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https://www.readbyqxmd.com/read/28820579/site-specific-conjugation-to-native-and-engineered-lysines-in-human-immunoglobulins-by-microbial-transglutaminase
#1
Jared Spidel, Benjamin Vaessen, Earl Albone, Xin Cheng, Arielle Verdi, J Bradford Kline
The use of microbial transglutaminase (MTG) to produce site-specific antibody-drug conjugates (ADCs) has thus far focused on transamidation of engineered acyl donor glutamine residues in an antibody based on the hypothesis that the lower specificity of MTG for acyl acceptor lysines may result in transamidation of multiple native lysine residues, thereby yielding heterogeneous products. We investigated the utilization of native IgG lysines as acyl acceptor sites for glutamine-based acyl donor substrates. Of the approximately 80 lysines in multiple recombinant IgG monoclonal antibodies (mAbs), none were transamidated...
August 18, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28819077/-gluten-ataxia-anti-transglutaminase-6-antibody-as-a-new-biomarker
#2
Kenji Sato, Kazunori Nanri
Gluten-related disorders (GRDs) are conditions that develop in response to the common trigger of gluten ingestion and manifest as a variety of clinical symptoms. GRDs have been considered rare in Asian countries, including Japan, because of lower consumption of wheat products than in Europe and the U.S.A. and differences in genetic background. Recently, however, GRDs, such as celiac disease and gluten ataxia, have been reported in Japan, albeit sporadically and their presence is now recognized in this country...
August 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28810589/phenotypic-switch-in-lung-interstitial-macrophage-polarization-in-an-ovalbumin-induced-mouse-model-of-asthma
#3
Hanxiang Nie, Ailing Wang, Qing He, Qiaoyu Yang, Linlin Liu, Guqin Zhang, Yi Huang, Xuhong Ding, Hongying Yu, Suping Hu
Macrophage phenotype and function varies according to their polarized state, which in turn is dependent on microenvironmental stimuli. Under normal physiological conditions, lung interstitial macrophages that express interleukin (IL)-10 are considered to serve regulatory roles in the prevention of allergic reactions in the airways. However, the phenotypic profile of lung interstitial macrophages during the pathophysiology of asthma remains unknown. In the current study, the phenotypic characteristics of lung interstitial macrophages were investigated in an ovalbumin (OVA)-induced mouse model of asthma...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810543/atorvastatin-has-a-protective-effect-in-a-mouse-model-of-bronchial-asthma-through-regulating-tissue-transglutaminase-and-triggering-receptor-expressed-on-myeloid-cells-1-expression
#4
Ming-Wei Liu, Rong Liu, Hai-Ying Wu, Mei Chen, Min-Na Dong, Yun-Qiao Huang, Chun-Hai Zhang, Yin-Zhong Wang, Jing Xia, Yang Shi, Feng-Mei Xie, Hua Luo, Xin-Yuan Zhao, Wei Wei, Mei-Xian Su
Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. Statin drugs have improved respiratory health and their therapeutic potential in asthma has been tested in clinical trials. However, the mechanism of action of statins in this context has remained elusive. The present study hypothesized that atorvastatin treatment of ovalbumin-exposed mice attenuates early features of airway remodeling via a mevalonate-dependent mechanism...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810029/celiac-disease-and-nonceliac-gluten-sensitivity-a-review
#5
Maureen M Leonard, Anna Sapone, Carlo Catassi, Alessio Fasano
Importance: The prevalence of gluten-related disorders is rising, and increasing numbers of individuals are empirically trying a gluten-free diet for a variety of signs and symptoms. This review aims to present current evidence regarding screening, diagnosis, and treatment for celiac disease and nonceliac gluten sensitivity. Observations: Celiac disease is a gluten-induced immune-mediated enteropathy characterized by a specific genetic genotype (HLA-DQ2 and HLA-DQ8 genes) and autoantibodies (antitissue transglutaminase and antiendomysial)...
August 15, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28808357/platelet-released-growth-factors-induce-differentiation-of-primary-keratinocytes
#6
Andreas Bayer, Mersedeh Tohidnezhad, Justus Lammel, Sebastian Lippross, Peter Behrendt, Tim Klüter, Thomas Pufe, Holger Jahr, Jochen Cremer, Franziska Rademacher, Regine Gläser, Jürgen Harder
Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs) or their clinically related formulations (e.g., Vivostat PRF®) came recently into the physicians' focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiation status of skin wounds in vivo...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28806297/adherence-to-a-gluten-free-diet-assessment-by-dietician-interview-and-serology
#7
Pooja Mehta, Zhaoxing Pan, Marisa Dzarnoski Riley, Edwin Liu
We aimed to 1) determine if tissue transglutaminase autoantibody (tTG) positivity was associated with dietitian-assessed adherence to a gluten-free diet in pediatric patients with celiac disease and 2) identify areas where adherence falters. We reviewed the records of children with celiac disease who had a standardized evaluation of adherence by a registered dietitian. A negative tTG value was not associated with good adherence (p = NS). Adherent and nonadherent children differed with respect to purposeful and accidental gluten exposure (p < 0...
August 11, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28805145/pdgf-vegf-related-receptor-affects-transglutaminase-activity-to-control-cell-migration-during-crustacean-hematopoiesis
#8
Kingkamon Junkunlo, Chadanat Noonin, Kenneth Söderhäll, Irene Söderhäll
The platelet-derived growth factor (PDGF) receptor, a tyrosine kinase receptor whose ligand is PDGF, is crucial in the transduction of extracellular signals into cells and mediates numerous processes, such as cell proliferation, differentiation, survival and migration. We demonstrate the important roles of a receptor tyrosine kinase related to the PDGF/VEGF family protein (PVR) in controlling hematopoietic progenitor cell migration by affecting extracellular transglutaminase (TGase) activity. Pl_PVR1, GenBank accession number KY444650, is highly expressed in hemocytes and the hematopoietic tissue (HPT)...
August 12, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28805084/covalent-immobilisation-of-transglutaminase-stability-and-applications-in-protein-pegylation
#9
Antonella Grigoletto, Anna Mero, Hiroki Yoshioka, Oddone Schiavon, Gianfranco Pasut
Microbial transglutaminase enzyme (mTGase) is an extremely useful enzyme that is increasingly employed in the food and pharmaceutical industries and as a tool for protein modification and tagging. The current study describes how we immobilised mTGase (iTGase) on a solid support to improve its stability during the PEGylation process by which polyethylene glycol chains are attached to protein and peptide drugs. When the enzyme was immobilised at the N-terminal sequence on agarose beads, it retained more than 53% of its starting activity...
August 13, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28797308/coeliac-disease-in-infants-antibodies-to-deamidated-gliadin-peptide-come-first
#10
Michele Arigliani, Francesca Rech Morassutti, Martina Fabris, Paola Melli, Elio Tonutti, Paola Cogo
BACKGROUND: The onset of coeliac disease (CD) in the first year of life is uncommon and the diagnosis can be challenging due to the suboptimal sensitivity of tissue transglutaminase antibodies (tTG) at this age and the many other possible causes of malabsorption in infants. Antibodies to deamidated gliadin peptides (anti-DGPs), especially IgG, may appear earlier than IgA anti-tTG in very young children with CD. CASE PRESENTATION: We report here on an 8-month-old child who was evaluated for failure to thrive, constipation and developmental delay...
August 10, 2017: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/28782118/undetectable-negative-tissue-transglutaminase-iga-antibodies-predict-mucosal-healing-in-treated-coeliac-disease-patients
#11
H Fang, K S King, J J Larson, M R Snyder, T T Wu, M J Gandhi, J A Murray
BACKGROUND: Tissue transglutaminase (tTG) immunoglobulin A (IgA) testing is a sensitive adjunct to the diagnosis of coeliac disease. The threshold for positivity was developed for diagnosis, with negative results reported as below the reference value (<4 U/mL). AIM: To investigate if an undetectable (tTG IgA<1.2 U/mL) is more predictive of healing compared to patients with negative but detectable serology (1.2-3.9 U/mL). METHODS: We performed a retrospective study of 402 treated coeliac disease patients seen at the Mayo Clinic with negative tTG IgA values drawn within 1 month of duodenal biopsy between January 2009 and December 2015...
August 7, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28781956/the-proteomic-profile-of-a-mouse-model-of-proliferative-vitreoretinopathy
#12
Bernadett Márkus, Zsuzsanna Pató, Zsolt Sarang, Réka Albert, József Tőzsér, Goran Petrovski, Éva Csősz
Proliferative vitreoretinopathy (PVR) develops as a complication of retinal detachment surgery and represents a devastating condition leading to serious vision loss. A good animal model that permits extensive functional studies and drug testing is crucial in finding better therapeutic modalities for PVR. A previously established mouse model, using dispase injection, was analyzed from the proteomic point of view, examining global protein profile changes by 2D electrophoresis, image analysis and HPLC-tandem mass spectrometry-based protein identification...
August 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28775095/transglutaminase-2-in-pulmonary-and-cardiac-tissue-remodeling-in-experimental-pulmonary-hypertension
#13
Krishna C Penumatsa, Deniz Toksoz, Rod R Warburton, Mousa Kharnaf, Ioana R Preston, Navin Kumar Kapur, Chaitan Khosla, Nicholas S Hill, Barry L Fanburg
Tissue matrix remodeling and fibrosis leading to loss of pulmonary arterial and right ventricular compliance are important features of both experimental and clinical pulmonary hypertension (PH). We have previously reported that transglutaminase 2 (TG2) is involved in PH development while others have shown it to be a crosslinking enzyme that participates in remodeling of extracellular matrix in fibrotic diseases in general. In the present studies, we used a mouse model of experimental PH (Sugen 5416 and hypoxia; SuHypoxia) and cultured primary human cardiac and pulmonary artery adventitial fibroblasts to evaluate the relationship of TG2 to the processes of fibrosis, protein crosslinking, extracellular matrix collagen accumulation and fibroblast to myofibroblast transformation...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28774822/browning-deficiency-and-low-mobilization-of-fatty-acids-in-gonadal-white-adipose-tissue-leads-to-decreased-cold-tolerance-of-transglutaminase-2-knock-out-mice
#14
András Mádi, Ixchelt Cuaranta-Monroy, Kinga Lénárt, Attila Pap, Zoltán András Mezei, Endre Kristóf, Anna Oláh, György Vámosi, Zsolt Bacsó, Péter Bai, László Fésüs
During cold-exposure 'beige' adipocytes with increased mitochondrial content are activated in white adipose tissue (WAT). These cells, similarly to brown adipocytes (BAT), dissipate stored chemical energy in the form of heat with the help of uncoupling protein 1 (UCP1). We investigated the effect of TG2 ablation on the function of ATs in mice. Although TG2(+/+) and TG2(-/-) mice had the same amount of WAT and BAT, we found that TG2(+/+) animals could tolerate acute cold exposure for 4h, whereas TG2(-/-) mice only for 3h...
July 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28771959/antibacterial-activity-and-cytotoxycity-of-gelatine-conjugated-lysine-based-peptides
#15
Maja Kaisersberger Vincek, Amram Mor, Selestina Gorgieva, Vanja Kokol
The effect of the coupling approach (chemical by using carbodiimide chemistry, and enzymatic by using transglutaminase) of a hydrophilic ε-poly-L-lysine (εPL) and a structurally-hydrophobic oligo-acyl-lysyl (OAK) to a gelatine (GEL) macromolecule, and their antibacterial activity against Gram-negative E. coli and Gram-positive S. aureus bacteria, as well as cytotoxicity to human osteoblast cells was studied as potential macromolecules for biomedical applications. Different spectroscopic (ultraviolet-visible, infrared, fluorescence, and electron paramagnetic resonance) and separation (size-exclusion chromatography and capillary zone electrophoresis) techniques, as well as zeta-potential analysis were performed to confirm the εPL/OAK covalent coupling and to determine their amount and orientation of the immobilization...
August 2, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28771896/dual-site-specifically-modified-antibodies-with-solid-phase-immobilized-microbial-transglutaminase
#16
Philipp Spycher, Christian A Amann, Jöri Wehrmüller, David R Hurwitz, Oliver Kreis, Andreas Ritler, Daniel Messmer, Andreas Küchler, Alain Blanc, Peter Walde, Martin Béhé, Roger Schibli
Microbial transglutaminase (MTG) has been stably solid-phase immobilized on glass microbeads using a second generation dendronized polymer. Immobilized MTG enabled the efficient generation of site-specifically conjugated proteins including scFvs and Fab-fragments as well as whole antibodies via distinct glutamines and unprecedented, also via lysines with various bifunctional substrates with defined stoichiometry. With this method we generated dual site-specifically modified antibodies comprising a fluorescent probe and a metal chelator for radiolabeling - a strategy anticipated to design antibodies for imaging and therapy...
August 3, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28771001/abrogation-of-immunogenic-properties-of-gliadin-peptides-through-transamidation-by-microbial-transglutaminase-is-acyl-acceptor-dependent
#17
Lin Zhou, Yvonne M C Kooy-Winkelaar, Robert A Cordfunke, Irina Dragan, Allan Thompson, Jan Wouter Drijfhout, Peter A van Veelen, Hongbing Chen, Frits Koning
Wheat gluten confers superior baking quality to wheat based products but elicits a pro-inflammatory immune response in patients with celiac disease. Transamidation of gluten by microbial transglutaminase (mTG) and tissue transglutaminase (tTG) reduces the immunogenicity of gluten; however, little information is available on the minimal modification sufficient to eliminate gliadin immunogenicity nor has the effectiveness of transamidation been studied with T-cell clones from patients. Here we demonstrate that mTG can efficiently couple three different acyl-acceptor molecules, l-lysine, glycine ethyl ester, and hydroxylamine, to gliadin peptides and protein...
August 17, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28768185/preparation-and-characterization-of-hydroxypropyl-chitosan-modified-with-nisin
#18
Chen Zhu, Shengqiong Zou, Ziqie Rao, Lian Min, Meng Liu, Liangling Liu, Lihong Fan
Nisin had been grafted to hydroxypropyl chitosan (HPCS) using microbial transglutaminase (MTGase) as biocatalyst. HPCS was synthesized from chitosan and propylene oxide under alkali condition. The chemical structures of derivatives were characterized by FT-IR and (1)H NMR spectroscopy. The process conditions were optimized from the aspects of the reaction time, the reaction temperature, the molar ratio of nisin to HPCS and the mass ratio of MTGase to HPCS. In this study, the results of moisture absorption and retention tests showed HPCS-nisin had moisture absorption and moisture retention abilities...
July 30, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28767399/effect-of-p53-on-pancreatic-cancer-glucose-tolerance-abnormalities-by-regulating-transglutaminase-2-in-resistance-to-glucose-metabolic-stress
#19
Xiao Su, Xiangyi He, Qiwen Ben, Weiyi Wang, Huan Song, Qiao Ye, Yi Zang, Weiguang Li, Ping Chen, Weiyan Yao, Yaozong Yuan
Pancreatic ductal adenocarcinoma (PanCa) is an extremely lethal disease characterized by mutations of p53 in up to 70% of cases. Our previous studies have confirmed that hyperglycemia may be the first clinical manifestation for the early diagnosis of PanCa. In this article, we showed that targeted knockdown of TG2 or p53 in tumor cells led to decreased cell survival in response to glucose deprivation, while this phenomenon was abolished by combined inhibition of TG2 and p53. We observed that inhibition of TG2 or p53 sensitized glucose deprivation resistance through an intracellular reactive oxygen species (ROS) pathway and the induction of Bcl-2...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28764076/a-sensitive-hplc-ms-ms-method-for-the-simultaneous-detection-of-microbial-transglutaminase-and-bovine-and-porcine-fibrinogen-thrombin-in-restructured-meat
#20
Wolfgang Jira, Fredi Schwägele
A sensitive HPLC-MS/MS method for the simultaneous detection of microbial transglutaminase (TG) from Streptomyces mobaraensis, and bovine and porcine fibrinogen/thrombin in restructured meat was developed using tryptic marker peptides of TG (five markers), and bovine and porcine fibrinogen (six markers each). Meat binding experiments with beef and pork were performed using a technical TG mixture (Activa, Ajinomoto), and bovine and porcine plasmapowder FG (PPFG; Sonac B.V.). The method developed allows the simultaneous detection of the use of these cold-set binders in raw and heated samples...
December 15, 2017: Food Chemistry
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