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Article ; Online: Cilofexor for the Treatment of Nonalcoholic Steatohepatitis.

Polyzos, Stergios A / Xanthopoulos, Konstantinos / Kountouras, Jannis

2021 Volume 20, Issue 2, Page(s) 111–113

MeSH term(s)	Azetidines ; Humans ; Isonicotinic Acids ; Non-alcoholic Fatty Liver Disease/diagnosis ; Non-alcoholic Fatty Liver Disease/drug therapy
Chemical Substances	Azetidines ; Isonicotinic Acids ; cilofexor (YUN2306954)
Language	English
Publishing date	2021-12-09
Publishing country	United Arab Emirates
Document type	Editorial
ZDB-ID	2192362-0
ISSN	1875-6212 ; 1570-1611
ISSN (online)	1875-6212
ISSN	1570-1611
DOI	10.2174/1570161119666211209161023
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Article ; Online: Inactivation of the Tumor Suppressor CYLD Sensitizes Mice to Breast Cancer Development.

Pseftogas, Athanasios / Xanthopoulos, Konstantinos / Siasiaridis, Athanasios / Poutahidis, Theofilos / Gonidas, Christos / Tsingotjidou, Anastasia / Hatzivassiliou, Eudoxia / Mosialos, George

Anticancer research

2024 Volume 44, Issue 5, Page(s) 1885–1894

Abstract: Background/aim: Breast cancer is a leading cause of cancer-related deaths among women. Down-regulation of the tumor suppressor gene Cyld in breast cancer has been linked to a poor prognosis. This study investigated the role of Cyld in breast cancer ... ...

Abstract	Background/aim: Breast cancer is a leading cause of cancer-related deaths among women. Down-regulation of the tumor suppressor gene Cyld in breast cancer has been linked to a poor prognosis. This study investigated the role of Cyld in breast cancer using conditional mutant mouse models carrying a Cyld mutation, which inactivates the deubiquitinating activity of its protein product CYLD in mammary epithelial cells. Materials and methods: We examined the potential of CYLD inactivation to induce mammary tumors spontaneously or modify the susceptibility of mice to mammary tumorigenesis by DMBA treatment or ErbB2 over-expression. Results: CYLD inactivation significantly increased susceptibility to breast cancer induced by either DMBA treatment or ErbB2 over-expression. Moreover, while CYLD inactivation alone did not lead to spontaneous mammary tumorigenesis, it did contribute to the formation of multifocal hyperplastic lesions in virgin mice of predominantly FVB/NJ background. Conclusion: Our study demonstrates the tumor enhancing potential of CYLD inactivation in mammary tumorigenesis in vivo and establishes novel relevant mouse models that can be exploited for developing prognostic and therapeutic protocols.
MeSH term(s)	Animals ; Deubiquitinating Enzyme CYLD/genetics ; Deubiquitinating Enzyme CYLD/metabolism ; Female ; Mice ; Breast Neoplasms/pathology ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Mammary Neoplasms, Experimental/pathology ; Mammary Neoplasms, Experimental/genetics ; Humans ; 9,10-Dimethyl-1,2-benzanthracene/toxicity ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; Mutation ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology
Chemical Substances	Deubiquitinating Enzyme CYLD (EC 3.4.19.12) ; CYLD protein, mouse (EC 3.4.19.12) ; Receptor, ErbB-2 (EC 2.7.10.1) ; 9,10-Dimethyl-1,2-benzanthracene (57-97-6) ; Tumor Suppressor Proteins
Language	English
Publishing date	2024-04-27
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.16990
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Zs.A 1642: Show issues

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Article ; Online: Age-Associated B Cells (ABCs) in the Prognosis, Diagnosis and Therapy of Systemic Lupus Erythematosus (SLE).

Sachinidis, Athanasios / Xanthopoulos, Konstantinos / Garyfallos, Alexandros

Mediterranean journal of rheumatology

2020 Volume 31, Issue 3, Page(s) 311–318

Abstract: The term "age-associated B cells" (ABCs) refers to a heterogeneous B cell subset ( ... ...

Abstract	The term "age-associated B cells" (ABCs) refers to a heterogeneous B cell subset (CD19
Language	English
Publishing date	2020-09-30
Publishing country	Greece
Document type	Journal Article ; Review
ZDB-ID	3019943-8
ISSN	2529-198X ; 2459-3516
ISSN (online)	2529-198X
ISSN	2459-3516
DOI	10.31138/mjr.31.3.311
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Article ; Online: Immunization with Genetically Modified Trypanosomes Provides Protection against Transmissible Spongiform Encephalopathies.

Triller, Gianna / Garyfallos, Dimitrios A / Papavasiliou, F Nina / Sklaviadis, Theodoros / Stavropoulos, Pete / Xanthopoulos, Konstantinos

International journal of molecular sciences

2022 Volume 23, Issue 18

Abstract: Transmissible spongiform encephalopathies are incurable neurodegenerative diseases, associated with the conversion of the physiological prion protein to its disease-associated counterpart. Even though immunization against transmissible spongiform ... ...

Abstract	Transmissible spongiform encephalopathies are incurable neurodegenerative diseases, associated with the conversion of the physiological prion protein to its disease-associated counterpart. Even though immunization against transmissible spongiform encephalopathies has shown great potential, immune tolerance effects impede the use of active immunization protocols for successful prophylaxis. In this study, we evaluate the use of trypanosomes as biological platforms for the presentation of a prion antigenic peptide to the host immune system. Using the engineered trypanosomes in an immunization protocol without the use of adjuvants led to the development of a humoral immune response against the prion protein in wild type mice, without the appearance of adverse reactions. The immune reaction elicited with this protocol displayed in vitro therapeutic potential and was further evaluated in a bioassay where immunized mice were partially protected in a representative murine model of prion diseases. Further studies are underway to better characterize the immune reaction and optimize the immunization protocol.
MeSH term(s)	Animals ; Immunization ; Mice ; Prion Diseases/prevention & control ; Prion Proteins ; Prions/genetics ; Trypanosoma ; Vaccination
Chemical Substances	Prion Proteins ; Prions
Language	English
Publishing date	2022-09-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231810629
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Article: Inactivation of Tumor Suppressor CYLD Inhibits Fibroblast Reprogramming to Pluripotency.

Bekas, Nikolaos / Samiotaki, Martina / Papathanasiou, Maria / Mokos, Panagiotis / Pseftogas, Athanasios / Xanthopoulos, Konstantinos / Thanos, Dimitris / Mosialos, George / Dafou, Dimitra

Cancers

2023 Volume 15, Issue 20

Abstract: ... ...

Abstract	CYLD
Language	English
Publishing date	2023-10-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15204997
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Article ; Online: Gene targeting in amyotrophic lateral sclerosis using causality-based feature selection and machine learning.

Founta, Kyriaki / Dafou, Dimitra / Kanata, Eirini / Sklaviadis, Theodoros / Zanos, Theodoros P / Gounaris, Anastasios / Xanthopoulos, Konstantinos

Molecular medicine (Cambridge, Mass.)

2023 Volume 29, Issue 1, Page(s) 12

Abstract: Background: Amyotrophic lateral sclerosis (ALS) is a rare progressive neurodegenerative disease that affects upper and lower motor neurons. As the molecular basis of the disease is still elusive, the development of high-throughput sequencing ... ...

Abstract	Background: Amyotrophic lateral sclerosis (ALS) is a rare progressive neurodegenerative disease that affects upper and lower motor neurons. As the molecular basis of the disease is still elusive, the development of high-throughput sequencing technologies, combined with data mining techniques and machine learning methods, could provide remarkable results in identifying pathogenetic mechanisms. High dimensionality is a major problem when applying machine learning techniques in biomedical data analysis, since a huge number of features is available for a limited number of samples. The aim of this study was to develop a methodology for training interpretable machine learning models in the classification of ALS and ALS-subtypes samples, using gene expression datasets. Methods: We performed dimensionality reduction in gene expression data using a semi-automated preprocessing systematic gene selection procedure using Statistically Equivalent Signature (SES), a causality-based feature selection algorithm, followed by Boosted Regression Trees (XGBoost) and Random Forest to train the machine learning classifiers. The SHapley Additive exPlanations (SHAP values) were used for interpretation of the machine learning classifiers. The methodology was developed and tested using two distinct publicly available ALS RNA-seq datasets. We evaluated the performance of SES as a dimensionality reduction method against: (a) Least Absolute Shrinkage and Selection Operator (LASSO), and (b) Local Outlier Factor (LOF). Results: The proposed methodology achieved 85.18% accuracy for the classification of cerebellum or frontal cortex samples as C9orf72-related familial ALS, sporadic ALS or healthy samples. Importantly, the genes identified as the most determinative have also been reported as disease-associated in ALS literature. When tested in the evaluation dataset, the methodology achieved 88.89% accuracy for the classification of sporadic ALS motor neuron samples. When LASSO was used as feature selection method instead of SES, the accuracy of the machine learning classifiers ranged from 74.07 to 96.30%, depending on tissue assessed, while LOF underperformed significantly (77.78% accuracy for the classification of pooled cerebellum and frontal cortex samples). Conclusions: Using SES, we addressed the challenge of high dimensionality in gene expression data analysis, and we trained accurate machine learning ALS classifiers, specific for the gene expression patterns of different disease subtypes and tissue samples, while identifying disease-associated genes.
MeSH term(s)	Humans ; Amyotrophic Lateral Sclerosis/genetics ; Neurodegenerative Diseases ; Machine Learning ; Gene Targeting
Language	English
Publishing date	2023-01-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1283676-x
ISSN	1528-3658 ; 1076-1551
ISSN (online)	1528-3658
ISSN	1076-1551
DOI	10.1186/s10020-023-00603-y
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Zs.A 4456: Show issues

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Article ; Online: Partial validation of a six-month high-fat diet and fructose-glucose drink combination as a mouse model of nonalcoholic fatty liver disease.

Makri, Evangelia S / Xanthopoulos, Konstantinos / Mavrommatis Parasidis, Panagiotis / Makri, Eleftheria / Pettas, Spyros / Tsingotjidou, Anastasia / Cheva, Angeliki / Ballaouri, Iris / Gerou, Spyridon / Goulas, Antonis / Polyzos, Stergios A

Endocrine

2024

Abstract: Purpose: The need to investigate the pathogenesis and treatment of nonalcoholic fatty liver disease (NAFLD) has led to the development of multiple mouse models. The aim of this study was to validate a fast food diet (FFD) mouse model that is introduced ... ...

Abstract	Purpose: The need to investigate the pathogenesis and treatment of nonalcoholic fatty liver disease (NAFLD) has led to the development of multiple mouse models. The aim of this study was to validate a fast food diet (FFD) mouse model that is introduced as being close to the human disease. Methods: Eight to nine weeks old male and female C57BL/6 J mice were randomly allocated to a FFD group or to a chow diet (CD) group. Every four weeks, mice were weighed, and blood samples were collected for the measurement of glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TGs) and total cholesterol. After 25 weeks, mice were sacrificed, and liver tissue was histologically evaluated. Results: FFD mice gained more weight (p = 0.049) and presented a higher liver-to-body weight ratio (p < 0.001) compared to CD mice. FFD group presented with greater steatosis, hepatocellular ballooning and NAFLD activity score (NAS), whereas lobular inflammation and fibrosis were not significantly different compared to CD. When stratified by sex, NAS was different between FFD and CD groups in both male and female mice. Group by time interaction was significant for weight, ALT and cholesterol, but not for glucose, AST and TGs. Conclusion: FFD mice presented with morphologic and biochemical features of NAFLD and with greater hepatic steatosis, hepatocellular ballooning and NAS, but not lobular inflammation and fibrosis, compared to CD mice. These results only partly validate the FFD mouse model for NAFLD, at least for a 6-month feeding period.
Language	English
Publishing date	2024-03-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1194484-5
ISSN	1559-0100 ; 1355-008X ; 0969-711X
ISSN (online)	1559-0100
ISSN	1355-008X ; 0969-711X
DOI	10.1007/s12020-024-03769-5
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Zs.A 3884: Show issues

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Article ; Online: Αnti-prion effects of anthocyanins.

Christoudia, Nikoletta / Bekas, Nikolaos / Kanata, Eirini / Chatziefsthathiou, Athanasia / Pettas, Spyros / Karagianni, Korina / Da Silva Correia, Susana Margarida / Schmitz, Matthias / Zerr, Inga / Tsamesidis, Ioannis / Xanthopoulos, Konstantinos / Dafou, Dimitra / Sklaviadis, Theodoros

Redox biology

2024 Volume 72, Page(s) 103133

Abstract: Prion diseases, also known as Transmissible Spongiform Encephalopathies (TSEs), are protein-based neurodegenerative disorders (NDs) affecting humans and animals. They are characterized by the conformational conversion of the normal cellular prion protein, ...

Abstract	Prion diseases, also known as Transmissible Spongiform Encephalopathies (TSEs), are protein-based neurodegenerative disorders (NDs) affecting humans and animals. They are characterized by the conformational conversion of the normal cellular prion protein, PrP
Language	English
Publishing date	2024-03-28
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2024.103133
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Article ; Online: A Systematic Review of Common and Brain-Disease-Specific RNA Editing Alterations Providing Novel Insights into Neurological and Neurodegenerative Disease Manifestations.

Karagianni, Korina / Pettas, Spyros / Christoforidou, Georgia / Kanata, Eirini / Bekas, Nikolaos / Xanthopoulos, Konstantinos / Dafou, Dimitra / Sklaviadis, Theodoros

Biomolecules

2022 Volume 12, Issue 3

Abstract: RNA editing contributes to transcriptome diversification through RNA modifications in relation to genome-encoded information (RNA-DNA differences, RDDs). The deamination of Adenosine (A) to Inosine (I) or Cytidine (C) to Uridine (U) is the most common ... ...

Abstract	RNA editing contributes to transcriptome diversification through RNA modifications in relation to genome-encoded information (RNA-DNA differences, RDDs). The deamination of Adenosine (A) to Inosine (I) or Cytidine (C) to Uridine (U) is the most common type of mammalian RNA editing. It occurs as a nuclear co- and/or post-transcriptional event catalyzed by ADARs (Adenosine deaminases acting on RNA) and APOBECs (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like genes). RNA editing may modify the structure, stability, and processing of a transcript. This review focuses on RNA editing in psychiatric, neurological, neurodegenerative (NDs), and autoimmune brain disorders in humans and rodent models. We discuss targeted studies that focus on RNA editing in specific neuron-enriched transcripts with well-established functions in neuronal activity, and transcriptome-wide studies, enabled by recent technological advances. We provide comparative editome analyses between human disease and corresponding animal models. Data suggest RNA editing to be an emerging mechanism in disease development, displaying common and disease-specific patterns. Commonly edited RNAs represent potential disease-associated targets for therapeutic and diagnostic values. Currently available data are primarily descriptive, calling for additional research to expand global editing profiles and to provide disease mechanistic insights. The potential use of RNA editing events as disease biomarkers and available tools for RNA editing identification, classification, ranking, and functional characterization that are being developed will enable comprehensive analyses for a better understanding of disease(s) pathogenesis and potential cures.
MeSH term(s)	Adenosine/genetics ; Adenosine/metabolism ; Adenosine Deaminase/genetics ; Adenosine Deaminase/metabolism ; Animals ; Brain/metabolism ; Brain Diseases ; Mammals/metabolism ; Neurodegenerative Diseases/genetics ; RNA ; RNA Editing/genetics
Chemical Substances	RNA (63231-63-0) ; Adenosine Deaminase (EC 3.5.4.4) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2022-03-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review ; Systematic Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12030465
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Article ; Online: Profiling Microglia through Single-Cell RNA Sequencing over the Course of Development, Aging, and Disease.

Pettas, Spyros / Karagianni, Korina / Kanata, Eirini / Chatziefstathiou, Athanasia / Christoudia, Nikoletta / Xanthopoulos, Konstantinos / Sklaviadis, Theodoros / Dafou, Dimitra

Cells

2022 Volume 11, Issue 15

Abstract: Microglia are macrophages present in the brain that function as the primary and most important source of immune response in the central nervous system (CNS). Regardless of their multitasking role, our knowledge regarding their molecular heterogeneity is ... ...

Abstract	Microglia are macrophages present in the brain that function as the primary and most important source of immune response in the central nervous system (CNS). Regardless of their multitasking role, our knowledge regarding their molecular heterogeneity is limited; due to technical restrictions, it is only possible to measure gene expression in cell populations, not individual cells, with the results reflecting average mRNA levels. Therefore, recent scientific approaches have focused on single-cell techniques such as single-cell RNA sequencing (scRNAseq), a powerful technique that enables the delineation of transcriptomic cell-to-cell differences, revealing subpopulations with distinct molecular and functional characteristics. Here, we summarize recent studies that focused on transcriptomic microglial subpopulation clustering and classify them into three distinct groups based on age, spatial distribution, and disease. Additionally, we cross-compare populations from different studies to identify expressional and functional overlaps between them.
MeSH term(s)	Central Nervous System ; Microglia/metabolism ; Sequence Analysis, RNA ; Transcriptome/genetics
Language	English
Publishing date	2022-08-02
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11152383
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