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Article ; Online: The Circulating Biomarkers League: Combining miRNAs with Cell-Free DNAs and Proteins.

Felekkis, Kyriacos / Papaneophytou, Christos

International journal of molecular sciences

2024 Volume 25, Issue 6

Abstract: The potential of liquid biopsy for the prognosis and diagnosis of diseases is unquestionable. Within the evolving landscape of disease diagnostics and personalized medicine, circulating microRNAs (c-miRNAs) stand out among the biomarkers found in blood ... ...

Abstract	The potential of liquid biopsy for the prognosis and diagnosis of diseases is unquestionable. Within the evolving landscape of disease diagnostics and personalized medicine, circulating microRNAs (c-miRNAs) stand out among the biomarkers found in blood circulation and other biological fluids due to their stability, specificity, and non-invasive detection in biofluids. However, the complexity of human diseases and the limitations inherent in single-marker diagnostics highlight the need for a more integrative approach. It has been recently suggested that a multi-analyte approach offers advantages over the single-analyte approach in the prognosis and diagnosis of diseases. In this review, we explore the potential of combining three well-studied classes of biomarkers found in blood circulation and other biofluids-miRNAs, DNAs, and proteins-to enhance the accuracy and efficacy of disease detection and monitoring. Initially, we provide an overview of each biomarker class and discuss their main advantages and disadvantages highlighting the superiority of c-miRNAs over the other classes of biomarkers. Additionally, we discuss the challenges and future directions in integrating these biomarkers into clinical practice, emphasizing the need for standardized protocols and further validation studies. This integrated approach has the potential to revolutionize precision medicine by offering insights into disease mechanisms, facilitating early detection, and guiding personalized therapeutic strategies. The collaborative power of c-miRNAs with other biomarkers represents a promising frontier in the comprehensive understanding and management of complex diseases. Nevertheless, several challenges must be addressed before this approach can be translated into clinical practice.
MeSH term(s)	Humans ; MicroRNAs/genetics ; Cell-Free Nucleic Acids ; Biomarkers, Tumor ; Biomarkers ; Liquid Biopsy
Chemical Substances	MicroRNAs ; Cell-Free Nucleic Acids ; Biomarkers, Tumor ; Biomarkers
Language	English
Publishing date	2024-03-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25063403
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Exploring the Feasibility of Circulating miRNAs as Diagnostic and Prognostic Biomarkers in Osteoarthritis: Challenges and Opportunities.

Felekkis, Kyriacos / Pieri, Myrtani / Papaneophytou, Christos

International journal of molecular sciences

2023 Volume 24, Issue 17

Abstract: Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by progressive cartilage degradation and joint inflammation. As the most common aging-related joint disease, OA is marked by inadequate extracellular matrix synthesis and the ... ...

Abstract	Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by progressive cartilage degradation and joint inflammation. As the most common aging-related joint disease, OA is marked by inadequate extracellular matrix synthesis and the breakdown of articular cartilage. However, traditional diagnostic methods for OA, relying on clinical assessments and radiographic imaging, often need to catch up in detecting early-stage disease or i accurately predicting its progression. Consequently, there is a growing interest in identifying reliable biomarkers that can facilitate early diagnosis and prognosis of OA. MicroRNAs (miRNAs) have emerged as potential candidates due to their involvement in various cellular processes, including cartilage homeostasis and inflammation. This review explores the feasibility of circulating miRNAs as diagnostic and prognostic biomarkers in OA, focusing on knee OA while shedding light on the challenges and opportunities associated with their implementation in clinical practice.
MeSH term(s)	Humans ; Circulating MicroRNA ; Feasibility Studies ; Prognosis ; MicroRNAs/genetics ; Inflammation ; Osteoarthritis, Knee
Chemical Substances	Circulating MicroRNA ; MicroRNAs
Language	English
Publishing date	2023-08-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241713144
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Article ; Online: MicroRNAs and Aging: Biomarkers or Therapeutic Targets?

Felekkis, Kyriacos

Current aging science

2017 Volume 10, Issue 2, Page(s) 80–82

Abstract: Understanding the molecular mechanism of aging is of utmost importance to the scientific communities. To date, various theories have been proposed and many of them were evaluated as potential targets in the battle against aging. MicroRNAs, the universal ... ...

Abstract	Understanding the molecular mechanism of aging is of utmost importance to the scientific communities. To date, various theories have been proposed and many of them were evaluated as potential targets in the battle against aging. MicroRNAs, the universal gene expression regulators, were found to be associated with the aging process as many of them have been linked to biological process associated with cellular deterioration. In this short report, we briefly review the contribution of miRNAs to the aging process and offer an opinion as to how the knowledge of the role of these molecules in aging can be utilized.
Language	English
Publishing date	2017
Publishing country	United Arab Emirates
Document type	Journal Article
ISSN	1874-6128
ISSN (online)	1874-6128
DOI	10.2174/1874609808666161124130206
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Article ; Online: Alterations in Circulating miRNA Levels after Infection with SARS-CoV-2 Could Contribute to the Development of Cardiovascular Diseases: What We Know So Far.

Pieri, Myrtani / Vayianos, Panayiotis / Nicolaidou, Vicky / Felekkis, Kyriacos / Papaneophytou, Christos

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and poses significant complications for cardiovascular disease (CVD) patients. MicroRNAs (miRNAs) are small non-coding RNAs that ... ...

Abstract	The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and poses significant complications for cardiovascular disease (CVD) patients. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and influence several physiological and pathological processes, including CVD. This critical review aims to expand upon the current literature concerning miRNA deregulation during the SARS-CoV-2 infection, focusing on cardio-specific miRNAs and their association with various CVDs, including cardiac remodeling, arrhythmias, and atherosclerosis after SARS-CoV-2 infection. Despite the scarcity of research in this area, our findings suggest that changes in the expression levels of particular COVID-19-related miRNAs, including miR-146a, miR-27/miR-27a-5p, miR-451, miR-486-5p, miR-21, miR-155, and miR-133a, may be linked to CVDs. While our analysis did not conclusively determine the impact of SARS-CoV-2 infection on the profile and/or expression levels of cardiac-specific miRNAs, we proposed a potential mechanism by which the miRNAs mentioned above may contribute to the development of these two pathologies. Further research on the relationship between SARS-CoV-2, CVDs, and microRNAs will significantly enhance our understanding of this connection and may lead to the use of these miRNAs as biomarkers or therapeutic targets for both pathologies.
MeSH term(s)	Humans ; SARS-CoV-2/metabolism ; Cardiovascular Diseases/genetics ; COVID-19/genetics ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Circulating MicroRNA
Chemical Substances	MicroRNAs ; Circulating MicroRNA
Language	English
Publishing date	2023-01-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24032380
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Article ; Online: Challenges in Using Circulating Micro-RNAs as Biomarkers for Cardiovascular Diseases.

Felekkis, Kyriacos / Papaneophytou, Christos

International journal of molecular sciences

2020 Volume 21, Issue 2

Abstract: Micro-RNAs (miRNAs) play a pivotal role in the development and physiology of the cardiovascular system while they have been associated with multiple cardiovascular diseases (CVDs). Several cardiac miRNAs are detectable in circulation (circulating miRNAs; ...

Abstract	Micro-RNAs (miRNAs) play a pivotal role in the development and physiology of the cardiovascular system while they have been associated with multiple cardiovascular diseases (CVDs). Several cardiac miRNAs are detectable in circulation (circulating miRNAs; c-miRNAs) and are emerging as diagnostic and therapeutic biomarkers for CVDs. c-miRNAs exhibit numerous essential characteristics of biomarkers while they are extremely stable in circulation, their expression is tissue-/disease-specific, and they can be easily detected using sequence-specific amplification methods. These features of c-miRNAs are helpful in the development of non-invasive assays to monitor the progress of CVDs. Despite significant progress in the detection of c-miRNAs in serum and plasma, there are many contradictory publications on the alterations of cardiac c-miRNAs concentration in circulation. The aim of this review is to examine the pre-analytical and analytical factors affecting the quantification of c-miRNAs and provide general guidelines to increase the accuracy of the diagnostic tests in order to improve future research on cardiac c-miRNAs.
MeSH term(s)	Biomarkers/blood ; Biomarkers/metabolism ; Cardiovascular Diseases/blood ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/therapy ; Gene Expression Regulation ; Humans ; MicroRNAs/antagonists & inhibitors ; MicroRNAs/blood ; MicroRNAs/genetics ; Molecular Targeted Therapy/methods ; Myocardium/metabolism ; Myocardium/pathology ; Prognosis ; Sensitivity and Specificity
Chemical Substances	Biomarkers ; MicroRNAs
Language	English
Publishing date	2020-01-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21020561
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Article ; Online: Exploring the Dynamic Relationship between the Gut Microbiome and Body Composition across the Human Lifespan: A Systematic Review.

Komodromou, Ifigeneia / Andreou, Eleni / Vlahoyiannis, Angelos / Christofidou, Maria / Felekkis, Kyriacos / Pieri, Myrtani / Giannaki, Christoforos D

Nutrients

2024 Volume 16, Issue 5

Abstract: This systematic review aimed to identify different gut microbiome profiles across the human lifespan and to correlate such profiles with the body composition. PubMed, Scopus, and Cochrane were searched from inception to March 2022. Sixty studies were ... ...

Abstract	This systematic review aimed to identify different gut microbiome profiles across the human lifespan and to correlate such profiles with the body composition. PubMed, Scopus, and Cochrane were searched from inception to March 2022. Sixty studies were included in this systematic review. Overall, the gut microbiome composition in overweight participants exhibited decreased α-diversity, decreased levels of the phylum
MeSH term(s)	Humans ; Gastrointestinal Microbiome ; Overweight ; Longevity ; Obesity ; Firmicutes ; Bacteroidetes ; Body Composition
Language	English
Publishing date	2024-02-26
Publishing country	Switzerland
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu16050660
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Article ; Online: Detection of SARS-CoV-2-Specific Antibodies in Human Breast Milk and Their Neutralizing Capacity after COVID-19 Vaccination: A Systematic Review.

Nicolaidou, Vicky / Georgiou, Rafaela / Christofidou, Maria / Felekkis, Kyriacos / Pieri, Myrtani / Papaneophytou, Christos

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: SARS-CoV-2 is the virus that causes the infectious disease known as Corona Virus Disease 2019 (COVID-19). The severe impact of the virus on humans is undeniable, which is why effective vaccines were highly anticipated. As of 12 January 2022, nine ... ...

Abstract	SARS-CoV-2 is the virus that causes the infectious disease known as Corona Virus Disease 2019 (COVID-19). The severe impact of the virus on humans is undeniable, which is why effective vaccines were highly anticipated. As of 12 January 2022, nine vaccines have obtained Emergency Use Listing by the World Health Organization (WHO), and four of these are approved or authorized by the Centers for Disease Control and Prevention (CDC) in the United States. The initial clinical trials studying COVID-19 vaccine efficacy excluded pregnant and lactating individuals, meaning that data on the effects of the vaccine on breast milk were lacking. Until today, none of the authorized vaccines have been approved for use in individuals under six months. During the first months of life, babies do not produce their own antibodies; therefore, antibodies contained in their mothers' breastmilk are a critical protective mechanism. Several studies have shown the presence of SARS-CoV-2 antibodies in the breast milk of women who have been vaccinated or had been naturally infected. However, whether these are protective is still unclear. Additionally, research on the BNT162b2 mRNA vaccine developed by Pfizer-BioNTech and the mRNA-1273 vaccine developed by Moderna suggests that these vaccines do not release significant amounts, if any, of mRNA into breast milk. Hence, there is no evidence that vaccination of the mother poses any risk to the breastfed infant, while the antibodies present in breast milk may offer protection against the virus. The primary objective of this systematic review is to summarize the current understanding of the presence of immunoglobulins in human milk that are elicited by SARS-CoV-2 vaccines and to evaluate their ability to neutralize the virus. Additionally, we aim to quantify the side effects experienced by lactating mothers who have been vaccinated, as well as the potential for adverse effects in their infants. This study is critical because it can help inform decision-making by examining the current understanding of antibody secretion in breastmilk. This is particularly important because, although the virus tends to be less severe in younger individuals, infants who contract the disease are at a higher risk of requiring hospitalization compared to older children.
MeSH term(s)	Infant ; Child ; Humans ; Female ; Adolescent ; COVID-19 Vaccines ; Milk, Human ; SARS-CoV-2 ; 2019-nCoV Vaccine mRNA-1273 ; BNT162 Vaccine ; Lactation ; COVID-19/prevention & control ; Antibodies, Viral ; Vaccination ; Drug-Related Side Effects and Adverse Reactions ; Antibodies, Neutralizing
Chemical Substances	COVID-19 Vaccines ; 2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; BNT162 Vaccine ; Antibodies, Viral ; Antibodies, Neutralizing
Language	English
Publishing date	2023-02-03
Publishing country	Switzerland
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24032957
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Article ; Online: Variability in the levels of exosomal miRNAs among human subjects could be explained by differential interactions of exosomes with the endothelium.

Felekkis, Kyriacos / Pieri, Myrtani / Papaneophytou, Christos

IUBMB life

2021 Volume 73, Issue 12, Page(s) 1400–1405

Abstract: Exosomes are 30-100 nm endosome-derived membrane vesicles, that contain specific RNA transcripts including mRNAs, and microRNAs (miRNAs) and have been implicated in cell-to-cell communication. Exosomal miRNAs in blood circulation have been attracting ... ...

Abstract	Exosomes are 30-100 nm endosome-derived membrane vesicles, that contain specific RNA transcripts including mRNAs, and microRNAs (miRNAs) and have been implicated in cell-to-cell communication. Exosomal miRNAs in blood circulation have been attracting major interest as potential diagnostic and prognostic biomarkers in a variety of diseases including stroke, cancer, and inflammatory disorders. Despite the progress made in the utilization of circulating exosomal miRNAs as biomarkers for various human diseases and conditions, there are still difficulties in functionally utilizing such methods in the clinic due to the high variability observed among subjects. Attempts to use miRNA signatures have improved but have not eliminated the problem. Additionally, standardized laboratory practices may partially reduce variability but there is still an unknown biological factor that hinders the proper use of miRNAs as biomarkers. We hypothesize that this variability might be partially attributed to a differential interaction among circulating exosomes carrying those miRNAs with endothelial surface molecules that themselves may vary among individuals due to secondary conditions, for example, inflammation status. This differential interaction could potentially add variability to the level of the examined miRNA that is not directly attributed to the primary condition under study.
MeSH term(s)	Endothelium ; Exosomes/genetics ; Humans ; MicroRNAs/genetics ; RNA, Messenger ; Research Subjects
Chemical Substances	MicroRNAs ; RNA, Messenger
Language	English
Publishing date	2021-11-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1492141-8
ISSN	1521-6551 ; 1521-6543
ISSN (online)	1521-6551
ISSN	1521-6543
DOI	10.1002/iub.2575
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Article ; Online: A bovine miRNA, bta-miR-154c, withstands in vitro human digestion but does not affect cell viability of colorectal human cell lines after transfection.

Pieri, Myrtani / Theori, Elena / Dweep, Harsh / Flourentzou, Myrofora / Kalampalika, Foteini / Maniori, Maria-Arsenia / Papagregoriou, Gregory / Papaneophytou, Christos / Felekkis, Kyriacos

FEBS open bio

2022 Volume 12, Issue 5, Page(s) 925–936

Abstract: Colorectal cancer (CRC) is the third most frequent human cancer with over 1.3 million new cases globally. CRC is a complex disease caused by interactions between genetic and environmental factors; in particular, high consumption of red meat, including ... ...

Abstract	Colorectal cancer (CRC) is the third most frequent human cancer with over 1.3 million new cases globally. CRC is a complex disease caused by interactions between genetic and environmental factors; in particular, high consumption of red meat, including beef, is considered a risk factor for CRC initiation and progression. Recent data demonstrate that exogenous microRNAs (miRNAs) entering the body via ingestion could pose an effect on the consumer. In this study, we focused on bovine miRNAs that do not share a seed sequence with humans and mice. We identified bta-miR-154c, a bovine miRNA found in edible parts of beef and predicted via cross-species bioinformatic analysis to affect cancer-related pathways in human cells. When bovine tissue was subjected to cooking and a simulation of human digestion, bta-miR-154c was still detected after all procedures, albeit at reduced concentrations. However, lipofection of bta-miR-154c in three different colorectal human cell lines did not affect their viability as evaluated at various time points and concentrations. These data indicate that bta-miR-154c (a) may affect cancer-related pathways in human cells, (b) can withstand digestion and be detected after all stages of an in vitro digestion protocol, but (c) it does not appear to alter epithelial cell viability after entering human enterocytes, even at supraphysiological amounts. Further experiments will elucidate whether bta-miR-154c exerts a different functional effect on the human gut epithelium, which may cause it to contribute to CRC progression through its consumption.
MeSH term(s)	Animals ; Cattle ; Cell Line ; Cell Survival/genetics ; Colorectal Neoplasms/genetics ; Digestion ; Humans ; Mice ; MicroRNAs/metabolism ; Transfection
Chemical Substances	MicroRNAs
Language	English
Publishing date	2022-03-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2651702-4
ISSN	2211-5463 ; 2211-5463
ISSN (online)	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.13402
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Article ; Online: Survival of Vaccine-Induced Human Milk SARS-CoV-2 IgG, IgA and SIgA Immunoglobulins across Simulated Human Infant Gastrointestinal Digestion.

Pieri, Myrtani / Maniori, Maria-Arsenia / Shahabian, Lucy / Kanaan, Elie / Paphiti-Demetriou, Irene / Pipis, Spyros / Felekkis, Kyriakos / Nicolaidou, Vicky / Papaneophytou, Christos

Nutrients

2022 Volume 14, Issue 16

Abstract: Breastfeeding can be a vital way of acquiring passive immunity via the transfer of antibodies from the mother to the breastfeeding infant. Recent evidence points to the fact that human milk contains immunoglobulins (Ig) against the SARS-CoV-2 virus, ... ...

Abstract	Breastfeeding can be a vital way of acquiring passive immunity via the transfer of antibodies from the mother to the breastfeeding infant. Recent evidence points to the fact that human milk contains immunoglobulins (Ig) against the SARS-CoV-2 virus, either after natural infection or vaccination, but whether these antibodies can resist enzymatic degradation during digestion in the infant gastrointestinal (GI) tract or indeed protect the consumers remains inconclusive. Herein, we evaluated the levels of IgG, IgA, and secretory IgA (SIgA) antibodies against the spike protein of SARS-CoV-2 in 43 lactating mothers who received at least two doses of either an mRNA-based vaccine (Pfizer/BioNTech, Moderna; n = 34) or an adenovirus-based vaccine (AstraZeneca; n = 9). We also accessed the potential persistence of SARS-CoV-2 IgA, IgG, and secretory IgA (SIgA) antibodies from vaccinated women in the GI tract of the infants by means of a static in vitro digestion protocol. Our data depict that, although slightly reduced, the IgA antibodies produced after vaccination resist both the gastric and intestinal phases of infant digestion, whereas the IgGs are more prone to degradation in both phases of digestion. Additionally, SIgA antibodies were found to greatly resist the gastric phase of digestion albeit showing some reduction during the intestinal phase. The evaluation of the vaccine induced Ig profile of breastmilk, and the extent to which these antibodies can resist digestion in the infant GI tract provide important information about the potential protective role of this form of passive immunity that could help decision making during the COVID-19 pandemic and beyond.
MeSH term(s)	Antibodies, Viral ; COVID-19/prevention & control ; Digestion ; Female ; Humans ; Immunoglobulin A ; Immunoglobulin A, Secretory ; Immunoglobulin G ; Infant ; Lactation ; Milk, Human ; Pandemics ; SARS-CoV-2 ; Vaccines
Chemical Substances	Antibodies, Viral ; Immunoglobulin A ; Immunoglobulin A, Secretory ; Immunoglobulin G ; Vaccines
Language	English
Publishing date	2022-08-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14163368
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