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  1. Article: Role of

    Ciarambino, Tiziana / Crispino, Pietro / Minervini, Giovanni / Giordano, Mauro

    Biomedicines

    2024  Volume 12, Issue 2

    Abstract: The therapeutic management of atherosclerosis focuses almost exclusively on the reduction of plasma cholesterol levels. An important role in the genesis and evolution of atherosclerosis is played by chronic inflammation in promoting thrombosis phenomena ... ...

    Abstract The therapeutic management of atherosclerosis focuses almost exclusively on the reduction of plasma cholesterol levels. An important role in the genesis and evolution of atherosclerosis is played by chronic inflammation in promoting thrombosis phenomena after atheroma rupture. This review aims to take stock of the knowledge so far accumulated on the role of endemic HP infection in atherosclerosis. The studies produced so far have demonstrated a causal relationship between Helicobacter pylori (HP) and CVD. In a previous study, we demonstrated in HP-positive patients that thrombin and plasma fragment 1 + 2 production was proportionally related to tumor necrosis factor-alpha levels and that eradication of the infection resulted in a reduction of inflammation. At the end of our review, we can state that HP slightly affects the risk of CVD, particularly if the infection is associated with cytotoxic damage, and HP screening could have a clinically significant role in patients with a high risk of CVD. Considering the high prevalence of HP infection, an infection screening could be of great clinical utility in patients at high risk of CVD.
    Language English
    Publishing date 2024-02-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines12020400
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Cerebral Sinus Vein Thrombosis and Gender: A Not Entirely Casual Relationship.

    Ciarambino, Tiziana / Crispino, Pietro / Minervini, Giovanni / Giordano, Mauro

    Biomedicines

    2023  Volume 11, Issue 5

    Abstract: Cerebral sinus venous thrombosis (CSVT) is a relatively rare acute disorder of cerebral circulation, but it can potentially be associated with serious sequelae and a poor prognosis. The neurological manifestations associated with it are often not ... ...

    Abstract Cerebral sinus venous thrombosis (CSVT) is a relatively rare acute disorder of cerebral circulation, but it can potentially be associated with serious sequelae and a poor prognosis. The neurological manifestations associated with it are often not adequately taken into consideration given the extreme variability and nuances of its clinical presentation and given the need for radiological methods suitable for this type of diagnosis. CSVT is usually more common in women, but so far there are little data available in the literature on sex-specific characteristics regarding this pathology. CSVT is the result of multiple conditions and is therefore to be considered a multifactorial disease where at least one risk factor is present in over 80% of cases. From the literature, we learn that congenital or acquired prothrombotic states are to be considered extremely associated with the occurrence of an acute episode of CSVT and its recurrences. It is, therefore, necessary to fully know the origins and natural history of CSVT, in order to implement the diagnostic and therapeutic pathways of these neurological manifestations. In this report, we summarize the main causes of CSVT considering the possible influence of gender, bearing in mind that most of the causes listed above are pathological conditions closely linked to the female sex.
    Language English
    Publishing date 2023-04-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11051280
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: COVID-19 and Frailty.

    Ciarambino, Tiziana / Crispino, Pietro / Minervini, Giovanni / Giordano, Mauro

    Vaccines

    2023  Volume 11, Issue 3

    Abstract: Older age is a major risk factor for adverse outcomes of COVID-19, potentially due to immunosenescence and chronic low-grade inflammation, both characteristics of older adults which synergistically contribute to their vulnerability. Furthermore, older ... ...

    Abstract Older age is a major risk factor for adverse outcomes of COVID-19, potentially due to immunosenescence and chronic low-grade inflammation, both characteristics of older adults which synergistically contribute to their vulnerability. Furthermore, older age is also associated with decreased kidney function and is consequently associated with an increased risk of cardiovascular disease. All of this in the course of COVID-19 infection can worsen and promote the progression of chronic kidney damage and all its sequelae. Frailty is a condition characterized by the decline in function of several homeostatic systems, leading to increased vulnerability to stressors and risk of adverse health outcomes. Thus, it is very likely that frailty, together with comorbidities, may have contributed to the high vulnerability to severe clinical manifestations and deaths from COVID-19 among older people. The combination of viral infection and chronic inflammation in the elderly could cause multiple unforeseen harmful consequences, affecting overall disability and mortality rates. In post-COVID-19 patients, inflammation has been implicated in sarcopenia progression, functional activity decline, and dementia. After the pandemic, it is imperative to shine a spotlight on these sequelae so that we can be prepared for the future outcomes of the ongoing pandemic. Here, we discuss the potential long-term consequences of SARS-CoV-2 infection and its possibility of causing permanent damage to the precarious balance existing in the frail elderly with multiple pathologies.
    Language English
    Publishing date 2023-03-07
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines11030606
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Structural Characterization of Hypoxia Inducible Factor α-Prolyl Hydroxylase Domain 2 Interaction through MD Simulations.

    Camagni, Giorgia F / Minervini, Giovanni / Tosatto, Silvio C E

    International journal of molecular sciences

    2023  Volume 24, Issue 5

    Abstract: The Prolyl Hydroxylases (PHDs) are an enzymatic family that regulates cell oxygen-sensing. PHDs hydroxylate hypoxia-inducible transcription factors α (HIFs-α) driving their proteasomal degradation. Hypoxia inhibits PHDs activity, inducing HIFs-α ... ...

    Abstract The Prolyl Hydroxylases (PHDs) are an enzymatic family that regulates cell oxygen-sensing. PHDs hydroxylate hypoxia-inducible transcription factors α (HIFs-α) driving their proteasomal degradation. Hypoxia inhibits PHDs activity, inducing HIFs-α stabilization and cell adaptation to hypoxia. As a hallmark of cancer, hypoxia promotes neo-angiogenesis and cell proliferation. PHD isoforms are thought to have a variable impact on tumor progression. All isoforms hydroxylate HIF-α (HIF-1,2,3α) with different affinities. However, what determines these differences and how they pair with tumor growth is poorly understood. Here, molecular dynamics simulations were used to characterize the PHD2 binding properties in complexes with HIF-1α and HIF-2α. In parallel, conservation analysis and binding free energy calculations were performed to better understand PHD2 substrate affinity. Our data suggest a direct association between the PHD2 C-terminus and HIF-2α that is not observed in the PHD2/HIF-1α complex. Furthermore, our results indicate that phosphorylation of a PHD2 residue, Thr405, causes a variation in binding energy, despite the fact that this PTM has only a limited structural impact on PHD2/HIFs-α complexes. Collectively, our findings suggest that the PHD2 C-terminus may act as a molecular regulator of PHD's activity.
    MeSH term(s) Humans ; Cell Line, Tumor ; Hypoxia/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/chemistry ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Prolyl Hydroxylases/chemistry ; Protein Isoforms/chemistry ; Protein Isoforms/metabolism ; Protein Domains
    Chemical Substances Hypoxia-Inducible Factor 1, alpha Subunit ; Prolyl Hydroxylases (EC 1.14.11.-) ; Protein Isoforms
    Language English
    Publishing date 2023-03-01
    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/ijms24054710
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Vitamin D: Can Gender Medicine Have a Role?

    Ciarambino, Tiziana / Crispino, Pietro / Minervini, Giovanni / Giordano, Mauro

    Biomedicines

    2023  Volume 11, Issue 6

    Abstract: This narrative review aims to shed light on the role of gender differences, on the biological and molecular functions in the main pathological mechanisms that recognize the role of vitamin D. Vitamin D deficiency is widespread worldwide, but it is still ... ...

    Abstract This narrative review aims to shed light on the role of gender differences, on the biological and molecular functions in the main pathological mechanisms that recognize the role of vitamin D. Vitamin D deficiency is widespread worldwide, but it is still very controversial whether the amount of vitamin D taken daily is actually the only problem related to its biological functions. Currently, the plasma concentration of 25-hydroxyvitamin D represents the only indicator of the circulating blood quota. The concept is that the biological function of vitamin D is not only linked to its circulating levels, but it is hypothesized that its biological functions depend, above all, on its total bioavailability. In particular, vitamin D circulates for the most part linked to albumin and vitamin D binding protein (DBP), which depend on various pathological conditions and physiologically, above all, the function of the latter is regulated by estrogens, glucocorticoids, and inflammatory cytokines. During her life, women undergo various changes in the hormonal and sexual sphere concerning menarche, possible pregnancies, and breastfeeding but also the use of contraceptives and, finally, the transition from the period of fertility to menopause. Each of these phases presents specific needs and, consequently, sometimes also specific criticalities. Studies on young women have shown that vitamin D deficiency is present in 58 to 91% of cases. Obesity, metabolic disorders, and variation in estrogen contraction may affect vitamin D deficiency due to the decreased bioavailability from dietary sources due to deposition in body fat compartments.
    Language English
    Publishing date 2023-06-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11061762
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Molecular Effects of Mutations in Human Genetic Diseases.

    Leonardi, Emanuela / Savojardo, Castrense / Minervini, Giovanni

    International journal of molecular sciences

    2022  Volume 23, Issue 12

    Abstract: Next-generation sequencing (NGS) has enormously improved the identification of disease-candidate genetic variants [ ... ]. ...

    Abstract Next-generation sequencing (NGS) has enormously improved the identification of disease-candidate genetic variants [...].
    MeSH term(s) High-Throughput Nucleotide Sequencing ; Humans ; Mutation
    Language English
    Publishing date 2022-06-08
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23126408
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: COVID-19 and Frailty

    Tiziana Ciarambino / Pietro Crispino / Giovanni Minervini / Mauro Giordano

    Vaccines, Vol 11, Iss 606, p

    2023  Volume 606

    Abstract: Older age is a major risk factor for adverse outcomes of COVID-19, potentially due to immunosenescence and chronic low-grade inflammation, both characteristics of older adults which synergistically contribute to their vulnerability. Furthermore, older ... ...

    Abstract Older age is a major risk factor for adverse outcomes of COVID-19, potentially due to immunosenescence and chronic low-grade inflammation, both characteristics of older adults which synergistically contribute to their vulnerability. Furthermore, older age is also associated with decreased kidney function and is consequently associated with an increased risk of cardiovascular disease. All of this in the course of COVID-19 infection can worsen and promote the progression of chronic kidney damage and all its sequelae. Frailty is a condition characterized by the decline in function of several homeostatic systems, leading to increased vulnerability to stressors and risk of adverse health outcomes. Thus, it is very likely that frailty, together with comorbidities, may have contributed to the high vulnerability to severe clinical manifestations and deaths from COVID-19 among older people. The combination of viral infection and chronic inflammation in the elderly could cause multiple unforeseen harmful consequences, affecting overall disability and mortality rates. In post-COVID-19 patients, inflammation has been implicated in sarcopenia progression, functional activity decline, and dementia. After the pandemic, it is imperative to shine a spotlight on these sequelae so that we can be prepared for the future outcomes of the ongoing pandemic. Here, we discuss the potential long-term consequences of SARS-CoV-2 infection and its possibility of causing permanent damage to the precarious balance existing in the frail elderly with multiple pathologies.
    Keywords SARS-CoV-2 infection ; COVID-19 ; elderly ; frailty ; pandemic ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Vitamin D

    Tiziana Ciarambino / Pietro Crispino / Giovanni Minervini / Mauro Giordano

    Biomedicines, Vol 11, Iss 1762, p

    Can Gender Medicine Have a Role?

    2023  Volume 1762

    Abstract: This narrative review aims to shed light on the role of gender differences, on the biological and molecular functions in the main pathological mechanisms that recognize the role of vitamin D. Vitamin D deficiency is widespread worldwide, but it is still ... ...

    Abstract This narrative review aims to shed light on the role of gender differences, on the biological and molecular functions in the main pathological mechanisms that recognize the role of vitamin D. Vitamin D deficiency is widespread worldwide, but it is still very controversial whether the amount of vitamin D taken daily is actually the only problem related to its biological functions. Currently, the plasma concentration of 25-hydroxyvitamin D represents the only indicator of the circulating blood quota. The concept is that the biological function of vitamin D is not only linked to its circulating levels, but it is hypothesized that its biological functions depend, above all, on its total bioavailability. In particular, vitamin D circulates for the most part linked to albumin and vitamin D binding protein (DBP), which depend on various pathological conditions and physiologically, above all, the function of the latter is regulated by estrogens, glucocorticoids, and inflammatory cytokines. During her life, women undergo various changes in the hormonal and sexual sphere concerning menarche, possible pregnancies, and breastfeeding but also the use of contraceptives and, finally, the transition from the period of fertility to menopause. Each of these phases presents specific needs and, consequently, sometimes also specific criticalities. Studies on young women have shown that vitamin D deficiency is present in 58 to 91% of cases. Obesity, metabolic disorders, and variation in estrogen contraction may affect vitamin D deficiency due to the decreased bioavailability from dietary sources due to deposition in body fat compartments.
    Keywords gender differences ; vitamin D ; biological functions ; estrogens ; glucocorticoids ; inflammatory cytokines ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Mocafe: a comprehensive Python library for simulating cancer development with Phase Field Models.

    Pradelli, Franco / Minervini, Giovanni / Tosatto, Silvio C E

    Bioinformatics (Oxford, England)

    2022  Volume 38, Issue 18, Page(s) 4440–4441

    Abstract: Summary: Mathematical models are effective in studying cancer development at different scales from metabolism to tissue. Phase Field Models (PFMs) have been shown to reproduce accurately cancer growth and other related phenomena, including expression of ...

    Abstract Summary: Mathematical models are effective in studying cancer development at different scales from metabolism to tissue. Phase Field Models (PFMs) have been shown to reproduce accurately cancer growth and other related phenomena, including expression of relevant molecules, extracellular matrix remodeling and angiogenesis. However, implementations of such models are rarely published, reducing access to these techniques. To reduce this gap, we developed Mocafe, a modular open-source Python package that implements some of the most important PFMs reported in the literature. Mocafe is designed to handle both PFMs purely based on differential equations and hybrid agent-based PFMs. Moreover, Mocafe is meant to be extensible, allowing the inclusion of new models in future releases.
    Availability and implementation: Mocafe is a Python package based on FEniCS, a popular computing platform for solving partial differential equations. The source code, extensive documentation and demos are provided on GitHub at URL: https://github.com/BioComputingUP/mocafe. Moreover, we uploaded on Zenodo an archive of the package, which is available at https://doi.org/10.5281/zenodo.6366052.
    MeSH term(s) Humans ; Software ; Documentation ; Libraries ; Neoplasms
    Language English
    Publishing date 2022-07-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btac521
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Structural Characterization of Hypoxia Inducible Factor α—Prolyl Hydroxylase Domain 2 Interaction through MD Simulations

    Giorgia F. Camagni / Giovanni Minervini / Silvio C. E. Tosatto

    International Journal of Molecular Sciences, Vol 24, Iss 4710, p

    2023  Volume 4710

    Abstract: The Prolyl Hydroxylases (PHDs) are an enzymatic family that regulates cell oxygen-sensing. PHDs hydroxylate hypoxia-inducible transcription factors α (HIFs-α) driving their proteasomal degradation. Hypoxia inhibits PHDs activity, inducing HIFs-α ... ...

    Abstract The Prolyl Hydroxylases (PHDs) are an enzymatic family that regulates cell oxygen-sensing. PHDs hydroxylate hypoxia-inducible transcription factors α (HIFs-α) driving their proteasomal degradation. Hypoxia inhibits PHDs activity, inducing HIFs-α stabilization and cell adaptation to hypoxia. As a hallmark of cancer, hypoxia promotes neo-angiogenesis and cell proliferation. PHD isoforms are thought to have a variable impact on tumor progression. All isoforms hydroxylate HIF-α (HIF-1,2,3α) with different affinities. However, what determines these differences and how they pair with tumor growth is poorly understood. Here, molecular dynamics simulations were used to characterize the PHD2 binding properties in complexes with HIF-1α and HIF-2α. In parallel, conservation analysis and binding free energy calculations were performed to better understand PHD2 substrate affinity. Our data suggest a direct association between the PHD2 C-terminus and HIF-2α that is not observed in the PHD2/HIF-1α complex. Furthermore, our results indicate that phosphorylation of a PHD2 residue, Thr405, causes a variation in binding energy, despite the fact that this PTM has only a limited structural impact on PHD2/HIFs-α complexes. Collectively, our findings suggest that the PHD2 C-terminus may act as a molecular regulator of PHD’s activity.
    Keywords molecular dynamics simulation ; hypoxia ; hypoxia-inducible factor ; HIF-prolyl hydroxylases ; VHL ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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