- Phosphine-Dependent Photoinitiation of Alkyl Thiols under Near-UV Light Facilitates User-Friendly Peptide Desulfurization. [Journal Article]J Am Chem Soc. 2023 Jan 18; 145(2):1053-1061.JA
- Peptides are steadily gaining importance as pharmaceutical targets, and efficient, green methods for their preparation are critically needed. A key deficiency in the synthetic toolbox is the lack of an industrially viable peptide desulfurization method. Without this tool, the powerful native chemical ligation reaction typically used to assemble polypeptides and proteins remains out of reach for i…
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- Antifibrinolytics use during surgery for oncological spine diseases: A systematic review. [Review]
- CONCLUSIONS: In this review, we found that TXA may diminish intraoperative blood loss, the need for transfusion and postoperative drainage from surgical drains when used in OSD without major increase in rates of DVT or PE.
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- Aprotinin does not Impair Vascular Function in Patients Undergoing Coronary Artery Bypass Graft Surgery. [Journal Article]Horm Metab Res. 2023 Jan; 55(1):65-74.HM
- Bleeding is a major complication in coronary artery bypass graft surgery. Antifibrinolytic agents like serine protease inhibitor aprotinin can decrease postoperative bleeding and complications of cardiac surgery. However, the effects of aprotinin on vascular function are not completely elucidated. We compared the ex vivo vascular function of left internal mammary arteries from patients undergoing…
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- Serine proteases mediate leukocyte recruitment and hepatic microvascular injury in the acute phase following extended hepatectomy. [Journal Article]Microcirculation. 2023 Jan; 30(1):e12796.M
- CONCLUSIONS: Endothelial activation and leukocyte recruitment in the liver in response to the increment of sinusoidal shear rate were hallmarks in the acute phase after liver resection. SPs mediated leukocyte recruitment and contributed to the impairment of sinusoidal perfusion in an ICAM-1-dependent manner in the acute phase after liver resection.
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- Protein 3D Hydration: A Case of Bovine Pancreatic Trypsin Inhibitor. [Journal Article]
- Characterization of the hydrated state of a protein is crucial for understanding its structural stability and function. In the present study, we have investigated the 3D hydration structure of the protein BPTI (bovine pancreatic trypsin inhibitor) by molecular dynamics (MD) and the integral equation method in the three-dimensional reference interaction site model (3D-RISM) approach. Both methods …
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- Water Network in the Binding Pocket of Fluorinated BPTI-Trypsin Complexes─Insights from Simulation and Experiment. [Journal Article]J Phys Chem B. 2022 12 08; 126(48):9985-9999.JP
- Structural waters in the S1 binding pocket of β-trypsin are critical for the stabilization of the complex of β-trypsin with its inhibitor bovine pancreatic trypsin inhibitor (BPTI). The inhibitor strength of BPTI can be modulated by replacing the critical lysine residue at the P1 position by non-natural amino acids. We study BPTI variants in which the critical Lys15 in BPTI has been replaced by α…
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- Lung injury following cardiopulmonary bypass: a clinical update. [Review]Expert Rev Cardiovasc Ther. 2022 Nov; 20(11):871-880.ER
- Cardiopulmonary bypass (CPB) is an integral component of cardiac surgery; however, one of its most critical complications is acute lung injury induced by multiple factors including systemic inflammatory response.
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- Modulation of thromboinflammation in hospitalized COVID-19 patients with aprotinin, low molecular weight heparin, and anakinra: The DAWn-Antico study. [Journal Article]
- CONCLUSIONS: In hospitalized COVID-19 patients, modulation of thromboinflammation with high-dose aprotinin and LMWH with or without anakinra did not improve outcome in patients with moderate to severe COVID-19.
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- Bovine pancreatic trypsin inhibitor and soybean Kunitz trypsin inhibitor: Differential effects on proteases and larval development of the soybean pest Anticarsia gemmatalis (Lepidoptera: Noctuidae). [Journal Article]Pestic Biochem Physiol. 2022 Oct; 187:105188.PB
- Pest management is challenged with resistant herbivores and problems regarding human health and environmental issues. Indeed, the greatest challenge to modern agriculture is to protect crops from pests and still maintain environmental quality. This study aimed to analyze by in silico, in vitro, and in vivo approaches to the feasibility of using the inhibitory protein extracted from mammals - Bovi…
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- Elevated Pre- and Postoperative ROTEM™ Clot Lysis Indices Indicate Reduced Clot Retraction and Increased Mortality in Patients Undergoing Liver Transplantation. [Journal Article]
- CONCLUSIONS: Both pre- and postoperative ROTEM™ clot lysis indices predict mortality in patients following liver transplantation. Inhibitor experiments reveal that the clot lysis index is not an indicator of fibrinolysis, but indicates platelet clot retraction. The marked increase of clot lysis index during liver transplantation is caused by a decrease in clot retraction with eventual consequences for clot stability, retraction of wound margins, and reperfusion of vessels in case of thrombosis.
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- Melanoma Mediated Disruption of Brain Endothelial Barrier Integrity Is Not Prevented by the Inhibition of Matrix Metalloproteinases and Proteases. [Journal Article]
- We have previously shown that human melanoma cells rapidly decrease human brain endothelial barrier strength. Our findings showed a fast mechanism of melanoma mediated barrier disruption, which was localised to the paracellular junctions of the brain endothelial cells. Melanoma cells are known to release molecules which cleave the surrounding matrix and allow traversal within and out of their met…
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- Prophylactic Use of Antifibrinolytics During Pediatric Cardiac Surgery With Cardiopulmonary Bypass on Postoperative Bleeding and Transfusion: A Systematic Review and Meta-Analysis. [Meta-Analysis]Pediatr Crit Care Med. 2022 11 01; 23(11):e517-e529.PC
- CONCLUSIONS: Antifibrinolytics are effective at decreasing blood loss and blood product requirement in children undergoing cardiac surgery with CPB although the quality of evidence is only moderate.
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- The Efficacy of Aprotinin Combinations with Selected Antiviral Drugs in Mouse Models of Influenza Pneumonia and Coronavirus Infection Caused by SARS-CoV-2. [Journal Article]
- The efficacy of aprotinin combinations with selected antiviral-drugs treatment of influenza virus and coronavirus (SARS-CoV-2) infection was studied in mice models of influenza pneumonia and COVID-19. The high efficacy of the combinations in reducing virus titer in lungs and body weight loss and in increasing the survival rate were demonstrated. This preclinical study can be considered a confirma…
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- The degradation of gelatin/alginate/fibrin hydrogels is cell type dependent and can be modulated by targeting fibrinolysis. [Journal Article]
- In tissue engineering, cell origin is important to ensure outcome quality. However, the impact of the cell type chosen for seeding in a biocompatible matrix has been less investigated. Here, we investigated the capacity of primary and immortalized fibroblasts of distinct origins to degrade a gelatin/alginate/fibrin (GAF)-based biomaterial. We further established that fibrin was targeted by degrad…
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- Characterizing Metastable States with the Help of Machine Learning. [Journal Article]J Chem Theory Comput. 2022 Sep 13; 18(9):5195-5202.JC
- Present-day atomistic simulations generate long trajectories of ever more complex systems. Analyzing these data, discovering metastable states, and uncovering their nature are becoming increasingly challenging. In this paper, we first use the variational approach to conformation dynamics to discover the slowest dynamical modes of the simulations. This allows the different metastable states of the…
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- Optimizing Blood Loss and Management in Craniosynostosis Surgery: A Systematic Review of Outcomes Over the Last 40 Years. [Journal Article]Cleft Palate Craniofac J. 2022 Jul 28 [Online ahead of print]CP
- Surgical correction of craniosynostosis can involve significant blood loss. Rates of allogenic blood transfusion have been reported to approach 100%. Multiple interventions have been described to reduce blood loss and transfusion requirements. The aim of this study was to analyze various approaches over the last 4 decades to optimize blood loss and management during craniosynostosis surgery.
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- Therapeutic use of α2-antiplasmin as an antifibrinolytic and hemostatic agent in surgery and regenerative medicine. [Journal Article]
- The biomaterial fibrin is widely used as a clinical tissue sealant in surgery. In preclinical research, fibrin is also extensively studied as a carrier material for growth factor delivery. In these applications, premature fibrin degradation leads to recurrent bleeding, tissue dehiscence and limited regenerative efficacy. Therefore, fibrinolysis inhibitors have been added to clinical fibrin formul…
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- Use and safety of aprotinin in routine clinical practice: A European postauthorisation safety study conducted in patients undergoing cardiac surgery. [Journal Article]
- CONCLUSIONS: The data in the NApaR indicated that in this patient population, at high risk of death or blood loss undergoing cardiac surgery, including complex cardiac surgeries other than iCABG, the incidence of adverse events is in line with data from current literature, where aprotinin was not used.
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- The Anti-Angiogenic and Anti-Proliferative Activity of Methyl Hydroxychalcone. [Journal Article]
- CONCLUSIONS: This study showed that methyl hydroxychalcone significantly inhibits the angiogenesis process, blocking the VEGF signaling pathway in HUVECs and could be a potential promising angiogenesis inhibitor lead compound.
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- Methodological considerations for ghrelin isoforms assay in clinical evaluation in anorexia nervosa. [Journal Article]
- The growing interest concerning the role of metabolic sensors in various eating disorders requires the implementation of a strict methodology to collect, store and process blood samples in clinical studies. In particular, measurement of isoforms of the appetite-stimulating hormone, ghrelin, has been challenging in clinical settings. Indeed the acyl ghrelin (AG) isoform is rapidly degraded into de…
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- A Narrative Review of 99mTc-Aprotinin in the Diagnosis of Cardiac Amyloidosis and a New Life for an Unfairly Abandoned Drug. [Review]
- Several studies investigated the use of 99mTc-labelled Aprotinin as an amyloid seeker some years ago. In vitro tests showed high binding affinity for several types of amyloid fibrils accompanied by an excellent specificity. Initial human studies demonstrated good accuracy in detecting cardiac involvement. Scintigraphy results were confirmed in a group of 28 endomyocardial biopsies. Unfortunately,…
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- Proteolytic Activity against the Distal Polybasic Tract of the Gamma Subunit of the Epithelial Sodium Channel ENaC in Nephrotic Urine. [Journal Article]
- CONCLUSIONS: Nephrotic urine from both humans and mice contains aprotinin-sensitive proteolytic activity against the distal polybasic tract of γ-ENaC, reflecting excretion of active proteases in the urine or proteasuria.
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- Rodent models to study sodium retention in experimental nephrotic syndrome. [Review]Acta Physiol (Oxf). 2022 07; 235(3):e13844.AP
- Sodium retention and edema are hallmarks of nephrotic syndrome (NS). Different experimental rodent models have been established for simulating NS, however, not all of them feature sodium retention which requires proteinuria to exceed a certain threshold. In rats, puromycin aminonucleoside nephrosis (PAN) is a classic NS model introduced in 1955 that was adopted as doxorubicin-induced nephropathy …
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- Survey of Dipeptidyl Peptidase III Inhibitors: From Small Molecules of Microbial or Synthetic Origin to Aprotinin. [Review]
- Dipeptidyl peptidase III (DPP III) was originally thought to be a housekeeping enzyme that contributes to intracellular peptide catabolism. More specific roles for this cytosolic metallopeptidase, in the renin-angiotensin system and oxidative stress regulation, were confirmed, or recognized, only recently. To prove indicated (patho)physiological functions of DPP III in cancer progression, catarac…
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- Transmembrane serine protease 2 (TMPRSS2) proteolytically activates the epithelial sodium channel (ENaC) by cleaving the channel's γ-subunit. [Journal Article]
- The epithelial sodium channel (ENaC) is a heterotrimer consisting of α-, β-, and γ-subunits. Channel activation requires proteolytic release of inhibitory tracts from the extracellular domains of α-ENaC and γ-ENaC; however, the proteases involved in the removal of the γ-inhibitory tract remain unclear. In several epithelial tissues, ENaC is coexpressed with the transmembrane serine protease 2 (TM…
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- Optimizing the performance of 68Ga labeled FSHR ligand in prostate cancer model by co-administration of aprotinin. [Journal Article]Int J Radiat Biol. 2022; 98(10):1571-1580.IJ
- CONCLUSIONS: With the aid of a serine protease inhibitor, the performance of the 68Ga labeled peptide was optimized, which may benefit further clinical application.
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- Perioperative anaphylaxis to fibrin sealants in children with Noonan Syndrome: A retrospective study. [Journal Article]
- CONCLUSIONS: Given that fibrin sealants are typically used in various surgical practices and although the anaphylaxis reactions in such cases are rare, it is essential to be cautious in patients with RASopathies who are at a high risk of developing anaphylaxis.
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- Aprotinin treatment against SARS-CoV-2: A randomized phase III study to evaluate the safety and efficacy of a pan-protease inhibitor for moderate COVID-19. [Randomized Controlled Trial]
- CONCLUSIONS: Inhaled aprotinin may improve standard treatment and clinical outcomes in hospitalized patients with COVID-19, resulting in a shorter treatment time and hospitalization compared with the placebo group. The administration of aprotinin was safe.
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- Rapid Rational Design of Cyclic Peptides Mimicking Protein-Protein Interfaces. [Journal Article]
- The cPEPmatch approach is a rapid computational methodology for the rational design of cyclic peptides to target desired regions of protein-protein interfaces. The method selects cyclic peptides that structurally match backbone structures of short segments at a protein-protein interface. In a second step, the cyclic peptides act as templates for designed binders by adapting the amino acid side ch…
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