Publications by authors named "Hairong Bao"

13 Publications

  • Page 1 of 1

Sulforaphane suppresses lipopolysaccharide- and Pam3CysSerLys4-mediated inflammation in chronic obstructive pulmonary disease via toll-like receptors.

FEBS Open Bio 2021 May 1;11(5):1313-1321. Epub 2021 May 1.

Department of Gerontal Respiratory Medicine, The First Hospital of Lanzhou University, China.

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airway that represents a large global disease burden. Inflammation is a prominent feature of COPD and represents an important target for treatment. Toll-like receptors (TLRs) are pattern recognition receptors that detect invading microorganisms and nonmicrobial endogenous molecules to trigger inflammatory responses during host defense and tissue repair. The TLR signaling pathway is closely linked to the pathogenesis of COPD. Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, is well known for its anti-inflammatory activities. However, the molecular function of SFN in inhibition of COPD inflammation has yet to be fully elucidated. In this study, we investigated the effects of SFN on lipopolysaccharide (LPS)- or Pam3CysSerLys4 (Pam3CSK4)-induced inflammation in monocyte-derived macrophages (MDMs) from patients with COPD. MDMs from patients with COPD showed higher expression levels of TLR2, TLR4 and downstream myeloid differentiation factor 88 (MyD88) than healthy controls, along with increased secretion of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) (P < 0.05). Stimulation with TLR ligands (Pam3CSK4 and LPS) up-regulated the levels of TLR2, TLR4 and MyD88 in MDMs from patients with COPD and induced the release of IL-6 and TNF-α (P < 0.05). Pretreatment of MDMs from patients with COPD with SFN significantly suppressed Pam3CSK4- or LPS-induced TLR2, TLR4 and MyD88 expression, along with a reduction in the production of IL-6 and TNF-α (P < 0.05). Collectively, these data indicate that SFN exerts its anti-inflammatory activity in COPD by modulating the TLR pathway. SFN may represent a potential therapeutic agent for the treatment of COPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/2211-5463.13118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091816PMC
May 2021

Association between atmospheric PM and daily outpatient visits for children's respiratory diseases in Lanzhou.

Int J Biometeorol 2021 Feb 15. Epub 2021 Feb 15.

Department of Gerontal Respiratory Medicine, The First Hospital of Lanzhou University, Lanzhou, 730050, China.

The relationship between fine particulate matter (PM) and respiratory disease outcomes among children aged 0 to 14 years in Lanzhou, China, was evaluated. We utilized a generalized additive model linked by a quasi-Poisson distribution to examine the associations between PM and paediatric respiratory outpatient visits for time lags of 0 up to 7 days, and stratified by gender, age, and season. Cases of respiratory disease in children were collected from 3 large hospitals for the years 2014-2017 and then linked with air pollutant concentrations from 4 air quality monitoring stations by date. We observed positive and significant associations between PM and respiratory disease from the lag to lag 7, and from lag01 to lag07, with ER reaching the maximum value at lag07. For each 10 μg/m increase in PM (lag07), the associated increment in respiratory diseases was 2.83% (95% CI 1.80%-3.86%). Males were more sensitive to the adverse effects, and the association was more significant in spring (from March to May) and winter (from December to the next February). Overall, the child group (age 3-6 years) demonstrated a higher risk of respiratory disease after PM exposure. The associations between ambient PM and respiratory hospital outpatients among young children became partially attenuated after the adjustment for gaseous pollutants in subgroups. The exposure-response curves were positive and generally nonlinear but flatted at concentrations over 60 μg/m. This research found a significant association between ambient PM levels and hospital outpatient visits in child with respiratory diseases in Lanzhou, China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00484-021-02080-6DOI Listing
February 2021

Morphological, immunohistochemical, and genetic analyses of bronchiolar adenoma and its putative variants.

J Pathol Clin Res 2021 May 5;7(3):287-300. Epub 2021 Jan 5.

Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, PR China.

We collected 26 cases of bronchiolar adenoma (BA) and its variants, and performed a comprehensive characterization using a combination of morphological, immunohistochemical, and genetic assessments. Of these 26, 13 were classic bilayered cases, including 10 proximal and 3 distal-type BAs. Of note, we also identified 13 cases that lacked a continuous basal cell layer. In five cases, the adenomas were partially classic bilayered, leaving a single layer of columnar or cuboidal epithelial cells in some areas of the lesion (BA with monolayered cell lesions). In the other eight cases, the glandular or papillary structures were entirely composed of monolayered columnar or cuboidal epithelial cells, which were morphologically identical to the luminal epithelial cells of classic BA (monolayered BA-like lesions). Immunohistochemical analysis revealed thyroid transcription factor 1 expression by ciliated columnar epithelial cells, basal cells, and nonciliated columnar and cuboidal epithelial cells. Basal cells also expressed p40 and p63. Twenty-five cases underwent next-generation sequencing using a 422-cancer-gene panel (GeneseeqPrime). Oncogenic driver mutations were detected in 23 cases, including 13 (52%) with EGFR mutations, 4 (16%) with KRAS G12D/V mutations, 3 (12%) with BRAF V600E mutations, 2 (8%) with ERBB2 exon 20 insertions, and 1 (4%) with a RET fusion. EGFR exon 20 insertions were present in 100% of BAs with monolayered cell lesions, 37.5% of monolayered BA-like lesions, and 8% of classic BA (Fisher's exact test, p = 0.002, false discovery rate = 0.014). Collectively, our study revealed a gradual morphological transition between BA and its variants. The genetic composition of BAs with monolayered structures differed significantly from those of classic BAs or lung adenocarcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cjp2.197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072999PMC
May 2021

Evaluating the diagnostic accuracy of a ctDNA methylation classifier for incidental lung nodules: protocol for a prospective, observational, and multicenter clinical trial of 10,560 cases.

Transl Lung Cancer Res 2020 Oct;9(5):2016-2026

Department of Respiration, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Background: Lung nodules are a diagnostic challenge. Current clinical management of lung nodule patients is inefficient and therefore causes patient misclassification, which increases healthcare expenses. However, a precise and robust lung nodule classifier to minimize discomfort for patients and healthcare costs is still lacking. The aim of the present protocol is to evaluate the effectiveness of using a liquid biopsy classifier to diagnose nodules compared to physician estimates and whether the classifier can reduce the number of unnecessary biopsies in benign cases.

Methods: A prospective cohort of 10,560 patients enrolled at 23 clinical centers in China with non-calcified pulmonary nodules, ranging from 0.5 to 3 cm in diameter, indicated by LDCT or CT will be included. After signed consent forms, the participants' pulmonary nodules will be assessed using three evaluation tools: (I) physician cancer probability estimates (II) validated lung nodule risk models, including Mayo Clinic and Veteran's Affairs models (III) ctDNA methylation classifier previously established. Each patient will undergo LDCT/CT follow-ups for 2 to 3 years and their information and one blood sample will be collected at baseline, 3, 6, 12, 24 and 36 months. The primary study outcomes will be the diagnostic accuracy of the methylation classifier in the cohort. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) will be used to compare the diagnostic value of each testing tool in differentiating benign and malignant pulmonary nodules.

Discussion: We are conducting an observational study to explore the accuracy of using a ctDNA methylation classifier for incidental lung nodules diagnosis.

Trial Registration: Clinicaltrials.gov NCT03651986.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tlcr-20-701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653103PMC
October 2020

Revalue associations of short-term exposure to air pollution with respiratory hospital admissions in Lanzhou, China after the control and treatment of current pollution.

Int J Hyg Environ Health 2021 Jan 7;231:113658. Epub 2020 Nov 7.

Department of Gerontal Respiratory Medicine, The First Hospital of Lanzhou University, Lanzhou, 730000, China.

Significant progress has been made in air pollution control Lanzhou, China recently, however, there was only one study so far on the assessment on health gains from air quality improvement after adopting strict air pollution control measures. The present study aimed to estimate the short-term effects of six criteria air pollutants including PM, PM, NO, SO, CO and O on respiratory admissions in Lanzhou, China, then compare the results of our study with those earlier studies conducted in Lanzhou before the implementation of air pollution control measures. Data on daily hospital admissions from the three largest hospitals in Lanzhou and daily air pollution concentration and meteorological variable were collected during a 4-year period (2014-2017). A generalized additive model; adjusted for long-term trend, seasonality, and other potential confounders was done to quantitatively assess the influences of air pollutants on daily respiratory admissions and analyze the influences of different seasons, sexes, and age groups. The most apparent effects for PM, PM, SO, CO and O on respiratory hospitalizations were observed at lag6, and lag7, respectively, and a 10μg/m increase in PM, PM, SO, CO and O concentration were associated with 0.885% (95%CI: 0.414%~1.358%), 0.328% (95%CI: 0.145%~0.511%), 3.005% (95%CI: 1.689%~4.339%), 3.199% (95%CI: 0.912%~5.537%) for CO, 0.733% (95%Cl: 0.263%~1.205%) increase in respiratory admission, respectively. No remarkable association was found between NO and respiratory disease hospitalisation. Females and younger groups were more susceptible to air pollutant than males and elderly groups. Together, we demonstrated that the positive associations were more pronounced in the cold season than in the warm season. The findings in present study suggest that even in Lanzhou, where air quality has been improved dramatically, positive associations still exist between air pollution and daily number of total respiratory admission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijheh.2020.113658DOI Listing
January 2021

Association between ambient particulate matter and hospital outpatient visits for chronic obstructive pulmonary disease in Lanzhou, China.

Environ Sci Pollut Res Int 2020 Jun 22;27(18):22843-22854. Epub 2020 Apr 22.

The First People's Hospital of Lanzhou City, Lanzhou, 730050, China.

Until now, a number of epidemiological studies have focused on the association between ambient particulate matter pollution and chronic obstructive pulmonary disease (COPD), especially in developed countries. There are limited evidences on the association between short-term exposure to particulate matters (PM, PM, and PM) and overall hospital outpatient visits for COPD at the same time in China. Thus, a time-series analysis on the short-term association between three subtypes of PM (PM, PM, and PM) and daily hospital outpatients for COPD in Lanzhou, China was conducted, from 2014 to 2017.An over dispersed, generalized additive model was used to analyze the associations after controlling for time trend, weather conditions, day of the week, and holidays. Stratified analyses were also performed by age and gender. The results disclosed that a 10-μg/m increase in PM concentration at a lag of 0-7 days was associated with 1.190% (95% CI 0.176~2.215%). For PM, therewere not statistically significant effects at any lag days, but we could find the greatest effect at lag07 that a 10-μg/m increase in concentration was associated with 0.014% (95% CI - 0.065~0.093%). PM also exerted a high effect for COPD (0.185% increase; 95% CI - 0.046~0.417%) when 6 days of exposures (lag6), however, no significance relationship could be found. For COPD among males, positive results were observed for PM with lags of 0-7 days, a 10-μg/m increase was 1.184% (95% CI 0.095~2.284%). The effect of PM on females was also most significant at lag07, a 10-μg/m increase was 1.254% (95% CI 0.053~2.469%). For those aged < 65 years old, PM was not statistically significant at all lag days, but it reached the maximum at lag07, a 10-μg/m increase was 0.978% (95% CI - 0.139~2.108%). For those aged 65 ≥ years old and older, PM had a statistically significant lag effect at lag1, lag2, lag3, lag02, lag03, lag04, lag05, lag06, and lag07, and it was most significant at lag07; a 10-μg/m increase was 1.906% (95% CI 0.553~3.277%). Short-term exposure to PM was associated with increased risk of hospital visits for COPD. In particular, the elderly (aged ≥ 65 years old) and males were relatively more sensitive to PM, and were affected right away after the PM concentration went up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-08797-yDOI Listing
June 2020

Tumor-derived DNA from pleural effusion supernatant as a promising alternative to tumor tissue in genomic profiling of advanced lung cancer.

Theranostics 2019 28;9(19):5532-5541. Epub 2019 Jul 28.

Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Pleural effusion (PE) is commonly observed in advanced lung cancer and was suggested to contain both cell-free tumor DNA and tumor cells. Molecular profiling of PE represents a minimally invasive approach of detecting tumor driver mutations for clinical decision making, especially when tumor tissues are not available. The objective of this study is to investigate the efficacy and precision of detecting gene alterations in PE samples to address the feasibility in clinical use. Sixty-three metastatic lung cancer patients with (n=30, cohort 1) or without (n=33, cohort 2) matched tumor tissues were enrolled in this study. PE and plasma samples of each patient were collected simultaneously. Supernatant and cell precipitate of PE were processed separately to extract cfDNA (PE-cfDNA) and sediment DNA (sDNA). All samples were subjected to targeted next-generation sequencing (NGS) of 416 cancer-related genes. PE supernatants contain more abundant tumor DNA than PE sediments and plasma samples, suggested by higher mutant allele frequencies (MAF) and elevated mutation detection rate in PE-cfDNA (98.4% vs. 90.5% in PE sDNA vs. 87% in plasma cfDNA). In Cohort 1 with matched tumor tissue, tumor mutational burden (TMB) of PE-cfDNA was similar as tumor tissues (6.4 vs. 5.6), but significantly higher than PE sDNA (median TMB: 3.3) and plasma cfDNA (median TMB: 3.4). Ninety-three percent (27 out of 29) of tissue-determined driver mutations were detected in PE-cfDNA, including alterations in , , , , , and , while only 62% were captured in plasma cfDNA. PE-cfDNA also has the highest detection rate of driver mutations in the full cohort (71% vs. 68% in PE sDNA vs. 59% in plasma cfDNA). Mutation detection from cytological negative and hemorrhagic PE is challenging. Comparatively, PE-cfDNA demonstrated absolute superiority than PE sDNA in such a scenario, suggesting that it is an independent source of tumor DNA and therefore less influenced by the abundance of tumor cells. Genomic profiling of PE-cfDNA offers an alternative, and potentially more meticulous approach in assessing tumor genomics in advanced lung cancer when tumor tissue is not available. Our data further demonstrate that in hemorrhagic or cytologically negative PE samples, PE-cfDNA has higher mutation detection sensitivity than sDNA and plasma cfDNA, and therefore is a more reliable source for genetic testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.34070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735385PMC
September 2020

Association between alcohol consumption and mild cognitive impairment: A protocol of dose-response meta-analysis.

Medicine (Baltimore) 2019 Jul;98(27):e16098

Evidence-Based Medicine Center of Lanzhou University.

Objective: The objective of this study is to investigate the potential dose-response association between alcohol consumption and the risk of mild cognitive impairment (MCI).

Methods: We will perform a dose-response meta-analysis (DRMA) of cohort studies to explore the dose-response relationship between alcohol intake and MCI. A comprehensive literature search of PubMed, EMBASE, The Cochrane Library, Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP, and Wan-Fang Database will be conducted. Two investigators will independently select studies, extract data, and assess the quality of the included study. The Newcastle-Ottawa Scale will be used to assess the quality of include studies. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and A MeaSurement Tool to Assess systematic Reviews (AMSTAR) will be used to assess the quality of evidence and methodological quality. Any disagreement will be resolved by the third investigator. We will use the hazard ratio as the effect indicator, and piecewise linear regression model and restricted cubic spline model will be used for linear and nonlinear trend estimation, respectively. There is no requirement of ethical approval and informed consent.

Discussion: This is the first DRMA to explore the dose-response relationship between alcohol intake and MCI. We predict it will provide high-quality evidence to prevent clinical MCI and dementia.

Registration: The DRMA is registered in the PROSPERO (CRD42019127261) international prospective register of systematic review.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000016098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635151PMC
July 2019

Concomitant resistance mechanisms to multiple tyrosine kinase inhibitors in ALK-positive non-small cell lung cancer.

Lung Cancer 2019 01 22;127:19-24. Epub 2018 Nov 22.

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Objectives: ALK tyrosine kinase inhibitors (TKIs), including crizotinib and several next generation TKIs, have demonstrated beneficial clinical outcomes in ALK-positive non-small cell lung cancer (NSCLC). However, resistance mechanisms following multiple TKI treatments in ALK-positive NSCLC are not fully elucidated.

Materials And Methods: Mutation profiles of 422 cancer-relevant genes in 52 patients with post-TKI biopsy samples were analyzed using next-generation sequencing (NGS), and compared between patients receiving crizotinib alone (n = 35) and multi-TKIs (n = 17).

Results: EML4-ALK variant 3 is the most frequent ALK variants in this cohort, followed by EML4-ALK variant 1. Half of the patients harbored ALK activating mutations upon progression on crizotinib treatment. After multi-TKIs treatment, 59% of the cases developed resistant ALK mutations, and concomitant ALK activating mutations were more commonly observed in this cohort (P = 0.031). Specifically, ALK G1269 A, L1196 M, and C1156Y substitutions were more common in crizotinib-alone samples, while ALK G1202R was significantly more enriched post-multi-TKIs (P = 0.009). Activated bypass signaling tended to be more prevalent in patients post-multi-TKIs. Furthermore, dual activation of ALK and bypass signaling was more frequently found in the multi-TKIs group (5/17, 29%) in contrast to crizotinib-alone (2/35, 6%) (P = 0.031). Additionally, concurrent TP53 mutation demonstrated significantly shorter progression-free survival (PFS) compared with TP53 wildtype in crizotinib-alone group (median PFS: 8 vs 13 months, Hazard Ratio = 1.494, P = 0.019).

Conclusion: Concurrent ALK activating mutations and/or upregulated bypass signaling are more enriched in patients undergoing multiple ALK TKI treatments compared to crizotinib alone. Concomitant TP53 mutation correlated to unfavorable survival when receiving a single TKI crizotinib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2018.11.024DOI Listing
January 2019

EGFR and ERBB2 Germline Mutations in Chinese Lung Cancer Patients and Their Roles in Genetic Susceptibility to Cancer.

J Thorac Oncol 2019 04 2;14(4):732-736. Epub 2019 Jan 2.

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Introduction: Inherited genetic determinants of lung cancer risk remain relatively elusive. Germline mutations in EGFR and erb-b2 receptor tyrosine kinase 2 (ERBB2) have been previously reported in lung cancers that may be associated with genetic susceptibility to lung cancer.

Methods: We retrospectively analyzed a cohort of 12,833 Chinese lung cancer patients tested by targeted next-generation sequencing. Patients with EGFR and ERBB2 germline mutations were identified, and their clinical information and family history were summarized. Growth factor independency of EGFR germline mutations was further analyzed in vitro.

Results: Eight different heterozygous EGFR germline mutations from 14 adenocarcinoma patients (0.12%) were identified within or adjacent to the kinase domain, including K757R (n = 5), R831H (n = 2), D1014N (n = 2), G724S, V786M, T790M, L792F, and L844V. Only one patient harbored the ERBB2-V1128I germline mutation. Five of 15 patients had family history of cancer. Notably, the patient with EGFR-T790M germline mutation had multiple maternal family members diagnosed with lung cancers, strongly supporting its role in inherited lung cancer. Concurrent known somatic driver mutations were not detected in 5 patients at diagnosis, 1 of whom harbored the EGFR-L844V germline mutation and showed superior response to afatinib. Consistently, EGFR-K757R and L844V mutations were able to be interleukin 3 - independent in vitro and were sensitive to EGFR tyrosine kinase inhibitors.

Conclusions: EGFR/ERBB2 germline mutations were found to be rare in Chinese lung cancer patients with more diversity other than the previously reported EGFR-T790M, with EGFR-K757R being the most common EGFR germline mutation. Patients with EGFR germline mutations without other known driver mutations might benefit from tyrosine kinase inhibitor treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2018.12.006DOI Listing
April 2019

[Effects of PM2.5 on phagocytic function of alveolar macrophages in chronic obstructive pulmonary disease mice].

Zhonghua Yi Xue Za Zhi 2016 Jan;96(4):301-5

Department of Gerontal Respiratory Medicine, the First Hospital of Lanzhou University, Lanzhou 730000, China.

Objective: To investigate the effects of fine particulate matter with a mean aerodynamic diameter ≤2.5 μm (PM2.5) collected from Lanzhou city on phagocytic function of alveolar macrophages (AM) in chronic obstructive pulmonary disease (COPD) mice.

Methods: Forty male mice were randomly divided into four groups: healthy group, healthy PM2.5 group, COPD group and COPD PM2.5 group. COPD mice were established by cigarette smoking. PM2.5 (10 mg/kg) collected by air sampler was intratracheally instilled in healthy PM2.5 group and COPD PM2.5 group. Mice were sacrificed after 14 days, and alveolar macrophages (AM) were isolated. Mean fluorescence intensity (MFI) and the positive percent of alveolar macrophages engulfing flurescein isothiocyanate-labeled Escherichia coli (FITC-E.coli) (AM%) were detected by flow cytometry. Total antioxidative capacity (TAC) was measured by O-phenanthroline colorimetry. Malondialdehyde (MDA) was measured by thiobarbiturieacid colorimetry and myeloperoxidase (MPO) was measured by O-dianisidine colorimetry.

Results: The peak inspiratory flow (PIF), peak expiratory flow (PEF) and dynamic compliance (Cdyn) of COPD group were significantly lower than healthy control group. The pathology of COPD group showed disruption of alveolar septa, formation of emphysema, and that the number of alveoli had a significant reduction. The MFI and AM% in COPD group were significant lower than healthy group (14.1±1.7 vs 43.2±6.1, 9.2%±2.3% vs 69.1%±8.3%)(all P<0.01). Comparing to healthy group and COPD group, the MFI and AM% in healthy PM2.5 group (20.3±4.5, 40.4%±4.4%) and COPD PM2.5 group (7.5±1.3, 6.0%±2.2%) were respectively lowered. The level of TAC in COPD group was significantly lower than healthy group [(3.10±0.64) vs (15.43±0.69)U/mg], the levels of MDA and MPO in COPD group were higher than healthy group[(2.72±0.13) vs (1.31±0.16) nmol/mg, (1.63±0.11) vs (0.92±0.13)U/g] (all P<0.01). In both healthy PM2.5 group and COPD PM2.5 group, the levels of TAC [(6.75±1.06), (2.34±0.61) U/mg] were lower than their corresponding control group; while the levels of MDA [(1.96±0.31), (3.20±0.19) nmol/mg] and the levels of MPO [(1.01±0.19), (1.74±0.13) U/g] were increased (all P<0.01). For the COPD group at baseline and after the intervention of PM2.5, the MFI and AM% showed positive correlation with the levels of TAC, and negative correlation with the levels of MDA , and negative correlation with the levels of MPO (all P<0.05). For health group at baseline and after the intervention PM2.5, the above relationships still existed (all P<0.05).

Conclusion: PM2.5 can damage phagocytosis of AM and exacerbate oxidative stress in COPD mice, and AM phagocytosis impairment by PM2.5 is closely associated with oxidative stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.issn.0376-2491.2016.04.016DOI Listing
January 2016

[Effects of sulforaphane on Toll-like receptor 4/myeloid differentiation factor 88 pathway of monocyte-derived macrophages from patients with chronic obstructive pulmonary disease].

Zhonghua Jie He He Hu Xi Za Zhi 2014 Apr;37(4):250-4

Department of Gerontal Respiratory Medicine, the First Hospital of Lanzhou University, Lanzhou 730000, China.

Objective: To explore the effects of sulforaphane on Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) pathway and its downstream inflammatory cytokines in patients with chronic obstructive pulmonary disease (COPD).

Methods: From Jan. 2012 to Mar. 2013, thirty-two stable COPD patients and thirty healthy donors (non-COPD group) from the First Hospital of Lanzhou University were recruited. The peripheral blood monocytes were isolated and induced to macrophages (monocyte-derived macrophages, MDMs). The MDMs of COPD patients were divided into a blank control group, a LPS group, a sulforaphane group, a sulforaphane and LPS group (combined group), while the MDMs from the non-COPD group received no drug intervention. The number of cells in each group was 3×10(6). The mRNA and protein expression of TLR4 and MyD88 were measured with real-time PCR and Western blot. The TNF-α and IL-6 levels in the culture supernatant were measured with ELISA. Oneway ANOVA and LSD-t test were used for statistical analysis.

Results: The levels of mRNA and protein of TLR4 and MyD88 and the contents of TNF-α and IL-6 in the culture supernatant were higher in the blank control group [3.7 ± 0.5, 1.9 ± 0.4, 0.45 ± 0.18, 1.11 ± 0.65, (31 ± 4) and (43 ± 5) µg/L] than those in the non-COPD group [1.00, 1.00, 0.26 ± 0.14, 0.58 ± 0.40, (19 ± 2) and (29 ± 4) µg/L] (t = 2.19-12.11, P < 0.05 or P < 0.01). After LPS treatment (LPS group), the above parameters [5.5 ± 1.1, 3.4 ± 1.6, 0.65 ± 0.20, 1.66 ± 0.64, (47 ± 4) and (54 ± 5) µg/L] were increased as compared to those in the blank control group (t = 2.39-11.9, P < 0.05 or P < 0.01), but after sulforaphane treatment(Sulforaphane group), these parameters [2.2 ± 0.4, 1.0 ± 0.6, 0.25 ± 0.09, 0.62 ± 0.34, (20 ± 3) and (27 ± 4) µg/L] were decreased as compared to those in the blank control group (t = 2.13-8.46, P < 0.05 or P < 0.01). Similarly, these parameters in the combined group [3.2 ± 0.5, 1.5 ± 0.8, 0.33 ± 0.11, 0.77 ± 0.25, (31 ± 3) and (33 ± 4) µg/L] were also remarkably decreased as compared to those in the LPS group (t = 3.87-12.24, all P < 0.01).

Conclusions: The TLR4/MyD88 pathway was activated and its downstream inflammatory cytokines were increased in macrophages from COPD patients. Sulforaphane could inhibit the TLR4/MyD88 pathway and reduce the releasing of downstream inflammatory cytokines, suggesting that sulforaphane may have an anti-inflammatory effect in COPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2014

[Effects of cigarette smoke on phagocytosed function of monocyte-derived macrophage in chronic obstructive pulmonary disease patients].

Zhonghua Yi Xue Za Zhi 2014 Apr;94(12):895-8

Department of Gerontal Respiratory Medicine, First Hospital, Lanzhou University, Lanzhou 730000, China.

Objective: To explore the effects of cigarette smoke extract (CSE) on phagocytosizing function of monocyte-derived macrophages (MDMs) in patients with chronic obstructive pulmonary disease (COPD).

Methods: From January 2012 to March 2013, peripheral blood monocytes were isolated from 32 stable COPD patients and 32 healthy controls at First Hospital, Lanzhou University. MDM was induced and cultured from monocytes in vitro. The MDMs from COPD patients and healthy controls were divided into 4 groups of COPD non-CSE (conventional culture), COPD CSE (4% CSE treatment for 6 h), healthy non-CSE (conventional culture) and healthy CSE (4% CSE treatment for 6 h). Flow cytometry (mean fluorescence intensity, MFI) and laser scanning confocal microscopy (fluorescence grey level) were applied to detect the ability of MDM phagocytosed fluorescein-labeled Escherichia coli (FITC-E.coli). Total antioxidative capacity (TAC) was measured by o-phenanthroline colorimetry. Malondialdehyde (MDA) was measured by thiobarbituric acid colorimetry and glutathione peroxidase (GSH-PX) by 5, 5'-dithiobis-2-nitrobenzoic acid (DTNB) method.

Results: MFI and fluorescence grey level in COPD non-CSE group (20.2 ± 2.2, 51.5 ± 5.8) significantly decreased than those in healthy non-CSE group (56.9 ± 6.7, 87.3 ± 7.3). And in COPD CSE (7.6 ± 0.7, 14.1 ± 3.4) and healthy CSE groups (48.0 ± 5.4, 69.7 ± 6.0) decreased more than those in COPD non-CSE and healthy non-CSE groups (all P < 0.01). The levels of TAC and GSH-PX in COPD non-CSE group ((4.1 ± 0.5), (47.1 ± 4.1) U/ml) were lower than those in healthy non-CSE group ((5.1 ± 0.6), (88.4 ± 2.3) U/ml). And in COPD CSE and healthy CSE groups ((3.1 ± 0.4), (26.8 ± 6.2) U/ml) and (4.5 ± 0.4), (72.3 ± 5.1) U/ml) were respectively lower than those in COPD non-CSE and healthy non-CSE groups (all P < 0.01). The content of MDA in COPD non-CSE group was higher than that in healthy non-CSE group [(4.8 ± 0.5) vs (2.1 ± 0.4) µmol/L)]. And in COPD CSE and healthy CSE groups ((7.7 ± 0.9), (3.0 ± 0.6)µmol/L) were higher than those in COPD non-CSE and healthy non-CSE groups (all P < 0.01). At basic status, positive correlations existed between MFI and TAC, GSH-PX (r = 0.523, 0.818, P = 0.038, 0.001) while negative correlations between MFI and MDA (r = -0.501, P = 0.048) in COPD patients and after CSE treatment, the above relationships still existed (r = 0.704, 0.716, -0.522, P = 0.002, 0.002, 0.038).

Conclusions: Cigarette smoke can reduce the phagocytosizing ability of MDM in COPD patients. And it may be related with oxidative stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2014