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1.
Carbohydr Polym ; 233: 115858, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32059909

RESUMO

Various nanoparticles have been developed for tumor-targeted drug delivery. However, nanoparticles with effective targeting and intelligent release capacity are still deficient. Herein, we present new pH-responsive and neutral charged nanoparticles for tumor-targeted anticancer drug delivery. Oxidized starch was synthesized and simultaneously modified by cholesterol and imidazole to obtain amphiphilic cholesterol/imidazole modified oxidized-starch (Cho-Imi-OS). Cho-Imi-OS easily self-assembled into nanoparticles by dialysis. Curcumin was selected as model drug to be encapsulated into the hydrophobic core of nanoparticles. The results showed that curcumin would effectively accumulate in cancer cells by encapsulating into the nanoparticles owing to the nano-sized structure and near neutral charged property of nanoparticles. Curcumin was released faster at pH 5.5 than that at pH 7.4 from the curcumin-loaded nanoparticles (Cur-NPs), indicating the pH-triggered release capacity of Cur-NPs after endocytosis by endosomes since the pH is low to 5.0∼6.0 in endosomes. Naturally, Cur-NPs showed significantly strong inhibitory effect on cancer cells.

2.
Int Immunopharmacol ; 81: 106261, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32058928

RESUMO

Exacerbation of chronic obstructive pulmonary disease (COPD) is characterized by acute airway inflammation and mucus hypersecretion, which is by far the most costly aspect of its management. Thus, it is essential to develop therapeutics with low side effects for CODP exacerbation. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated as the major active component of Chinese herbal medicine Danshen. Although it possesses anti-inflammatory, anti-oxidative and anti-apoptotic properties, it remains unknown whether STS protects against COPD exacerbation. In this study, we challenged cigarette smoke (CS)-exposed mice with lipopolysaccharide (LPS), and then treated these mice with STS. We found that STS significantly ameliorated pulmonary inflammatory responses, mucus hypersecretion and lung function decline in CS-exposed mice challenged with LPS. STS treatment also significantly attenuated increased IL-6 and IL-8 releases from cigarette smoke extract (CSE)-treated human bronchial epithelial cells (16HBE) challenged with LPS. Mechanistically, STS reduced activation of ERK1/2 and NF-κB in lungs of CS-exposed mice and CSE-treated 16HBE cells challenged with LPS. Taken together, STS protects against acute exacerbation of CS-induced lung injury, which provides a promising and potential therapeutic avenue to halt acute exacerbation of COPD.

3.
J Trace Elem Med Biol ; 59: 126454, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31954213

RESUMO

BACKGROUND: Manganese (Mn) ions play a crucial role in the immune response. The immunotoxicity of Mn is rarely reported compared with the neurotoxicity of Mn. OBJECTIVES: The purpose of this study was to investigate the associations between chronic Mn exposure and immunological parameters in occupational Mn-exposed workers. METHODS: A total of 538 workers were selected from the follow-up of manganese-exposed workers healthy cohort (MEWHC) in 2017. We divided the workers into the low-exposure group and the high-exposure group by the cutoff of the manganese-time weighted average (Mn-TWA) setting at 0.15 mg/m3. We examined serum immunological parameters by the immunoturbidimetric method and leukocyte counts and ratios in blood routine. Then we used the generalized linear model analyses and spline analyses to explore the associations between external exposure of Mn and multiple immunological parameters adjusted for variables. Based on the epidemiological analyses, we used Elisa (enzyme-linked immune sorbent assay) to detect plasma complement C3 of Mn-exposed rats. RESULTS: In male workers, the mean value of complement C3 was 1.20 ±â€¯0.16 g/L in the high-exposure group, which was significantly lower as compared to the low-exposure group (1.25 ±â€¯0.18 g/L, P = 0.023). The generalize linear models' analyses showed that complement C3 value had a significantly negative association with external exposure of Mn included adjustment for variables (ß = -0.04, P = 0.035). Moreover, in male rats, the high-exposure group also had a lower level of complement C3 compared with the low-exposure group (P < 0.001). None significant association was observed in immunological parameters among female workers and rats (all P > 0.05). CONCLUSIONS: Mn exposure from inhalable dust was associated with decreased complement C3 among occupationally Mn-exposed male individuals but not in female workers, which was further confirmed by the rat model. Further research into the possible mechanism of C3 reduction is needed in the future.

4.
Carbohydr Polym ; 230: 115573, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887939

RESUMO

Many kinds of multi-drug-resistant microorganisms have appeared. Moreover, monotherapy is increasingly no longer adequate for many complicated bacterial infections. Therefore, development of efficient combination antibacterial agent is becoming crucial. Herein, we present a hybrid antibacterial agent with enhanced antibacterial activity and high aqueous dissolubility based on silver nanoparticles and curcumin. The silver nanoparticles were firstly synthesized using oxidized amylose as an environmentally friendly reducing agent and stabilizer. Then, curcumin was added into the above mixture to get the hybrid antibacterial agent. The hybrid antibacterial agent presented high dissolubility in aqueous solution and enhanced antibacterial activity. In addition, the hybrid antibacterial agent presented good antioxidant activity and cell compatibility. Overall, the developed hybrid antibacterial agent has a potential to combat multiple bacteria-induced infections of wound surfaces.

5.
Environ Sci Pollut Res Int ; 27(1): 482-489, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31797269

RESUMO

Despite well documents for manganese-induced neurological deficits, limited researches are available for effects of manganese (Mn) exposure on the bone. Here we aimed to explore the associations between long-term occupational Mn exposure and bone quality among retired workers. We conducted a cross-sectional study of 304 exposed subjects (n, male = 161 and female = 143) and 277 control retired workers (n, male = 65 and female = 212) recruited from a ferromanganese refinery. Self-reported occupation types were used as exposure classification confirmed by expert consultation. Bone quality was measured by quantitative ultrasound (QUS). In sex-stratified analyses throughout, stiffness index (SI) and T-score levels of the participants in the highest exposed group [tertile 3 of Mn cumulative exposure index (Mn-CEI)] were significantly lower as compared with the control group among female workers (SI, mean, 61.60 vs. 68.17; T-score, mean, -3.01 vs. -2.34, both P < 0.05). In addition, SI and T-score were found to be negatively associated with Mn-CEI only in the highest exposure group as compared with the female controls (both P = 0.01). However, we did not find the significant difference for SI or T-score among the male subjects in exposure models and the male controls (P > 0.05). Our results suggest that female retired workers in the highest Mn-exposed model (tertile 3 of Mn-CEI) potentially experience a higher risk of developing osteoporosis compared with the female controls. Further investigations on possible mechanisms on bone quality alteration are needed in the future.

6.
Redox Biol ; 28: 101356, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31704583

RESUMO

Airway remodeling is one of the characteristics for chronic obstructive pulmonary disease (COPD). The mechanism underlying airway remodeling is associated with epithelial-mesenchymal transition (EMT) in the small airways of smokers and patients with COPD. Sirtuin 1 (SIRT1) is able to reduce oxidative stress, and to modulate EMT. Here, we investigated the effects and mechanisms of hydrogen sulfide (H2S) on pulmonary EMT in vitro and in vivo. We found that H2S donor NaHS inhibited cigarette smoke (CS)-induced airway remodeling, EMT and collagen deposition in mouse lungs. In human bronchial epithelial 16HBE cells, NaHS treatment also reduced CS extract (CSE)-induced EMT, collagen deposition and oxidative stress. Mechanistically, NaHS upregulated SIRT1 expression, but inhibited activation of TGF-ß1/Smad3 signaling in vivo and in vitro. SIRT1 inhibition by a specific inhibitor EX527 significantly attenuated or abolished the ability of NaHS to reverse the CSE-induced oxidative stress. SIRT1 inhibition also abolished the protection of NaHS against CSE-induced EMT. Moreover, SIRT1 activation attenuated CSE-induced EMT by modifying TGF-ß1-mediated Smad3 transactivation. In conclusion, H2S prevented CS-induced airway remodeling in mice by reversing oxidative stress and EMT, which was partially ameliorated by SIRT1 activation. These findings suggest that H2S may have therapeutic potential for the prevention and treatment of COPD.

7.
Mater Sci Eng C Mater Biol Appl ; 106: 110185, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753345

RESUMO

Silver nanoparticles (AgNPs) are effective antimicrobial reagent, especially for the treatment of multidrug-resistant microorganisms. However, it is difficult to remove the residual harmful reducing agents in AgNPs synthesized by the traditional chemical reduction method. In addition, AgNPs exhibit cytotoxicity when exposed directly to cells for biomedical applications and will rapidly aggregate in aqueous environment. Herein, we develop a new route to synthesize submicron-particles containing AgNPs (κC@Ag MPs) with high aqueous stability, robust antibacterial activity and low cytotoxicity. AgNPs were firstly greenly synthesized using κ-carrageenan as environmental friendly reducing and stabilizing agent under heating in aqueous solution. Then the AgNPs were immobilized in the net of κ-carrageenan by adding KCl to obtain κC@Ag MPs. The results indicated that κC@Ag MPs were quite stable without any agglomeration and precipitation in aqueous solution for more than three months. κC@Ag MPs exhibited robust antibacterial activity against Gram-positive and Gram-negative bacteria, even better than that of pure AgNPs. Notably, κC@Ag MPs maintained the long-lasting retention of antibacterial activity. In addition, κC@Ag MPs possessed well cytocompatibility towards the L02 and L929 cells. Overall, κC@Ag MPs may have prospective application as effective and sustainable antibacterial agent in biomedical fields.

8.
Environ Pollut ; 258: 113683, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31838386

RESUMO

Few studies specifically address the possible associations between multiple-metal exposures and liver damage among the occupational population. This study aimed to explore the cross-sectional relationships of plasma metals with liver function parameters. For 571 on-the-spot workers in the manganese-exposed workers healthy cohort (MEWHC), we determined liver function parameters: total bilirubin (TBILI), direct bilirubin (DBILI), indirect bilirubin (IBILI), alanine transaminase (ALT) and aspartate transaminase (AST). Total concentrations of 22 plasma metals were measured by ICP-MS. The LASSO (least absolute shrinkage and selection operator) penalized regression model was applied for selecting plasma metals independently associated with liver function parameters. Multiple linear regression analyses and restricted cubic spline (RCS) were utilized for identifying the exposure-response relationship of plasma metals with liver function parameters. After adjusting for covariates and selected metals, a 1-SD increase in log-10 transformed levels of iron was associated with increases in the levels of TBILI, DBILI and IBILI by 20.3%, 12.1% and 23.7%, respectively; similar increases in molybdenum for decreases in levels of TBILI, DBILI and IBILI by 6.1%, 2.6% and 8.3%, respectively. The effect of a 1-SD increase in plasma copper corresponded decreases of 3.2%, 3.4% and 5.0% in TBILI, AST and ALT levels, respectively. The spline analyses further clarified the non-linear relationships between plasma iron and bilirubin whilst negative linear relationships for plasma molybdenum and bilirubin. Plasma iron was positively whilst plasma molybdenum was negatively associated with increased serum bilirubin levels. Further studies are needed to validate these associations and uncover the underlying mechanisms.

9.
Int Immunopharmacol ; : 105979, 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31771816

RESUMO

Chronic obstructive pulmonary fibrosis (COPD) is a chronic and fatal lung disease with few treatment options. Sodium hydrosulfide (NaHS), a donor of hydrogen sulfide (H2S), was found to alleviate cigarette smoke (CS)-induced emphysema in mice, however, the underlying mechanisms have not yet been clarified. In this study, we investigated its effects on COPD in a CS-induced mouse model in vivo and in cigarette smoke extract (CSE)-stimulated alveolar epithelial A549 cells in vitro. The results showed that NaHS not only relieved emphysema, but also improved pulmonary function in CS-exposed mice. NaHS significantly increased the expressions of tight junction proteins (i.e., ZO-1, Occludin and claudin-1), and reduced apoptosis and secretion of pro-inflammatory cytokines (i.e., TNF-α, IL-6 and IL-1ß) in CS-exposed mouse lungs and CSE-incubated A549 cells, indicating H2S inhibits CS-induced inflammation, injury and apoptosis in alveolar epithelial cells. NaHS also upregulated prolyl hydroxylase (PHD)2, and suppressed hypoxia-inducible factor (HIF)-1α expression in vivo and in vitro, suggesting H2S inhibits CS-induced activation of PHD2/HIF-1α axis. Moreover, NaHS inhibited CS-induced phosphorylation of ERK, JNK and p38 MAPK in vivo and in vitro, and treatment with their inhibitors reversed CSE-induced ZO-1 expression and inflammation in A549 cells. These results suggest that NaHS may prevent emphysema via the suppression of PHD2/HIF-1α/MAPK signaling pathway, and subsequently inhibition of inflammation, epithelial cell injury and apoptosis, and may be a novel strategy for the treatment of COPD.

10.
Sci Rep ; 9(1): 7398, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31068652

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

11.
ACS Appl Mater Interfaces ; 11(1): 269-277, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30525427

RESUMO

The porous microstructure of scaffolds is an essential consideration for tissue engineering, which plays an important role for cell adhesion, migration, and proliferation. It is crucial to choose optimum pore sizes of scaffolds for the treatment of various damaged tissues. Therefore, the proper porosity is the significant factor that should be considered when designing tissue scaffolds. Herein, we develop an improved emulsion template method to fabricate gelatin-based scaffolds with controllable pore structure. Gelatin droplets were first prepared by emulsification and then solidified by genipin to prepare gelatin microspheres. The microspheres were used as a template for the fabrication of porous scaffolds, which were gathered and tightened together by dialdehyde amylose. The results showed that emulsification can produce gelatin microspheres with narrow size distribution. The size of gelatin microspheres was easily controlled by adjusting the concentration of gelatin and the speed of mechanical agitation. The gelatin-based scaffolds presented macroporous and interconnected structure. It is interesting that the pore size of scaffolds was directly related to the size of gelatin microspheres, displaying the same trend of change in size. It indicated that the gelatin microspheres can be used as the proper template to fabricate gelatin-based scaffold with a desired pore structure. In addition, the gelatin-based scaffolds possessed good blood compatibility and cytocompatibility. Overall, the gelatin-based scaffolds exhibited great potential in tissue engineering.


Assuntos
Gelatina/química , Teste de Materiais , Microesferas , Tecidos Suporte/química , Animais , Adesão Celular , Linhagem Celular , Humanos , Camundongos , Porosidade , Coelhos , Engenharia Tecidual
12.
J Thorac Dis ; 10(6): 3232-3243, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30069319

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is a chronic lung disease with limited treatment options. Hydrogen (H2) has been shown to be anti-oxidative and anti-inflammatory. This study aimed to evaluate the beneficial effects of H2 inhalation on COPD development in mice. Methods: A COPD mouse model was established in male C57BL mice by cigarette smoke (CS) exposure. The H2 intervention was administered by atomisation inhalation. Lung functions were assessed by using Buxco lung function measurement system. The inflammatory cells were counted and the levels of IL-6 and KC in BALF were assayed with ELISA. The lung tissue was subjected to H&E or PAS or Masson's trichrome stain. Furthermore, 16HBE cells were used to evaluate the effects of H2 on signaling change caused by hydrogen peroxide (H2O2). H2O2 was used to treat 16HBE cells with or without H2 pretreatment. The IL-6 and IL-8 levels in cell culture medium were measured. The levels of phosphorylated ERK1/2 and nucleic NF-κB in lungs and 16HBE cells were determined. Results: H2 ameliorated CS-induced lung function decline, emphysema, inflammatory cell infiltration, small-airway remodelling, goblet-cell hyperplasia in tracheal epithelium and activated ERK1/2 and NF-κB in mouse lung. In 16HBE airway cells, H2O2 increased IL-6 and IL-8 secretion in conjunction with ERK1/2 and NF-κB activation. These changes were reduced by H2 treatment. Conclusions: These findings demonstrated that H2 inhalation could inhibit CS-induced COPD development in mice, which is associated with reduced ERK1/2 and NF-κB-dependent inflammatory responses.

13.
Exp Physiol ; 103(11): 1532-1542, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30070749

RESUMO

NEW FINDINGS: What is the central question of this study? In this study, by using motor vehicle exhaust (MVE) exposure with or without lipopolysaccharide (LPS) instillation, we established, evaluated and compared MVE, LPS and MVE+LPS treatment-induced chronic obstructive pulmonary disease (COPD) models in mice. What is the main finding and its importance? Our study demonstrated that the combination of chronic exposure to MVE with early LPS instillation can establish a mouse model with some features of COPD, which will allow researchers to investigate the underlying molecular mechanisms linking air pollution and COPD pathogenesis. ABSTRACT: Although it is well established that motor vehicle exhaust (MVE) has a close association with the occurrence and exacerbation of chronic obstructive pulmonary disease (COPD), very little is known about the combined effects of MVE and intermittent or chronic subclinical inflammation on COPD pathogenesis. Therefore, given the crucial role of inflammation in the development of COPD, we wanted to establish an animal model of COPD using both MVE exposure and airway inflammation, which could mimic the clinical pathological changes observed in COPD patients and greatly benefit the study of the molecular mechanisms of COPD. In the present study, we report that mice undergoing chronic exposure to MVE and intratracheal instillation of lipopolysaccharide (LPS) successfully established COPD, as characterized by persistent air flow limitation, airway inflammation, inflammatory cytokine production, emphysema and small airway remodelling. Moreover, the mice showed significant changes in ventricular and vascular pathology, including an increase in right ventricular pressure, right ventricular hypertrophy and remodelling of pulmonary arterial walls. We have thus established a new mouse COPD model by combining chronic MVE exposure with early intratracheal instillation of LPS, which will allow us to study the relationship between air pollution and the development of COPD and to investigate the underlying molecular mechanisms.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Lipopolissacarídeos/efeitos adversos , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Animais , Modelos Animais de Doenças , Camundongos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
14.
BMC Public Health ; 18(1): 944, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30068329

RESUMO

BACKGROUND: Long-term excess exposure to environmental manganese (Mn) can lead to multi-system damage, especially in occupational populations. Therefore, we established a manganese-exposed workers healthy cohort (MEWHC), focusing on the systemic health effects related to Mn exposure. Here, we aimed to describe the follow-up activity for the MEWHC study and establish a standardized biological sample bank for the scientific management of high-quality biospecimens and the attached data from 2011 to 2017. METHODS: Baseline examinations for onsite workers were conducted, and the biobank for the MEWHC was first established in 2011; follow-up examinations occurred four times between July 2012 and November 2017. All questionnaires, clinical data and biological samples were routinely collected during each follow-up activity. Additional workers were recruited in 2016, which further enriched the resources of the biobank. RESULTS: A total of 2359 onsite workers and 612 retired workers at a ferromanganese refinery were enrolled in the prospective cohort, and their biological samples were obtained in the preliminary baseline survey and the follow-up investigation, including 2971 blood and urine samples from the cohort. In addition, 1524 hair samples, 1404 nail (toe and finger nails) and 1226 fecal samples were also collected. All specimens were preserved in the biobank, and the data were scientifically managed using a computer system. CONCLUSIONS: The MEWHC study in China provides an effective way to obtain biological samples such as plasma, DNA, hair and urine for storage in a biobank for further study. The standardized management of various samples is crucial for accessing high-quality biospecimens.


Assuntos
Bancos de Espécimes Biológicos , Monitoramento Ambiental/métodos , Ferro/análise , Manganês/análise , Exposição Ocupacional/análise , Adulto , China , Feminino , Seguimentos , Humanos , Ferro/toxicidade , Masculino , Manganês/toxicidade , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Saúde do Trabalhador , Estudos Prospectivos
15.
Food Res Int ; 111: 237-243, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30007682

RESUMO

Consumers demand more alternatives of riskless antibacterial agents to prevent microbial contamination in food industry. Oxidized carbohydrate may be a potential option as new antibacterial agent. However, the relatively weak antibacterial property of oxidized carbohydrate is not satisfactory. In this paper, dialdehyde ß-cyclodextrins with different oxidation degree were prepared by periodate oxidation and their antibacterial properties were systematically studied. The results showed that multi-aldehyde groups were successfully introduced into ß-cyclodextrin molecules by periodate oxidation. The aqueous solubility and stability of dialdehyde ß-cyclodextrins were improved as expected. It is interesting that dialdehyde ß-cyclodextrins possessed outstanding antibacterial activity against both Gram-positive and Gram-negative bacteria. The minimal inhibitory concentrations against E. coli, S. aureus and B. subtilis reached 0.63, 1.25 and 0.63 mg/mL, respectively. Moreover, dialdehyde ß-cyclodextrins effectively inhibited bacterial growth on the surface of apples. The results demonstrated that oxidized oligosaccharide with multi-aldehyde groups and good dispersibility in aqueous solution possessed satisfactory antibacterial activity, which can be used as new antibacterial agent in food industry.


Assuntos
Antibacterianos/análise , Antibacterianos/química , beta-Ciclodextrinas/análise , beta-Ciclodextrinas/química , Oxirredução , Solubilidade , Difração de Raios X
16.
Environ Sci Pollut Res Int ; 25(26): 26259-26266, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29978313

RESUMO

TiO2 shows great potential as ideal and powerful photocatalyst to degrade and eliminate harmful organic pollutants from waste water. It is desirable to prepare anatase TiO2 with good aqueous solubility and photocatalytic activity for water decontamination. In this paper, water-soluble TiO2 nanoparticles were successfully prepared using polytetramethylene ether glycol (PTMG), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) as stabilizers. The anatase phase of TiO2 was well controlled by introduction of HCl in the reaction system. The results showed that all the polymer-capped TiO2 were well dissolved in water and their aqueous solutions could maintain stable for more than 2 months. The photocatalytic activities of polymer-capped TiO2 were evaluated by monitoring the degradation of Rhodamine B (RhB) with Degussa P25 as a control. The results showed that all the polymer-capped TiO2 presented better photocatalytic activity than that of Degussa P25. PTMG capped TiO2 exhibited the longest average lifetime of charge carriers, indicating the lowest charge recombination rate. Thus, PTMG capped TiO2 presented the best photocatalytic activity. In summary, PTMG, PEG, and PPG can be used as stabilizers to prepare water-soluble TiO2. PTMG is an ideal stabilizer for the synthesis of water-soluble TiO2 with good photocatalytic activity.


Assuntos
Glicóis/química , Nanopartículas/química , Fotólise , Titânio/química , Poluentes Químicos da Água/química , Polímeros/química , Rodaminas , Águas Residuárias , Água , Purificação da Água/métodos
17.
Sci Rep ; 8(1): 7609, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29765063

RESUMO

Long non-coding RNAs (lncRNAs) have critical regulatory roles in protein-coding gene expression. Aberrant expression profiles of lncRNAs have been observed in various human diseases. In this study, we investigated transcriptome profiles in lung tissues of chronic cigarette smoke (CS)-induced COPD mouse model. We found that 109 lncRNAs and 260 mRNAs were significantly differential expressed in lungs of chronic CS-induced COPD mouse model compared with control animals. GO and KEGG analyses indicated that differentially expressed lncRNAs associated protein-coding genes were mainly involved in protein processing of endoplasmic reticulum pathway, and taurine and hypotaurine metabolism pathway. The combination of high throughput data analysis and the results of qRT-PCR validation in lungs of chronic CS-induced COPD mouse model, 16HBE cells with CSE treatment and PBMC from patients with COPD revealed that NR_102714 and its associated protein-coding gene UCHL1 might be involved in the development of COPD both in mouse and human. In conclusion, our study demonstrated that aberrant expression profiles of lncRNAs and mRNAs existed in lungs of chronic CS-induced COPD mouse model. From animal models perspective, these results might provide further clues to investigate biological functions of lncRNAs and their potential target protein-coding genes in the pathogenesis of COPD.


Assuntos
Perfilação da Expressão Gênica/métodos , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , RNA Longo não Codificante/genética , Produtos do Tabaco/efeitos adversos , Ubiquitina Tiolesterase/genética , Células A549 , Animais , Células Cultivadas , Modelos Animais de Doenças , Regulação da Expressão Gênica , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Pulmão/química , Pulmão/efeitos dos fármacos , Masculino , Camundongos , Doença Pulmonar Obstrutiva Crônica/genética , Análise de Sequência de RNA
18.
Front Pharmacol ; 9: 263, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29765317

RESUMO

Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, can mediate its effect through inhibiting HIF-1α-induced oxidative stress and inflammation in cigarette smoke (CS)-induced COPD in mice. Here, we found that STS improved pulmonary function, ameliorated emphysema and decreased the infiltration of inflammatory cells in the lungs of CS-exposed mice. STS reduced CS- and cigarette smoke extract (CSE)-induced upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in the lungs and macrophages. STS also inhibited CSE-induced reactive oxygen species (ROS) production, as well as the upregulation of heme oxygenase (HO)-1, NOX1 and matrix metalloproteinase (MMP)-9 in macrophages. In addition, STS suppressed HIF-1α expression in vivo and in vitro, and pretreatment with HIF-1α siRNA reduced CSE-induced elevation of TNF-α, IL-1ß, and HO-1 content in the macrophages. Moreover, we found that STS inhibited CSE-induced the phosphorylation of ERK, p38 MAPK and JNK in macrophages, and inhibition of these signaling molecules significantly repressed CSE-induced HIF-1α expression. It indicated that STS inhibits CSE-induced HIF-1α expression likely by blocking MAPK signaling. Furthermore, STS also promoted HIF-1α protein degradation in CSE-stimulated macrophages. Taken together, these results suggest that STS prevents COPD development possibly through the inhibition of HIF-1α signaling, and may be a novel strategy for the treatment of COPD.

19.
Carbohydr Polym ; 192: 118-125, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29691003

RESUMO

Dialdehyde-amyloses, dicarboxyl-amyloses and dialdehyde-carboxyl-amyloses with different oxidation levels were prepared and used to study the effects of aldehyde and carboxyl groups on the antibacterial activity of oxidized amyloses. The results showed that dicarboxyl-amyloses presented antibacterial activity through acidic pH effect produced by carboxyl groups, which was easily reduced or eliminated by adjusting pH. Dialdehyde-amyloses possessed a broad-spectrum antibacterial activity owing to the reactivity of aldehyde groups rather than acidic pH effect. Aldehyde would irreversibly damage bacterial cell wall and cytoplasmic membrane, resulting in decay and death of bacterial cells. It is interesting that the antibacterial properties of dialdehyde-carboxyl-amyloses were improved to some extent compared to dialdehyde-amyloses. The improvement of antibacterial effect of dialdehyde-carboxyl-amyloses may be due to the increasing dispersibility endowed by carboxyl groups, which could effectively enhance the interaction between dialdehyde-carboxyl-amyloses and bacteria. As a result, carboxyl group could act as a promising synergistic group against bacteria with aldehyde group.


Assuntos
Aldeídos/química , Amilose/química , Amilose/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Concentração de Íons de Hidrogênio , Oxirredução , Solubilidade
20.
Mol Clin Oncol ; 8(1): 38-46, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29387395

RESUMO

Increasing evidence supports a key role for the bone morphogenetic protein (BMP) signaling pathway in lung vasculogenesis and angiogenesis. Genetic variations in BMP genes have been found to be correlated with cancer risk. In particular, the mutation in the 3'-untranslated region of BMPs may significantly affect gene function, leading to cancer susceptibility. The aim of the present study was to determine whether genetic variations in the components of the BMP family are associated with lung cancer risk. A total of 314 tag single-nucleotide polymorphisms were identified in 18 genes, which are considered to either compose or regulate BMPs, and their association with lung cancer risk was evaluated in a two-stage case-control study with 4,680 cases and controls. A consistently significant association of SMAD5 rs12719482 with elevated lung cancer risk was observed in the three types of sources of populations (adjusted additive model in the combined population: Odds ratio=1.32, 95% confidence interval: 1.16-1.51). The lung cancer risk statistically significantly increased with the increasing number of variant alleles of SMAD5 rs12719482 in a dose-dependent pattern (P for trend=4.9×10-5). Consistent evidence was identified for a significant interaction between the rs12719482 and cigarette smoking, performed as either a continuous or discrete variable. These findings indicated that SMAD5 rs12719482 may be a possible candidate marker for susceptibility to lung cancer in the Chinese population.

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