Gábor Nardai
Semmelweis University, Traumatology, Post-Doc
The stress, or heat-shock proteins are essential for the homeostasis of living cells. Their role in the intracellular transport, refolding, or elimination of proteins becomes especially important after any unusual stimuli (stress) of the... more
The stress, or heat-shock proteins are essential for the homeostasis of living cells. Their role in the intracellular transport, refolding, or elimination of proteins becomes especially important after any unusual stimuli (stress) of the cell. This central role explains why stress proteins represent one of the most conservative structures of living cells. Human and bacterial stress proteins also show a homology as high, as 50%. This structural similarity links the immune responses against bacterial infections with a number of autoimmune diseases, such as lupus erythematosus, rheumatoid arthritis and insulin dependent diabetes mellitus, IDDM. In the end of our review we also discuss the possible role of stress proteins in protection against cardiac ischaemia and their putative role in aging.
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Chaperone-related immune dysfunctions: an emergent property of distorted chaperone-networks
Bevezetés: A COVID–19-pandémia során az intenzív osztályon kezelt betegek halálozása, bár országonként eltérő, de mindenütt drámaian nagy volt (20–60%). A rizikófaktorok azonosítása segítséget nyújt a betegség patomechanizmusának... more
Bevezetés: A COVID–19-pandémia során az intenzív osztályon kezelt betegek halálozása, bár országonként eltérő, de mindenütt drámaian nagy volt (20–60%). A rizikófaktorok azonosítása segítséget nyújt a betegség patomechanizmusának megértésében, és támpontot ad a veszélyeztetett betegek kiszűréséhez, a prognózis becsléséhez és esetleg a megfelelő kezelési modalitás alkalmazásához is. Célkitűzés: Intenzív osztályunkra felvett betegeken végzett vizsgálatunk a demográfiai és állapotsúlyossági faktorok elemzése mellett a kezelési modalitás változásának hatását is vizsgálta a súlyos állapotú fertőzött betegek kimenetelére a COVID–19-járvány 3. és 4. hullámában. Módszer: Retrospektív, megfigyeléses vizsgálatban rögzítettük a súlyos légzési elégtelenséggel, koronavírus-fertőzés miatt felvett betegeink demográfiai, klinikai, kezelési és kimeneteli adatait. Eredmények: Összesen 88 beteg adatait dolgoztuk fel. A betegek 53%-a volt férfi, az életkor medián értéke 65 év, a medián BMI 29 kg/m2 vol...
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Abstract. Protection against oxidative stress is highly interrelated with the function of the most ancient cellular defense system, the network of molecular chaperones, heat shock, or stress-proteins. These ubiquitous, conserved proteins... more
Abstract. Protection against oxidative stress is highly interrelated with the function of the most ancient cellular defense system, the network of molecular chaperones, heat shock, or stress-proteins. These ubiquitous, conserved proteins help other proteins and macromolecules to fold or re-fold and reach their final, native conformation. Redox regulation of protein folding becomes especially important during the preparation of extracellular proteins to the outside oxidative milieu, which should take place in a gradual and step-by-step controlled manner in the endoplasmic reticulum or in the periplasm. Several chaperones, such as members of the Hsp33 family in yeast and the plethora of small heat shock proteins as well as one of the major chaperones, Hsp70 are able to act against cytoplasmic oxidative damage. Abrupt changes of cellular redox status lead to chaperone induction. The function of several chaperones is tightly regulated by the surrounding redox conditions. Moreover, our r...
Chaperone-related immune dysfunctions: an emergent property of distorted chaperone-networks
Research Interests: Biology, Medicine, Clinical Practice, Autoimmune Disease, Endoplasmic Reticulum, and 7 moreAntigen Presentation, Clinical Sciences, Toll-Like Receptors Therapeutics Pharmacology, Protein Kinase, Heat Shock Protein, Pharmacology and Therapeutics in Dentistry, and Pharmacology and pharmaceutical sciences
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Research Interests: Protein Folding, Biology, Medicine, Molecular chaperones, Protein Secretion, and 15 moreAnimals, Male, Endoplasmic Reticulum, Biochemical, Ascorbic Acid, Rats, Wistar Rats, Heat Shock Proteins, Heat Shock Protein, Streptozotocin, Experimental Diabetes Mellitus Type 1 and 2, Diabetic Rat, Biochemistry and cell biology, Rat Liver, and Medical biochemistry and metabolomics
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Munkank soran azonositottuk a citoplazma leggyakoribb stresszfeherjeje, a Hsp90 masodik, C-terminalis nukleotid kotőhelyet, valamint e feherje taxol-kotőhelyet, amely uj Hsp90 tamadaspontu gyogyszerek tervezesere ad lehetőseget.... more
Munkank soran azonositottuk a citoplazma leggyakoribb stresszfeherjeje, a Hsp90 masodik, C-terminalis nukleotid kotőhelyet, valamint e feherje taxol-kotőhelyet, amely uj Hsp90 tamadaspontu gyogyszerek tervezesere ad lehetőseget. Bebizonyitottuk, hogy a Hsp90 inhibitorok hatasmodjaban a megtamadott sejtek erőteljesebb lizise is reszt vesz. A chaperonok rendezetlen regioin alapulo uj elmeletet dolgoztunk ki műkodesuk megertesere. Elemeztuk a chaperonok szerepet az oregedes soran kulonos tekintettel az apoptozist gatlo tulajdonsagaikra. Az endoplazmatikus retikulum chaperonjai műkodesi mechanizmusanak szamos uj elemet tartuk fel egeszseges, es kronikus stressznek kitett sejtekben. Szamos uj szempontot adtunk a chaperonok szerepenek megertesere a sejt molekula-halozataiban. Ezek legfontosabbikakent felismertuk, hogy a halozatok gyenge kolcsonhatasai reszt vesznek minden komplex rendszer stabilizalasaban. Kidolgoztunk es reszben bizonyitottunk egy uj gyogyszertervezesi paradigmat, amely ...
Stress proteins or in other words heat shock proteins form an ancient defense system of our cells. They are necessary to prevent the aggregation of damaged proteins and to help their refolding after stress. Stress protein-assisted... more
Stress proteins or in other words heat shock proteins form an ancient defense system of our cells. They are necessary to prevent the aggregation of damaged proteins and to help their refolding after stress. Stress protein-assisted remodeling of protein structure is an important step of many cellular processes, such as protein transport, signaling and protein degradation. Stress proteins have a key role in many diseases. Thus they 1. protect our cells against the deteriorating effects of ischemia/reperfusion in myocardiac infarcts or in stroke; 2. protect transplanted tissues and organs; 3. act against the multiple damage of chronic diseases such as diabetes, or neurodegenerative diseases (Alzheimer's and Parkinson's disease); 4. participate in the etiology of several autoimmune diseases; 5. their activation, and role in antigen presentation can be used as an anticancer-therapy; 6. stress proteins increase longevity, and lastly 7. stress proteins act as a buffer of phenotypic...
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Ch ha an ng ge es s o of f c ce el ll lu ul la ar r r re ed do ox x h ho om me eo os st ta as si is s a an nd d p pr ro ot te ei in n f fo ol ld di in ng g i in n d di ia ab be et te es s Chaperones are conserved and abundant proteins of... more
Ch ha an ng ge es s o of f c ce el ll lu ul la ar r r re ed do ox x h ho om me eo os st ta as si is s a an nd d p pr ro ot te ei in n f fo ol ld di in ng g i in n d di ia ab be et te es s Chaperones are conserved and abundant proteins of the cell. They not only help to fold the newly synthesized proteins to get their final structure, but are also involved in many other events of the cellular life, such as signal transduction or protein degradation. A subset of chaperones takes part in the the formation of disulfide bonds, ion pairs and in the prolin cis-trans isomerisation of folding proteins. Disulfide bond formation is necessary for the active, functioning state of most secreted or plasma membrane proteins. Chaperones involved in disulfide bond formation need a highly regulated redox environment, which is provided by the lumen of the endoplasmic reticulum. The redox balance is maintained by many enzymatic systems, as well as by a permanent supply of coenzymes taking part in the el...
Advanced Trauma Life Support (ATLS) programs are recognized as the standard educational trauma program worldwide. Data suggest that ATLS has a positive impact on the value of trauma care. The ATLS Hungary program has been started in 2005,... more
Advanced Trauma Life Support (ATLS) programs are recognized as the standard educational trauma program worldwide. Data suggest that ATLS has a positive impact on the value of trauma care. The ATLS Hungary program has been started in 2005, celebrating its 10-year anniversary this year. In the present brief communication a brief overview is provided on the program.Student evaluation and statistical data about the participants were collected throughout the 10-year history of the Hungarian program.Student evaluation shows a high level of satisfaction amongst the participating doctors. Most participants are working in higher level centers. The Hungarian program shows good quality according to the participants. Establishing at least one new center is crucial to be able to provide the course for every professional interested in it or required to take it.
Perioperative transfusion in patients undergoing orthopedic surgery increases the number of postoperative complications. Thus, we have introduced an institution-tailored perioperative blood management program (PBM) to decrease the amount... more
Perioperative transfusion in patients undergoing orthopedic surgery increases the number of postoperative complications. Thus, we have introduced an institution-tailored perioperative blood management program (PBM) to decrease the amount of blood transfused in patients going through primary total hip replacement (THR) surgery. We have conducted a before-after observational cohort study in two predetermined observational periods. Demographic and clinical data, ASA scores, laboratory parameters, features of surgical procedure, and anesthesia were registered. Parameters of perioperative fluid administration, transfusion rate, and postoperative complications were also assessed. One hundred patients in the first and 108 patients in the second observational period were enrolled. Eventhough the ratio of posttraumatic THR procedures increased (9% vs. 17%), the PBM protocol has been utilized effectively and a significant decrease in perioperative blood transfusion rate has been observed (61%...
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Purpose Trauma is a leading cause of mortality, with major bleeding and trauma-induced coagulopathy (TIC) contributing to negative patient outcomes. Treatments for TIC include tranexamic acid (TXA), fresh frozen plasma (FFP), and... more
Purpose Trauma is a leading cause of mortality, with major bleeding and trauma-induced coagulopathy (TIC) contributing to negative patient outcomes. Treatments for TIC include tranexamic acid (TXA), fresh frozen plasma (FFP), and coagulation factor concentrates (CFCs, e.g. prothrombin complex concentrates [PCCs] and fibrinogen concentrate [FCH]). Guidelines for TIC management vary across Europe and a clear definition of TIC is still lacking. Methods An advisory board involving European trauma experts was held on 02 February 2019, to discuss clinical experience in the management of trauma-related bleeding and recommendations from European guidelines, focusing on CFC use (mainly FCH). This review summarises the discussions, including TIC definitions, gaps in the guidelines that affect their implementation, and barriers to use of CFCs, with suggested solutions. Results A definition of TIC, which incorporates clinical (e.g. severe bleeding) and laboratory parameters (e.g. low fibrinogen...
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Stress proteins or in other words heat shock proteins form an ancient defense system of our cells. They are necessary to prevent the aggregation of damaged proteins and to help their refolding after stress. Stress protein-assisted... more
Stress proteins or in other words heat shock proteins form an ancient defense system of our cells. They are necessary to prevent the aggregation of damaged proteins and to help their refolding after stress. Stress protein-assisted remodeling of protein structure is an important step of many cellular processes, such as protein transport, signaling and protein degradation. Stress proteins have a key role in many diseases. Thus they 1. protect our cells against the deteriorating effects of ischemia/reperfusion in myocardiac infarcts or in stroke; 2. protect transplanted tissues and organs; 3. act against the multiple damage of chronic diseases such as diabetes, or neurodegenerative diseases (Alzheimer's and Parkinson's disease); 4. participate in the etiology of several autoimmune diseases; 5. their activation, and role in antigen presentation can be used as an anticancer-therapy; 6. stress proteins increase longevity, and lastly 7. stress proteins act as a buffer of phenotypic...
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UK114, the goat liver tumour antigen, is a member of a widely distributed family of conserved low-molecular-mass proteins (YER057c/YjgF/UK114), the function of which is ill understood. To the various orthologues diverse functions have... more
UK114, the goat liver tumour antigen, is a member of a widely distributed family of conserved low-molecular-mass proteins (YER057c/YjgF/UK114), the function of which is ill understood. To the various orthologues diverse functions have been ascribed, such as translation inhibition, regulation of purine repressor or calpain activation. Owing to a limited sequence similarity to Hsp90 (heat-shock protein 90), they have also been proposed to be molecular chaperones; however, this has never been tested. In the present paper, we report the cloning and characterization of the Drosophila orthologue, DUK114. In brief, DUK114 had no effect that would have qualified it as a calpain activator. In contrast, it proved to be a very potent molecular chaperone in in vitro assays. In a heat-aggregation test, it significantly decelerated the formation of citrate synthase aggregates. In a reverse assay, the recovery of the enzyme from urea- and heat-induced denatured states was accelerated almost 3-fold...