int ; 70(1): 81-88, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32444304

RESUMO

BACKGROUND: The deterioration of pulmonary function, such as FEV1-decline, is strongly associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). However, few investigations shed light on useful biomarkers for predicting the decline of pulmonary function. We evaluated whether thymus and activation-regulated chemokine (TARC), a Th2 inflammation marker, could predict rapid FEV1-decline in COPD patients. METHODS: We recruited 161 patients with stable COPD and performed pulmonary function test once every six months. At the time of registration, blood tests, including serum levels of TARC were performed. We assessed the correlation between changes in parameters of pulmonary function tests and serum levels of TARC. The rapid-decline in pulmonary function was determined using 25th percentile of change in FEV1 or FEV1 percent predicted (%FEV1) per year. RESULTS: In the FEV1-rapid-decline group, the frequency of exacerbations, the degree of emphysema, and serum levels of TARC was higher than in the non-rapid-decline group. When using %FEV1 as a classifier instead of FEV1, age, the frequency of exacerbations, the degree of emphysema and serum levels of TARC in the rapid-decline group was significantly greater than those in the non-rapid-decline group. In univariate logistic regression analysis, TARC was the significant predictive factor for rapid-decline group. In multivariate analysis adjusted for emphysema, serum levels of TARC are independently significant predicting factors for the rapid-decline group. CONCLUSIONS: TARC is an independent predictive biomarker for the rapid-decline in FEV1. Measuring serum TARC levels may help the management of COPD patients by predicting the risk of FEV1 decline.


Assuntos
Biomarcadores , Quimiocina CCL17/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Quimiocinas/sangue , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Prognóstico , Doença Pulmonar Obstrutiva Crônica/etiologia , Curva ROC , Testes de Função Respiratória , Índice de Gravidade de Doença , Células Th2/imunologia , Células Th2/metabolismo
12.
Mol Psychiatry ; 26(2): 556-567, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-31758091

RESUMO

Parkinson's disease (PD) is an α-synucleinopathy characterized by the progressive loss of specific neuronal populations. Here, we develop a novel approach to transvascularly deliver proteins of complex quaternary structures, including α-synuclein preformed fibrils (pff). We show that a single systemic administration of α-synuclein pff triggers pathological transformation of endogenous α-synuclein in non-transgenic rats, which leads to neurodegeneration in discrete brain regions. Specifically, pff-exposed animals displayed a progressive deterioration in gastrointestinal and olfactory functions, which corresponded with the presence of cellular pathology in the central and enteric nervous systems. The α-synuclein pathology generated was both time dependent and region specific. Interestingly, the most significant neuropathological changes were observed in those brain regions affected in the early stages of PD. Our data therefore demonstrate for the first time that a single, transvascular administration of α-synuclein pff can lead to selective regional neuropathology resembling the premotor stage of idiopathic PD. Furthermore, this novel delivery approach could also be used to deliver a range of other pathogenic, as well as therapeutic, protein cargos transvascularly to the brain.


Assuntos
Sistema Nervoso Entérico , Doença de Parkinson , Animais , Encéfalo/metabolismo , Sistema Nervoso Entérico/metabolismo , Humanos , Neurônios/metabolismo , alfa-Sinucleína/metabolismo
13.
Front Toxicol ; 3: 649666, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35295130

RESUMO

The development of nanotechnology has propagated the use of nanoparticles (NPs) in various fields including industry, agriculture, engineering, cosmetics, or medicine. The use of nanoparticles in cosmetics and dermal-based products is increasing owing to their higher surface area and unique physiochemical properties. Silver (Ag) NPs' excellent broad-spectrum antibacterial property and zinc oxide (ZnO) NPs' ability to confer better ultraviolet (UV) protection has led to their maximal use in cosmetics and dermal products. While the consideration for use of nanoparticles is increasing, concerns have been raised regarding their potential negative impacts. Although used in various dermal products, Ag and ZnO NPs' skin sensitization (SS) potential has not been well-investigated using in vitro alternative test methods. The human Cell Line Activation Test (h-CLAT) that evaluates the ability of chemicals to upregulate the expression of CD86 and CD54 in THP-1 cell line was used to assess the skin sensitizing potential of these NPs. The h-CLAT assay was conducted following OECD TG 442E. NPs inducing relative fluorescence intensity of CD86 ≥ 150% and/or CD54 ≥ 200% in at least two out of three independent runs were predicted to be positive. Thus, Ag (20, 50, and 80 nm) NPs and ZnO NPs were all predicted to be positive in terms of SS possibility using the h-CLAT prediction model. Although further confirmatory tests addressing other key events (KEs) of SS adverse outcome pathway (AOP) should be carried out, this study gave an insight into the need for cautious use of Ag and ZnO NPs based skincare or dermal products owing to their probable skin sensitizing potency.

14.
Toxicol Ind Health ; 37(1): 1-8, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33295265

RESUMO

Household products often contain an antimicrobial agent such as biocides, polyhexamethylene guanidine (PHMG), triclosan (TCS), and propylene glycol (PG) as an excipient to dissolve the active ingredients. The skin sensitization (SS) potentials of each of these substances or mixtures of PHMG or TCS with PG have not been investigated through in vitro alternative test methods. The in vitro alternative assay called human Cell Line Activation Test (h-CLAT) served to address these issues. The h-CLAT assay was conducted in accordance with OECD TG 442E. On three independent runs, all the three substances were predicted to be sensitizers according to the SS positivity with relative fluorescence intensity of CD86 ≥ 150% and/or CD54 ≥ 200% at any tested concentrations. Mixtures of PHMG or TCS with PG at ratios of 9:1, 4:1, or 1:4 weight/volume were all positive in terms of SS potential. Since humans can be occupationally or environmentally exposed to mixtures of excipients with active ingredients of biocides, the present study may give insights into further investigations of the SS potentials of various chemical mixtures.


Assuntos
Anti-Infecciosos Locais/efeitos adversos , Exposição Ambiental/efeitos adversos , Guanidinas/efeitos adversos , Propilenoglicóis/efeitos adversos , Triclosan/efeitos adversos , Anti-Infecciosos Locais/química , Linhagem Celular , Relação Dose-Resposta a Droga , Excipientes , Guanidinas/química , Humanos , Exposição Ocupacional/efeitos adversos , Propilenoglicóis/química , Testes de Irritação da Pele , Triclosan/química
15.
EXCLI J ; 19: 1610-1614, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33437226

RESUMO

In this study, we investigated whether pulmonary function tests such as forced oscillation technique parameters could predict perioperative respiratory complications. In the results of our study, perioperative respiratory complications cannot be predicted using the results of preoperative pulmonary function tests and forced oscillation technique parameters. Patients who are judged by comprehensive preoperative judgment to be suitable for general anesthesia may not need to consider the risk of perioperative complications using pulmonary function test.

16.
Am J Respir Cell Mol Biol ; 62(5): 588-597, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31726018

RESUMO

Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD). Smoking susceptibility is important for the onset and development of COPD. We previously reported an association between serum iron concentrations and pulmonary function in male smokers. However, the mechanism governing smoking susceptibility in relation to iron deficiency is unclear; this study aimed to elucidate this mechanism. C57BL/6 male mice were fed an iron-deficient or normal diet and then exposed to cigarette smoke. BAL, histological analysis, and pulmonary function tests were performed after cigarette smoke exposure. Human alveolar type II epithelial A549 cells were treated with an iron chelator. Subsequently, A549 cells were exposed to cigarette smoke extract. In mice exposed to cigarette smoke for 2 weeks, the concentration of alveolar macrophages in the BAL fluid recovered from iron-deficient mice was significantly higher than that in normal diet mice. IL-6 and MCP-1 (monocyte chemotactic protein 1) concentrations in the BAL fluid increased significantly from baseline in iron-deficient mice, but not in normal diet mice. In mice exposed to cigarette smoke for 8 weeks, the pathological mean linear intercepts, physiological total lung capacity, and functional residual capacity in the lungs of iron-deficient mice were significantly greater than in normal diet mice. Phosphorylation of NF-κB was enhanced in the lungs of iron-deficient mice exposed to cigarette smoke and in the iron-chelating A549 cells exposed to cigarette smoke extract. Iron deficiency exaggerated cigarette smoke-induced pulmonary inflammation, suggesting that it may accelerate COPD development.


Assuntos
Enfisema/etiologia , Deficiências de Ferro , Fumar/efeitos adversos , Células A549 , Animais , Líquido da Lavagem Broncoalveolar , Dieta , Suplementos Nutricionais , Modelos Animais de Doenças , Enfisema/sangue , Contagem de Eritrócitos , Humanos , Inflamação/sangue , Inflamação/complicações , Inflamação/patologia , Íons , Ferro/sangue , Quelantes de Ferro/farmacologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos
17.
EXCLI J ; 18: 1062-1070, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839762

RESUMO

When examining patients with acute inflammatory respiratory diseases, it is difficult to distinguish between infectious pneumonia and interstitial pneumonia and predict patient prognosis at the beginning of treatment. In this study, we assessed whether endothelial selectin (E-selectin) predicts the outcome of patients with acute inflammatory respiratory diseases. We measured E-selectin serum levels in 101 patients who were admitted to our respiratory care unit between January 2013 and December 2013 because of acute inflammatory respiratory diseases that were eventually diagnosed as interstitial pneumonia (n = 38) and lower respiratory tract infection (n = 63). Seven of these patients (n = 101) died. The pneumonia severity score was significantly higher and the oxygen saturation of arterial blood measured by pulse oximeter (SpO2)/fraction of inspiratory oxygen (FiO2) was significantly lower in the deceased patients than in the surviving patients. There were significantly fewer peripheral lymphocytes and significantly higher E-selectin serum levels in the deceased patients than in the surviving patients. In the multiple logistic regression analysis, the E-selectin serum levels and SpO2/FiO2 ratio were independent predictive factors of prognosis. The risk of death during acute respiratory disease was determined using a receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) was 0.871 as calculated from the ES, and the cutoff value was 6453.04 pg/ml, with a sensitivity of 1.00 and a specificity of 0.72 (p = 0.0027). E-selectin may be a useful biomarker for predicting the prognosis of patients with acute inflammatory respiratory diseases.

18.
Toxicol Ind Health ; 35(10): 638-646, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31771499

RESUMO

The guanidine family of antimicrobial agents, which includes polyhexamethylene guanidine phosphate (PHMG) and oligo(2-(2-ethoxy)ethoxyethyl) guanidinium chloride (PGH), and chlorophenol biocidal chemicals such as 2,4,4'-trichloro-2'-hydroxydiphenyl ether (triclosan) are used in various occupational and environmental biocidal applications. The excipient propylene glycol (PG) is used to dissolve the active ingredients. The skin sensitization (SS) potential of these substances has not been systemically investigated and is still debated. Moreover, mixtures of PHMG, PGH, or triclosan with PG have not been evaluated for SS potency. An in vivo assay known as the local lymph node assay: 5-bromo-2-deoxyuridine-flow cytometry method (LLNA: BrdU-FCM) was recently adopted as an alternative testing method and was used to address these issues. Via the LLNA: BrdU-FCM, PHMG, PGH, and triclosan were predicted to be sensitizers, while PG was predicted to be a nonsensitizer. In addition, d-limonene, which is used as a flavoring in various consumer products, was also predicted to be a sensitizer, although no unanimous conclusion has been reached regarding its SS potential. Mixtures of PHMG, PGH, triclosan, or d-limonene with PG at ratios of 9:1, 4:1, and 1:4 (w/w) were all positive in terms of SS potential, indicating that the PG excipient does not influence the SS predictions of these chemicals. Since humans can be occupationally and environmentally exposed to mixtures of excipients with active ingredients, the present study may give insight into further investigations of the SS potentials of various chemical mixtures.


Assuntos
Guanidinas/efeitos adversos , Hipersensibilidade Imediata/induzido quimicamente , Polímeros/efeitos adversos , Propilenoglicóis/efeitos adversos , Pele/efeitos dos fármacos , Triclosan/efeitos adversos , Animais , Relação Dose-Resposta a Droga , Excipientes/efeitos adversos , Excipientes/química , Feminino , Guanidinas/química , Limoneno , Ensaio Local de Linfonodo , Camundongos , Camundongos Endogâmicos BALB C , Polímeros/química , Propilenoglicóis/química , Triclosan/química
19.
J Microbiol Biotechnol ; 29(12): 1957-1968, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31752061

RESUMO

Tetraselmis is a green algal genus, some of whose species are important in aquaculture as well as biotechnology. In algal culture, fluorescent lamps, traditional light source for culturing algae, are now being replaced by a cost-effective light-emitting diodes (LEDs). In this study, we investigated the effect of LED light of different wavelengths (white, red, yellow, and blue) on the growth of Tetraselmis suecica and its associated microbial community structures using the next-generation sequencing (NGS). The fastest growth rate of T. suecica was shown in the red light, whereas the slowest was in yellow. The highest OTUs (3426) were identified on day 0, whereas the lowest ones (308) were found on day 15 under red light. The top 100 OTUs associated with day 0 and day 5 cultures of T. suecica under the red and yellow LED were compared. Only 26 OTUs were commonly identified among four samples. The highest numbers of unique OTUs were identified at day 0, indicating the high degree of initial microbial diversity of the T. suecica inoculum. The red light-unique OTUs occupied 34.98%, whereas the yellow-specific OTUs accounted for only 2.2%. This result suggested a higher degree of interaction in T. suecica culture under the red light, where stronger photosynthesis occurs. Apparently, the microbial community associated with T. suecica related to the oxygen produced by algal photosynthesis. This result may expand our knowledge about the algaebacteria consortia, which would be useful for various biotechnological applications including wastewater treatment, bioremediation, and sustainable aquaculture.


Assuntos
Clorófitas/crescimento & desenvolvimento , Clorófitas/microbiologia , Clorófitas/efeitos da radiação , Sequenciamento de Nucleotídeos em Larga Escala , Luz , Microbiota/fisiologia , Aquicultura , Bactérias/classificação , Bactérias/genética , Clorófitas/genética , Cor , Metagenômica , Microbiota/genética , Oxigênio/metabolismo , Fotossíntese
20.
Toxicol Ind Health ; 35(8): 507-519, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31462197

RESUMO

In commercial products such as household deodorants or biocides, didecyldimethylammonium chloride (DDAC) often serves as an antimicrobial agent, citral serves as a fragrance agent, and the excipient ethylene glycol (EG) is used to dissolve the active ingredients. The skin sensitization (SS) potentials of each of these substances are still being debated. Moreover, mixtures of DDAC or citral with EG have not been evaluated for SS potency. The in vitro alternative assay called human Cell Line Activation Test (h-CLAT) and Direct Peptide Reactivity Assay (DPRA) served to address these issues. On three independent runs of h-CLAT, DDAC and citral were predicted to be sensitizers while EG was predicted to be a non-sensitizer and also by the DPRA. Mixtures of DDAC or citral with EG at ratios of 7:3 and 1:4 w/v were all positive by the h-CLAT in terms of SS potential but SS potency was mitigated as the proportion of EG increased. Citral and its EG mixtures were all positive but DDAC and its EG mixtures were all negative by the DPRA, indicating that the DPRA method is not suitable for chemicals with pro-hapten characteristics. Since humans can be occupationally or environmentally exposed to mixtures of excipients with active ingredients, the present study may give insights into further investigations of the SS potentials of various chemical mixtures.


Assuntos
Monoterpenos Acíclicos/efeitos adversos , Etilenoglicol/efeitos adversos , Excipientes/efeitos adversos , Compostos de Amônio Quaternário/efeitos adversos , Testes de Irritação da Pele/métodos , Pele/efeitos dos fármacos , Monoterpenos Acíclicos/administração & dosagem , Alternativas aos Testes com Animais/métodos , Antígeno B7-2/metabolismo , Bioensaio/métodos , Linhagem Celular , Etilenoglicol/administração & dosagem , Excipientes/administração & dosagem , Humanos , Molécula 1 de Adesão Intercelular/metabolismo
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