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Melatonin alleviates alcoholic liver disease via EGFR-BRG1-TERT axis regulation

Acta Pharmaceutica Sinica B 2023年第1期13卷 100-112页

作者： Zhaodi Che Yali Song Chengfang Xu Wei Li Zhiyong Dong Cunchuan Wang Yixing Ren Kwok-Fai So George L.Tipoe Fei Wang Jia Xiao Clinical Medicine research Institute and department of Metabolic and Bariatric Surgery the First Affiliated Hospital of Jinan UniversityGuangzhou 510632China department of Obstetrics the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Faculty of Pharmaceutical Sciences Toho UniversityChiba 2748510Japan department of General Surgery and Institute of Hepato-Biliary-Pancreas and Intestinal DiseaseAffiliated Hospital of North Sichuan Medical CollegeNanchong 637000China GMH Institute of CNS Regeneration Guangdong Medical Key Laboratory of Brain Function and DiseasesJinan UniversityGuangzhou 510632China School of biomedical Sciences LKS Faculty of Medicinethe University of Hong KongHong KongChina Division of Gastroenterology Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen 518107China

Chronic alcohol consumption causes liver steatosis,cell death,and ***(MLT)is reported to alleviate alcoholic liver disease(ALD)-induced ***,its direct regulating targets in hepatocytes are not fully *** the current study,a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of *** ameliorated ethanol-induced hepatocyte injury in both cell and animal models(optimal doses of 10μmol/L and 5 mg/kg,respectively),including lowered liver steatosis,cell death,and ***-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase(TERT)was a key downstream effector of *** assay found that epidermal growth factor receptor(EGFR)on the hepatocyte surface was a direct binding and regulating target of *** specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection,partly through the regulation of nuclear brahma-related gene-1(BRG1).Long-term administration(90 days)of MLT in healthy mice did not cause evident adverse *** conclusion,MLT is an efficacious and safe agent for ALD *** direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT *** might be used as a complimentary agent for alcoholics.

关键词： Alcoholic liver disease Melatonin Binding receptor TERT EGFR BRG1 Biophysics Safety

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Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure

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Bioactive Materials 2023年第10期28卷 112-131页

作者： Yuanyuan Jin Jiabin Zhang Yanteng Xu Ke Yi Fenfang Li Huicong Zhou Haixia Wang Hon Fai Chan Yeh-Hsing Lao Shixian Lv Yu Tao Mingqiang Li Laboratory of Biomaterials and Translational Medicine Center for NanomedicineThe Third Affiliated HospitalSun Yat-sen UniversityGuangzhou510630China Guangdong Provincial Key Laboratory of Liver Disease research Guangzhou510630China School of Materials Science and Engineering Peking UniversityBeijing100871China Institute for Tissue Engineering and Regenerative Medicine School of Biomedical ScienceThe Chinese University of Hong Kong999077Hong KongChina department of Pharmaceutical Sciences University at BuffaloThe State University of New YorkBuffaloNY14214USA

Reactive oxygen species(ROS)-associated oxidative stress,inflammation storm,and massive hepatocyte necrosis are the typical manifestations of acute liver failure(ALF),therefore specific therapeutic interventions are essential for the devastating ***,we developed a platform consisting of versatile biomimetic copper oxide nanozymes(Cu NZs)-loaded PLGA nanofibers(Cu NZs@PLGA nanofibers)and decellularized extracellular matrix(dECM)hydrogels for delivery of human adipose-derived mesenchymal stem/stromal cells-derived hepatocyte-like cells(hADMSCs-derived HLCs)(HLCs/Cu NZs@fiber/dECM).Cu NZs@PLGA nanofibers could conspicuously scavenge excessive ROS at the early stage of ALF,and reduce the massive accumulation of pro-inflammatory cytokines,herein efficiently preventing the deterioration of hepatocytes ***,Cu NZs@PLGA nanofibers also exhibited a cytoprotection effect on the transplanted ***,HLCs with hepatic-specific biofunctions and anti-inflammatory activity acted as a promising alternative cell source for ALF *** dECM hydrogels further provided the desirable 3D environment and favorably improved the hepatic functions of *** addition,the pro-angiogenesis activity of Cu NZs@PLGA nanofibers also facilitated the integration of the whole implant with the host ***,HLCs/Cu NZs@fiber/dECM performed excellent synergistic therapeutic efficacy on ALF *** strategy using Cu NZs@PLGA nanofiber-reinforced dECM hydrogels for HLCs in situ delivery is a promising approach for ALF therapy and shows great potential for clinical translation.

关键词： Acute liver failure Nanozyme Hepatocyte-like cells Human adipose-derived mesenchymal stem/stromal cells Electrospun nanofiber

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T cell epitopes in SARS-CoV-2 proteins are substantially conserved in the Omicron variant

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Cellular & Molecular Immunology 2022年第3期19卷 447-448页

作者： Seong Jin Choi Dong-Uk Kim Ji Yun Noh Sangwoo Kim Su-Hyung Park Hye Won Jeong Eui-Cheol Shin Division of Infectious Disease Department of Internal MedicineSeoul National University HospitalSeoulRepublic of Korea Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology(KAIST)DaejeonRepublic of Korea Division of Infectious Diseases Department of Internal MedicineKorea University College of MedicineSeoulRepublic of Korea department of biomedical Systems Informatics Graduate School of Medical ScienceBrain Korea 21 ProjectYonsei University College of MedicineSeoulRepublic of Korea department of Internal Medicine Chungbuk National University College of MedicineCheongjuRepublic of Korea The Center for Viral Immunology Korea Virus Research InstituteInstitute for Basic Science(IBS)DaejeonRepublic of Korea

In November 2021,the Omicron variant(B.1.1.529)emerged and was designated a variant of concern(VOC)by the World Health ***,Omicron was reported to extensively escape neutralizing antibodies elicited by COVID-19 vaccination or natural infection[1,2,3].However,whether Omicron evades the T cell immunity elicited by COVID-19 vaccination or natural infection remains to be *** address this issue,we analyzed the amino acid sequences of T cell epitopes identified from the original SARS-CoV-2 strain(Wuhan-Hu-1)in the Omicron variant(hCoV-19/South Africa/CERI-KRISP-K032284/2021).

关键词： neutral conserved elucidated

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＂Fluidic Diode＂ for Passive Unidirectional Liquid Transport Bioinspired by the Spermathecae of Fleas

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Journal of Bionic Engineering 2018年第1期15卷 42-56页

作者： Gerda Buchberger Alexander Kogler Agnes Weth Richard Baumgartner Philipp Comanns Siegfried Bauer Werner Baumgartner Institute of biomedical Mechatronics Johannes Kepler University Linz Altenberger Str. 69 A-4040 Linz Austria institute of Experimental Physics Department of Soft Matter Physics Johannes Kepler University Linz Altenberger Str. 69 A-4040 Linz Austria Institute of Biology II RWTH Aachen University Worringerweg 3 D-52074 Aachen Germany

We present a device for passive unidirectional liquid transport. The capillary channels used are bioinspired by the shape of the spermathecae （receptaculum seminis） of rabbit fleas （Spilopsyllus cuniculi） and rat fleas （Xenopsytla cheopis）. The spermatheca is an organ of female fleas that stores sperm until suitable conditions to lay eggs are found. We translated and multiplied the natural form and function of a spermatheca to create a continuous capillary system from which we designed our microfluidic device based directly on the model from nature. Applying the Young-Laplace equation, we derived a theoretical description of local liquid transport, which enables model-guided design. We arranged the bioinspired capillaries in parallel and engraved them in poly（methyl methacrylate）（PMMA） plates by CO2 laser ablation. The fabricated structures transport soapy water passively （i.e., without external energy input） in the forward direction at velocities of about 1 mm＇s i while halting the liquid fronts completely in the backward direction. The bio- inspired capillary channels are capable of unidirectional liquid transport against gravity. Distance and velocity measurements prove the feasibility of the concept. Unidirectional passive liquid transport might be advantageous in technical surfaces for liquid man- agement, for instance, in biomedical microfluidics, lab-on-chip, lubrication, electronics cooling and in micro-analysis devices.

关键词： liquid diode wetting passive unidirectional liquid transport capillary bioinspired

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The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors

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Journal of Pharmaceutical Analysis 2021年第2期11卷 174-182页

作者： Mirza Muhammad Faran Ashraf Baig Chengfei Zhang Muhammad Furqan Akhtar Ammara Saleem Jahanzeb Mudassir Laboratory of biomedical&Pharmaceutical Engineering of Stem Cells research Restorative Dental SciencesFaculty of DentistryThe University of Hong Kong999077Hong KongPR China State Key Laboratory of Analytical Chemistry for Life Sciences School of Chemistry and Chemical EngineeringNanjing UniversityNanjing210023PR China Faculty of Pharmacy Bahauddin Zakariya UniversityMultan60000Pakistan Riphah Institute of Pharmaceutical Sciences Riphah International UniversityLahorePakistan department of Pharmacology Faculty of Pharmaceutical SciencesGovernment College University FaisalabadFaisalabadPakistan

DNA-nanotechnology-based nano-architecture scaffolds based on circular strands were designed in the form of DNA-nanowires(DNA-NWs) as a polymer of DNA-triangles. Circularizing a scaffold strand(84-NT) was the critical step followed by annealing with various staple strands to make stiff DNAtriangles. Atomic force microcopy(AFM), native polyacrylamide gel electrophoresis(PAGE), UVanalysis, MTT-assay, flow cytometry, and confocal imaging were performed to assess the formulated DNA-NWs and cisplatin(CPT) loading. The AFM and confocal microscopy images revealed a uniform shape and size distribution of the DNA-NWs, with lengths ranging from 2 to 4 mm and diameters ranging from 150 to 300 nm. One sharp band at the top of the lane(500 bp level) with the loss of electrophoretic mobility during the PAGE(native) gel analysis revealed the successful fabrication of DNA-NWs. The loading efficiency of CPT ranged from 66.85% to 97.35%. MTT and flow cytometry results showed biocompatibility of the blank DNA-NWs even at 95% concentration compared with the CPT-loaded DNANWs. The CPT-loaded DNA-NWs exhibited enhanced apoptosis(22%) compared to the apoptosis(7%)induced by the blank DNA-NWs. The release of CPT from the DNA-NWs was sustained at < 75% for 6 h in the presence of serum, demonstrating suitability for systemic applications. The IC_(50) of CPT@DNA-NWs was reduced to 12.8 nM CPT, as compared with the free CPT solution exhibiting an IC_(50) of 51.2 n *** imaging revealed the targetability, surface binding, and slow internalization of the DNA-NWs in the scavenger-receptor-rich cancer cell line(HepG2) compared with the control cell line.

关键词： Cisplatin(CPT) DNA-nanowires(DNA-NWs) HepG2 resistant cancer cells Scavenger receptors

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A new analytical solution for calculation the displacement and shear stress of fully grouted rock bolts and numerical verifications

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International Journal of Mining Science and Technology 2016年第6期26卷 1073-1079页

作者： Ghadimi Mostafa Shariar Koroush Jalalifar Hossein department of Mining Engineering Science and Research Branch Islamic Azad University Tehran *** Iran Faculty of Mining Metallurgy and Petroleum Engineering Amir Kabir University of Technology Tehran 158754413 Iran department of Petroleum and Mining Engineering Shahid Bahonar University of Kerman Kerman *** Iran

In presence of difficult conditions in coal mining roadways, an adequate stabilization of the excavation boundary is required to ensure a safe progress of the construction. The stabilization of the roadways can be improved by fully grouted rock bolt, offering properties optimal to the purpose and versatility in use. investigations of load transfer between the bolt and grout indicate that the bolt profile shape and spacing play an important role in improving the shear strength between the bolt and the surrounding strata. This study proposes a new analytical solution for calculation displacement and shear stress in a fully encapsulated rock bolt in jointed rocks. The main characteristics of the analytical solution consider the bolt profile and jump plane under pull test conditions. The performance of the proposed analytical solution, for three types of different bolt profile configurations, is validated by ANSYS software. The results show there is a good agreement between analytical and numerical methods. Studies indicate that the rate of displacement and shear stress from the bolt to the rock exponentially decayed. This exponential reduction in displacement and shear stress are dependent on the bolt characteristics such as: rib height, rib spacing, rib width and grout thickness, material and joint properties.

关键词： Fully grouted bolt Jointed rock Displacement Shear stress

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Photodynamic therapy based on organic small molecular fluorescent dyes

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Chinese Chemical Letters 2019年第10期30卷 1689-1703页

作者： Li Li Yisha Chen Weijie Chen Ying Tan Haiyan Chen Jun Yin department of biomedical Engineering School of EngineeringState Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China Key Laboratory of Pesticide and Chemical Biology Ministry of EducationHubei International Scientific and Technological Cooperation Base of Pesticide and Green SynthesisInternational Joint Research Center for Intelligent BiosensingTechnology and HealthCollege of ChemistryCentral China Normal UniversityWuhan 430079China State Key Laboratory of Chemical Oncogenomics Key Laboratory of Chemical Biologythe Graduate School at ShenzhenTsinghua UniversityShenzhen 518055China

Photodynamic therapy(PDT) has shown promise as an effective treatment modality for cancer and other localized diseases due to its noninvasive properties and spatiotemporal selectivity. Near-infrared(NIR)fluorescent dyes based on organic small molecules are characterized with low cytotoxicity, good biocompatibility and excellent phototoxicity, which are widely used in PDT. In this review, we attempt to summarize the development of imaging-induced PDT based on organic small molecules and classify it according to the structures of dyes including cyanines, 4,4-difluoro-4-bora-3 a,4 a-diaza-s-indacene(BODIPY) analogues, phthalocyanine and other agents such as rhodamine analogues.

关键词： Near-infrared fluorescent dyes Photodynamic therapy Cyanine BODIPY Phthalocyanine

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Effect of Elastic Modulus on Biomechanical Properties of Lumbar Interbody Fusion Cage

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Journal of Materials Science & Technology 2009年第3期25卷 325-328页

作者： Yue Zhu Fusheng Li Shujun Li Yulin Hao Rui Yang department of Orthopaedics the First Affiliated Hospital of China Medical University Shenyang 110001 China department of Bone Tumor The Peoplers Hospital of Liaoning Province Shenyang 110016 China Shenyang National Laboratory for Materials Science Institute of Metal Research Chinese Academy of Sciences Shenyang 110016 China

This work focuses on the influence of elastic modulus on biomechanical properties of lumbar interbody fusion cages by selecting two titanium alloys with different elastic modulus. They were made by a new β type alloy with chemical composition of Ti-24Nb-4Zr-7.6Sn having low Young＇s modulus -50 GPa and by a conventional biomedical alloy Ti-6Al-4V having Young＇s modulus -110 GPa. The results showed that the designed cages with low modulus （LMC） and high modulus （HMC） can keep identical compression load -9.8 kN and endure fatigue cycles higher than 5× 10^6 without functional or mechanical failure under 2.0 kN axial compression. The anti-subsidence ability of both group cages were examined by axial compression of thoracic spine specimens （T9-T10） dissected freshly from the calf with averaged age of 6 months. The results showed that the LMC has better anti-subsidence ability than the HMC （p〈0.05）. The above results suggest that the cage with low elastic modulus has great potential for clinical applications.

关键词： Titanium alloy Lumbar Interbody fusion cage Biomechanics

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Effect of size and crystalline phase of TiO2 nanotubes on cell behaviors: A high throughput study using gradient TiO2 nanotubes

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Bioactive Materials 2020年第4期5卷 1062-1070页

作者： Yanran Li Si Wang Yuanjun Dong Ping Mu Yun Yang Xiangyang Liu Changjian Lin Qiaoling Huang research Institute for Biomimetics and Soft Matter Fujian Provincial Key Laboratory for Soft Functional Materials ResearchDepartment of PhysicsCollege of Physical Science and TechnologyXiamen UniversityXiamen361005China department of Physics National University of Singapore2 Science Drive 3117542Singapore State Key Laboratory for Physical Chemistry of Solid Surfaces Department of ChemistryCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China

The research of TiO2 nanotubes(TNTs)in the field of biomedicine has been increasingly ***,given the diversity of the nanoscale dimension and controversial reports,our understanding of the structure-property relationships of TNTs is not yet *** this paper,gradient TNTs with a wide diameter range of 20-350 nm were achieved by bipolar electrochemistry and utilized for a thorough high-throughput study of the effect of nanotube dimension and crystalline phase on protein adsorption and cell *** indicated that protein adsorption escalated with nanotube dimension whereas cell proliferation and differentiation are preferred on small diameter(research about how cell responses to TNTs with a wide diameter range and provide scientific guidance for the optimal design of biomedical materials.

关键词： Gradient TiO2 nanotubes High-throughput screening Protein adsorption Cell proliferation Cell differentiation

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Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer

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Chinese Medical Journal 2024年第2期137卷 209-221页

作者： Shi Qiu Yaqi Qiu Linghui Deng Ling Nie Liming Ge Xiaonan Zheng Di Jin Kun Jin Xianghong Zhou Xingyang Su Boyu Cai Jiakun Li Xiang Tu Lina Gong Liangren Liu Zhenhua Liu Yige Bao Jianzhong Ai Tianhai Lin Lu Yang Qiang Wei department of Urology Institute of UrologyNational Clinical Research Center for Geriatrics and Center of Biomedical Big DataWest China Hospital of Sichuan UniversityChengduSichuan 610041China department of Molecular Oncology Institute of Oncology Research(IOR)Oncology Institute of Southern Switzerland(IOSI)Bellinzona 6500Switzerland department of Science and Drug Technology University of TurinTurinItaly National Clinical research Center of Geriatrics The Center of Gerontology and GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610000China department of Pathology West China HospitalSichuan UniversityChengduSichuan 610041China department of Pharmaceutics and Bioengineering School of Chemical EngineeringSichuan UniversityChengduSichuan 610000China

Background:Bladder cancer,characterized by a high potential of tumor recurrence,has high lifelong monitoring and treatment *** date,tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer ***,the existence of soft tumor cells in bladder tumors remains ***,our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer ***:The stiffness of bladder cancer cells was determined by atomic force microscopy(AFM).The modified microfluidic chip was utilized to separate soft cells,and the 3D Matrigel culture system was to maintain the softness of tumor *** patterns of integrinβ8(ITGB8),protein kinase B(AKT),and mammalian target of rapamycin(mTOR)were determined by Western *** immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59(TRIM59).The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor ***:Using our newly designed microfluidic approach,we identified a small fraction of soft tumor cells in bladder cancer *** importantly,the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens,in which the number of soft tumor cells was associated with tumor ***,we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor ***,we detected a remarkable up-regulation in ITGB8,TRIM59,and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent ***:The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and ***,the soft tumor cells become more sensitive to chemother

关键词： Soft tumor cells 3D Matrigel Stemness Non-muscle invasive bladder neoplasms Microfluidic analytical techniques

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