| 1. |
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| 2. |
- Chyzhma, Ruslana, et al.
(författare)
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Potential role of hydroxyapatite nanocrystalline for early diagnostics of ovarian cancer
- 2021
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Ingår i: Diagnostics. - : MDPI. - 2075-4418. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Calcification is one of the clinical and morphological manifestations of ovarian tumors and it begins at the initial stages of carcinogenesis. Thus, this process can be used for the early diagnostics of some malignant ovarian tumors. We compared the results of ultrasound and histology and found that calcifications of a size less than 200 μm are not detected by ultrasound. These calcified structures are round fragile particles of different sizes. In the EDX (Energy-dispersive X-ray spectroscopy) spectra, the main lines were from Ca and P, and the ratio of these elements corresponds to hydroxyapatite. Thus, we established that hydroxyapatite is the main mineral component of ovarian psammoma bodies and could be used for early diagnostics of ovarian malignant neoplasia.
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| 3. |
- Chyzhma, Ruslana, et al.
(författare)
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The study of the nanocrystalline structure of psammoma bodies of serous ovarian carcinoma
- 2022
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Ingår i: 2022 IEEE 12th international conference nanomaterials. - : IEEE. - 9781665489829 - 9781665489836 ; , s. NRA03-1-NRA03-4
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Konferensbidrag (refereegranskat)abstract
- Psammoma Bodies (PBs) are concentric calcined structures. The formation of PBs begins during the initial stages of carcinogenesis, which is an important feature for the diagnostics of serous ovarian carcinoma. The aim of our work was to study the nanocrystalline structure of PBs of serous ovarian carcinoma for practical use in diagnostics. According to the size, these structures were divided into 3 groups: large - more than 200μm, medium - 71-199μm, and small - up to 70μm. The structure of PBs was represented by lamellae and interlamellar layers. The mean thickness of the lamellae was 0.65 ± 0.02μm, and the thickness of the inter-lamellar layers was 3.7 ± 0.17μm. A strong correlation between the thickness of the interlamellar layer and the size of PBs was found for all groups of calcifications. It has been found that PBs consisted of hydroxyapatite and contained proteins. Therefore, based on the nanocrystalline structure and morphometric characteristics of PBs, this pattern can be used in practice for the early diagnosis of serous ovarian cancer.
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| 4. |
- Grüning, Björn, et al.
(författare)
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Bioconda: A sustainable and comprehensive software distribution for the life sciences
- 2017
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We present Bioconda (https://bioconda.github.io), a distribution of bioinformatics software for the lightweight, multi-platform and language-agnostic package manager Conda. Currently, Bioconda offers a collection of over 3000 software packages, which is continuously maintained, updated, and extended by a growing global community of more than 200 contributors. Bioconda improves analysis reproducibility by allowing users to define isolated environments with defined software versions, all of which are easily installed and managed without administrative privileges.
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| 5. |
- Horvath, Istvan, et al.
(författare)
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Co-aggregation of pro-inflammatory S100A9 with alpha-synuclein in Parkinson's disease : ex vivo and in vitro studies
- 2018
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic neuroinflammation is a hallmark of Parkinson's disease (PD) pathophysiology, associated with increased levels of pro-inflammatory factors in PD brain tissues. The pro-inflammatory mediator and highly amyloidogenic protein S100A9 is involved in the amyloid-neuroinflammatory cascade in Alzheimer's disease. This is the first report on the co-aggregation of alpha-synuclein (alpha-syn) and S100A9 both in vitro and ex vivo in PD brain. Methods: Single and sequential immunohistochemistry, immunofluorescence, scanning electron and atomic force (AFM) microscopies were used to analyze the ex vivo PD brain tissues for S100A9 and alpha-syn location and aggregation. In vitro studies revealing S100A9 and alpha-syn interaction and co-aggregation were conducted by NMR, circular dichroism, Thioflavin-T fluorescence, AFM, and surface plasmon resonance methods. Results: Co-localized and co-aggregated S100A9 and alpha-syn were found in 20% Lewy bodies and 77% neuronal cells in the substantia nigra; both proteins were also observed in Lewy bodies in PD frontal lobe (Braak stages 4-6). Lewy bodies were characterized by ca. 10-23 mu m outer diameter, with S100A9 and alpha-syn being co-localized in the same lamellar structures. S100A9 was also detected in neurons and blood vessels of the aged patients without PD, but in much lesser extent. In vitro S100A9 and alpha-syn were shown to interact with each other via the alpha-syn C-terminus with an apparent dissociation constant of ca. 5 mu M. Their co-aggregation occurred significantly faster and led to formation of larger amyloid aggregates than the self-assembly of individual proteins. S100A9 amyloid oligomers were more toxic than those of alpha-syn, while co-aggregation of both proteins mitigated the cytotoxicity of S100A9 oligomers. Conclusions: We suggest that sustained neuroinflammation promoting the spread of amyloidogenic S100A9 in the brain tissues may trigger the amyloid cascade involving alpha-syn and S100A9 and leading to PD, similar to the effect of S100A9 and A beta co-aggregation in Alzheimer's disease. The finding of S100A9 involvement in PD may open a new avenue for therapeutic interventions targeting S100A9 and preventing its amyloid self-assembly in affected brain tissues.
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| 6. |
- Horvath, Istvan, et al.
(författare)
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Pro-inflammatory S100A9 Protein as a Robust Biomarker Differentiating Early Stages of Cognitive Impairment in Alzheimer's Disease
- 2016
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 7:1, s. 34-39
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Tidskriftsartikel (refereegranskat)abstract
- Pro-inflammatory protein S100A9 was established as a biomarker of dementia progression and compared with others such as Aβ1-42 and tau-proteins. CSF samples from 104 stringently diagnosed individuals divided into five subgroups were analyzed, including nondemented controls, stable mild cognitive impairment (SMCI), mild cognitive impairment due to Alzheimer's disease (MCI-AD), Alzheimer's disease (AD), and vascular dementia (VaD) patients. ELISA, dot-blotting, and electrochemical impedance spectroscopy were used as research methods. The S100A9 and Aβ1-42 levels correlated with each other: their CSF content decreased already at the SMCI stage and declined further under MCI-AD, AD, and VaD conditions. Immunohistochemical analysis also revealed involvement of both Aβ1-42 and S100A9 in the amyloid-neuroinflammatory cascade already during SMCI. Tau proteins were not yet altered in SMCI; however their contents increased during MCI-AD and AD, diagnosing later dementia stages. Thus, four biomarkers together, reflecting different underlying pathological causes, can accurately differentiate dementia progression and also distinguish AD from VaD.
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| 7. |
- Iashchishyn, Igor A., et al.
(författare)
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Intranasally Administered S100A9 Amyloids Induced Cellular Stress, Amyloid Seeding, and Behavioral Impairment in Aged Mice
- 2018
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 9:6, s. 1338-1348
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid formation and neuroinflammation are major features of Alzheimer's disease pathology. Proinflammatory mediator S100A9 was shown to act as a link between the amyloid and neuroinflammatory cascades in Alzheimer's disease, leading together with Aβ to plaque formation, neuronal loss and memory impairment. In order to examine if S100A9 alone in its native and amyloid states can induce neuronal stress and memory impairment, we have administered S100A9 species intranasally to aged mice. Single and sequential immunohistochemistry and passive avoidance behavioral test were conducted to evaluate the consequences. Administered S100A9 species induced widespread cellular stress responses in cerebral structures, including frontal lobe, hippocampus and cerebellum. These were manifested by increased levels of S100A9, Box, and to a lesser extent activated caspase-3 immunopositive cells. Upon administration of S100A9 fibrils, the amyloid oligomerization was observed in the brain tissues, which can further exacerbate cellular stress. The cellular stress responses correlated with significantly increased training and decreased retention latencies measured in the passive avoidance test for the SI00A9 treated animal groups. Remarkably, the effect size in the behavioral tests was moderate already in the group treated with native S100A9, while the effect sizes were large in the groups administered S100A9 amyloid oligomers or fibrils. The findings demonstrate the brain susceptibility to neurotoxic damage of S100A9 species leading to behavioral and memory impairments. Intranasal administration of S100A9 species proved to be an effective method to study amyloid induced brain dysfunctions, and 5100A9 itself may be postulated as a target to allay early stage neurodegenerative and neuroinflammatory processes.
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| 8. |
- Javaheri, Anahita, et al.
(författare)
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Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs
- 2017
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Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori specifically colonizes the human gastric epithelium and is the major causative agent for ulcer disease and gastric cancer development. Here, we identify members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family as receptors of H. pylori and show that HopQ is the surface-exposed adhesin that specifically binds human CEACAM1, CEACAM3, CEACAM5 and CEACAM6. HopQ-CEACAM binding is glycan-independent and targeted to the N-domain. H. pylori binding induces CEACAM1-mediated signalling, and the HopQ-CEACAM1 interaction enables translocation of the virulence factor CagA into host cells and enhances the release of pro-inflammatory mediators such as interleukin-8. Based on the crystal structure of HopQ, we found that a beta-hairpin insertion (HopQ-ID) in HopQ's extracellular 3+4 helix bundle domain is important for CEACAM binding. A peptide derived from this domain competitively inhibits HopQ-mediated activation of the Cag virulence pathway, as genetic or antibody-mediated abrogation of the HopQ function shows. Together, our data suggest the HopQ-CEACAM1 interaction to be a potentially promising novel therapeutic target to combat H. pylori-associated diseases.
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| 9. |
- Kolomiiets, Olena, et al.
(författare)
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The expression of prolactin receptors in benign breast tumors is not associated with serum prolactin level
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:24
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Tidskriftsartikel (refereegranskat)abstract
- The role of prolactin (PRL) and its receptors in the initiation and development of benign breast tumors (BBT) has not been sufficiently studied. An imbalance in the system of hormone homeostasis is crucial in the development of BBT. In particular, an association between elevated prolactin levels and the development of BBT has been reported. Our study showed no significant differences between PRL receptor (PRL-R) expression in BBT tissue under normal and elevated serum PRL levels. There was also no significant correlation between age, PRL-R expression in BBT tissue, intact tissue, and PRL level in the serum. There was a strong significant correlation (p < 0.01; r = 0.92) between PRL-R expression in BBT samples and intact breast tissue, which did not depend on the serum PRL level. There was also no significant difference in the expression of the proliferative marker Ki-67 in BBT tissues from women with normal and elevated levels of serum PRL (p > 0.05). No signs of PRL and its receptors were detected in the BBT cystic fluid women with elevated serum PRL levels. In summary, our prospective study showed that the expression of PRL-R in the tissue of BBT and physiological breast tissue does not depend on the level of serum PRL.
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| 10. |
- Tran, Phong, et al.
(författare)
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Imbalanced dNTP pools induce mutator and cancer phenotypes in mice
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The high accuracy of DNA replication is achieved through the nucleotide selectivity of DNA polymerases, polymerase proofreading, and the mismatch repair (MMR) system that act in series. While defects in proofreading and MMR are strongly associated with the development of cancers, decreased nucleotide selectivity due to mutations in replicative DNA polymerases is an uncommon driver of cancer development. Because nucleotide selectivity can also be decreased by imbalanced dNTP pools, we investigated to what extent imbalanced dNTP pools can induce cancers. To this end we developed a mouse model with a mutation in the allosteric specificity site of ribonucleotide reductase, which is responsible for the balanced production of dNTPs. These mice had ~2-fold increased dCTP and dTTP levels and normal dATP and dGTP levels. Despite this mild dNTP pool imbalance, mutant mice had a higher incidence and an earlier onset of cancers, and these were different from the cancers that developed in wild-type controls. Because dNTP pool imbalances can be caused by defects in a plethora of genes, we propose that decreased nucleotide selectivity might be a major factor contributing to the development of spontaneous cancers.
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