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https://read.qxmd.com/read/30753824/antitumor-responses-in-the-absence-of-toxicity-in-solid-tumors-by-targeting-b7-h3-via-chimeric-antigen-receptor-t-cells
#1
Hongwei Du, Koichi Hirabayashi, Sarah Ahn, Nancy Porterfield Kren, Stephanie Ann Montgomery, Xinhui Wang, Karthik Tiruthani, Bhalchandra Mirlekar, Daniel Michaud, Kevin Greene, Silvia Gabriela Herrera, Yang Xu, Chuang Sun, Yuhui Chen, Xingcong Ma, Cristina Rosa Ferrone, Yuliya Pylayeva-Gupta, Jen Jen Yeh, Rihe Liu, Barbara Savoldo, Soldano Ferrone, Gianpietro Dotti
The high expression across multiple tumor types and restricted expression in normal tissues make B7-H3 an attractive target for immunotherapy. We generated chimeric antigen receptor (CAR) T cells targeting B7-H3 (B7-H3.CAR-Ts) and found that B7-H3.CAR-Ts controlled the growth of pancreatic ductal adenocarcinoma, ovarian cancer and neuroblastoma in vitro and in orthotopic and metastatic xenograft mouse models, which included patient-derived xenograft. We also found that 4-1BB co-stimulation promotes lower PD-1 expression in B7-H3...
February 11, 2019: Cancer Cell
https://read.qxmd.com/read/30745877/sudden-heart-rate-reduction-upon-optogenetic-release-of-acetylcholine-from-cardiac-parasympathetic-neurons-in-perfused-hearts
#2
Angel Moreno, Kendal Endicott, Matthew Skancke, Mary Kate Dwyer, Jaclyn Brennan, Igor R Efimov, Gregory Trachiotis, David Mendelowitz, Matthew W Kay
The balance of sympathetic and parasympathetic tone provides exquisite control of heart rate and contractility and has also been shown to modulate coronary flow and inflammation. Understanding how autonomic balance is altered by cardiac disease is an active area of research, and developing new ways to control this balance provides insights into disease therapies. However, achieving acute neuron-specific stimulation of autonomic neurons can be difficult in experiments that measure the acute effects of nerve stimulation on the heart...
2019: Frontiers in Physiology
https://read.qxmd.com/read/30737892/evaluation-of-the-ability-of-immune-humanized-mice-to-demonstrate-cd20-specific-cytotoxicity-induced-by-ofatumumab
#3
Kenrick M Semple, Carlos M Gonzaléz, Melissa Zarr, Jose' Austin, Vikram Patel, Kristina E Howard
CD20 monoclonal antibodies are well-established therapeutics for the treatment of B-cell malignancies. Several mechanisms of target cell killing occur from anti-CD20 therapy including complement-dependent cell lysis (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Human Fc Receptors (FcR) are required to mediate these functions and are either not present or not cross-reactive in mice and most animal species. In contrast, some non-human primates have cross-reactive FcR however, their cellular expression and function may differ from humans...
February 9, 2019: Clinical and Translational Science
https://read.qxmd.com/read/30736310/identification-of-qtl-related-to-ros-formation-under-hypoxia-and-their-association-with-waterlogging-and-salt-tolerance-in-barley
#4
Muhammad Bilal Gill, Fanrong Zeng, Lana Shabala, Guoping Zhang, Min Yu, Vadim Demidchik, Sergey Shabala, Meixue Zhou
Waterlogging is a serious environmental problem that limits agricultural production in low-lying rainfed areas around the world. The major constraint that plants face in a waterlogging situation is the reduced oxygen availability. Accordingly, all previous efforts of plant breeders focused on traits providing adequate supply of oxygen to roots under waterlogging conditions, such as enhanced aerenchyma formation or reduced radial oxygen loss. However, reduced oxygen concentration in waterlogged soils also leads to oxygen deficiency in plant tissues, resulting in an excessive accumulation of reactive oxygen species (ROS) in plants...
February 6, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30723095/type-i-interferon-induces-cxcl13-to-support-ectopic-germinal-center-formation
#5
Alice E Denton, Silvia Innocentin, Edward J Carr, Barry M Bradford, Fanny Lafouresse, Neil A Mabbott, Urs Mörbe, Burkhard Ludewig, Joanna R Groom, Kim L Good-Jacobson, Michelle A Linterman
Ectopic lymphoid structures form in a wide range of inflammatory conditions, including infection, autoimmune disease, and cancer. In the context of infection, this response can be beneficial for the host: influenza A virus infection-induced pulmonary ectopic germinal centers give rise to more broadly cross-reactive antibody responses, thereby generating cross-strain protection. However, despite the ubiquity of ectopic lymphoid structures and their role in both health and disease, little is known about the mechanisms by which inflammation is able to convert a peripheral tissue into one that resembles a secondary lymphoid organ...
February 5, 2019: Journal of Experimental Medicine
https://read.qxmd.com/read/30714539/mitochondrial-common-deletion-level-in-blood-new-insight-into-the-effects-of-age-and-body-mass-index
#6
Mahboube Ahmadi, Masoud Golalipour, Nader Mansour Samaei
BACKGROUND: Age-related decrease in the mitochondrial activity has been reported in several tissues. Reactive Oxygen Species (ROS) produced from defected mitochondria leads to aging and accumulate through time. However, studies about the mitochondrial DNA mutation level in blood is contradictory. Other lifestyle factors may modify the effects of age in post-mitotic tissues such as blood. The BMI represents the sum of the various lifestyle factors. OBJECTIVE: We proposed that age, obesity and mtDNA deletion are three ROS producing factors, which may interact with each other and induce senescence...
February 1, 2019: Current Aging Science
https://read.qxmd.com/read/30713784/affinity-enhanced-t-cell-receptors-for-adoptive-t-cell-therapy-targeting-mage-a10-strategy-for-selection-of-an-optimal-candidate
#7
Ellen C Border, Joseph P Sanderson, Thomas Weissensteiner, Andrew B Gerry, Nicholas J Pumphrey
Circulating T-cells that have passed thymic selection generally bear T-cell receptors (TCRs) with sub-optimal affinity for cancer-associated antigens, resulting in a limited ability to detect and eliminate tumor cells. Engineering TCRs to increase their affinity for cancer targets is a promising strategy for generating T-cells with enhanced potency for adoptive immunotherapy in cancer patients. However, this manipulation also risks generating cross-reactivity to antigens expressed by normal tissue, with potentially serious consequences...
2019: Oncoimmunology
https://read.qxmd.com/read/30703499/the-era-of-nitric-oxide-in-plant-biology-twenty-years-tying-up-loose-ends
#8
REVIEW
Fiorella Del Castello, Andrés Nejamkin, Raul Cassia, Natalia Correa-Aragunde, Belén Fernández, Noelia Foresi, Cristina Lombardo, Leonor Ramirez, Lorenzo Lamattina
Nitric oxide (NO) is an essential signal molecule to maintain cellular homeostasis in uni and pluricellular organisms. Conceptually, NO intervenes as much in sustaining basal metabolic processes, as in firing cellular responses to changes in internal and external conditions, and also in guiding the return to basal conditions. Behind these unusual capabilities of NO is the chemistry of this molecule, an unstable, reactive, free radical and short half-life gas. It is a lipophilic molecule that crosses all the barriers that biological membranes can impose...
January 28, 2019: Nitric Oxide: Biology and Chemistry
https://read.qxmd.com/read/30703122/a-prrsv-gp5-mosaic-vaccine-protection-of-pigs-from-challenge-and-ex-vivo-detection-of-ifn%C3%AE-responses-against-several-genotype-2-strains
#9
Junru Cui, Caitlin M O'Connell, Antonio Costa, Yan Pan, Joan A Smyth, Paulo H Verardi, Diane J Burgess, Herbert J Van Kruiningen, Antonio E Garmendia
Porcine reproductive and respiratory syndrome virus (PRRSV), is a highly mutable RNA virus that affects swine worldwide and its control is very challenging due to its formidable heterogeneity in the field. In the present study, DNA vaccines constructed with PRRSV GP5-Mosaic sequences were complexed to cationic liposomes and administered to experimental pigs by intradermal and intramuscular injection, followed by three boosters 14, 28 and 42 days later. The GP5-Mosaic vaccine thus formulated was immunogenic and induced protection from challenge in vaccinated pigs comparable to that induced by a wild type (VR2332) GP5 DNA vaccine (GP5-WT)...
2019: PloS One
https://read.qxmd.com/read/30688265/-kai-xin-san-ameliorates-scopolamine-induced-cognitive-dysfunction
#10
Yu-Min Xu, Xin-Chen Wang, Ting-Ting Xu, Hong-Ying Li, Shang-Yan Hei, Na-Chuan Luo, Hong Wang, Wei Zhao, Shu-Huan Fang, Yun-Bo Chen, Li Guan, Yong-Qi Fang, Shi-Jie Zhang, Qi Wang, Wei-Xiong Liang
Kai Xin San (KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups (which received physiological saline), the doses of KXS (0...
May 2019: Neural Regeneration Research
https://read.qxmd.com/read/30683742/intranasal-immunization-with-the-commensal-streptococcus-mitis-confers-protective-immunity-against-pneumococcal-lung-infection
#11
Sudhanshu Shekhar, Rabia Khan, Karl Schenck, Fernanda Cristina Petersen
Streptococcus pneumoniae is a bacterial pathogen that causes various diseases of public health concern worldwide. Current pneumococcal vaccines target the capsular polysaccharide surrounding the cells. However, only up to 13 of more than 90 pneumococcal capsular serotypes are represented in the current conjugate vaccines. In this study, we used two experimental approaches to evaluate the potential of Streptococcus mitis , a commensal that exhibits immune cross-reactivity with S. pneumoniae , to confer protective immunity to S...
January 25, 2019: Applied and Environmental Microbiology
https://read.qxmd.com/read/30674848/thiol-mediated-chemoselective-strategies-for-in-situ-formation-of-hydrogels
#12
REVIEW
Jing Su
Hydrogels are three-dimensional networks composed of hydrated polymer chains and have been a material of choice for many biomedical applications such as drug delivery, biosensing, and tissue engineering due to their unique biocompatibility, tunable physical characteristics, flexible methods of synthesis, and range of constituents. In many cases, methods for crosslinking polymer precursors to form hydrogels would benefit from being highly selective in order to avoid cross-reactivity with components of biological systems leading to adverse effects...
September 2, 2018: Gels
https://read.qxmd.com/read/30671739/clinical-translation-of-68-ga-ga-nota-anti-mmr-sdab-for-pet-ct-imaging-of-protumorigenic-macrophages
#13
Catarina Xavier, Anneleen Blykers, Damya Laoui, Evangelia Bolli, Ilse Vaneyken, Jessica Bridoux, Henri Baudhuin, Geert Raes, Hendrik Everaert, Kiavash Movahedi, Jo A Van Ginderachter, Nick Devoogdt, Vicky Caveliers, Tony Lahoutte, Marleen Keyaerts
PURPOSE: Macrophage mannose receptor (MMR, CD206) expressing tumor-associated macrophages (TAM) are protumorigenic and was reported to negatively impact therapy responsiveness and is associated with higher chances of tumor relapse following multiple treatment regimens in preclinical tumor models. Since the distribution of immune cells within the tumor is often heterogeneous, sampling "errors" using tissue biopsies will occur. In order to overcome this limitation, we propose positron emission tomography (PET)/X-ray computed tomography (CT) imaging using 68 Ga-labeled anti-MMR single-domain antibody fragment (sdAb) to assess the presence of these protumorigenic TAM...
January 22, 2019: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://read.qxmd.com/read/30668611/seroprevalence-cross-antigenicity-and-circulation-sphere-of-bat-borne-hantaviruses-revealed-by-serological-and-antigenic-analyses
#14
Lin Xu, Jianmin Wu, Qi Li, Yamei Wei, Zhizhou Tan, Jianqiu Cai, Huancheng Guo, Ling'en Yang, Xiaohong Huang, Jing Chen, Fuqiang Zhang, Biao He, Changchun Tu
Bats are newly identified reservoirs of hantaviruses (HVs) among which very divergent HVs have been discovered in recent years. However, their significance for public health remains unclear since their seroprevalence as well as antigenic relationship with human-infecting HVs have not been investigated. In the present study archived tissues of 1,419 bats of 22 species from 6 families collected in 5 south and southwest provinces in China were screened by pan-HV RT-PCR following viral metagenomic analysis. As a result nine HVs have been identified in two bat species in two provinces and phylogenetically classified into two species, Laibin virus (LAIV, ICTV approved species, 1 strain) and Xuan son virus (XSV, proposed species, 8 strains)...
January 22, 2019: PLoS Pathogens
https://read.qxmd.com/read/30663210/conformation-specific-antibodies-against-multiple-amyloid-protofibril-species-from-a-single-amyloid-immunogen
#15
Alessandra Bonito-Oliva, Sophia Schedin-Weiss, Shahab S Younesi, Ann Tiiman, Carolina Adura, Navid Paknejad, Matt Brendel, Yevgeniy Romin, Ronald J Parchem, Caroline Graff, Vladana Vukojević, Lars O Tjernberg, Lars Terenius, Bengt Winblad, Thomas P Sakmar, W Vallen Graham
We engineered and employed a chaperone-like amyloid-binding protein Nucleobindin 1 (NUCB1) to stabilize human islet amyloid polypeptide (hIAPP) protofibrils for use as immunogen in mice. We obtained multiple monoclonal antibody (mAb) clones that were reactive against hIAPP protofibrils. A secondary screen was carried out to identify clones that cross-reacted with amyloid beta-peptide (Aβ42) protofibrils, but not with Aβ40 monomers. These mAbs were further characterized in several in vitro assays, in immunohistological studies of a mouse model of Alzheimer's disease (AD) and in AD patient brain tissue...
January 20, 2019: Journal of Cellular and Molecular Medicine
https://read.qxmd.com/read/30626427/a-rare-population-of-tumor-antigen-specific-cd4-cd8-double-positive-%C3%AE-%C3%AE-t-lymphocytes-uniquely-provide-cd8-independent-tcr-genes-for-engineering-therapeutic-t-cells
#16
Junko Matsuzaki, Takemasa Tsuji, Thinle Chodon, Courtney Ryan, Richard C Koya, Kunle Odunsi
BACKGROUND: High-affinity tumor antigen-specific T-cell receptor (TCR) gene is required to engineer potent T cells for therapeutic treatment of cancer patients. However, discovery of suitable therapeutic TCR genes is hampered by the fact that naturally occurring tumor antigen-specific TCRs are generally of low-affinity, and artificial modification of TCRs can mediate cross-reactivity to other antigens expressed in normal tissues. Here, we discovered a naturally occurring T-cell clone which expressed high-affinity HLA-A*02:01 (A*02)-restricted TCR against NY-ESO-1 from a patient who had NY-ESO-1-expressing ovarian tumor...
January 9, 2019: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30624285/the-microbiome-in-systemic-autoimmune-disease-mechanistic-insights-from-recent-studies
#17
Carina Dehner, Rebecca Fine, Martin A Kriegel
PURPOSE OF REVIEW: The resident bacterial communities and the host immune system have coevolved for millennia. However, recent changes in modern societies have disrupted this coevolutionary homeostasis and contributed to a rise in immune-mediated conditions. The purpose of this review is to provide an overview of recently elucidated mechanisms of how certain taxa within the bacterial microbiome propagate autoimmunity. RECENT FINDINGS: Interactions between the bacterial microbiome with innate and adaptive immune cells propagate autoreactivity, chronic inflammation, and tissue damage in susceptible hosts...
January 7, 2019: Current Opinion in Rheumatology
https://read.qxmd.com/read/30611197/changes-in-the-sublingual-microcirculation-following-aortic-surgery-under-balanced-or-total-intravenous-anaesthesia-a-prospective-observational-study
#18
Silvia Loggi, Nicoletta Mininno, Elisa Damiani, Benedetto Marini, Erica Adrario, Claudia Scorcella, Roberta Domizi, Andrea Carsetti, Simona Pantanetti, Gabriele Pagliariccio, Luciano Carbonari, Abele Donati
BACKGROUND: In vascular surgery with aortic cross-clamping, ischemia/reperfusion injury induces systemic haemodynamic and microcirculatory disturbances. Different anaesthetic regimens may have a varying impact on tissue perfusion. The aim of this study was to explore changes in microvascular perfusion in patients undergoing elective open abdominal aortic aneurysm repair under balanced or total intravenous anaesthesia. METHODS: Prospective observational study. Patients undergoing elective open infrarenal abdominal aortic aneurysm repair received balanced (desflurane + remifentanil, n = 20) or total intravenous anaesthesia (TIVA, propofol + remifentanil using target-controlled infusion, n = 20) according to the clinician's decision...
January 5, 2019: BMC Anesthesiology
https://read.qxmd.com/read/30593966/neuroprotective-effects-of-tocilizumab-on-experimentally-induced-spinal-cord-ischemia-reperfusion-injury
#19
Yasar Karatas, Mehmet Fatih Erdi, Bülent Kaya, Fatih Keskin, Gökhan Cüce, Ibrahim Kılınc, Mehmet Uyar, Emir Kaan Izci, Erdal Kalkan
STUDY DESIGN: Experimental rabbit spinal cord ischemia-reperfusion (I/R) inury model. OBJECTIVES: We aimed to evaluate neuroprotective effects of tocilizumab on spinal cord I/R inury. SETTING: Animal Research Laboratory, Necmettin Erbakan University, Meram School of Medicine, Konya, Turkey. METHODS: Twenty four adult New Zealand rabbits were randomly divided into three groups: Group 1, control group (n=8); Group 2, ischemia-reperfusion (I/R) group and group 3 (n=8), I/R injury+ tocilizumab (4 mg/kg,ip) treatment group...
December 26, 2018: World Neurosurgery
https://read.qxmd.com/read/30582800/ros-sensitive-cross-linked-polyethylenimine-for-red-light-activated-sirna-therapy
#20
Junxia Wang, Xinyu He, Song Shen, Ziyang Cao, Xianzhu Yang
The extremely inefficient endosomal escape and intracellular release are the central barriers for effective nanocarrier-mediated RNA interference (RNAi) therapeutics. Accelerating endosomal escape and triggering intracellular release with red or near-infrared light are of particular interest due to its spatiotemporal controllability, great tissue penetration, and minimal phototoxicity. As a proof-of-concept, we explored an innovative siRNA delivery system, TKPEI-Ce6, that is prepared by the linking reaction of branched polyethylenimine, a reactive oxygen species (ROS)-labile crosslinker, poly(ethylene glycol), and chlorin e6 (Ce6)...
December 24, 2018: ACS Applied Materials & Interfaces
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