38 results on '"Xiaohong Song"'
Search Results
2. Comparison of pancreatic microcirculation profiles in spontaneously hypertensive rats and Wistar-kyoto rats by laser doppler and wavelet transform analysis
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Honggang Zhang, Ruijuan Xiu, Mingming Liu, Xiaohong Song, Ailing Li, Jian Zhang, Yuan Li, and Bing Wang
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Male ,0301 basic medicine ,medicine.medical_specialty ,Physiology ,Wavelet Analysis ,Blood Pressure ,Vasomotion ,030204 cardiovascular system & hematology ,Nitric Oxide ,Rats, Inbred WKY ,Microcirculation ,Superoxide dismutase ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Griess test ,Enos ,Rats, Inbred SHR ,Internal medicine ,Laser-Doppler Flowmetry ,medicine ,Animals ,Pancreas ,Endothelin-1 ,biology ,Chemistry ,Articles ,General Medicine ,Laser Doppler velocimetry ,Malondialdehyde ,biology.organism_classification ,Rats ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Hypertension ,biology.protein ,Perfusion - Abstract
Pancreatic microcirculatory dysfunction emerged as a novel mechanism in the development of hypertension. However, the changes of pancreatic microcirculation profiles in hypertension remain unknown. Pancreatic microcirculatory blood distribution pattern and microvascular vasomotion of spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs) were determined by laser Doppler. Wavelet transform analysis was performed to convert micro-hemodynamic signals into time-frequency domains, based on which amplitude spectral scalograms were constructed. The amplitudes of characteristic oscillators were compared between SHRs and WKYs. The expression of eNOS was determined by immunohistochemistry, and plasma nitrite/nitrate levels were measured by Griess reaction. Additionally, endothelin-1, malondialdehyde, superoxide dismutase and interleukin-6 were determined by enzyme-linked immunosorbent assay. SHRs exhibited a lower scale blood distribution pattern with decreased average blood perfusion, frequency and amplitude. Wavelet transform spectral analysis revealed significantly reduced amplitudes of endothelial oscillators. Besides reduced expression of eNOS, the blood microcirculatory chemistry complements micro-hemodynamic profiles as demonstrated by an increase in plasma nitrite/nitrate, endothelin-1, malondialdehyde, interleukin-6 and a decrease of superoxide dismutase in SHRs. Here, we described abnormal pancreatic microcirculation profiles in SHRs, including disarranged blood distribution pattern, impaired microvascular vasomotion and reduced amplitudes of endothelial oscillators.
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- 2020
3. Pancreatic Microcirculation Profiles in the Progression of Hypertension in Spontaneously Hypertensive Rats
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Bing Wang, Jian Zhang, Ruijuan Xiu, Ailing Li, Yuan Li, Xiaohong Song, Mingming Liu, and Honggang Zhang
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medicine.medical_specialty ,hypertension ,Endothelium ,Original Contributions ,Ajhype/Ajh-03 ,Wavelet Analysis ,Vasomotion ,Blood Pressure ,030204 cardiovascular system & hematology ,Rats, Inbred WKY ,Microcirculation ,Superoxide dismutase ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,microcirculation profiles ,Internal medicine ,Malondialdehyde ,Rats, Inbred SHR ,oscillator ,Internal Medicine ,medicine ,Animals ,AcademicSubjects/MED00200 ,Pancreas ,030304 developmental biology ,0303 health sciences ,blood distribution pattern ,biology ,Endothelin-1 ,business.industry ,Superoxide Dismutase ,Hemodynamics ,microvascular vasomotion ,Rats ,Vasomotor System ,medicine.anatomical_structure ,Endocrinology ,Blood pressure ,chemistry ,biology.protein ,Disease Progression ,Blood Vessels ,AcademicSubjects/SCI00960 ,business ,Perfusion - Abstract
BACKGROUND Emerging evidence indicates that the pancreas serves as a major source of degrading protease activities and that uncontrolled proteolytic receptor cleavage occurs under hypertensive conditions, which leading to systemic dysfunction and end-organic damage. However, changes in pancreatic microcirculation profiles during the progression of hypertension remain unknown. METHODS Pancreatic microcirculatory blood distribution patterns and microvascular vasomotion of spontaneously hypertensive rats (SHRs) and normotensive control Wistar Kyoto rats at 5, 8, 13, and 18 weeks of age were determined. Wavelet transform analysis was performed to convert pancreatic microhemodynamic signals into time–frequency domains and construct 3-dimensional spectral scalograms. The amplitudes of characteristic oscillators including endothelial, neurogenic, myogenic, respiratory, and cardiac oscillators were compared among groups. Plasma nitrite/nitrate levels were measured using a Griess reaction. Additionally, endothelin-1, malondialdehyde, superoxide dismutase, and interleukin-6 levels were determined by enzyme-linked immunosorbent assay. RESULTS SHRs exhibited a reduced blood distribution pattern with progressively decreased average blood perfusion, amplitude, and frequency of microvascular vasomotion. Wavelet transform spectral analysis revealed significantly reduced amplitudes of endothelial oscillators from 8- to 18-week-old SHRs. Additionally, the blood microcirculatory chemistry complements explained the microhemodynamic profiles partially, as demonstrated by an increase in plasma nitrite/nitrate, endothelin-1, malondialdehyde, and interleukin-6 levels and a decreased superoxide dismutase level in SHRs. CONCLUSIONS Pancreatic microcirculation profiles are abnormal in the progression of hypertension in SHRs, including a disarranged blood distribution pattern, impaired microvascular vasomotion, and reduced amplitudes of endothelial oscillators., Graphical Abstract Graphical Abstract
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- 2020
4. Occurrence, distribution, and health risk assessment of quinolone antibiotics in water, sediment, and fish species of Qingshitan reservoir, South China
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Safdar Bashir, Honghu Zeng, Yuanmin Mo, Bin Kang, Xiaohong Song, Zhongbing Chen, Liangliang Huang, Saeed Rad, and Zhiqiang Wu
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Quality Control ,China ,Geologic Sediments ,Fish farming ,0211 other engineering and technologies ,Sewage ,lcsh:Medicine ,02 engineering and technology ,010501 environmental sciences ,Quinolones ,01 natural sciences ,Risk Assessment ,Article ,Toxicology ,Rivers ,Animals ,Turbidity ,lcsh:Science ,0105 earth and related environmental sciences ,021110 strategic, defence & security studies ,Multidisciplinary ,Health risk assessment ,Ecology ,business.industry ,lcsh:R ,Fishes ,Anti-Bacterial Agents ,Water resources ,Environmental sciences ,Wastewater ,Bioaccumulation ,Environmental science ,lcsh:Q ,Risk assessment ,business ,Water Pollutants, Chemical ,Environmental Monitoring - Abstract
The residual antibiotics in the environment have lately caused widespread concerns. However, little information is available on the antibiotic bioaccumulation and its health risk in drinking water resources of South China. Therefore, the occurrence, distribution, and health risk of four quinolone antibiotics including ofloxacin (OFX), norfloxacin (NOR), ciprofloxacin (CIP), and enrofloxacin (ENR) in the Qingshitan reservoir using high-performance liquid chromatography were investigated. Results revealed that the concentrations in water, sediment, and edible fish ranged from 3.49–660.13 ng/L, 1.03–722.18 μg/kg, and 6.73–968.66 μg/kg, respectively. The ecological risk assessment via the risk quotient (RQ) method showed that the values in sediment were all greater than 1, posing a high risk to the environment. The health risk index of water samples was at the maximum acceptable level, with OFX at the top while the rest were at the medium risk level. The main edible fish kinds of the reservoir had high dietary safety and the highest contaminations were found in carnivorous feeding habits and demersal habitat fishes with OFX as the highest magnitude. Source identification and correlation analysis using SPSS showed significant relationships between NOR with pH and turbidity (in water), as well as total phosphor (TP) and total organic carbon (TOC) in sediment. NOR was the highest in sediment which mostly sourced from livestock wastewater, croplands irrigation drain water, and stormwater. Correlations between CIP and ENR with TP were significant, while OFX was positively associated with total nitrogen (TN) which mainly originated from urban sewage as well as directly dosed drugs in fish farms. In conclusion, our results are of great significance for ensuring the safety of drinking water and aquatic products in this region.
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- 2020
5. Quantitative analysis of asbestos in drinking water and its migration in mice using fourier-transform infrared spectroscopy and inductively coupled plasma optical emission spectrometry
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Lijie Zang, Haitao Wang, Li Hongyan, Ming Zhang, Wentao Li, Bei Zheng, and Xiaohong Song
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Male ,Infrared spectroscopy ,Fresh Water ,02 engineering and technology ,medicine.disease_cause ,01 natural sciences ,Biochemistry ,Asbestos ,Analytical Chemistry ,Limit of Detection ,Spectroscopy, Fourier Transform Infrared ,medicine ,Animals ,Environmental Chemistry ,Least-Squares Analysis ,Fourier transform infrared spectroscopy ,Spectroscopy ,Optical emission spectrometry ,Mice, Inbred BALB C ,Chromatography ,Chemistry ,Drinking Water ,010401 analytical chemistry ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Liver ,Inductively coupled plasma ,0210 nano-technology ,Quantitative analysis (chemistry) ,Water Pollutants, Chemical - Abstract
The presence of asbestos in the environment has caused concern because exposure to asbestos can cause diseases such as stomach and pancreatic cancer. However, suitable up-to-date methods for quantitatively analyzing asbestos and assessing the toxicity of asbestos have not been developed. In this study, asbestos in drinking water was characterized using a stepwise multiple differential infra-red spectra method and a partial least squares method. The in vivo migration of ingested asbestos in mice was then investigated using the technique. The quantification limit of six kinds of asbestos by using inductively coupled plasma optical emission spectrometry and Fourier-transform infrared spectroscopy in water are respectively from 0.0468 to 0.0705 mg/L, from 0.0039 to 0.0064 mg/L. The relative standard deviations were respectively less than 2.85% and 3.81%. The recoveries of the test asbestos were respectively more than 95.10% and 95.38%. Asbestos was found mainly to accumulate in the livers of mice. The Fourier-transform infra-red spectroscopy inductively coupled plasma optical emission spectrometry method can be used to detect and precisely quantify asbestos in water samples and in animal tissues.
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- 2019
6. Tetanus vaccine-induced human neutralizing antibodies provide full protection against neurotoxin challenge in mice
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Liu Yujiao, Zhang Guanying, Meng Hao, Shuling Liu, Pengfei Fan, Chen Yi, Rui Yu, Peng Du, Xiaohong Song, Chen Zhengshan, Yu Changming, Dong Yunzhu, Wei Chen, Fang Ting, Chi Xiangyang, and Jianmin Li
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0301 basic medicine ,Diphtheria-Tetanus Vaccine ,Time Factors ,Clostridium tetani ,medicine.drug_class ,Immunology ,Biology ,medicine.disease_cause ,Monoclonal antibody ,Diphtheria-Tetanus-acellular Pertussis Vaccines ,Epitope ,03 medical and health sciences ,Epitopes ,0302 clinical medicine ,Immunogenicity, Vaccine ,Antibody Specificity ,medicine ,Tetanus Toxoid ,Immunology and Allergy ,Animals ,Humans ,Neutralizing antibody ,Pharmacology ,Mice, Inbred BALB C ,Tetanus ,Vaccination ,Toxoid ,Antibodies, Monoclonal ,medicine.disease ,Virology ,Antibodies, Bacterial ,Antibodies, Neutralizing ,body regions ,Disease Models, Animal ,030104 developmental biology ,Tetanus vaccine ,030220 oncology & carcinogenesis ,biology.protein ,Female ,Antibody ,medicine.drug - Abstract
Clostridium tetani causes life-threatening disease by producing tetanus neurotoxin (TeNT), one of the most toxic protein substances. Toxicosis can be prevented and cured by administration of anti-TeNT neutralizing antibodies. Here, we identified a series of monoclonal antibodies (mAbs) derived from memory B cells of a healthy adult immunized with the C-terminal domain of TeNT (TeNT-Hc). Thirteen mAbs bound to both tetanus toxoid (TT) and TeNT-Hc, while two mAbs recognized only TT. VH3-23 was the most frequently used germline gene in these TT-binding mAbs, and the pairwise identity values of the VH gene sequences ranged from 27% to 69%. Three of these mAbs—T3, T7, and T9-6—completely protected mice from challenge with 2× LD50 of TeNT, and two (T2 and T18) significantly prolonged the survival time. The five neutralizing mAbs recognized distinct epitopes on TT, with binding affinities ranging from 0.123 to 11.9 nM. Our study provides promising therapeutic candidates for tetanus.
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- 2020
7. Distinct expression patterns of seven crucial microRNAs during early embryonic development in medaka (Oryzias latipes)
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Xiaohong Song, Ramji K. Bhandari, and Xuegeng Wang
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Male ,Oryzias ,Embryonic Development ,Article ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,Genetics ,Animals ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Transition (genetics) ,biology ,Embryogenesis ,Gene Expression Regulation, Developmental ,Embryo ,biology.organism_classification ,Sperm ,Spermatozoa ,Cell biology ,MicroRNAs ,Expression (architecture) ,Oocytes ,Maternal to zygotic transition ,Female ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
MicroRNAs (i.e. miRNAs) are small non-coding RNAs that play essential modulation roles in embryonic development in vertebrates. Paternal and maternal miRNAs contribute to the development of post-fertilization embryo and zygotic genome activation. The pattern of expression and their roles in embryonic development of medaka are not clearly understood. The present study, therefore, examined a temporal expression of seven miRNAs, ola-let-7a, ola-miR-202-3p, ola-miR-126-3p, ola-miR-122, ola-miR-92a, ola-miR-125a-3p and ola-miR-430a in sperm, oocytes, and embryos during early developmental stages. Three unique expression patterns of miRNAs were observed. ola-let7a, ola-miR-202-3p and ola-miR-126-3p showed both paternal and maternal expression, and ola-miR-122, ola-miR-92a, ola-miR-125a-3p showed maternal expression only. The expression of six out of seven miRNAs significantly decreased after maternal-zygotic transition (MZT), whereas ola-miR-430a expression initiated only after MZT. The temporal dynamic expression of these miRNAs suggests their potential roles in early embryogenesis and genome-zygotic activation in medaka.
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- 2020
8. Multimodal Device and Computer Algorithm-Based Monitoring of Pancreatic Microcirculation Profiles In Vivo
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Bing Wang, Honggang Zhang, Ailing Li, Xiaohong Song, Ruijuan Xiu, Yuan Li, Jian Zhang, and Mingming Liu
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Male ,Time Factors ,Computer science ,Endocrinology, Diabetes and Metabolism ,Hemoglobin oxygen saturation ,Diagnostic Techniques, Cardiovascular ,Boundary values ,blood perfusion ,Partial oxygen ,Po2 - partial oxygen pressure ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Imaging, Three-Dimensional ,In vivo ,Internal Medicine ,medicine ,Animals ,Humans ,rHb - relative amount of hemoglobin ,IQR - interquartile range ,Pancreas ,Pancreatic microcirculation ,So2 - hemoglobin oxygen saturation ,3-D - 3-dimensional ,Mice, Inbred BALB C ,Hepatology ,Microcirculation ,hemoglobin oxygen saturation ,Hemodynamics ,Models, Cardiovascular ,Equipment Design ,Original Articles ,Computer algorithm ,Data set ,Oxygen ,pancreatic microcirculation profiles ,medicine.anatomical_structure ,PU - perfusion unit ,030220 oncology & carcinogenesis ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,partial oxygen pressure ,030211 gastroenterology & hepatology ,relative amount of hemoglobin ,Algorithms ,Biomedical engineering - Abstract
Supplemental digital content is available in the text., Objectives Pancreatic microcirculation has an essential role in orchestrating pancreatic homeostasis. Inherent complexity and technological limitation lead to interobserver variability and 1-sided microcirculatory data. Here, we introduce a multimodal device and computer algorithm–based platform for monitoring and visualizing integrated pancreatic microcirculation profiles. Methods After anesthetizing and exposing pancreas tissue of BALB/c mice, probes of Oxygen to See, Microx TX3, and MoorVMS-LDF2 were positioned at pancreas in situ to capture the pancreatic microcirculatory oxygen (hemoglobin oxygen saturation, relative amount of hemoglobin, and partial oxygen pressure) and microhemodynamic data (microvascular blood perfusion and velocity). To assess and visualize pancreatic microcirculation profiles, raw data of pancreatic microcirculation profiles were processed and transformed using interquartile range and min-max normalization by Python and Apache ECharts. Results The multimodal device–based platform was established and 3-dimensional microcirculatory modules were constructed. Raw data sets of pancreatic microcirculatory oxygen and microhemodynamic were collected. The outlier of data set was adjusted to the boundary value and raw data set was preprocessed. Normalized pancreatic microcirculation profiles were integrated into the 3-dimensional histogram and scatter modules, respectively. The 3-dimensional modules of pancreatic microcirculation profiles were then generated. Conclusions We established a multimodal device and computer algorithm–based monitoring platform for visualizing integrated pancreatic microcirculation profiles.
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- 2020
9. Fc-Based Recombinant Henipavirus Vaccines Elicit Broad Neutralizing Antibody Responses in Mice
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Ruihua Li, Wei Chen, Chen Yi, Xiaohong Song, Xiaodong Zai, Meirong Wang, Junjie Xu, Ying Yin, Yaohui Li, and Liu Yujiao
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0301 basic medicine ,henipavirus ,viruses ,lcsh:QR1-502 ,Enzyme-Linked Immunosorbent Assay ,Antibodies, Viral ,lcsh:Microbiology ,Article ,Virus ,Hendra Virus ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Viral Envelope Proteins ,Antigen ,Neutralization Tests ,Virology ,vaccine ,parasitic diseases ,Animals ,030212 general & internal medicine ,Neutralizing antibody ,Phylogeny ,Henipavirus Infections ,chemistry.chemical_classification ,Vaccines, Synthetic ,biology ,attachment glycoprotein ,Immunogenicity ,Nipah Virus ,virus diseases ,biology.organism_classification ,Fusion protein ,digestive system diseases ,Immunoglobulin Fc Fragments ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,chemistry ,biology.protein ,Glycoprotein ,Broadly Neutralizing Antibodies ,Henipavirus - Abstract
The genus Henipavirus (HNVs) includes two fatal viruses, namely Nipah virus (NiV) and Hendra virus (HeV). Since 1994, NiV and HeV have been endemic to the Asia&ndash, Pacific region and responsible for more than 600 cases of infections. Two emerging HNVs, Ghana virus (GhV) and Mojiang virus (MojV), are speculated to be associated with unrecognized human diseases in Africa and China, respectively. Despite many efforts to develop vaccines against henipaviral diseases, there is presently no licensed human vaccine. As HNVs are highly pathogenic and diverse, it is necessary to develop universal vaccines to prevent future outbreaks. The attachment enveloped glycoprotein (G protein) of HNVs mediates HNV attachment to the host cell&rsquo, s surface receptors. G proteins have been used as a protective antigen in many vaccine candidates for HNVs. We performed quantitative studies on the antibody responses elicited by the G proteins of NiV, HeV, GhV, and MojV. We found that the G proteins of NiV and HeV elicited only a limited cross-reactive antibody response. Further, there was no cross-protection between MojV, GhV, and highly pathogenic HNVs. We then constructed a bivalent vaccine where the G proteins of NiV and HeV were fused with the human IgG1 Fc domain. The immunogenicity of the bivalent vaccine was compared with that of monovalent vaccines. Our results revealed that the Fc-based bivalent vaccine elicited a potent antibody response against both NiV and HeV. We also constructed a tetravalent Fc heterodimer fusion protein that contains the G protein domains of four HNVs. Immunization with the tetravalent vaccine elicited broad antibody responses against NiV, HeV, GhV, and MojV in mice, indicating compatibility among the four antigens in the Fc-fusion protein. These data suggest that our novel bivalent and tetravalent Fc-fusion proteins may be efficient candidates to prevent HNV infection.
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- 2020
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10. Characterization of Two Neutralizing Antibodies against Rift Valley Fever Virus Gn Protein
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Shengnan Zhang, Shuling Liu, Changming Yu, Zhang Guanying, Chen Zhengshan, Meng Hao, Xianzhu Xia, Chi Xiangyang, Liu Yujiao, Pengfei Fan, Chen Yi, Xiaohong Song, Dong Yunzhu, and Jianmin Li
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0301 basic medicine ,Human Adenoviruses ,Models, Molecular ,Rift Valley fever virus ,Rift Valley Fever ,critical residues ,viruses ,030106 microbiology ,Molecular Conformation ,lcsh:QR1-502 ,Severe disease ,Enzyme-Linked Immunosorbent Assay ,Antibodies, Viral ,Virus ,Article ,lcsh:Microbiology ,law.invention ,Cell Line ,03 medical and health sciences ,Epitopes ,Structure-Activity Relationship ,Viral Envelope Proteins ,law ,Neutralization Tests ,Virology ,Animals ,Humans ,chemistry.chemical_classification ,biology ,rift valley fever virus (rvfv) ,Antibodies, Neutralizing ,Macaca mulatta ,neutralizing antibody (nab) ,030104 developmental biology ,Infectious Diseases ,chemistry ,biology.protein ,Recombinant DNA ,Immunization ,gn protein ,Antibody ,Glycoprotein ,Protein Binding - Abstract
The Rift Valley fever virus (RVFV) is an arthropod-borne virus that can not only cause severe disease in domestic animals but also in humans. However, the licensed vaccines or available therapeutics for humans do not exist. Here, we report two Gn-specific neutralizing antibodies (NAbs), isolated from a rhesus monkey immunized with recombinant human adenoviruses type 4 expressing Rift Valley fever virus Gn and Gc protein (rHAdV4-GnGcopt). The two NAbs were both able to protect host cells from RVFV infection. The interactions between NAbs and Gn were then characterized to demonstrate that these two NAbs might preclude RVFV glycoprotein rearrangement, hindering the exposure of fusion loops in Gc to endosomal membranes after the virus invades the host cell. The target region for the two NAbs is located in the Gn domain III, implying that Gn is a desired target for developing vaccines and neutralizing antibodies against RVFV.
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- 2020
11. Diversity and Complexity of the Large Surface Protein Family in the Compacted Genomes of Multiple Pneumocystis Species
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Koen K. A. Van Rompay, Yueqin Liu, Honghui Wang, Daniel Margolis, Jun Song, Robert V Blair, Richard A. Lempicki, Chao-Hung Lee, Christiane Weissenbacher-Lang, Bapi Pahar, Claire M. Jardine, Xiaohong Song, Geetha Kutty, Liang Ma, Vanessa M. Hirsch, Joseph A. Kovacs, Xilong Deng, Alice Latinne, Jamie L. Rothenburger, Antti Sukura, Jason M. Brenchley, Sabrina Thapar, Rebekah I. Keesler, Serge Morand, Li Peng, Melanie T. Cushion, Da-Wei Huang, Zehua Chen, Jie Xu, Lisa R. Bishop, Christina A. Cuomo, Ousmane H. Cissé, Magali Chabé, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Veterinary Biosciences, Helsinki One Health (HOH), Antti Sukura / Principal Investigator, Veterinary Pathology and Parasitology, and Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE)
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[SDV]Life Sciences [q-bio] ,Disease ,Pneumocystis pneumonia ,Genome ,ANTIGENIC VARIATION ,Phylogeny ,Immunodeficiency ,Mammals ,Genetics ,11832 Microbiology and virology ,0303 health sciences ,Membrane Glycoproteins ,1184 Genetics, developmental biology, physiology ,GLYCOPROTEIN ,RABBITS ,QR1-502 ,3. Good health ,classification ,EXPRESSION SITE ,major surface glycoprotein ,Genome, Fungal ,Research Article ,GENES ,Biology ,Microbiology ,SEQUENCE ,Host-Microbe Biology ,Evolution, Molecular ,Fungal Proteins ,03 medical and health sciences ,Phylogenetics ,Sequence Homology, Nucleic Acid ,Virology ,Antigenic variation ,medicine ,Animals ,WILD NORWAY RATS ,Gene ,030304 developmental biology ,IDENTIFICATION ,030306 microbiology ,Pneumocystis ,phylogenetic analysis ,Genetic Variation ,medicine.disease ,Rats ,SP NOV ,CARINII ,Adaptation ,conserved domains - Abstract
Pneumocystis continues to be a major cause of disease in humans with immunodeficiency, especially those with HIV/AIDS and organ transplants, and is being seen with increasing frequency worldwide in patients treated with immunodepleting monoclonal antibodies. Annual health care associated with Pneumocystis pneumonia costs ∼$475 million dollars in the United States alone. In addition to causing overt disease in immunodeficient individuals, Pneumocystis can cause subclinical infection or colonization in healthy individuals, which may play an important role in species preservation and disease transmission. Our work sheds new light on the diversity and complexity of the msg superfamily and strongly suggests that the versatility of this superfamily reflects multiple functions, including antigenic variation to allow immune evasion and optimal adaptation to host environmental conditions to promote efficient infection and transmission. These findings are essential to consider in developing new diagnostic and therapeutic strategies., Pneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multicopy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneumocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins and provide a detailed description of the classification, unique characteristics, and phylogenetic relatedness of five Msg families. We further describe, for the first time, the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. carinii from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests multiple functions for this superfamily rather than just conferring antigenic variation to allow immune evasion as previously believed. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology.
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- 2020
12. Histopathology and transcriptome reveals the tissue-specific hepatotoxicity and gills injury in mosquitofish (Gambusia affinis) induced by sublethal concentration of triclosan
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Huang Liangliang, Yan Xiaoyu, Xiaohong Song, Huang Yuequn, Li Xin, Xuegeng Wang, Yanpeng Liang, and Honghu Zeng
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Gills ,Male ,Gill ,medicine.medical_specialty ,animal structures ,Cytoplasmic inclusion ,Health, Toxicology and Mutagenesis ,0211 other engineering and technologies ,Histopathology ,02 engineering and technology ,010501 environmental sciences ,01 natural sciences ,Environmental pollution ,Transcriptome ,Cyprinodontiformes ,Random Allocation ,Anti-Infective Agents ,medicine ,Animals ,GE1-350 ,0105 earth and related environmental sciences ,021110 strategic, defence & security studies ,Dose-Response Relationship, Drug ,Mosquitofish ,Toxicity ,biology ,fungi ,Public Health, Environmental and Occupational Health ,Lipid metabolism ,General Medicine ,biology.organism_classification ,Pollution ,Molecular biology ,Triclosan ,Environmental sciences ,Liver ,TD172-193.5 ,Organ Specificity ,Lipogenesis - Abstract
Triclosan (TCS), a ubiquitous antimicrobial agent, has been frequently detected in wild fish, leading to concerns regarding TCS safety in the aquatic environment. The present work aims to investigate the TCS-mediated effects on various tissues (the liver, gills, brain, and testes) of wild-sourced adult mosquitofish based on histological analysis and transcriptome. Severe morphological injuries were only found in the liver and gills. The histopathological alterations in the liver were characterized by cytoplasmic vacuolation and degeneration, eosinophilic cytoplasmic inclusions, and nuclear polymorphism. The gill lesions contained epithelial lifting, intraepithelial edema, fusion and shortening of the secondary lamellae. Consistently, the numbers of differently expressed genes (DEGs) identified by transcriptome were in the order of liver (1627) > gills (182) > brain (9) > testes (4). Trend-aligned histopathological and transcriptomic changes in the 4 tissues, suggesting the tissue-specific response manner of mosquitofish to TCS, and the liver and gills were the target organs. TCS interrupted many biological pathways associated with lipogenesis and lipid metabolism, transmembrane transporters, protein synthesis, and carbohydrate metabolism in the liver, and it induced nonspecific immune response in the gills. TCS-triggered hepatotoxicity and gills damnification may lead to inflammation, apoptosis, diseases, and even death in mosquitofish. TCS showed moderate acute toxicity and bioaccumulative property on mosquitofish, suggesting that prolonged or massive use of TCS may pose an ecological risk.
- Published
- 2021
13. Developmental abnormalities and epigenetic alterations in medaka (Oryzias latipes) embryos induced by triclosan exposure
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Ramji K. Bhandari, Xuegeng Wang, and Xiaohong Song
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Epigenomics ,Male ,Embryo, Nonmammalian ,Environmental Engineering ,Methyltransferase ,Health, Toxicology and Mutagenesis ,Oryzias ,0208 environmental biotechnology ,02 engineering and technology ,Endocrine Disruptors ,010501 environmental sciences ,01 natural sciences ,Epigenesis, Genetic ,Andrology ,medicine ,Animals ,Environmental Chemistry ,Epigenetics ,Aromatase ,Yolk sac ,0105 earth and related environmental sciences ,biology ,fungi ,Embryogenesis ,Public Health, Environmental and Occupational Health ,Embryo ,General Medicine ,General Chemistry ,DNA Methylation ,biology.organism_classification ,Pollution ,Triclosan ,020801 environmental engineering ,Germ Cells ,medicine.anatomical_structure ,embryonic structures ,DNA methylation ,biology.protein ,Water Pollutants, Chemical - Abstract
Triclosan (TCS), an antibacterial and antifungal agent present in some consumer products, has been detected in the environment at varying concentrations. TCS exposure has been found to cause developmental abnormalities and endocrine disruption in various species of fish. It is not clearly understood whether TCS exposure causes epigenetic alterations in developing embryos and their germ cells. In the present study, we examined the effects of TCS exposure (0, 50, 100 and,200 μg/L) on embryonic development and primordial germ cells (PGCs), which are precursors of sperm and eggs, in medaka (Oyzias latipes). Developmental TCS exposure from 8 hours post-fertilization through 15 days post-fertilization (dpf) resulted in several developmental abnormalities, including enlarged yolk sac, decreased head trunk angle (HTA), and severe edema in the pericardial region. The male ratio increased in the 100 μg/L TCS exposure group, which was negatively correlated with the expression of cyp19ala (a gene encoding aromatase) and arα (androgen receptor alpha). Developmental 50 μg/L TCS exposure resulted in global hypomethylation in the whole body but not in the isolated PGCs. Expression of the gene encoding DNA methyltransferases (dnmt1 and dnmt3aa) was decreased by 50 μg/L TCS exposure both in the whole body and PGCs. TCS altered the expression of genes encoding enzymes involved in DNA methylation and demethylation in PGCs, suggesting epigenetic effects on germ cells. The present results demonstrate that the embryos exposed to the tested concentrations of TCS develop deformities during the early life stages and that the TCS within this range possesses an aromatase inhibitor property potential enough to alter sex ratios of developing embryos.
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- 2020
14. Immunization With a Novel Human Type 5 Adenovirus-Vectored Vaccine Expressing the Premembrane and Envelope Proteins of Zika Virus Provides Consistent and Sterilizing Protection in Multiple Immunocompetent and Immunocompromised Animal Models
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Kin-Hang Kok, Chris Chung-Sing Chan, Anna Jinxia Zhang, Cyril C. Y. Yip, Wei Chen, Jian-Piao Cai, Lihua Hou, Mengsu Zhao, Qiang Guo, Xiaohong Song, Kwok-Yung Yuen, Changpeng Ren, Shipo Wu, Busen Wang, Vincent Kwok-Man Poon, Wen Yanbo, Kwok-Hung Chan, and Jasper Fuk-Woo Chan
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0301 basic medicine ,viruses ,Genetic Vectors ,Antibodies, Viral ,Zika virus ,03 medical and health sciences ,Immunocompromised Host ,0302 clinical medicine ,Immune system ,Viral Envelope Proteins ,Immunity ,Immunology and Allergy ,Animals ,030212 general & internal medicine ,Neutralizing antibody ,Drug Carriers ,Immunity, Cellular ,Mice, Inbred BALB C ,Vaccines, Synthetic ,biology ,Zika Virus Infection ,Adenoviruses, Human ,virus diseases ,Animal Structures ,Viral Vaccines ,Zika Virus ,Viral Load ,biology.organism_classification ,Virology ,Antibodies, Neutralizing ,Immunity, Humoral ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,Blood ,Treatment Outcome ,Immunization ,biology.protein ,Female ,Antibody ,Immunocompetence ,Viral load - Abstract
Background Zika virus (ZIKV) infection may be associated with severe complications and disseminated via both vector-borne and nonvector-borne routes. Adenovirus-vectored vaccines represent a favorable controlling measure for the ZIKV epidemic because they have been shown to be safe, immunogenic, and rapidly generable for other emerging viral infections. Evaluations of 2 previously reported adenovirus-vectored ZIKV vaccines were performed using nonlethal animal models and/or nonepidemic ZIKV strain. Methods We constructed 2 novel human adenovirus 5 (Ad5)-vectored vaccines containing the ZIKV premembrane-envelope (Ad5-Sig-prM-Env) and envelope (Ad5-Env) proteins, respectively, and evaluated them in multiple nonlethal and lethal animal models using epidemic ZIKV strains. Results Both vaccines elicited robust humoral and cellular immune responses in immunocompetent BALB/c mice. Dexamethasone-immunosuppressed mice vaccinated with either vaccine demonstrated robust and durable antibody responses and significantly lower blood and tissue viral loads than controls (P < .05). Similar findings were also observed in interferon-α/β receptor-deficient A129 mice. In both of these immunocompromised animal models, Ad5-Sig-prM-Env-vaccinated mice had significantly (P < .05) higher titers of anti-ZIKV-specific neutralizing antibody titers and lower (undetectable) viral loads than Ad5-Env-vaccinated mice. The close correlation between the neutralizing antibody titer and viral load helped to explain the better protective effect of Ad5-Sig-prM-Env than Ad5-Env. Anamnestic response was absent in Ad5-Sig-prM-Env-vaccinated A129 mice. Conclusions Ad5-Sig-prM-Env provided sterilizing protection against ZIKV infection in mice.
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- 2017
15. [Screening of full human anthrax lethal factor neutralizing antibody in transgenic mice]
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Xiaolin, Wang, Xiangyang, Chi, Ju, Liu, Weicen, Liu, Shuling, Liu, Shunfang, Qiu, Zhonghua, Wen, Pengfei, Fan, Kun, Liu, Xiaohong, Song, Ling, Fu, Jun, Zhang, and Changming, Yu
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Anthrax ,Antigens, Bacterial ,Epitopes ,Mice ,Bacillus anthracis ,Bacterial Toxins ,Animals ,Humans ,Mice, Transgenic ,Antibodies, Monoclonal, Humanized ,Antibodies, Bacterial ,Antibodies, Neutralizing ,Respiratory Tract Infections - Abstract
Anthrax is a highly lethal infectious disease caused by the spore-forming bacterium Bacillus anthracis. The major virulence factor of B. anthracis consists of protective antigen (PA), lethal factor (LF) and edema factor (EF). PA binds with LF to form lethal toxin (LT), and PA binds with EF to form edema toxin (ET). Antibiotics is hard to work in advanced anthrax infections, because injuries and deaths of the infected are mainly caused by lethal toxin (LT). Thus, the therapeutic neutralizing antibody is the most effective treatment of anthrax. Currently most of the anthrax toxin antibodies are monoclonal antibodies (MAbs) for PA and US FDA has approved ABTHRAX humanized PA monoclonal antibody for the treatment of inhalational anthrax. Once B. anthracis was artificially reconstructed or PA had mutations within recognized neutralization epitopes, anti-PA MAbs would no longer be effective. Therefore, anti-LF MAbs is an important supplement for anthrax treatment. Most of the anti-LF antibodies are murine or chimeric antibodies. By contrast, fully human MAbs can avoid the high immunogenicity of murine antibodies. First, we used LF to immunize the transgenic mice and used fluorescent cell sorting to get antigen-specific memory B cells from transgenic mice spleen lymphocytes. By single cell PCR method, we quickly found two strains of anti-LF MAbs with binding activity, 1D7 and 2B9. Transiently transfected Expi 293F cells to obtain MAbs protein after purification. Both 1D7 and 2B9 efficiently neutralized LT in vitro, and had good synergistic effect when mixed with anti-PA MAbs. In summary, combining the advantages of transgenic mice, fluorescent cell sorting and single-cell PCR methods, this study shows new ideas and methods for the rapid screening of fully human monoclonal antibodies.炭疽是由炭疽芽孢杆菌引起的严重威胁人类健康的传染病。炭疽毒素包括3 种蛋白质成分:保护性抗原 (PA)、致死因子 (LF) 和水肿因子 (EF)。PA 与LF 形成致死毒素 (LT),与EF 形成水肿毒素 (ET)。由于致死毒素 (LT) 在感染者损伤及死亡中发挥主要作用,因此在炭疽感染晚期单纯使用抗生素治疗难以发挥疗效,治疗性中和抗体成为目前最有效的炭疽治疗药物。目前国外获得的炭疽毒素抗体多为炭疽PA 抗体,美国FDA 已批准瑞西巴库 (人源PA 单抗) 用于吸入性炭疽的治疗。一旦炭疽芽孢杆菌被人为改构或PA 中和表位发生突变,针对PA 单一表位的抗体将可能失效,因此针对LF 的抗体将成为炭疽治疗的有效补充。目前国外已有的LF 抗体多为鼠源抗体和嵌合抗体,而全人源抗体可以避免鼠源抗体免疫原性高等缺点。本研究首先用LF 抗原免疫人抗体转基因小鼠,利用流式细胞仪从小鼠脾淋巴细胞中分选抗原特异的记忆B 细胞,通过单细胞PCR 方法快速获得两株具有结合活性的抗LF 单抗1D7 和2B9。瞬时转染Expi 293F 细胞制备抗体,通过毒素中和实验 (TNA) 发现1D7 和2B9 在细胞模型中均显示较好的中和活性,并且与PA 单抗联合使用时,表现出较好的协同作用。总之,本文利用转基因小鼠、流式分选技术和单细胞PCR 技术的优势,快速筛选到全人源LF 抗体,为快速筛选全人源单克隆抗体开辟了新的思路与方法。.
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- 2017
16. Baf53a is involved in survival of mouse ES cells, which can be compensated by Baf53b
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Shin-ichi Horike, Bo Zhu, Atsushi Ueda, Takashi Yokota, Xiaohong Song, and Tadayuki Akagi
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0301 basic medicine ,Homeobox protein NANOG ,Programmed cell death ,Chromosomal Proteins, Non-Histone ,Cellular differentiation ,lcsh:Medicine ,Caspase 3 ,Biology ,Article ,03 medical and health sciences ,Mice ,Conditional gene knockout ,Animals ,lcsh:Science ,Cells, Cultured ,Cell Proliferation ,Regulation of gene expression ,Mice, Knockout ,Multidisciplinary ,Cell growth ,lcsh:R ,Cell Differentiation ,Mouse Embryonic Stem Cells ,Chromatin Assembly and Disassembly ,Embryonic stem cell ,Actins ,Cell biology ,DNA-Binding Proteins ,030104 developmental biology ,Gene Expression Regulation ,lcsh:Q - Abstract
金沢大学医薬保健研究域医学系, The human Baf (Brg1/Brm associated factor) complex, also known as the mammalian SWI/SNF chromatin-remodeling complex, is involved in a variety of cellular processes. The pluripotency and self-renewal abilities are major characteristics of embryonic stem (ES) cells and are regulated by the ES cell-specific BAF (esBAF) complex. Baf53a is one of the subunits of the esBAF complex. Here, we found that Baf53a was expressed in undifferentiated ES cells and that it interacted with Oct3/4. Analyses of tetracycline-inducible Baf53a conditional knockout ES cells revealed that the undifferentiated markers, including Nanog and Oct3/4, were expressed in Baf53a-deficient ES cells; however, growth of the cells was repressed, and expression of p53, p21, and cleaved Caspase 3 was increased. Cell death of Baf53a-deficient ES cells was rescued by overexpression of Baf53a, but not by the Baf53a M3 mutant (E388A/R389A/R390A). Interestingly, Baf53b, a homologue of Baf53a, rescued cell death of Baf53a-deficient ES cells. Baf53a-deficient ES cells overexpressing exogenous Baf53a or Baf53b remained in the undifferentiated state, proliferated, and repressed expression of p21. In summary, our findings suggest that Baf53a is involved in the survival of ES cells by regulating p53 and Caspase3, and that Baf53b is able to compensate for this functional aspect of Baf53a. © 2017 The Author(s).
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- 2017
17. Enterovirus 71 Inhibits Cellular Type I Interferon Signaling by Downregulating JAK1 Protein Expression
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Wei Chen, Xiangyang Chi, Xiaohong Song, Xinghui Zhao, Ying Liu, Ling Fu, Rui Yu, Yingqun Yu, Ju Liu, Lihua Hou, Zhe Zhang, Shipo Wu, and Xiaopeng Zhang
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Protein subunit ,Immunology ,Down-Regulation ,Receptor, Interferon alpha-beta ,macromolecular substances ,Cell Line ,Downregulation and upregulation ,Interferon ,Virology ,Chlorocebus aethiops ,Rhabdomyosarcoma ,Enterovirus 71 ,medicine ,Animals ,Humans ,Phosphorylation ,Receptor ,Vero Cells ,biology ,musculoskeletal, neural, and ocular physiology ,food and beverages ,STAT2 Transcription Factor ,Janus Kinase 1 ,Fibroblasts ,biology.organism_classification ,Enterovirus A, Human ,Protein Subunits ,STAT1 Transcription Factor ,nervous system ,Cell culture ,Interferon Type I ,Vero cell ,Molecular Medicine ,Protein Tyrosine Phosphatases ,Signal Transduction ,medicine.drug - Abstract
Enterovirus 71 (EV71) infection can cause severe disease and lead to death in children. Recurring outbreaks of EV71 have been reported in several countries. Interferons (IFNs) have been used for decades to treat several types of viral infection, but have a limited ability to inhibit EV71 replication. Herein, we intend to investigate the mechanisms by which EV71 inhibits the cellular type I IFN response. In this study, MRC-5 (human embryonic lung fibroblast) or RD (human rhabdomyosarcoma) cells were infected with EV71, and then treated with or without IFN-α2b. Cells were harvested and analyzed by flow cytometry to determine the level of IFNAR1. Cell lysis were prepared to detect the levels of STAT1, STAT2, phosphorylated STAT1, phosphorylated STAT2, IFNAR1, JAK1, and TYK2 by Western blotting. The phosphorylation of STAT1 and STAT2 induced by IFN were inhibited without significant downregulation of IFNAR1 in EV71-infected cells. The EV71-induced suppression of STAT1 and STAT2 phosphorylation was not rescued by the protein tyrosine phosphatases inhibitor, and was independent of suppressor of cytokine signaling protein 1/3 levels. The phosphorylation of JAK1 and TYK2 were inhibited accompanied by EV71-induced downregulation of JAK1, which occurred at a post-transcriptional level and was proteasome independent. JAK1 expression did not decrease, and IFN-α-stimulated STAT1 and STAT2 phosphorylation were not blocked in HEK293T cells overexpressing the EV71 viral protein 2A or 3C. This study demonstrates that EV71 inhibits the cellular type I IFN antiviral pathway by downregulating JAK1, while the expression of IFNAR1 does not significantly alter in EV71-infected cells. Additionally, the EV71 viral proteins 2A and 3C do not act as antagonists of cellular type I IFN signaling.
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- 2014
18. The combinatorial guidance activities of draxin and Tsukushi are essential for forebrain commissure formation
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Ayako Ito, Hideaki Tanaka, Iftekhar Bin Naser, M. Asrafuzzaman Riyadh, Giasuddin Ahmed, Xiaohong Song, Kunimasa Ohta, Yohei Shinmyo, Mahmud Hossain, and Athary Felemban
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Heterozygote ,Time Factors ,Neurite ,Corpus callosum ,Draxin ,Anterior commissure ,Biology ,Ligands ,Mice ,Prosencephalon ,medicine ,Animals ,Molecular Biology ,Tsukushi ,Mice, Knockout ,Dose-Response Relationship, Drug ,Models, Genetic ,Genetic interaction ,Axon guidance ,Wnt signaling pathway ,Brain ,Gene Expression Regulation, Developmental ,Anatomy ,Cell Biology ,Commissure ,Axons ,Cell biology ,Phenotype ,medicine.anatomical_structure ,Culture Media, Conditioned ,Knockout mouse ,Forebrain ,Intercellular Signaling Peptides and Proteins ,Proteoglycans ,Neuron ,Signal Transduction ,Developmental Biology - Abstract
We have shown that draxin is a repulsive axon guidance molecule for a variety of neuron classes and that genetic deletion of draxin in mice results in the absence of all forebrain commissures. Moreover, we also identified a secreted molecule, Tsukushi (TSK), that belongs to the small leucine-rich proteoglycan family (SLRP) and inhibits signaling molecules, such as BMP and Wnt. TSK knockout mice show malformation of the corpus callosum (CC) and agenesis of the anterior commissure (AC), suggesting the importance of TSK function in forebrain commissure formation. There is a possibility that the combined function of these two proteins is essential for the formation of these commissures. In this study, we investigate this possibility by generating draxin/TSK doubly heterozygous mice and comparing their forebrain commissure phenotypes with those of singly heterozygous mice. We found that, although draxin and TSK did not interact directly, their genetic interaction was evident from the significantly higher prevalence of CC malformation and agenesis of the AC in the draxin/TSK doubly heterozygous mice. Importantly, in this study, we demonstrated a new function of TSK in guiding anterior olfactory neuronal (AON) and cortical axons. TSK bound to and provided growth inhibitory signals dose-dependently to AON and cortical axons in outgrowth assay. TSK also induced growth cone collapse when applied acutely to these cultured neurons. Furthermore, TSK and draxin had additive effects in inhibiting cortical and AON neurite outgrowth. Thus, based on a combination of genetic analyses and in vitro experiments, we propose that the combined guidance activities of draxin and TSK regulate forebrain commissure formation.
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- 2013
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19. Comparative Immunogenicity of the Tetanus Toxoid and Recombinant Tetanus Vaccines in Mice, Rats, and Cynomolgus Monkeys
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Jianmin Li, Wei Chen, Xiaohong Song, Rui Yu, Ting Fang, Changming Yu, Shuling Liu, Junjie Xu, Lihua Hou, and Ling Fu
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0301 basic medicine ,Male ,Time Factors ,Health, Toxicology and Mutagenesis ,Immunization, Secondary ,lcsh:Medicine ,Booster dose ,immunogenicity ,Toxicology ,complex mixtures ,Article ,03 medical and health sciences ,Immunogenicity, Vaccine ,Species Specificity ,recombinant vaccine ,Immunity ,medicine ,Tetanus Toxoid ,Animals ,Rats, Wistar ,Immunization Schedule ,Mice, Inbred BALB C ,Vaccines, Synthetic ,030102 biochemistry & molecular biology ,business.industry ,Tetanus ,Immunogenicity ,lcsh:R ,Antibody titer ,Toxoid ,medicine.disease ,Virology ,Antibodies, Bacterial ,Titer ,Macaca fascicularis ,030104 developmental biology ,tetanus toxin ,toxoid vaccine ,booster vaccination efficacy ,Tetanus vaccine ,Immunology ,Models, Animal ,Female ,business ,medicine.drug - Abstract
Tetanus is caused by the tetanus neurotoxin (TeNT) and is one of the most dreaded diseases especially in the developing countries. The current vaccine against tetanus is based on an inactivated tetanus toxin, which is effective but has many drawbacks. In our previous study, we developed a recombinant tetanus vaccine based on protein TeNT-Hc, with clear advantages over the toxoid vaccine in terms of production, characterization, and homogeneity. In this study, the titers, growth extinction, and persistence of specific antibodies induced by the two types of vaccine in mice, rats, and cynomolgus monkeys were compared. The booster vaccination efficacy of the two types of vaccines at different time points and protection mechanism in animals were also compared. The recombinant tetanus vaccine induced persistent and better antibody titers and strengthened the immunity compared with the commercially available toxoid vaccine in animals. Our results provide a theoretical basis for the development of a safe and effective recombinant tetanus vaccine to enhance the immunity of adolescents and adults as a substitute for the current toxoid vaccine.
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- 2016
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20. Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts
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Yun Xia, Rebecca Deng, Qiandong Zeng, Lin Fan, Xiaoli Jiao, Yueqin Liu, Joshua Z. Levin, Emma Davey, Christina A. Cuomo, Geetha Kutty, Liang Ma, Bao Tran, Xiaohong Song, Sean M. Sykes, Lisa R. Bishop, Charles Huber, Castle Raley, Honghui Wang, Mayumi Ishihara, Da-Wei Huang, Xiaojun Hu, Michael Fitzgerald, Jonathan M. Goldberg, Pendexter Macdonald, Alexandre Melnikov, Laura Walsh, Robert M. Stephens, Xin Zheng, Emile Gogineni, Monica Sassi, Zehua Chen, Jun Yang, Giovanna Fantoni, Parastoo Azadi, Xilong Deng, Grace Handley, Bruce W. Birren, Brad T. Sherman, Chad Nusbaum, Sarah Young, Joseph A. Kovacs, Richard A. Lempicki, Kristine Jones, and Amr Abouelleil
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0301 basic medicine ,Proteases ,Science ,030106 microbiology ,Adaptation, Biological ,General Physics and Astronomy ,Biology ,Pneumocystis carinii ,Synteny ,Genome ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,Immune system ,Cell Wall ,parasitic diseases ,medicine ,Animals ,Humans ,Pneumocystis jirovecii ,Lung ,Transcription factor ,chemistry.chemical_classification ,Genetics ,Multidisciplinary ,fungi ,General Chemistry ,biology.organism_classification ,medicine.disease ,Virology ,Rats ,3. Good health ,chemistry ,Multigene Family ,Host-Pathogen Interactions ,Genome, Fungal ,Glycoprotein ,Pneumonia (non-human) ,Metabolic Networks and Pathways - Abstract
Pneumocystis jirovecii is a major cause of life-threatening pneumonia in immunosuppressed patients including transplant recipients and those with HIV/AIDS, yet surprisingly little is known about the biology of this fungal pathogen. Here we report near complete genome assemblies for three Pneumocystis species that infect humans, rats and mice. Pneumocystis genomes are highly compact relative to other fungi, with substantial reductions of ribosomal RNA genes, transporters, transcription factors and many metabolic pathways, but contain expansions of surface proteins, especially a unique and complex surface glycoprotein superfamily, as well as proteases and RNA processing proteins. Unexpectedly, the key fungal cell wall components chitin and outer chain N-mannans are absent, based on genome content and experimental validation. Our findings suggest that Pneumocystis has developed unique mechanisms of adaptation to life exclusively in mammalian hosts, including dependence on the lungs for gas and nutrients and highly efficient strategies to escape both host innate and acquired immune defenses., Pneumocystis jirovecii is a fungus that can cause life-threatening pneumonia in immunocompromised patients. Here, the authors sequence the genomes of P. jirovecii and two other Pneumocystis species, and show the unexpected absence of chitin (a near universal fungal cell wall component).
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- 2016
21. Preparation of CHO cell-derived rhIFN-ω-Fc with improved pharmacokinetics
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Jian-min Li, Chun’e Xu, Wei Chen, Changming Yu, Ting Yu, Jinglong Zhang, Xiaohong Song, Jun Zhang, Lihua Hou, Bing Li, Jun Ren, and Fu Ling
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Recombinant Fusion Proteins ,Immunoblotting ,Cell Culture Techniques ,Gene Expression ,Dot blot ,Antiviral Agents ,Chromatography, Affinity ,Cell Line ,law.invention ,Cricetulus ,Affinity chromatography ,Sequence Analysis, Protein ,law ,Cricetinae ,Virology ,Animals ,Humans ,Peptide sequence ,Pharmacology ,biology ,Chinese hamster ovary cell ,Vesiculovirus ,biology.organism_classification ,Molecular biology ,Fusion protein ,Immunoglobulin Fc Fragments ,Cell culture ,Vesicular stomatitis virus ,Interferon Type I ,Recombinant DNA ,Electrophoresis, Polyacrylamide Gel ,Rabbits ,Biotechnology - Abstract
Interferon-omega (IFN-ω) may be a useful, promising and alternative antiviral agent, in addition to IFN-α-2a and IFN-α-2b. To improve the pharmacokinetics of IFN-ω for clinical use, the recombinant human IFN-ω-Fc fusion protein (rhIFN-ω-Fc) was expressed in a Chinese hamster ovary cell line (CHO-S), due to the longer serum half-life of rhIFN-ω-Fc compared to the native IFN-ω protein, and purified by affinity chromatography. Physicochemical characterization of the purified fusion protein was performed by SDS-PAGE electrophoresis, dot blot analysis and N-terminal amino acid sequence analysis. The results show that rhIFN-ω-Fc was highly expressed at the predicted size and with the N-terminal amino acid sequence. The antiviral activity was determined by the ability of IFNs to inhibit the cytopathic effects (CPEs) of vesicular stomatitis virus (VSV) on the human amnion WISH cells. The rhIFN-ω-Fc expressed in CHO-S cells has a specific activity of 1.6×10(7) IU/mg compared to rhIFN-ω expressed in yeast, which has a specific activity of 7×10(7) IU/mg. Equimolar concentrations of rhFN-ω and rhIFN-ω-Fc were administered to rabbits for pharmacokinetics comparison. The terminal half-life of rhIFN-ω-Fc was 35 times higher than that of rhIFN-ω. Thus, rhIFN-ω-Fc can be used as a prospective antiviral candidate especially for the treatment of chronic viral disease, such as hepatitis C virus (HCV) infection.
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- 2011
22. Regulation of circadian gene expression in the kidney by light and food cues in rats
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Jiafeng Xu, Zhengwei Fu, Tao Wu, Hisanori Kato, Yue Dong, Yinhua Ni, and Xiaohong Song
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Male ,endocrine system ,medicine.medical_specialty ,Physiology ,CLOCK Proteins ,Circadian response ,Biology ,Kidney ,Feeding behavior ,Physiology (medical) ,Internal medicine ,Gene expression ,medicine ,Animals ,Circadian rhythm ,Rats, Wistar ,Oscillating gene ,Lighting ,ARNTL Transcription Factors ,Feeding Behavior ,Period Circadian Proteins ,Circadian Rhythm ,Rats ,Cryptochromes ,Endocrinology ,medicine.anatomical_structure ,Gene Expression Regulation ,Cues ,Neuroscience ,PER1 - Abstract
Although studies involving the circadian response to external time cues indicate that the peripheral clocks are dominated mainly by food cues, whether and how changes in the light and food cues affect the circadian rhythm of the renal clock is still largely unknown. In the present study, we found that the circadian phases of Bmal1, Clock, Cry1, Per1, and Per2 were altered differently by the stimuli of food and light cues in the kidney. After the individual reversal of the light-dark (LD) cycle for 7 days, Per1 displayed a 4-h phase delay, whereas the peak phases of Bmal1, Clock, Cry1 and Per2 almost remained the same as those in the control condition. With regard to the feeding-induced circadian resetting of the renal clock, we found that the resetting processes of clock genes could not be completed within 7 days, suggesting a weak synchronization effect of the food cue on the renal circadian clock. Moreover, the reentrainment of the clock genes was greatly enhanced after the reversal of both the feeding schedule and the LD cycle. Noticeably, the phases of Per1 and Clock were shifted most rapidly by 12 h within 3 days after the simultaneous reversal of the feeding schedule and the LD cycle, whereas their peak phases were only shifted by 4 h and 8 h, respectively, on the 7th day after the individual reversal of the feeding schedule. Thus Per1 and Clock may play important roles in the light-induced resetting of the circadian rhythms in the kidney.
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- 2010
23. Chimeric hepatitis B virus core particles carrying an epitope of anthrax protective antigen induce protective immunity against Bacillus anthracis
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Xiaohong Song, Ying Yin, Dayong Dong, Junjie Xu, Guanlin Li, Wei Chen, Ling Fu, Shuling Liu, Jun Zhang, and Qiang Guo
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Hepatitis B virus ,Blotting, Western ,Guinea Pigs ,Mutant Chimeric Proteins ,Enzyme-Linked Immunosorbent Assay ,Anthrax Vaccines ,Virus ,Epitope ,Microbiology ,Anthrax ,Epitopes ,Mice ,Adjuvants, Immunologic ,Antigen ,Neutralization Tests ,Animals ,Alum adjuvant ,Spores, Bacterial ,Mice, Inbred BALB C ,Vaccines, Synthetic ,Anthrax vaccines ,General Veterinary ,General Immunology and Microbiology ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Immunogenicity ,fungi ,Public Health, Environmental and Occupational Health ,virus diseases ,biology.organism_classification ,Hepatitis B Core Antigens ,Virology ,Bacillus anthracis ,Microscopy, Electron ,Infectious Diseases ,biology.protein ,Alum Compounds ,Molecular Medicine ,Electrophoresis, Polyacrylamide Gel ,Female ,Antibody ,Viral Fusion Proteins ,Plasmids - Abstract
The major aim of present study is to develop and evaluate chimeric virus-like particles (VLPs) displaying a neutralizing epitope of anthrax protective antigen (PA) as a potential vaccine against anthrax. The truncated hepatitis B virus core (HBc) protein (aa 1-144) was used as a carrier, and the 2beta2-2beta3 loop of the PA domain 2 (aa 302-325) which has been shown contains a dominant neutralizing epitope was inserted into the major immunodominant region (MIR) of the HBc. The recombinant protein HBc-N144-PA-loop2 was expressed in Escherichia coli, and was able to form HBc-like particles confirmed by electron microscopy. The immunogenicity of these chimeric particles was evaluated in mice and guinea pigs. In mice the HBc-N144-PA-loop2 was able to induce PA-epitope specific antibodies; in guinea pigs it was able to induce PA-epitope specific antibodies and anthrax toxin-neutralizing antibodies regardless of whether alum adjuvant was used or not, and was able to partially protect the immunized guinea pigs against virulent anthrax spores challenge. This study suggests chimeric HBc particles carrying a neutralizing epitope of PA can induce protective immunity against Bacillus anthracis.
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- 2008
24. Akhirin regulates the proliferation and differentiation of neural stem cells in intact and injured mouse spinal cord
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Felemban Athary M, Abdulhaleem, Xiaohong, Song, Rie, Kawano, Naohiro, Uezono, Ayako, Ito, Giasuddin, Ahmed, Mahmud, Hossain, Kinichi, Nakashima, Hideaki, Tanaka, and Kunimasa, Ohta
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Disease Models, Animal ,Mice ,Neural Stem Cells ,Ependyma ,Animals ,Nuclear Proteins ,Cell Differentiation ,Neuroglia ,Spinal Cord Injuries ,Cell Proliferation - Abstract
Although the central nervous system is considered a comparatively static tissue with limited cell turnover, cells with stem cell properties have been isolated from most neural tissues. The spinal cord ependymal cells show neural stem cell potential in vitro and in vivo in injured spinal cord. However, very little is known regarding the ependymal niche in the mouse spinal cord. We previously reported that a secreted factor, chick Akhirin, is expressed in the ciliary marginal zone of the eye, where it works as a heterophilic cell-adhesion molecule. Here, we describe a new crucial function for mouse Akhirin (M-AKH) in regulating the proliferation and differentiation of progenitors in the mouse spinal cord. During embryonic spinal cord development, M-AKH is transiently expressed in the central canal ependymal cells, which possess latent neural stem cell properties. Targeted inactivation of the AKH gene in mice causes a reduction in the size of the spinal cord and decreases BrdU incorporation in the spinal cord. Remarkably, the expression patterns of ependymal niche molecules in AKH knockout (AKH-/-) mice are different from those of AKH+/+, both in vitro and in vivo. Furthermore, we provide evidence that AKH expression in the central canal is rapidly upregulated in the injured spinal cord. Taken together, these results indicate that M-AKH plays a crucial role in mouse spinal cord formation by regulating the ependymal niche in the central canal.
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- 2014
25. Neuron type- and input pathway-dependent expression of Slc4a10 in adult mouse brains
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Motokazu Uchigashima, Kohtarou Konno, Masahiko Watanabe, Taisuke Miyazaki, Miwako Yamasaki, and Xiaohong Song
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Cerebellum ,Blotting, Western ,In situ hybridization ,Biology ,Neural Pathways ,Extracellular ,medicine ,Animals ,Chloride-Bicarbonate Antiporters ,RNA, Messenger ,In Situ Hybridization ,Neurons ,Symporters ,General Neuroscience ,Sodium-Bicarbonate Symporters ,Brain ,Dendrites ,Immunohistochemistry ,Cell biology ,Mice, Inbred C57BL ,Somatodendritic compartment ,medicine.anatomical_structure ,Parvalbumins ,nervous system ,Cerebral cortex ,Cerebellar cortex ,Cotransporter ,Neuroscience ,Intracellular - Abstract
Slc4a10 was originally identified as a Na(+) -driven Cl(-) /HCO3 (-) exchanger NCBE that transports extracellular Na(+) and HCO3 (-) in exchange for intracellular Cl(-) , whereas other studies argue against a Cl(-) -dependence for Na(+) -HCO3 (-) transport, and thus named it the electroneutral Na(+) /HCO3 (-) cotransporter NBCn2. Here we investigated Slc4a10 expression in adult mouse brains by in situ hybridization and immunohistochemistry. Slc4a10 mRNA was widely expressed, with higher levels in pyramidal cells in the hippocampus and cerebral cortex, parvalbumin-positive interneurons in the hippocampus, and Purkinje cells (PCs) in the cerebellum. Immunohistochemistry revealed an uneven distribution of Slc4a10 within the somatodendritic compartment of cerebellar neurons. In the cerebellar molecular layer, stellate cells and their innervation targets (i.e. PC dendrites in the superficial molecular layer) showed significantly higher labeling than basket cells and their targets (PC dendrites in the basal molecular layer and PC somata). Moreover, the distal dendritic trees of PCs (i.e. parallel fiber-targeted dendrites) had significantly greater labeling than the proximal dendrites (climbing fiber-targeted dendrites). These observations suggest that Slc4a10 expression is regulated in neuron type- and input pathway-dependent manners. Because such an elaborate regulation is also found for K(+) -Cl(-) cotransporter KCC2, a major neuronal Cl(-) extruder, we compared their expression. Slc4a10 and KCC2 overlapped in most somatodendritic elements. However, relative abundance was largely complementary in the cerebellar cortex, with particular enrichments of Slc4a10 in PC dendrites and KCC2 in molecular layer interneurons, granule cells and PC somata. These properties might reflect functional redundancy and distinction of these transporters, and their differential requirements by individual neurons and respective input domains.
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- 2014
26. Multiple roles of Equarin during lens development
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Hideaki Tanaka, Xiaohong Song, and Kunimasa Ohta
- Subjects
Extracellular Matrix Proteins ,DNA, Complementary ,Tumor Suppressor Proteins ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Cell Biology ,Anatomy ,Chick Embryo ,Biology ,Models, Biological ,eye diseases ,Avian Proteins ,Fibroblast Growth Factors ,medicine.anatomical_structure ,Lens (anatomy) ,Lens, Crystalline ,medicine ,Eye development ,Animals ,Intercellular Signaling Peptides and Proteins ,Eye Proteins ,Neuroscience ,Developmental Biology ,Glycoproteins ,Signal Transduction - Abstract
Since the days of Hans Spemann, the ocular lens has served as one of the most important developmental systems for elucidating the fundamental processes of induction and differentiation. Lens is an important source of signals that influence the eye development and a variety of genes expressed by the lens have been identified. The identification of additional molecule(s), especially secreted ones that might mediate signals, will extend our knowledge of the molecular mechanisms of eye and lens development. Here, we will introduce a soluble molecule, Equarin, and discuss its vital role in multiple aspects of lens development.
- Published
- 2013
27. [Preparation and biological activity analysis of chimeric antibody against capsular F1 antigen of Yersinia pestis]
- Author
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Jinlong, Zhang, Jun, Ren, Ting, Yu, Xiaohong, Song, Guangcheng, Fu, Shuling, Liu, Zhang, Zhang, Bing, Li, and Jianmin, Li
- Subjects
Mice ,Cricetulus ,Bacterial Proteins ,Yersinia pestis ,Cricetinae ,Immunoglobulin G ,Recombinant Fusion Proteins ,Animals ,Humans ,CHO Cells ,Polymerase Chain Reaction ,Bacterial Capsules - Abstract
To express human-mouse chimeric antibody against Yersinia pestis F1 capsular antigen (F1 antigen) and analyze its biological activities.The heavy chain gene of the chimeric antibody was obtained by fusing the variable region gene of the mouse mAb heavy chain with human IgG1 constant region gene. The light chain gene of the chimeric antibody was obtained by fusing the variable region gene of the mouse mAb light chain with the human kappa constant region gene. Both the heavy and light chain genes of the chimeric antibody were further verified by sequencing. The chimeric antibody heavy and light chain genes were inserted into EcoR I/Not I of pcDNA3.1 (+) to construct expression plasmids termed pcDNA3.1-L and pcDNA3.1-H, respectively. Then, two plasmids were mixed and transfected into CHO-S cells. Finally, the stable cell clone secreting chimeric antibody was obtained by G418 selection. The culture supernatants of serum-free medium were collected and the chimeric antibody was purified by MabSelect SuRe affinity chromatography. The purified chimeric antibody was analyzed by SDS-PAGE, Western blotting, ELISA and evaluated in the protective effect in vivo.PCR and sequencing analysis proved that plasmids pcDNA3.1-H and pcDNA3.1-L were correctly constructed. Dot blot showed that a cell line with high-level expression of chimeric antibody was obtained. SDS-PAGE and western blot showed that the chimeric antibody was successfully purified. ELISA showed that the chimeric antibody could specifically bind to F1 antigen. In vivo activity assay showed that 80% BALB/c mice treated with the chimeric antibody survived from 36 MLD virulent Yersinia pestis.The chimeric antibody against F1 antigen with neutralizing activity was successfully expressed in CHO-S cells, which laid a foundation for the preparation of anti-plague passive immunity agents.
- Published
- 2013
28. Equarin is involved in cell adhesion by means of heparan sulfate proteoglycan during lens development
- Author
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Hideaki Tanaka, Kiyotoshi Sekiguchi, Kunimasa Ohta, Xiaohong Song, and Yuya Sato
- Subjects
Morphogenesis ,Perlecan ,Chick Embryo ,Biology ,Fibroblast growth factor ,Heparan Sulfate Proteoglycans ,Models, Biological ,Extracellular matrix ,Chlorocebus aethiops ,Lens, Crystalline ,medicine ,Cell Adhesion ,Animals ,Actin ,Cytoskeleton ,Glycoproteins ,Extracellular Matrix Proteins ,Cell adhesion molecule ,Adhesion ,Immunohistochemistry ,Lens Fiber ,Cell biology ,Developmental dynamics ,medicine.anatomical_structure ,Lens (anatomy) ,COS Cells ,biology.protein ,Intercellular Signaling Peptides and Proteins ,Syndecan-3 ,Electrophoresis, Polyacrylamide Gel ,Developmental Biology - Abstract
Background: Adhesion molecules are known to be instructive for both development and differentiation. During lens differentiation, epithelial cells undergo vertical elongation, with the anterior and posterior tips of the elongating fiber cells sliding along the epithelium and capsule, respectively. These cellular processes are highly coordinated through cell adhesive interactions, actin cytoskeletal reorganization and contractile force generation. Alterations in extracellular matrix composition that interfere with these interactions can lead to defects that alter tissue morphogenesis and the state of differentiation. We have demonstrated that Equarin, which is a secreted molecule expressed in the equator region of the lens, plays an important role in chick lens fiber differentiation through fibroblast growth factor signaling. Results: Here, we explored the function of Equarin in chick lens cell adhesion. Equarin protein was expressed in the extracellular region of lens differentiating cells. We found that Equarin promoted lens cell adhesion through heparan sulfate proteoglycan. By biochemical analysis, we found that Equarin directly binds syndecan-3, which displayed a similar expression pattern to Equarin. Overexpression of Equarin resulted in altered actin localization. Conclusions: Equarin is involved in cell adhesion during fiber differentiation and development. Developmental Dynamics 242:23–29, 2013. © 2012 Wiley Periodicals, Inc.
- Published
- 2012
29. Antiviral potential of exogenous human omega interferon to inhibit pandemic 2009 A (H1N1) influenza virus
- Author
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Lihua Hou, Chun’e Xu, Rui Yu, Ling Fu, Ting Yu, Wei Chen, Shipo Wu, Guanlin Li, Shaoqiong Yi, Dayong Dong, and Xiaohong Song
- Subjects
viruses ,Immunology ,Guinea Pigs ,Biology ,medicine.disease_cause ,Virus Replication ,H5N1 genetic structure ,Antiviral Agents ,Virus ,Microbiology ,Cell Line ,Influenza A Virus, H1N1 Subtype ,Orthomyxoviridae Infections ,Interferon ,Virology ,Pandemic ,medicine ,Influenza A virus ,Animals ,Humans ,Lung ,Pandemics ,Administration, Intranasal ,virus diseases ,Recombinant Proteins ,Disease Models, Animal ,Cell culture ,Interferon Type I ,Molecular Medicine ,Nasal administration ,Female ,Caco-2 Cells ,Viral load ,medicine.drug - Abstract
The pandemic 2009 H1N1 influenza virus broke out in North America and spread rapidly throughout the world. The type I interferon (IFN) response represents one of the first lines of defense against influenza virus infections. In this study, the protective potential of human exogenous IFN-ω against pandemic 2009 A (H1N1) influenza virus was assessed both in vitro and in guinea pigs. The viral loads of pandemic 2009 A (H1N1) influenza virus strains A/California/04/2009 and A/Beijing/501/2009 were reduced by up to 5000-fold in Caco-2 cells by the addition of human IFN-ω. With daily intranasal treatment with human IFN-ω the viral load of pandemic 2009 A (H1N1) influenza virus strain A/California/04/2009 decreased by 1000-fold in lung tissues of guinea pigs. These results provide strong support for the application of human IFN-ω pretreatment to human influenza control.
- Published
- 2011
30. A conformational change of C fragment of tetanus neurotoxin reduces its ganglioside-binding activity but does not destroy its immunogenicity
- Author
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Ting Fang, Ling Fu, Shuling Liu, Wei Chen, Changming Yu, Shaoqiong Yi, Xiaohong Song, Rui Yu, Lihua Hou, and Ting Yu
- Subjects
Microbiology (medical) ,Conformational change ,Protein Conformation ,Clinical Biochemistry ,Immunology ,Cell Line ,Mice ,Protein structure ,Tetanus Toxin ,Ganglioside binding ,Gangliosides ,Tetanus Toxoid ,Immunology and Allergy ,Animals ,Disulfides ,Mice, Inbred BALB C ,Ganglioside ,Tetanus ,Chemistry ,Immunogenicity ,Toxoid ,Metalloendopeptidases ,Toxoids ,Vaccine Research ,Survival Analysis ,Rats ,body regions ,Biochemistry ,Cell culture ,Immunoglobulin G ,Antitoxins ,Cysteine - Abstract
The C fragment of tetanus neurotoxin (TeNT-Hc) with different conformations was observed due to the four cysteine residues within it which could form different intramolecular disulfide bonds. In this study, we prepared and compared three types of monomeric TeNT-Hc with different conformational components: free sulfhydryls (50 kDa), bound sulfhydryls (44 kDa), and a mixture of the two conformational proteins (half 50 kDa and half 44 kDa). TeNT-Hc with bound sulfhydryls reduced its binding activity to ganglioside GT1band neuronal PC-12 cells compared to what was seen for TeNT-Hc with free sulfhydryls. However, there was no significant difference among their immunogenicities in mice, including induction of antitetanus toxoid IgG titers, antibody types, and protective capacities against tetanus neurotoxin challenge. Our results showed that the conformational changes of TeNT-Hc resulting from disulfide bond formation reduced its ganglioside-binding activity but did not destroy its immunogenicity, and the protein still retained continuous B cell and T cell epitopes; that is, the presence of the ganglioside-binding site within TeNT-Hc may be not essential for the induction of a fully protective antitetanus response. TeNT-Hc with bound sulfhydryls may be developed into an ideal human vaccine with a lower potential for side effects.
- Published
- 2011
31. Theacrine, a purine alkaloid with anti-inflammatory and analgesic activities
- Author
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Xiaohong Song, Chuangxing Ye, Xiaorong Yang, Xin-Qiang Zheng, Jing Li, and Yuanyuan Wang
- Subjects
Male ,medicine.drug_class ,Analgesic ,Anti-Inflammatory Agents ,Drug Evaluation, Preclinical ,Pain ,Pharmacology ,Anti-inflammatory ,law.invention ,chemistry.chemical_compound ,Mice ,law ,Oral administration ,Drug Discovery ,medicine ,Animals ,Theacrine ,Inflammation ,Analgesics ,Plant Extracts ,Alkaloid ,Camellia ,General Medicine ,Acute toxicity ,Uric Acid ,chemistry ,Female ,Phytotherapy ,Caffeine - Abstract
The anti-inflammatory and analgesic effects of theacrine (1, 3, 7, 9-tetramethyluric acid), a purine alkaloid which is abundantly present in Camellia kucha, were investigated. Xylene-induced ear edema, acetic acid-induced vascular permeability and lambda-carrageenan-induced paw edema were used to investigate anti-inflammatory activity, and acetic acid-induced writhing and hot-plate tests were used to determine analgesic effect. Oral administration of theacrine (8-32 mg/kg) induced dose-related anti-inflammatory and analgesic effects. On the other hand, oral caffeine administration (8-32 mg/kg) did not show an inhibitory effect on the inhibition of inflammatory response or cause analgesia. Additionally, the result of the acute toxicity test showed that the LD(50) of theacrine was 810.6 mg/kg (769.5-858.0mg/kg). The data obtained suggest theacrine possessed analgesic and anti-inflammatory activities.
- Published
- 2010
32. Fusion protein of Delta 27LFn and EFn has the potential as a novel anthrax toxin inhibitor
- Author
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Qiang Guo, Wei Chen, Ling Fu, Yirong Kong, Dayong Dong, Jian Zhao, Lihua Hou, Changming Yu, Chenguang Cai, Xiaohong Song, and Junjie Xu
- Subjects
Male ,Anthrax toxin ,Recombinant Fusion Proteins ,Bacterial Toxins ,Biophysics ,Biology ,medicine.disease_cause ,Biochemistry ,Microbiology ,Toxin inhibitor ,Structural Biology ,Genetics ,medicine ,Animals ,PA-binding domain of EF ,Lethal toxin ,Molecular Biology ,DNA Primers ,chemistry.chemical_classification ,Antigens, Bacterial ,Base Sequence ,Toxin ,Cell model ,Cell Biology ,Fusion protein ,Molecular biology ,Rats, Inbred F344 ,Amino acid ,Rats ,PA-binding domain of LF ,chemistry ,Anthrax lethal factor ,Electrophoresis, Polyacrylamide Gel ,Binding domain - Abstract
PA-binding domain of LF (LFn) or PA-binding domain of EF (EFn) is the anthrax protective antigen (PA) binding domain of anthrax lethal factor (LF) or edema factor (EF). Here we show the development of a novel anthrax toxin inhibitor, fusion protein of N-terminal 27 amino acids deletion of LFn (Δ27LFn) and EFn. In a cell model of intoxication, fusion protein of Δ27LFn and EFn (Δ27LFn–EFn) was a 62-fold more potent toxin inhibitor than LFn or EFn, and this increased activity corresponded to a 39-fold higher PA-binding affinity by Biacore analysis. More importantly, Δ27LFn–EFn could protect the highly susceptible Fischer 344 rats from anthrax lethal toxin challenge. This work suggested that Δ27LFn–EFn has the potential as a candidate therapeutic agent against anthrax. Structured summary MINT- 7014735 , MINT- 7014747 , MINT- 7014761 : PA63 (uniprotkb: P13423 ) and LF (uniprotkb: P15917 ) bind (MI: 0407 ) by surface plasmon resonance (MI: 0107 )
- Published
- 2009
33. Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins
- Author
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Hong Ding, Kunzer Aaron R, Kennan C. Marsh, Saul H. Rosenberg, Jessica Adickes, Wang Xilu, Steven W. Elmore, Stephen W. Fesik, Haichao Zhang, Alexander R. Shoemaker, Joy Bauch, Stephen K. Tahir, Xiufen Yang, Paul Nimmer, Michael D. Wendt, Cheol-Min Park, Xiaohong Song, Milan Bruncko, and Christin Tse
- Subjects
BH3 Mimetic ABT-737 ,Cell Survival ,medicine.medical_treatment ,Drug Evaluation, Preclinical ,Administration, Oral ,Pharmacology ,medicine.disease_cause ,Cell Line ,Mice ,Structure-Activity Relationship ,In vivo ,Oral administration ,Drug Discovery ,medicine ,Animals ,Humans ,B-cell lymphoma ,Chemotherapy ,Sulfonamides ,Molecular Structure ,Chemistry ,Cancer ,medicine.disease ,Xenograft Model Antitumor Assays ,Proto-Oncogene Proteins c-bcl-2 ,Apoptosis ,Molecular Medicine ,Carcinogenesis - Abstract
Overexpression of prosurvival proteins such as Bcl-2 and Bcl-X L has been correlated with tumorigenesis and resistance to chemotherapy, and thus, the development of antagonists of these proteins may provide a novel means for the treatment of cancer. We recently described the discovery of 1 (ABT-737), which binds Bcl-2, Bcl-X L, and Bcl-w with high affinity, shows robust antitumor activity in murine tumor xenograft models, but is not orally bioavailable. Herein, we report that targeted modifications at three key positions of 1 resulted in a 20-fold improvement in the pharmacokinetic/pharmacodynamic relationship (PK/PD) between oral exposure (AUC) and in vitro efficacy in human tumor cell lines (EC 50). The resulting compound, 2 (ABT-263), is orally efficacious in an established xenograft model of human small cell lung cancer, inducing complete tumor regressions in all animals. Compound 2 is currently in multiple phase 1 clinical trials in patients with small cell lung cancer and hematological malignancies.
- Published
- 2008
34. Syntheses of potent, selective, and orally bioavailable indazole-pyridine series of protein kinase B/Akt inhibitors with reduced hypotension
- Author
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James S. Polakowski, Xiaohong Song, R.B. Diebold, Gui-Dong Zhu, Saul H. Rosenberg, Ran Guan, Gary Gintant, Jianchun Gong, Eric F. Johnson, Amanda M. Olson, Qun Li, Jennifer J. Bouska, Xuesong Liu, Keith W. Woods, Vincent S. Stoll, Thomas J Campbell, Klinghofer, Sheela A. Thomas, Mulugeta Mamo, Ruth L. Martin, Thomas D. Penning, Vincent L. Giranda, T. Li, Kennan C. Marsh, Viraj B. Gandhi, and Yan Luo
- Subjects
Models, Molecular ,Indazoles ,Stereochemistry ,Protein Conformation ,Pyridines ,Administration, Oral ,Biological Availability ,Crystallography, X-Ray ,Purkinje Fibers ,chemistry.chemical_compound ,Mice ,Structure-Activity Relationship ,Dogs ,In vivo ,Drug Discovery ,Animals ,Protein kinase A ,Protein kinase B ,Indazole ,biology ,Kinase ,Chemistry ,Stereoisomerism ,Rats ,Biochemistry ,Protein kinase domain ,Enzyme inhibitor ,biology.protein ,Molecular Medicine ,Pyrazoles ,Signal transduction ,Hypotension ,Proto-Oncogene Proteins c-akt - Abstract
Compound 7 was identified as a potent (IC50 = 14 nM), selective, and orally bioavailable (F = 70% in mouse) inhibitor of protein kinase B/Akt. While promising efficacy was observed in vivo, this compound showed effects on depolarization of Purkinje fibers in an in vitro assay and CV hypotension in vivo. Guided by an X-ray structure of 7 bound to protein kinase A, which has 80% homology with Akt in the kinase domain, our efforts have focused on structure-activity relationship (SAR) studies of the phenyl moiety, in an attempt to address the cardiovascular liability and further improve the Akt potency. A novel and efficient synthetic route toward diversely substituted phenyl derivatives of 7 was developed utilizing a copper-mediated aziridine ring-opening reaction as the key step. To improve the selectivity of these Akt inhibitors over other protein kinases, a nitrogen atom was incorporated into selected phenyl analogues of 7 at the C-6 position of the methyl indazole scaffold. These modifications resulted in the discovery of inhibitor 37c with greater potency (IC50 = 0.6 nM vs Akt), selectivity, and improved cardiovascular safety profile. The SARs, pharmacokinetic profile, and CV safety of selected Akt inhibitors will be discussed.
- Published
- 2007
35. Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL
- Author
-
Shi-Chu Ng ng, Xiaohong Song, Milan Bruncko, Cheol-Min Park, Steven W. Elmore, Stephen W. Fesik, Kunzer Aaron R, Wendt Michael D, Saul H. Rosenberg, Mcclellan William J, Barbara A. Belli, Wang Xilu, Thorsten Oost, Andrew M. Petros, Darlene Martineau, Alexander R. Shoemaker, Haichao Zhang, Mary K. Joseph, Michael J. Mitten, Paul Nimmer, Tilman Oltersdorf, and Hong Ding
- Subjects
Models, Molecular ,Lymphoma ,Transplantation, Heterologous ,Follicular lymphoma ,bcl-X Protein ,Bcl-xL ,Antineoplastic Agents ,Mice, SCID ,Piperazines ,Nitrophenols ,Mice ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,medicine ,Animals ,Humans ,Etoposide ,Sulfonamides ,biology ,Chemistry ,Biphenyl Compounds ,medicine.disease ,In vitro ,Transplantation ,Biochemistry ,Proto-Oncogene Proteins c-bcl-2 ,Cell culture ,Apoptosis ,Cancer cell ,Cancer research ,biology.protein ,Molecular Medicine ,Drug Screening Assays, Antitumor ,medicine.drug - Abstract
Overexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide.
- Published
- 2007
36. Identification of a novel 3,5-disubstituted pyridine as a potent, selective, and orally active inhibitor of Akt1 kinase
- Author
-
Yan Luo, Saul H. Rosenberg, Garrick Packard, Tongmei Li, Amanda M. Olson, Xuesong Liu, Keith W. Woods, Eric F. Johnson, Qun Li, Kennan C. Marsh, Vered Klinghofer, John P. Fischer, Shayna R. Magnone, Sheela A. Thomas, Ran Guan, Jennifer J. Bouska, Xiaohong Song, Yan Shi, Vincent L. Giranda, and Robert B. Diebold
- Subjects
Stereochemistry ,Pyridines ,Clinical Biochemistry ,Pharmaceutical Science ,AKT1 ,Administration, Oral ,Protein Serine-Threonine Kinases ,Biochemistry ,Chemical synthesis ,3-Phosphoinositide-Dependent Protein Kinases ,chemistry.chemical_compound ,Mice ,Structure-Activity Relationship ,Drug Discovery ,Pyridine ,Animals ,Enzyme Inhibitors ,Protein kinase A ,Molecular Biology ,Protein kinase B ,Bicyclic molecule ,biology ,Organic Chemistry ,In vitro ,chemistry ,Enzyme inhibitor ,biology.protein ,Molecular Medicine ,Proto-Oncogene Proteins c-akt - Abstract
Based on lead compounds 2 and 3 a series of 3,5-disubstituted pyridines have been designed and evaluated for inhibition of AKT/PKB. Modifications at the 3 position of the pyridine ring led to a number of potent compounds with improved physical properties, resulting in the identification of 11g as a promising, orally active Akt inhibitor. The synthesis, structure–activity relationship studies, and pharmacokinetic data are presented in this paper.
- Published
- 2006
37. The 2beta2-2beta3 loop of anthrax protective antigen contains a dominant neutralizing epitope
- Author
-
Jian Zhao, Junjie Xu, Xiaohong Song, Wei Chen, Ling Fu, Dayong Dong, Guanlin Li, Qiang Guo, and Jun Zhang
- Subjects
medicine.drug_class ,Anthrax toxin ,Bacterial Toxins ,Biophysics ,Monoclonal antibody ,Biochemistry ,Epitope ,Protein Structure, Secondary ,Epitopes ,Mice ,Antigen ,Consensus Sequence ,medicine ,Animals ,Chymotrypsin ,Trypsin ,Molecular Biology ,Antigens, Bacterial ,Anthrax vaccines ,biology ,Linear epitope ,Chemistry ,Antibodies, Monoclonal ,Cell Biology ,biology.organism_classification ,Virology ,Bacillus anthracis ,Epitope mapping ,Epitope Mapping - Abstract
Anthrax toxin consists of three proteins, protective antigen (PA), lethal factor, and edema factor. PA is the major component in the current anthrax vaccine, but the antigenic epitopes on it are not well-defined. We generated a pool of toxin-neutralizing anti-PA monoclonal antibodies (MAbs) to analyze the neutralizing epitopes of PA. Nine toxin-neutralizing MAbs obtained were found bound to three different domains of PA respectively, among which three MAbs with the strongest toxin-neutralizing activity recognized the same epitope within domain 2. This epitope was fine mapped to the chymotrypsin-sensitive site, (312)SFFD(315), in the 2beta(2)-2beta(3) loop of PA, using phage-displayed random peptide libraries and mutation analysis. The result demonstrated for the first time that the 2beta(2)-2beta(3) loop, which is involved in the transition of PA oligomers from prepore to pore, contains a dominant neutralizing epitope. This work contributes to the immunological and functional analysis of PA and offers perspective for the development of a new epitope vaccine against anthrax.
- Published
- 2006
38. Equarin is involved as an FGF signaling modulator in chick lens differentiation
- Author
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Athary Felemban, Kunimasa Ohta, Hiroshi Ochiai, Takashi Yamamoto, Yuya Sato, Ayako Ito, Mahmud Hossain, Kiyotoshi Sekiguchi, Xiaohong Song, and Hideaki Tanaka
- Subjects
Equarin ,Blotting, Western ,Molecular Sequence Data ,Endogeny ,Chick Embryo ,Biology ,In ovo ,Fibroblast growth factor ,Chick ,Avian Proteins ,FGF signaling ,Lens ,Downregulation and upregulation ,In vivo ,Sequence Homology, Nucleic Acid ,Chlorocebus aethiops ,Lens, Crystalline ,medicine ,Animals ,Eye Proteins ,Molecular Biology ,Cells, Cultured ,In Situ Hybridization ,Base Sequence ,Electroporation ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Cell Biology ,Molecular biology ,Immunohistochemistry ,beta-Crystallins ,In vitro ,Cell biology ,Fibroblast Growth Factors ,medicine.anatomical_structure ,Zinc-finger nucleases (ZFNs) ,Lens (anatomy) ,Differentiation ,COS Cells ,Mutation ,Chickens ,Heparan Sulfate Proteoglycans ,Developmental Biology ,Protein Binding ,Signal Transduction - Abstract
Lens growth involves the proliferation of epithelial cells, followed by their migration to the equator region and differentiation into secondary fiber cells. It is widely accepted that fibroblast growth factor (FGF) signaling is required for the differentiation of lens epithelial cells into crystallin-rich fibers, but this signaling is insufficient to induce full differentiation. To better understand lens development, investigatory and functional analyses of novel molecules are required. Here, we demonstrate that Equarin, which is a novel secreted molecule, was expressed exclusively in the lens equator region during chick lens development. Equarin upregulated the expression of fiber markers, as demonstrated using in ovo electroporation. In a primary lens cell culture, Equarin promoted the biochemical and morphological changes associated with the differentiation of lens epithelial cells to fibers. A loss-of-function analysis was performed using zinc-finger nucleases targeting the Equarin gene. Lens cell differentiation was markedly inhibited when endogenous Equarin was blocked, indicating that Equarin was essential for normal chick lens differentiation. Furthermore, biochemical analysis showed that Equarin directly bound to FGFs and heparan sulfate proteoglycan and thereby upregulated the expression of phospho-ERK1/2 (ERK-P) proteins, the downstream of the FGF signaling pathway, in vivo and in vitro. Conversely, the absence of endogenous Equarin clearly diminished FGF-induced fiber differentiation. Taken together, our results suggest that Equarin is involved as an FGF modulator in chick lens differentiation.
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