43 results on '"Xing, Pei"'
Search Results
2. Periodontitis Exacerbates Benign Prostatic Hyperplasia through Regulation of Oxidative Stress and Inflammation
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Tong Deng, Jia-Min Gu, Lan Wu, Cheng Li, Ming-Juan Zhao, Weiguang Li, Xing-Pei Guo, Xian-Tao Zeng, and Cheng Fang
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Lipopolysaccharides ,Male ,Aging ,medicine.medical_treatment ,Prostatic Hyperplasia ,Apoptosis ,medicine.disease_cause ,urologic and male genital diseases ,Biochemistry ,Rats, Sprague-Dawley ,Prostate ,Testosterone ,biology ,General Medicine ,Hyperplasia ,medicine.anatomical_structure ,Cytokine ,Disease Progression ,Cytokines ,medicine.symptom ,Inflammation Mediators ,Porphyromonas gingivalis ,Research Article ,Signal Transduction ,medicine.medical_specialty ,Article Subject ,Inflammation ,Proinflammatory cytokine ,Cell Line ,Internal medicine ,medicine ,Alveolar Process ,Animals ,Humans ,Periodontitis ,Cell Proliferation ,QH573-671 ,business.industry ,Cell Biology ,medicine.disease ,biology.organism_classification ,Disease Models, Animal ,Oxidative Stress ,Endocrinology ,Cytology ,business ,Apoptosis Regulatory Proteins ,Reactive Oxygen Species ,Oxidative stress - Abstract
Epidemiological studies demonstrate that men with periodontitis are also susceptible to benign prostatic hyperplasia (BPH) and that periodontal treatment can improve the prostatic symptom. However, molecular links of this relationship are largely unknown. The goal of the current study was to elucidate the effects of experimental periodontitis on the hyperplasia of prostate and whether oxidative stress and inflammation participated in this process. For this purpose, ligature-induced periodontitis, testosterone-induced BPH, and the composite models in rats were established. Four weeks later, all the rats were sacrificed and the following items were measured: alveolar bone loss and histological examination of periodontal tissues were taken to assess the establishment of periodontitis model, prostate index and histological examination of prostate tissues were taken to test the establishment of the BPH model, inflammatory cytokines in plasma were assessed, and Bax/Bcl-2 proteins related to cell apoptosis were analyzed via western blot analysis. To further investigate whether oxidative stress participates in the aggravation of BPH, in vitro models were also conducted to measure the production of intracellular reactive oxygen species (ROS) and hydrogen peroxide (H2O2) concentration. We found that simultaneous periodontitis and BPH synergistically aggravated prostate histological changes, significantly increased Ki67 proliferation, and reduced apoptosis in rat prostate tissues. Also, our results showed that periodontal ligation induced increased Bcl-2 protein expression, whereas Bax expression was decreased in BPH rats than in normal rats. Compared with the control group, periodontitis and BPH both significantly enhanced inflammatory cytokine levels of TNF-α, IL-6, IL-1β, and CRP. Furthermore, Porphyromonas gingivalis lipopolysaccharide induced enhanced generation of intracellular expression of ROS and H2O2 in BPH-1 cells. Our experimental evidence demonstrated that periodontitis might promote BPH development through regulation of oxidative stress and inflammatory process, thus providing new strategies for prevention and treatment of BPH.
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- 2021
3. Antibody-siRNA conjugates (ARCs) using multifunctional peptide as a tumor enzyme cleavable linker mediated effective intracellular delivery of siRNA
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Kyuri Lee, Huining He, Stefan Barth, Jiancheng Wang, Junxiao Ye, Lu Sun, Xing Pei, Nan Li, Zhili Yu, Weiran Cao, Victor C. Yang, Fei Yu, Xiaojuan Zhang, and Jianxin Wang
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chemistry.chemical_classification ,Small interfering RNA ,Immunoconjugates ,Chemistry ,Pharmaceutical Science ,Mice, Nude ,Peptide ,Cell-Penetrating Peptides ,In vitro ,Green fluorescent protein ,Cell biology ,Mice ,In vivo ,Cell Line, Tumor ,Cell-penetrating peptide ,Gene silencing ,Animals ,Prospective Studies ,RNA, Small Interfering ,Linker - Abstract
The tissue-specific targeted delivery and efficient cellular uptake of siRNAs are the main obstacles to their clinical application. Antibody-siRNA-conjugates (ARCs) can deliver siRNA by exploiting the targeting property of antibodies like antibody-drug conjugates (ADCs). However, the effective conjugation of antibodies and siRNAs and the release of siRNAs specifically at target sites have posed challenges to the development of ARCs. In this study, the successful conjugation of antibodies and siRNAs was achieved using a multifunctional peptide as a linker, composed of a cell-penetrating peptide (CPP) and a substrate peptide (SP), which is highly expressed in solid tumors. The resulting antibody-multifunctional peptide (SP-CPP)-siRNA system delivered the siRNA to target tumor cells by the specific binding of the antibody. Once the enzymes on the tumor cell surface hydrolyzed the substrate peptide linker, siRNA-CPP was released from ARCs. The released siRNA-CPP entered the targeted cells via the cellular penetrating ability of CPP, resulting in improved siRNA-mediated gene silencing efficiency, verified both in vitro and in vivo. After intravenous administration, the designed ARCs achieved approximately 66.7% EGFP (Enhanced Green Fluorescent Protein) downregulation efficiency in nude mice xenografted with the HCT116-EGFP tumor model. The proposed system provides a prospective choice for ARC production and the safe and efficient delivery of siRNAs.
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- 2021
4. Local delivery of cardiac stem cells overexpressing HIF-1α promotes angiogenesis and muscular tissue repair in a hind limb ischemia model
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Nana Wang, Jiyoung Shin, Victor C. Yang, Heejung Kim, Xing Pei, Seung Jin Lee, Huining He, Minjoo Lee, and Miyun Yoon
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Angiogenesis ,Pharmaceutical Science ,Neovascularization, Physiologic ,02 engineering and technology ,03 medical and health sciences ,Mice ,Peripheral Arterial Disease ,Fibrosis ,Ischemia ,medicine ,Animals ,Therapeutic angiogenesis ,030304 developmental biology ,0303 health sciences ,biology ,Neovascularization, Pathologic ,business.industry ,Cell Differentiation ,Mesenchymal Stem Cells ,Critical limb ischemia ,Transfection ,Hypoxia (medical) ,021001 nanoscience & nanotechnology ,medicine.disease ,Hypoxia-Inducible Factor 1, alpha Subunit ,Cancer research ,biology.protein ,Stem cell ,medicine.symptom ,0210 nano-technology ,business ,Platelet-derived growth factor receptor - Abstract
Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease, associated with significant risk of limb loss, morbidity and mortality; however, there remains unmet therapeutic needs for arterial revascularization and ischemic tissue repair. Stem cell therapies have emerged as compelling candidates due to beneficial proangiogenic and immunosuppressive function. Nevertheless, in vivo efficacy was insufficient in proliferation, differentiation and survival/engraftment rate. Cardiac stem cells (CSCs) was firstly attempted for CLI as a novel therapeutic modality to provide superior angiogenic potency to bone marrow-derived stem cells (BMSCs). It was noted that CSCs demonstrated 3.2-fold in HGF, 2.9-fold in VEGF and 8.7-fold in PDGF-B higher gene expressions compared to BMSCs. To enhance the hypoxia-induced proangiogenic effect, CSCs were transfected with hypoxia-inducible factor-1 alpha (HIF-1α) by using electroporation method, specifically optimized for CSCs yielding 45.77% of transfection efficiency and 89.75% of viability. HIF-1α overexpression significantly increased CSC survival in hypoxia, proangiogenic factors production and endothelial differentiation. In mouse hind limb ischemia model, local intramuscular delivery of CSC overexpressing HIF-1α (HIF-CSC) significantly improved the blood flow recovery. Histological analysis revealed that muscle degeneration and fibrosis in the ischemic limb were attenuated. Local delivery of HIF-CSC might be a promising option for ischemic tissue restoration.
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- 2019
5. Low-dose Sinapic Acid Abates the Pyroptosis of Macrophages by Downregulation of lncRNA-MALAT1 in Rats With Diabetic Atherosclerosis
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Yigang Fan, Yong Han, Xing Pei, Hong Qiu, Jie Geng, and Hongyan Tian
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Blood Glucose ,Male ,0301 basic medicine ,Programmed cell death ,Coumaric Acids ,Cell ,Anti-Inflammatory Agents ,Down-Regulation ,Diabetes Mellitus, Experimental ,Rats, Sprague-Dawley ,03 medical and health sciences ,Downregulation and upregulation ,Pyroptosis ,medicine ,Animals ,Hypoglycemic Agents ,Macrophage ,Cells, Cultured ,Pharmacology ,Gene knockdown ,Dose-Response Relationship, Drug ,Chemistry ,Macrophages ,Transfection ,Atherosclerosis ,Endothelin 1 ,Molecular biology ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,RNA, Long Noncoding ,Inflammation Mediators ,Cardiology and Cardiovascular Medicine ,Biomarkers ,Signal Transduction - Abstract
Pyroptosis is a type of programmed cell death, which has been associated with multiple inflammatory diseases including diabetic atherosclerosis (DA). This study aims to explore the role of sinapic acid (SA) in the pyroptosis of macrophages in DA. Our results from the in vivo experiments showed that low-dose (≤50 mg/kg) chronic SA administration suppressed serum endothelin 1 (ET-1) and interleukin-1β (IL-1β) contents, pyroptotic death of bone marrow-derived macrophages, and the expression of pyroptotic proteins ASC, NRLP3, and caspase-1. Besides, lncRNA-metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was robustly upregulated in the macrophages of rats with DA and could be lowered by low-dose SA administration. Gene overexpression and knockdown experiments showed that MALAT1 had a modestly positive effect on the pyroptosis of normal macrophages. Moreover, in macrophages incubated with high-glucose and Ox-LDL, 1-μM SA treatment displayed a suppressive effect on the cell pyroptosis similar to that of MALAT1 knockdown. Transfection of the pcDNA-MALAT1 expression vector counteracted the decrease in MALAT1 expression and macrophage pyroptosis caused by SA. In conclusion, low-dose SA can abate the pyroptosis of macrophages by downregulation of lncRNA-MALAT1 in rats with DA.
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- 2018
6. Thymoquinone Inhibits Angiotensin II-Induced Proliferation and Migration of Vascular Smooth Muscle Cells Through the AMPK/PPARγ/PGC-1α Pathway
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Yigang Fan, Xing Pei, Xiaoli Li, Yong Han, and Heming Chen
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Male ,0301 basic medicine ,Vascular smooth muscle ,Peroxisome proliferator-activated receptor ,AMP-Activated Protein Kinases ,Muscle, Smooth, Vascular ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,0302 clinical medicine ,AMP-activated protein kinase ,Cell Movement ,Benzoquinones ,Cyclin D1 ,Thymoquinone ,chemistry.chemical_classification ,biology ,Angiotensin II ,Cell Cycle ,General Medicine ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,Cell biology ,030220 oncology & carcinogenesis ,cardiovascular system ,Signal transduction ,Signal Transduction ,Cyclin-Dependent Kinase Inhibitor p21 ,medicine.medical_specialty ,Myocytes, Smooth Muscle ,Primary Cell Culture ,03 medical and health sciences ,Internal medicine ,Genetics ,medicine ,Animals ,Molecular Biology ,Cell Proliferation ,Reactive oxygen species ,Dose-Response Relationship, Drug ,Superoxide Dismutase ,NADPH Oxidases ,AMPK ,Cell Biology ,Rats ,PPAR gamma ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,chemistry ,biology.protein ,Reactive Oxygen Species - Abstract
The proliferation and migration of vascular smooth muscle cells (VSMCs) play crucial roles in the pathogenesis of diabetes and its complications. Thymoquinone (TQ) is the primary bioactive component of Nigella sativa L. seed oil, which exhibits antihyperglycemic effect in diabetic rats, but its role in VSMC proliferation and migration has not been investigated. The results of MTT assay and flow cytometry assay indicated that TQ dose-dependently inhibited angiotensin II (Ang II)-induced VSMCs' cell cycle progression, as well as cyclin D1 expression, whereas p21 expression was altered conversely. TQ dose-dependently suppressed Ang II-induced VSMC migration accompanied by reduced MMP-9 expression. In addition, we observed the elevated reactive oxygen species (ROS) generation and NADPH oxidase activity and reduced superoxide dismutase activity in Ang II-treated VSMCs, which were dose-dependently reversed by TQ. Western blot analysis indicated that TQ dose-dependently restored Ang II-inhibited expression of p-AMPK, PPARγ, and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) proteins. Furthermore, adenosine monophosphate-activated protein kinase (AMPK) inhibitor Compound C and PGC-1α siRNA transfection abrogated the activation of TQ on Ang II-inhibited AMPK/PPARγ/PGC-1α signaling, but abolished the inhibitory effects of TQ on Ang II-induced VSMC proliferation and migration, as well as ROS generation. Taken together, these results demonstrated that TQ inhibited Ang II-induced VSMC proliferation and migration through the AMPK/PPARγ/PGC-1α pathway.
- Published
- 2016
7. Cell-penetrating peptide enhanced insulin buccal absorption
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Stefan Barth, You Xu, Xing Pei, Victor C. Yang, Fei Yu, Huining He, Nana Wang, Xiaojuan Zhang, Yiyue Guo, Jianxin Wang, and Seung Jin Lee
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Male ,Swine ,medicine.medical_treatment ,Pharmaceutical Science ,Cell-Penetrating Peptides ,02 engineering and technology ,Pharmacology ,medicine.disease_cause ,Oral Mucosal Absorption ,030226 pharmacology & pharmacy ,Permeability ,Polyethylene Glycols ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Hypoglycemic Agents ,Insulin ,Buccal Absorption ,Chemistry ,Mouth Mucosa ,Buccal administration ,021001 nanoscience & nanotechnology ,Bioavailability ,Cell-penetrating peptide ,Rabbits ,Irritation ,0210 nano-technology ,Conjugate - Abstract
Non-injectable delivery of peptides and proteins is not feasible due to the limitations of large molecular mass, high hydrophilic properties, and gastrointestinal degradation. Therefore, proposing a new method to solve this problem is a burning issue. The objective of this study was to propose a novel protein delivery strategy to overcome the poor efficacy and irritation of buccal insulin delivery. In this study, we applied a conjugate of cell-penetrating peptides (LMWP) and insulin (INS-PEG-LMWP) for buccal delivery. INS-PEG-LMWP was prepared using insulin solution and mixture as references. The transport behaviour, in vivo bioactivity, hypoglycaemic effect, and safety of INS-PEG-LMWP were systematically characterised. An in vitro study demonstrated that the uptake and transportation of INS-PEG-LMWP across buccal mucosal multilayers significantly increased. By comparing the effects of different endocytic inhibitors on INS-PEG-LMWP uptake, the conjugate might be delivered via an energy independent, electrostatically adsorbed pathway. INS-PEG-LMWP's relative pharmacological bioavailability was high and its relative bioavailability was up to 26.86%, demonstrating no visible mucosal irritation. Cell-penetrating peptides are likely to become a reliable and safe tool for overcoming insulin's low permeability through the epithelial multilayers, the major barrier to buccal delivery.
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- 2020
8. Gammaherpesvirus infection and malignant disease in rhesus macaques experimentally infected with SIV or SHIV
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Scott W. Wong, Gregory Q. Del Prete, Claes Ohlen, Andrew C. Warner, Rebecca Kiser, Michael Piatak, Marshall Thompson, Vickie Marshall, Jeffrey D. Lifson, Yelena Golubeva, Jeremy Smedley, Denise Whitby, Rhonda MacAllister, Benjamin Holdridge, Jacob D. Estes, Xing Pei Hao, Vicky Coalter, Claire Deleage, Wendell J. Miley, Elaine S. Jaffe, Miriam R. Anver, Nazzarena Labo, and Catherine Brands
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0301 basic medicine ,RNA viruses ,Fibrosarcoma ,viruses ,Simian Acquired Immunodeficiency Syndrome ,Monkeys ,medicine.disease_cause ,Pathology and Laboratory Medicine ,Macaque ,Hematologic Cancers and Related Disorders ,Immunodeficiency Viruses ,Neoplasms ,Medicine and Health Sciences ,Gammaherpesvirinae ,Rhadinovirus ,lcsh:QH301-705.5 ,Immunodeficiency ,Mammals ,biology ,Coinfection ,Sarcomas ,Eukaryota ,virus diseases ,Hematology ,Animal Models ,Herpesviridae Infections ,Rhesus lymphocryptovirus ,Viral Load ,3. Good health ,Oncology ,SIV ,Experimental Organism Systems ,Medical Microbiology ,Viral Pathogens ,Viruses ,Vertebrates ,Infectious diseases ,Lymphomas ,Simian Immunodeficiency Virus ,Pathogens ,Viral load ,Research Article ,HIV infections ,Primates ,lcsh:Immunologic diseases. Allergy ,Herpesviruses ,Immunology ,Viral diseases ,Research and Analysis Methods ,Microbiology ,Virus ,03 medical and health sciences ,biology.animal ,Virology ,Old World monkeys ,Retroviruses ,Genetics ,medicine ,Animals ,Molecular Biology ,Microbial Pathogens ,Biology and life sciences ,Rhesus Monkeys ,Lentivirus ,Organisms ,Cancers and Neoplasms ,Simian immunodeficiency virus ,biology.organism_classification ,medicine.disease ,Macaca mulatta ,Tumor Virus Infections ,030104 developmental biology ,lcsh:Biology (General) ,Amniotes ,Parasitology ,DNA viruses ,lcsh:RC581-607 ,Viral Transmission and Infection - Abstract
Human gammaherpesviruses are associated with malignancies in HIV infected individuals; in macaques used in non-human primate models of HIV infection, gammaherpesvirus infections also occur. Limited data on prevalence and tumorigenicity of macaque gammaherpesviruses, mostly cross-sectional analyses of small series, are available. We comprehensively examine all three-rhesus macaque gammaherpesviruses -Rhesus rhadinovirus (RRV), Rhesus Lymphocryptovirus (RLCV) and Retroperitoneal Fibromatosis Herpesvirus (RFHV) in macaques experimentally infected with Simian Immunodeficiency Virus or Simian Human Immunodeficiency Virus (SIV/SHIV) in studies spanning 15 years at the AIDS and Cancer Virus Program of the Frederick National Laboratory for Cancer Research. We evaluated 18 animals with malignancies (16 lymphomas, one fibrosarcoma and one carcinoma) and 32 controls. We developed real time quantitative PCR assays for each gammaherpesvirus DNA viral load (VL) in malignant and non-tumor tissues; we also characterized the tumors using immunohistochemistry and in situ hybridization. Furthermore, we retrospectively quantified gammaherpesvirus DNA VL and SIV/SHIV RNA VL in longitudinally-collected PBMCs and plasma, respectively. One or more gammaherpesviruses were detected in 17 tumors; generally, one was predominant, and the relevant DNA VL in the tumor was very high compared to surrounding tissues. RLCV was predominant in tumors resembling diffuse large B cell lymphomas; in a Burkitt-like lymphoma, RRV was predominant; and in the fibrosarcoma, RFHV was predominant. Median RRV and RLCV PBMC DNA VL were significantly higher in cases than controls; SIV/SHIV VL and RLCV VL were independently associated with cancer. Local regressions showed that longitudinal VL patterns in cases and controls, from SIV infection to necropsy, differed for each gammaherpesvirus: while RFHV VL increased only slightly in all animals, RLCV and RRV VL increased significantly and continued to increase steeply in cases; in controls, VL flattened. In conclusion, the data suggest that gammaherpesviruses may play a significant role in tumorogenesis in macaques infected with immunodeficiency viruses., Author summary Human gammaherpesviruses cause malignancies in HIV infected persons; in SIV infected macaques, gammaherpesvirus infections also occur. To understand the potential role of the rhesus gammaherpesviruses, RRV, RFHV and RLCV in cancers occurring in monkeys during SIV and SHIV studies spanning the last 15 years, we developed assays to measure the DNA viral load (VL) of each virus in these tumors and unaffected macaque tissues. We further characterized the tumors using immunohistochemistry and in situ hybridization, and quantified gammaherpesvirus DNA VL in PBMCs collected longitudinally during the original studies. We examined 18 animals with tumors and 32 controls. In all tumors, we detected one or more gammaherpesviruses; generally, one virus was predominant and very abundant compared to surrounding non-tumor tissues. SIV RNA VL in plasma and RLCV VL in PBMCs were independently associated with cancer risk. The longitudinal patterns of gammaherpesviruses VL, from SIV infection to death differed in cases and controls: while RFHV VL increased only slightly in all animals, RLCV VL and RRV VL increased significantly and continued to increase in cases, but flattened in controls. These data suggest that gammaherpesviruses may play a significant role in tumorogenesis in macaques infected with immunodeficiency viruses.
- Published
- 2018
9. SIV-induced Translocation of Bacterial Products in the Liver Mobilizes Myeloid Dendritic and Natural Killer Cells Associated With Liver Damage
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Ryan P. Traslavina, Jason M. Brenchley, Nichole R. Klatt, Jacob D. Estes, Jamie L. Schafer, Tristan I. Evans, Xing Pei Hao, Haiying Li, and R. Keith Reeves
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0301 basic medicine ,Myeloid ,Simian Acquired Immunodeficiency Syndrome ,Apoptosis ,Hepatitis, Animal ,Biology ,Major Articles and Brief Reports ,03 medical and health sciences ,Liver disease ,Antigen ,medicine ,Animals ,Immunology and Allergy ,Cytotoxic T cell ,Myeloid Cells ,CXCL16 ,Receptors, CXCR ,Hepatitis ,Innate immune system ,medicine.disease ,Natural killer T cell ,Macaca mulatta ,Killer Cells, Natural ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Gene Expression Regulation ,Liver ,Immunology ,Simian Immunodeficiency Virus ,Chemokines, CXC - Abstract
Disruption of the mucosal epithelium during lentivirus infections permits translocation of microbial products into circulation, causing immune activation and driving disease. Although the liver directly filters blood from the intestine and is the first line of defense against gut-derived antigens, the effects of microbial products on the liver are unclear. In livers of normal macaques, minute levels of bacterial products were detectable, but increased 20-fold in simian immunodeficiency virus (SIV)–infected animals. Increased microbial products in the liver induced production of the chemoattractant CXCL16 by myeloid dendritic cells (mDCs), causing subsequent recruitment of hypercytotoxic natural killer (NK) cells expressing the CXCL16 receptor, CXCR6. Microbial accumulation, mDC activation, and cytotoxic NK cell frequencies were significantly correlated with markers of liver damage, and SIV-infected animals consistently had evidence of hepatitis and fibrosis. Collectively, these data indicate that SIV-associated accumulation of microbial products in the liver initiates a cascade of innate immune activation, resulting in liver damage.
- Published
- 2015
10. Disposable Copper-Based Electrochemical Sensor for Anodic Stripping Voltammetry
- Author
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William R. Heineman, Wenjing Kang, Ian Papautsky, Wei Yue, Adam Bange, and Xing Pei
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Point-of-Care Systems ,Analytical chemistry ,chemistry.chemical_element ,02 engineering and technology ,Zinc ,Electrochemistry ,01 natural sciences ,Article ,Analytical Chemistry ,Blood serum ,Lab-On-A-Chip Devices ,Animals ,Electrodes ,010401 analytical chemistry ,Serum Albumin, Bovine ,021001 nanoscience & nanotechnology ,Copper ,0104 chemical sciences ,Electrochemical gas sensor ,Anodic stripping voltammetry ,chemistry ,Electrode ,Microtechnology ,Cattle ,0210 nano-technology ,Platinum - Abstract
In this work, we report the first copper-based point-of-care sensor for electrochemical measurements demonstrated by zinc determination in blood serum. Heavy metals require careful monitoring, yet current methods are too complex for a point-of-care system. Electrochemistry offers a simple approach to metal detection on the microscale, but traditional carbon, gold (Au), or platinum (Pt) electrodes are difficult or expensive to microfabricate, preventing widespread use. Our sensor features a new low-cost electrode material, copper, which offers simple fabrication and compatibility with microfabrication and PCB processing, while maintaining competitive performance in electrochemical detection. Anodic stripping voltammetry of zinc using our new copper-based sensors exhibited a 140 nM (9.0 ppb) limit of detection (calculated) and sensitivity greater than 1 μA/μM in the acetate buffer. The sensor was also able to determine zinc in a bovine serum extract, and the results were verified with independent sensor measurements. These results demonstrate the advantageous qualities of this lab-on-a-chip electrochemical sensor for clinical applications, which include a small sample volume (μL scale), reduced cost, short response time, and high accuracy at low concentrations of analyte.
- Published
- 2014
11. CPP-Assisted Intracellular Drug Delivery, What Is Next?
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Zhili Yu, Junbo Gong, Xing Pei, Victor C. Yang, Junxiao Ye, Ergang Liu, Sunhui Chen, Pengwei Zhang, Huining He, and Meong Cheol Shin
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0301 basic medicine ,Drug ,intracellular delivery ,media_common.quotation_subject ,Normal tissue ,Antineoplastic Agents ,02 engineering and technology ,Review ,Cell-Penetrating Peptides ,Pharmacology ,Biology ,Organ distribution ,Catalysis ,Permeability ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,Neoplasms ,Animals ,Humans ,Tissue Distribution ,Tissue distribution ,Physical and Theoretical Chemistry ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,media_common ,pH and enzyme triggered drug delivery system ,Drug Carriers ,Organic Chemistry ,CPPs ,General Medicine ,Hydrogen-Ion Concentration ,021001 nanoscience & nanotechnology ,Endocytosis ,Computer Science Applications ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cancer research ,Intracellular drug delivery ,0210 nano-technology ,Drug carrier ,Cell penetration - Abstract
For the past 20 years, we have witnessed an unprecedented and, indeed, rather miraculous event of how cell-penetrating peptides (CPPs), the naturally originated penetrating enhancers, help overcome the membrane barrier that has hindered the access of bio-macromolecular compounds such as genes and proteins into cells, thereby denying their clinical potential to become potent anti-cancer drugs. By taking the advantage of the unique cell-translocation property of these short peptides, various payloads of proteins, nucleic acids, or even nanoparticle-based carriers were delivered into all cell types with unparalleled efficiency. However, non-specific CPP-mediated cell penetration into normal tissues can lead to widespread organ distribution of the payloads, thereby reducing the therapeutic efficacy of the drug and at the same time increasing the drug-induced toxic effects. In view of these challenges, we present herein a review of the new designs of CPP-linked vehicles and strategies to achieve highly effective yet less toxic chemotherapy in combating tumor oncology.
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- 2016
12. Reduced Inflammation and Lymphoid Tissue Immunopathology in Rhesus Macaques Receiving Anti–Tumor Necrosis Factor Treatment During Primary Simian Immunodeficiency Virus Infection
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Jeremy Smedley, Mirko Paiardini, Levelle D. Harris, Rhonda MacAllister, Charles M. Trubey, W. Gregory Alvord, Jeffrey D. Lifson, Octavio A. Quiñones, David R. Morcock, Jacob D. Estes, Michael Piatak, Brian Tabb, Xing Pei Hao, Guido Silvestri, and Jason M. Brenchley
- Subjects
Male ,Chemokine ,T-Lymphocytes ,Anti-Inflammatory Agents ,Simian Acquired Immunodeficiency Syndrome ,Inflammation ,Biology ,Antibodies, Monoclonal, Humanized ,Lymphocyte Activation ,Proinflammatory cytokine ,Pathogenesis ,Random Allocation ,Immune system ,Cell Movement ,Immunopathology ,medicine ,Animals ,Immunology and Allergy ,Tumor Necrosis Factor-alpha ,Macrophages ,Adalimumab ,Viral Load ,Fibrosis ,Macaca mulatta ,CD4 Lymphocyte Count ,Retroviruses, Simian ,Infectious Diseases ,Gene Expression Regulation ,Immunology ,biology.protein ,Cytokines ,RNA, Viral ,Tumor necrosis factor alpha ,Lymph Nodes ,medicine.symptom ,Viral load - Abstract
(See the editorial commentary by Michael on pages 875–6.) Persistent immune activation is a hallmark of human immunodeficiency virus type 1 (HIV-1) infection in humans and simian immunodeficiency virus (SIV) infection in rhesus macaques. In progressive HIV/SIV infections, the level of immune activation has been demonstrated to be a stronger predictor of disease progression than either plasma viral load or peripheral CD4+ T-cell count [1, 2]. Acute infection is associated with the development of intense immune activation that remains abnormally high throughout the course of infection in the absence of antiretroviral treatment (ART). This persistent pathological immune activation is associated with elevated proinflammatory cytokine and coagulation markers that correlate with an increased risk of death among HIV-positive patients [3]. In SIV-infected monkeys and HIV-infected humans, early augmentation of proinflammatory cytokines and chemokines in lymphoid tissues may play a key role in modulating disease progression [4, 5]. Notably, early high expression of both proinflammatory and antiinflammatory molecules in lymphoid tissues has been proposed to contribute to enhanced immune activation, resulting in tissue damage rather than viral control, thus driving disease progression [4, 6]. Dissecting the elements of the acute inflammatory response that lead to chronic immune activation and disease progression may provide insights that can aid the development of specific adjunctive therapies that may limit inflammation-induced tissue damage and thereby improve the prognosis of HIV-infected individuals. The inflammatory response to infections reflects the aggregate effects of various cytokines and other soluble factors produced by multiple cellular populations. Tumor necrosis factor (TNF) has been identified as a key regulator and amplifier of inflammatory responses, with effects on the innate and adaptive immune systems [7–9]. TNF has been proposed to contribute to the overall pathogenesis of HIV/SIV infection, enhancing viral propagation, lymphocyte depletion, and clinical manifestations of disease. High TNF levels have been shown to be associated with all stages of HIV-1 infection, with increased TNF expression in the plasma and lymphoid tissues during acute HIV-1 infection [10, 11]. Sequential plasma samples collected during the eclipse and exponential viral expansion phases of acute HIV-1 infection demonstrated rapid and robust inflammatory responses, including early and sustained increases in TNF, that likely have immunopathological consequences by promoting immune activation, viral replication, and CD4+ T-cell loss [12]. In nonhuman-primate models, elevated TNF expression has been shown in the serum, peripheral blood mononuclear cells, lymph nodes, and brain of infected animals in temporal association with SIV replication during acute infection [13–15]. In contrast, studies of nonprogressive and apathogenic SIV infection in natural hosts of SIV have shown a lack of TNF upregulation throughout the acute and chronic stages of SIV infection [16], suggesting that differences in the host acute inflammatory response may be critically important in pathogenesis and disease progression. Since TNF inhibitors are used to treat a range of inflammatory conditions [17, 18], and given the data suggesting that TNF may play a key role in the acute inflammatory response to HIV/SIV infection, we evaluated the effect of anti-TNF antibody (adalimumab; Humira) treatment during the first 12 weeks of SIV infection in a small, nonhuman-primate study. While treatment did not affect viral replication dynamics or systemic T-cell activation profiles, inhibition of the biological activity of TNF reduced proinflammatory gene expression in lymphoid tissues during acute infection and attenuated antiinflammatory responses to SIV associated with pathological damage of lymphoid tissues [6]. Specifically, TNF blockade attenuated 3 manifestations of inflammation associated with SIV infection: (1) infiltration of CD163+ macrophages and neutrophils into the paracortical T-cell zone, (2) transforming growth factor β (TGF-β) expression in the T-cell zone, and (3) lymphoid tissue fibrosis, which was associated with less CD4+ T-cell loss, demonstrating that modulation of inflammatory responses to HIV/SIV infection may beneficially affect pathogenesis, independent of any direct effects on viral replication.
- Published
- 2012
13. Depletion of CD4+ T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques
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Elena V. Ryzhova, Yanjie Yi, James G. Else, Lawrence R. Sternberg, Ronald G. Collman, Alexandra M. Ortiz, Bing Li, Paul M. Carnathan, Brian Tabb, Sarah J. Ratcliffe, Jessica C. Engram, Xing Pei Hao, Francisco Gonzalez-Scarano, Elizabeth M. Cramer, Nichole R. Klatt, Benton Lawson, Jason M. Brenchley, Dawn M. Little, Mirko Paiardini, Aftab A Ansari, Jacob D. Estes, Cynthia A. Derdeyn, and Guido Silvestri
- Subjects
CD4-Positive T-Lymphocytes ,viruses ,T cell ,Simian Acquired Immunodeficiency Syndrome ,Viremia ,Biology ,Virus Replication ,medicine.disease_cause ,Lymphocyte Depletion ,Immune system ,In vivo ,medicine ,Animals ,Antilymphocyte Serum ,DNA Primers ,Base Sequence ,virus diseases ,General Medicine ,Viral Load ,Simian immunodeficiency virus ,medicine.disease ,Macaca mulatta ,Virology ,medicine.anatomical_structure ,Viral replication ,CD4 Antigens ,Immunology ,RNA, Viral ,Simian Immunodeficiency Virus ,Viral load ,CD8 ,Research Article - Abstract
CD4+ T cells play a central role in the immunopathogenesis of HIV/AIDS, and their depletion during chronic HIV infection is a hallmark of disease progression. However, the relative contribution of CD4+ T cells as mediators of antiviral immune responses and targets for virus replication is still unclear. Here, we have generated data in SIV-infected rhesus macaques (RMs) that suggest that CD4+ T cells are essential in establishing control of virus replication during acute infection. To directly assess the role of CD4+ T cells during primary SIV infection, we in vivo depleted these cells from RMs prior to infecting the primates with a pathogenic strain of SIV. Compared with undepleted animals, CD4+ lymphocyte-depleted RMs showed a similar peak of viremia, but did not manifest any post-peak decline of virus replication despite CD8+ T cell- and B cell-mediated SIV-specific immune responses comparable to those observed in control animals. Interestingly, depleted animals displayed rapid disease progression, which was associated with increased virus replication in non-T cells as well as the emergence of CD4-independent SIV-envelopes. Our results suggest that the antiviral CD4+ T cell response may play an important role in limiting SIV replication, which has implications for the design of HIV vaccines.
- Published
- 2011
14. Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection
- Author
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Jan Kristoff, Peter L. Choyke, Luis D. Giavedoni, Charles M. Trubey, Marcelino Bernardo, Nichole R. Klatt, Srinivas S. Rao, Jacob D. Estes, Jason M. Brenchley, Claire Deleage, Amy Xu, Cristian Apetrei, Brandon F. Keele, Gregory Q. Del Prete, David R. Morcock, Carissa Lucero, Baris Turkbey, Jeffrey D. Lifson, W. Gregory Alvord, Xing Pei Hao, Ivona Pandrea, and Jeremy Smedley
- Subjects
Male ,animal diseases ,Simian Acquired Immunodeficiency Syndrome ,General Physics and Astronomy ,Inflammation ,Biology ,medicine.disease_cause ,Article ,General Biochemistry, Genetics and Molecular Biology ,Pathogenesis ,medicine ,Animals ,Colitis ,Gastrointestinal tract ,Multidisciplinary ,Dextran Sulfate ,Experimental colitis ,RNA ,General Chemistry ,Simian immunodeficiency virus ,medicine.disease ,Macaca mulatta ,Chemically-induced colitis ,3. Good health ,Gastrointestinal Tract ,Immunology ,Female ,Simian Immunodeficiency Virus ,medicine.symptom - Abstract
Mucosal damage to the gastrointestinal (GI) tract with resulting microbial translocation is hypothesized to significantly contribute to the heightened and persistent chronic inflammation and immune activation characteristic to HIV infection. Here we employ a non-human primate model of chemically induced colitis in SIV-uninfected rhesus macaques that we developed using dextran sulfate sodium (DSS), to directly test this hypothesis. DSS treatment results in GI barrier damage with associated microbial translocation, inflammation and immune activation. The progression and severity of colitis are longitudinally monitored by a magnetic resonance imaging approach. DSS treatment of SIV-infected African green monkeys, a natural host species for SIV that does not manifest GI tract damage or chronic immune activation during infection, results in colitis with elevated levels of plasma SIV RNA, sCD14, LPS, CRP and mucosal CD4+ T-cell loss. Together these results support the hypothesis that GI tract damage leading to local and systemic microbial translocation, and associated immune activation, are important determinants of AIDS pathogenesis., HIV-1 infection in humans and SIV infection in rhesus macaques are associated with mucosal damage to the gastrointestinal tract, microbial translocation and chronic immune activation. Here the authors develop a non-human primate DSS colitis model that recapitulates these aspects of the disease in uninfected rhesus macaques.
- Published
- 2015
15. Different Doses of Nitric Oxide Donor Prevent Osteoporosis in Ovariectomized Rats
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Fu-Xing Pei, Ying-Jie Hao, Yu Tang, and Feng-Bao Chen
- Subjects
medicine.medical_specialty ,Ovariectomy ,Osteoporosis ,chemistry.chemical_element ,Calcium ,Nitric oxide ,Rats, Sprague-Dawley ,Nitroglycerin ,Random Allocation ,chemistry.chemical_compound ,Dry weight ,Bone Density ,Internal medicine ,Bone cell ,Animals ,Medicine ,Nitric Oxide Donors ,Orthopedics and Sports Medicine ,Bone mineral ,Analysis of Variance ,Estradiol ,business.industry ,General Medicine ,medicine.disease ,Rats ,Endocrinology ,chemistry ,Ovariectomized rat ,Female ,Surgery ,business ,medicine.drug - Abstract
Nitric oxide has important effects on bone cell function. To verify that nitric oxide can protect against bone loss associated with estrogen deficiency, which is dependent on different concentrations of nitric oxide, we applied different doses of nitric oxide to ovariectomized rats. Fifty 12-week-old Sprague-Dawley female rats had ovariectomies, and 10 rats had sham operations. The ovariectomized rats were randomized into five groups: ovariectomized only; 17-beta-estradiol; low-dose nitroglycerin; middle-dose nitroglycerin; and high-dose nitroglycerin. After 12 weeks, the bone mineral density, dry weight, ash weight, calcium content, and nitric oxide concentration were determined. Compared with these same measurements in the sham-operated group, the bone mineral density, dry weight, ash weight, calcium content, and nitric oxide concentration decreased in the control group. Treatment with low-dose nitroglycerin, middle-dose nitroglycerin, and 17-beta-estradiol maintained bone mineral density and reversed the effects of ovariectomy on dry weight, ash weight and calcium content when compared with those in the control group. There were no differences in the bone mineral density, dry weight, ash weight, or calcium concentration between the ovariectomized-only rats and the rats treated with high-dose nitroglycerin. Results of this study suggest that nitric oxide treatment can counteract bone loss in ovariectomized rats. Furthermore, supplementation with a similar or slightly greater than physiologic concentration of nitric oxide has a potentially positive impact on osteoporosis.
- Published
- 2005
16. Paddlefish strike at artificial dipoles simulating the weak electric fields of planktonic prey
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Lon A. Wilkens, Xing Pei, and Winfried Wojtenek
- Subjects
Sensory Receptor Cells ,Physiology ,Video Recording ,Aquatic Science ,Zooplankton ,Daphnia ,Predation ,Electric field ,Paddlefish ,Animals ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Response Frequency ,biology ,Ecology ,Fishes ,Feeding Behavior ,Mechanics ,biology.organism_classification ,Electric Stimulation ,Dipole ,Amplitude ,Data Interpretation, Statistical ,Predatory Behavior ,Insect Science ,Animal Science and Zoology - Abstract
The freshwater paddlefish Polyodon spathula (Polyodontidae) feeds primarily on the water flea (Daphnia sp.), and previous studies suggest that these fish detect their planktonic prey using their rostral electrosensory system. Zooplankton produce direct-current and oscillating alternating-current electric fields containing multiple frequencies and amplitudes. We asked whether an inanimate electric field is sufficient to elicit paddlefish strikes equivalent to their feeding behavior. Juvenile paddlefish respond to artificial dipole stimuli by investigating the electric field and striking at the dipole electrode tips. These behavioral responses, scored as strikes, exhibit a bandpass characteristic with a maximum response between 5 and 15 Hz. Responses were less frequent at higher (20, 30, 40, 50 Hz) and lower (0.1, 0.5, 1 Hz) test frequencies, with a steep drop-off below 5 Hz. Strike rates also varied with stimulus intensity. Response frequency was greatest at 0.25 μA peak-to-peak amplitude, with reduced responses at lower and higher amplitudes (0.125 and 1.25 μA). Striking behavior was also influenced by water conductivity: strike rate was reduced at higher water conductivity. Dipole-elicited strikes exhibit behavioral plasticity. Fish habituate to repetitive dipole stimuli that are not reinforced by prey capture, and they dishabituate after food reinforcement. These experiments characterize paddlefish feeding strikes towards dipole electrodes at signal frequencies and intensities simulating the electric fields of zooplankton, their natural prey, and demonstrate that electric fields are sufficient to elicit feeding behavior. The results support the conclusion that paddlefish use their passive electrosensory system for planktivorous feeding.
- Published
- 2001
17. SIV-induced Translocation of Bacterial Products in the Liver Mobilizes Myeloid Dendritic and Natural Killer Cells Associated With Liver Damage.
- Author
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Evans, Tristan I., Haiying Li, Schafer, Jamie L., Klatt, Nichole R., Xing-Pei Hao, Traslavina, Ryan P., Estes, Jacob D., Brenchley, Jason M., Reeves, R. Keith, Li, Haiying, and Hao, Xing-Pei
- Subjects
CHROMOSOMAL translocation ,SIMIAN immunodeficiency virus ,KILLER cells ,LIVER injuries ,LIVER diseases ,DENDRITIC cells ,LENTIVIRUS diseases ,ANIMAL experimentation ,ANIMALS ,APOPTOSIS ,CELL receptors ,CELLS ,CYTOKINES ,GENES ,LIVER ,PRIMATES ,RESEARCH funding ,RNA virus infections ,DISEASE complications ,PHYSIOLOGY - Abstract
Disruption of the mucosal epithelium during lentivirus infections permits translocation of microbial products into circulation, causing immune activation and driving disease. Although the liver directly filters blood from the intestine and is the first line of defense against gut-derived antigens, the effects of microbial products on the liver are unclear. In livers of normal macaques, minute levels of bacterial products were detectable, but increased 20-fold in simian immunodeficiency virus (SIV)-infected animals. Increased microbial products in the liver induced production of the chemoattractant CXCL16 by myeloid dendritic cells (mDCs), causing subsequent recruitment of hypercytotoxic natural killer (NK) cells expressing the CXCL16 receptor, CXCR6. Microbial accumulation, mDC activation, and cytotoxic NK cell frequencies were significantly correlated with markers of liver damage, and SIV-infected animals consistently had evidence of hepatitis and fibrosis. Collectively, these data indicate that SIV-associated accumulation of microbial products in the liver initiates a cascade of innate immune activation, resulting in liver damage. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
18. Gammaherpesvirus infection and malignant disease in rhesus macaques experimentally infected with SIV or SHIV.
- Author
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Marshall, Vickie A., Labo, Nazzarena, Hao, Xing-Pei, Holdridge, Benjamin, Thompson, Marshall, Miley, Wendell, Brands, Catherine, Coalter, Vicky, Kiser, Rebecca, Anver, Miriam, Golubeva, Yelena, Warner, Andrew, Jaffe, Elaine S., Jr.Piatak, Michael, Wong, Scott W., Ohlen, Claes, MacAllister, Rhonda, Smedley, Jeremy, Deleage, Claire, and Del Prete, Gregory Q.
- Subjects
HERPESVIRUSES ,HIV-positive persons ,MACAQUES ,ANIMAL models in research ,SIMIAN immunodeficiency virus - Abstract
Human gammaherpesviruses are associated with malignancies in HIV infected individuals; in macaques used in non-human primate models of HIV infection, gammaherpesvirus infections also occur. Limited data on prevalence and tumorigenicity of macaque gammaherpesviruses, mostly cross-sectional analyses of small series, are available. We comprehensively examine all three-rhesus macaque gammaherpesviruses -Rhesus rhadinovirus (RRV), Rhesus Lymphocryptovirus (RLCV) and Retroperitoneal Fibromatosis Herpesvirus (RFHV) in macaques experimentally infected with Simian Immunodeficiency Virus or Simian Human Immunodeficiency Virus (SIV/SHIV) in studies spanning 15 years at the AIDS and Cancer Virus Program of the Frederick National Laboratory for Cancer Research. We evaluated 18 animals with malignancies (16 lymphomas, one fibrosarcoma and one carcinoma) and 32 controls. We developed real time quantitative PCR assays for each gammaherpesvirus DNA viral load (VL) in malignant and non-tumor tissues; we also characterized the tumors using immunohistochemistry and in situ hybridization. Furthermore, we retrospectively quantified gammaherpesvirus DNA VL and SIV/SHIV RNA VL in longitudinally-collected PBMCs and plasma, respectively. One or more gammaherpesviruses were detected in 17 tumors; generally, one was predominant, and the relevant DNA VL in the tumor was very high compared to surrounding tissues. RLCV was predominant in tumors resembling diffuse large B cell lymphomas; in a Burkitt-like lymphoma, RRV was predominant; and in the fibrosarcoma, RFHV was predominant. Median RRV and RLCV PBMC DNA VL were significantly higher in cases than controls; SIV/SHIV VL and RLCV VL were independently associated with cancer. Local regressions showed that longitudinal VL patterns in cases and controls, from SIV infection to necropsy, differed for each gammaherpesvirus: while RFHV VL increased only slightly in all animals, RLCV and RRV VL increased significantly and continued to increase steeply in cases; in controls, VL flattened. In conclusion, the data suggest that gammaherpesviruses may play a significant role in tumorogenesis in macaques infected with immunodeficiency viruses. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
19. Bone functions as a novel endocrine organ in energy metabolism
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Xiang, Chen, Hao-ming, Tian, Fu-xing, Pei, and Xi-jie, Yu
- Subjects
Osteocalcin ,Animals ,Humans ,Energy Metabolism ,Bone and Bones - Published
- 2012
20. Glucocorticoids affect the metabolism of bone marrow stromal cells and lead to osteonecrosis of the femoral head: a review
- Author
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Gang, Tan, Peng-de, Kang, and Fu-Xing, Pei
- Subjects
Osteonecrosis ,Animals ,Humans ,Bone Marrow Cells ,Femur Head ,Stromal Cells ,Glucocorticoids - Abstract
To review the recent developments in the mechanisms of glucocorticoids induced osteonecrosis of femoral head (ONFH) and introduce a new theory of ONFH.Both Chinese- and English-language literatures were searched using MEDLINE (1997 - 2011), Pubmed (1997 - 2011) and the Index of Chinese-language Literature (1997 - 2011).Data from published articles about mechanisms of glucocorticoids induced ONFH in recent domestic and foreign literature were selected. Data extraction Data were mainly extracted from 61 articles which are listed in the reference section of this review.Glucocorticoids are steroid hormones secreted by the adrenal cortex that play a pivotal role in the regulation of a variety of developmental, metabolic and immune functions. However, high dose of exogenous glucocorticoids usage is the most common non-traumatic cause of ONFH. Glucocorticoids can affect the metabolisms of osteoblasts, osteoclasts, bone marrow stromal cells and adipocytes which decrease osteoblasts formation but increase adipocytes formation and cause ONFH finally.Glucocorticoids affect the differentiation of mesenchymal stem cells, through activating or inhibiting the related transcript regulators of osteogenesis and adipogenesis. At last, the size and volume of mesenchymal stem cells derived adipocytes will increase amazingly, but the osteoblasts will be decreased obviously. In the meantime, the activity of the osteoclasts will be activated. So, these mechanisms work together and lead to ONFH.
- Published
- 2012
21. Restricted replication of xenotropic murine leukemia virus-related virus in pigtailed macaques
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Xing Pei Hao, Brandon F. Keele, Jacob D. Estes, Chawaree Chaipan, Gregory Q. Del Prete, James D. Roser, Kunio Nagashima, Jeffrey D. Lifson, Jeremy Smedley, Abigail Lara, Vineet N. KewalRamani, Mary F. Kearney, Vinay K. Pathak, Julian W. Bess, Ann Wiegand, Elena Chertova, Rhonda MacAllister, John M. Coffin, Charles M. Trubey, Jon Spindler, and Kyeong Eun Lee
- Subjects
Male ,Xenotropic murine leukemia virus-related virus ,Immunology ,Somatic hypermutation ,Antibodies, Viral ,Virus Replication ,Microbiology ,Virus ,Retrovirus ,Interferon ,Virology ,medicine ,Animals ,Humans ,Phylogeny ,biology ,virus diseases ,biology.organism_classification ,medicine.disease ,Leukemia ,Disease Models, Animal ,Viral replication ,Insect Science ,biology.protein ,Pathogenesis and Immunity ,Antibody ,Macaca nemestrina ,medicine.drug ,Retroviridae Infections - Abstract
Although xenotropic murine leukemia virus-related virus (XMRV) has been previously linked to prostate cancer and myalgic encephalomyelitis/chronic fatigue syndrome, recent data indicate that results interpreted as evidence of human XMRV infection reflect laboratory contamination rather than authentic in vivo infection. Nevertheless, XMRV is a retrovirus of undefined pathogenic potential that is able to replicate in human cells. Here we describe a comprehensive analysis of two male pigtailed macaques ( Macaca nemestrina ) experimentally infected with XMRV. Following intravenous inoculation with >10 10 RNA copy equivalents of XMRV, viral replication was limited and transient, peaking at ≤2,200 viral RNA (vRNA) copies/ml plasma and becoming undetectable by 4 weeks postinfection, though viral DNA (vDNA) in peripheral blood mononuclear cells remained detectable through 119 days of follow-up. Similarly, vRNA was not detectable in lymph nodes by in situ hybridization despite detectable vDNA. Sequencing of cell-associated vDNA revealed extensive G-to-A hypermutation, suggestive of APOBEC-mediated viral restriction. Consistent with limited viral replication, we found transient upregulation of type I interferon responses that returned to baseline by 2 weeks postinfection, no detectable cellular immune responses, and limited or no spread to prostate tissue. Antibody responses, including neutralizing antibodies, however, were detectable by 2 weeks postinfection and maintained throughout the study. Both animals were healthy for the duration of follow-up. These findings indicate that XMRV replication and spread were limited in pigtailed macaques, predominantly by APOBEC-mediated hypermutation. Given that human APOBEC proteins restrict XMRV infection in vitro , human XMRV infection, if it occurred, would be expected to be characterized by similarly limited viral replication and spread.
- Published
- 2012
22. [Histological and biomechanical study of repairing rabbit radius segmental bone defect with porous titanium]
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Hong-fang, Zhang, Chao-yong, Zhao, Hong-song, Fan, Hui, Zhang, Fu-xing, Pei, and Guang-lin, Wang
- Subjects
Male ,Titanium ,Radius ,Bone Regeneration ,Tissue Scaffolds ,Bone Substitutes ,Animals ,Biocompatible Materials ,Prostheses and Implants ,Rabbits ,Porosity - Abstract
To investigate the therapeutic effects of porous titanium (Ti) on the recovery of rabbit radial bone defect.Bone defects were artificially made in 30 New Zealand rabbits by resecting the 1 cm substantial osseo with periosteum of both radii. The left anterior limbs were implanted with porous titanium, while the right anterior limbs with porous hydroxyapatite (HA). The rabbits were sacrificed at three time points. Both the radii healing statuses were observed by histology and histomorphometry analyses by means of computer graphic processing at the end of 8, 12 and 24 weeks, and biomechanical analyses at the end of 12 and 24 weeks.The histology examination showed that mass newly formed bone had grown into most pores of both the specimens. Along with prolongation of times after operation, the ingrowths of bone cells and effects of bone remodeling in the research side were nearly the same as those in the control side at the end of 12 and 24 weeks. The interface between the new bone and implants showed tight contact in both the groups without an obvious fibrous tissue. The results of histomorphometrical analyses showed that a statistically significant difference was not obtained for % bone area (bone area/ gross implant) between both the groups (P0.05).However, the results of maximum failure load for the Ti group and the HA group were (107.34±27.44) N and (93.42±21.18) N at the end of 12 weeks, (118.56±24.65) N and (102.15±23.37) N at the end of 24 weeks, respectively. Biomechanical properties of the Ti group was stronger than that of the HA group, however, a statistically significant difference was not obtained between both the groups (P=0.102).Porous titanium scaffold can promote the formation of new bone, which contributes to the healing of long tubular bone defect. The porous titanium can enhance the bone repairing effect on segmental bone defect nearly the same as porous hydroxyapatite .
- Published
- 2011
23. [Changes of microarchitecture and biomechanical properties in callus during fracture healing in ovariectomized rats]
- Author
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Jian-xiong, Mu, Bin, Shen, Jing, Yang, Yong, Li, Zong-ke, Zhou, Peng-de, Kang, and Fu-xing, Pei
- Subjects
Fracture Healing ,Tibial Fractures ,Random Allocation ,Bone Density ,Ovariectomy ,Animals ,Osteoporosis ,Female ,Bony Callus ,Collagen Type I ,Biomechanical Phenomena ,Rats - Abstract
To study the changes of biomechanical properties and microarchitecture in callus during the healing process of osteoporotic fracture.Ovariectomy (OVX) was performed on SD rats to establish osteoporotic rat model. Osteotomy was performed on both groups of rats with OVX and sham operations to establish bone fracture. Bone mineral density (BMD), area of type I collagen, biomechanical properties, and microarchitecture of the fractured bones during healing process were measured.The BMD of both groups of rats were significantly lower at the 12th week than at the 6th week after fracture (P0.05). Both groups of rats had significantly higher biomechanical strength and area of type I collagen at the 12th week than at the 6th week after fracture (P0.05). The OVX group of rats had significantly lower structure model index (SMI) values than the sham group at both 6th and 12th week after fracture (P0.05). Higher values of SMI appeared at the 12th week than at the 6th week in both groups of rats (P0.05).During the healing of fracture, the BMD of the newly-formed bone reaches its peak value at the 6th week after fracture, which is earlier than the occurrence of peak biomechanical strength, area of type I collagen, and SMI. Although the collagen and aggravation of mineral determine the biomechanical properties, BMD by itself may not be able to determine the biomechanical strength because of the change of the 3-D structure of the callus. The combination of collagen and microarchitecture may act as a factor that determines the biomechanical strength of callus independent of BMD.
- Published
- 2011
24. The effect of Kashin-Beck disease-affected feed and T-2 toxin on the bone development of Wistar rats
- Author
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Denglu, Yan, Pengde, Kang, Jing, Yang, Bing, Shen, Zongke, Zhou, Lijun, Duan, Jiayun, Deng, Hui, Huang, and Fu-Xing, Pei
- Subjects
Cartilage, Articular ,Kashin-Beck Disease ,Male ,Bone Development ,Tibia ,Iohexol ,Age Factors ,Food Contamination ,Weaning ,Weight Gain ,Animal Feed ,Rats ,Methylene Blue ,Disease Models, Animal ,Necrosis ,T-2 Toxin ,Chondrocytes ,Animals ,Humans ,Female ,Collagen ,Growth Plate ,Rats, Wistar - Abstract
To investigate the effect of Kashin-Beck disease (KBD)-affected feed and T-2 toxin on the bone development of Wistar rats.Seventy-eight ablactation Wistal rats (50% male and 50% female) weighing approximately 65 g were obtained from Sichuan Medical Center (Chengdu, China), and were randomly assigned to three groups (Groups A, B and C). Group A had 24 rats and were fed with commercial rat feed (control); Group B had 30 rats and were fed with commercial rat feed and T2 toxin by intragastric administration; and Group C had 24 rats and were fed with the KBD-affected feed. The histological sections were stained with hematoxylin and eosin (HE) and Masson dye.Weight gain was fastest Group A rats and Group C rats had the lowest weight gain (P0.05). There were no epiphyseal plate chondrocyte necroses in the control group at the first, second, and fourth weeks. In the T-2 toxin group, two rats had chondrocyte-focus necroses at the labrocyte cell zone at the second week. At the fourth week, six rats had chondrocyte-focus or lamellar necroses at the labrocyte cell zone. Three rats had focus necrosis at the proliferation cell zone, and there were three rats with penetration necrosis. In the KBD-affected group, one rat had chondrocyte-focus necrosis at the labrocyte cell zone at the second week and seven rats had chondrocyte-focus necrosis at the labrocyte cell zone at the fourth week. And at the same time, two rats had focus necrosis at the proliferation cell zone, three rats had lamellar necrosis at the labrocyte cell zone, four had focus necrosis at the labrocyte cell zone, and two rats had penetration necrosis. The epiphyseal plate Masson dye of the control group showed deep blue collogen coloration and in the KBD-affected group and T-2 toxin group, collogen showed a pale blue color, the drum dyeing was uneven, and the collogen was showed an absence of color in the region of the necrosis.With KBD-affected feed or T-2 toxin intervention, rats had focus necrosis and lamellar necrosis at the epiphyseal plate. KBD-affected feed rats had less weight gain than T-2 toxin intervention rats, which means there were other etiological factors in KBD-affected feed.
- Published
- 2010
25. The neurophysiological correlates of colour and brightness contrast in lateral geniculate neurons
- Author
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J. M. Crook, Sabine Kastner, Xing Pei, Chao Yi Li, and Otto D. Creutzfeldt
- Subjects
Brightness ,genetic structures ,Population ,Luminance ,Contrast Sensitivity ,Optics ,Parvocellular cell ,Geniculate ,Animals ,Humans ,education ,Neurons ,Physics ,education.field_of_study ,business.industry ,General Neuroscience ,Geniculate Bodies ,Macaca fascicularis ,Receptive field ,Darkness ,Evoked Potentials, Visual ,sense organs ,Visual Fields ,business ,Color Perception ,Photic Stimulation ,Photopic vision - Abstract
The colour of an object is changed by surround colours so that the perceived colour is shifted in a direction complementary to the surround colour. To investigate the physiological mechanism underlying this phenomenon, we recorded from 260 neurons in the parvo-cellular lateral geniculate nucleus (P-LGN) of anaesthetized monkeys (Macaca fascicularis), and measured their responses to 1.0–2.0° diameter spots of equiluminant light of various spectral composition, centered over their receptive field (spectral response function, SRF). Five classes of colour opponent neurons and two groups of light inhibited cells were distinguished following the classification proposed by Creutzfeldt et al. (1979). In each cell we repeated the SRF measurement while an outer surround (inner diameter 5°, outer diameter 20°) was continuously illuminated with blue (452 nm) or red (664 nm) light of the same luminance as the center spots. The 1.0–1.5° gap between the center and the surround was illuminated with a dim white background light (0.5–1cd/m2). During blue surround illumination, neurons with an excitatory input from S-or M-cones (narrowand wide-band/short-wavelength sensitive cells, NSand WS-cells, respectively) showed a strong attenuation of responses to blue and green center spots, while their maintained discharge rate (MDR) increased. During red surround illumination the on-minus-off-responses of NS- and WS-cells showed a clear increment. L-cone excited WL-cells (wide-band/long-wavelength sensitive) showed a decrement of on-responses to red, yellow and green center spots during red surround illumination and, in the majority, also an increment of MDR. The response attenuation of narrow-band/long-wavelength sensitive (NL)-cellls was more variable, but their on-minus-off-responses were also clearly reduced in the average during red surrounds. Blue surround illumination affected WL-cell responses little and less consistently than those of NL-cells, but often broadened the SRF also in the WL-cells towards shorter wavelengths. The M-cone excited and S-cone suppressed WM-cells were strongly suppressed by blue but only little affected by red surround illumination. The changes of spectral responsiveness came out clearly in the group averages of the different cell classes, but snowed some variation between individual cells in each group. The zero-crossing wavelengths derived from on-minus-off-responses were also characteristically shifted towards wavelengths complementary to those of the surround. The direction of changes of spectral responsiveness of P-LGN-cells are thus consistent with psychophysical colour contrast and colour induction effects which imply that light of one spectral region in the surround reduces the contribution of light from that same spectral region in the (broad band or composite) object colour. Surrounds of any colour also decrease the brightness of a central coloured or achromatic light (darkness induction). We calculated the population response of P-LGN-units by summing the activity of all WS-, WM- and WL-cells and subtracting that of all NS- and NL-cells. The SRF of this population response closely resembled the spectral brightness function for equiluminous lights rather than the photopic luminosity function. With red or blue surrounds, this population SRF was lowered nearly parallel across the whole spectrum to about 0.7 of the amplitude of the control. In a psychophysical test on 4 observers we estimated the darkness induction of an equiluminous surround in a stimulus arrangement identical to the neurophysiological experiment, and found a brightness reduction for white, blue, green and red center stimuli to 0.5–0.7 of the brightness values without surround. This indicates that the neurophysiological results may be directly related to perception, and that P-LGN-cells not only signal for chroma but also for brightness, but in different combinations. The results indicate that both an additive (direct excitation or suppression of activity) and a multiplicative mechanism (change of gain control) must be involved in brightness and colour contrast perception. As mechanisms for the surround effects horizontal cell interactions appear not to be sufficient, and a direct adaptive effect on receptors feeding positive or negative (opponent) signals into the ganglion cells receptive fields by straylight from the surround must be seriously considered. This will be examined in the following companion paper. The results indicate that changes of spectral and brightness responses in a colour contrast situation sufficient to explain corresponding changes in perception are found already in geniculate neurons and their retinal afferents. This applies to mechanisms for colour constancy as well in as much as they are related to colour contrast.
- Published
- 1991
26. The neurophysiological correlates of colour and brightness contrast in lateral geniculate neurons
- Author
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A. Valberg, Otto D. Creutzfeldt, Xing Pei, and Sabine Kastner
- Subjects
Adult ,genetic structures ,Lateral geniculate nucleus ,Models, Biological ,Retinal ganglion ,Contrast Sensitivity ,Optics ,Parvocellular cell ,Lens, Crystalline ,Geniculate ,medicine ,Animals ,Humans ,Chromatic scale ,Neurons ,Physics ,Retina ,Adaptation, Ocular ,business.industry ,General Neuroscience ,Geniculate Bodies ,Middle Aged ,Macaca fascicularis ,Electrophysiology ,medicine.anatomical_structure ,Receptive field ,sense organs ,Visual Fields ,business ,Neuroscience ,Color Perception ,Photic Stimulation - Abstract
We report on experiments which were undertaken in an attempt to clarify mechanisms underlying the contrast effects of chromatic surround illumination on spectral responsiveness of cells in the parvocellular layers of the LGN (P-LGN-cells), that had been demonstrated under standard conditions in the preceding companion paper. The experiments were done in anesthetized macaques (Macaca fascicularis). In some neurons, S-potentials were recorded together with the post-synaptic action potentials, and all effects seen in P-LGN-cells were present already in their retinal afferents indicating their retinal origin. The responsiveness of the cells for center stimuli of different wavelengths and during illumination of the receptive field center or the outer surround was determined. Continuous outer surround illumination altered maintained discharge rate (MDR), sensitivity and gain of P-LGN and retinal ganglion cells in the same way and empirically not distinguishable from direct illumination of the receptive field. Responses to surround flashes showed the same dependence on spectral composition as those to center flashes. Adaptation and excitation caused by outer surround illumination (inner diameter 5 degrees, outer diameter 20 degrees) were, in the average, ten times weaker than those exerted by light of the same spectral composition shone directly into the receptive field. Surround effects decreased proportional to r-2. Excitation by outer surround flashes was reduced by adaptation of the receptive field center in the same manner as responses to center flashes. The findings indicate that outer surround light has a direct excitatory and adaptive effect on the excitatory or inhibitory cones feeding into the receptive field. This indicates that straylight from the surround into the center could be responsible for the adaptive and excitatory effects of surround illumination. The straylight fraction from the remote surround into the receptive field must be higher, however, than that estimated from the psychophysically determined point spread function. It comes closer to earlier direct straylight measurements in excised eyes, but may be enhanced by chromatic aberration. If a surround of excitatory colour is flashed simultaneously with an excitatory center stimulus, additivity of center and surround excitation is observed only at low center intensities, while at higher center intensities the gain for center excitation is reduced similar to adaptive gain control. This could be explained by lateral interaction through horizontal connections in the retina, which decays within seconds, while adaptation of the cones feeding into the receptive field center is fully effective only after about 3 s.(ABSTRACT TRUNCATED AT 400 WORDS)
- Published
- 1991
27. Role of the extensive area outside the x-cell receptive field in brightness information transmission
- Author
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H.-C. Von Mitzlaff, Yi-Xiong Zhow, Chao-Yi Li, and Xing Pei
- Subjects
Retinal Ganglion Cells ,Physics ,Brightness ,Information transmission ,Light ,business.industry ,Models, Neurological ,Action Potentials ,Geniculate Bodies ,Neural Inhibition ,Retinal ganglion ,Sensory Systems ,Contrast Sensitivity ,Photometry ,Ophthalmology ,Electrophysiology ,Optics ,Receptive field ,Cats ,Animals ,Visual Fields ,business ,Neuroscience ,Mathematics - Abstract
Stimulus area-response functions of retinal ganglion cells show an extensive disinhibitory region (DIR) outside the classical receptive field (RF). The DIR has a wide summation area but low sensitivity. Spatial responses of the retinal ganglion cells have been simulated in a model which takes into account also the properties of the DIR. By scanning the RF and its DIR with a visual image and reconstructing the transferred image for single cells, it is shown that these properties of the DIR are beneficial in the transmission of area brightness and image grey scales.
- Published
- 1991
28. [Initial immunoreaction study on PVA/n-HA + PA66 biological composite material after being implanted into animal body]
- Author
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Tao, Guo, Tian-fu, Yang, Jia-qi, Wu, Yang, Liu, Yu-bao, Li, and Fu-xing, Pei
- Subjects
Male ,Rats, Sprague-Dawley ,Mice ,Nylons ,Random Allocation ,Polyvinyl Alcohol ,Animals ,Biocompatible Materials ,Female ,Hydroxyapatites ,Prostheses and Implants ,Rats - Abstract
To observe immunoreaction to PVA/n-HA+ PA66 biological composite material after being implanted into animal body.PVA/n-HA+PA66 composite materials were implanted into mouse subcutaneous tissue. Histologial examination was performed at 2, 4, 6 weeks, the amount of CD3, CD4+, CD8+ in blood and IL-1, IL-6, TNF-alpha in spleen cells was measured at the same time.The amount of CD3, CD4+, CD8+ in mouse blood and IL-1, IL-6, TNF-alpha in mouse spleen cells were not different with the control groups at 2, 4, 6 weeks (P0.05). The fibrous tissue and some blood vessels were found growing into the porous materials, which resulted in composite materials intergration of proliferative structure. The reject reaction was not found.PVA/n-HA+PA66 biological composite material does not cause immune rejection after being implanted into animal body, verifying its good biocompatibility.
- Published
- 2008
29. [Treatment of early avascular necrosis of femoral head by core decompression and transplantation of human hepatic growth factor gene-modified osteoblasts: experiment with rabbits]
- Author
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Hong-Sheng, Dang, Fu-Xing, Pei, Bin, Shen, Jing, Yang, Zong-Ke, Zhou, Fang, Lu, and Wen-Zhen, Peng
- Subjects
Osteoblasts ,Treatment Outcome ,Cell Transplantation ,Femur Head Necrosis ,Hepatocyte Growth Factor ,Osteogenesis ,Animals ,Humans ,Neovascularization, Physiologic ,Rabbits ,Transfection ,Cells, Cultured ,Plasmids - Abstract
To evaluate the effects of transplantation of human hepatocyte growth factor (hHGF) gene-modified osteoblasts combined with core decompression in treatment of avascular necrosis of femoral head (ANFH).The plasmid pcDNA3.1(+)-hHGF containing hHGF gene was constructed. Osteoblasts were isolated from fetal rabbits, cultured, and transfect3d with the plasmid pcDNA3.1(+)-hHGF or blank plasmid pcDNA3.1(+), or used as controls. Thirty-six adult New Zealand rabbits were made into ANFH models, underwent core decompression, and were randomly divided into 3 groups. Group A, transplanted with osteoblasts transfected with pcDNA3.1(+)-hHGF plasmid, Group B, transplanted with osteoblasts not transfected with pcDNA3.1(+)-hHGF plasmid, and Group C, injected with PBS medium. 2, 4, and 8 weeks later samples of femoral head were obtained to undergo CT, histological examination, and capillary ink infusion so as to observe the angiogenesis and osteogenesis.The pcDNA3.1(+)-hHGF transfected osteoblasts showed stable expression of hHGF. The numbers of newly formed vessels of the femoral heads of the group transfected with pcDNA3.1(+)-hHGF-transfected osteoblasts 2 and 4 weeks later were (29.47 +/- 1.64) and (34.02 +/- 1.72)/cm2 respectively, both significantly higher than those of the group transfected with blank plasmid-transfected osteoblasts [(20.61 +/- 1.91) and (25.57 + 2.20)/cm2 respectively, both P0. 01]. Eight weeks later the numbers of mature trabecular bone and bone marrow of Groups A and B were significantly higher than those of Group C.Core decompression combined with transplantation of HGF gene-modified osteoblasts promotes angiogenesis, enhances bone formation, and improves the restoration of avascular necrosis of femoral head.
- Published
- 2008
30. Relationship among bone mineral density, collagen composition, and biomechanical properties of callus in the healing of osteoporotic fracture
- Author
-
Bin, Shen, Jian-xiong, Mu, and Fu-xing, Pei
- Subjects
Fracture Healing ,Isoenzymes ,Male ,Rats, Sprague-Dawley ,Bone Density ,Tartrate-Resistant Acid Phosphatase ,Acid Phosphatase ,Animals ,Collagen ,Bony Callus ,Collagen Type I ,Biomechanical Phenomena ,Rats - Abstract
To study the change and relationship among bone mineral density (BMD), collagen composition and biomechanical properties of the callus in the healing process of osteoporotic fracture.The osteoporotic rat model and fracture model were established through bilateral ovariectomy (OVX) and osteotomy of the middle shaft of the right hind tibiae, respectively. Ninety female SD rats were randomly divided into OVX group and sham group. With the samples of blood and callus, roentgenographic and histological observation were performed for the assessment of the healing progress of the fracture, and the serum concentration of TRAP-5b, proportion of type I collagen, BMD and biomechanical properties of the callus were measured.The OVX group experienced a significant delay of fracture healing. The mean serum concentration of TRAP-5b of rats in the OVX group was much higher than that in the sham group after the operation (P less than 0.05), but the difference at the same time point after fracture was smaller than that before fracture (P less than 0.05). The BMD of the callus in both groups reached the peak value at the 6 th week after fracture while the proportion of the type I collagen and the biomechanical strength reached the peak at the 8th week.The deficiency of estrogen after the ovariectomy could induce the up-regulation of the osteoclasts activities, whereas the potency of further activation after fracture was depressed. Although the synthesis of collagen together with its mineralization determines the biomechanical properties of new bone, the accumulation of collagen could be assessed as an index in the prediction of biomechanical strength of bones independent of the bone mineral deposition.
- Published
- 2007
31. [Establishment of orthotopic model of MG-63 osteosarcoma]
- Author
-
Wei, Li, Jian-Cheng, Zeng, Fu-Xing, Pei, and Qiang, Huang
- Subjects
Male ,Disease Models, Animal ,Mice ,Osteosarcoma ,Cell Transformation, Neoplastic ,Cell Line, Tumor ,Animals ,Humans ,Mice, Nude ,Female ,Femur ,Tomography, X-Ray Computed ,Cell Proliferation - Abstract
To establish an orthotopic transplantation model of human osteosarcoma in nude mice.The cell suspensions of serial passage of MG-63 cell line with high tumor formation rate were implanted into the distal femur of nude mice. The tumor tissue were treated with routine pathologic HE stain and observed under microscope, and made to the x-ray inspection.In two weeks, the neoplasm was found to grow at local tissue of nude mice, and also found in x-ray film when it was after implant operated for 4 weeks. The typical characteristics of osteosarcoma of tumor tissue were found under microscope. The tumor formation rate of tumor tissue transplantation was 100% and the tumor formation rate of MG-63 cell suspension was 70%.The orthotopic transplantation model of osteosarcoma in nude mice is well established and provides a more similar human internal milieu for researches of osteosarcoma.
- Published
- 2007
32. Changes of microstructure and mineralized tissue in the middle and late phase of osteoporotic fracture healing in rats
- Author
-
Ying-jie, Hao, Hao, Yingjie, Ge, Zhang, Zhang, Ge, Yi-sheng, Wang, Wang, Yisheng, Ling, Qin, Qin, Ling, W Y, Hung, Kwoksui, Leung, Leung, Kwoksui, Fu-xing, Pei, and Pei, Fuxing
- Subjects
medicine.medical_specialty ,Histology ,Time Factors ,Tomography Scanners, X-Ray Computed ,Bone density ,Physiology ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Dentistry ,Bone healing ,Rats, Sprague-Dawley ,Bone Density ,medicine ,Animals ,Quantitative computed tomography ,Bone mineral ,Fracture Healing ,Femur fracture ,medicine.diagnostic_test ,business.industry ,medicine.disease ,Surgery ,Osteotomy ,Rats ,Callus ,Ovariectomized rat ,Female ,Stress, Mechanical ,business - Abstract
Background: With osteoporosis emerged as one of the most important health issues, more and more investigations are focusing on osteoporotic fracture healing. However, there are few studies on the changes of microstructure and mineralized tissue of newly formed callus. Objective: We established an osteoporotic fracture rat model to evaluate the changes of microstructure and mineralized tissue during osteoporotic fracture healing. Materials and methods: A mid-shaft femur fracture model was established 12 weeks after ovariectomy as an osteoporotic fracture group (OPF group). Femurs were then harvested at 4 weeks, 8 weeks and 12 weeks after fracture for peripheral quantitative computed tomography (pQCT), micro-computed tomography (MicroCT), histology and biomechanical test. A sham-operated group was used for comparison, i.e. the normal fracture group (NF group). Results: The pQCT-derived total external callus area in the OPF group was smaller than that in the NF group at 4 weeks after fracture (Pb0.05), whereas it was 21% larger in the OPF group than that in the NF group at 12 weeks after fracture (Pb0.01). The pQCT-derived bone mineral density in the OPF group was significantly inferior to the NF group at all the time points (Pb0.05 for all the time points, respectively). MicroCT data, at 12 weeks after fracture, showed the total callus, bony callus, and newly formed bone was approximately 20% lower in the OPF group than that in the NP group, and the total connectivity was 56% lower in the OPF group as compared to the NF group. Biomechanical test data, at 12 weeks after fracture, showed that the failure load of the left femur of OPF group was 17% less compared to that of the NF group (Pb0.01), and 15% lower bending stiffness (Pb0.05), 20% lower bending stress (Pb0.01), and 28% lower energy at failure (Pb0.01) were observed in the OPF group as compared to the NF group. Conclusion: The decrease in mineralized tissue and the not well connected microstructure in newly formed callus may explain the decline of mechanical impairment of fracture healing in the ovariectomized rats.
- Published
- 2007
33. [Experimental study on the proliferation and function of osteoblast cell induced by pBLAST49-mVEGF gene transfection]
- Author
-
Gang, Zhong, Fu-xing, Pei, Sheng-fu, Li, and Yu-bo, Fan
- Subjects
Rats, Sprague-Dawley ,Vascular Endothelial Growth Factor A ,Osteoblasts ,Animals, Newborn ,Cell Cycle ,Animals ,Transfection ,Immunohistochemistry ,Cells, Cultured ,Collagen Type I ,Cell Proliferation ,Rats - Abstract
To assess the effects of extra VEGF gene expression on the proliferation of osteoblast cell.The extra VEGF gene was induced into osteoblast cell. Then the expression of extra VEGF gene was detected, and its effects on the cell proliferation curve, cell cycle, on the synthesis of type I collagen and on the secretion of osteocalcium of osteoblast cell were investigated.At the first two days of culture, the cell number of pBLAST49-mVEGF gene transfer group was larger than that of the control group, yet no statistically significant difference was seen between the two groups (P0.05); however, significant difference was observed from the 3rd day of culture (P0.05). The (G2/M+S)% of the 1-5 generation osteoblast cell in pBLAST49-mVEGF gene transfer group was higher than that of the control group, there was significant difference between them (P0.05). The concentration of osteocalcium and expression of type I collagen of the 1-5 generation osteoblast cell in pBLAST49-mVEGF gene transfer group were significantly higher than those of the control group (P0.05).pBLAST49-mVEGF gene transfer can improve the proliferation and function of osteoblast cell.
- Published
- 2006
34. Expression and effect of Caspase-3 in neurons after tractive spinal cord injury in rats
- Author
-
Lei, Liu, Fu-xing, Pei, Kang-lai, Tang, Jian-zhong, Xu, and Qi-hong, Li
- Subjects
Rats, Sprague-Dawley ,Caspase 3 ,Caspases ,In Situ Nick-End Labeling ,Animals ,Apoptosis ,Flow Cytometry ,Immunohistochemistry ,Spinal Cord Injuries ,Rats - Abstract
To investigate Caspase-3 expression and its role in neuronal apoptosis.The T13-L2 spinal cord of rats was injured by traction after the amplitude of P1-N1 wave, monitored by a cortical somatosensory evoked potential (CSEP) monitor, decreased to seventy percent of that before operation. Then rats were killed in 6 h, 1 d, 4 d, 7 d, 14 d and 21 d respectively after operation. Flow cytometer terminal deoxynucleotldyl transferease-mediated biotinylated deoxynuridine triphosphate nick end labeling (TUNEL), Caspase-3 activity assay and immunohistochemical method were applied to investigate Caspase-3 expression in the spinal cord tissue and to study neuronal apoptosis in rats.After spinal cord injury, apoptotic cells detected by flow cytometry and TUNEL-positive cells were significantly more, and positive immunohistochemical staining of Caspase-3 and Caspase-3 activity were significantly higher in Group injury than in Groups control and laminectomy, respectively (P0.05, P0.01). Similar trend of changes was noticed in apoptotic cells, TUNEL-positive cells and positive immunohistochemical staining of Caspase-3, all of which reached their respective peak 7 days after operation. Caspase-3 activity reached its peak, however, 4 days postoperatively.Increased expression and activity of Caspase-3 protein in neurons after tractive spinal cord injury is the biochemical signal of early spinal cell apoptosis. It is of great significance for understanding the mechanism of spinal cord injury.
- Published
- 2005
35. [Effect of basic fibroblast growth factor on change of caspase 3 gene expression after distractive spinal cord injury in rats]
- Author
-
Lei, Liu, Fu-xing, Pei, Kang-lai, Tang, Jian-zhong, Xu, and Qi-hong, Li
- Subjects
Male ,Neurons ,Rats, Sprague-Dawley ,Random Allocation ,Caspase 3 ,Caspases ,Evoked Potentials, Somatosensory ,Animals ,Apoptosis ,Female ,Fibroblast Growth Factor 2 ,Spinal Cord Injuries ,Rats - Abstract
To observe the effects of basic fibroblast growth factor (bFGF) on neuronal apoptosis and caspase 3 gene expression after spinal cord injury.Forty-five SD rats were randomly divided into 3 equal groups: normal group (n = 5, with the spinal cord intact), treatment group [n = 20, with their spinal cord at T13-L2 injured by distraction till the cortical somatosensory evoked potential (CSEP) decreased by 70% and then a thin plastic tube inserted into the subarachnoid cavity below the injured level for perfusion of bFGF 20 microg immediately, and 1, 2, 3, 4, 8, 12, and 24 hours after injury], and control group (n = 20, with their spinal cord at T13-L2 injured by distraction till the CSEP decreased by 70% and then a thin plastic tube inserted into the subarachnoid cavity below the injured level for perfusion of normal saline of the same volume at the same time points). CSEP was tested by electrophysiological technique to record the latent time of P1 wave and the amplitude of P1-N1. Combined behavioral score (CBS) was used to evaluate the function of spinal cord, including motivation, sensation, reflex, and coordination of actions. The rats were killed at the days 1, 4, 7, 14, and 21 postoperatively. A segment of spinal cord T13-L2 1.5 cm long was taken out to be fixed and sliced. Flow cytometry was used to detect the neuronal cell apoptosis. Imunohistochemistry and TUNEL were used to examine the expression of caspase 3.The CBS value of the normal group was 0, and the CBS values at different time points of the treatment group were all lower than those of the control group (P0.05 or P0.05). The values of latent time of P1 wave 4 approximately 21 days after injury of the 2 injury groups were all longer than that of the normal group, those of the treatment group being significantly shorter than those of the control group. The values of P1-N1 amplitude 4 approximately 21 days after injury of the 2 injury groups were all lower than that of the normal group, those of the treatment group being significantly lower than those of the control group (P0.05 or P0.01). TUNEL showed that the apoptotic cell numbers at different time points of the 2 injury groups were lower than that of the normal group, those of the treatment group being significantly lower than those of the control group (P0.05 or P0.01). Immunohistochemistry showed that the numbers of caspase 3 positive cells at different time points of the 2 injury groups were all lower than that of the normal group, those of the treatment group being significantly lower than those of the control group (P0.05 or P0.01). The active fluorescence values at different time points of the 2 injury groups were all higher than those of the normal group, those of the treatment group being significantly lower than those of the control group (P0.05 or P0.01).bFGF inhibits the expression of caspase 3 protein, reduces the caspase 3 activity, lessens the secondary cell apoptosis in the injured spinal cord, and promotes nerve function recovery of spinal cord.
- Published
- 2005
36. Effect of basic fibroblast growth factor on the expression of glial fibrillary acidic protein after tractive spinal cord injury in rats
- Author
-
Lei, Liu, Bo, Lü, Chong-qi, Tu, Lei-ting, Chi, Guang-lin, Wang, and Fu-xing, Pei
- Subjects
Rats, Sprague-Dawley ,Disease Models, Animal ,Reference Values ,Traction ,Evoked Potentials, Somatosensory ,Glial Fibrillary Acidic Protein ,Animals ,Fibroblast Growth Factor 2 ,Recovery of Function ,Immunohistochemistry ,Spinal Cord Injuries ,Rats - Abstract
To investigate the effects of basic fibroblast growth factor (bFGF) on the expression of glial fibrillary acidic protein (GFAP) after tractive spinal cord injury in rats and to explore the recovery of spinal cord function.The rats were subjected to tractive spinal cord injury at T13-L2. Cortical somatosensory-evoked potential (CSEP) was closely monitored and when P1-N1 wave amplitude decreased to 70% of that before operation, a small-bore catheter was inserted below the injured plane through subarachnoid cavity. In the treatment groups, 20 microl of bFGF solution (containing 20 microg of bFGF) was injected through the catheter right after the operation and 1, 2, 3, 4, 8, 12 and 24 h postoperatively. In the control group, same volume of normal saline was injected and every four rats were killed at 1, 4, 7, 14 and 21 d after the operation. Combined behavior score (CBS) and electro-physiological examination were adopted to evaluate function recovery. Expression of GFAP was observed by immuno-histochemical staining and was analyzed quantitatively by computer image analysis.There was statistically significant difference in GFAP-positive cells between bFGF treatment group and the control group (P0.01). Similar tendency was indicated by the results of CBS and CSEP.bFGF can induce large expression of GFAP after tractive spinal cord injury in rats and promote spinal function recovery, which is highly important for spinal cord regeneration.
- Published
- 2005
37. [An experimental study of cell apoptosis and correlative gene expression after tractive spinal cord injury in rats]
- Author
-
Lei, Liu, Bin, Shen, Jing, Yang, Bo, Lü, Xiao-ning, Yang, Zong-ke, Zhou, and Fu-xing, Pei
- Subjects
Male ,Rats, Sprague-Dawley ,Disease Models, Animal ,Proto-Oncogene Proteins c-bcl-2 ,Animals ,Gene Expression ,Apoptosis ,Female ,Genes, p53 ,Spinal Cord Injuries ,Genes, bcl-2 ,Rats ,bcl-2-Associated X Protein - Abstract
To observe the cell apoptosis after tractive spinal cord injury in rats, determine expression of apoptosis correlative genes, and study the molecular mechanism of cell apoptosis.The T(13)-L(2) spinal cord of rats was injured by traction after the amplitude of P1-N1 wave decreased to 70% in postoperation than in preoperation through cortical somatosensory evoked potential (CSEP) monitor. Then rats were killed in 30 min, 6 h, 1, 4, 7, 14 and 21 d respectively after operation (n = 4). Cell apoptosis was examined by the flow cytometer and terminal deoxynucleotidyl transferase-mediated DUTP-biotin nick end labeling (TUNEL) reaction, the expression of p53, bax and bc1-2 genes was tested with immunohistochemistry.The flow cytometer test and TUNEL method showed that the apoptosis cell ratio raised in 6 h and reached at peak in 7 d after injury, and then declined till 21 d, they showed significant difference (P0.05, 0.01). TUNEL method showed that injured group had a large number of apoptosis glial cells in white matter. Immunohistochemical staining showed that the positive expression of p53, bax and bc1-2 protein raised at 6 h, expression of p53 protein reached at peak in 4 d, bax and bc1-2 protein reached at peak in 7 d after injury. Compared with control group and laminectomy group, the injured group showed significant difference (P0.05, 0.01).There is cell apoptosis phenomenon after tractive spinal cord injury in rats. Morphology indicates that apoptosis includes neurons and glialcytes, which is an important form of cell death and pathological changes in secondary lesion period after tractive spinal cord. There exist high expression of apoptosis correlative gene p53 and bax after spinal cord injury, they may play an important role in reduction of cells to apoptosis.
- Published
- 2005
38. Observation and establishment of an animal model of tractive spinal cord injury in rats
- Author
-
Lei, Liu, Lei-Ting, Chi, Zhong-Qi, Tu, Bin, Sheng, Zong-Ke, Zhou, and Fu-Xing, Pei
- Subjects
Male ,Rats, Sprague-Dawley ,Traction ,Models, Animal ,Animals ,Female ,Spinal Cord Injuries ,Rats - Abstract
To establish an animal model of tractive spinal cord injury in rats in order to investigate its pathophysiological changes and clinical significance.T(12)-L(3) spines were tracted longitudinally with a special spinal retractor that was put on the proccessus transverses of T(12)-L(3) vertebrae of the rat after exposing T(13)-L(2) spinal cord via dual laminectomy. At the same tine, the spinal cord function was monitored by cortical somatosensory evoked potential (CSEP). Rats were randomly divided into four groups according to the amplitude of CSEP P(1)-N(1) wave, the amount of the decreasing P(1)-N(1) wave was 30% (the 30% group), 50% (the 50% group) and 70% (the 70% group), respectively. After traction, the changes of the neural behavioral function in rats were observed and the morphological structure of the spinal cord was analyzed quantitatively with image analysis system of computer.With traction of spine, compared with the control group, the 30% group had no marked difference in combined behavioral score (CBS), neuron count, section area of neuron and Nissl body density, but the 50% and 70% groups had marked difference (P0.01). Light microscope showed that the neuron volume was slightly small and the Nissl body was reduced lightly in the 30% group; the neuron space was enlarged and the neuron was degenerative, reductive, and dissolved, and the spinal cord structure was destroyed in the 50% and 70% groups.The animal model of tractive spinal cord injury in rats is a reproducible, graded and clinic mimic. The model in this article provides a valuable assistance in further understanding etiopathology and screening effective measures of therapy and prophylaxis of the injury.
- Published
- 2004
39. [Effect of interleukin-1 on expression of interleukin-1 receptor in KM mice sciatic nerves before and after injuries]
- Author
-
Ji-shan, Yuan, Fu-xing, Pei, and Zhi-ming, Yang
- Subjects
Male ,Disease Models, Animal ,Mice ,Animals ,Receptors, Interleukin-1 ,Schwann Cells ,Immunohistochemistry ,Sciatic Nerve ,Interleukin-1 ,Nerve Regeneration - Abstract
To study the expression of interleukin-1 receptor in normal mice sciatic nerves and in transected sciatic nerves treated with or without extrinsic interleukin-1 locally at different periods.Seventy-two KM mice were equally divided into two groups. All the left sciatic nerves were transected. The stumps in experimental group were soaked in liquid with interleukin-1, whereas those in control group without interleukin-1. Then all the stumps were repaired end to end. At the 3rd hour, 1st day, 3rd day, 7th day, 14th day, and 28th day after operation respectively, every proximal stump was dissected and the expression of interleukin-1 receptor was carried out by immunohistochemistry method (LSAB method). The expression level of interleukin-1 of ten normal sciatic nerves of mice was studied, too.Normal nerves showed interleukin-1 receptor expression on the membrane of Schwann cells. After nerve injury, the interleukin-1 receptor expression increased biphasically in both groups, but the intensity of increase was lower in the experimental group than in the control group.Schwann cell is the target cell of interleukin-1.
- Published
- 2003
40. Light enhances hydrodynamic signaling in the multimodal caudal photoreceptor interneurons of the crayfish
- Author
-
Xing Pei, Lon A. Wilkens, and Frank Moss
- Subjects
Physics ,Backward walking ,Communication ,CPR activity ,Physiology ,business.industry ,General Neuroscience ,Stimulation ,Astacoidea ,Crayfish ,Tonic (physiology) ,Ganglion ,Light intensity ,medicine.anatomical_structure ,Abdominal ganglion ,Interneurons ,Neural Pathways ,medicine ,Animals ,Photoreceptor Cells, Invertebrate ,business ,Neuroscience ,Photic Stimulation - Abstract
1. The caudal photoreceptor (CPR) interneurons in the sixth abdominal ganglion of the crayfish are complex, multi-modal interneurons. These cells respond directly to light with tonic spike discharges, and they integrate synaptic input from an array of fili-form mechanoreceptors on the tailfan. They also provide input to rostral command centers, inducing backward walking at high firing frequencies, and thus directly influence behavior. 2. We recorded CPR activity in response to weak hydrodynamic stimulation of the tailfan mechanoreceptors while under varying intensities of light shined on the sixth ganglion. Spike trains were characterized according to the mean discharge rate (MDR) and the power spectrum from which the signal-to-noise ratio (SNR) was calculated. 3. Illumination of the CPR enhances the efficiency of transmitting mechanosensory signals. It does so by increasing the SNR of mechanosensory input received from tailfan receptors. A sevenfold, nonlinear increase in the SNRs was observed with increasing light intensity, an effect especially pronounced for weak hydrodynamic stimuli. In comparison with the dark, illumination of the ganglion lowered the hydrodynamic threshold and heightened the response to suprathreshold stimulation. Unlike the SNR, the MDR is little affected by mechanosensory input. 4. These results are compared with simulated electronic activity from an analogue threshold model and are discussed with respect to the mechanism of stochastic resonance.
- Published
- 1996
41. Detecting low dimensional dynamics in biological experiments
- Author
-
Xing Pei and Frank Moss
- Subjects
Computer Networks and Communications ,business.industry ,Stochastic process ,Computer science ,Dynamics (mechanics) ,Action Potentials ,Sensory system ,General Medicine ,Astacoidea ,Action (physics) ,Ganglia, Invertebrate ,Nonlinear system ,Nonlinear Dynamics ,Animals ,Photoreceptor Cells, Invertebrate ,Artificial intelligence ,Noise (video) ,Limit (mathematics) ,business ,Biological system ,Constant (mathematics) ,Mechanoreceptors ,Photic Stimulation - Abstract
We discuss the well-known problems associated with efforts to detect and characterize chaos and other low dimensional dynamics in biological settings. We propose a new method which shows promise for addressing these problems, and we demonstrate its effectiveness in an experiment with the crayfish sensory system. Recordings of action potentials in this system are the data. We begin with a pair of assumptions: that the times of firings of neural action potentials are largely determined by high dimensional random processes or “noise”; and that most biological files are non stationary, so that only relatively short files can be obtained under approximately constant conditions. The method is thus statistical in nature. It is designed to recognize individual “events” in the form of particular sequences of time intervals between action potentials which are the signatures of certain well defined dynamical behaviors. We show that chaos can be distinguished from limit cycles, even when the dynamics is heavily contaminated with noise. Extracellular recordings from the crayfish caudal photoreceptor, obtained while hydrodynamically stimulating the array of hair receptors on the tailfan, are used to illustrate the method.
- Published
- 1996
42. Characterization of low-dimensional dynamics in the crayfish caudal photoreceptor
- Author
-
Xing Pei and Frank Moss
- Subjects
Infinite set ,Multidisciplinary ,Series (mathematics) ,Ecology ,Noise (signal processing) ,Dynamics (mechanics) ,Action Potentials ,Astacoidea ,Biology ,Crayfish ,Characterization (materials science) ,Nonlinear Dynamics ,Dissipative system ,Animals ,Photoreceptor Cells, Invertebrate ,Biological system ,Deterministic system - Abstract
ATTEMPTS to detect and characterize chaos in biological systems are of considerable interest, especially in medical science, where successful demonstrations may lead to new diagnostic tools and therapies1. Unfortunately, conventional methods for identifying chaos often yield equivocal results when applied to biological data2–8, which are usually heavily contaminated with noise. For such applications, a new technique1 based on the detection of unstable periodic orbits holds promise. Infinite sets of unstable periodic orbits underlie chaos in dissipative systems4,9; accordingly, the new method searches a time series only for rare events8 characteristic of these unstable orbits10, rather than analysing the structure of the series as a whole. Here we demonstrate the efficacy of the method when applied to the dynamics of the crayfish caudal photoreceptor (subject to stimuli representative of the animal's natural habitat). Our findings confirm the existence of low-dimensional dynamics in the system, and strongly suggest the existence of deterministic chaos. More importantly, these results demonstrate the power of methods based on the detection of unstable periodic orbits for identifying low-dimensional dynamics—and, in particular, chaos—in biological systems.
- Published
- 1996
43. Extensive disinhibitory region beyond the classical receptive field of cat retinal ganglion cells
- Author
-
Chao-Yi Li, Xing Pei, Xing-Zhen Xu, Yi-Xiong Zhou, Fang-Tu Qiu, and Cheng-Quan Tang
- Subjects
Physics ,Retinal Ganglion Cells ,Retina ,Time Factors ,Optic tract ,Neural Inhibition ,Optic Nerve ,Stimulus (physiology) ,Retinal ganglion ,Sensory Systems ,Tonic (physiology) ,Photometry ,Ophthalmology ,Electrophysiology ,medicine.anatomical_structure ,Pattern Recognition, Visual ,Receptive field ,Optic nerve ,medicine ,Cats ,Animals ,Neuroscience ,Photic Stimulation - Abstract
Forty-three single fibres were recorded from cat optic tract. They were tested with flashing lines of different lengths and/or spots of different dimensions. The area of centre excitation and of surround inhibition were represented in the length (or dimension)-response functions by the steep rising and falling phases, respectively. For most of the cells, a secondary gentle rise was seen when the stimulus extended beyond the inhibitory surround, indicating an extensive disinhibitory region (DIR) outside the classical receptive field (RF). Disinhibition appeared and developed concurrently with surround inhibition at stimulus intensities between 3 and 30 cd/m2, being represented in the phasic or the tonic component of responses depending on the cell type recorded.
- Published
- 1992
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