Publications by authors named "Shenggang Ding"

11 Publications

  • Page 1 of 1

Nano-metal-organic-frameworks for treating HO-Secreting bacteria alleviate pulmonary injury and prevent systemic sepsis.

Biomaterials 2021 Dec 2;279:121237. Epub 2021 Nov 2.

Department of Radiology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230001, PR China; Intelligent Nanomedicine Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, PR China. Electronic address:

As a vital bacteria-secreted toxin, hydrogen peroxide (HO) can destroy infected tissues and increase vascular permeability, leading to life-threatening systemic bacteremia or sepsis. No strategy that can alleviate HO-induced injury and prevent systemic sepsis has been reported. Herein, as a proof of concept, we demonstrate the use of HO-reactive metal-organic framework nanosystems (MOFs) for treating HO-secreting bacteria. In mice infected with Streptococcus pneumoniae (S. pneumoniae) isolated from patients, MOFs efficiently accumulate in the lungs after systemic administration due to infection-induced alveolar-capillary barrier dysfunction. Moreover, MOFs sequester pneumococcal HO, reduce endothelial DNA damage, and prevent systemic dissemination of bacteria. In addition, this nanosystem exhibits excellent chemodynamic bactericidal effects against drug-resistant bacteria. Through synergistic therapy with the antibiotic ampicillin, MOFs eliminate over 98% of invading S. pneumoniae, resulting in a survival rate of greater than 90% in mice infected with a lethal dose of S. pneumoniae. This work opens up new paths for the clinical treatment of toxin-secreting bacteria.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121237DOI Listing
December 2021

IL-17 stimulates neutrophils to release S100A8/A9 to promote lung epithelial cell apoptosis in Mycoplasma pneumoniae-induced pneumonia in children.

Biomed Pharmacother 2021 Nov 22;143:112184. Epub 2021 Sep 22.

Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China. Electronic address:

Mycoplasma pneumoniae-induced pneumonia (MPP) is a common cause of community-acquired respiratory tract infections, increasing risk of morbidity and mortality, in children. However, diagnosing early-stage MPP is difficult owing to the lack of good diagnostic methods. Here, we examined the protein profile of bronchoalveolar lavage fluid (BALF) and found that S100A8/A9 was highly expressed. Enzyme-linked immunosorbent assays used to assess protein levels in serum samples indicated that S100A8/A9 concentrations were also increased in serum obtained from children with MPP, with no change in S100A8/A9 levels in children with viral or bacterial pneumonia. In vitro, S100A8/A9 treatment significantly increased apoptosis in a human alveolar basal epithelial cell line (A549 cells). Bioinformatics analyses indicated that up-regulated S100A8/A9 proteins participated in the interleukin (IL)-17 signaling pathway. The origin of the increased S100A8/A9 was investigated in A549 cells and in neutrophils obtained from children with MPP. Treatment of neutrophils, but not of A549 cells, with IL-17A released S100A8/A9 into the culture medium. In summary, we demonstrated that S100A8/A9, possibly released from neutrophils, is a new potential biomarker for the clinical diagnosis of children MPP and involved in the development of this disease through enhancing apoptosis of alveolar basal epithelial cells.
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http://dx.doi.org/10.1016/j.biopha.2021.112184DOI Listing
November 2021

Epidemiological characteristics and clinical manifestations of pediatric patients with COVID-19 in China: A multicenter retrospective study.

Pediatr Investig 2021 Aug 12:e12282. Epub 2021 Aug 12.

Chinese University of Hong Kong Shatin Hong Kong China.

Importance: The Coronavirus disease 2019 (COVID-19) global pandemic poses a considerable challenge for pediatricians.

Objective: This study aimed to identify the epidemiological characteristics and clinical features of pediatric patients with COVID-19 in China.

Methods: This multicenter retrospective study included pediatric patients from 46 hospitals in China, covering 12 provinces and two municipalities. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were analyzed.

Results: In total, 211 pediatric patients with COVID-19 were included in this study. The median age was 7.0 years (range: 22 days to 18 years). Approximately 16.3% of the patients exhibited asymptomatic infections, 23.0% had upper respiratory tract infections, and 60.7% had pneumonia, including two with severe pneumonia and one with critical illness. Approximately 78.7% of the pediatric patients occurred in familial clusters. The most three common symptoms or signs at onset in children with COVID-19 were fever (54.5%), cough (49.3%), and pharyngeal congestion (20.8%). Only 17.6% of the patients presented with decreased lymphocyte count, whereas 13.6% had increased lymphocyte count. Among the patients with pneumonia who exhibited abnormal chest computed tomography findings, 18.2% (23/127) of the patients had no other symptoms. Generally, the chest radiographs showed abnormalities that affected both lungs (49.6%); ground-glass opacity (47.2%) was the most common manifestation. The cure and improvement rates were 86.7% (183/211) and 13.3% (28/211), respectively. Only one patient with an underlying condition received invasive mechanical ventilation; none of the patients died.

Interpretation: Similar to adults, children of all age groups are susceptible to COVID-19. Fortunately, most pediatric patients have mild symptoms or remain asymptomatic, despite the high incidence of pneumonia. Decreased proportions of white blood cells and lymphocytes are less frequent in children than in adults.
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http://dx.doi.org/10.1002/ped4.12282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441896PMC
August 2021

Comparison of Clinical Characteristics Among COVID-19 and Non-COVID-19 Pediatric Pneumonias: A Multicenter Cross-Sectional Study.

Front Cell Infect Microbiol 2021 1;11:663884. Epub 2021 Jul 1.

Department of Pediatrics, Yichang Central People's Hospital, Yichang, China.

Background: The pandemic of Coronavirus Disease 2019 (COVID-19) brings new challenges for pediatricians, especially in the differentiation with non-COVID-19 pneumonia in the peak season of pneumonia. We aimed to compare the clinical characteristics of pediatric patients with COVID-19 and other respiratory pathogens infected pneumonias.

Methods: We conducted a multi-center, cross-sectional study of pediatric inpatients in China. Based on pathogenic test results, pediatric patients were divided into three groups, including COVID-19 pneumonia group, Non-COVID-19 viral (NCV) pneumonia group and Non-viral (NV) pneumonia group. Their clinical characteristics were compared by Kruskal-Wallis H test or chi-square test.

Results: A total of 636 pediatric pneumonia inpatients, among which 87 in COVID-19 group, 194 in NCV group, and 355 in NV group, were included in analysis. Compared with NCV and NV patients, COVID-19 patients were older (median age 6.33, IQR 2.00-12.00 years), and relatively fewer COVID-19 patients presented fever (63.2%), cough (60.9%), shortness of breath (1.1%), and abnormal pulmonary auscultation (18.4%). The results were verified by the comparison of COVID-19, respiratory syncytial virus (RSV) and influenza A (IFA) pneumonia patients. Approximately 42.5%, 44.8%, and 12.6% of the COVID-19 patients presented simply ground-glass opacity (GGO), simply consolidation, and the both changes on computed tomography (CT) scans, respectively; the proportions were similar as those in NCV and NV group (p>0.05). Only 47.1% of COVID-19 patients had both lungs pneumonia, which was significantly lower than that proportion of nearly 80% in the other two groups. COVID-19 patients presented lower proportions of increased white blood cell count (16.5%) and abnormal procalcitonin (PCT) (10.7%), and a higher proportion of decreased lymphocyte count (44.0%) compared with the other two groups.

Conclusion: Majority clinical characteristics of pediatric COVID-19 pneumonia patients were milder than non-COVID-19 patients. However, lymphocytopenia remained a prominent feature of COVID-19 pediatric pneumonia.
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http://dx.doi.org/10.3389/fcimb.2021.663884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281119PMC
July 2021

Voluntary-Opsonization-Enabled Precision Nanomedicines for Inflammation Treatment.

Adv Mater 2021 Jan 9;33(3):e2006160. Epub 2020 Dec 9.

Institutes for Life Sciences, School of Biomedical Sciences and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangdong, 510006, P. R. China.

Nanomedicines that target specific blood cells represent an emerging strategy to improve drug biodistribution. However, the protein corona usually disrupts nanomedicine targeting to cells and tissues. Herein, instead of exploring synthetic methods to mitigate the impact of the protein corona, its natural interactions with blood cells are leveraged and turn the protein corona into an active ingredient in treating lung inflammation. It is discovered that molecularly engineered liposomes with inverse phosphocholine lipids rapidly enrich complement fragment iC3b by "voluntary opsonization," which triggers neutrophil hijacking through complement receptor 3 phagocytosis. This neutrophil targeting is cell-state dependent as only those activated by acute inflammation display efficient neutrophil reconstruction. The liposome-loaded neutrophils migrate across the alveolar-capillary barrier, accumulate in the inflamed lung parenchyma within hours, and release their payloads to kill the bacteria. This work shows that, in addition to biological cells, the protein corona can be a new platform for active and precision nanomedicine.
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http://dx.doi.org/10.1002/adma.202006160DOI Listing
January 2021

Photo-Degradable Micelles Capable of Releasing of Carbon Monoxide under Visible Light Irradiation.

Macromol Rapid Commun 2020 Sep 9;41(18):e2000323. Epub 2020 Aug 9.

ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, 4072, Australia.

Carbon monoxide (CO) has emerged as a potential therapeutic agent for the treatment of many diseases. However, the therapeutic outcome is highly dependent on the dosages and administration sites. Hence, there is mounting interest in the development of CO-releasing materials to accomplish site-specific and dose-controlled delivery of CO. Herein, a micellar nanoparticle platform for the photo-mediated release of CO by using amphiphilic triblock copolymers bearing CO-releasing moieties of 3-hydroxylflavone (3-HF) derivatives within the middle blocks is developed. These micelles are relatively stable without CO leakage but undergo visible light-mediated CO release and simultaneous main chain scission. Moreover, these micellar nanoparticles are cytocompatible regardless of light irradiation, which shows unique anti-inflammatory performance only after light irradiation as a result of photo-triggered CO release. This work may represent the first example of main-chain degradable micellar nanocarriers with controlled CO-releasing performance for potential anti-inflammatory applications.
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http://dx.doi.org/10.1002/marc.202000323DOI Listing
September 2020

TRPV4 Complexes With the Na/Ca Exchanger and IP Receptor 1 to Regulate Local Intracellular Calcium and Tracheal Tension in Mice.

Front Physiol 2019 6;10:1471. Epub 2019 Dec 6.

School of Basic Medical Sciences, Anhui Medical University, Hefei, China.

Intracellular Ca is critical for regulating airway smooth muscle (ASM) tension. A rapid rise in the intracellular Ca concentration ([Ca]) of ASM cells is crucial for modulating the intensity and length of the ASM contraction. Because this rapid increase in [Ca] largely depends on the balance between Ca released from intracellular Ca stores and extracellular Ca entry, exploring the mechanisms mediating Ca transport is critical for understanding ASM contractility and the pathogenesis of bronchial contraction disorders. Transient receptor potential vanilloid 4 (TRPV4) is a highly Ca-permeable non-selective cation channel that mediates Ca influx to increase [Ca], which then directly or indirectly regulates the contraction and relaxation of ASM. The [Ca] returns to basal levels through several uptake and extrusion pumps, such as the sarco(endo)plasmic reticulum Ca ATPase and inositol 1,4,5-trisphosphate receptors (IPRs), the plasmalemmal Ca ATPase, and the plasma membrane Na/Ca exchanger (NCX). Thus, to further understand ASM tension regulation in normal and diseased tissue, the present study examined whether an interaction exists among TRPV4, IPRs, and NCX. The TRPV4-specific and potent agonist GSK1016790A increased [Ca] in mouse ASM cells, an effect that was completely blocked by the TRPV4-specific antagonist HC067047. However, GSK1016790A induced relaxation in mouse tracheal rings precontracted with carbachol . To determine the mechanism underlying this TRPV4-induced relaxation of ASM, we blocked specific downstream molecules. We found that the GSK1016790A-induced relaxation was abolished by the NCX inhibitors KB-R7943 and LiCl but not by specific inhibitors of the Ca-activated large-, intermediate-, or small-conductance K channels (BK, IK, and SK, respectively). The results of co-immunoprecipitation (co-IP) assays showed an interaction of TRPV4 and IPR with NCX. Taken together, these findings support a physical and functional interaction of TRPV4 and IPR with NCXs as a novel TRPV4-mediated Ca signaling mechanism and suggest a potential target for regulation of ASM tension and treatment of respiratory diseases, especially tracheal spasm.
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http://dx.doi.org/10.3389/fphys.2019.01471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910018PMC
December 2019

Cationic micelle: A promising nanocarrier for gene delivery with high transfection efficiency.

J Gene Med 2019 07 9;21(7):e3101. Epub 2019 Jul 9.

CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, China.

Micelles have demonstrated an excellent ability to deliver several different types of therapeutic agents, including chemotherapy drugs, proteins, small-interfering RNA and DNA, into tumor cells. Cationic micelles, comprising self-assemblies of amphiphilic cationic polymers, have exhibited tremendous promise with respect to the delivery of therapy genes and gene transfection. To date, research in the field has focused on achieving an enhanced stability of the micellar assembly, prolonged circulation times and controlled release of the gene. This review focuses on the micelles as a nanosized carrier system for gene delivery, the system-related modifications for cytoplasm release, stability and biocompatibility, and clinic trials. In accordance with the development of synthetic chemistry and self-assembly technology, the structures and functionalities of micelles can be precisely controlled, and hence the synthetic micelles not only efficiently condense DNA, but also facilitate DNA endocytosis, endosomal escape, DNA uptake and nuclear transport, resulting in a comparable gene transfection of virus.
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http://dx.doi.org/10.1002/jgm.3101DOI Listing
July 2019

Autophagy inhibition promotes phagocytosis of macrophage and protects mice from methicillin-resistant staphylococcus aureus pneumonia.

J Cell Biochem 2018 06 7;119(6):4808-4814. Epub 2018 Mar 7.

Department of Paediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

The present study is to investigate the effect of autophagy in macrophages and the protection of mouse models against MRSA invasion, which provide new potential therapeutic direction for lung infection. The effect of ST239 in macrophages were analyzed by Western blot. The immunofluorescence was used to observe the influence of autophagy inhibitor 3-MA in macrophages. Then we established MRSA mice model and the models were divided into different groups of drugs. The effect of autophagy in macrophage with MRSA and the changes of lung pathological in the mouse model was analyzed by flow cytometry and immunohistochemistry. The ability of phagocytic decreases when ST239 infected the macrophages. And the autophagy-related genes Beclin-1, LC3-I, and LC3-II protein expression significantly increased. GFP-LC3 immunostaining showed that GFP-LC3 was significantly over-expressed in ST239-infected macrophages. Then we found the autophagy inhibitors 3-MA could make the expression of autophagy-related genes Beclin-1, LC3-I, and LC3-II decreased, the number of ST239 decreased, and the ability of macrophages phagocytosed MRSA increasing. In the mouse model we performed the same assay, the results showed that the percentage of macrophages in the mouse model treated with 3-MA was increased compared to the ST239 mouse model and that the number of bacteria in right lung significantly reduced. Lung cells treated with3-MA significantly improved the lesion of ST239 lung cell disease. Inhibition of autophagy can increase the ability of macrophages phagocytosed MRSA, and it is a suitable target for preventing or treating MRSA infection.
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http://dx.doi.org/10.1002/jcb.26677DOI Listing
June 2018

Fluorinated PEG-Polypeptide Polyplex Micelles Have Good Serum-Resistance and Low Cytotoxicity for Gene Delivery.

Macromol Biosci 2017 08 19;17(8). Epub 2017 May 19.

CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China.

A novel PEGylation polypeptide, poly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-cysteine) (PEG-PLL-PCys) triblock copolymer is synthesized via the sequential ring-opening polymerization of amino acid N-carboxyanhydrides initiated by methoxypolyethylene glycol amine (mPEG-NH , M is 2 kDa). Subsequently, the obtained polypeptide is partially conjugated with fluorocarbon chains via disulfide exchange reaction. PLL segment can condense plasmid DNA through an electrostatic force to form a complex core, PEG segment surrounding the complex like a corona can prevent the complex from precipitation and reduce the adsorption of serum, while PCys segment with fluorocarbon can enhance the cellular uptake and the stability of the formed polyplex micelles in physiological conditions. Experiment results exhibit that the fluorinated polypeptides have low cytotoxicity and good gene transfection efficiency even in the presence of 50% fetal bovine serum.
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http://dx.doi.org/10.1002/mabi.201700114DOI Listing
August 2017

Decreased Interleukin-10 Responses in Children with Severe Mycoplasma pneumoniae Pneumonia.

PLoS One 2016 11;11(1):e0146397. Epub 2016 Jan 11.

Department of Microbiology, Anhui Medical University, Hefei, Anhui, China.

Several cytokines may play roles in the immunological pathogenesis of mycoplasmal pneumonia caused by Mycoplasma pneumoniae. In this study, we investigated serum cytokine profiles in children with mycoplasmal pneumonia. The serum levels of interleukin (IL)-8, IL-10, and IL-18 were examined using ELISA kits in 34 patients with M. pneumoniae infection (Group 1, 11 with severe mycoplasmal pneumonia; Group 2, 13 with mild mycoplasmal pneumonia; Group 3, 10 with asthma) and 32 age-matched, non-infected controls. The serum levels of IL-8, IL-10, and IL-18 increased significantly in patients with mycoplasmal pneumonia compared with those in controls (P<0.01). The serum levels of IL-10 decreased significantly in Group 1 compared with those in Group 2 (P<0.01). The serum levels of IL-18 increased significantly in Group 1 compared with those in Group 2 (P<0.01). The serum levels of IL-10 and IL-18 decreased significantly in 10 M. pneumoniae-infected patients with asthma compared with those in 24 M. pneumoniae-infected patients without asthma (P<0.01). We examined the level of interleukins (IL-8, IL-10 and IL-18) after the patients started therapy. The data showed that IL-18 were lower after therapy (P<0.01). Collectively, our data suggested that these cytokines may be involved in the pathogenesis of mycoplasmal pneumonia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146397PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708986PMC
July 2016
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