35 results on '"Picheng Zhao"'
Search Results
2. Presenilin1 regulates Th1 and Th17 effector responses but is not required for experimental autoimmune encephalomyelitis.
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Matthew Cummings, Anitha Christy Sigamani Arumanayagam, Picheng Zhao, Sunil Kannanganat, Olaf Stuve, Nitin J Karandikar, and Todd N Eagar
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Medicine ,Science - Abstract
Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) where pathology is thought to be regulated by autoreactive T cells of the Th1 and Th17 phenotype. In this study we sought to understand the functions of Presenilin 1 (PSEN1) in regulating T cell effector responses in the experimental autoimmune encephalomyelitis (EAE) murine model of MS. PSEN1 is the catalytic subunit of γ-secretase a multimolecular protease that mediates intramembranous proteolysis. γ-secretase is known to regulate several pathways of immune importance. Here we examine the effects of disrupting PSEN1 functions on EAE and T effector differentiation using small molecule inhibitors of γ-secretase (GSI) and T cell-specific conditional knockout mice (PSEN1 cKO). Surprisingly, blocking PSEN1 function by GSI treatment or PSEN1 cKO had little effect on the development or course of MOG35-55-induced EAE. In vivo GSI administration reduced the number of myelin antigen-specific T cells and suppressed Th1 and Th17 differentiation following immunization. In vitro, GSI treatment inhibited Th1 differentiation in neutral but not IL-12 polarizing conditions. Th17 differentiation was also suppressed by the presence of GSI in all conditions and GSI-treated Th17 T cells failed to induce EAE following adoptive transfer. PSEN cKO T cells showed reduced Th1 and Th17 differentiation. We conclude that γ-secretase and PSEN1-dependent signals are involved in T effector responses in vivo and potently regulate T effector differentiation in vitro, however, they are dispensable for EAE.
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- 2018
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3. Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307
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S. Wesley Long, Randall J. Olsen, Todd N. Eagar, Stephen B. Beres, Picheng Zhao, James J. Davis, Thomas Brettin, Fangfang Xia, and James M. Musser
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Microbiology ,QR1-502 - Abstract
ABSTRACT Klebsiella pneumoniae is a major human pathogen responsible for high morbidity and mortality rates. The emergence and spread of strains resistant to multiple antimicrobial agents and documented large nosocomial outbreaks are especially concerning. To develop new therapeutic strategies for K. pneumoniae, it is imperative to understand the population genomic structure of strains causing human infections. To address this knowledge gap, we sequenced the genomes of 1,777 extended-spectrum beta-lactamase-producing K. pneumoniae strains cultured from patients in the 2,000-bed Houston Methodist Hospital system between September 2011 and May 2015, representing a comprehensive, population-based strain sample. Strains of largely uncharacterized clonal group 307 (CG307) caused more infections than those of well-studied epidemic CG258. Strains varied markedly in gene content and had an extensive array of small and very large plasmids, often containing antimicrobial resistance genes. Some patients with multiple strains cultured over time were infected with genetically distinct clones. We identified 15 strains expressing the New Delhi metallo-beta-lactamase 1 (NDM-1) enzyme that confers broad resistance to nearly all beta-lactam antibiotics. Transcriptome sequencing analysis of 10 phylogenetically diverse strains showed that the global transcriptome of each strain was unique and highly variable. Experimental mouse infection provided new information about immunological parameters of host-pathogen interaction. We exploited the large data set to develop whole-genome sequence-based classifiers that accurately predict clinical antimicrobial resistance for 12 of the 16 antibiotics tested. We conclude that analysis of large, comprehensive, population-based strain samples can assist understanding of the molecular diversity of these organisms and contribute to enhanced translational research. IMPORTANCE Klebsiella pneumoniae causes human infections that are increasingly difficult to treat because many strains are resistant to multiple antibiotics. Clonal group 258 (CG258) organisms have caused outbreaks in health care settings worldwide. Using a comprehensive population-based sample of extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae strains, we show that a relatively uncommon clonal type, CG307, caused the plurality of ESBL-producing K. pneumoniae infections in our patients. We discovered that CG307 strains have been abundant in Houston for many years. As assessed by experimental mouse infection, CG307 strains were as virulent as pandemic CG258 strains. Our results may portend the emergence of an especially successful clonal group of antibiotic-resistant K. pneumoniae.
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- 2017
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4. In Vivo Near-Infrared Noninvasive Glucose Measurement and Detection in Humans
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Tongshuai Han, null Jin Liu, null Rong Liu, Wenliang Chen, Mingfei Yao, Xueyu Liu, Qing Ge, Zengfu Zhang, Chenxi Li, Yuxiang Wang, Picheng Zhao, Di Sun, and Kexin Xu
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Blood Glucose ,Glucose ,Spectroscopy, Near-Infrared ,Humans ,Glucose Tolerance Test ,Signal-To-Noise Ratio ,Instrumentation ,Spectroscopy - Abstract
In optical noninvasive glucose detection, how to detect the glucose-caused signals from the constant human variations and disturbed probing conditions is always the biggest challenge. Developing effective measurement strategies is essential to realize the detection. A near-infrared (NIR) spectroscopy-based strategy is studied to effectively solve the in vivo measurement issues, obtaining clean blood glucose-caused signals. Two solutions composing our strategy are applied to the NIR spectroscopy-based measurement system to acquire clean raw signals in the data collection, which are a customized high signal-to-noise ratio multi-ring InGaAs detector to reduce the influence of human variations, and a fixing and aiming method to reproduce a consistent measurement condition. Seventeen cases of glucose tolerance test (GTT) on healthy and diabetic volunteers were conducted to validate the strategy. The human experiment results clearly show that the expected blood glucose changes have been detected at 1550 nm. The average correlation coefficient of the 17 cases of GTT between light signal and glucose reference reaches 0.84. The proposed measurement strategy is verified feasible for the glucose detecting in vivo. The strategy provides references to further studies and product developments for the NIR spectroscopy-based glucose measurement and references to other optical measurements in vivo.
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- 2022
5. Treatment of Coronavirus Disease 2019 Patients with Convalescent Plasma Reveals a Signal of Significantly Decreased Mortality
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Bevin Valdez Lopez, Edward A. Graviss, Duc T. Nguyen, Paul A. Christensen, Jimmy Gollihar, James M. Musser, John Rogers, Picheng Zhao, Randall J. Olsen, Eric Salazar, Todd N. Eagar, Xin Yi, Ahmed Shehabeldin, Christopher Leveque, Brian Castillo, Jian Chen, David Joseph, and David W. Bernard
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Pneumonia, Viral ,Blood Component Transfusion ,Article ,Pathology and Forensic Medicine ,Betacoronavirus ,Plasma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Epidemiology ,Humans ,Medicine ,Prospective Studies ,030212 general & internal medicine ,Prospective cohort study ,Pandemics ,COVID-19 Serotherapy ,Aged ,Aged, 80 and over ,biology ,SARS-CoV-2 ,business.industry ,Immunization, Passive ,COVID-19 ,Middle Aged ,Interim analysis ,medicine.disease ,Titer ,Pneumonia ,030104 developmental biology ,biology.protein ,Breathing ,Female ,Antibody ,Coronavirus Infections ,business ,Body mass index - Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread globally, and proven treatments are limited. Transfusion of convalescent plasma collected from donors who have recovered from COVID-19 is among many approaches being studied as potentially efficacious therapy. We are conducting a prospective, propensity score-matched study assessing the efficacy of COVID-19 convalescent plasma transfusion versus standard of care as treatment for severe and/or critical COVID-19. We present herein the results of an interim analysis of 316 patients enrolled at Houston Methodist hospitals from March 28 to July 6, 2020. Of the 316 transfused patients, 136 met a 28-day outcome and were matched to 251 non-transfused control COVID-19 patients. Matching criteria included age, sex, body mass index, comorbidities, and baseline ventilation requirement 48 hours from admission, and in a second matching analysis, ventilation status at day 0. Variability in the timing of transfusion relative to admission and titer of antibodies of plasma transfused allowed for analysis in specific matched cohorts. The analysis showed a significant reduction (P = 0.047) in mortality within 28 days, specifically in patients transfused within 72 hours of admission with plasma with an anti-spike protein receptor binding domain titer of ≥1:1350. These data suggest that treatment of COVID-19 with high anti-receptor binding domain IgG titer convalescent plasma is efficacious in early-disease patients.
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- 2020
6. Rapamycin-Loaded Biomimetic Nanoparticles Reverse Vascular Inflammation
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Tomoyuki Naoi, Ennio Tasciotti, Manuela Sushnitha, Barry H. Trachtenberg, John P. Cooke, Roman A. Sukhovershin, Roberto Molinaro, Assaf Zinger, Christian Boada, Jonathan O. Martinez, Kelly A. Hartman, Picheng Zhao, and Christopher Tsao
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0301 basic medicine ,1,2-Dipalmitoylphosphatidylcholine ,Physiology ,Drug Evaluation, Preclinical ,Inflammation ,02 engineering and technology ,Mechanistic Target of Rapamycin Complex 1 ,Mice ,Random Allocation ,03 medical and health sciences ,Apolipoproteins E ,Biomimetics ,Animals ,Medicine ,Aorta ,Sirolimus ,Aortitis ,Neovascularization, Pathologic ,business.industry ,Vascular inflammation ,Vascular disease ,Macrophages ,Cryoelectron Microscopy ,Membrane Proteins ,Macrophage Activation ,Biomimetic nanoparticles ,Atherosclerosis ,021001 nanoscience & nanotechnology ,medicine.disease ,Plaque, Atherosclerotic ,Mice, Inbred C57BL ,C-Reactive Protein ,030104 developmental biology ,Organ Specificity ,Drug delivery ,Phosphatidylcholines ,Cancer research ,Cytokines ,Nanoparticles ,medicine.symptom ,0210 nano-technology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Rationale: Through localized delivery of rapamycin via a biomimetic drug delivery system, it is possible to reduce vascular inflammation and thus the progression of vascular disease. Objective: Use biomimetic nanoparticles to deliver rapamycin to the vessel wall to reduce inflammation in an in vivo model of atherosclerosis after a short dosing schedule. Methods and Results: Biomimetic nanoparticles (leukosomes) were synthesized using membrane proteins purified from activated J774 macrophages. Rapamycin-loaded nanoparticles were characterized using dynamic light scattering and were found to have a diameter of 108±2.3 nm, a surface charge of −15.4±14.4 mV, and a polydispersity index of 0.11 +/ 0.2. For in vivo studies, ApoE −/− mice were fed a high-fat diet for 12 weeks. Mice were injected with either PBS, free rapamycin (5 mg/kg), or rapamycin-loaded leukosomes (Leuko-Rapa; 5 mg/kg) once daily for 7 days. In mice treated with Leuko-Rapa, flow cytometry of disaggregated aortic tissue revealed fewer proliferating macrophages in the aorta (15.6±9.79 %) compared with untreated mice (30.2±13.34 %) and rapamycin alone (26.8±9.87 %). Decreased macrophage proliferation correlated with decreased levels of MCP (monocyte chemoattractant protein)-1 and IL (interleukin)-b1 in mice treated with Leuko-Rapa. Furthermore, Leuko-Rapa–treated mice also displayed significantly decreased MMP (matrix metalloproteinases) activity in the aorta (mean difference 2554±363.9, P =9.95122×10 −6 ). No significant changes in metabolic or inflammation markers observed in liver metabolic assays. Histological analysis showed improvements in lung morphology, with no alterations in heart, spleen, lung, or liver in Leuko-Rapa–treated mice. Conclusions: We showed that our biomimetic nanoparticles showed a decrease in proliferating macrophage population that was accompanied by the reduction of key proinflammatory cytokines and changes in plaque morphology. This proof-of-concept showed that our platform was capable of suppressing macrophage proliferation within the aorta after a short dosing schedule (7 days) and with a favorable toxicity profile. This treatment could be a promising intervention for the acute stabilization of late-stage plaques.
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- 2020
7. Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages
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Xin Wang, Christian Boada, Claudia Corbo, Anna Pastò, Federica Giordano, Jonathan O. Martinez, Assaf Zinger, Picheng Zhao, Ennio Tasciotti, Roberto Molinaro, Francesca Taraballi, Kelly A. Hartman, Molinaro, R, Pasto, A, Corbo, C, Taraballi, F, Giordano, F, Martinez, J, Zhao, P, Wang, X, Zinger, A, Boada, C, Hartman, K, and Tasciotti, E
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Extracellular Vesicle ,Macrophage ,medicine.drug_class ,Anti-Inflammatory Agents ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Anti-inflammatory ,Cell Line ,Sepsis ,Extracellular Vesicles ,Mice ,Nanoparticle ,Biomimetic Materials ,Gene expression ,Animals ,Medicine ,General Materials Science ,Mice, Inbred BALB C ,Endothelial Cell ,Monokine ,Animal ,business.industry ,Cell adhesion molecule ,Macrophages ,Monokines ,Endothelial Cells ,021001 nanoscience & nanotechnology ,medicine.disease ,In vitro ,0104 chemical sciences ,Anti-Inflammatory Agent ,Cell culture ,Cancer research ,Nanoparticles ,Nanomedicine ,0210 nano-technology ,business ,Biomimetic Material - Abstract
Despite numerous advances in medical treatment, sepsis remains one of the leading causes of death worldwide. Sepsis is characterized by the involvement of all organs and tissues as a consequence of blood poisoning, resulting in organ failure and eventually death. Effective treatment remains an unmet need and novel approaches are urgently needed. The growing evidence of clinical and biological heterogeneity of sepsis suggests precision medicine as a possible key for achieving therapeutic breakthroughs. In this scenario, biomimetic nanomedicine represents a promising avenue for the treatment of inflammatory diseases, including sepsis. We investigated the role of macrophage-derived biomimetic nanoparticles, namely leukosomes, in a lipopolysaccharide-induced murine model of sepsis. We observed that treatment with leukosomes was associated with significantly prolonged survival. In vitro studies elucidated the potential mechanism of action of these biomimetic vesicles. The direct treatment of endothelial cells (ECs) with leukosomes did not alter the gene expression profile of EC-associated cell adhesion molecules. In contrast, the interaction of leukosomes with macrophages induced a decrease of pro-inflammatory genes (IL-6, IL-1b, and TNF-α), an increase of anti-inflammatory ones (IL-10 and TGF-β), and indirectly an anti-inflammatory response on ECs. Taken together, these results showed the ability of leukosomes to regulate the inflammatory response in target cells, acting as a bioactive nanotherapeutic.
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- 2019
8. Limited window for donation of convalescent plasma with high live-virus neutralizing antibody titers for COVID-19 immunotherapy
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Suresh V. Kuchipudi, Denver Greenawalt, David W. Bernard, Eric Salazar, James M. Musser, Picheng Zhao, Allen M. Minns, Paul A. Christensen, Catherine M. Herzog, Xin Yi, Abhinay Gontu, Ruth H. Nissly, Meera Surendran Nair, Jimmy Gollihar, Vivek Kapur, Scott E. Lindner, Ian M. Bird, Indira Poojary, Robab Katani, Brian Castillo, Todd N. Eagar, Matthew J. Ferrari, Christopher Leveque, Sreenidhi Srinivasan, Randall M. Rossi, Randall J. Olsen, and Jian Chen
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Adult ,Male ,0301 basic medicine ,Time Factors ,QH301-705.5 ,viruses ,medicine.medical_treatment ,Medicine (miscellaneous) ,Blood Donors ,Antibodies, Viral ,Severity of Illness Index ,Article ,General Biochemistry, Genetics and Molecular Biology ,Neutralization ,Immunoglobulin G ,Young Adult ,03 medical and health sciences ,Applied immunology ,0302 clinical medicine ,medicine ,Humans ,Longitudinal Studies ,030212 general & internal medicine ,Biology (General) ,Neutralizing antibody ,Aged ,biology ,SARS-CoV-2 ,business.industry ,Age Factors ,Antibody titer ,COVID-19 ,Immunotherapy ,Middle Aged ,Antibodies, Neutralizing ,Titer ,030104 developmental biology ,Immunoglobulin M ,Immunology ,biology.protein ,Female ,Antibody ,General Agricultural and Biological Sciences ,business - Abstract
Millions of individuals who have recovered from SARS-CoV-2 infection may be eligible to participate in convalescent plasma donor programs, yet the optimal window for donating high neutralizing titer convalescent plasma for COVID-19 immunotherapy remains unknown. Here we studied the response trajectories of antibodies directed to the SARS-CoV-2 surface spike glycoprotein and in vitro SARS-CoV-2 live virus neutralizing titers (VN) in 175 convalescent donors longitudinally sampled for up to 142 days post onset of symptoms (DPO). We observed robust IgM, IgG, and viral neutralization responses to SARS-CoV-2 that persist, in the aggregate, for at least 100 DPO. However, there is a notable decline in VN titers ≥160 for convalescent plasma therapy, starting 60 DPO. The results also show that individuals 30 years of age or younger have significantly lower VN, IgG and IgM antibody titers than those in the older age groups; and individuals with greater disease severity also have significantly higher IgM and IgG antibody titers. Taken together, these findings define the optimal window for donating convalescent plasma useful for immunotherapy of COVID-19 patients and reveal important predictors of an ideal plasma donor., Gontu et al. conducted a longitudinal study in COVID patients in which they assessed the response trajectories of antibodies directed to the SARS-CoV-2 surface spike glycoprotein and in vitro SARS-CoV-2 live virus neutralizing titers. Their measurements demonstrate the presence of an optimum window for convalescent plasma donation as well as predictions of the most suitable donor type.
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- 2021
9. Convalescent plasma anti–SARS-CoV-2 spike protein ectodomain and receptor-binding domain IgG correlate with virus neutralization
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Jimmy Gollihar, David Bernard, Vivek Kapur, Abhinay Gontu, Gregory C. Ippolito, Sreenidhi Srinivasan, Randall M. Rossi, Indira Poojary, Laura I. Prugar, Randall J. Olsen, Eric Salazar, Peter J. Hudson, Jose A. Cardona, James M. Musser, Ian M. Bird, Zhicheng Jin, Nicole M. Josleyn, Todd N. Eagar, Denver Greenawalt, Picheng Zhao, Kathleen E. Huie, John M. Dye, Dalton M Towers, Suresh V. Kuchipudi, Jian Chen, Andrew S. Herbert, Christopher Leveque, Xin Yi, Isabella M. Cattadori, Ruth H. Nissly, Brian Castillo, Jason J. Lavinder, S. Wesley Long, and Paul A. Christensen
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Adult ,Male ,0301 basic medicine ,Adolescent ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Antibodies, Viral ,Asymptomatic ,Article ,Immunoglobulin G ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,COVID-19 Serotherapy ,Aged ,biology ,SARS-CoV-2 ,business.industry ,Immunization, Passive ,COVID-19 ,General Medicine ,Middle Aged ,Acquired immune system ,Antibodies, Neutralizing ,In vitro ,Titer ,030104 developmental biology ,Ectodomain ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Female ,medicine.symptom ,Antibody ,business ,Research Article - Abstract
Newly emerged pathogens such as SARS-CoV-2 highlight the urgent need for assays that detect levels of neutralizing antibodies that may be protective. We studied the relationship between anti-spike ectodomain (ECD) and anti-receptor binding domain (RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by two different in vitro assays using convalescent plasma samples obtained from 68 COVID-19 patients, including 13 who donated plasma multiple times. Only 23% (16/68) of donors had been hospitalized. We also studied 16 samples from subjects found to have anti-spike protein IgG during surveillance screening of asymptomatic individuals. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers, and in vitro VN titer. Anti-RBD plasma IgG correlated slightly better than anti-ECD IgG titer with VN titer. The probability of a VN titer ≥160 was 80% or greater with anti-RBD or anti-ECD titers of ≥1:1350. Thirty-seven percent (25/68) of convalescent plasma donors lacked VN titers ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease either VN or IgG titers. Analysis of 2,814 asymptomatic adults found 27 individuals with anti-RBD or anti-ECD IgG titers of ≥1:1350, and evidence of VN ≥1:160. Taken together, we conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titer of ≥1:1350 may provide critical information about protection against COVID-19 disease.
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- 2020
10. Early transfusion of a large cohort of COVID-19 patients with high titer anti-SARS-CoV-2 spike protein IgG convalescent plasma confirms a signal of significantly decreased mortality
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David Joseph, David W. Bernard, Jimmy Gollihar, Bevin Valdez Lopez, John Rogers, James M. Musser, Duc T. Nguyen, Ahmed Shehabeldin, Randall J. Olsen, Paul A. Christensen, Faisal Masud, Xin Yi, Christopher Leveque, Eric Salazar, Picheng Zhao, Jian Chen, Edward A. Graviss, Todd N. Eagar, and Brian Castillo
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Emergency Use Authorization ,medicine.medical_specialty ,Convalescent plasma ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Interim analysis ,Gastroenterology ,Titer ,Internal medicine ,Cohort ,medicine ,High titer ,business - Abstract
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 remains a global threat with few proven efficacious treatments. Transfusion of convalescent plasma collected from donors who have recovered from COVID-19 disease has emerged as a promising therapy and has been granted emergency use authorization by the U.S. Food and Drug Administration (FDA). We recently reported results from interim analysis of a propensity-score matched study suggesting that early treatment of COVID-19 patients with convalescent plasma containing high titer anti-spike protein receptor binding domain (RBD) IgG significantly decreases mortality. We here present results from 60-day follow up of our cohort of 351 transfused hospitalized patients. Prospective determination of ELISA anti-RBD IgG titer facilitated selection and transfusion of the highest titer units available. Retrospective analysis by the Ortho VITROS IgG assay revealed a median signal/cutoff (S/C) ratio of 24.0 for transfused units, a value far exceeding the recently FDA-required cutoff of 12.0 for designation of high titer convalescent plasma. With respect to altering mortality, our analysis identified an optimal window of 44 hours post-hospitalization for transfusing COVID-19 patients with high titer convalescent plasma. In the aggregate, the analysis confirms and extends our previous preliminary finding that transfusion of COVID-19 patients soon after hospitalization with high titer anti-spike protein RBD IgG present in convalescent plasma significantly reduces mortality.
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- 2020
11. Limited window for donation of convalescent plasma with high live-virus neutralizing antibodies for COVID-19 immunotherapy
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Xin Yi, Ruth H. Nissly, Jian Chen, Catherine M. Herzog, Matthew J. Ferrari, Allen M. Minns, Christopher Leveque, Suresh V. Kuchipudi, Scott E. Lindner, Paul A. Christensen, Todd N. Eagar, Denver Greenawalt, Eric Salazar, David W. Bernard, Vivek Kapur, Robab Katani, James M. Musser, Indira Poojary, Abhinay Gontu, Meera Surendran Nair, Ian M. Bird, Jimmy Gollihar, Brian Castillo, Picheng Zhao, Sreenidhi Srinivasan, Randall M. Rossi, and Randall J. Olsen
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chemistry.chemical_classification ,biology ,business.industry ,medicine.medical_treatment ,Immunotherapy ,Neutralization ,In vitro ,Titer ,chemistry ,Ectodomain ,Immunology ,medicine ,biology.protein ,Knowledge deficit ,Antibody ,Glycoprotein ,business - Abstract
The optimal timeframe for donating convalescent plasma to be used for COVID-19 immunotherapy is unknown. To address this important knowledge deficit, we determinedin vitrolive-virus neutralizing capacity and persistence of IgM and IgG antibody responses against the receptor-binding domain and S1 ectodomain of the SARS-CoV-2 spike glycoprotein in 540 convalescent plasma samples obtained from 175 COVID-19 plasma donors for up to 142 days post-symptom onset. Robust IgM, IgG, and viral neutralization responses to SARS-CoV-2 persist, in the aggregate, for at least 100 days post-symptom onset. However, a notable acceleration in decline in virus neutralization titers ≥160, a value suitable for convalescent plasma therapy, was observed starting 60 days after first symptom onset. Together, these findings better define the optimal window for donating convalescent plasma useful for immunotherapy of COVID-19 patients and reveal important predictors of an ideal plasma donor, including age and COVID-19 disease severity score.One Sentence SummaryEvaluation of SARS-CoV-2 anti-spike protein IgM, IgG, and live-virus neutralizing titer profiles reveals that the optimal window for donating convalescent plasma for use in immunotherapy is within the first 60 days of symptom onset.
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- 2020
12. Relationship between Anti-Spike Protein Antibody Titers and SARS-CoV-2In VitroVirus Neutralization in Convalescent Plasma
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Ruth H. Nissly, Laura I. Prugar, Peter J. Hudson, Eric Salazar, Nicole Joselyn, S. Wesley Long, Abinhay Gontu, Picheng Zhao, José Rubén Parra Cardona, Vivek Kapur, Suresh V. Kuchipudi, Zhicheng Jin, Denver Greenawalt, Sreenidhi Srinivasan, David W. Bernard, Randall M. Rossi, Randall J. Olsen, Jason J. Lavinder, Indira Poojary, Ian M. Bird, Andrew S. Herbert, Xin Yi, Isabella M. Cattadori, Gregory C. Ippolito, John M. Dye, Dalton M Towers, Brian Castillo, James M. Musser, Jian Chen, Paul A. Christensen, Jimmy Gollihar, Kathleen E. Huie, Todd N. Eagar, and Christopher Leveque
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Convalescent plasma ,biology ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Antibody titer ,Asymptomatic ,In vitro ,Titer ,Blood plasma ,Immunology ,biology.protein ,Medicine ,Antibody ,medicine.symptom ,business - Abstract
Newly emerged pathogens such as SARS-CoV-2 highlight the urgent need for assays that detect levels of neutralizing antibodies that may be protective. We studied the relationship between anti-spike ectodomain (ECD) and anti-receptor binding domain (RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by two differentin vitroassays using convalescent plasma samples obtained from 68 COVID-19 patients, including 13 who donated plasma multiple times. Only 23% (16/68) of donors had been hospitalized. We also studied 16 samples from subjects found to have anti-spike protein IgG during surveillance screening of asymptomatic individuals. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers, andin vitroVN titer. Anti-RBD plasma IgG correlated slightly better than anti-ECD IgG titer with VN titer. The probability of a VN titer ≥160 was 80% or greater with anti-RBD or anti-ECD titers of ≥1:1350. Thirty-seven percent (25/68) of convalescent plasma donors lacked VN titers ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease either VN or IgG titers. Analysis of 2,814 asymptomatic adults found 27 individuals with anti-RBD or anti-ECD IgG titers of ≥1:1350, and evidence of VN ≥1:160. Taken together, we conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titer of ≥1:1350 may provide critical information about protection against COVID-19 disease.
- Published
- 2020
13. Two-stage induced differentiation of OCT4+/Nanog+ stem-like cells in lung adenocarcinoma
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Yanwei Zhang, Xifeng Wu, David W. Chang, Yuqing Lou, Qianggang Dong, Meili Ma, Lixia Wu, Jinsu Huang, Baohui Han, Picheng Zhao, and Rong Li
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0301 basic medicine ,Homeobox protein NANOG ,cancer stem cell ,Lung Neoplasms ,Time Factors ,Cellular differentiation ,vitamin D ,Antineoplastic Agents ,Mice, SCID ,OCT4 ,Adenocarcinoma ,Hydroxamic Acids ,03 medical and health sciences ,0302 clinical medicine ,Cancer stem cell ,Mice, Inbred NOD ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Clonogenic assay ,Cholecalciferol ,Vorinostat ,business.industry ,Transdifferentiation ,Nanog Homeobox Protein ,Cell Differentiation ,differentiation ,Vitamins ,medicine.disease ,lung adenocarcinoma ,Hypoxia-Inducible Factor 1, alpha Subunit ,Xenograft Model Antitumor Assays ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Neoplastic Stem Cells ,Female ,RNA Interference ,Stem cell ,Cisplatin ,business ,Octamer Transcription Factor-3 ,Research Paper - Abstract
Stem-like cells in solid tumors are purported to contribute to cancer development and poor treatment outcome. The abilities to self-renew, differentiate, and resist anticancer therapies are hallmarks of these rare cells, and steering them into lineage commitment may be one strategy to curb cancer development or progression. Vitamin D is a prohormone that can alter cell growth and differentiation and may induce the differentiation cancer stem-like cells. In this study, octamer-binding transcription factor 4 (OCT4)-positive/Nanog homeobox (Nanog)- positive lung adenocarcinoma stem-like cells (LACSCs) were enriched from spheroid cultured SPC-A1 cells and differentiated by a two-stage induction (TSI) method, which involved knockdown of hypoxia-inducible factor 1-alpha (HIF1α) expression (first stage) followed by sequential induction with 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3, VD3) and suberoylanilide hydroxamic acid (SAHA) treatment (second stage). The results showed the HIF1α-knockdowned cells displayed diminished cell invasion and clonogenic activities. Moreover, the TSI cells highly expressed tumor suppressor protein p63 (P63) and forkhead box J1 (FOXJ1) and lost stem cell characteristics, including absent expression of OCT4 and Nanog. These cells regained sensitivity to cisplatin in vitro while losing tumorigenic capacity and decreased tumor cell proliferation in vivo. Our results suggest that induced transdifferentiation of LACSCs by vitamin D and SAHA may become novel therapeutic avenue to alter tumor cell phenotypes and improve patient outcome. SIGNIFICANCE STATEMENT The development and progression of lung cancer may involve rare population of stem-like cells that have the ability to grow, differentiate, and resist drug treatment. However, current therapeutic strategies have mostly focused on tumor characteristics and neglected the potential source of cells that may contribute to poor clinical outcome. We generated lung adenocarcinoma stem-like cells from spheroid culture and induced their transdifferentiation by a two-stage method of knocking down HIF1α expression followed by vitamin Dand suberoylanilide hydroxamic acid (VD3/SAHA) treatment. We observed the induced cells lost stem-like characteristics, regained sensitivity to cisplatin, and displayed reduced tumorigenic capacity. These findings suggest that targeting stem-like cells by reverting them to more specialized state may be an approach to treat lung cancer.
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- 2016
14. Serpin-9 and -13 regulate hemolymph proteases during immune responses of Manduca sexta
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Haobo Jiang, Yan He, Xiaolong Cao, Subrahmanyam Rayaprolu, Picheng Zhao, Xiuhong Wang, and Yang Wang
- Subjects
0301 basic medicine ,Proteases ,animal structures ,medicine.medical_treatment ,Cathepsin G ,Serpin ,Biochemistry ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Hemolymph ,Manduca ,medicine ,Animals ,Amino Acid Sequence ,Molecular Biology ,Serpins ,Serine protease ,Enzyme Precursors ,Protease ,biology ,Elastase ,fungi ,Trypsin ,carbohydrates (lipids) ,030104 developmental biology ,chemistry ,Insect Science ,Larva ,embryonic structures ,biology.protein ,Insect Proteins ,030217 neurology & neurosurgery ,Catechol Oxidase ,medicine.drug ,Peptide Hydrolases - Abstract
Serpins are a superfamily of proteins, most of which inhibit cognate serine proteases by forming inactive acyl-enzyme complexes. In the tobacco hornworm Manduca sexta, serpin-1, -3 through -7 negatively regulate a hemolymph serine protease system that activates precursors of the serine protease homologs (SPHs), phenoloxidases (POs), Spatzles, and other cytokines. Here we report the cloning and characterization of M. sexta serpin-9 and -13. Serpin-9, a 402-residue protein most similar to Drosophila Spn77Ba, has R366 at the P1 position right before the cleavage site; Serpin-13, a 444-residue ortholog of Drosophila Spn28Dc, is longer than the other seven serpins and has R410 as the P1 residue. Both serpins are mainly produced in fat body and secreted into plasma to function. While their mRNA and protein levels were not up-regulated upon immune challenge, they blocked protease activities and affected proPO activation in hemolymph. Serpin-9 inhibited human neutrophil elastase, cathepsin G, trypsin, and chymotrypsin to different extents; serpin-13 reduced trypsin activity to approximately 10% at a molar ratio of 4:1 (serpin: enzyme). Serpin-9 was cleaved at Arg366 by the enzymes with different specificity, but serpin-13 had four P1 sites (Arg410 for trypsin-like proteases, Gly406 and Ala409 for the elastase and Thr404 for cathepsin G). Supplementation of induced cell-free hemolymph (IP, P for plasma) with recombinant serpin-9 did not noticeably affect proPO activation, but slightly reduced the PO activity increase after 0–50% ammonium sulfate fraction of the IP had been elicited by bacteria. In comparison, addition of recombinant serpin-13 significantly inhibited proPO activation in IP and the suppression was stronger in the fraction of IP. Serpin-9- and -13-containing protein complexes were isolated from IP using their antibodies. Hemolymph protease-1 precursor (proHP1), HP6 and HP8 were found to be associated with serpin-9, whereas proHP1, HP2 and HP6 were pulled downed with serpin-13. These results indicate that both serpins regulate immune proteases in hemolymph of M. sexta larvae.
- Published
- 2017
15. Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307
- Author
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Picheng Zhao, Fangfang Xia, James J. Davis, Randall J. Olsen, Thomas Brettin, James M. Musser, S. Wesley Long, Todd N. Eagar, and Stephen B. Beres
- Subjects
0301 basic medicine ,DNA, Bacterial ,Klebsiella pneumoniae ,medicine.drug_class ,030106 microbiology ,Population ,Antibiotics ,Virulence ,Human pathogen ,Drug resistance ,Microbial Sensitivity Tests ,Microbiology ,beta-Lactamases ,Disease Outbreaks ,03 medical and health sciences ,Mice ,Antibiotic resistance ,Virology ,Drug Resistance, Multiple, Bacterial ,medicine ,Animals ,Humans ,education ,Escherichia coli Infections ,education.field_of_study ,biology ,Gene Expression Profiling ,Outbreak ,High-Throughput Nucleotide Sequencing ,biology.organism_classification ,Texas ,QR1-502 ,Anti-Bacterial Agents ,Bacterial Typing Techniques ,Electrophoresis, Gel, Pulsed-Field ,Klebsiella Infections ,Molecular Typing ,Host-Pathogen Interactions ,Metagenomics ,Genome, Bacterial ,Research Article ,Plasmids - Abstract
Klebsiella pneumoniae is a major human pathogen responsible for high morbidity and mortality rates. The emergence and spread of strains resistant to multiple antimicrobial agents and documented large nosocomial outbreaks are especially concerning. To develop new therapeutic strategies for K. pneumoniae, it is imperative to understand the population genomic structure of strains causing human infections. To address this knowledge gap, we sequenced the genomes of 1,777 extended-spectrum beta-lactamase-producing K. pneumoniae strains cultured from patients in the 2,000-bed Houston Methodist Hospital system between September 2011 and May 2015, representing a comprehensive, population-based strain sample. Strains of largely uncharacterized clonal group 307 (CG307) caused more infections than those of well-studied epidemic CG258. Strains varied markedly in gene content and had an extensive array of small and very large plasmids, often containing antimicrobial resistance genes. Some patients with multiple strains cultured over time were infected with genetically distinct clones. We identified 15 strains expressing the New Delhi metallo-beta-lactamase 1 (NDM-1) enzyme that confers broad resistance to nearly all beta-lactam antibiotics. Transcriptome sequencing analysis of 10 phylogenetically diverse strains showed that the global transcriptome of each strain was unique and highly variable. Experimental mouse infection provided new information about immunological parameters of host-pathogen interaction. We exploited the large data set to develop whole-genome sequence-based classifiers that accurately predict clinical antimicrobial resistance for 12 of the 16 antibiotics tested. We conclude that analysis of large, comprehensive, population-based strain samples can assist understanding of the molecular diversity of these organisms and contribute to enhanced translational research., IMPORTANCE Klebsiella pneumoniae causes human infections that are increasingly difficult to treat because many strains are resistant to multiple antibiotics. Clonal group 258 (CG258) organisms have caused outbreaks in health care settings worldwide. Using a comprehensive population-based sample of extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae strains, we show that a relatively uncommon clonal type, CG307, caused the plurality of ESBL-producing K. pneumoniae infections in our patients. We discovered that CG307 strains have been abundant in Houston for many years. As assessed by experimental mouse infection, CG307 strains were as virulent as pandemic CG258 strains. Our results may portend the emergence of an especially successful clonal group of antibiotic-resistant K. pneumoniae.
- Published
- 2017
16. Inhibition of the Purinergic Pathway Prolongs Mouse Lung Allograft Survival
- Author
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Xiao Wu, Paolo Fiorina, Xiaofeng Su, Khadija Iken, Andrea Vergani, Carmen Fotino, Gary A. Visner, Moufida Ben Nasr, Kaifeng Liu, Picheng Zhao, and Dawei Jiang
- Subjects
CD4-Positive T-Lymphocytes ,Graft Rejection ,Pulmonary and Respiratory Medicine ,Time Factors ,Purinergic P2X Receptor Antagonists ,medicine.medical_treatment ,Suramin ,Clinical Biochemistry ,CD8-Positive T-Lymphocytes ,Biology ,Major histocompatibility complex ,Mice ,Adenosine Triphosphate ,medicine ,Animals ,Lung transplantation ,Lung ,Molecular Biology ,Mice, Inbred BALB C ,Graft Survival ,Purinergic receptor ,Immunosuppression ,Cell Biology ,respiratory system ,Allografts ,Mice, Inbred C57BL ,Transplantation ,surgical procedures, operative ,medicine.anatomical_structure ,Histocompatibility ,Immunology ,biology.protein ,Cancer research ,Receptors, Purinergic P2X7 ,Immunosuppressive Agents ,CD8 ,Lung Transplantation ,Signal Transduction ,medicine.drug - Abstract
Lung transplantation has limited survival with current immunosuppression. ATP is released from activated T cells, which act as costimulatory molecules through binding to the purinergic receptor P2XR7. We investigated the role of blocking the ATP/purinergic pathway, primarily P2XR7, using its inhibitor oxidized ATP (oATP) in modulating rejection of mouse lung allografts. Mouse lung transplants were performed using mice with major histocompatibility complex mismatch, BALB/c to C57BL6. Recipients received suramin or oATP, and lung allografts were evaluated 15 to ≥ 60 days after transplantation. Recipients were also treated with oATP after the onset of moderate to severe rejection to determine its ability to rescue lung allografts. Outcomes measures included lung function, histology, thoracic imaging, and allo-immune responses. Blocking purinergic receptors with the nonselective inhibitor suramin or with the P2XR7-selective inhibitor oATP reduced acute rejection and prolonged lung allograft survival for ≥ 60 days with no progression in severity. There were fewer inflammatory cells within lung allografts, less rejection, and improved lung function, which was maintained over time. CD4 and CD8 T cells were reduced within lung allografts with impaired activation with prolonged impairment of CD8 responses. In vitro, oATP reduced CD8 activation of Th1 inflammatory cytokines IFN-γ and TNF-α and cytolytic machinery, granzyme B. Cotreatment with immunosuppressive agents, cyclosporine, rapamycin, or CTLA-4Ig resulted in no additive benefits, and oATP alone resulted in better outcomes than cyclosporine alone. This study illustrates a potential new pathway to target in hopes of prolonging survival of lung transplant recipients.
- Published
- 2014
17. SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells
- Author
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Lifei Hou, Eileen Remold-O'Donnell, Mark S. Sundrud, Picheng Zhao, and Kalamo Farley
- Subjects
animal diseases ,T cell ,Immunology ,Spleen ,Biology ,Lymphocyte Activation ,CXCR3 ,Flow cytometry ,Mice ,Immune system ,Orthomyxoviridae Infections ,T-Lymphocyte Subsets ,RAR-related orphan receptor gamma ,medicine ,Animals ,Homeostasis ,Immunology and Allergy ,Serpins ,Cell Proliferation ,Oligonucleotide Array Sequence Analysis ,Mice, Knockout ,medicine.diagnostic_test ,Cell growth ,Inflammation, Extracellular Mediators, & Effector Molecules ,Receptors, Antigen, T-Cell, gamma-delta ,Cell Biology ,Flow Cytometry ,Molecular biology ,medicine.anatomical_structure ,CD4 Antigens ,Th17 Cells ,Female ,Interleukin 17 - Abstract
SerpinB1 is an endogenous inhibitor of serine proteases recognized for its anti-inflammatory and host-protective properties. Although loss of serpinB1 in mice does not result in gross immune deregulation, serpinb1a−/− mice display increased mortality and inflammation-associated morbidity upon challenge with influenza virus. Here, we show that IL-17A+ γδ and CD4+ Th17 cells are already expanded in the lungs of serpinb1a−/− mice at steady-state. Both γδ and αβ+ CD4+ CCR6+ T cells isolated from the lungs of naive serpinb1a−/− mice displayed a skewed transcriptional profile relative to WT cells, including increased Th17 signature transcripts [Il17a, l17f, and Rorc (RORγt)] and decreased Th1 signature transcripts [Ifng, Cxcr3, and Tbx21 (T-bet)] in γδ T cells. In addition to the lung, IL-17A+ γδ and CD4+ Th17 cells were increased in the spleen of naive serpinb1a−/− mice, despite normal αβ and γδ T cell development in the thymus. Within the γδ T cell compartment, loss of serpinb1a prompted selective expansion of Vγ4+ and Vγ6/Vδ1+ cells, which also displayed elevated expression of the proliferating cell nuclear antigen, Ki-67, and IL-17A. Given that serpinb1a is preferentially expressed in WT IL-17A+ γδ and CD4+ Th17 cell subsets vis-à-vis other T cell lineages, our findings reveal a novel function of serpinB1 in limiting untoward expansion of lymphocytes with a Th17 phenotype.
- Published
- 2013
18. Presenilin1 regulates Th1 and Th17 effector responses but is not required for experimental autoimmune encephalomyelitis
- Author
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Nitin J. Karandikar, Todd N. Eagar, Sunil Kannanganat, Anithachristy S. Arumanayagam, Olaf Stüve, Picheng Zhao, and Matthew Cummings
- Subjects
0301 basic medicine ,Adoptive cell transfer ,Physiology ,Encephalomyelitis ,Cellular differentiation ,lcsh:Medicine ,Mice ,White Blood Cells ,Spectrum Analysis Techniques ,0302 clinical medicine ,Cell Signaling ,Dibenzazepines ,Animal Cells ,Immune Physiology ,Conditional gene knockout ,Medicine and Health Sciences ,Cell Cycle and Cell Division ,lcsh:Science ,Mice, Knockout ,Notch Signaling ,Innate Immune System ,Multidisciplinary ,T Cells ,Effector ,Interleukin-17 ,Experimental autoimmune encephalomyelitis ,Cell Differentiation ,Neurodegenerative Diseases ,Animal Models ,Nuclear Receptor Subfamily 1, Group F, Member 3 ,Flow Cytometry ,3. Good health ,Cell biology ,medicine.anatomical_structure ,Neurology ,Experimental Organism Systems ,Spectrophotometry ,Cell Processes ,Cytokines ,Female ,Cytophotometry ,Cellular Types ,Research Article ,Signal Transduction ,Encephalomyelitis, Autoimmune, Experimental ,Multiple Sclerosis ,Immune Cells ,T cell ,Immunology ,Mouse Models ,Biology ,Research and Analysis Methods ,Autoimmune Diseases ,03 medical and health sciences ,Model Organisms ,Immune system ,Presenilin-1 ,medicine ,Animals ,Cell Proliferation ,Blood Cells ,lcsh:R ,Granulocyte-Macrophage Colony-Stimulating Factor ,Biology and Life Sciences ,Cell Biology ,Th1 Cells ,Molecular Development ,medicine.disease ,Demyelinating Disorders ,Mice, Inbred C57BL ,030104 developmental biology ,Immune System ,Interleukin-2 ,Th17 Cells ,lcsh:Q ,Clinical Immunology ,Amyloid Precursor Protein Secretases ,Clinical Medicine ,Developmental Biology ,030215 immunology - Abstract
Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) where pathology is thought to be regulated by autoreactive T cells of the Th1 and Th17 phenotype. In this study we sought to understand the functions of Presenilin 1 (PSEN1) in regulating T cell effector responses in the experimental autoimmune encephalomyelitis (EAE) murine model of MS. PSEN1 is the catalytic subunit of γ-secretase a multimolecular protease that mediates intramembranous proteolysis. γ-secretase is known to regulate several pathways of immune importance. Here we examine the effects of disrupting PSEN1 functions on EAE and T effector differentiation using small molecule inhibitors of γ-secretase (GSI) and T cell-specific conditional knockout mice (PSEN1 cKO). Surprisingly, blocking PSEN1 function by GSI treatment or PSEN1 cKO had little effect on the development or course of MOG35-55-induced EAE. In vivo GSI administration reduced the number of myelin antigen-specific T cells and suppressed Th1 and Th17 differentiation following immunization. In vitro, GSI treatment inhibited Th1 differentiation in neutral but not IL-12 polarizing conditions. Th17 differentiation was also suppressed by the presence of GSI in all conditions and GSI-treated Th17 T cells failed to induce EAE following adoptive transfer. PSEN cKO T cells showed reduced Th1 and Th17 differentiation. We conclude that γ-secretase and PSEN1-dependent signals are involved in T effector responses in vivo and potently regulate T effector differentiation in vitro, however, they are dispensable for EAE.
- Published
- 2018
19. Broad-spectrum antimicrobial activity of the reactive compounds generated in vitro by Manduca sexta phenoloxidase
- Author
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Yang Wang, Picheng Zhao, Haobo Jiang, and Jiajing Li
- Subjects
Dopamine ,Bacillus cereus ,Bacillus subtilis ,medicine.disease_cause ,Biochemistry ,Article ,Substrate Specificity ,Microbiology ,Pichia pastoris ,chemistry.chemical_compound ,Manduca ,Escherichia coli ,medicine ,Animals ,Molecular Biology ,biology ,Monophenol Monooxygenase ,fungi ,Prophenoloxidase ,biology.organism_classification ,Anti-Bacterial Agents ,Enzyme Activation ,Kinetics ,chemistry ,Insect Science ,Dopachrome ,Insect Proteins ,Micrococcus luteus ,Bacteria - Abstract
Although quinone production and melanin formation are widely recognized as an integral part of the insect defense system, experimental evidence is lacking that the proteolytic activation of prophenoloxidase participates in the direct killing of invading microbes-active phenoloxidase generates quinones that polymerize to form melanin. Here, we report the antimicrobial effect of reactive intermediates produced in phenoloxidase-catalyzed reactions. After being treated with Manduca sexta phenoloxidase and dopamine, Escherichia coli and Bacillus subtilis ceased to grow, whereas the growth of Pichia pastoris was slightly affected. Microscopic analysis showed melanin deposition on cell surface, aggregation of bacteria, and loss of cell mobility. Viability tests revealed major decreases in the bacterial colony counts and, since the decrease remained significant after dispersion of the cell clumps, the reactive compounds were surmised to have aggregated and killed E. coli and B. subtilis cells. Under the experimental conditions, 60-94% of the Gram-negative bacteria (E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Salmonella typhimurium) and 52-99% of the Gram-positive bacteria (Bacillus cereus, B. subtilis, Micrococcus luteus, and Staphylococcus aureus) were killed. In the presence of phenoloxidase, dopamine or 5,6-dihydroxyindole (DHI) exhibited much higher antibacterial activity than L-dopa, N-acetyldopamine (NADA) or N-beta-alanyldopamine (NBAD) did, suggesting that DHI and its oxidation products were cytotoxic. The antifungal activity of DHI was detected using P. pastoris, Saccharomyces cerevisiae, Candida albicans, and Beauveria bassiana. These results established that prophenoloxidase activation is an integral component of the insect defense system involving a multitude of enzymes (e.g. proteinases, oxidases, and dopachrome conversion enzyme (DCE)), which immobilizes and kills invading microorganisms.
- Published
- 2007
20. IL-9 and Th9 cells: progress and challenges
- Author
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Xian Chang Li, Rafik M. Ghobrial, Xiang Xiao, and Picheng Zhao
- Subjects
Bodily Secretions ,Helper T lymphocyte ,medicine.medical_treatment ,Immunology ,Antigen presentation ,Inflammation ,Biology ,Lymphocyte Activation ,Th2 Cells ,Transforming Growth Factor beta ,medicine ,Hypersensitivity ,Immunology and Allergy ,Animals ,Humans ,Interleukin 9 ,Mast Cells ,Receptor ,Transcription factor ,Interleukin 4 ,Invited Review ,Interleukin-9 ,Cell Differentiation ,General Medicine ,Receptor Cross-Talk ,T-Lymphocytes, Helper-Inducer ,Cell biology ,Receptors, Interleukin-4 ,Cytokine ,medicine.symptom ,Signal Transduction - Abstract
T(h)9 cells are a new subset of helper T cells, and the signature cytokine for T(h)9 cells is IL-9. Both T(h)9 cells and T(h)9 products are implicated in multiple disease settings. Thus, a clear understanding of how T(h)9 cells are induced and controlled is an important and clinically relevant issue. There are different molecular pathways identified thus far in the induction of T(h)9 cells, and activation of such diverse pathways requires integration of signals from TGF-β and IL-4 cytokine receptors as well as costimulatory molecules. These signals converge on the induction of multiple transcription factors that collectively drive the development of T(h)9 cells.
- Published
- 2013
21. Biochemical properties, expression profiles, and tissue localization of orthologous acetylcholinesterase-2 in the mosquito, Anopheles gambiae
- Author
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Haobo Jiang, Picheng Zhao, and Yang Wang
- Subjects
Male ,medicine.medical_treatment ,Anopheles gambiae ,Molecular Sequence Data ,Real-Time Polymerase Chain Reaction ,Biochemistry ,Article ,Substrate Specificity ,chemistry.chemical_compound ,Malaoxon ,Carbaryl ,Anopheles ,medicine ,Animals ,Cholinergic synapse ,Amino Acid Sequence ,Molecular Biology ,Protease ,biology ,Paraoxon ,Base Sequence ,Organophosphate ,Sequence Analysis, DNA ,biology.organism_classification ,Molecular biology ,Acetylcholinesterase ,Immunohistochemistry ,Cholinergic Neurons ,Recombinant Proteins ,Kinetics ,chemistry ,Insect Science ,Insect Proteins ,Female ,Baculoviridae ,Head ,medicine.drug - Abstract
Acetylcholinesterases (AChEs) catalyze the hydrolysis of acetylcholine, a neurotransmitter for cholinergic neurotransmission in animals. Most insects studied so far possess two AChE genes: ace-1 paralogous and ace-2 orthologous to Drosophila melanogaster ace . We characterized the catalytic domain of Anopheles gambiae AChE1 in a previous study ( Jiang et al., 2009 ) and report here biochemical properties of A . gambiae AChE2 expressed in Sf 9 cells. An unknown protease in the expression system cleaved the recombinant AChE2 next to Arg 110 , yielding two non-covalently associated polypeptides. A mixture of the intact and cleaved AChE2 had a specific activity of 72.3 U/mg, much lower than that of A . gambiae AChE1 (523 U/mg). The order of V max / K M values for the model substrates was acetylthiocholine > propionylthiocholine ≈ acetyl-(β-methyl)thiocholine > butyrylthiocholine. The IC 50 's for eserine, carbaryl, BW284C51, paraoxon and malaoxon were 1.32, 13.6, 26.8, 192 and 294 nM, respectively. A . gambiae AChE2 bound eserine and carbaryl stronger than paraoxon and malaoxon, whereas eserine and malaoxon modified the active site Ser 232 faster than carbaryl or paraoxon did. Consequently, the k i 's were 1.173, 0.245, 0.029 and 0.018 μM −1 min −1 for eserine, carbaryl, paraoxon and malaoxon, respectively. Quantitative polymerase chain reactions showed a similar pattern of ace-1 and ace-2 expression. Their mRNAs were abundant in early embryos, greatly decreased in late embryos, larvae, pupae, and pharate adult, and became abundant again in adults. Both transcripts were higher in head and abdomen than thorax of adults and higher in male than female mosquitoes. Transcript levels of ace-1 were 1.9- to 361.8-fold higher than those of ace-2 , depending on developmental stages and body parts. Cross-reacting polyclonal antibodies detected AChEs in adult brains, thoracic ganglia, and genital/rectal area. Activity assays, immunoblotting, and tandem mass spectrometric analysis indicated that A . gambiae AChE1 is responsible for most of acetylthiocholine hydrolysis in the head extracts. Taken together, these data indicate that A . gambiae AChE2 may play a less significant role than AChE1 does in the mosquito nervous system.
- Published
- 2012
22. A serpinB1 regulatory mechanism is essential for restricting neutrophil extracellular trap generation
- Author
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Picheng Zhao, J. Michael Stolley, Eileen Remold-O'Donnell, Kalamo Farley, and Jessica Cooley
- Subjects
Programmed cell death ,Cytoplasm ,Mice, 129 Strain ,Neutrophils ,Immunology ,Inflammation ,Bone Marrow Cells ,Biology ,Article ,Mice ,In vivo ,medicine ,Pneumonia, Bacterial ,Immunology and Allergy ,Animals ,Humans ,Genetic Predisposition to Disease ,Pseudomonas Infections ,Cells, Cultured ,Serpins ,Cell Nucleus ,Mice, Knockout ,Cell Death ,SERPINB1 ,Extracellular Fluid ,Neutrophil extracellular traps ,In vitro ,Cell biology ,Mice, Inbred C57BL ,Cell nucleus ,Protein Transport ,medicine.anatomical_structure ,Female ,medicine.symptom - Abstract
NETosis (neutrophil extracellular trap [NET] generation), a programmed death pathway initiated in mature neutrophils by pathogens and inflammatory mediators, can be a protective process that sequesters microbes and prevents spread of infection, but it can also be a pathological process that causes inflammation and serious tissue injury. Little is known about the regulatory mechanism. Previously, we demonstrated that serpinb1-deficient mice are highly susceptible to pulmonary bacterial and viral infections due to inflammation and tissue injury associated with increased neutrophilic death. In this study, we used in vitro and in vivo approaches to investigate whether SerpinB1 regulates NETosis. We found that serpinb1-deficient bone marrow and lung neutrophils are hypersusceptible to NETosis induced by multiple mediators in both an NADPH-dependent and -independent manner, indicating a deeply rooted regulatory role in NETosis. This role is further supported by increased nuclear expansion (representing chromatin decondensation) of PMA-treated serpinb1-deficient neutrophils compared with wild-type, by migration of SerpinB1 from the cytoplasm to the nucleus of human neutrophils that is coincident with or preceding early conversion of lobulated (segmented) nuclei to delobulated (spherical) morphology, as well as by the finding that exogenous human recombinant SerpinB1 abrogates NET production. NETosis of serpinb1-deficient neutrophils is also increased in vivo during Pseudomonas aeruginosa lung infection. The findings identify a previously unrecognized regulatory mechanism involving SerpinB1 that restricts the production of NETs.
- Published
- 2012
23. Heterologous expression, purification, and biochemical characterization of a greenbug (Schizaphis graminum) acetylcholinesterase encoded by a paralogous gene (ace-1)
- Author
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Kun Yan Zhu, Haobo Jiang, and Picheng Zhao
- Subjects
Stereochemistry ,Health, Toxicology and Mutagenesis ,Recombinant Fusion Proteins ,Iodide ,Genes, Insect ,Toxicology ,Transfection ,Biochemistry ,Michaelis–Menten kinetics ,Article ,Choline ,Substrate Specificity ,chemistry.chemical_compound ,Malaoxon ,Catalytic Domain ,Enzyme Stability ,medicine ,Animals ,Cholinergic synapse ,Molecular Biology ,Cholinesterase ,chemistry.chemical_classification ,biology ,Paraoxon ,Temperature ,General Medicine ,Hydrogen-Ion Concentration ,Acetylcholinesterase ,Molecular Weight ,Kinetics ,Enzyme ,chemistry ,Acetylthiocholine ,Aphids ,biology.protein ,Molecular Medicine ,Insect Proteins ,Cholinesterase Inhibitors ,Dimerization ,medicine.drug - Abstract
Acetylcholinesterase is a critical enzyme in the regulation of cholinergic neurotransmission in insects. To produce Schizaphis graminum acetylcholinesterase-1 for structure-function analysis, we constructed a recombinant baculovirus to infect Sf9 cells, which secreted the soluble protein at a final concentration of 4.0 mg/L. The purified enzyme had an apparent M(r) of 70 and 130 kDa in the reducing and nonreducing SDS-polyacrylamide gels, respectively, indicating that it formed a dimer via an intermolecular disulfide bond. The fresh enzyme had a specific activity of 245 U/mg, which stabilized at a lower level (115 U/mg) in storage. The Michaelis constant and maximum velocity were 88.3 +/- 9.6 microM and 133.2 +/- 1.6 U/mg for acetylthiocholine iodide, 113.9 +/- 12.5 muM and 106.4 +/- 3.0 U/mg for acetyl(beta-methyl)thiocholine iodide, 68.9 +/- 7.8 microM and 76.7 +/- 1.0 U/mg for propionylthiocholine iodide, and 201.1 +/- 21.0 microM and 4.4 +/- 0.1 U/mg for S-butyrylthiocholine iodide, respectively. The IC(50) values (5 min, room temperature) of ethopropazine, BW284C51, carbaryl, eserine, malaoxon, and paraoxon were 102, 1.66, 0.94, 0.20, 0.061, 0.016 microM, respectively. The bimolecular reaction constants (k(i)) were (6.50 +/- 0.40) x 10(4) for carbaryl, (1.00 +/- 0.16) x 10(5) for eserine, (4.70 +/- 0.13) x 10(5) for malaoxon, and (9.06 +/- 0.23) x 10(5) M(-1) min(-1) for paraoxon. The enzyme was also inhibited by one of its products, choline, at concentrations higher than 20 mM, suggesting that choline bound to an anionic site and regulated the enzymatic activity.
- Published
- 2010
24. OX40 signaling activates epigenetic mechanisms to repress Th17 cells and Th17-related autoimmune diseases (LYM5P.708)
- Author
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Xiang Xiao, Xiaomin Shi, Yihui Fan, xiaolong zhang, minhao wu, wentao liu, Picheng Zhao, chenglin wu, Laurie Minze, Rafik Ghobrial, and Xian Li
- Subjects
Immunology ,Immunology and Allergy - Abstract
Th17 cells produce copious amount of IL-17, which mediates host antimicrobial responses and autoimmune diseases. The exact mechanisms that control Th17 homeostasis, especially those that inhibit Th17 differentiation, remain incompletely defined. Here, we found that the T cell costimulatory molecule OX40 is a potent repressor of Th17 cells and Th17-mediated autoimmune disease. Under Th17-polarizing conditions in vitro, engagement of OX40 strongly inhibited IL-17 production despite enhanced cell survival and proliferation. Mechanistically, OX40 engagement induced sustained activation of both canonical and non-canonical NF-kB pathways, and it is RelB that mediated dominant suppression of Th17 cells that is independent of p52 and p50. RelB directly recruited H3K9 methyltransferases G9a and Setdb1 upon binding to IL-17 locus, and this resulted in di- and tri-methylation of H3K9, which led to a closed epigenetic configuration of IL-17 locus that prevents RORγt binding to IL-17 locus. Conversely, inhibition of histone methyltransferase activity significantly reversed OX40-mediated suppression of Th17 cells. Importantly, in an EAE model, stimulation of OX40 in vivo inhibited the disease process, while RelB-deficient CD4+ T cells induced exacerbated disease. In conclusion, our study identified a new mechanism in the control of Th17 cells, and this mechanism relies on OX40 induced repressive epigenetic process. This finding may have important therapeutic implications in the clinic.
- Published
- 2015
25. Role of Macrophage Subsets in Chronic Allograft Rejection and Novel Strategies to Target Them
- Author
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Chin-Lee Wu, X. Shi, Xian Chang Li, Xiang Xiao, W. Liu, Zhiyong Guo, Picheng Zhao, Y. Peng, and Xiaoshun He
- Subjects
Transplantation ,Allograft rejection ,business.industry ,Immunology ,Macrophage ,Medicine ,business - Published
- 2014
26. New Insights On T Cell Apoptosis in the Induction of Treg-Dependent Dominant Tolerance
- Author
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X. Li, Y. Peng, C. Wu, W. Liu, Picheng Zhao, X. Xiao, X. Shi, and Rafik M. Ghobrial
- Subjects
Transplantation ,T-cell apoptosis ,Chemistry ,Cell biology - Published
- 2014
27. Defining and Refining Tfh Cells in Antibody Responses and The Role of OX40 Costimulation
- Author
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Y. Peng, Xiang Xiao, Xian Chang Li, Chin-Lee Wu, W. Liu, X. Shi, and Picheng Zhao
- Subjects
Transplantation ,Antibody response ,Chemistry ,Refining ,Immunology - Published
- 2014
28. SerpinB1 is essential for regulation of neutrophil extracellular trap (NET) generation (118.3)
- Author
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Kalamo Farley, James Stolley, Picheng Zhao, Jessica Cooley, and Eileen Remold-O'Donnell
- Subjects
Immunology ,Immunology and Allergy - Abstract
NETosis, a programmed death pathway induced in mature neutrophils by pathogens and inflammatory mediators, can be either a protective process that prevents spread of microbial infection or a pathological process that causes severe tissue damage and inflammation. Little is known about the mechanisms that regulate such a diverse functional spectrum. Previously we demonstrated serpinB1 null mice are highly susceptible to pulmonary Pseudomonas aeruginosa infection due to increased pathology mediated neutrophilic death. Using in vitro and in vivo approaches we examine the regulatory role of SerpinB1 in NETosis. We found bone marrow or LPS-derived serpinB1 null neutrophils are remarkably prone to NETosis in both NADPH-dependent and independent manner. A regulatory role for SerpinB1 in NETosis is also supported by the increased number of neutrophils with expanded nuclei, likely representing chromatin decondensation, and by finding that exogenous rSERPINB1 abrogates NET production. Importantly, during P. aeruginosa lung infection 4 times more NETs were harvested from serpinb1-/- mice than WT mice. The total number of in vitro activated serpinB1-/- neutrophils that died was not different from wild-type, indicating that the primary protective role of SerpinB1 is determining whether activated neutrophils die by the highly injurious NETs mechanism or by a less phlogistic mode, generating apoptotic-like cells with shrunken appearance and small nuclei.
- Published
- 2012
29. A comparative analysis of serpin genes in the silkworm genome
- Author
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Zou, Zhen, primary, Picheng, Zhao, additional, Weng, Hua, additional, Mita, Kazuei, additional, and Jiang, Haobo, additional
- Published
- 2009
- Full Text
- View/download PDF
30. Inhibition of the Purinergic Pathway Prolongs Mouse Lung Allograft Survival.
- Author
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Kaifeng Liu, Vergani, Andrea, Picheng Zhao, Nasr, Moufida Ben, Xiao Wu, Khadija Iken, Dawei Jiang, Xiaofeng Su, Carmen Fotino, Fiorina, Paolo, and Visner, Gary A.
- Published
- 2014
- Full Text
- View/download PDF
31. Increased Surfactant Protein D Fails to Improve Bacterial Clearance and Inflammation in serpinB1-/- Mice.
- Author
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Stolley, J. Michael, Dapeng Gong, Farley, Kalamo, Picheng Zhao, Cooley, Jessica, Crouch, Erika C., Benarafa, Charaf, and Remold-O'Donnel, Eileen
- Published
- 2012
- Full Text
- View/download PDF
32. Biomimetic proteolipid vesicles for targeting inflamed tissues
- Author
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Francesca Taraballi, Silvia Minardi, Iman K. Yazdi, Alessandro Parodi, A. De Vita, Claudia Corbo, Ennio Tasciotti, E. De Rosa, Jonathan O. Martinez, N. E. Toledano Furman, Michael B. Sherman, Xin Wang, Michael Evangelopoulos, Roberto Molinaro, Picheng Zhao, Molinaro, R, Corbo, C, Martinez, J, Taraballi, F, Evangelopoulos, M, Minardi, S, Yazdi, I, Zhao, P, De Rosa, E, Sherman, M, De Vita, A, Toledano Furman, N, Wang, X, Parodi, A, and Tasciotti, E
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0301 basic medicine ,Biodistribution ,Proteolipids ,Inflammation ,02 engineering and technology ,Biomimetic Materials ,Drug Carriers ,Leukocytes ,Membrane Proteins ,Pharmacology ,Article ,03 medical and health sciences ,medicine ,General Materials Science ,Liposome ,Chemistry ,Mechanical Engineering ,Vesicle ,leukocyte-like vesicles, drug delivery, targeting, inflammation ,General Chemistry ,Mononuclear phagocyte system ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Cell biology ,030104 developmental biology ,Membrane protein ,Mechanics of Materials ,Drug delivery ,medicine.symptom ,0210 nano-technology ,Drug carrier - Abstract
A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of biological barriers that limit their optimal biodistribution. Bioinspired drug-delivery carriers formulated by bottom-up or top-down strategies have emerged as an alternative approach to evade the mononuclear phagocytic system and facilitate the transport across the endothelial vessel wall. Here, we describe a method that leverages the advantages of bottom-up and top-down strategies to incorporate proteins derived from the leukocyte plasma membrane into lipid nanoparticles. The resulting proteolipid vesicles - which we refer to as leukosomes - retained the versatility and physicochemical properties typical of liposomal formulations, preferentially targeted inflamed vasculature, enabled the selective and effective delivery of dexamethasone to inflamed tissues, and reduced phlogosis in a localized model of inflammation.
33. Comparative genomic analysis of the Tribolium immune system
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Picheng Zhao, Charles Hetru, Dan Hultmark, Haobo Jiang, Michael Williams, Niranji Sumathipala, Zhiqiang Lu, Zhen Zou, and Jay D. Evans
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0106 biological sciences ,animal structures ,Anopheles gambiae ,Genome, Insect ,Molecular Sequence Data ,chemical and pharmacologic phenomena ,Genes, Insect ,Biology ,01 natural sciences ,Genome ,03 medical and health sciences ,Phylogenetics ,Genetic model ,Anopheles ,Animals ,Amino Acid Sequence ,Gene ,Phylogeny ,030304 developmental biology ,Genetics ,0303 health sciences ,Tribolium ,Innate immune system ,Phylogenetic tree ,Research ,fungi ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Immunity, Innate ,010602 entomology ,Drosophila melanogaster ,Immune System ,bacteria ,Signal Transduction - Abstract
The annotation, and comparison with homologous genes in other species, of immunity-related genes in the Tribolium castaneum genome allowed the identification of around 300 candidate defense proteins, and revealed a framework of information on Tribolium immunity., Background Tribolium castaneum is a species of Coleoptera, the largest and most diverse order of all eukaryotes. Components of the innate immune system are hardly known in this insect, which is in a key phylogenetic position to inform us about genetic innovations accompanying the evolution of holometabolous insects. We have annotated immunity-related genes and compared them with homologous molecules from other species. Results Around 300 candidate defense proteins are identified based on sequence similarity to homologs known to participate in immune responses. In most cases, paralog counts are lower than those of Drosophila melanogaster or Anopheles gambiae but are substantially higher than those of Apis mellifera. The genome contains probable orthologs for nearly all members of the Toll, IMD, and JAK/STAT pathways. While total numbers of the clip-domain serine proteinases are approximately equal in the fly (29), mosquito (32) and beetle (30), lineage-specific expansion of the family is discovered in all three species. Sixteen of the thirty-one serpin genes form a large cluster in a 50 kb region that resulted from extensive gene duplications. Among the nine Toll-like proteins, four are orthologous to Drosophila Toll. The presence of scavenger receptors and other related proteins indicates a role of cellular responses in the entire system. The structures of some antimicrobial peptides drastically differ from those in other orders of insects. Conclusion A framework of information on Tribolium immunity is established, which may serve as a stepping stone for future genetic analyses of defense responses in a nondrosophiline genetic model insect.
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34. A SerpinBl Regulatory Mechanism Is Essential for Restricting Neutrophil Extracellular Trap Generation.
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Farley, Kalamo, Stolley, J. Michael, Picheng Zhao, Cooley, Jessica, and Remold-0'Donnell, Eileen
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SERPINS , *NEUTROPHILS , *APOPTOSIS , *INFLAMMATION , *TISSUE wounds , *NICOTINAMIDE adenine dinucleotide phosphate , *LABORATORY mice - Abstract
NETosis (neutrophil extracellular trap [NET] generation), a programmed death pathway initiated in mature neutrophils by patho-gens and inflammatory mediators, can be a protective process that sequesters microbes and prevents spread of infection, but it can also be a pathological process that causes inflammation and serious tissue injury. Little is known about the regulatory mechanism. Previously, we demonstrated that serpinbl-deficient mice are highly susceptible to pulmonary bacterial and viral infections due to inflammation and tissue injury associated with increased neutrophilic death. In this study, we used in vitro and in vivo approaches to investigate whether SerpinBl regulates NETosis. We found that serpinbl -deficient bone marrow and lung neutrophils are hypersusceptible to NETosis induced by multiple mediators in both an NADPH-dependent and -independent manner, indicating a deeply rooted regulatory role in NETosis. This role is further supported by increased nuclear expansion (representing chromatin decondensation) of PMA-treated serpi'nW-deficient neutrophils compared with wild-type, by migration of SerpinBl from the cytoplasm to the nucleus of human neutrophils that is coincident with or preceding early conversion of lobulated (segmented) nuclei to delobulated (spherical) morphology, as well as by the finding that exogenous human recombinant SerpinBl abrogates NET production. NETosis of serpinbl-deficient neutrophils is also increased in vivo during Pseudomonas aeruginosa lung infection. The findings identify a previously unrecognized regulatory mechanism involving SerpinBl that restricts the production of NETs. [ABSTRACT FROM AUTHOR]
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- 2012
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35. Convalescent plasma anti-SARS-CoV-2 spike protein ectodomain and receptor-binding domain IgG correlate with virus neutralization.
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Salazar, Eric, Kuchipudi, Suresh V., Christensen, Paul A., Eagar, Todd, Xin Yi, Picheng Zhao, Zhicheng Jin, Long, S. Wesley, Olsen, Randall J., Jian Chen, Castillo, Brian, Leveque, Christopher, Towers, Dalton, Lavinder, Jason, Gollihar, Jimmy, Cardona, Jose, Ippolito, Gregory, Nissly, Ruth, Bird, Ian, and Greenawalt, Denver
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CONVALESCENT plasma , *COVID-19 treatment , *SARS-CoV-2 , *TITERS - Abstract
The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the urgent need for assays that detect protective levels of neutralizing antibodies. We studied the relationship among anti-spike ectodomain (anti-ECD), anti-receptor-binding domain (anti-RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by 2 in vitro assays using convalescent plasma samples from 68 patients with COVID-19. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers and in vitro VN titers. The probability of a VN titer of ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment, was ≥80% when anti-RBD or anti-ECD titers were ≥1:1350. Of all donors, 37% lacked VN titers of ≥160. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease VN or IgG titers. Analysis of 2814 asymptomatic adults found 73 individuals with anti-ECD IgG titers of ≥1:50 and strong positive correlation with anti-RBD and VN titers. Fourteen of these individuals had VN titers of ≥1:160, and all of them had anti-RBD titers of ≥1:1350. We conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titers of ≥1:1350 may provide critical information about protection against COVID-19 disease. [ABSTRACT FROM AUTHOR]
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- 2020
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