Publications by authors named "Shucheng Hua"

55 Publications

The protective role of Zingerone in a murine asthma model via activation of the AMPK/Nrf2/HO-1 pathway.

Food Funct 2021 Apr 16;12(7):3120-3131. Epub 2021 Mar 16.

Department of Respiratory Medicine, Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun 130021, Jilin, P.R. China.

Asthma is one of the most common illnesses associated with chronic airway inflammation; however, there are currently no effective therapies apart from glucocorticoids. Zingerone (ZIN), an active compound isolated from ginger, has been reported to have a broad spectrum of pharmacological properties. In this study, Zingerone was administrated to HO-stimulated mouse airway epithelial cell line MLE12 cells and asthmatic mice. The concentration of cytokines was evaluated using enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE), Periodic Acid-Schiff (PAS) and Masson staining were used for histological analyses. Protein levels in cells or lung tissues were determined using western blot, immunohistochemistry staining. The results showed that treatment with Zingerone dramatically inhibited oxidative stress and the inflammatory response in MLE12 cells stimulated with HO and asthmatic mice. Furthermore, Zingerone treatment could decrease the expression of phosphorylated (p)-IκBα and p65 (nuclear) and increase the expression of phosphorylation of AMP-activated protein kinase (p-AMPK), nuclear factor erythroid-2-related factor 2 (Nrf2), and hemeoxygenase-1 (HO-1) to alleviate oxidative damage and inflammation both in vivo and in vitro. In addition, Zingerone treatment reduced the exudation and infiltration of inflammatory cells and suppressed goblet cell hyperplasia in a murine asthma model. Treatment with Zingerone also decreased the level of interleukin (IL)-4, IL-5, IL-13, and increased the level of interferon gamma (IFN-γ) in the BALF and attenuated airway hyperresponsiveness (AHR). However, inhibition of AMPK or Nrf2 suppressed the cellular protective, antioxidative, and anti-inflammatory properties of Zingerone. Taken together, these results demonstrate that Zingerone possesses the potential to relieve asthma via upregulating the AMPK/Nrf2/HO-1 signaling pathway.
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http://dx.doi.org/10.1039/d0fo01583kDOI Listing
April 2021

Perspectives and controversies regarding the use of natural products for the treatment of lung cancer.

Cancer Med 2021 Apr 2;10(7):2396-2422. Epub 2021 Mar 2.

Department of Respiratory Medicine, Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, Jilin, P.R. China.

Lung cancer is the leading cause of cancer-related mortality both in men and women and accounts for 18.4% of all cancer-related deaths. Although advanced therapy methods have been developed, the prognosis of lung cancer patients remains extremely poor. Over the past few decades, clinicians and researchers have found that chemical compounds extracted from natural products may be useful for treating lung cancer. Drug formulations derived from natural compounds, such as paclitaxel, doxorubicin, and camptothecin, have been successfully used as chemotherapeutics for lung cancer. In recent years, hundreds of new natural compounds that can be used to treat lung cancer have been found through basic and sub-clinical research. However, there has not been a corresponding increase in the number of drugs that have been used in a clinical setting. The probable reasons may include low solubility, limited absorption, unfavorable metabolism, and severe side effects. In this review, we present a summary of the natural compounds that have been proven to be effective for the treatment of lung cancer, as well as an understanding of the mechanisms underlying their pharmacological effects. We have also highlighted current controversies and have attempted to provide solutions for the clinical translation of these compounds.
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http://dx.doi.org/10.1002/cam4.3660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982634PMC
April 2021

Epidemiological and clinical characteristics of 2019 novel coronavirus disease (COVID-19) in Jilin, China: A descriptive study.

Medicine (Baltimore) 2020 Nov;99(47):e23407

Department of Respiratory Medicine, Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, the First Hospital of Jilin University, Changchun, PR China.

Coronavirus diseases 2019 (COVID-19) has become a global pandemic. To add to the scarce information on this disease, here, we investigated the epidemiological and clinical characteristics of 93 hospitalized patients with COVID-19 in Jilin, China from January 22 to March 15, 2020.We retrospectively investigated the demographic information, recent exposure history, clinical symptoms or signs, comorbidity, chest computed tomographic (CT) scan or X-ray results, laboratory test results, diagnostic classification, treatment, length of hospitalization, complications, and outcomes.Of the 93 patients, 54 were male and 39 female. More than half of these patients had a history of exposure to infected patients. The mean incubation period was 10.4 days in 87 patients, where the data was available. The 5 most common symptoms of illness onset were fever, cough, expectoration, fatigue, and dyspnea. One patient was asymptomatic. The imaging results were abnormal in majority of the patients. Almost one-third of the patients had lymphopenia. All patients received antiviral therapy, 84 patients were treated with antibiotics and 54 received different doses of the hormone for methylprednisolone. In addition, 72 patients used traditional Chinese medicine. Oxygen therapy, high nasal flow oxygen, non-invasive ventilator, invasive ventilator and extracorporeal membrane oxygenation (ECMO) were used symptomatically in different patients. Except 1 patient who died during treatment, all others were discharged.The average incubation time is prolonged in the present analysis, as compared to that in other reports. A few patients symptoms improved but CT exacerbated. Therefore, we suggest that close follow-up observation is still required after discharge.
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http://dx.doi.org/10.1097/MD.0000000000023407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676609PMC
November 2020

Digital PCR is a sensitive new technique for SARS-CoV-2 detection in clinical applications.

Clin Chim Acta 2020 Dec 4;511:346-351. Epub 2020 Nov 4.

Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, China. Electronic address:

The global coronavirus disease 2019 (COVID-19) pandemic has posed great challenges in people's daily lives. Highly sensitive laboratory techniques played a critical role in clinical COVID-19 diagnosis and management. In this study the feasibility of using a new digital PCR-based detection assay for clinical COVID-19 diagnosis was investigated by comparing its performance with that of RT-PCR. Clinical patient samples and samples obtained from potentially contaminated environments were analyzed. The study included 10 patients with confirmed COVID-19 diagnoses, 32 validated samples of various types derived from different clinical timepoints and sites, and 148 environmentally derived samples. SARS-CoV-2 nucleic acids were more readily detected in respiratory tract samples (35.0%). In analyses of environmentally derived samples, the positivity rate of air samples was higher than that of surface samples, probably due to differences in virus concentrations. Digital PCR detected SARS-CoV-2 in several samples that had previously been deemed negative, including 3 patient-derived samples and 5 environmentally derived samples. In this study digital PCR exhibited higher sensitivity than conventional RT-PCR, suggesting that it may be a useful new method for clinical SARS-CoV-2 detection. Improvement of SARS-CoV-2 detection would substantially reduce the rates of false-negative COVID-19 test results, in particular those pertaining to asymptomatic carriers.
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http://dx.doi.org/10.1016/j.cca.2020.10.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641518PMC
December 2020

Clinical characteristics of family-clustered onset of coronavirus disease 2019 in Jilin Province, China.

Virulence 2020 12;11(1):1240-1249

Department of Respiratory Medicine, First Hospital of Jilin University, Jilin University , Changchun, China.

Eight members of a big family with laboratory-confirmed COVID-19 pneumonia were admitted to First Hospital of Jilin University, Changchun, China, from 28 January to 5 February 2020. The clinical records, laboratory results, and chest computed tomography (CT) scans were retrospectively reviewed. Throat swab samples were positive for severe acute respiratory syndrome coronavirus 2, confirmed by the Center for Disease Control and Prevention of Changchun. All eight patients had fever of different degrees; and 6, 3, and 2 had cough; diarrhea; and sore throat. With disease progression, the percentage of lymphocytes in older patients increased, CT images worsened, and the ratio of lymphocytes increased when images revealed inflammation absorption. Although the CT images showed ground-glass opacities in the youngest patient, his lymphocyte count did not decrease with mild clinical symptoms, and the images showed that inflammation was quickly absorbed. Only the oldest patient developed critical illness. The C reaction protein (CRP) levels of Patient 5 increased significantly, and the rate of decline was the slowest, while his condition was the most severe. The clinical manifestations of COVID-19 in this family cluster varied with contact, age, and underlying disease. Lymphocyte count and quality of chest CT images appeared inversely associated with disease severity. CRP changes may be an indicator of disease severity and prognosis.
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http://dx.doi.org/10.1080/21505594.2020.1816075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549897PMC
December 2020

Caspase-3 inhibitor inhibits enterovirus D68 production.

J Microbiol 2020 Sep 1;58(9):812-820. Epub 2020 Sep 1.

Department of Internal Medicine, The First Hospital of Jilin University, Jilin University, Changchun, 130000, P. R. China.

Enterovirus D68 (EVD68) is an emerging pathogen that recently caused a large worldwide outbreak of severe respiratory disease in children. However, the relationship between EVD68 and host cells remains unclear. Caspases are involved in cell death, immune response, and even viral production. We found that caspase-3 was activated during EVD68 replication to induce apoptosis. Caspase-3 inhibitor (Z-DEVD-FMK) inhibited viral production, protected host cells from the cytopathic effects of EVD68 infection, and prevented EVD68 from regulating the host cell cycle at G0/G1. Meanwhile, caspase-3 activator (PAC-1) increased EVD68 production. EVD68 infection therefore activates caspase-3 for virus production. This knowledge provides a potential direction for the prevention and treatment of disease related to EVD68.
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http://dx.doi.org/10.1007/s12275-020-0241-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459088PMC
September 2020

GBP5 Is an Interferon-Induced Inhibitor of Respiratory Syncytial Virus.

J Virol 2020 10 14;94(21). Epub 2020 Oct 14.

Institute of Virology and AIDS Research, the First Hospital of Jilin University, Changchun, People's Republic of China

Guanylate binding protein 5 (GBP5) belongs to the GTPase subfamily, which is mainly induced by interferon gamma (IFN-γ) and is involved in many important cellular processes, including inflammasome activation and innate immunity against a wide variety of microbial pathogens. However, it is unknown whether GBP5 inhibits respiratory syncytial virus (RSV) infection. In this study, we identified GBP5 as an effector of the anti-RSV activity of IFN-γ and found that in children, the weaker immune response, especially the weaker IFN-γ response and the decreased GBP5 expression, leads to RSV susceptibility. Furthermore, we revealed that GBP5 reduced the cell-associated levels of the RSV small hydrophobic (SH) protein, which was identified as a viroporin. In contrast, overexpression of the SH protein rescued RSV replication in the presence of GBP5. The GBP5-induced decrease in intracellular SH protein levels is because GBP5 promotes the release of the SH protein into the cell culture. Moreover, the GBP5 C583A mutants with changes at the C terminus or the GBP5 ΔC mutant lacking the C-terminal region, which impairs GBP5 localization in the Golgi, could not inhibit RSV infection, whereas the GTPase-defective GBP5 maintained RSV inhibition, suggesting that Golgi localization but not the GTPase activity of GBP5 is required for RSV inhibition. Interestingly, we found that RSV infection or RSV G protein downregulates GBP5 expression by upregulating DZIP3, an E3 ligase, which induces GBP5 degradation through the K48 ubiquitination and proteasomal pathways. Thus, this study reveals a complicated interplay between host restrictive factor GBP5 and RSV infection and provides important information for understanding the pathogenesis of RSV. RSV is a highly contagious virus that causes multiple infections in infants within their first year of life. It can also easily cause infection in elderly or immunocompromised individuals, suggesting that individual differences in immunity play an important role in RSV infection. Therefore, exploring the pathogenic mechanisms of RSV and identifying essential genes which inhibit RSV infection are necessary to develop an effective strategy to control RSV infection. Here, we report that the IFN-inducible gene potently inhibits RSV replication by reducing the cell-associated levels of the RSV small hydrophobic (SH) protein, which is a viroporin. In contrast, the RSV G protein was shown to upregulate the expression of the DZIP3 protein, an E3 ligase that degrades GBP5 through the proteasomal pathway. Our study provides important information for the understanding of the pathogenic mechanisms of RSV and host immunity as well as the complicated interplay between the virus and host.
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http://dx.doi.org/10.1128/JVI.01407-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565618PMC
October 2020

Increased IL-10+CD206+CD14+M2-like macrophages in alveolar lavage fluid of patients with small cell lung cancer.

Cancer Immunol Immunother 2020 Dec 24;69(12):2547-2560. Epub 2020 Jun 24.

Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China.

There are significant differences in pathology, etiology, clinical features, and treatment options between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). However, the differences of macrophage distribution and its associated function between SCLC and NSCLC are not fully investigated. Through methods of flow cytometry and cytometric bead array, we examined the levels of various subtypes of macrophages, monocytes, and regulatory T cells (Tregs) as well as interleukin (IL)-10 in bronchoalveolar lavage fluid (BALF) of patients with SCLC or NSCLC. Our study showed that the frequency of CD14+, CD206+CD14+ and IL-10+CD206+CD14+M2-like macrophages were significantly increased, with simultaneously elevated IL-10 in BALF of SCLC patients, as compared to those in BALF of NSCLC patients. Furthermore, the increased frequency of IL-10+CD206+CD14+M2-like macrophages and elevated level of IL-10 in BALF of SCLC patients were positively correlated with advanced tumor stage, but negatively correlated with their survival time. On the other hand, the level of supernatant IL-10 and frequency of IL-10+CD206+CD14+M2-like macrophages in SCLC patients were positively correlated. The frequency of above mentioned macrophages was also positively correlated with that of Foxp3+CD25+CD4+Tregs. Compared to NSCLC patients, the level of circulating IL-10+CD206+CD14+M2-like monocytes in SCLC patients were significantly increased after chemotherapy. Overall, increased IL-10+CD206+CD14+M2-like macrophages were an important feature of SCLC, rather than NSCLC, and it is associated with development of SCLC.
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http://dx.doi.org/10.1007/s00262-020-02639-zDOI Listing
December 2020

Letter to the editor: indacaterol/glycopyrronium/mometasone furoate compared with salmeterol/fluticasone propionate in patients with asthma: a randomized controlled cross-over study.

Respir Res 2020 Apr 15;21(1):87. Epub 2020 Apr 15.

Novartis Institutes for Biomedical Research, Basel, Switzerland.

Indacaterol (IND; 150 μg), glycopyrronium (GLY; 50 μg) and mometasone furoate (MF; 160 μg [high-dose ICS] and 80 μg [medium-dose ICS]) have been formulated as a once-daily (o.d.) fixed-dose combination treatment delivered via the Breezhaler® device for the treatment of patients with asthma. In this randomized (n = 116), double-blind, double-dummy, active comparator-controlled, three-period cross-over study we evaluated the benefit of o.d. IND/GLY/MF versus twice daily (b.i.d.) salmeterol/fluticasone propionate combination (SFC; 50/500 μg; high-dose ICS) treatment (NCT03063086). Overall, 107 patients completed the study. The study met its primary objective by demonstrating superiority of o.d. IND/GLY/MF at medium and high-dose ICS over b.i.d. SFC (high-dose ICS) in peak FEV after 21 days of treatment (+ 172 mL with high-dose and + 159 mL with medium-dose IND/GLY/MF versus SFC, p < 0.0001 for each comparison). We also observed that a higher percentage of patients did not need rescue medicine with IND/GLY/MF (high-dose ICS, 58%; medium-dose ICS, 52%) compared with SFC (45%) during the last week of each treatment period. Study treatments were well-tolerated with no relevant differences in tolerability between both IND/GLY/MF doses and SFC. In conclusion, both doses of IND/GLY/MF provided superior lung function benefits compared with twice-daily, standard-of-care SFC at the highest approved dose. TRIAL REGISTRATION: ClinicalTrials.gov, (Identifier: NCT03063086), EudraCT start date: May 11, 2017; First patient first visit / study initiation date: May 31, 2017.
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http://dx.doi.org/10.1186/s12931-020-01349-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160900PMC
April 2020

A novel radiomic nomogram for predicting epidermal growth factor receptor mutation in peripheral lung adenocarcinoma.

Phys Med Biol 2020 03 6;65(5):055012. Epub 2020 Mar 6.

Department of Radiology, the First Hospital of Jilin University, 130021 Changchun, People's Republic of China. These authors contributed equally to this work.

To predict the epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma using quantitative radiomic biomarkers and semantic features. We analyzed the computed tomography (CT) images and medical record data of 104 patients with lung adenocarcinoma who underwent surgical excision and EGFR mutation detection from 2016 to 2018 at our center. CT radiomic and semantic features that reflect the tumors' heterogeneity and phenotype were extracted from preoperative non-enhanced CT scans. The least absolute shrinkage and selection operator method was applied to select the most distinguishable features. Three logistic regression models were built to predict the EGFR mutation status by combining the CT semantic with clinicopathological characteristics, using the radiomic features alone, and by combining the radiomic and clinicopathological features. Receiver operating characteristic (ROC) curve analysis was performed using five-fold cross-validation and the mean area under the curve (AUC) values were calculated and compared between the models to obtain the optimal model for predicting EGFR mutation. Furthermore, radiomic nomograms were constructed to demonstrate the performance of the model. In total, 1025 radiomic features were extracted and reduced to 13 features as the most important predictors to build the radiomic signature. The combined radiomic and clinicopathological features model was developed based on the radiomic signature, sex, smoking, vascular infiltration, and pathohistological type. The AUC was 0.90  ±  0.02 for the training, 0.88  ±  0.11 for the verification, and 0.894 for the test dataset. This model was superior to the other prediction models that used the combined CT semantic and clinicopathological features (AUC for the test dataset: 0.768) and radiomic features alone (AUC for the test dataset: 0.837). The prediction model built by radiomic biomarkers and clinicopathological features, including the radiomic signature, sex, smoking, vascular infiltration, and pathological type, outperformed the other two models and could effectively predict the EGFR mutation status in patients with peripheral lung adenocarcinoma. The radiomic nomogram of this model is expected to become an effective biomarker for patients with lung adenocarcinoma requiring adjuvant targeted treatment.
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http://dx.doi.org/10.1088/1361-6560/ab6f98DOI Listing
March 2020

A promising role of interferon regulatory factor 5 as an early warning biomarker for the development of human non-small cell lung cancer.

Lung Cancer 2019 09 9;135:47-55. Epub 2019 Jul 9.

Department of Respiratory Medicine, The First Affiliated Hospital of Jilin University, Jilin University, Changchun, Jilin, 130021, PR China. Electronic address:

Objectives: Non-small cell lung cancer (NSCLC) accounts for 85%-90% of lung cancer cases and is a covert disease lacking early symptoms. Since cancer is recognised as an inflammation-associated condition, we analysed the relationship between the expression of interferon regulatory factor 5 (IRF5), a key transcription factor controlling inflammatory responses, and NSCLC development with the aim of identifying a warning biomarker for early diagnosis of the disease.

Materials And Methods: The expression of IRF5 and its associated inflammatory factors IL-6, IL-10, IP-10, and TNF-α in the peripheral blood of NSCLC patients (n = 66) and healthy controls (n = 42) was analysed by quantitative RT-PCR, flow cytometry, and a cytometric bead array. IRF5 protein expression in NSCLC tissues (n = 102) was detected by Western blotting. The diagnostic value of IRF5 expression was determined by a receiver-operating characteristic (ROC) curve analysis.

Results: The protein levels of IRF5, IL-6, and IP-10 were significantly higher in the peripheral blood of NSCLC patients than in that of healthy controls. IP-10 levels in plasma and IL-10 mRNA expression in white blood cells (WBCs) were significantly upregulated in early-stage NSCLC, whereas plasma IL-6 and IL-10 were elevated in the progressive stage. IRF5 protein levels in WBCs were positively correlated with plasma IP-10 but negatively correlated with plasma IL-10. Furthermore, the mRNA and protein levels of IRF5 in WBCs were significantly elevated in patients with early stage NSCLC compared to those in the progressive stage. Additionally, IRF5 protein levels were significantly lower in NSCLC tumour tissues than those in normal lung tissues.

Conclusions: IRF5 levels in WBCs can be significantly upregulated in early stage NSCLC and were shown to have diagnostic value as an early warning biomarker of NSCLC development.
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http://dx.doi.org/10.1016/j.lungcan.2019.07.008DOI Listing
September 2019

Analyzing the percentage of different PD-1 T cell subsets in peripheral blood and bronchoalveolar lavage fluid of small cell lung cancer patients: A prospective study.

Clin Exp Pharmacol Physiol 2019 12 30;46(12):1074-1083. Epub 2019 Aug 30.

Genetic Diagnosis Centre, The First Hospital of Jilin University, Changchun, China.

The present study was designed to evaluate the percentage of different programmed cell death-1 (PD-1) T cell subsets in peripheral blood and bronchoalveolar lavage fluid (BALF) of small cell lung cancer (SCLC) patients. The percentages of PD-1 T cell subsets in peripheral blood and BALF samples obtained from 52 lung cancer and 20 pneumonia patients, and 20 healthy controls were examined by flow cytometry. In addition, clinical parameters, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, were also determined using Spearman's correlation test to assess their association with PD-1 T cell subsets. These present results revealed that the percentage of circulating PD-1 Tfh and peripheral helper T cells (Tph) cells significantly increased in peripheral blood of SCLC patients, when compared to non-small cell lung cancer (NSCLC) pneumonia patients and healthy controls. In addition, PD-1 Tfh cells were also significantly enhanced in patients in the extensive-stage group. In contrast, the BALF samples of SCLC patients exhibited a significant decrease in percentage of Tph cells. An overall imbalance was observed between PD-1 Tfh and Tph cells in both compartments. Furthermore, SCLC patients exhibited a significant decrease in the percentage of circulating PD-1 Tfh and Tph cells following chemotherapy, and the in vitro analysis revealed that the concentration of IL-2 and IFN-γ derived from PD-1 + Tfh cells in SCLC were significantly lower than that from NSCLC. However, this had no significant correlation with disease severity. The present study indicated that elevated circulating PD-1 T cells can primarily be used as a biomarker for disease diagnosis and a potential therapeutic target.
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http://dx.doi.org/10.1111/1440-1681.13153DOI Listing
December 2019

The protective effect of interfering TLR9-IRF5 signaling pathway on the development of CVB3-induced myocarditis.

Clin Immunol 2019 10 4;207:24-35. Epub 2019 Jul 4.

Department of Molecular Biology in College of Basic Medical Sciences and Institute of Pediatrics in First Hospital, Jilin University, Changchun 130021, PR China. Electronic address:

Since toll-like receptor 9 (TLR9) or interferon regulatory factor 5 (IRF5) was reported to be associated with the development of myocarditis, we wondered if the TLR9-IRF5 pathway could contribute to the development of coxsackievirus B3 (CVB3)-induced myocarditis. We detected signaling molecules of TLR9-IRF5 pathway in CVB3-infected patients and mice. The results showed that TLR9, IRF5 and its downstream molecules such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly increased, and the increase was correlated with the severity of heart injury during CVB3 infection. In addition, we demonstrated that an AAAG ODN with IRF5 interfering activities significantly decreased the levels of the TLR9-IRF5 pathway molecules in hearts, spleens as well as white blood cells, and alleviated the myocarditis in CVB3-infected mice. The data suggest that interfering TLR9-IRF5 pathway could be an approach to treat CVB3-induced myocarditis.
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http://dx.doi.org/10.1016/j.clim.2019.07.002DOI Listing
October 2019

IL-23 and dendritic cells: What are the roles of their mutual attachment in immune response and immunotherapy?

Cytokine 2019 08 24;120:78-84. Epub 2019 Apr 24.

Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, 130 021 Jinlin, China. Electronic address:

Interleukin-23 (IL-23) is a cytokine that is composed of the subunits p19 and p40, while its receptor (IL-23R) consists of two subunits, that is, IL-23Rα and IL-12Rβ1. The interaction between IL-23 and IL-23R is necessary for exerting cardinal biological effects upon certain cell types, including promotion of memory T cell proliferation and Th17 cell-mediated IL-17 secretion. Accordingly, dendritic cells (DCs) are one of the main sources for IL-23 secretion. Interestingly, IL-23R is also present on the DC plasma membrane, suggesting that IL-23 potentially acts on DCs via an autocrine manner. In this review, we have summarized a variety of IL-23-mediated effects on the intracellular signaling pathways such as Janus kinase 2, tyrosine kinase 2, signal transducer and activator of transcription (STAT), mitogen-activated protein kinase signaling, and so forth, which may underlie numerous processes such as DC maturation, antigen presentation, T cell proliferation/activation, and cytokine secretion, which may be implicated in many immune-related diseases through IL-23/DC interactions. Accordingly, these signaling pathways are extensively involved in the pathogenesis and progression of numerous diseases, including autoimmune disease (e.g., atopic dermatitis, asthma, and multiple sclerosis) and infection (e.g., bacterial, fungal, and viral infections). Taken together, they are potentially applicable to novel but promising strategies for treating numerous diseases associated with the mutual attachment of IL-23 and DCs.
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http://dx.doi.org/10.1016/j.cyto.2019.02.018DOI Listing
August 2019

Elevated Circulating CD4CD25Foxp3 Regulatory T Cells in Patients with Nonsmall Cell Lung Cancer.

Cancer Biother Radiopharm 2019 Jun 29;34(5):325-333. Epub 2019 Mar 29.

1 Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, China.

CD4CD25Foxp3 regulatory T (Treg) cell-mediated immunosuppression has been implicated as a crucial mechanism of tumor immune cell escape in nonsmall cell lung cancer (NSCLC). However, little is known concerning the specific role of CD4CD25Foxp3 Treg cells in NSCLC. The aim of this study was to investigate the frequency of circulating CD4CD25Foxp3 Treg cells and their role in NSCLC. The frequencies of Treg, T helper (Th)1, Th2, and Th17 cells in peripheral blood were separately measured in 36 NSCLC patients and 20 healthy controls (HCs) using flow cytometry. Serum cytokine concentrations were determined using cytometric bead arrays. The frequencies of circulating CD4CD25 T cells and CD4CD25Foxp3 and CD4CD25Foxp3 Treg cells were significantly higher in advanced-stage NSCLC patients compared with patients with limited-stage NSCLC. The frequencies of circulating CD4CD25Foxp3 and CD4CD25Foxp3 Treg cells were negatively correlated with interleukin (IL)-17, but positively correlated with serum IL-10 levels. In addition, the Th17/CD4CD25Foxp3 Treg cell ratios were negatively correlated with serum cytokeratin 19 fragment (CYFRA 21-1) concentrations in patients with NSCLC. Moreover, coculturing CD4CD25Foxp3 Treg cells and CD14 monocytes resulted in a higher frequency of CD206CD14 M2-like monocytes compared with CD14 monocytes. Elevated circulating CD4CD25Foxp3 Treg cells may be involved in the pathogenesis of NSCLC.
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http://dx.doi.org/10.1089/cbr.2018.2672DOI Listing
June 2019

Attenuation of interferon regulatory factor 7 activity in local infectious sites of trachea and lung for preventing the development of acute lung injury caused by influenza A virus.

Immunology 2019 05 27;157(1):37-51. Epub 2019 Feb 27.

Department of Molecular Biology in College of Basic Medical Sciences and Institute of Pediatrics in The First Hospital of Jilin University, Jilin University, Changchun, Jilin, China.

The excessive activation of interferon regulatory factor 7 (IRF7) promotes the development of acute lung injury (ALI) caused by influenza A virus (IAV). However, the deficiency of IRF7 increases the susceptibility to deadly IAV infection in both humans and mice. To test whether the attenuation rather than the abolishment of IRF7 activity in local infectious sites could alleviate IAV-induced ALI, we established IAV-infected mouse model and trachea/lung-tissue culture systems, and designed two IRF7-interfering oligodeoxynucleotides, IRF7-rODN M1 and IRF7-rODN A1, based on the mouse and human consensus sequences of IRF7-binding sites of Ifna/IFNA genes, respectively. In the model mice, we found a close relationship between the IAV-induced ALI and the level/activity of IRF7 in local infectious sites, and also found that the reduced IRF7 level or activity in the lungs of mice treated with IRF7-rODN M1 led to decreased mRNA levels of Ifna genes, reduced neutrophil infiltration in the lungs and prolonged survival of mice. Furthermore, we found that the effects of IRF7-rODN M1 on alleviating IAV-induced ALI could be correlated to the reduced translocation of IRF7, caused by the IRF7-rODN M1, from cytosol to nucleus in IAV-infected cells. These data suggest that the proper attenuation of IRF7 activity in local infectious sites could be a novel approach for treating IAV-induced ALI.
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http://dx.doi.org/10.1111/imm.13045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459777PMC
May 2019

Genetic variants of interferon regulatory factor 5 associated with the risk of community-acquired pneumonia.

Gene 2018 Dec 31;679:73-80. Epub 2018 Aug 31.

Department of Respiratory Medicine, The First Affiliated Hospital of Jilin University, Changchun 130021, PR China. Electronic address:

Interferon regulatory factor 5 (IRF5) is a key transcription factor involved in the control of the expression of pro-inflammatory cytokines and immune responses to infection, and multiple polymorphisms of the IFR5 gene have been shown to be associated with autoimmune and infectious diseases. Several studies have investigated single nucleotide polymorphisms (SNPs) in a number of genes associated with the susceptibility to or severity and outcome of community-acquired pneumonia (CAP), but no research has yet been conducted on the role of IRF5 gene polymorphisms in CAP. In this study, we investigated the effects of four IFR5 variants, rs77571059, rs2004640, rs10954213, and rs3807306 on the susceptibility to CAP by genotyping 228 CAP patients and 177 healthy donors. Our results indicated that IFR5 variants rs77571059 and rs2004640 and haplotype GTAA were associated with the susceptibility to CAP and rs77571059 was related to the severity of the disease, suggesting that IFR5 variants may contribute to the pathogenesis of CAP and may serve as prognostic markers of CAP susceptibility and outcome.
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http://dx.doi.org/10.1016/j.gene.2018.08.080DOI Listing
December 2018

Association of Variability and Pharmacogenomics With Bioequivalence of Gefitinib in Healthy Male Subjects.

Front Pharmacol 2018 7;9:849. Epub 2018 Aug 7.

The First Affiliated Hospital of Jilin University, Changchun, China.

The aim of the study was to explore the association of pharmacokinetic variability and pharmacogenomics with the bioequivalence of orally administered gefitinib (Iressa®, AstraZeneca) provided by three sponsors in healthy subjects. The study designs were randomized, open-label, and two-period crossover studies in both fasting and fed healthy subjects. In one fasting study, the sample size was enlarged from 30 to 60 for the failing study. Each study subject received a 250-mg gefitinib tablet with a 21-day washout. The plasma concentrations were measured using LC-MS/MS, and pharmacokinetic parameters were determined by noncompartmental methods. Genetic analyses of CYP3A4, CYP3A5, and CYP2D6 alleles were carried out by the polymerase chain reaction (PCR). Two hundred and sixty healthy male subjects were enrolled. The median maximum plasma concentration (T) was 4-5 h, and the mean elimination half-life (t) was 18-26 h. The maximum plasma concentration (C) and area under the curve (AUC) increased but T and t were unaffected by the intake of high-fat food. Three fed and two fasting studies achieved a plausible bioequivalence. The intake of high-fat food decreased the intra-subject variability significantly. In addition, CYP2D6 was associated with gefitinib exposure and may contribute to the high inter-subject variability, but it did not influence the bioequivalence result. Gefitinib is well tolerated, and the bioequivalence is easier to achieve under fed conditions compared to fasting conditions. The 90% confidence interval (CI) of geometric mean ratio (GMR) can be narrowed when the sample size is enlarged without changing the formulation-related technology.
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http://dx.doi.org/10.3389/fphar.2018.00849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090208PMC
August 2018

miR-144-5p Enhances the Radiosensitivity of Non-Small-Cell Lung Cancer Cells via Targeting ATF2.

Biomed Res Int 2018 12;2018:5109497. Epub 2018 Apr 12.

Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, China.

MicroRNAs (miRNAs or miRs) regulate gene expression at the posttranscriptional level and are involved in many biological processes such as cell proliferation and migration, stem cell differentiation, inflammation, and apoptosis. In particular, miR-144-3p is downregulated in various cancers, and its overexpression inhibits the proliferation and metastasis of cancer cells. However, the role of miR-144-5p in non-small-cell lung cancer (NSCLC), especially radiosensitivity, is unknown. In this study, we found that miR-144-5p was downregulated in NSCLC clinical specimens as well as NSCLC cell lines exposed to radiation. Enhanced expression of miR-144-5p promoted the radiosensitivity of NSCLC cells and A549 cell mouse xenografts . Furthermore, we identified activating transcription factor 2 (ATF2) as the direct and functional target of miR-144-5p using integrated bioinformatics analysis and a luciferase reporter assay. In addition, restoration of ATF2 expression inhibited miR-144-5p-induced NSCLC cell sensitivity to radiation and . Our findings suggest that deregulation of the miR-144-5p/ATF2 axis plays an important role in NSCLC cell radiosensitivity, thus representing a new potential therapeutic target for NSCLC.
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http://dx.doi.org/10.1155/2018/5109497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5925000PMC
October 2018

Expression Levels of Interferon Regulatory Factor 5 (IRF5) and Related Inflammatory Cytokines Associated with Severity, Prognosis, and Causative Pathogen in Patients with Community-Acquired Pneumonia.

Med Sci Monit 2018 May 30;24:3620-3630. Epub 2018 May 30.

Department of Molecular Biology, College of Basic Medical Sciences and Institute of Pediatrics, First Hospital, Jilin University, Changchun, Jilin, China (mainland).

BACKGROUND Community-acquired pneumonia (CAP) is a common disease with significant morbidity and mortality. Interferon regulatory factor 5 (IRF5), which induces type I interferons (IFNs) and cytokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and interferon gamma-induced protein (IP)10, is a key transcription factor involved in controlling the expression of proinflammatory cytokines and responses to infection. Here, we carefully investigated the role of IRF5 in regulating immune responses to CAP. MATERIAL AND METHODS QRT-PCR was used to detect the mRNA levels of IRF5, IL-6, IL-10, IP10, TNF-α, and IFN-α in the peripheral blood of 71 CAP patients and 31 healthy controls, as well as in the bronchoalveolar lavage cells of 20 patients with CAP and 23 patients with lung cancer (using samples from the unaffected lung). Flow cytometry was performed to detect the protein level of IRF5, and a CBA flex set was used to detect the levels of these cytokines in the volunteers. RESULTS The expression levels of IRF5 and its related cytokines were significantly increased in CAP patients compared with the controls. Additionally, IRF5, IL-6, IL-10, and IP10 levels were found to be related with the severity of CAP. Furthermore, the levels of IRF5 and IFN-a increased significantly in the early phase of pneumonia caused by influenza virus infection. CONCLUSIONS IRF5 and its related inflammatory cytokines are associated with the severity, prognosis, and causative pathogen of CAP patients. This finding may provide new drug targets for the prevention and treatment of severe pneumonia caused by influenza virus.
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http://dx.doi.org/10.12659/MSM.910756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004935PMC
May 2018

Immunological Approaches Towards Cancer and Inflammation: A Cross Talk.

Front Immunol 2018 20;9:563. Epub 2018 Mar 20.

Department of Respiration, The First Hospital of Jilin University, Changchun, China.

The inflammation is the protective response of the body against various harmful stimuli; however, the aberrant and inappropriate activation tends to become harmful. The acute inflammatory response tends to resolved once the offending agent is subside but this acute response becomes chronic in nature when the body is unable to successfully neutralized the noxious stimuli. This chronic inflammatory microenvironment is associated with the release of various pro-inflammatory and oncogenic mediators such as nitric oxide (NO), cytokines [IL-1β, IL-2, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)], growth factor, and chemokines. These mediators make the inflammatory microenvironment more vulnerable toward tumorigenesis. The pro-inflammatory mediators released during the chronic inflammation tends to induce several molecular signaling cascades such as nuclear factor kappa B, MAPKinase, nuclear factor erythroid 2-related factor 2, phosphoinositide-3-kinase, Janus kinases/STAT, Wnt/B-catenin, and cyclic AMP response element binding protein. The immune system and its components have a pleiotropic effect on inflammation and cancer progression. Immune components such as T cells, natural killer cells, macrophages, and neutrophils either inhibit or enhance tumor initiation depending on the type of tumor and immune cells involved. Tumor-associated macrophages and tumor-associated neutrophils are pro-tumorigenic cells highly prevalent in inflammation-mediated tumors. Similarly, presence of T regulatory (Treg) cells in an inflammatory and tumor setting suppresses the immune system, thus paving the way for oncogenesis. However, Treg cells also inhibit autoimmune inflammation. By contrast, cytotoxic T cells and T helper cells confer antitumor immunity and are associated with better prognosis in patients with cancer. Cytotoxic T cells inflict a direct cytotoxic effect on cells expressing oncogenic markers. Currently, several anti-inflammatory and antitumor therapies are under trials in which these immune cells are exploited. Adoptive cell transfer composed of tumor-infiltrating lymphocytes has been tried for the treatment of tumors after their expansion. Mediators released by cells in a tumorigenic and inflammatory microenvironment cross talk with nearby cells, either promoting or inhibiting inflammation and cancer. Recently, several cytokine-based therapies are either being developed or are under trial to treat such types of manifestations. Monoclonal antibodies directed against TNF-α, VEGF, and IL-6 has shown promising results to ameliorate inflammation and cancer, while direct administration of IL-2 has been shown to cause tumor regression.
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http://dx.doi.org/10.3389/fimmu.2018.00563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5890100PMC
May 2019

LINE1 contributes to autoimmunity through both RIG-I- and MDA5-mediated RNA sensing pathways.

J Autoimmun 2018 06 7;90:105-115. Epub 2018 Mar 7.

Institute of Virology and AIDS Research, The First Hospital of Jilin University, 519 E. Minzhu St., Changchun, Jilin 130061, China; Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China. Electronic address:

Improper host immune activation leads to the development of the autoimmune disease Aicardi-Goutières syndrome (AGS), which is attributed to defined genetic mutations in such proteins as TREX1 and ADAR1. The mechanism of immune activation in AGS patients has not been thoroughly elucidated to date. In this study, we report that endogenous LINE1 components trigger IFNβ production in multiple human cell types, including those defective for cGAS/STING-mediated DNA sensing. In these cells, LINE1 DNA synthesis and retrotransposition were not required for LINE1-triggered immune activation, but RNA sensing pathways were essential. LINE1-triggered immune activation could be suppressed by diverse LINE1 inhibitors, including AGS-associated proteins targeting LINE1 RNA or proteins. However, AGS-associated ADAR1 or TREX1 mutants were defective in suppressing LINE1 retrotransposition or LINE1-triggered immune activation. Therefore, we have revealed a new function for LINE1 as an endogenous trigger of innate immune activation, which is important for understanding the molecular basis of IFN-based autoimmune diseases and may offer new intervention strategies.
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http://dx.doi.org/10.1016/j.jaut.2018.02.007DOI Listing
June 2018

Antibiotics induce polarization of pleural macrophages to M2-like phenotype in patients with tuberculous pleuritis.

Sci Rep 2017 11 3;7(1):14982. Epub 2017 Nov 3.

Department of Translational Medicine, The First Hospital, Jilin University, Changchun, 130061, China.

Pleural macrophages play critical roles in pathogenesis of tuberculous pleuritis, but very little is known about their response to anti-tuberculosis antibiotics treatment. Here, we examined whether and how pleural macrophages change in phenotype, transcription and function following antibiotics treatment in patients with tuberculous pleuritis. Results show pro-inflammatory cytokines were down-regulated significantly post antibiotic treatment in the pleural effusions and pleural macrophages up-regulated markers characteristic of M2 macrophages such as CD163 and CD206. Differential expression analysis of transcriptomes from four paired samples before and after treatment identified 230 treatment-specific responsive genes in pleural macrophages. Functional analysis identified interferon-related pathway to be the most responsive genes and further confirmed macrophage polarization to M2-like phenotype. We further demonstrate that expression of a significant fraction of responsive genes was modulated directly by antibiotics in pleural macrophages in vitro. Our results conclude that pleural macrophages polarize from M1-like to M2-like phenotype within a mean of 3.5 days post antibiotics treatment, which is dependent on both pleural cytokine environment and direct modulatory effects of antibiotics. The treatment-specific genes could be used to study the roles of pleural macrophages in the pathogenesis of tuberculous pleuritis and to monitor the response to antibiotics treatment.
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http://dx.doi.org/10.1038/s41598-017-14808-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5670217PMC
November 2017

MicroRNA-196b Inhibits Cell Growth and Metastasis of Lung Cancer Cells by Targeting Runx2.

Cell Physiol Biochem 2017 27;43(2):757-767. Epub 2017 Sep 27.

Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, China.

Background/aims: Lung cancer is one of the most common causes of cancer related deaths worldwide. The role of several microRNAs (miRNAs) including miR-196b in different cancers has already been established. The study was aimed to explore the role of miR-196b in lung cancer and its possible underlying mechanism.

Methods: Human lung cancer cell line A549 was transfected with miR-196b mimic, miR-196b inhibitor and corresponding controls. Then cell viability, migration, invasion, and apoptosis of A549 lung cancer cells either with overexpression or with suppression of miR-196b were estimated sequentially. Next, dual luciferase activity assay was performed to clarify whether Runx2 was a direct target of miR-196b. Finally, the expressions of main factors associated with epithelial mesenchymal transition (EMT), PI3K/AKT/GSK3β, Smad, and JNK pathways were detected by western blot.

Results: MiR-196b expression was significantly decreased in A549, H1650 and H1299 cell lines compared with in WI-38 and HEL-1 cell lines. Overexpression of miR-196b suppressed cell viability, migration, invasion, and induced apoptosis as well as inhibited TGF-β induced EMT process in A549 cells. In addition, Runx2 was a putative target of miR-196b, and Runx2 silence remarkably increased cell apoptosis and abolished the promotive effects of miR-196b suppression on cell viability, migration and invasion. Finally, miR-196b also mediated its action by inactivation of PI3K/AKT/GSK3β, Smad, and JNK pathways by down-regulation of Runx2.

Conclusion: MiR-196b functions as a tumor suppressor that inhibited cell growth and metastasis of lung cancer cells by targeting Runx2. These findings provided further evidences for treatment of lung cancer.
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http://dx.doi.org/10.1159/000481559DOI Listing
October 2017

An oligodeoxynucleotide with AAAG repeats significantly attenuates burn-induced systemic inflammatory responses via inhibiting interferon regulatory factor 5 pathway.

Mol Med 2017 09 14;23:166-176. Epub 2017 Jun 14.

Department of Immunology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun, 130021, China.

Previously, we showed that an oligodeoxynucleotide with AAAG repeats (AAAG ODN) rescued mice from fatal acute lung injury (ALI) induced by influenza virus and inhibited production of tumor necrosis factor-α (TNF-α) in the injured lungs. However, the underlying mechanisms remain to be elucidated. Upon the bioinformatic analysis revealing that the AAAG ODN is consensus to interferon regulatory factor 5 (IRF5) binding site in the cis-regulatory elements of proinflammatory cytokines, we tried to explore whether the AAAG ODN could attenuate burn injury induced systemic inflammatory responses via inhibiting IRF5 pathway. Using the mouse model with sterile systemic inflammation induced by burn injury, we found that AAAG ODN prolonged the life span of the mice, decreased the expression of IRF5 at injured skin, reduced the production of TNF-α and IL-6 in blood and injured skin, and attenuated the ALI. Furthermore, AAAG ODN could bind IRF5 and inhibit the nuclear translocation of IRF5 in THP-1 cells. The data suggested that the AAAG ODN could act as a cytoplasmic decoy capable of interfering the function of IRF5, and be developed as a drug candidate for the treatment of inflammatory diseases.
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http://dx.doi.org/10.2119/molmed.2016.00243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583065PMC
September 2017

Betulin exhibits anti-inflammatory activity in LPS-stimulated macrophages and endotoxin-shocked mice through an AMPK/AKT/Nrf2-dependent mechanism.

Cell Death Dis 2017 05 18;8(5):e2798. Epub 2017 May 18.

Institute of Translational Medicine, Department of Respiratory Medicine, The First Hospital, Jilin University, Changchun 130001, China.

Continued oxidative stress can lead to chronic inflammation, which in turn could mediate most chronic diseases including cancer. Nuclear factor erythroid 2-related factor (Nrf2), a critical transcriptional activator for antioxidative responses, has envolved to be an attractive drug target for the treatment or prevention of human diseases. In the present study, we investigated the effects and mechanisms of betulin on Nrf2 activation and its involvement in the lipopolysaccharide (LPS)-triggered inflammatory system. In macrophages, betulin activated the Nrf2 signaling pathway and increased Nrf2-targeted antioxidant and detoxifying enzymes, including NADPH, quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), γ-glutamyl cysteine synthetase catalytic subunit (GCLC) and modifier subunit (GCLM) in a dose and time dependent manner. Importantly, we found betulin-induced activation of Nrf2 is AMPK/AKT/GSK3β dependent, as pharmacologically inactivating AMPK blocked the activating effect of betulin on AKT, GSK3β and Nrf2. Furthermore, betulin attenuated LPS-induced inflammatory mediators (iNOS and COX-2) and MAPK inflammatory signaling pathway. The effect of betulin on HO-1 and NQO1 upregulation, iNOS and COX-2 the downregulation, and survival time extension was largely weakened when Nrf2 was depleted in vitro and in vivo. Our results demonstrate that the AMPK/AKT/Nrf2 pathways are essential for the anti-inflammatory effects of betulin in LPS-stimulated macrophages and endotoxin-shocked mice.
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http://dx.doi.org/10.1038/cddis.2017.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520743PMC
May 2017

Erratum to: Suppression of Spry4 enhances cancer stem cell properties of human MDA-MB-231 breast carcinoma cells.

Cancer Cell Int 2017 11;17:53. Epub 2017 May 11.

Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 USA.

[This corrects the article DOI: 10.1186/s12935-016-0292-7.].
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http://dx.doi.org/10.1186/s12935-017-0423-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427597PMC
May 2017

An AAAG-Rich Oligodeoxynucleotide Rescues Mice from Bacterial Septic Peritonitis by Interfering Interferon Regulatory Factor 5.

Int J Mol Sci 2017 May 11;18(5). Epub 2017 May 11.

Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021, China.

A previous study found that an AAAG-rich Oligodeoxynucleotide (ODN), designated as MS19, could lessen the acute lung inflammatory injury (ALII) in mice infected by influenza viruses. Bioinformatics analysis found that MS19 is consensus with the binding site of interferon regulatory factor 5 (IRF5) in the regulatory elements of pro-inflammatory genes. This study established a septic peritonitis model in Institute of Cancer Research (ICR) mice infected with (), and found that MS19 prolonged the survival of the mice and down-regulated the expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). In cultured RAW264.7 cells, MS19 significantly reduced the expression of iNOS, IRF5, IL-6, and TNF-α and inhibited the nuclear translocation of IRF5. This data may provide a new insight for understanding how MS19 reduces the excessive inflammatory responses in sepsis.
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http://dx.doi.org/10.3390/ijms18051034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454946PMC
May 2017

Associations of Overweight, Obesity and Related Factors with Sleep-Related Breathing Disorders and Snoring in Adolescents: A Cross-Sectional Survey.

Int J Environ Res Public Health 2017 02 15;14(2). Epub 2017 Feb 15.

Pulmonary Division & Sleep Center, The First Hospital of Jilin University, Changchun 130021, China.

: Sleep-related breathing disorders (SRBD) have been identified as a major public health problem closely related to adolescent obesity. We aimed to estimate the prevalences of SRBD and snoring in adolescents in Changchun City, Northeastern China, and to evaluate the associated factors in this population. In total, 1955 adolescents aged 11-18 years were recruited in Changchun City using stratified cluster sampling. Parents and caretakers of children completed the questionnaires, which included demographic characteristics, anthropometric parameters and a pediatric sleep questionnaire (SRBD scale). Logistic regression was used to analyze the relationship between SRBD, snoring and other factors. The prevalences of SRBD and snoring in our population were 3.7% and 3.3%, respectively, and the prevalences of overweight and obesity were 12.6% and 4.9%. Multivariate logistic regression showed that urban residence (OR = 2.356, 95%CI: 1.251-4.435) and post-term birth (OR = 3.275, 95%CI: 1.396-7.683) were significantly associated with SRBD. Preterm birth (OR = 2.255, 95%CI: 1.021-4.980) and parental education level of university and above (OR = 0.265, 95%CI: 0.083-0.850) were significantly associated with snoring. Overweight (OR = 2.063, 95%CI: 1.062-4.006) was also related to snoring. : The prevalences of SRBD and snoring were similar to those reported in previous studies. Urban residence and post-term birth were important influencing factors for SRBD; overweight, highest parental education level (university and above) and preterm birth were key factors affecting snoring in adolescents.
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http://dx.doi.org/10.3390/ijerph14020194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334748PMC
February 2017