Papers by Tatiana Syrovets
BMC Complementary Medicine and Therapies
BMC Complementary Medicine and Therapies
Background Complementary medicine (CM) is frequently used by patients, but little is known about ... more Background Complementary medicine (CM) is frequently used by patients, but little is known about the usage of CM in surgical patients. The study aimed to elucidate the relevance of CM in surgery. Methods This cross-sectional, multi-center survey utilized a paper-based questionnaire consisting of 21 questions to capture CM usage and interest as well as CM communication in visceral and thoracic surgical patients being hospitalized at the corresponding departments of surgery at the University Medical Centers in Freiburg, Heidelberg und Ulm, Germany. Results Overall, 151 patients consented to the survey. On average, current CM usage was stated by 44% of patients. Most frequently used CM approaches were physical exercise (63%), nutritional supplements (59%) and herbal medicine (56%). Strong interest in CM counselling was stated by 51% of patients. Almost 80% of patients wanted to be treated in a holistic manner and desired for reliable information about CM as well as CM informed physicia...
Food and Chemical Toxicology, 2022
Breast cancer is the most common cancer and the leading cause of cancer-related mortality among f... more Breast cancer is the most common cancer and the leading cause of cancer-related mortality among females worldwide. From the leaves of Callistemon citrinus, we have isolated a novel phloroglucinol dimer, calcitrinone A, and analyzed its potential anticancer activity using the triple-negative breast cancer cell line MDA-MB-231. Calcitrinone A decreased the total intracellular ATP levels, inhibited proliferation, and induced apoptosis in MDA-MB-231 cells, but was less toxic to peripheral blood mononuclear cells. The antiproliferative and apoptosis-inducing effects of calcitrinone A were confirmed in vivo using breast cancer xenografts grown on chick chorioallantoic membranes. Mechanistic analysis showed mitochondrial membrane-potential dissipation and interference with energy-yielding processes resulting in cell accumulation in the S phase of the cell cycle. Seahorse assay analysis revealed an early inhibition of mitochondrial oxidative phosphorylation (OXPHOS). At the molecular level, calcitrinone A inhibited activity of the succinate-coenzyme Q reductase (SQR) (mitochondrial complex II). In silico docking identified the coenzyme Q binding pocket as a possible high affinity binding site for calcitrinone A in SQR. Inhibition of complex II was accompanied by strong elevation of mitochondrial superoxide and cytoplasmic ROS. Calcitrinone A might be a promising anticancer lead compound acting through the interference with the mitochondrial complex II activity.
The FASEB Journal, 2015
Amyloid β (Aβ) fibrils are strongly involved in the pathogenesis of Alzheimer's diseases. The... more Amyloid β (Aβ) fibrils are strongly involved in the pathogenesis of Alzheimer's diseases. The Aβ oligomers represent a non-fibrillar intermediate state of fibril formation.Here we explored the potential of Aβ peptide oligomers as a novel class of biological nanoparticles for macrophage targeting. This study shows that Aβ(1-40) peptide oligomers have a near-spheroid shape and due to a β-sheet assembly possess a compact, quasi-crystalline architecture. Additionally, FRET analysis revealed that Aβ(1-40) are structurally dynamic. Hence, they represent highly structured and biocompatible nanoparticles, which can be readily degraded by natural enzymes. Macrophages play a major role in immunity and tissue repair. However, recent evidence implicates them in progression of atherosclerosis, fibrosis, tumor initiation and development. In this context, specific labeling and imaging of macrophages are of special interest for diagnostic and therapeutic applications. We found that oligomeric Aβ(1-40) is preferentially t...
BMC Complementary Medicine and Therapies, 2021
Background The results of recent surveys indicate that more than 50% of the German population has... more Background The results of recent surveys indicate that more than 50% of the German population has experience with complementary and alternative medicine (CAM) or uses CAM regularly. This study investigated the CAM usage and CAM-related needs of hospitalized patients at university medical centres in the state of Baden-Württemberg, Germany. Methods A multi-centre, paper-based, pseudonymous survey was carried out by the members of the Academic Centre for Complementary and Integrative Medicine. Patients of all ages, regardless of sex, diagnosis and treatment, who were hospitalized in the Department of Cardiology, Gastroenterology, Oncology, Gynaecology or Surgery at the university medical centres in Freiburg, Heidelberg, Tübingen and Ulm were eligible for inclusion. Results Of the 1275 eligible patients, 67% (n = 854) consented to participate in the survey. Forty-eight percent of the study participants stated that they were currently using CAM. The most frequently used therapies were ex...
Bioorganic Chemistry, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Phytomedicine, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
International Journal of Pharmaceutics, 2019
Thrombosis and Haemostasis, 1996
SummaryThe objective of this study was to characterize the plasmin-induced stimulation of leukotr... more SummaryThe objective of this study was to characterize the plasmin-induced stimulation of leukotriene (LT) B4 biosynthesis in human peripheral monocytes (PM). Plasmin up to 175 × 10-3 CTA U/ml triggers a concentration-dependent release of 5-lipoxygenase-derived LTB4 while release of the cyclooxygenase products thromboxane (TX) B2 and prostaglandin (PG) E2 remained unaffected. The stimulatory effect appeared to be specific in as much as 1) it was found in PM, but not in polymorphonuclear neutrophils (PMN), 2) it requires the lysine binding sites of plasmin molecule since it was inhibited by the lysine analogues 6-aminohexanoic acid (6-AHA) and trans-4(aminometh-yl)cyclohexane-l-carboxylic acid (t-AMCA), 3) the intact catalytic center of plasmin is required since neither plasminogen nor catalytic center-blocked plasmin share the stimulatory effect of active plasmin, 4) other serine proteases such as a-chymotrypsin, human neutrophil elastase and cathepsin G did not stimulate release of...
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, Jan 11, 2017
Oleanolic acid derivatives exhibit potent anticancer activities against numerous types of cancer.... more Oleanolic acid derivatives exhibit potent anticancer activities against numerous types of cancer. However, the antitumor activity of oleanolic acid methylester (OAME), an oleanolic acid derivative, against prostate cancer has not been studied. Hence, the present work was conducted to study the anticancer activities of OAME. Viability assay showed that treatment of cancer cells with OAME induced a significant cell death in concentration- and time-dependent manner. Of note, OAME displayed a selective cytotoxicity against cancer cells compared to normal epithelial cells. Cells treated with OAME exhibited cell cycle arrest at both G1 and G2. Apoptotic induction potential of OAME was demonstrated using Annexin V assay, caspase activation, and DNA fragmentation methods Mechanistically, the results revealed that OAME strongly impacted the intrinsic apoptotic pathway in a concentration-dependent manner, as demonstrated by loss of mitochondrial membrane potential and release cytochrome c int...
Zeitschrift für Phytotherapie, 2006
Biomaterials, 2016
Macrophages are key regulators of innate and adaptive immune responses. Exposure to microenvironm... more Macrophages are key regulators of innate and adaptive immune responses. Exposure to microenvironmental stimuli determines their polarization into proinflammatory M1 and anti-inflammatory M2 macrophages. M1 exhibit high expression of proinflammatory TNF-α and IL-1β, and M2 promote tissue repair, but likewise support tumor growth and cause immune suppression by expressing IL-10. Thus, the M1/M2 balance critically determines tissue homeostasis. By using carboxyl- (PS-COOH) and amino-functionalized (PS-NH2) polystyrene nanoparticles, the effects of surface decoration on the polarization of human macrophages were investigated. The nanoparticles did not compromise macrophage viability nor did they affect the expression of the M1 markers CD86, NOS2, TNF-α, and IL-1β. By contrast, in M2, both nanoparticles impaired expression of scavenger receptor CD163 and CD200R, and the release of IL-10. PS-NH2 also inhibited phagocytosis of Escherichia coli by both, M1 and M2. PS-COOH did not impair phagocytosis by M2, but increased protein mass in M1 and M2, TGF-β1 release by M1, and ATP levels in M2. Thus, nanoparticles skew the M2 macrophage polarization without affecting M1 markers. Given the critical role of the M1 and M2 polarization for the immunological balance in patients with cancer or chronic inflammation, functionalized nanoparticles might serve as tools for reprogramming the M1/M2 polarization.
Cytokine
Besides its generally recognized significance in fibrinolysis, plasmin has gained increasing reco... more Besides its generally recognized significance in fibrinolysis, plasmin has gained increasing recognition as a potent stimulus for a variety of cells. However, little is known so far, how locally generated plasmin might affect the immune system. Here we show that plasmin elicits the expression of the CC-chemokine ligand 20 (CCL20, MIP-3 α ) in human dendritic cells. Stimulation of monocyte-derived dendritic cells with plasmin induced a concentration- and time-dependent expression of CCL20 mRNA and protein, whereas catalytically inactivated plasmin remained ineffective implying the necessity for proteolytic activation. The plasmin-induced CCL20 expression was preceded by activation of the transcription factor nuclear factor κ -light-chain enhancer of activated B cells (NF- κ B) as shown by phosphorylation of the NF- κ B inhibitor α (I κ B α ) and by binding of active p65 to NF- κ B consensus sequences. Pharmacological inhibitors revealed that the plasmin-induced CCL20 expression was dependent on the serine/threonine-specific protein kinase B (Akt)- and the extracellular-signal-regulated kinases (ERK)1/2-mediated activation of NF- κ B, whereas the p38 mitogen-activated protein kinase pathway did not play a significant role. Thus, plasmin activates dendritic cells to release the chemokine CCL20, which might facilitate accumulation of CCR6 + immune cells in areas of plasmin generation such as inflamed tissues and atherosclerotic lesions, where we could indeed demonstrate colocalization of plasmin, dendritic cells, and CCL20.
Molecular Immunology, 2011
Journal of Thrombosis and Haemostasis, 2006
We have previously demonstrated that plasmin acts as potent proinflammatory activator of human pe... more We have previously demonstrated that plasmin acts as potent proinflammatory activator of human peripheral monocytes leading to activation of protein kinase cascades and a number of transcription factors. An uncompromised proteolytic activity was essential for the plasmin-mediated monocyte activation pointing to the necessity of a proteolytic activation of the signaling receptor. Despite considerable efforts, little progress has been made so far in the identification of a signal-transducing plasmin receptor. Here we identify the annexin A2 heterotetramer, composed of annexin A2 and S100A10, as receptor for the plasmin-induced signaling in human monocytes. Monocytes express the annexin A2 heterotetramer on the cell surface as shown by i) flow cytometry, ii) fluorescence microscopy, and iii) co-immunoprecipitation of biotinylated cell surface proteins. Binding of plasmin to annexin A2 and S100A10 on monocytes was verified by biotin transfer from plasmin labeled with a trifunctional crosslinker. Antibodies directed against annexin A2 or S100A10 inhibited the chemotaxis elicited by plasmin, but not that induced by the standard chemoattractant fMLP. A control antibody directed against the thrombin receptor PAR-1 had no effect on the plasmin-mediated chemotaxis suggesting that PAR-1 is not involved. Further, downregulation of the annexin A2 or S100A10 expression in monocytes by antisense oligodeoxynucleotides impaired the chemotactic response to plasmin, but not that to fMLP. Antisense oligodeoxynucleotides similarly decreased the TNF-alpha release by plasmin-but not by LPS-stimulated monocytes. At the molecular level, stimulation with plasmin, but not with catalytically inactivated plasmin, induced cleavage of annexin A2 and dissociation of the annexin A2 heterotetramer complex. In contrast to annexin A2, S100A10 is not a substrate for plasmin. Substitution of lysine to alanine in position 27 abolished the cleavage of recombinant annexin A2 in vitro indicating a single cleavage site. These data shed new light on the plasmin-induced signaling; taken together they identify the annexin A2 heterotetramer in human monocytes as a signaling receptor activated by plasmin via proteolysis.
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Papers by Tatiana Syrovets