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Article: Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors.

Selinger, Martin / Věchtová, Pavlína / Tykalová, Hana / Ošlejšková, Petra / Rumlová, Michaela / Štěrba, Ján / Grubhoffer, Libor

Computational and structural biotechnology journal

2022 Volume 20, Page(s) 2759–2777

Abstract: Tick-borne encephalitis virus (TBEV), the most medically relevant tick-transmitted flavivirus in Eurasia, targets the host central nervous system and frequently causes severe encephalitis. The severity of TBEV-induced neuropathogenesis is highly cell- ... ...

Abstract	Tick-borne encephalitis virus (TBEV), the most medically relevant tick-transmitted flavivirus in Eurasia, targets the host central nervous system and frequently causes severe encephalitis. The severity of TBEV-induced neuropathogenesis is highly cell-type specific and the exact mechanism responsible for such differences has not been fully described yet. Thus, we performed a comprehensive analysis of alterations in host poly-(A)/miRNA/lncRNA expression upon TBEV infection
Language	English
Publishing date	2022-05-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2022.05.052
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Article ; Online: Exploring the effects of topoisomerase II inhibitor XK469 on anthracycline cardiotoxicity and DNA damage.

Keresteš, Veronika / Kubeš, Jan / Applová, Lenka / Kollárová, Petra / Lenčová-Popelová, Olga / Melnikova, Iuliia / Karabanovich, Galina / Khazeem, Mushtaq M / Bavlovič-Piskáčková, Hana / Štěrbová-Kovaříková, Petra / Austin, Caroline A / Roh, Jaroslav / Štěrba, Martin / Šimůnek, Tomáš / Jirkovská, Anna

Toxicological sciences : an official journal of the Society of Toxicology

2024 Volume 198, Issue 2, Page(s) 288–302

Abstract: Anthracyclines, such as doxorubicin (adriamycin), daunorubicin, or epirubicin, rank among the most effective agents in classical anticancer chemotherapy. However, cardiotoxicity remains the main limitation of their clinical use. Topoisomerase IIβ has ... ...

Abstract	Anthracyclines, such as doxorubicin (adriamycin), daunorubicin, or epirubicin, rank among the most effective agents in classical anticancer chemotherapy. However, cardiotoxicity remains the main limitation of their clinical use. Topoisomerase IIβ has recently been identified as a plausible target of anthracyclines in cardiomyocytes. We examined the putative topoisomerase IIβ selective agent XK469 as a potential cardioprotective and designed several new analogs. In our experiments, XK469 inhibited both topoisomerase isoforms (α and β) and did not induce topoisomerase II covalent complexes in isolated cardiomyocytes and HL-60, but induced proteasomal degradation of topoisomerase II in these cell types. The cardioprotective potential of XK469 was studied on rat neonatal cardiomyocytes, where dexrazoxane (ICRF-187), the only clinically approved cardioprotective, was effective. Initially, XK469 prevented daunorubicin-induced toxicity and p53 phosphorylation in cardiomyocytes. However, it only partially prevented the phosphorylation of H2AX and did not affect DNA damage measured by Comet Assay. It also did not compromise the daunorubicin antiproliferative effect in HL-60 leukemic cells. When administered to rabbits to evaluate its cardioprotective potential in vivo, XK469 failed to prevent the daunorubicin-induced cardiac toxicity in either acute or chronic settings. In the following in vitro analysis, we found that prolonged and continuous exposure of rat neonatal cardiomyocytes to XK469 led to significant toxicity. In conclusion, this study provides important evidence on the effects of XK469 and its combination with daunorubicin in clinically relevant doses in cardiomyocytes. Despite its promising characteristics, long-term treatments and in vivo experiments have not confirmed its cardioprotective potential.
MeSH term(s)	Rats ; Animals ; Rabbits ; Topoisomerase II Inhibitors/toxicity ; Topoisomerase II Inhibitors/therapeutic use ; Anthracyclines/toxicity ; Anthracyclines/therapeutic use ; Cardiotoxicity ; Daunorubicin/toxicity ; Daunorubicin/therapeutic use ; Doxorubicin/toxicity ; Antibiotics, Antineoplastic/toxicity ; DNA Topoisomerases, Type II/metabolism ; DNA Topoisomerases, Type II/therapeutic use ; DNA Damage ; Quinoxalines
Chemical Substances	Topoisomerase II Inhibitors ; Anthracyclines ; XK 469 ; Daunorubicin (ZS7284E0ZP) ; Doxorubicin (80168379AG) ; Antibiotics, Antineoplastic ; DNA Topoisomerases, Type II (EC 5.99.1.3) ; Quinoxalines
Language	English
Publishing date	2024-01-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1420885-4
ISSN	1096-0929 ; 1096-6080
ISSN (online)	1096-0929
ISSN	1096-6080
DOI	10.1093/toxsci/kfae008
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Article ; Online: Targeted treatment of severe vascular malformations harboring PIK3CA and TEK mutations with alpelisib is highly effective with limited toxicity.

Sterba, Martin / Pokorna, Petra / Faberova, Renata / Pinkova, Blanka / Skotakova, Jarmila / Seehofnerova, Anna / Blatny, Jan / Janigova, Lucia / Koskova, Olga / Palova, Hana / Mahdal, Michal / Pazourek, Lukas / Jabandziev, Petr / Slaby, Ondrej / Mudry, Peter / Sterba, Jaroslav

Scientific reports

2023 Volume 13, Issue 1, Page(s) 10499

Abstract: This was a prospective cohort study of eighteen patients with large and debilitating vascular malformations with one or more major systemic complications. In all patients, we discovered activating alterations in either TEK or PIK3CA. Based on these ... ...

Abstract	This was a prospective cohort study of eighteen patients with large and debilitating vascular malformations with one or more major systemic complications. In all patients, we discovered activating alterations in either TEK or PIK3CA. Based on these findings, targeted treatment using the PI3K inhibitor alpelisib was started with regular check-ups, therapy duration varied from 6 to 31 months. In all patients, marked improvement in quality of life was observed. We observed radiological improvement in fourteen patients (two of them being on combination with either propranolol or sirolimus), stable disease in 2 patients. For 2 patients, an MRI scan was not available as they were shortly on treatment, however, a clinically visible response in size reduction or structure regression, together with pain relief was observed. In patients with elevated D-dimer levels before alpelisib administration, a major improvement was noted, suggesting its biomarker role. We observed overall very good tolerance of the treatment, documenting a single patient with grade 3 hyperglycemia. Patients with size reduction were offered local therapies wherever possible. Our report presents a promising approach for the treatment of VMs harboring different targetable TEK and PIK3CA gene mutations with a low toxicity profile and high efficacy.
MeSH term(s)	Humans ; Phosphatidylinositol 3-Kinases/genetics ; Prospective Studies ; Quality of Life ; Class I Phosphatidylinositol 3-Kinases/genetics ; Mutation
Chemical Substances	Alpelisib (08W5N2C97Q) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Class I Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; PIK3CA protein, human (EC 2.7.1.137)
Language	English
Publishing date	2023-06-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-37468-4
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Article: Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors

Selinger, Martin / Věchtová, Pavlína / Tykalová, Hana / Ošlejšková, Petra / Rumlová, Michaela / Štěrba, Ján / Grubhoffer, Libor

Computational and Structural Biotechnology Journal. 2022 May 27,

2022

Abstract	Tick-borne encephalitis virus (TBEV), the most medically relevant tick-transmitted flavivirus in Eurasia, targets the host central nervous system and frequently causes severe encephalitis. The severity of TBEV-induced neuropathogenesis is highly cell-type specific and the exact mechanism responsible for such differences has not been fully described yet. Thus, we performed a comprehensive analysis of alterations in host poly-(A)/miRNA/lncRNA expression upon TBEV infection in vitro in human primary neurons (high cytopathic effect) and astrocytes (low cytopathic effect). Infection with severe but not mild TBEV strain resulted in a high neuronal death rate. In comparison, infection with either of TBEV strains in human astrocytes did not. Differential expression and splicing analyses with an in silico prediction of miRNA/mRNA/lncRNA/vd-sRNA networks found significant changes in inflammatory and immune response pathways, nervous system development and regulation of mitosis in TBEV Hypr-infected neurons. Candidate mechanisms responsible for the aforementioned phenomena include specific regulation of host mRNA levels via differentially expressed miRNAs/lncRNAs or vd-sRNAs mimicking endogenous miRNAs and virus-driven modulation of host pre-mRNA splicing. We suggest that these factors are responsible for the observed differences in the virulence manifestation of both TBEV strains in different cell lines. This work brings the first complex overview of alterations in the transcriptome of human astrocytes and neurons during the infection by two TBEV strains of different virulence. The resulting data could serve as a starting point for further studies dealing with the mechanism of TBEV-host interactions and the related processes of TBEV pathogenesis.
Keywords	Tick-borne encephalitis virus ; astrocytes ; biotechnology ; central nervous system ; computer simulation ; cytopathogenicity ; encephalitis ; gene expression regulation ; humans ; immune response ; microRNA ; mitosis ; mortality ; neurodevelopment ; neurons ; pathogenesis ; prediction ; transcriptome ; virulence ; Eurasia
Language	English
Dates of publication	2022-0527
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2022.05.052
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Article: Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit model.

Adamcova, Michaela / Parova, Helena / Lencova-Popelova, Olga / Kollarova-Brazdova, Petra / Baranova, Ivana / Slavickova, Marcela / Stverakova, Tereza / Mikyskova, Petra Sauer / Mazurova, Yvona / Sterba, Martin

Frontiers in pharmacology

2024 Volume 14, Page(s) 1298172

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2024-01-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1298172
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Article ; Online: Changes in Cognition and Hemodynamics 1 Year after Carotid Endarterectomy for Asymptomatic Stenosis.

Košťál, Petr / Mrhálek, Tomáš / Kajanová, Alena / Bombic, Martin / Kubále, Jiří / Šterba, Luděk / Ostrý, Svatopluk / Fiedler, Jiří

Journal of neurological surgery. Part A, Central European neurosurgery

2021 Volume 82, Issue 6, Page(s) 505–511

Abstract: Objectives: The impact of a change in hemodynamics on cognitive skills in patients with asymptomatic carotid stenosis (ACS) after carotid endarterectomy (CEA) remains unclear. The aim of this study was to evaluate the results of CEA for ACS at 1 year ... ...

Abstract	Objectives: The impact of a change in hemodynamics on cognitive skills in patients with asymptomatic carotid stenosis (ACS) after carotid endarterectomy (CEA) remains unclear. The aim of this study was to evaluate the results of CEA for ACS at 1 year by assessing the changes in anterior, middle, and posterior cerebral artery blood flow in tandem with changes in cognitive efficiency. Methods: Flow volume in cerebral arteries using quantitative magnetic resonance angiography was measured in a group of 14 males and 5 females before and at 1 year after CEA for ACS. Cognitive efficiency was assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The values of flow volume were processed using simple ratio (SR) and were used for covariance analyses with changes in cognitive skills after CEA. Results: A significant improvement in cognitive efficiency indexes of immediate memory and visuospatial perception at 1 year after CEA for ACS was observed. Simultaneously, a significant deterioration of speech index was noted. During the analysis of association between flow and cognition, the highest correlation could be seen between the middle cerebral artery (MCA) flow and the visuospatial perception. A change in posterior cerebral artery (PCA) flow was associated with an increase in immediate memory index and anterior cerebral artery (ACA) flow change with the speech index. Conclusion: Convergence of data supporting the association between revascularization and cognitive improvement were added in a small, single-center cohort of ACS patients undergoing CEA. No significant differences in cognition were seen between preoperative findings and at 1 year after CEA. Visuospatial perception improvement was linked to flow change in MCA, immediate memory improvement to flow change in PCA, and speech index change to flow change in ACA. Methodical limitations of this small study preclude formulating larger generalizations. Hemodynamic factors in CEA should be assessed in a larger-scale study.
MeSH term(s)	Carotid Stenosis/diagnostic imaging ; Carotid Stenosis/surgery ; Cerebrovascular Circulation ; Cognition ; Constriction, Pathologic ; Endarterectomy, Carotid ; Female ; Hemodynamics ; Humans ; Male
Language	English
Publishing date	2021-02-14
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2651663-9
ISSN	2193-6323 ; 2193-6315
ISSN (online)	2193-6323
ISSN	2193-6315
DOI	10.1055/s-0040-1720985
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Article ; Online: Unicuspid Aortic Valve in Patients Undergoing the Ross Procedure.

Gofus, Jan / Fila, Petr / Vobornik, Martin / Ondrasek, Jiri / Nemec, Petr / Sterba, Jan / Cermakova, Eva / Tuna, Martin / Vojacek, Jan

The Annals of thoracic surgery

2022 Volume 115, Issue 3, Page(s) 626–631

Abstract: Background: The prevalence and outcomes of the unicuspid aortic valve (UAV) in patients undergoing the Ross procedure have been strongly underreported in the current literature. We sought to evaluate this in comparison with bicuspid (BAV) and tricuspid ... ...

Abstract	Background: The prevalence and outcomes of the unicuspid aortic valve (UAV) in patients undergoing the Ross procedure have been strongly underreported in the current literature. We sought to evaluate this in comparison with bicuspid (BAV) and tricuspid valve (TAV) in our Ross cohort. Methods: This was a retrospective observational study of patients undergoing the Ross procedure at 2 dedicated centers between 2009 and 2020. Primary end points were the risks of midterm autograft reoperation and the onset of at least moderate aortic regurgitation during follow-up. The secondary end point was to compare the perioperative outcomes between the groups. Results: Included in the analysis were 286 patients, of those 39% with UAV, 52% with BAV, and 9% with TAV. UAV patients were operated on at the youngest age (P < .001) and more often for a combined hemodynamic aortic valve pathology (P = .02). They had the largest aortic root dimensions: annulus (P = .01), Valsalva sinuses (P = .11), sinotubular junction (P = .001), and ascending aorta (P < .0001). The risks of reoperation (P = .86) and the onset of aortic regurgitation (P = .75) were comparable among the groups over the follow-up of 4.1 years. There was no difference in perioperative outcomes. Conclusions: UAV is a separate unit characterized by a distinct hemodynamic pathology and generated aortopathy. It is not associated with a higher risk of reoperation or new onset of aortic regurgitation after the Ross procedure in the midterm postoperatively. At the current state, UAV remains acceptable for the Ross procedure.
MeSH term(s)	Humans ; Aortic Valve Insufficiency/surgery ; Heart Valve Diseases/surgery ; Aortic Valve/surgery ; Aorta/surgery ; Retrospective Studies
Language	English
Publishing date	2022-04-14
Publishing country	Netherlands
Document type	Observational Study ; Journal Article
ZDB-ID	211007-6
ISSN	1552-6259 ; 0003-4975
ISSN (online)	1552-6259
ISSN	0003-4975
DOI	10.1016/j.athoracsur.2022.03.061
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Article: Development of a Rat Model of Intra-Amniotic Inflammation

Stranik, Jaroslav / Kacerovsky, Marian / Sterba, Martin / Andrys, Ctirad / Abad, Cilia / Staud, Frantisek / Micuda, Stanislav / Soucek, Ondrej / Jacobsson, Bo / Musilova, Ivana

Frontiers in pharmacology

2022 Volume 13, Page(s) 871193

Abstract: Objectives: ...

Abstract	Objectives:
Language	English
Publishing date	2022-04-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.871193
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Article ; Online: Tree species-rich open oak woodlands within scattered urban landscapes promote biodiversity

Andreas, Michal / Prausová, Romana / Brestovanská, Tereza / Hostinská, Lucie / Kalábová, Markéta / Bogusch, Petr / Halda, Josef P. / Rada, Patrik / Štěrba, Ladislav / Čížek, Martin / Horák, Jakub

Urban Forestry & Urban Greening. 2023 May, v. 83 p.127914-

2023

Abstract: It is becoming increasingly evident that cities are important places for biodiversity. Biodiverse urban forests are vital green areas within cities and have favorable impacts on the citizens, including their health. We focused on the effect of the urban ... ...

Abstract	It is becoming increasingly evident that cities are important places for biodiversity. Biodiverse urban forests are vital green areas within cities and have favorable impacts on the citizens, including their health. We focused on the effect of the urban forest environment on biodiversity in Prague, the capital of the Czech Republic. We used a multi-taxon approach with five taxa of different ecological demands: butterflies, bees and wasps, vascular plants, mosses, and lichens. We modeled their responses to the various urban forest attributes at four hierarchical levels – plot, permeability, forest, and landscape. Our results revealed that temporally continuous forests dominated by native oaks with open canopies, a high number of admixed and interspersed tree species and shrubs, together with scattered trees in the surrounding landscape, were optimal biodiverse forest environments. The most influential parameter that positively influenced bees and wasps, plants, and lichens at the plot level was canopy openness. We found that the permeability was suitable mainly on 20 m surroundings and increasing coverage of native oaks and tree species richness were the most important parameters. Continuity was the only found parameter that influenced mosses at the forest level. Scattered tree vegetation was the most important landscape parameter and positively drove the species richness of bees and wasps. Forest management methods can relatively easily solve the improvement of the scattered light gap structure within urban forests. Applying traditional forest management (pasture management, controlled burning and/or coppicing) is also an option but requires sensitive communication with the public. The canopy cover has been used as an indicator of urban forest health conditions, now indicating that artificial disturbances could be important issues for urban forest management and planning in the future. Therefore, active forest management is an essential method for biodiversity maintenance. We conclude that urban forests have a high potential for increasing native biodiversity. The response of the studied groups in urban forests was complementary. The resulting biodiverse stages of urban forests are akin to the established idea of the open temperate deciduous woodlands.
Keywords	canopy ; coppicing ; forest health ; forest management ; landscapes ; pasture management ; permeability ; species richness ; trees ; urban forestry ; urban forests ; Czech Republic ; City forests ; Green infrastructure ; Multi-taxon approach ; Native tree vegetation ; Sparse canopy
Language	English
Dates of publication	2023-05
Publishing place	Elsevier GmbH
Document type	Article ; Online
ISSN	1618-8667
DOI	10.1016/j.ufug.2023.127914
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Forest Management Plan in Domogt Sharyn Gol, Mongolia is Elaborated on Ecological and Sustainable Principles

Smola Martin / Kusbach Antonín / Štěrba Tadeáš / Adolt Radim / Nečas Michal

Journal of Landscape Ecology, Vol 12, Iss 2, Pp 92-

2019 Volume 115

Abstract: A forest management plan based on ecological principles and forest management sustainability was elaborated for the Domogt Sharyn Gol Company, Mongolia. We presented possibility of use of principles and methods traditionally utilized in forest management ...

Abstract	A forest management plan based on ecological principles and forest management sustainability was elaborated for the Domogt Sharyn Gol Company, Mongolia. We presented possibility of use of principles and methods traditionally utilized in forest management planning in the Czech Republic. A used methodology was adjusted for the forestry legislature in Mongolia.
Keywords	forest management plan ; mongolia ; forest classification ; sustainable management ; operational inventory ; Ecology ; QH540-549.5
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	Sciendo
Document type	Article ; Online
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