Publications by authors named "Jinling Gao"

9 Publications

  • Page 1 of 1

Polyhexamethylene guanidine aerosol triggers pulmonary fibrosis concomitant with elevated surface tension via inhibiting pulmonary surfactant.

J Hazard Mater 2021 Jul 13;420:126642. Epub 2021 Jul 13.

Department of Environmental and Occupational Health, School of Public Health, Qingdao University, Qingdao 266071, China. Electronic address:

Environmental chemicals inhalation exposure could induce pulmonary fibrosis, which is characterized by the excessive proliferation of fibroblasts and accumulation of extracellular matrix components, in which surface tension usually plays vital roles. Polyhexamethylene guanidine (PHMG) was first recognized as a potential hazard ingredient in humidifier disinfectants, which caused an outbreak of pulmonary fibrosis in South Korea. However, the underlying mechanisms involved in PHMG-induced pulmonary fibrosis have not yet been fully elucidated. Therefore, this study mainly focuses on the effect of PHMG on surface tension to unveil the influence and involved mechanisms in PHMG-induced pulmonary fibrosis. C57BL/6J mice were exposed to sub-acute PHMG aerosol for 8 weeks. The results indicated that PHMG induced pulmonary fibrosis combined with elevated surface tension. Results from in vitro study further confirmed PHMG elevated surface tension by inhibited pulmonary surfactant. Mechanistically, PHMG suppressed the key surfactant protein SP-B and SP-C by inhibiting protein expression and block their active sites. The present study, for the first time, revealed the molecular mechanism of PHMG-induced pulmonary fibrosis based on pulmonary surfactant inhibition mediated surface tension elevated. And pulmonary surfactant may be a potential target for further intervention to prevent PHMG-induced fibrosis or alleviate the symptom of relevant patients.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126642DOI Listing
July 2021

Time-course effect of ultrasmall superparamagnetic iron oxide nanoparticles on intracellular iron metabolism and ferroptosis activation.

Nanotoxicology 2021 04 16;15(3):366-379. Epub 2021 Jan 16.

School of Public Health, Qingdao University, Qingdao, China.

Ferroptosis is an iron-dependent cell death caused by excessive peroxidation of polyunsaturated fatty acids. It can be activated by iron-based nanoparticles as a potential cancer therapeutic target. However, the intracellular transformation of iron-based nanoparticles is still ambiguous and the subsequent ferroptosis mechanism is also obscure. Here, we identified the time-course metabolism of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) in cells by using X-ray absorption near edge structure spectroscopy. Also, the integrated quantitative transcriptome and proteome data obtained from the cells exposed to USPIO exhibited hallmark features of ferroptosis. With the chemical species of iron oxide transforming to ferritin, the intracellular GPX4 down-regulated, and lipid peroxide began to accumulate. These results provide evidence that the intracellular metabolism of USPIO induced ferroptosis in a time-dependent manner, and iron over-loaded in cytoplasm along with lipid peroxidation of the membrane are involved in the detailed mechanism of ferroptosis signaling activation.
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http://dx.doi.org/10.1080/17435390.2021.1872112DOI Listing
April 2021

Occupational exposure to carbon black nanoparticles increases inflammatory vascular disease risk: an implication of an ex vivo biosensor assay.

Part Fibre Toxicol 2020 09 29;17(1):47. Epub 2020 Sep 29.

Department of Occupational and Environmental Health, School of Public Health, Qingdao University, Qingdao, 266021, China.

Background: Among manufactured or engineered nanoparticles, carbon black (CB) has largest production worldwide and is also an occupational respiratory hazard commonly seen in rubber industry. Few studies have assessed the risk for cardiovascular disease in carbon black exposed populations. An endothelial biosensor assay was used to quantify the capacity of sera from 82 carbon black packers (CBP) and 106 non-CBPs to induce endothelial cell activation ex vivo. The mediation effect of circulatory proinflammatory factors on the association between carbon black exposure and endothelial cell activation was assessed and further validated using in vitro intervention experiments.

Results: The average elemental carbon level inside carbon black bagging facilities was 657.0 μg/m, which was 164-fold higher than that seen in reference areas (4.0 μg/m). A global index was extracted from mRNA expression of seven candidate biosensor genes using principal component analysis and used to quantify the magnitude of endothelial cell activation. This global index was found to be significantly altered in CBPs compared to non-CBPs (P < 0.0001), however this difference did not vary by smoking status (P = 0.74). Individual gene analyses identified that de novo expression of key adhesion molecules (e.g., ICAM and VCAM) and chemotactic factors (e.g., CCL2, CCL5, and CXCL8) responsible for the recruitment of leukocytes was dramatically induced in CBPs with CXCL8 showing the highest fold of induction (relative quantification = 9.1, P < 0.0001). The combination of mediation analyses and in vitro functional validation confirmed TNF-α, IL-1β, and IL-6 as important circulatory factors mediating the effects of carbon black exposure on endothelial cell activation responses.

Conclusions: Inflammatory mediators in sera from CBPs may bridge carbon black exposure and endothelial cell activation response assessed ex vivo. CBPs may have elevated risk for cardiovascular diseases when comorbidity exists. Our study may serve as a benchmark for understanding health effects of engineered carbon based nanoparticles with environmental and occupational health relevance.
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http://dx.doi.org/10.1186/s12989-020-00378-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523398PMC
September 2020

Electrospinning Induced Orientation of Protein Fibrils.

Biomacromolecules 2020 07 8;21(7):2772-2785. Epub 2020 Jun 8.

Department of Food Science and Technology, The Ohio State University, 2015 Fyffe Rd., Columbus, Ohio 43210, United States.

Amyloid-like fibrils are prepared from protein in the lab by controlled heat treatments, yet these must be further assembled to match the desirable mechanical and structural properties of biological fibers. Here, β-lactoglobulin fibrils were incorporated into poly(ethylene oxide) fibers of 40-180 nm diameter by electrospinning. Protein fibrils presented as short segments dispersed within electrospun fibers, with no change in fibril diameter after electrospinning. Imaging analysis revealed fibrils were aligned within 20° relative to the fiber long axis, and alignment was further confirmed by polarized FTIR and anisotropic SAXS/WAXS scattering patterns. The elastic modulus of fibers increased with protein fibril content from 0.8 to 2 GPa, which is superior to reported values of silk, collagen, and gelatin. The present setup allows for manufacture of large quantities of polymeric fibers containing protein fibrils with varied diameter and mechanical strength, endowing great potential for a variety of applications.
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http://dx.doi.org/10.1021/acs.biomac.0c00500DOI Listing
July 2020

High-content analysis of particulate matters-induced oxidative stress and organelle dysfunction in vitro.

Toxicol In Vitro 2019 Sep 25;59:263-274. Epub 2019 Apr 25.

School of Public Health, Qingdao University, 38 Dengzhou Road, Qingdao 266021, China; National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Beijing 100050, China. Electronic address:

Oxidative stress is usually considered to be a common mechanism by which particulate matter (PM) exposure induces adverse effects. However, the further biological events such as organelle dysfunction following oxidative stress remain to be explored. In this study, we applied high-content screening (HCS) technique to investigate the toxicological effects of carbon black (CB), diesel exhaust particle (DEP) and PM2.5 on oxidative stress and organelle function in human bronchial epithelial cell (16HBE), human embryo lung fibroblast cell (HELF) and human umbilical vein endothelial cell (HUVEC) which were used to represent distinct regions of the lung, and compared the toxicity impacts of different PMs and the sensitiveness of cell lines. We found three types of PMs induced mitochondrial dysfunction in three cell lines and lysosomal alkalinization in HUVEC while only CB triggered endoplasmic reticulum (ER) stress in 16HBE and HUVEC, and oxidative stress might mediate these processes. Moreover, CB basically exhibited more potent toxicity compared with DEP and PM2.5, which might be attributed to its less oxygen content. Finally, the finding that PMs-induced toxicity impacts exhibited a cell-type dependent manner might provide some information to help to understand the sensitivity of different tissue in the lung.
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http://dx.doi.org/10.1016/j.tiv.2019.04.026DOI Listing
September 2019

High-speed X-ray visualization of dynamic crack initiation and propagation in bone.

Acta Biomater 2019 05 26;90:278-286. Epub 2019 Mar 26.

School of Aeronautics and Astronautics, Purdue University, 701 West Stadium Avenue, West Lafayette, IN 47907, USA; School of Materials Engineering, Purdue University, 701 West Stadium Avenue, West Lafayette, IN 47907, USA.

The initiation and propagation of physiological cracks in porcine cortical and cancellous bone under high rate loading were visualized using high-speed synchrotron X-ray phase-contrast imaging (PCI) to characterize their fracture behaviors under dynamic loading conditions. A modified Kolsky compression bar was used to apply dynamic three-point flexural loadings on notched specimens and images of the fracture processes were recorded using a synchronized high-speed synchrotron X-ray imaging set-up. Three-dimensional synchrotron X-ray tomography was conducted to examine the initial microstructure of the bone before high-rate experiments. The experimental results showed that the locations of fracture initiations were not significantly different between the two types of bone. However, the crack velocities in cortical bone were higher than in cancellous bone. Crack deflections at osteonal cement lines, a prime toughening mechanism in bone at low rates, were observed in the cortical bone under dynamic loading in this study. Fracture toughening mechanisms, such as uncracked ligament bridging and bridging in crack wake were also observed for the two types of bone. The results also revealed that the fracture toughness of cortical bone was higher than cancellous bone. The crack was deflected to some extent at osteon cement line in cortical bone instead of comparatively penetrating straight through the microstructures in cancellous bone. STATEMENT OF SIGNIFICANCE: Fracture toughness is with great importance to study for crack risk prediction in bone. For those cracks in bone, most of them are associated with impact events, such as sport accidents. Consequently, we visualized, in real-time, the entire processes of dynamic fractures in notched cortical bone and cancellous bone specimens using synchrotron X-ray phase contrast imaging. The onset location of crack initiation was found independent on the bone type. We also found that, although the extent was diminished, crack deflections at osteon cement lines, a major toughening mechanism in transversely orientated cortical bone at quasi-static rate, were still played a role in resisting cracking in dynamically loaded specimen. These finding help researchers to understand the dynamic fracture behaviors in bone.
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http://dx.doi.org/10.1016/j.actbio.2019.03.045DOI Listing
May 2019

Gd-Metallofullerenol nanoparticles cause intracellular accumulation of PDGFR-α and morphology alteration of fibroblasts.

Nanoscale 2019 Mar;11(11):4743-4750

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.

Gadolinium-metallofullerenols ([email protected](OH)22) are a promising agent for cancer therapy and have shown beneficial effects in regulating the tumor microenvironment with low toxicity. However, the underlying mechanism by which [email protected](OH)22 interacts with fibroblasts remains unclear. In order to explore the critical role that activated fibroblasts play in tumorigenesis and fibrosis, we investigated the regulatory effect of [email protected](OH)22 in fibroblast activation and oncogenic transformation, and found that the PDGFR-α is an essential molecule in modulating the morphology and functional changes in fibroblasts after [email protected](OH)22 treatment. Apart from increasing the PDGFR-α protein level, [email protected](OH)22 nanoparticles also significantly increased the protein level of Rab5, which is required for regulating PDGFR-α endosomal recycling. The Rab5-mediated recycling of PDGFR-α maybe attributed to the [email protected](OH)22 regulated inhibition of fibroblast activation. Overall, our work demonstrated that [email protected](OH)22 nanoparticles can attenuate the PDGF-stimulated phosphorylation of PDGFR-α in fibroblasts and suppress the fibroblast activation by interrupting endosomal recycling. These findings may be contributed to the collagen accumulation for encaging cancer.
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http://dx.doi.org/10.1039/c8nr08667bDOI Listing
March 2019

Role of sodium-hydrogen exchanger isoform 1 in regulating hepatocyte apoptosis induced by hyperammonaemia.

Gastroenterol Hepatol 2018 Oct 19;41(8):490-497. Epub 2018 Jul 19.

Department of Basic Medicine, Nursing College, Zhengzhou University, Zhengzhou, Henan, PR China.

Background: The "secondary injury" theory of liver failure indicated that hyperammonaemia due to liver failure causes further deterioration of hepatocytes. Our previous studies have demonstrated that high blood ammonia levels may lead to hepatocyte apoptosis, as NHCl loading caused metabolic acidosis and an increase in sodium-hydrogen exchanger isoform 1 (NHE1). In this study, we established a hyperammonia hepatocyte model to determine the role of NHE1 in the regulation of hepatocyte apoptosis induced by NHCl.

Materials And Methods: In current studies, intracellular pH (pHi) and NHE1 activity were analyzed using the pHi-sensitive dye BCECF-AM. The results showed that intracellular pH dropped and NHE1 activity increased in hepatocytes under NHCl treatment. As expected, decreased pHi induced by NHCl was associated with increased apoptosis, low cell proliferation and ATP depletion, which was exacerbated by exposure to the NHE1 inhibitor cariporide. We also found that NHCl treatment stimulated PI3K and Akt phosphorylation and this effect was considerably reduced by NHE1 inhibition.

Conclusion: This study highlighted the significant role of NHE1 in the regulation of cell apoptosis induced by hyperammonaemia.
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http://dx.doi.org/10.1016/j.gastrohep.2018.05.026DOI Listing
October 2018

Ghrelin protects human umbilical vein endothelial cells against advanced glycation end products-induced apoptosis via NO/cGMP signaling.

Int J Clin Exp Med 2015 15;8(9):15269-75. Epub 2015 Sep 15.

Department of Internal Medicine, Harbin Turbine Hospital Harbin 150046, China.

Objectives: The aim of this study was to investigate the intracellular mechanism involved in the anti-apoptotic effect of ghrelin on human umbilical vein endothelial cells (HUVECs).

Methods: HUVECs were pretreated with ghrelin before exposure to 200 μg/ml advanced glycation end products (AGEs)-BSA for 48 h. Cell viability and apoptosis were determined by MTT assay and Annexin V/PI staining. Intracellular cGMP levels evaluation and cGMP analogs were employed to explore possible mechanisms.

Results: The inhibitory effect on AGEs induced HUVECs apoptosis could be exerted by ghrelin and co-incubation with growth hormone secretagogue receptor (GHSR)-1a antagonist [D-Lys(3)]-GHRP-6 abolished this inhibition. Decreased cGMP level in AGEs induced HUVECs apoptosis was restored by ghrelin pretreatment and abolished by [D-Lys(3)]-GHRP-6 co-incubation. cGMP analogs (8 Br-cGMP and DB-cGMP) pretreatment also exhibited inhibitory effect on AGEs induced HUVECs apoptosis.

Conclusions: Our results demonstrated that ghrelin produces a protective effect on HUVECs through GHS-R1a and cGMP/NO signaling pathway mediates the effect of ghrelin. These observations suggest a novel intracellular mechanism in the process of AGEs induced HUVECs apoptosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658902PMC
December 2015
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