Publications by authors named "Junbo Xia"

9 Publications

  • Page 1 of 1

1,25-Dihydroxyvitamin D3 Supplementation during Pregnancy Is Associated with Allergic Rhinitis in the Offspring by Modulating Immunity.

J Immunol Res 2021 14;2021:6638119. Epub 2021 Apr 14.

Department of Otolaryngology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China.

Background: Maternal supplementation with 1,25-dihydroxyvitamin D3 (VD3) has immunologic effects on the developing fetus through multiple pathways. This study was aimed at investigating the effects of VD3 supplementation on immune dysregulation in the offspring during allergic rhinitis.

Methods: Different doses of VD3 as well as control were given to pregnant female mice. Ovalbumin (OVA) challenge and aluminum hydroxide gel in sterile saline were used to induce allergic rhinitis in offspring mice. Nasal lavage fluids (NLF) were collected, and eosinophils were counted in NLF 24 hours after the OVA challenge. Th1, Th2, Th17, and Treg subtype-relevant cytokines, including IFN-, IL-4, IL-10, IL-17, TGF-, and OVA-IgE levels from the blood and NLF of offspring mice, were detected by the enzyme-linked immunosorbent assay (ELISA) method. The Treg subtype was analyzed by flow cytometry. Treg cells were purified from offspring and were adoptively transferred to OVA-sensitized allogenic offspring mice. The outcomes were assessed in allogenic offspring.

Results: Our data showed that VD3 supplementation significantly decreased the number of eosinophils, basophils, and lymphocytes in the peripheral blood and NLF. The proportion of CD4CD25FoxP3Tregs had a positive correlation with VD3 in a dose-dependent manner. The levels of serum IgE, IL-4, and IL-17 were decreased while the expressions of IFN-, IL-10, and TGF- were significantly enhanced in VD3 supplementation groups. Adoptive transfer CD4CD25FoxP3Tregs of VD3 supplementation groups promoted Th1 and suppressed Th2 responses in the offspring during allergic rhinitis.

Conclusion: Our findings indicated that low dose VD3 supply in pregnant mice's diet suppressed Th2 and Th17 responses in allergic rhinitis by elevating the Th1 subtype and the proportion of CD4CD25FoxP3Tregs in offspring. It suggested that low dose VD3 supply may have the potential to act as a new therapeutic strategy for allergic rhinitis.
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http://dx.doi.org/10.1155/2021/6638119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062205PMC
April 2021

Serum exosomal microRNAs as predictive markers for EGFR mutations in non-small-cell lung cancer.

J Clin Lab Anal 2021 May 8;35(5):e23743. Epub 2021 Mar 8.

Department of Infectious Diseases, Affiliated Hangzhou First people's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Current therapeutic drugs show positive effects on non-small-cell lung cancer (NSCLC) patients with mutant epidermal growth factor receptor (EGFR) expression, whereas a lesser beneficial effect is generally noted on NSCLC patients with wild-type EGFR. Therefore, identification of new detection methods for the accurate clinical diagnosis of NSCLC is essential.

Methods: In this study, tumor-derived exosomes from the plasma of EGFR mutation and wild-type NSCLC patients were isolated. Extensive exosomal miRNA profiling of EGFR mutation and wild-type NSCLC patients, in comparison with healthy individuals, was performed using miRNA-sequencing analysis.

Results: The variation of exosomal miRNA expression between control group (NR) and NCSLC samples (AM and AW) was identified. 96 significantly different expressed miRNAs were identified. Of these, 39 miRNAs were upregulated and 57 were downregulated. 11 miRNAs were downregulated, and 31 miRNAs were upregulated in the miRNA expression between NR and AM. Compared with healthy donors, 54 upregulated miRNAs and 36 downregulated miRNAs were observed in samples from AW patients. 40 different expressed miRNAs were identified in AM samples, compared with AW. Ten of upregulated miRNAs are miR-260, miR-1169, miR-117, miR-15b-5p, miRNA-731, miR-342-5p, miR- 898, miR-1384, miR-56, and miR-1214. Ten of downregulated miRNAs are miR-99b-5p, miR-1116, miR-689, miR-818, miR-604, miR-72, miR-955, miR-403, miR-1228, and miR-836.

Conclusion: The exosomal miR-1169 and miR-260 as potential candidates, which contain specific characteristics that can distinguish between wild-type EGFR and mutant EGFR NSCLC patients in early-stage cancers.
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http://dx.doi.org/10.1002/jcla.23743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128312PMC
May 2021

Ganoderic acid DM induces autophagic apoptosis in non-small cell lung cancer cells by inhibiting the PI3K/Akt/mTOR activity.

Chem Biol Interact 2020 Jan 23;316:108932. Epub 2019 Dec 23.

Department of Infectious Diseases, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, 310006, Hangzhou, Zhejiang, China. Electronic address:

The incidence and mortality of lung cancer are the highest among cancer-related deaths. However, the long-term use of currently available cytotoxic drugs can increase genetic alterations in cancer cells and cause drug-resistance, which significantly limits their usage. Since current systemic treatment options are limited, effective chemotherapeutic agents are urgently needed for non-small cell lung cancer (NSCLC) treatment. In this study, we demonstrated that ganoderic acid DM (GA-DM) could increase apoptosis in A549 and NCI-H460 NSCLC cells. GA-DM treatment decreased the protein expression levels of Bcl-2 and increased the expression levels of Bax, cleaved caspase-3 and cleaved PRAP. Furthermore, GA-DM could promote autophagic flux, and the cytotoxic effect against cancer cells of GA-DM was significantly inhibited by targeted suppression of autophagy, suggesting that autophagy contributed to GA-DM-induced cell death in NSCLC. Moreover, GA-DM clearly induced autophagy by inactivating the PI3K/Akt/mTOR pathway. When overexpression of Akt reactivated Akt/mTOR pathway in A549 or NCI-H460 cells, the increase of autophagy related marker LC3B-II and apoptosis related protein cleaved PARP and cleaved caspase 3 and the ration of apoptotic cells by GA-DM was reversed, suggesting that GA-DM promoted autophagy and apoptosis by inhibiting Akt/mTOR pathway-mediated autophagy induction. In conclusion, our study indicated that GA-DM can induce autophagic apoptosis in NSCLC by inhibiting Akt/mTOR activity. (209 words).
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http://dx.doi.org/10.1016/j.cbi.2019.108932DOI Listing
January 2020

Frequency of Signs and Symptoms in Persons With Asthma.

Respir Care 2020 Feb 29;65(2):252-264. Epub 2019 Oct 29.

Institution of Respiratory Disease, Xinqiao Hospital of 3rd Military Medical University, Chongqing, China.

Background: Signs and symptoms of asthma are well established; however, no study has been performed to rank them. Therefore, we performed this systematic review and meta-analysis to determine the pooled frequencies of different signs and symptoms of asthma in subjects age ≥ 14 y to develop a patient-specific questionnaire.

Methods: Specific search queries were developed to include records published in Embase, PubMed, Cochrane Library, and Google Scholar, until November 2016. We planned to include randomized controlled trials (RCTs) and observational studies for determining the pooled proportions of signs and symptoms and association between combination of symptoms and asthma severity in subjects age ≥ 14 y. The quality assessment was performed using 3 parameters: reported number or percentage of subjects with asthma symptoms, respiratory disorder history, and method for data collection.

Results: Of the 4,939 records retrieved, 67 observational studies ( = 57,033 subjects; age ≥ 14 y) were considered eligible for inclusion in the analysis. A total of 10 symptoms were reported across the studies, with pooled proportions of nasal congestion, sleep disturbances, breathlessness, chest tightness, and wheezing being 61.57%, 56.56%, 50.31%, 50.41%, and 46.97%, respectively. In records of medical history, the pooled proportion of rhinitis was 76.37%, followed by allergy/atopy at 63.53%. The pooled proportion of asthma medication use was 83.27%. In terms of the symptom combinations, the combination of wheezing, breathlessness, chest tightness, and cough was reported in 71.26% of subjects from 4 studies ( = 12,014 subjects). Nasal congestion, sleep disturbance, and chest tightness were the most common symptoms of asthma, followed by wheezing and breathlessness with a combination of symptoms (ie, wheezing, breathlessness, chest tightness, and cough) affecting the highest proportion of subjects.

Conclusions: Asthma severity was dependent on variety of symptoms, consisting mostly of wheezing, breathlessness, chest tightness, and cough. On the basis of our analysis, we recommend a combination of symptoms be included in diagnostic-based questionnaires to aid early diagnosis.
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http://dx.doi.org/10.4187/respcare.06714DOI Listing
February 2020

Modified Si-Jun-Zi-Tang Attenuates Airway Inflammation in a Murine Model of Chronic Asthma by Inhibiting Teff Cells via the mTORC1 Pathway.

Front Pharmacol 2019 27;10:161. Epub 2019 Feb 27.

Department of Respiratory Diseases, Affiliated Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.

Modified Si-Jun-Zi-Tang (MSJZT), a multi-herb formulation, is frequently used in traditional Chinese medicine for patients during the remission stage of asthma. However, the pharmacological basis underlying the effects of MSJZT on asthma has yet to be elucidated. This study aims at evaluating the anti-asthmatic effects of MSJZT and investigating its possible mechanism. A chronic murine model of asthma was established by sensitization and repeated challenge with ovalbumin (OVA) in female BALB/c mice, followed with oral administration of MSJZT during remission, and then mouse were re-challenged by OVA. The chemical profile of MSJZT was analyzed by high-performance liquid chromatography. The characteristic features of allergic asthma, including airway hyperreactivity, histopathology, cytokine levels (IL-4, -5, -13, -17, and INF-γ), T regulatory (Treg) lymphocytes (Foxp3+CD4+CD25+), and T effector (Teff) lymphocytes (Foxp3-CD25+CD4+) in bronchoalveolar lavage fluid (BALF), and downstream proteins of mTORC1/2 signaling pathway were examined. MSJZT markedly suppressed airway hyper-responsiveness to aerosolized methacholine, and reduced levels of IL-4, IL-5, and IL-13 in the BALF. Histological studies showed that MSJZT significantly reduced inflammatory infiltration in lung tissues. The percentage and absolute number of Teff cells were suppressed to a remarkable level by MSJZT without affecting Treg cells. Furthermore, MSJZT effectively inhibited the mTORC1 activity, but exerted limited effects on mTORC2, as assessed by the phosphorylation of the mTORC1 and mTORC2 substrates, S6 ribosomal protein, p70 S6 kinase, mTOR S2481, and Akt, respectively. MSJZT attenuated chronic airway inflammation in a mouse model of asthma by inhibiting Teff cells, which occurred, at least in part, via modulation of the mTORC1 signaling pathway.
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http://dx.doi.org/10.3389/fphar.2019.00161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400882PMC
February 2019

Ganoderic Acid A improves high fat diet-induced obesity, lipid accumulation and insulin sensitivity through regulating SREBP pathway.

Chem Biol Interact 2018 Jun 29;290:77-87. Epub 2018 May 29.

Department of Pulmonary Medicine Hangzhou First People's Hospital, Nanjing Medical University, 310006, Hangzhou, Zhejiang, China. Electronic address:

Obesity and its major co-morbidity, type 2 diabetes, have been an alarming epidemic prevalence without an effective treatment available. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. Therefore, inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Here, we identify a small molecule, Ganoderic Acid A (GAA), inhibits the SREBP expression and decreases the cellular levels of cholesterol and fatty acid in vitro. GAA also ameliorates body weight gain and fat accumulation in liver or adipose tissues, and improves serum lipid levels and insulin sensitivity in high fat diet (HFD)-induced obese mice. Consistently, GAA regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Taken together, GAA could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance.
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http://dx.doi.org/10.1016/j.cbi.2018.05.014DOI Listing
June 2018

Astragaloside IV Ameliorates Airway Inflammation in an Established Murine Model of Asthma by Inhibiting the mTORC1 Signaling Pathway.

Evid Based Complement Alternat Med 2017 25;2017:4037086. Epub 2017 Oct 25.

Department of Respiratory Diseases, Hangzhou First People's Hospital, The Fourth Clinical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, China.

Astragaloside IV (AS-IV), a main active constituent of , has been confirmed to have antiasthmatic effects. However, it remained unclear whether the beneficial effects of AS-IV on asthma were attributed to the mTOR inhibition; this issue was the focus of the present work. BALB/c mice were sensitized and challenged with ovalbumin followed with 3 weeks of rest/recovery and then reexposure to ovalbumin. AS-IV was administrated during the time of rest and reexposure. The characteristic features of allergic asthma, including airway hyperreactivity, histopathology, cytokines (IL-4, IL-5, IL-13, IL-17, and INF-), and CD4CD25Foxp3Treg cells in bronchoalveolar lavage fluid (BALF), and downstream proteins of mTORC1/2 signaling were examined. AS-IV markedly suppressed airway hyperresponsiveness and reduced IL-4, IL-5, and IL-17 levels and increased INF- levels in the BALF. Histological studies showed that AS-IV markedly decreased inflammatory infiltration in the lung tissues. Notably, AS-IV inhibited mTORC1 activity, whereas it had limited effects on mTORC2, as assessed by phosphorylation of mTORC1 and mTORC2 substrates S6 ribosomal protein, p70 S6 Kinase, and Akt, respectively. CD4CD25Foxp3Treg cells in BALF were not significantly changed by AS-IV. Together, these results suggest that the antiasthmatic effects of AS-IV were at least partially from inhibiting the mTORC1 signaling pathway.
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http://dx.doi.org/10.1155/2017/4037086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676443PMC
October 2017

Three cases of avian-origin influenza A (H7N9) virus infection in Zhejiang Province, China: case report and literature review.

Intern Med 2014 15;53(20):2397-400. Epub 2014 Oct 15.

Department of Respiratory Disease, the First People's Hospital of Hangzhou, Nanjing Medical University, China.

This report provides information on the clinical characteristics and treatment of three patients with avian influenza A (H7N9) virus treated in Zhejiang Province, China. The infection was characterized by respiratory symptoms, fever, rapid progression, and significant hypoxemia. Laboratory tests showed a low level or decrease in leukocytes. It is recommended that neuraminidase inhibitors be administered at early stage of the disease.
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http://dx.doi.org/10.2169/internalmedicine.53.2514DOI Listing
June 2015

Suppression of allergic inflammation by allergen-DNA-modified dendritic cells depends on the induction of Foxp3+ Regulatory T cells.

Scand J Immunol 2008 Feb;67(2):140-51

Institute of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

CD4(+)CD25(+)Foxp3(+)Regulatory T cells (Tregs) play important roles in regulating allergic inflammation. To analyse if allergen-DNA-modified dendritic cells (DC) can suppress allergic responses and what roles Treg cells play in DC-based allergen-specific immunotherapy. Immature DC were transfected with retrovirus encoding Der p2 DNA, and administered to mice that sensitized and challenged with Der p2 protein. After Treg cells were depleted with anti-CD25 mAb, mice were re-challenged to observe the airway inflammation, and Treg cells in spleen CD4(+) T cells. And responses of spleen CD4(+) T cells to Der p2 were determined. Co-culture of naïve CD4(+) T cells with allergen-modified DC induced Foxp3+ Tregs. Sensitized and challenged mice developed allergic airway inflammation and Th2 responses, and decreased Foxp3(+) Tregs. Treatment with allergen-modified-DC suppressed airway inflammation and Th2 responses, and increased IL-10 and IFN-gamma production and Foxp3(+) Tregs significantly; and eliminated the responses of CD4(+) T cells to allergen. Administration of anit-CD25 mAb eliminated all the effects of modified-DC except for the increasing of IFN-gamma. Allergen-modified DC can induce immune tolerance to allergens and reverse the established Th2 responses induced by allergen, with dependence on the induction of Foxp3(+) Tregs.
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http://dx.doi.org/10.1111/j.1365-3083.2007.02050.xDOI Listing
February 2008