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Article ; Online: Preliminary Comparison of Fractional Absorption of Zinc Sulphate, Zinc Gluconate, and Zinc Aspartate after Oral Supple-Mentation in Healthy Human Volunteers.

Piacenza, Francesco / Giacconi, Robertina / Costarelli, Laura / Malavolta, Marco

2023 Volume 15, Issue 8

Abstract: 1) Background: Zinc is generally used as a nutritional supplement for individuals at nutritional risk, such as older adults. This preliminary study investigated the fractional Zn absorption (FZA) after the supplementation on eight healthy volunteers ... ...

Abstract	(1) Background: Zinc is generally used as a nutritional supplement for individuals at nutritional risk, such as older adults. This preliminary study investigated the fractional Zn absorption (FZA) after the supplementation on eight healthy volunteers with three different Zn complexes acquired with milk. (2) Methods: The design was a double-blind, three-period crossover trial. The volunteers were randomly divided into three groups. Each individual consumed 200 mL of bovine milk and rotated through a simultaneous administration of a single oral dose of
MeSH term(s)	Humans ; Aged ; Zinc Sulfate ; Healthy Volunteers ; Aspartic Acid ; Intestinal Absorption ; Zinc ; Gluconates
Chemical Substances	Zinc Sulfate (7733-02-0) ; zinc aspartate (4OC7QTI23H) ; Aspartic Acid (30KYC7MIAI) ; Zinc (J41CSQ7QDS) ; Gluconates
Language	English
Publishing date	2023-04-13
Publishing country	Switzerland
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15081885
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Article ; Online: Early Benefits with Potential Long-Term Risks of a Comprehensive Intervention on Serum Cortisol Levels and Cognitive Performance in Patients with Alzheimer's Disease.

Balietti, Marta / Galeazzi, Roberta / Giacconi, Robertina / Santillo, Elpidio / Giuli, Cinzia

Journal of Alzheimer's disease reports

2023 Volume 7, Issue 1, Page(s) 1445–1453

Abstract: Background: Elevated cortisol levels represent a risk factor for Alzheimer's disease (AD), prompting treatments to lower hormone concentrations for preventive or therapeutic purposes.: Objective: To assess the efficacy of a comprehensive intervention ...

Abstract	Background: Elevated cortisol levels represent a risk factor for Alzheimer's disease (AD), prompting treatments to lower hormone concentrations for preventive or therapeutic purposes. Objective: To assess the efficacy of a comprehensive intervention (CI) in modulating serum cortisol levels in patients with AD. Methods: CI consisted in a 2-month protocol involving cognitive stimulation, psychological support, lifestyle guidance, leisure activities, and socialization. AD subjects were randomly assigned to experimental (EG, Results: Baseline evaluations revealed that higher cortisol levels correlated with worse cognitive status (higher CDR and ADAS-Cog values and lower MMSE scores), increased depressive symptoms, and reduced physical and social engagement. Following CI, EG exhibited reduced cortisol levels, improved overall cognitive status, and enhanced verbal working memory and executive functions compared to CG. However, at the 24-month follow-up, EG displayed a rebound effect, characterized by elevated cortisol levels and cognitive decline compared to CG. Conclusions: These findings strengthen the adverse relationship between excessive cortisol and deficits in cognition/behavior in AD, demonstrate the short-term benefits of CI, and emphasize the potential long-term risks, which may be attributed to the fragile nature of the AD brain. Comprehensive interventions can yield positive results, but careful calibration of type and duration is necessary, considering disease progression and the potential need for re-administration.
Language	English
Publishing date	2023-12-29
Publishing country	Netherlands
Document type	Journal Article
ISSN	2542-4823
ISSN (online)	2542-4823
DOI	10.3233/ADR-230125
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Article ; Online: Platelet Total PLA

Balietti, Marta / Casoli, Tiziana / Giacconi, Robertina / Giuli, Cinzia

Rejuvenation research

2021 Volume 25, Issue 1, Page(s) 16–24

Abstract: Alzheimer's disease (AD) has no cure, mainly because of late diagnosis. Early diagnostic biomarkers are crucial. Phospholipases ... ...

Abstract	Alzheimer's disease (AD) has no cure, mainly because of late diagnosis. Early diagnostic biomarkers are crucial. Phospholipases A
MeSH term(s)	Aged ; Alzheimer Disease/diagnosis ; Alzheimer Disease/pathology ; Biomarkers ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/etiology ; Copper/blood ; Disease Progression ; Humans ; Oxidative Stress ; Phospholipases A2/metabolism ; Zinc/blood
Chemical Substances	Biomarkers ; Copper (789U1901C5) ; Phospholipases A2 (EC 3.1.1.4) ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2021-12-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2150779-X
ISSN	1557-8577 ; 1549-1684
ISSN (online)	1557-8577
ISSN	1549-1684
DOI	10.1089/rej.2021.0020
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Article ; Online: Spreading Senescent Cells' Burden and Emerging Therapeutic Targets for Frailty.

Marcozzi, Serena / Bigossi, Giorgia / Giuliani, Maria Elisa / Lai, Giovanni / Giacconi, Robertina / Piacenza, Francesco / Malavolta, Marco

Cells

2023 Volume 12, Issue 18

Abstract: The spreading of senescent cells' burden holds profound implications for frailty, prompting the exploration of novel therapeutic targets. In this perspective review, we delve into the intricate mechanisms underlying senescent cell spreading, its ... ...

Abstract	The spreading of senescent cells' burden holds profound implications for frailty, prompting the exploration of novel therapeutic targets. In this perspective review, we delve into the intricate mechanisms underlying senescent cell spreading, its implications for frailty, and its therapeutic development. We have focused our attention on the emerging age-related biological factors, such as microbiome and virome alterations, elucidating their significant contribution to the loss of control over the accumulation rate of senescent cells, particularly affecting key frailty domains, the musculoskeletal system and cerebral functions. We believe that gaining an understanding of these mechanisms could not only aid in elucidating the involvement of cellular senescence in frailty but also offer diverse therapeutic possibilities, potentially advancing the future development of tailored interventions for these highly diverse patients.
MeSH term(s)	Humans ; Frailty ; Age Factors ; Cellular Senescence ; Microbiota
Language	English
Publishing date	2023-09-15
Publishing country	Switzerland
Document type	Journal Article ; 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/cells12182287
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Article ; Online: Plasma cfDNA abundance as a prognostic biomarker for higher risk of death in geriatric cardiovascular patients.

Cardelli, Maurizio / Marchegiani, Francesca / Stripoli, Pierpaolo / Piacenza, Francesco / Recchioni, Rina / Di Rosa, Mirko / Giacconi, Robertina / Malavolta, Marco / Galeazzi, Roberta / Arosio, Beatrice / Cafarelli, Fiammetta / Spannella, Francesco / Cherubini, Antonio / Lattanzio, Fabrizia / Olivieri, Fabiola

Mechanisms of ageing and development

2024 Volume 219, Page(s) 111934

Abstract: The management of geriatric cardiovascular disease (CVD) patients with multimorbidity remains challenging and could potentially be improved by integrating clinical data with innovative prognostic biomarkers. In this context, the analysis of circulating ... ...

Abstract	The management of geriatric cardiovascular disease (CVD) patients with multimorbidity remains challenging and could potentially be improved by integrating clinical data with innovative prognostic biomarkers. In this context, the analysis of circulating analytes, including cell-free DNA (cfDNA), appears particularly promising. Here, we investigated circulating cfDNA (measured through the quantification of 247 bp and 115 bp Alu genomic fragments) in a cohort of 244 geriatric CVD patients with multimorbidity hospitalised for acute CVD or non-CVD events. Survival analysis showed a direct association between Alu 247 cfDNA abundance and risk of death, particularly evident in the first six months after admission for acute CVD events. Higher plasma cfDNA concentration was associated with mortality in the same period of time. The cfDNA integrity (Alu 247/115), although not associated with outcome, appeared to be useful in discriminating patients in whom Alu 247 cfDNA abundance is most effective as a prognostic biomarker. The cfDNA parameters were associated with several biochemical markers of inflammation and myocardial damage. In conclusion, an increase in plasma cfDNA abundance at hospital admission is indicative of a higher risk of death in geriatric CVD patients, especially after acute CVD events, and its analysis may be potentially useful for risk stratification.
Language	English
Publishing date	2024-04-09
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	183915-9
ISSN	1872-6216 ; 0047-6374
ISSN (online)	1872-6216
ISSN	0047-6374
DOI	10.1016/j.mad.2024.111934
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Zs.A 1012: Show issues

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Article ; Online: Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats.

Malavolta, Marco / Giacconi, Robertina / Brunetti, Dario / Provinciali, Mauro / Maggi, Fabrizio

Cells

2020 Volume 9, Issue 4

Abstract: The higher death rate caused by COVID-19 in older people, especially those with comorbidities, is a challenge for biomedical aging research. Here we explore the idea that an exacerbated inflammatory response, in particular that mediated by IL-6, may ... ...

Abstract	The higher death rate caused by COVID-19 in older people, especially those with comorbidities, is a challenge for biomedical aging research. Here we explore the idea that an exacerbated inflammatory response, in particular that mediated by IL-6, may drive the deleterious consequences of the infection. Data shows that other RNA viruses, such as influenza virus, can display enhanced replication efficiency in senescent cells, suggesting that the accumulation of senescent cells with aging and age-related diseases may play a role in this phenomenon. However, at present, we are completely unaware of the response to SARS-CoV and SARS-COV-2 occurring in senescent cells. We deem that this is a priority area of research because it could lead to the development of several therapeutic strategies based on senotherapeutics or prevent unsuccessful attempts. Two of these senotherapeutics, azithromycin and ruxolitinib, are currently undergoing testing for their efficacy in treating COVID-19. The potential of these strategies is not only for ameliorating the consequences of the current emergence of SARS-CoV-2, but also for the future emergence of new viruses or mutated ones for which we are completely unprepared and for which no vaccines are available.
MeSH term(s)	Aging/immunology ; Anti-Infective Agents/standards ; Anti-Infective Agents/therapeutic use ; Azithromycin/therapeutic use ; COVID-19 ; Cellular Senescence/immunology ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Global Health/trends ; Humans ; Interleukin-6/immunology ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; Pyrazoles/therapeutic use
Chemical Substances	Anti-Infective Agents ; Interleukin-6 ; Pyrazoles ; ruxolitinib (82S8X8XX8H) ; Azithromycin (83905-01-5)
Keywords	covid19
Language	English
Publishing date	2020-04-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9040909
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Article ; Online: Psycho-cognitive assessment and quality of life in older adults with chronic obstructive pulmonary disease-carrying the rs4713916 gene polymorphism (G/A) of gene FKBP5 and response to pulmonary rehabilitation: a proof of concept study.

Marcolongo, Federica / Scarlata, Simone / Tomino, Carlo / De Dominicis, Chiara / Giacconi, Robertina / Malavolta, Marco / Bonassi, Stefano / Russo, Patrizia / Prinzi, Giulia

Psychiatric genetics

2022 Volume 32, Issue 3, Page(s) 116–124

Abstract: Purpose: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and extra-pulmonary multi-morbidity including depression, anxiety and cognitive disorders. Several studies investigated the association of the FKBP5 gene polymorphisms ... ...

Abstract	Purpose: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and extra-pulmonary multi-morbidity including depression, anxiety and cognitive disorders. Several studies investigated the association of the FKBP5 gene polymorphisms with susceptibility to anxiety, depression, and behavioral disorders. The FKBP5 gene codifies the FKBP51 protein which modulates the glucocorticoid receptor in the adaptive stress response. Genetic variants of the FKBP5 gene have been associated to a higher risk of developing mental disorders. We analyzed the association of genetic variants and stress exposure investigating the susceptibility to psychological distress and the impact on cognitive balance and quality of life (QoL) of COPD patients carrying the rs4713916 polymorphism (G/A) and we examined its association, with COPD rehabilitative outcomes. Materials and methods: A pilot study evaluated cognitive, psychological, clinical alterations/disorders, QoL, and coping strategies in 70 older adults with COPD, undergoing pulmonary rehabilitation, stratified according to the FKBP5 rs4713916 genotype (GG or GA). Results: Carriers of rs4713916 polymorphisms (G/A) show better cognitive performances, a higher degree of independence in the daily living activities, better QoL, no presence of depressive mood and anxiety symptoms, no family history of psychiatric disorders, more ability to cope with stressors by avoiding emotions but demanding emotional support, and lesser use of anti-anxiety, anti-depressant, anti-psychotic, hypnotic-sedative drugs. No difference was found in the number of comorbidities. Conclusion: These results offer valuable insights into the role of FKBP5 in the complex network of mechanisms associated to clinical, psychological and behavioral features of COPD patients.
MeSH term(s)	Aged ; Cognition ; Humans ; Pilot Projects ; Polymorphism, Single Nucleotide/genetics ; Proof of Concept Study ; Pulmonary Disease, Chronic Obstructive/genetics ; Pulmonary Disease, Chronic Obstructive/psychology ; Pulmonary Disease, Chronic Obstructive/rehabilitation ; Quality of Life ; Tacrolimus Binding Proteins/genetics
Chemical Substances	Tacrolimus Binding Proteins (EC 5.2.1.-) ; tacrolimus binding protein 5 (EC 5.2.1.8)
Language	English
Publishing date	2022-01-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1067837-2
ISSN	1473-5873 ; 0955-8829
ISSN (online)	1473-5873
ISSN	0955-8829
DOI	10.1097/YPG.0000000000000308
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Article ; Online: Association of Inflammatory Mediators with Mitochondrial DNA Variants in Geriatric COVID-19 Patients.

Casoli, Tiziana / Bonfigli, Anna Rita / Rosa, Mirko Di / Giorgetti, Belinda / Balietti, Marta / Giacconi, Robertina / Cardelli, Maurizio / Piacenza, Francesco / Marchegiani, Francesca / Marcheselli, Fiorella / Recchioni, Rina / Galeazzi, Roberta / Vaiasicca, Salvatore / Lamedica, Adrianapia Maria / Fumagalli, Alessia / Ferrara, Letizia / Lattanzio, Fabrizia

Aging and disease

2024

Abstract: COVID-19 remains a serious concern for elderly individuals with underlying comorbidities. SARS-CoV-2 can target and damage mitochondria, potentially leading to mutations in mitochondrial DNA (mtDNA). This study aimed to evaluate single nucleotide ... ...

Abstract	COVID-19 remains a serious concern for elderly individuals with underlying comorbidities. SARS-CoV-2 can target and damage mitochondria, potentially leading to mutations in mitochondrial DNA (mtDNA). This study aimed to evaluate single nucleotide substitutions in mtDNA and analyze their correlation with inflammatory biomarkers in elderly COVID-19 patients. A total of 30 COVID-19 patients and 33 older adult controls without COVID-19 (aged over 65 years) were enrolled. mtDNA was extracted from buffy coat samples and sequenced using a chip-based resequencing system (MitoChip v2.0) which detects both homoplasmic and heteroplasmic mtDNA variants (40-60% heteroplasmy), and allows the assessment of low-level heteroplasmy (<10% heteroplasmy). Serum concentrations of IL-6, IFN-α, TNF-α and IL-10 were determined in patients by a high-sensitivity immunoassay. We found a higher burden of total heteroplasmic variants in COVID-19 patients compared to controls with a selective increment in ND1 and COIII genes. Low-level heteroplasmy was significantly elevated in COVID-19 patients, especially in genes of the respiratory complex I. Both heteroplasmic variant burden and low-level heteroplasmy were associated with increased levels of IL-6, TNF-α, and IFN-α. These findings suggest that SARS-CoV-2 may induce mtDNA mutations that are related to the degree of inflammation.
Language	English
Publishing date	2024-02-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2625789-0
ISSN	2152-5250 ; 2152-5250
ISSN (online)	2152-5250
ISSN	2152-5250
DOI	10.14336/AD.2023.1123
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Article ; Online: Effects of Human LAV-BPIFB4 Gene Therapy on the Epigenetic Clock and Health of Aged Mice.

Giuliani, Maria Elisa / Barbi, Veronica / Bigossi, Giorgia / Marcozzi, Serena / Giacconi, Robertina / Cardelli, Maurizio / Piacenza, Francesco / Orlando, Fiorenza / Ciaglia, Elena / Cattaneo, Monica / Mongelli, Alessia / Gaetano, Carlo / Provinciali, Mauro / Puca, Annibale Alessandro / Malavolta, Marco

International journal of molecular sciences

2023 Volume 24, Issue 7

Abstract: The homozygous genotype of the Longevity-Associated Variant (LAV) in Bactericidal/Permeability-Increasing Fold-Containing Family B member 4 (BPIFB4) is enriched in long-living individuals of three independent populations and its genetic transfer in C57BL/ ...

Abstract	The homozygous genotype of the Longevity-Associated Variant (LAV) in Bactericidal/Permeability-Increasing Fold-Containing Family B member 4 (BPIFB4) is enriched in long-living individuals of three independent populations and its genetic transfer in C57BL/6J mice showed a delay in frailty progression and improvement of several biomarkers of aging and multiple aspects of health. The C57BL/6J strain is a suitable model for studying therapies aimed at extending healthy aging and longevity due to its relatively short lifespan and the availability of aging biomarkers. Epigenetic clocks based on DNA methylation profiles are reliable molecular biomarkers of aging, while frailty measurement tools are used to evaluate overall health during aging. In this study, we show that the systemic gene transfer of LAV-BPIFB4 in aged C57BL/6J mice was associated with a significant reduction in the epigenetic clock-based biological age, as measured by a three CpG clock method. Furthermore, LAV-BPIFB4 gene transfer resulted in an improvement of the Vitality Score with a reduction in the Frailty Index. These findings further support the use of LAV-BPIFB4 gene therapy to induce beneficial effects on epigenetic mechanisms associated with aging and frailty in aged mice, with potential implications for future therapies to prevent frailty in humans.
MeSH term(s)	Humans ; Mice ; Animals ; Aged ; Longevity/genetics ; Frailty/genetics ; Mice, Inbred C57BL ; Epigenesis, Genetic ; Biomarkers ; Genetic Therapy ; DNA Methylation ; Intercellular Signaling Peptides and Proteins/genetics
Chemical Substances	Biomarkers ; BPIFB4 protein, human ; Intercellular Signaling Peptides and Proteins
Language	English
Publishing date	2023-03-30
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/ijms24076464
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Article ; Online: Dysfunctional macrophages in Alzheimer Disease: another piece of the "macroph-aging" puzzle?

Costarelli, Laura / Malavolta, Marco / Giacconi, Robertina / Provinciali, Mauro

Aging

2017 Volume 9, Issue 8, Page(s) 1865–1866

MeSH term(s)	Alzheimer Disease ; Amyloid beta-Peptides ; Animals ; Cyclin-Dependent Kinase Inhibitor p16 ; Macrophages ; Mice ; beta-Galactosidase
Chemical Substances	Amyloid beta-Peptides ; Cyclin-Dependent Kinase Inhibitor p16 ; beta-Galactosidase (EC 3.2.1.23)
Language	English
Publishing date	2017-08-21
Publishing country	United States
Document type	Journal Article ; Comment
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.101276
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