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Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic anhydrases IX and XII in normal and neoplastic colorectal mucosa

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World Journal of Gastroenterology 2005年第17期11卷 2616-2625页

作者： Antti J. Kivela Seppo Parkkila Juha Saarnio Tuomo J. Karttunen Jyrki Kivela Anna-Kaisa Parkkila Maria Bartosova vojtech mucha Michal Novak Abdul Waheed William S. Sly Hannu Rajaniemi Silvia Pastorekova Jaromir Pastorek Department of Anatomy and Cell Biology University of Oulu Finland Institute of Medical Technology University of Tampere and Tampere University Hospital Finland Department of Surgery University of Oulu Finland Department of Pathology University of Oulu Finland Institute of Dentistry University of Helsinki and Central Military Hospital Finland Department of Neurology Tampere University Hospital Finland Center of Molecular Medicine Institute of Virology Slovak Academy of SciencesBratislavaSlovak Republic Institute of Neuroimmunology Slovak Academy of Sciences BratislavaSlovak Republic Edward A. Doisy Department of Biochemistry and Molecular Biology Saint Louis University School of Medicine Missouri

AIM: To analyze possible relationships between CA ⅠⅩ/CA Ⅻ and pVHL expression in normal and neoplastic colorectal mucosa.METHODS: Immunohistochemical staining of 42 tissue specimens obtained from 17 cancer patients was performed to evaluate the distribution and semi-quantitatively assess the levels of CA ⅠⅩ, CA Ⅻ and pVHL. VHL mRNAs from 14 fresh-frozen tumors was amplified by RT-PCR and subjected to sequencing. CA9 and CA12 mRNA levels were analyzed by semi-quantitative RT-PCR in comparison with VEGFas an indicator of hypoxia that uncouples the pVHL control.RESULTS: Tumor tissues were associated with a borderline increase of CA ⅠⅩ staining signal and slight but significant decrease of CA Ⅻ immunoreactivity, whereas no association was found for pVHL. Sequence analysis of RT-PCR-amplified VHL mRNAs revealed no deletions/mutations, suggesting that they were VHL-competent. We did not observe any correlation between pVHL and CA ⅠⅩ/CA Ⅻ proteins as well as between VEGF and CA9 mRNAs, but the tumor-associated changes in mRNA levels of VEGF and CA12 showed a significant inverse relationship.CONCLUSION: Our results indicate that CA9 and CA12 are regulated by different intratumoral factors and that lack of apparent relationship between the levels of CA ⅠⅩ/CA Ⅻ and pVHL cannot be fully assigned to uncoupling of negative regulatory function of pVHL by tumor hypoxia signified by induced VEGF transcription. The interplay between the functional pVHL and CA ⅠⅩ/CA Ⅻ in colorectal tumors seems rather complex and is not evident merely at the expression levels.

关键词：结肠肿瘤直肠肿瘤肿瘤抑制物免疫组织化学基因表达

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A detailed mechanism of degradation behaviour of biodegradable as-ECAPed Zn-0.8Mg-0.2Sr with emphasis on localized corrosion attack

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Bioactive Materials 2023年第9期27卷 447-460页

作者： Jan Pinc Andrea Skolakova vojtech Hybasek Sarka Msallamova Petr Vertat Petr Ashcheulov Martin Vondracek Jan Duchon Ingrid McCarroll Matej Hývl Swarnendu Banerjee Jan Drahokoupil Jirí Kubasek Dalibor vojtech Jaroslav Capek Institute of Physics of the Czech Academy of Sciences Na Slovance 1999/2Prague 818221Czech Republic University of Chemistry and Technology Faculty of Chemical TechnologyDepartment of Metals and Corrosion EngineeringTechnicka 516628Praha 6-DejviceCzech Republic Max-Planck-Institut Für Eisenforschung Max-Planck-Straße 140237DüsseldorfGermany

In this study, advanced techniques such as atom probe tomography, atomic force microscopy, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy were used to determine the corrosion mechanism of the as-ECAPed Zn-0.8Mg-0.2Sr alloy. The influence of microstructural and surface features on the corrosion mechanism was investigated. Despite its significance, the surface composition before exposure is often neglected by the scientific community. The analyses revealed the formation of thin ZnO, MgO, and MgCO3 layers on the surface of the material before exposure. These layers participated in the formation of corrosion products, leading to the predominant occurrence of hydrozincite. In addition, the layers possessed different resistance to the environment, resulting in localized corrosion attacks. The segregation of Mg on the Zn grain boundaries with lower potential compared with the Zn-matrix was revealed by atom probe tomography and atomic force microscopy. The degradation process was initiated by the activity of micro-galvanic cells, specifically Zn - Mg2Zn11/SrZn13. This process led to the activity of the crevice corrosion mechanism and subsequent attack to a depth of 250 μm. The corrosion rate of the alloy determined by the weight loss method was 0.36 mm⋅a􀀀 1. Based on this detailed study, the degradation mechanism of the Zn-0.8Mg-0.2Sr alloy is proposed.

关键词： Biodegradable metals Zinc-based alloy Characterization Mechanism ECAP

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Enhanced macrophage polarization induced by COX-2 inhibitor-loaded Pd octahedral nanozymes for treatment of atherosclerosis

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Chinese Chemical Letters 2023年第1期34卷 262-269页

作者： Min Xu Chuchu Ren Yue Zhou Zbynek Heger Xiaoyang Liang vojtech Adam Nan Li School of Pharmaceutical Science and Technology Tianjin UniversityTainjin 300072China Department of Chemistry and Biochemistry Mendel University in BrnoBrno CZ-61300Czech Republic

Inhibition of foam cell formation is considered a promising treatment method for atherosclerosis,the leading cause of cardiovascular diseases worldwide.However,currently available therapeutic strategies have shown unsatisfactory clinical outcomes.Thus,herein,we design aloperine(ALO)-loaded and hyaluronic acid(HA)-modified palladium(Pd)octahedral nanozymes(Pd@HA/ALO)that can synergistically scavenge reactive oxygen species(ROS)and downregulate cyclooxygenase-2(COX-2)expression to induce macrophage polarization,thus inhibiting foam cell formation to attenuate atherosclerosis.Due to the targeted effect of HA on stabilin-2 and CD44,which are overexpressed in atherosclerotic plaques,Pd@HA/ALO can actively accumulate in atherosclerotic plaques.Subsequently,the antioxidative effects of Pd octahedral nanozymes are mediated by their intrinsic superoxide dismutase-and catalase-like activities capable of effective scavenging of ROS.In addition,anti-inflammatory effects are mediated by controlled,on-demand near-infrared-triggered ALO release leading to inhibition of COX-2 expression.Importantly,the combined therapy can promote the polarization of macrophages to the M2 subtype by upregulating Arg-1 and CD206 expression and downregulating expression of TNF-α,IL-1βand IL-6,thereby inhibiting atherosclerosis-related foam cell formation.In conclusion,the presented in vitro and in vivo data demonstrate that Pd@HA/ALO enhanced macrophage polarization to reduce plaque formation,identifying an attractive treatment strategy for cardiovascular disease.

关键词： Atherosclerosis COX-2 inhibitor Pd octahedral nanozyme Macrophage polarization Anti-inflammation Antioxidation

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3D numerical parametric study of the influence of open-pit mining sequence on existing tunnels

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International Journal of Mining Science and Technology 2017年第3期27卷 459-466页

作者： Beyabanaki Amir Reza Gall vojtech McMillen Jacobs Associates San Francisco CA 94105 USA Gall Zeidler Consultants Ashburn VA 20147 USA

The development of open-pit mines can adversely affect and even damage existing access tunnels. To ensure the safety and serviceability of them, it is essential to know potential adverse effects of the mining sequence on existing tunnels such as displacements of the lining and additional loads on the lining. In this paper, three-dimensional numerical parametric study is performed to explore this complex interaction.This study investigates the effects of different parameters that may affect the tunnel response. These parameters are: excavation sequence method, horizontal/vertical stress ratio, slope angle, and tunnel diameter. This study shows that the mining sequence affects the stability of the tunnels. The open-pit mining activities lead to both higher axial forces in rock bolts and normal forces and bending moments in the lining. The results of the analysis also demonstrate that the mining sequence causes tunnel heave and significant tensile forces in the lining. Based on the study in this paper a better understanding of the interaction between open-pit mining sequence and tunnels will be obtained.

关键词：既有隧道露天开采数值参数三维开挖顺序相互作用附加荷载可能影响

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Unveiling the nanotoxicological aspects of Se nanomaterials differing in size and morphology

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Bioactive Materials 2023年第2期20卷 489-500页

作者： Hana Stepankova Hana Michalkova Zbynek Splichal Lukas Richtera Pavel Svec Tomas Vaculovic Jan Pribyl Martin Kormunda Simona Rex vojtech Adam Zbynek Heger Department of Chemistry and Biochemistry Mendel University in BrnoZemedelska 1BrnoCZ-61300Czech Republic Central European Institute of Technology Brno University of TechnologyPurkynova 123BrnoCZ-61200Czech Republic Department of Chemistry Masaryk UniversityKamenice 5BrnoCZ-62500Czech Republic Institute of Laboratory Research on Geomaterials Faculty of Natural SciencesComenius University in BratislavaMlynska dolinaIlkovicova 684215 BratislavaSlovak Republic Central European Institute of Technology Masaryk UniversityKamenice 5BrnoCZ-62500Czech Republic Department of Physics Faculty of ScienceJ.E.Purkyne UniversityPasteurova 1Usti nad LabemCZ-40096Czech Republic

Although the general concept of nanotechnology relies on exploitation of size-dependent properties of nanoscaled materials,the relation between the size/morphology of nanoparticles with their biological activity remains not well understood.Therefore,we aimed at investigating the biological activity of Se nanoparticles,one of the most promising candidates of nanomaterials for biomedicine,possessing the same crystal structure,but differing in morphology(nanorods vs.spherical particles)and aspect ratios(AR,11.5 vs.22.3 vs.1.0)in human cells and BALB/c mice.Herein,we report that in case of nanorod-shaped Se nanomaterials,AR is a critical factor describing their cytotoxicity and biocompatibility.However,spherical nanoparticles(AR 1.0)do not fit this statement and exhibit markedly higher cytotoxicity than lower-AR Se nanorods.Beside of cytotoxicity,we also show that morphology and size substantially affect the uptake and intracellular fate of Se nanomaterials.In line with in vitro data,in vivo i.***.administration of Se nanomaterials revealed the highest toxicity for higher-AR nanorods followed by spherical nanoparticles and lower-AR nanorods.Moreover,we revealed that Se nanomaterials are able to alter intracellular redox homeostasis,and affect the acidic intracellular vesicles and cytoskeletal architecture in a size-and morphology-dependent manner.Although the tested nanoparticles were produced from the similar sources,their behavior differs markedly,since each type is promising for several various application scenarios,and the presented testing protocol could serve as a concept standardizing the biological relevance of the size and morphology of the various types of nanomaterials and nanoparticles.

关键词： Aspect ratio Biocompatibility Nanotoxicology Nanorods

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Remodeling of the liver fibrosis microenvironment based on nilotinib-loaded multicatalytic nanozymes with boosted antifibrogenic activity

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Acta Pharmaceutica Sinica B 2023年第12期13卷 5030-5047页

作者： Huaqing Jing Yingzi Ren Yue Zhou Min Xu Sona Krizkova Zbynek Heger Qiang Lu Siyu Wang Xiaoyang Liang vojtech Adam Nan Li Tianjin Key Laboratory of Drug Delivery&High-Eficiency School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin 300072China Department of Chemistry and Biochemistry Mendel University in BrnoBrno 61300Czech Republic

Liver fibrosis is a reversible pathological process caused by chronic liver damage and a major risk factor for hepatocellular carcinoma(HCC).Hepatic stellate cell(HSC)activation is considered the main target for liver fibrosis therapy.However,the efficiency of this strategy is limited due to the complex microenvironment of liver fibrosis,including excessive extracellular matrix(ECM)deposition and hypoxia-induced imbalanced ECM metabolism.Herein,nilotinib(NIL)-loaded hyaluronic acid(HA)-coated Ag@Pt nanotriangular nanozymes(APNH NTs)were developed to inhibit HSCs activation and remodel the microenvironment of liver fibrosis.APNH NTs efficiently eliminated intrahepatic reactive oxygen species(ROS)due to their inherent superoxide dismutase(SOD)and catalase(CAT)activities,thereby downregulating the expression of NADPH oxidase-4(NOX-4)and inhibiting HSCs activation.Simultaneously,the oxygen produced by the APNH NTs further alleviated the hypoxic microenvironment.Importantly,the released NIL promoted collagen depletion by suppressing the expression of tissue inhibitor of metalloproteinase-1(TIMP-1),thus synergistically remodeling the microenvironment of liver fibrosis.Notably,an in vivo study in CCl_(4)-induced mice revealed that APNH NTs exhibited significant antifibrogenic effects without obvious long-term toxicity.Taken together,the data from this work suggest that treatment with the synthesized APNH NTs provides an enlightening strategy for remodeling the microenvironment of liver fibrosis with boosted antifibrogenic activity.

关键词： Liver fibrosis Microenvironment remodeling HSCs ECM Collagen Hypoxia Nilotinib Nanozyme

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Proposed EU legislation to force changes in sewage sludge disposal:A case study

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Frontiers of Chemical Science and Engineering 2018年第4期12卷 660-669页

作者： vojtech Turek Bohuslav Kilkovsky Zdenek Jegla Petr Stehlik Institute of Process Engineering Faculty of Mechanical EngineeringBmo University of Tectmology61669 BmoCzech Republic

The consequences of changes planned in the European Union legislation relevant to the disposal of sewage sludges are discussed. A specific municipal waste water treatment plant is analyzed in terms of drying and subsequent combustion or pyrolysis of the produced stabilized sludge, and the respective net energy balances are carried out. A simplified economic analysis of the two disposal options is presented, which suggest that combustion of the sludge would be economically infeasible while pyrolysis of the sludge in a modular, self-sufficient container unit can bring a small financial benefit due to the selling of the produced phosphorus-rich biochar.

关键词： sewage sludge drying combustion pyrolysis

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A holistic approach for the investigation of lining response to mechanized tunneling induced construction loadings

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Underground Space 2018年第1期3卷 45-60页

作者： vojtech Ernst Gall Ahmed Marwan Mario Smarslik Markus Obel Peter Mark Gunther Meschke Inustitute for Structural Mechanics Ruhr University BochumBochunGermany Institute of Concrete Structures Ruhr University BochumBochumGermany

Design methods for segmental tunnel linings used in mechanized tunnel constructions typically employ numerical bedded beam mod-els and/or classical analytical solutions for the determination of structural forces(i.***.moments and shear and axial forces)and simple load spreading assumptions for the design of the reinforcement in joint areas.However effcient such methods may be,many physical details are often overlooked and/or oversimpliﬁed in the process of reducing the actual structure to a structural beam model,e.***.ana-lytically derived loadings are employed,the grouting and ground reactions are reduced to a spring bedding,and the conﬁnement due to grouting at the longitudinal joint is largely not considered in reinforcement design.Such a design process is not able to account for,or predict,the susceptibility of tunnel linings to often observed damages that,although they may not be structurally relevant,lead to ser-viceability or durability issues,such as crack development or chipping at the segment corners.Numerical methods,such as the Finite Element Method,provide an opportunity to model the segmental tunnel lining and its response to the entire TBM construction process and to explicitly model the crack development within individual segments using modern methods to model the discontinuities in struc-tures.In this contribution,a holistic modeling procedure for the representation of the tunnel lining within the tunneling process is pro-posed and compared to traditional lining models.A 3D process oriented Finite Element model is used to calculate the predicted forces on the tunnel lining and the obtained results are compared with those generated by traditional methods.Subsequently,the predicted defor-mations are then transferred to a detailed segment model in which the nonlinear response of the segment at the longitudinal joint is mod-eled using an interface element based approach to simulate concrete cracking.

关键词： Mechanized tunneling Segmental tunnel linings Finite element method

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Microstructure and mechanical properties of the micrograined hypoeutectic Zn–Mg alloy

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International Journal of Minerals,Metallurgy and Materials 2016年第10期23卷 1167-1176页

作者： J. Kubasek D.vojtech I.Pospisilova A.Michalcova J.Maixner Department of Metals and Corrosion Engineering University of Chemistry and Technology Prague Technicka 5 166 28 Prague 6 Czech Republic Laboratory of RTG Difractometry University of Chemistry and Technology Prague Technicka 5 166 28 Prague 6 Czech Republic

A biodegradable Zn alloy, Zn-1.6Mg, with the potential medical applications as a promising coating material for steel components was studied in this work. The alloy was prepared by three different procedures： gravity casting, hot extrusion, and a combination of rapid solidification and hot extrusion. The samples prepared were characterized by light microscopy, scanning electron microscopy, transmission electron microscopy, and X-ray diffraction analysis. Vickers hardness, tensile, and compressive tests were performed to determine the samples＇ mechanical properties. Structural examination reveals that the average grain sizes of samples prepared by gravity casting, hot extrusion, and rapid solidification followed by hot extrusion are 35.0, 9.7, and 2.1 μm, respectively. The micrograined sample with the finest grain size exhibits the highest hardness（Hv = 122 MPa）, compressive yield strength（382 MPa）, tensile yield strength（332 MPa）, ultimate tensile strength（370 MPa）, and elongation（9%）. This sample also demonstrates the lowest work hardening in tension and temporary softening in compression among the prepared samples. The mechanical behavior of the samples is discussed in relation to the structural characteristics, Hall-Petch relationship, and deformation mechanisms in fine-grained hexagonal-close-packed metals.

关键词： zinc magnesium alloys extrusion rapid solidification microstructure mechanical properties

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Parallel fluorescence and phosphorescence monitoring of singlet oxygen photosensitization in rats

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Journal of Innovative Optical Health Sciences 2015年第6期8卷 53-66页

作者： Roman Dedic Adam Stibal vojtech Vyklicky Miloslav Franek Antonin Svoboda Jan Hala Faculty of Mathematics and Physics Department of Chemical Physics and Optics Charles University in Prague Ke Karlovu 3 12116 Praha 2Czech Republic Third Faculty of Medicine Department of Normal Pathological and Clinical Physiology Charles University in Prague Ke Karlovu 412000 Praha 2Czech Republic

The time-and spectral-resolved set-up for measurements of weak infrared luminescence of photosensitizers(PSs)and singlet oxygen using optical lightguides was used on skin of laboratory animals in vivo.Wistar rats with abdominal incisions treated by methylis aminolevulinitis(MAL)were used as a model.A control group of animals with abdominal incisions was also tested.Spectrally resolved fluorescence of the PS was acquired during the treatment from the same spot.The intensity and spectral profile of the fiuorescence signal from the skin can be used to guide the detection setup to the investigated spots in the lesion.The rate of bleaching of Protoporphyrin IX band and appearance of a band of its photoproducts during the treatment can be characterized by the exposition ED,under which the latter becomes dominant feature infiuorescence spectrum.ED value differs statistically significantly between the normal skin and the lesion treated by MAL.No direct proportionality was found between the fluorescence signal and singlet oxygen production.Nevertheless,the strong fluorescence signal is necessary but not a su±cient condition for higher singlet oxygen production in vivo.ED value correlates rather well with production of singlet oxygen,but differently in lesion and normal skin.Lifetimes of singlet oxygen differ between spots outside and in the lesion.PS triplet state lifetimes exhibit weak di®erence between spots treated and untreated by MAL.

关键词： PDT dosimetry singlet oxygen Protoporphyrin IX time-resolved luminescence photodiagnosis

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