OSI-027 alleviates rapamycin insensitivity by modulation of mTORC2/AKT/TGF-β1 and mTORC1/4E-BP1 signaling in hyperoxia-induced lung injury infant rats

Long Li,Liang Mulin,Yanling Liu,Wang Pan,Dang Hongxing 대한독성 유전단백체 학회 2021 Molecular & cellular toxicology Vol.17 No.3

Background The mechanism of long time and high-concentration oxygen treatment leading to acute lung injury (ALI) or developmental lung disease in infants is currently unclear. Here we found that compared with the effect of rapamycin, pan-mTOR1/2 inhibitor OSI-027, alleviates hyperoxia-induced lung injury (HILI) by modulation of mTORC2/AKT/TGF-β1 and mTORC1/4E-BP1 signaling in infant rats. Objective Infant rats were treated with continuous inhalation of 90% medical oxygen. Normal saline, rapamycin, or OSI-027 was intraperitoneally injected, and the status of lung injury was tested on days 3, 7, and 14. The activation of mTOR/AKT/TGFβ1 and mTORC1/4E-BP1 signaling was confirmed by immunohistochemistry and Western blot analysis in normal and hyperoxia-treated live precision-cut lung tissues. The inhibitory effect of OSI-027 extended to the active state of other proteins implicated in mTOR1/2 signaling was demonstrated in hyperoxia-induced injured lung tissues. Results Our data demonstrate that hyperoxia-induced serious lung inflammation and fibrosis. OSI-027 significantly attenuated the pathological process of HILI, inhibit the phosphorylation of the primary downstream targets of mTORC1/C2, and reduce the activation of TGF-β1 signaling. Conclusions The results suggest that mTORC2/AKT/TGF-β1 and the rapamycin-insensitive mTORC1/4E-BP1 (Thr37/46) signaling has an important effect during HILI with a potential meaning for the progress of novel anti-hyperoxia-injury strategies. Background The mechanism of long time and high-concentration oxygen treatment leading to acute lung injury (ALI) or developmental lung disease in infants is currently unclear. Here we found that compared with the effect of rapamycin, pan-mTOR1/2 inhibitor OSI-027, alleviates hyperoxia-induced lung injury (HILI) by modulation of mTORC2/AKT/TGF-β1 and mTORC1/4E-BP1 signaling in infant rats. Objective Infant rats were treated with continuous inhalation of 90% medical oxygen. Normal saline, rapamycin, or OSI-027 was intraperitoneally injected, and the status of lung injury was tested on days 3, 7, and 14. The activation of mTOR/AKT/TGFβ1 and mTORC1/4E-BP1 signaling was confirmed by immunohistochemistry and Western blot analysis in normal and hyperoxia-treated live precision-cut lung tissues. The inhibitory effect of OSI-027 extended to the active state of other proteins implicated in mTOR1/2 signaling was demonstrated in hyperoxia-induced injured lung tissues. Results Our data demonstrate that hyperoxia-induced serious lung inflammation and fibrosis. OSI-027 significantly attenuated the pathological process of HILI, inhibit the phosphorylation of the primary downstream targets of mTORC1/C2, and reduce the activation of TGF-β1 signaling. Conclusions The results suggest that mTORC2/AKT/TGF-β1 and the rapamycin-insensitive mTORC1/4E-BP1 (Thr37/46) signaling has an important effect during HILI with a potential meaning for the progress of novel anti-hyperoxia-injury strategies.

Sterculic Acid and Its Analogues Are Potent Inhibitors of Toxoplasma gondii

Pan Hao,Intisar Q. M. Alaraj,Juma’a R. Al Dulayymi,Mark S. Baird,Jing Liu,Qun Liu 대한기생충학열대의학회 2016 The Korean Journal of Parasitology Vol.54 No.2

Shape error prediction and compensation of three-dimensional surface in flexibly-reconfigurable roll forming

Pan Liu,구태완,강범수 대한기계학회 2015 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.29 No.10

The Flexibly-reconfigurable roll forming (FRRF) scheme as one of the advanced continuous roll forming processes consists of upperand lower flexible rollers that can be controlled by each reconfigurable punch module. The shape error in the FRRF process often resultsin undesirable changes in the shape of the deformed surface and brings about a deviation in the precision of the deformed product. Thisstudy considers the changes in the shape error of a deformed configuration by controlling the non-uniform gap between both flexiblerollers in the transverse direction. A Non-uniform rational B-spline (NURBS) type control methodology is introduced based on the transversetarget curve and the thickness reduction ratio. The function for the transverse target curve is reconstructed by using a NURBS curve,and the function of the reduction ratios of the thickness is assumed to have linear increments. Finite element simulations are conductedfor the FRRF process with the AA5052-H32 sheet material by applying NURBS-type control methodology for both flexible rollers. Thetransverse shape error of the three-dimensional surface is predicted by using a numerical approach, and its results are experimentallyverified. A Reverse displacement compensation (RDC) method is adopted to compensate the transverse shape error of the deformedsurface. Consequently, the proposed RDC method is validated as a suitable approach to address the transverse shape error. This methodcontributes to further developing capabilities to modify the profiles of the upper and lower flexible rollers in the flexibly-reconfigurableroll forming process for various 3D surface parts.

Differently-charged graphene-based multilayer films by a layer-by-layer approach for oxygen gas barrier application

Liu, Hongyu,Wu, Jianping,Liu, Cuiyun,Pan, Bingli,Kim, Nam Hoon,Lee, Joong Hee Elsevier 2018 Composites Part B, Engineering Vol.155 No.-

<P><B>Abstract</B></P> <P>Polyelectrolyte-decorated graphene with positive and negative charges was prepared using graphene oxide as a precursor along with polyallylamine hydrochloride and poly (styrenesulfonate sodium) as surface modifiers, respectively. Driven by an electrostatic interaction, the as-obtained polyelectrolyte-decorated graphene sheets were self-assembled via a layer-by-layer method, producing graphene based composite multilayers. Field emission scanning electron microscopy (FE-SEM) images showed that the surface of composite film exhibited a mass of characteristic wrinkles of graphene. Interestingly, the cross-sectional FE-SEM of the film exhibited an unstratified structure, indicating a good dispersion of graphene sheets in the composite film. The results of oxygen gas permeability testing demonstrated that the resulting composite films exhibited excellent oxygen gas barrier properties. The oxygen gas transmission rate (OTR) of the composite film with 24 bilayers was as low as 1.2 cm<SUP>3</SUP> m<SUP>-2</SUP> d<SUP>-1</SUP>∙atm<SUP>−1</SUP>, exhibiting potential for use in packaging applications.</P>

Treatment of Hypothyroidism in a Dog

Liu, Pan Chen,Lai, Cheng Hung,Cheng, Feng Fang,Lee, Wei Ming 忠南大學校 獸醫科大學 附設 動物醫科學硏究所 2010 動物醫科學硏究誌 Vol.17 No.1

Fresh Washed Microbiota Transplantation Alters Gut Microbiota Metabolites to Ameliorate Sleeping Disorder Symptom of Autistic Children

Liu Nai-Hua,Liu Hong-Qian,Zheng Jia-Yi,Zhu Meng-Lu,Wu Li-Hao,Pan Hua-Feng,He Xing-Xiang 한국미생물학회 2023 The journal of microbiology Vol.61 No.8

Accumulating studies have raised concerns about gut dysbiosis associating autism spectrum disorder (ASD) and its related symptoms. However, the effect of gut microbiota modification on the Chinese ASD population and its underlying mechanism were still elusive. Herein, we enrolled 24 ASD children to perform the first course of fresh washed microbiota transplantation (WMT), 18 patients decided to participate the second course, 13 of which stayed to participate the third course, and there were 8 patients at the fourth course. Then we evaluated the effects of fresh WMT on these patients and their related symptoms. Our results found that the sleeping disorder symptom was positively interrelated to ASD, fresh WMT significantly alleviated ASD and its sleeping disorder and constipation symptoms. In addition, WMT stably and continuously downregulated Bacteroides/ Flavonifractor/Parasutterella while upregulated Prevotella_9 to decrease toxic metabolic production and improve detoxification by regulating glycolysis/myo-inositol/D-glucuronide/D-glucarate degradation, L-1,2-propanediol degradation, fatty acid β-oxidation. Thus, our results suggested that fresh WMT moderated gut microbiome to improve the behavioral and sleeping disorder symptoms of ASD via decrease toxic metabolic production and improve detoxification. Which thus provides a promising gut ecological strategy for ASD children and its related symptoms treatments.

An Approach to Test Generation for Web Applications

Pan Liu,Huaikou Miao,Hongwei Zeng,Lizhi Cai 보안공학연구지원센터(IJUNESST) 2013 International Journal of u- and e- Service, Scienc Vol.6 No.1

Numerical simulation of Rectangular Cup using High Strength Steel in Multi-Stage Deep Drawing Process

Pan Liu,Tae-Wan Ku(구태완),Beom-Soo Kang(강범수) 한국소성가공학회 2013 한국소성가공학회 학술대회 논문집 Vol.2013 No.5

The paper is mainly study multi-stage deep drawing process for rectangular cups with high strength steel using finite element analysis. The process mainly consists of five deep drawing stages, because of the aspect ratio about 5.7. Tool design and blank modification are presented by using each numerical simulation models from the first to the fifth drawing stage. Based on the design results of the initial blank, severe earing phenomenon is occurred at the upper flange part. To solve the severe earing phenomenon at the upper flange due to normal anisotropy of the used sheet material, initial blank modification is carried out. The simulation result is confirmed that the modified blank shape not only improves the quality of a deep-drawn product but also reduces the cost of production.

Suppression of SPARC Ameliorates Ovalbumin-induced Airway Remodeling via TGFβ1/Smad2 in Chronic Asthma

Pan Yun,Zhang Dong,Zhang Jintao,Liu Xiaofei,Xu Jiawei,Zeng Rong,Cui Wenjing,Liu Tian,Wang Junfei,Dong Liang 대한천식알레르기학회 2024 Allergy, Asthma & Immunology Research Vol.16 No.1

Purpose: Airway remodeling is a critical feature of asthma. Secreted protein acidic and rich in cysteine (SPARC), which plays a cardinal role in regulating cell-matrix interactions, has been implicated in various fibrotic diseases. However, the effect of SPARC in asthma remains unknown. Methods: We studied the expression of SPARC in human bronchial epithelial cells and serum of asthmatics as well as in the lung tissues of chronic asthma mice. The role of SPARC was examined by using a Lentivirus-mediated SPARC knockdown method in the ovalbumin (OVA)-induced asthma mice. The biological processes regulated by SPARC were identified using RNA sequencing. The function of SPARC in the remodeling process induced by transforming growth factor β1 (TGFβ1) was conducted by using SPARC small interfering RNA (siRNA) or recombinant human SPARC protein in 16HBE cells. Results: We observed that SPARC was up-regulated in human bronchial epithelia of asthmatics and the asthmatic mice. The levels of serum SPARC in asthmatics were also elevated and negatively correlated with the forced expiratory volume in one second (FEV1) to forced vital capacity ratio (FVC) (r = −0.485, P < 0.01) and FEV1 (%predicted) (r = −0.425, P = 0.001). In the chronic asthmatic mice, Lentivirus-mediated SPARC knockdown significantly decreased airway remodeling and airway hyper-responsiveness. According to gene set enrichment analysis, negatively enriched pathways found in the OVA + short hairpin-SPARC group included ECM organization and collagen formation. In the lung function studies, knockdown of SPARC by siRNA reduced the expression of remodeling-associated biomarkers, cell migration, and contraction by blocking the TGFβ1/Smad2 pathway. Addition of human recombinant SPARC protein promoted the TGFβ1-induced remodeling process, cell migration, and contraction in 16HBE cells via the TGFβ1/Smad2 pathway. Conclusions: Our studies provided evidence for the involvement of SPARC in the airway remodeling of asthma via the TGFβ1/Smad2 pathway.

V₂O₅ xerogel electrodes with much enhanced lithium-ion intercalation properties with N₂ annealing

Liu, Dawei,Liu, Yanyi,Garcia, Betzaida Batalla,Zhang, Qifeng,Pan, Anqiang,Jeong, Yoon-Ha,Cao, Guozhong The Royal Society of Chemistry 2009 Journal of materials chemistry Vol.19 No.46

<p>V<SUB>2</SUB>O<SUB>5</SUB> xerogel films were fabricated by casting V<SUB>2</SUB>O<SUB>5</SUB> sols onto FTO glass substrates and annealing at 300 °C for 3 hours in nitrogen and air. The films annealed in nitrogen and air possessed different grain size and crystallinity. Optical absorption measurements and electrochemical impedance analyses revealed a reduced optical bandgap and enhanced electrical conductivity of N<SUB>2</SUB> annealed V<SUB>2</SUB>O<SUB>5</SUB> film. Lithium ion intercalation measurements showed that at a charge/discharge current density of 600 mAg<SUP>−1</SUP>, the N<SUB>2</SUB> annealed sample possessed noticeably better lithium ion storage capability. In contrast to the air annealed sample, which started with a discharge capacity of 152 mAhg<SUP>−1</SUP> but after 50 cycles the capacity had decreased to a low value of only 44 mAhg<SUP>−1</SUP>, the N<SUB>2</SUB> annealed sample started with a low value of 68 mAhg<SUP>−1</SUP> but the capacity increased sharply to a high value of 158 mAhg<SUP>−1</SUP> at the 24<SUP>th</SUP> cycle, followed by little capacity degradation in later cycles and after 50 cycles, the discharge capacity was still as high as 148 mAhg<SUP>−1</SUP>. Much improved lithium ion intercalation capacity and cyclic stability could be attributed to surface defects V<SUP>4+</SUP> and/or V<SUP>3+</SUP> and associated oxygen vacancies introduced by N<SUB>2</SUB> annealing as well as much less crystallized vanadium oxide.</p> <P>Graphic Abstract</P><P>V<SUB>2</SUB>O<SUB>5</SUB> films annealed in N<SUB>2</SUB> exhibited a much improved lithium ion intercalation capability as compared to counterparts annealed in air, highly favoring potential application as lithium ion battery electrodes. <img src='http://pubs.rsc.org/ej/JM/2009/b914436f/b914436f-ga.gif'> </P>