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Article ; Online: Technical Advances in Circulating Cell-Free DNA Detection and Analysis for Personalized Medicine in Patients' Care.

Sorbini, Monica / Carradori, Tullia / Togliatto, Gabriele Maria / Vaisitti, Tiziana / Deaglio, Silvia

2024 Volume 14, Issue 4

Abstract: Circulating cell-free DNA (cfDNA) refers to small fragments of DNA molecules released after programmed cell death and necrosis in several body fluids such as blood, saliva, urine, and cerebrospinal fluid. The discovery of cfDNA has revolutionized the ... ...

Abstract	Circulating cell-free DNA (cfDNA) refers to small fragments of DNA molecules released after programmed cell death and necrosis in several body fluids such as blood, saliva, urine, and cerebrospinal fluid. The discovery of cfDNA has revolutionized the field of non-invasive diagnostics in the oncologic field, in prenatal testing, and in organ transplantation. Despite the potential of cfDNA and the solid results published in the recent literature, several challenges remain, represented by a low abundance, a need for highly sensitive assays, and analytical issues. In this review, the main technical advances in cfDNA analysis are presented and discussed, with a comprehensive examination of the current available methodologies applied in each field. Considering the potential advantages of cfDNA, this biomarker is increasing its consensus among clinicians, as it allows us to monitor patients' conditions in an easy and non-invasive way, offering a more personalized care. Nevertheless, cfDNA analysis is still considered a diagnostic marker to be further validated, and very few centers are implementing its analysis in routine diagnostics. As technical improvements are enhancing the performances of cfDNA analysis, its application will transversally improve patients' quality of life.
MeSH term(s)	Humans ; Precision Medicine/methods ; Cell-Free Nucleic Acids/blood ; Cell-Free Nucleic Acids/genetics ; Neoplasms/diagnosis ; Neoplasms/genetics ; Neoplasms/blood ; Biomarkers/blood ; Biomarkers/cerebrospinal fluid
Chemical Substances	Cell-Free Nucleic Acids ; Biomarkers
Language	English
Publishing date	2024-04-19
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom14040498
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Future Challenge of Reactive Oxygen Species (ROS) in Hypertension: From Bench to Bed Side.

Togliatto, Gabriele / Lombardo, Giusy / Brizzi, Maria Felice

International journal of molecular sciences

2017 Volume 18, Issue 9

Abstract: Reactive oxygen species (ROS) act as signaling molecules that control physiological processes, including cell adaptation to stress. Redox signaling via ROS has quite recently become the focus of much attention in numerous pathological contexts, including ...

Abstract	Reactive oxygen species (ROS) act as signaling molecules that control physiological processes, including cell adaptation to stress. Redox signaling via ROS has quite recently become the focus of much attention in numerous pathological contexts, including neurodegenerative diseases, kidney and cardiovascular disease. Imbalance in ROS formation and degradation has also been implicated in essential hypertension. Essential hypertension is characterized by multiple genetic and environmental factors which do not completely explain its associated risk factors. Thereby, even if advances in therapy have led to a significant reduction in hypertension-associated complications, to interfere with the unbalance of redox signals might represent an additional therapeutic challenge. The decrease of nitric oxide (NO) levels, the antioxidant activity commonly found in preclinical models of hypertension and the ability of antioxidant approaches to reduce ROS levels have spurred clinicians to investigate the contribution of ROS in humans. Indeed, particular effort has recently been devoted to understanding how redox signaling may contribute to vascular pathobiology in human hypertension. However, although biomarkers of oxidative stress have been found to positively correlate with blood pressure in preclinical model of hypertension, human data are less convincing. We herein provide an overview of the most relevant mechanisms via which oxidative stress might contribute to the pathophysiology of essential hypertension. Moreover, alternative approaches, which are directed towards improving antioxidant machinery and/or interfering with ROS production, are also discussed.
Language	English
Publishing date	2017-09-15
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/ijms18091988
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Article ; Online: The Future Challenge of Reactive Oxygen Species (ROS) in Hypertension

Gabriele Togliatto / Giusy Lombardo / Maria Felice Brizzi

International Journal of Molecular Sciences, Vol 18, Iss 9, p

From Bench to Bed Side

2017 Volume 1988

Abstract	Reactive oxygen species (ROS) act as signaling molecules that control physiological processes, including cell adaptation to stress. Redox signaling via ROS has quite recently become the focus of much attention in numerous pathological contexts, including neurodegenerative diseases, kidney and cardiovascular disease. Imbalance in ROS formation and degradation has also been implicated in essential hypertension. Essential hypertension is characterized by multiple genetic and environmental factors which do not completely explain its associated risk factors. Thereby, even if advances in therapy have led to a significant reduction in hypertension-associated complications, to interfere with the unbalance of redox signals might represent an additional therapeutic challenge. The decrease of nitric oxide (NO) levels, the antioxidant activity commonly found in preclinical models of hypertension and the ability of antioxidant approaches to reduce ROS levels have spurred clinicians to investigate the contribution of ROS in humans. Indeed, particular effort has recently been devoted to understanding how redox signaling may contribute to vascular pathobiology in human hypertension. However, although biomarkers of oxidative stress have been found to positively correlate with blood pressure in preclinical model of hypertension, human data are less convincing. We herein provide an overview of the most relevant mechanisms via which oxidative stress might contribute to the pathophysiology of essential hypertension. Moreover, alternative approaches, which are directed towards improving antioxidant machinery and/or interfering with ROS production, are also discussed.
Keywords	ROS ; hypertension ; mitochondria ; redox signaling ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2017-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Skewed Epigenetics: An Alternative Therapeutic Option for Diabetes Complications.

Togliatto, Gabriele / Dentelli, Patrizia / Brizzi, Maria Felice

Journal of diabetes research

2015 Volume 2015, Page(s) 373708

Abstract: Vascular complications are major causes of morbidity and mortality in type 2 diabetes patients. Mitochondrial reactive oxygen species (ROS) generation and a lack of efficient antioxidant machinery, a result of hyperglycaemia, mainly contribute to this ... ...

Abstract	Vascular complications are major causes of morbidity and mortality in type 2 diabetes patients. Mitochondrial reactive oxygen species (ROS) generation and a lack of efficient antioxidant machinery, a result of hyperglycaemia, mainly contribute to this problem. Although advances in therapy have significantly reduced both morbidity and mortality in diabetic individuals, diabetes-associated vascular complications are still one of the most challenging health problems worldwide. New healing options are urgently needed as current therapeutics are failing to improve long-term outcomes. Particular effort has recently been devoted to understanding the functional relationship between chromatin structure regulation and the persistent change in gene expression which is driven by hyperglycaemia and which accounts for long-lasting diabetic complications. A detailed investigation into epigenetic chromatin modifications in type 2 diabetes is underway. This will be particularly useful in the design of mechanism-based therapeutics which interfere with long-lasting activating epigenetics and improve patient outcomes. We herein provide an overview of the most relevant mechanisms that account for hyperglycaemia-induced changes in chromatin structure; the most relevant mechanism is called "metabolic memory."
MeSH term(s)	Chromatin Assembly and Disassembly/genetics ; Diabetes Mellitus, Type 2/genetics ; Diabetic Angiopathies/genetics ; Diabetic Angiopathies/therapy ; Epigenesis, Genetic ; Humans ; Hyperglycemia/genetics
Language	English
Publishing date	2015-04-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2711897-6
ISSN	2314-6753 ; 2314-6745
ISSN (online)	2314-6753
ISSN	2314-6745
DOI	10.1155/2015/373708
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Article ; Online: Validation of a Simple, Rapid, and Cost-Effective Method for Acute Rejection Monitoring in Lung Transplant Recipients.

Transplant international : official journal of the European Society for Organ Transplantation

2022 Volume 35, Page(s) 10546

Abstract: Despite advances in immunosuppression therapy, acute rejection remains the leading cause of graft dysfunction in lung transplant recipients. Donor-derived cell-free DNA is increasingly being considered as a valuable biomarker of acute rejection in ... ...

Abstract	Despite advances in immunosuppression therapy, acute rejection remains the leading cause of graft dysfunction in lung transplant recipients. Donor-derived cell-free DNA is increasingly being considered as a valuable biomarker of acute rejection in several solid organ transplants. We present a technically improved molecular method based on digital PCR that targets the mismatch between the recipient and donor at the
MeSH term(s)	Cell-Free Nucleic Acids ; Cost-Benefit Analysis ; Graft Rejection/etiology ; Humans ; Lung ; Tissue Donors ; Transplant Recipients
Chemical Substances	Cell-Free Nucleic Acids
Language	English
Publishing date	2022-06-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	639435-8
ISSN	1432-2277 ; 0934-0874
ISSN (online)	1432-2277
ISSN	0934-0874
DOI	10.3389/ti.2022.10546
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Article ; Online: Rs12778366 single nucleotide polymorphism of Sirtuin 1 (SIRT1) and response to resveratrol supplementation in patients with type 2 diabetes mellitus.

Gambino, Roberto / Fanni, Giovanni / Togliatto, Gabriele / Ponzo, Valentina / Goitre, Ilaria / Cassader, Maurizio / Brizzi, Maria Felice / Bo, Simona

Acta diabetologica

2019 Volume 56, Issue 8, Page(s) 963–966

MeSH term(s)	Aged ; Case-Control Studies ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/metabolism ; Dietary Supplements/analysis ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Resveratrol/administration & dosage ; Sirtuin 1/genetics ; Sirtuin 1/metabolism
Chemical Substances	SIRT1 protein, human (EC 3.5.1.-) ; Sirtuin 1 (EC 3.5.1.-) ; Resveratrol (Q369O8926L)
Language	English
Publishing date	2019-04-12
Publishing country	Germany
Document type	Journal Article ; Observational Study
ZDB-ID	1097676-0
ISSN	1432-5233 ; 0940-5429
ISSN (online)	1432-5233
ISSN	0940-5429
DOI	10.1007/s00592-019-01341-6
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Article ; Online: Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes.

Pomatto, Margherita / Gai, Chiara / Negro, Federica / Cedrino, Massimo / Grange, Cristina / Ceccotti, Elena / Togliatto, Gabriele / Collino, Federica / Tapparo, Marta / Figliolini, Federico / Lopatina, Tatiana / Brizzi, Maria Felice / Camussi, Giovanni

International journal of molecular sciences

2021 Volume 22, Issue 8

Abstract: Extracellular vesicles (EVs) derived from mesenchymal stem cells isolated from both bone marrow (BMSCs) and adipose tissue (ADSCs) show potential therapeutic effects. These vesicles often show a similar beneficial effect on tissue regeneration, but in ... ...

Abstract	Extracellular vesicles (EVs) derived from mesenchymal stem cells isolated from both bone marrow (BMSCs) and adipose tissue (ADSCs) show potential therapeutic effects. These vesicles often show a similar beneficial effect on tissue regeneration, but in some contexts, they exert different biological properties. To date, a comparison of their molecular cargo that could explain the different biological effect is not available. Here, we demonstrated that ADSC-EVs, and not BMSC-EVs, promote wound healing on a murine model of diabetic wounds. Besides a general similarity, the bioinformatic analysis of their protein and miRNA cargo highlighted important differences between these two types of EVs. Molecules present exclusively in ADSC-EVs were highly correlated to angiogenesis, whereas those expressed in BMSC-EVs were preferentially involved in cellular proliferation. Finally, in vitro analysis confirmed that both ADSC and BMSC-EVs exploited beneficial effect on cells involved in skin wound healing such as fibroblasts, keratinocytes and endothelial cells, but through different cellular processes. Consistent with the bioinformatic analyses, BMSC-EVs were shown to mainly promote proliferation, whereas ADSC-EVs demonstrated a major effect on angiogenesis. Taken together, these results provide deeper comparative information on the cargo of ADSC-EVs and BMSC-EVs and the impact on regenerative processes essential for diabetic wound healing.
MeSH term(s)	Adipose Tissue/cytology ; Animals ; Bone Marrow Cells ; Diabetes Complications/therapy ; Exosomes/metabolism ; Exosomes/ultrastructure ; Extracellular Vesicles/metabolism ; Extracellular Vesicles/ultrastructure ; Flow Cytometry ; Gene Expression Profiling ; Immunohistochemistry ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Mice ; Ulcer/etiology ; Ulcer/therapy ; Wound Healing
Language	English
Publishing date	2021-04-08
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/ijms22083851
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Article ; Online: Renal Regenerative Potential of Extracellular Vesicles Derived from miRNA-Engineered Mesenchymal Stromal Cells.

Tapparo, Marta / Bruno, Stefania / Collino, Federica / Togliatto, Gabriele / Deregibus, Maria Chiara / Provero, Paolo / Wen, Sicheng / Quesenberry, Peter J / Camussi, Giovanni

International journal of molecular sciences

2019 Volume 20, Issue 10

Abstract: Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) possess pro-regenerative potential in different animal models with renal injury. EVs contain different molecules, including proteins, lipids and nucleic acids. Among the shuttled ... ...

Abstract	Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) possess pro-regenerative potential in different animal models with renal injury. EVs contain different molecules, including proteins, lipids and nucleic acids. Among the shuttled molecules, miRNAs have a relevant role in the pro-regenerative effects of EVs and are a promising target for therapeutic interventions. The aim of this study was to increase the content of specific miRNAs in EVs that are known to be involved in the pro-regenerative effect of EVs, and to assess the capacity of modified EVs to contribute to renal regeneration in in vivo models with acute kidney injuries. To this purpose, MSCs were transiently transfected with specific miRNA mimics by electroporation. Molecular analyses showed that, after transfection, MSCs and derived EVs were efficiently enriched in the selected miRNAs. In vitro and in vivo experiments indicated that EVs engineered with miRNAs maintained their pro-regenerative effects. Of relevance, engineered EVs were more effective than EVs derived from naïve MSCs when used at suboptimal doses. This suggests the potential use of a low amount of EVs (82.5 × 10
MeSH term(s)	Acute Kidney Injury/therapy ; Animals ; Cells, Cultured ; Extracellular Vesicles/genetics ; Extracellular Vesicles/transplantation ; Humans ; Male ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/metabolism ; Mice ; Mice, SCID ; MicroRNAs/genetics ; MicroRNAs/metabolism ; RNAi Therapeutics/methods ; Regeneration
Chemical Substances	MicroRNAs
Language	English
Publishing date	2019-05-14
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/ijms20102381
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Article ; Online: Differential Therapeutic Effect of Extracellular Vesicles Derived by Bone Marrow and Adipose Mesenchymal Stem Cells on Wound Healing of Diabetic Ulcers and Correlation to Their Cargoes

Margherita Pomatto / Chiara Gai / Federica Negro / Massimo Cedrino / Cristina Grange / Elena Ceccotti / Gabriele Togliatto / Federica Collino / Marta Tapparo / Federico Figliolini / Tatiana Lopatina / Maria Felice Brizzi / Giovanni Camussi

International Journal of Molecular Sciences, Vol 22, Iss 3851, p

2021 Volume 3851

Abstract	Extracellular vesicles (EVs) derived from mesenchymal stem cells isolated from both bone marrow (BMSCs) and adipose tissue (ADSCs) show potential therapeutic effects. These vesicles often show a similar beneficial effect on tissue regeneration, but in some contexts, they exert different biological properties. To date, a comparison of their molecular cargo that could explain the different biological effect is not available. Here, we demonstrated that ADSC-EVs, and not BMSC-EVs, promote wound healing on a murine model of diabetic wounds. Besides a general similarity, the bioinformatic analysis of their protein and miRNA cargo highlighted important differences between these two types of EVs. Molecules present exclusively in ADSC-EVs were highly correlated to angiogenesis, whereas those expressed in BMSC-EVs were preferentially involved in cellular proliferation. Finally, in vitro analysis confirmed that both ADSC and BMSC-EVs exploited beneficial effect on cells involved in skin wound healing such as fibroblasts, keratinocytes and endothelial cells, but through different cellular processes. Consistent with the bioinformatic analyses, BMSC-EVs were shown to mainly promote proliferation, whereas ADSC-EVs demonstrated a major effect on angiogenesis. Taken together, these results provide deeper comparative information on the cargo of ADSC-EVs and BMSC-EVs and the impact on regenerative processes essential for diabetic wound healing.
Keywords	wound healing ; MSC ; exosome ; extracellular vesicle ; diabetes ; adipose ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571 ; 500
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Renal Regenerative Potential of Extracellular Vesicles Derived from miRNA-Engineered Mesenchymal Stromal Cells

Marta Tapparo / Stefania Bruno / Federica Collino / Gabriele Togliatto / Maria Chiara Deregibus / Paolo Provero / Sicheng Wen / Peter J. Quesenberry / Giovanni Camussi

International Journal of Molecular Sciences, Vol 20, Iss 10, p

2019 Volume 2381

Abstract	Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) possess pro-regenerative potential in different animal models with renal injury. EVs contain different molecules, including proteins, lipids and nucleic acids. Among the shuttled molecules, miRNAs have a relevant role in the pro-regenerative effects of EVs and are a promising target for therapeutic interventions. The aim of this study was to increase the content of specific miRNAs in EVs that are known to be involved in the pro-regenerative effect of EVs, and to assess the capacity of modified EVs to contribute to renal regeneration in in vivo models with acute kidney injuries. To this purpose, MSCs were transiently transfected with specific miRNA mimics by electroporation. Molecular analyses showed that, after transfection, MSCs and derived EVs were efficiently enriched in the selected miRNAs. In vitro and in vivo experiments indicated that EVs engineered with miRNAs maintained their pro-regenerative effects. Of relevance, engineered EVs were more effective than EVs derived from naïve MSCs when used at suboptimal doses. This suggests the potential use of a low amount of EVs (82.5 × 10 6 ) to obtain the renal regenerative effect.
Keywords	mesenchymal stromal cells ; extracellular vesicles ; acute kidney injury ; modified-MSCs ; microRNA ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	500 ; 616
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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