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  1. Article ; Online: Rare Causes of Hypercalcemia.

    Saponaro, Federica

    Endocrinology and metabolism clinics of North America

    2021  Volume 50, Issue 4, Page(s) 769–779

    Abstract: This article discusses rare causes of hypercalcemia. Hypercalcemia can rarely be associated with immobilization, genetic diseases in children such as Williams-Beuren syndrome, Hypophosphatasia, Jansen Metaphyseal Chondrodysplasia (JMC), cosmetic ... ...

    Abstract This article discusses rare causes of hypercalcemia. Hypercalcemia can rarely be associated with immobilization, genetic diseases in children such as Williams-Beuren syndrome, Hypophosphatasia, Jansen Metaphyseal Chondrodysplasia (JMC), cosmetic injection, milk-alkali syndrome (MAS), calcium sulfate beads administration, manganese intoxication, postacute kidney failure recovery, and Paget's disease.
    MeSH term(s) Calcium ; Child ; Humans ; Hypercalcemia/diagnosis ; Hypercalcemia/etiology ; Hypercalcemia/therapy
    Chemical Substances Calcium (SY7Q814VUP)
    Language English
    Publishing date 2021-11-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 92116-6
    ISSN 1558-4410 ; 0889-8529
    ISSN (online) 1558-4410
    ISSN 0889-8529
    DOI 10.1016/j.ecl.2021.07.004
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  2. Article: Editorial: Calcium Metabolism: Hormonal Crosstalk, Pathophysiology and Disease.

    Battafarano, Giulia / Chiellini, Grazia / Saponaro, Federica

    Frontiers in medicine

    2022  Volume 9, Page(s) 899416

    Language English
    Publishing date 2022-04-25
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2022.899416
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  3. Article: Parathyroid Hormone (PTH)-Related Peptides Family: An Intriguing Role in the Central Nervous System.

    Dettori, Cristina / Ronca, Francesca / Scalese, Marco / Saponaro, Federica

    Journal of personalized medicine

    2023  Volume 13, Issue 5

    Abstract: Parathyroid Hormone (PTH) plays a crucial role in the maintenance of calcium homeostasis directly acting on bone and kidneys and indirectly on the intestine. However, a large family of PTH-related peptides exists that exerts other physiological effects ... ...

    Abstract Parathyroid Hormone (PTH) plays a crucial role in the maintenance of calcium homeostasis directly acting on bone and kidneys and indirectly on the intestine. However, a large family of PTH-related peptides exists that exerts other physiological effects on different tissues and organs, such as the Central Nervous System (CNS). In humans, PTH-related peptides are Parathyroid Hormone (PTH), PTH-like hormones (PTHrP and PTHLH), and tuberoinfundibular peptide of 39 (TIP39 or PTH2). With different affinities, these ligands can bind parathyroid receptor type 1 (PTH1R) and type 2 (PTH2R), which are part of the type II G-protein-coupled-receptors (GPCRs) family. The PTH/PTHrP/PTH1R system has been found to be expressed in many areas of the brain (hippocampus, amygdala, hypothalamus, caudate nucleus, corpus callosum, subthalamic nucleus, thalamus, substantia nigra, cerebellum), and literature data suggest the system exercises a protective action against neuroinflammation and neurodegeneration, with positive effects on memory and hyperalgesia. TIP39 is a small peptide belonging to the PTH-related family with a high affinity for PTH2R in the CNS. The TIP39/PTH2R system has been proposed to mediate many regulatory and functional roles in the brain and to modulate auditory, nociceptive, and sexual maturation functions. This review aims to summarize the knowledge of PTH-related peptides distribution and functions in the CNS and to highlight the gaps that still need to be filled.
    Language English
    Publishing date 2023-04-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662248-8
    ISSN 2075-4426
    ISSN 2075-4426
    DOI 10.3390/jpm13050714
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  4. Article ; Online: Editorial

    Giulia Battafarano / Grazia Chiellini / Federica Saponaro

    Frontiers in Medicine, Vol

    Calcium Metabolism: Hormonal Crosstalk, Pathophysiology and Disease

    2022  Volume 9

    Keywords calcium homeostasis ; calcium metabolism ; bone diseases ; calcium disorders ; mineral homeostasis ; PTH ; Medicine (General) ; R5-920
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
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  5. Article ; Online: An Update on Vitamin D Metabolism.

    Saponaro, Federica / Saba, Alessandro / Zucchi, Riccardo

    International journal of molecular sciences

    2020  Volume 21, Issue 18

    Abstract: Vitamin D is a steroid hormone classically involved in the calcium metabolism and bone homeostasis. Recently, new and interesting aspects of vitamin D metabolism has been elucidated, namely the special role of the skin, the metabolic control of liver ... ...

    Abstract Vitamin D is a steroid hormone classically involved in the calcium metabolism and bone homeostasis. Recently, new and interesting aspects of vitamin D metabolism has been elucidated, namely the special role of the skin, the metabolic control of liver hydroxylase CYP2R1, the specificity of 1α-hydroxylase in different tissues and cell types and the genomic, non-genomic and epigenomic effects of vitamin D receptor, which will be addressed in the present review. Moreover, in the last decades, several extraskeletal effects which can be attributed to vitamin D have been shown. These beneficial effects will be here summarized, focusing on the immune system and cardiovascular system.
    MeSH term(s) 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism ; Animals ; Bone and Bones/metabolism ; Calcitriol/metabolism ; Cytochrome P-450 Enzyme System/metabolism ; Cytochrome P450 Family 2/metabolism ; Homeostasis ; Humans ; Lipid Metabolism ; Mixed Function Oxygenases/metabolism ; Receptors, Calcitriol/metabolism ; Skin/metabolism ; Vitamin D/metabolism ; Vitamin D3 24-Hydroxylase/metabolism
    Chemical Substances Receptors, Calcitriol ; VDR protein, human ; Vitamin D (1406-16-2) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Mixed Function Oxygenases (EC 1.-) ; Cytochrome P450 Family 2 (EC 1.14.14.1) ; Vitamin D3 24-Hydroxylase (EC 1.14.15.16) ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (EC 1.14.15.18) ; Calcitriol (FXC9231JVH)
    Keywords covid19
    Language English
    Publishing date 2020-09-08
    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/ijms21186573
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  6. Article ; Online: Transthyretin Stabilization: An Emerging Strategy for the Treatment of Alzheimer's Disease?

    Saponaro, Federica / Kim, Jin Hae / Chiellini, Grazia

    International journal of molecular sciences

    2020  Volume 21, Issue 22

    Abstract: Transthyretin (TTR), previously named prealbumin is a plasma protein secreted mainly by the liver and choroid plexus (CP) that is a carrier for thyroid hormones (THs) and retinol (vitamin A). The structure of TTR, with four monomers rich in β-chains in a ...

    Abstract Transthyretin (TTR), previously named prealbumin is a plasma protein secreted mainly by the liver and choroid plexus (CP) that is a carrier for thyroid hormones (THs) and retinol (vitamin A). The structure of TTR, with four monomers rich in β-chains in a globular tetrameric protein, accounts for the predisposition of the protein to aggregate in fibrils, leading to a rare and severe disease, namely transthyretin amyloidosis (ATTR). Much effort has been made and still is required to find new therapeutic compounds that can stabilize TTR ("kinetic stabilization") and prevent the amyloid genetic process. Moreover, TTR is an interesting therapeutic target for neurodegenerative diseases due to its recognized neuroprotective properties in the cognitive impairment context and interestingly in Alzheimer's disease (AD). Much evidence has been collected regarding the neuroprotective effects in AD, including through in vitro and in vivo studies as well as a wide range of clinical series. Despite this supported hypothesis of neuroprotection for TTR, the mechanisms are still not completely clear. The aim of this review is to highlight the most relevant findings on the neuroprotective role of TTR, and to summarize the recent progress on the development of TTR tetramer stabilizers.
    MeSH term(s) Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Alzheimer Disease/therapy ; Amyloid Neuropathies, Familial/genetics ; Amyloid Neuropathies, Familial/metabolism ; Amyloid Neuropathies, Familial/pathology ; Amyloid Neuropathies, Familial/therapy ; Humans ; Prealbumin/genetics ; Prealbumin/metabolism ; Protein Stability
    Chemical Substances Prealbumin ; TTR protein, human
    Language English
    Publishing date 2020-11-17
    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/ijms21228672
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  7. Article ; Online: T1AM/TAAR1 System Reduces Inflammatory Response and β-Amyloid Toxicity in Human Microglial HMC3 Cell Line.

    Polini, Beatrice / Ricardi, Caterina / Bertolini, Andrea / Carnicelli, Vittoria / Rutigliano, Grazia / Saponaro, Federica / Zucchi, Riccardo / Chiellini, Grazia

    International journal of molecular sciences

    2023  Volume 24, Issue 14

    Abstract: Microglial dysfunction is one of the hallmarks and leading causes of common neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD). All these pathologies are characterized by aberrant aggregation of disease- ... ...

    Abstract Microglial dysfunction is one of the hallmarks and leading causes of common neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD). All these pathologies are characterized by aberrant aggregation of disease-causing proteins in the brain, which can directly activate microglia, trigger microglia-mediated neuroinflammation, and increase oxidative stress. Inhibition of glial activation may represent a therapeutic target to alleviate neurodegeneration. Recently, 3-iodothyronamine (T1AM), an endogenous derivative of thyroid hormone (TH) able to interact directly with a specific GPCR known as trace amine-associated receptor 1 (TAAR1), gained interest for its ability to promote neuroprotection in several models. Nevertheless, T1AM's effects on microglial disfunction remain still elusive. In the present work we investigated whether T1AM could inhibit the inflammatory response of human HMC3 microglial cells to LPS/TNFα or β-amyloid peptide 25-35 (Aβ25-35) stimuli. The results of ELISA and qPCR assays revealed that T1AM was able to reduce microglia-mediated inflammatory response by inhibiting the release of proinflammatory factors, including IL-6, TNFα, NF-kB, MCP1, and MIP1, while promoting the release of anti-inflammatory mediators, such as IL-10. Notably, T1AM anti-inflammatory action in HMC3 cells turned out to be a TAAR1-mediated response, further increasing the relevance of the T1AM/TAAR1 system in the management of NDDs.
    MeSH term(s) Humans ; Anti-Inflammatory Agents/pharmacology ; Cell Line ; Inflammation ; Microglia/metabolism ; Neurodegenerative Diseases/metabolism ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances 3-iodothyronamine ; Anti-Inflammatory Agents ; Trace amine-associated receptor 1 (XMC8VP6RI2) ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2023-07-17
    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/ijms241411569
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  8. Article: Performance in Behavioral Testing in an Animal Model of Post-Surgical Hypoparathyroidism.

    Dettori, Cristina / Ronca, Francesca / Di Buono, Giulia / Saba, Alessandro / Di Lupo, Francesca / Polini, Beatrice / Ricardi, Caterina / Frascarelli, Sabina / Cetani, Filomena / Marcocci, Claudio / Zucchi, Riccardo / Chiellini, Grazia / Scalese, Marco / Saponaro, Federica

    Journal of personalized medicine

    2024  Volume 14, Issue 2

    Abstract: Background: Hypoparathyroidism (HypoPT) is characterized by hypocalcemia and undetectable/inappropriately low PTH. Post-surgical HypoPT (PS-HypoPT) is the most common cause. Patients with PS-HypoPT present neuropsychological symptoms, probably due to ... ...

    Abstract Background: Hypoparathyroidism (HypoPT) is characterized by hypocalcemia and undetectable/inappropriately low PTH. Post-surgical HypoPT (PS-HypoPT) is the most common cause. Patients with PS-HypoPT present neuropsychological symptoms, probably due to the PTH deprivation in the central nervous system (CNS). However, these mechanisms are still not elucidated. The aim of this study was to evaluate the effects of PTH deprivation on CNS in an animal model of PS-HypoPT via a cognitive/behavioral assessment approach.
    Methods: A surgical rat model of PS-HypoPT was obtained and treated with calcium to maintain normocalcemia. Twenty PS-HypoPT rats and twenty sham-operated controls (Crl) underwent behavioral testing in a Morris Water Maze (MWM), Open Field (OF), and Elevated Plus Maze (EPM).
    Results: In the MWM, PTx rats showed a higher Escape Latency Time compared to Crl rats (
    Conclusions: This animal model of PS-HypoPT shows an impairment in spatial memory, which improved after training, and a marked anxiety-like behavior, resembling the condition of patients with PS-HypoPT. Further studies are needed to elucidate mechanisms.
    Language English
    Publishing date 2024-02-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662248-8
    ISSN 2075-4426
    ISSN 2075-4426
    DOI 10.3390/jpm14020215
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  9. Article ; Online: An Update on Vitamin D Metabolism

    Federica Saponaro / Alessandro Saba / Riccardo Zucchi

    International Journal of Molecular Sciences, Vol 21, Iss 6573, p

    2020  Volume 6573

    Abstract: Vitamin D is a steroid hormone classically involved in the calcium metabolism and bone homeostasis. Recently, new and interesting aspects of vitamin D metabolism has been elucidated, namely the special role of the skin, the metabolic control of liver ... ...

    Abstract Vitamin D is a steroid hormone classically involved in the calcium metabolism and bone homeostasis. Recently, new and interesting aspects of vitamin D metabolism has been elucidated, namely the special role of the skin, the metabolic control of liver hydroxylase CYP2R1, the specificity of 1α-hydroxylase in different tissues and cell types and the genomic, non-genomic and epigenomic effects of vitamin D receptor, which will be addressed in the present review. Moreover, in the last decades, several extraskeletal effects which can be attributed to vitamin D have been shown. These beneficial effects will be here summarized, focusing on the immune system and cardiovascular system.
    Keywords vitamin D ; vitamin D receptor ; VDR ; 1,25(OH) 2 D ; 25OH-vitamin D ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
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  10. Article ; Online: Novel thyroid hormones.

    Zucchi, Riccardo / Rutigliano, Grazia / Saponaro, Federica

    Endocrine

    2019  Volume 66, Issue 1, Page(s) 95–104

    Abstract: The field of thyroid hormone signaling has grown more complex in recent years. In particular, it has been suggested that some thyroid hormone derivatives, tentatively named "novel thyroid hormones" or "active thyroid hormone metabolites", may act as ... ...

    Abstract The field of thyroid hormone signaling has grown more complex in recent years. In particular, it has been suggested that some thyroid hormone derivatives, tentatively named "novel thyroid hormones" or "active thyroid hormone metabolites", may act as independent chemical messengers. They include 3,5-diiodothyronine (T2), 3-iodothyronamine (T1AM), and several iodothyroacetic acids, i.e., 3,5,3',5'-thyroacetic acid (TA4), 3,5,3'-thyroacetic acid (TA3), and 3-thyroacetic acid (TA1). We summarize the present knowledge on these compounds, namely their biosynthetic pathways, endogenous levels, molecular targets, and the functional effects elicited in experimental preparations or intact animals after exogenous administration. Their physiological and pathophysiological role is discussed, and potential therapeutic applications are outlined. The requirements needed to qualify these substances as chemical messengers must still be validated, although promising evidence has been collected. At present, the best candidate to the role of independent chemical messenger appears to be T1AM, and its most interesting effects concern metabolism and brain function. The responses elicited in experimental animals have suggested potential therapeutic applications. TA3 has an established role in thyroid hormone resistance syndromes, and is under investigation in Allen-Herndon-Dudley syndrome. Other potential targets are represented by obesity and dyslipidemia (for T2 and T1AM); dementia and degenerative brain disease (for T1AM and TA1); cancer (for T1AM and TA4). Another intriguing and unexplored question is the potential relevance of these metabolites in the clinical picture of hypothyroidism and in the response to replacement therapy.
    MeSH term(s) Animals ; Diiodothyronines/metabolism ; Humans ; Thyronines/metabolism ; Thyroxine/analogs & derivatives ; Thyroxine/metabolism ; Triiodothyronine/analogs & derivatives ; Triiodothyronine/metabolism
    Chemical Substances 3-iodothyronamine ; Diiodothyronines ; Thyronines ; Triiodothyronine (06LU7C9H1V) ; 3,3',5-triiodothyroacetic acid (29OQ9EU4R1) ; 3,5-diiodothyronine (534-51-0) ; tetraiodothyroacetic acid (PA7UX1FFYQ) ; Thyroxine (Q51BO43MG4)
    Language English
    Publishing date 2019-07-20
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1194484-5
    ISSN 1559-0100 ; 1355-008X ; 0969-711X
    ISSN (online) 1559-0100
    ISSN 1355-008X ; 0969-711X
    DOI 10.1007/s12020-019-02018-4
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3884: Show issues Location:
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