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Article ; Online: Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington’s Disease Models

Letizia Pruccoli / Carlo Breda / Gabriella Teti / Mirella Falconi / Flaviano Giorgini / Andrea Tarozzi

Pharmaceuticals, Vol 14, Iss 1044, p

2021 Volume 1044

Abstract: Huntington’s disease (HD) is a neurodegenerative disorder caused by an abnormal CAG trinucleotide repeat expansion within exon 1 of the huntingtin (HTT) gene. This mutation leads to the production of mutant HTT (mHTT) protein which triggers neuronal ... ...

Abstract	Huntington’s disease (HD) is a neurodegenerative disorder caused by an abnormal CAG trinucleotide repeat expansion within exon 1 of the huntingtin (HTT) gene. This mutation leads to the production of mutant HTT (mHTT) protein which triggers neuronal death through several mechanisms. Here, we investigated the neuroprotective effects of esculetin (ESC), a bioactive phenolic compound, in an inducible PC12 model and a transgenic Drosophila melanogaster model of HD, both of which express mHTT fragments. ESC partially inhibited the progression of mHTT aggregation and reduced neuronal death through its ability to counteract the oxidative stress and mitochondria impairment elicited by mHTT in the PC12 model. The ability of ESC to counteract neuronal death was also confirmed in the transgenic Drosophila model. Although ESC did not modify the lifespan of the transgenic Drosophila , it still seemed to have a positive impact on the HD phenotype of this model. Based on our findings, ESC may be further studied as a potential neuroprotective agent in a rodent transgenic model of HD.
Keywords	Huntington’s disease ; huntingtin ; mitochondrial dysfunction ; oxidative stress ; neuroprotection ; esculetin ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Subject code	612
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Progesterone Prolongs Viability and Anti-inflammatory Functions of Explanted Preterm Ovine Amniotic Membrane

Angelo Canciello / Gabriella Teti / Eleonora Mazzotti / Mirella Falconi / Valentina Russo / Antonio Giordano / Barbara Barboni

Frontiers in Bioengineering and Biotechnology, Vol

2020 Volume 8

Abstract: Amniotic membrane (AM) is considered an important medical device with many applications in regenerative medicine. The therapeutic properties of AM are due to its resistant extracellular matrix and to the large number of bioactive molecules released by ... ...

Abstract	Amniotic membrane (AM) is considered an important medical device with many applications in regenerative medicine. The therapeutic properties of AM are due to its resistant extracellular matrix and to the large number of bioactive molecules released by its cells. An important goal that still remains to be achieved is the identification of cultural and preservation protocols able to maintain in time the membrane morphology and the biological properties of its cells. Recently, our research group demonstrated that progesterone (P4) is crucial in preventing the loss of the epithelial phenotype of amniotic epithelial cells in vitro. Followed by this premise, it has been evaluated whether P4 may also affect AM properties in a short-term culture. Results confirm that P4 preserves AM integrity and architecture with respect to untreated AM, which showed alterations in morphology. Transmission electron microscopy (TEM) analyses demonstrate that P4 also maintains unaltered cell–cell junctions, nuclear status, and intracellular organelles. On the contrary, an untreated AM experienced an extensive cell death and a strong reduction of immunomodulatory properties, measured in terms of anti-inflammatory cytokine expression and secretion. Overall, these results could open to new strategies to ameliorate the protocols for cryopreservation and tissue culture, which represent preliminary stages of AM application in regenerative medicine.
Keywords	amniotic membrane ; amniotic epithelial stem cells ; progesterone ; tissue culture ; regenerative medicine ; immunomodulation ; Biotechnology ; TP248.13-248.65
Subject code	571
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Assessment of the structural and functional characteristics of human mesenchymal stem cells associated with a prolonged exposure of morphine

Francesco Carano / Gabriella Teti / Alessandra Ruggeri / Francesca Chiarini / Arianna Giorgetti / Maria C. Mazzotti / Paolo Fais / Mirella Falconi

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 12

Abstract: Abstract The discovery of the expression of opioid receptors in the skin and their role in orchestrating the process of tissue repair gave rise to questions regarding the potential effects of clinical morphine treatment in wound healing. Although short ... ...

Abstract	Abstract The discovery of the expression of opioid receptors in the skin and their role in orchestrating the process of tissue repair gave rise to questions regarding the potential effects of clinical morphine treatment in wound healing. Although short term treatment was reported to improve tissue regeneration, in vivo chronic administration was associated to an impairment of the physiological healing process and systemic fibrosis. Human mesenchymal stem cells (hMSCs) play a fundamental role in tissue regeneration. In this regard, acute morphine exposition was recently reported to impact negatively on the functional characteristics of hMSCs, but little is currently known about its long-term effects. To determine how a prolonged treatment could impair their functional characteristics, we exposed hMSCs to increasing morphine concentrations respectively for nine and eighteen days, evaluating in particular the fibrogenic potential exerted by the long-term exposition. Our results showed a time dependent cell viability decline, and conditions compatible with a cellular senescent state. Ultrastructural and protein expression analysis were indicative of increased autophagy, suggesting a relation to a detoxification activity. In addition, the enhanced transcription observed for the genes involved in the synthesis and regulation of type I collagen suggested the possibility that a prolonged morphine treatment might exert its fibrotic potential risk, even involving the hMSCs.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Three-Dimensional Virtual Anatomy as a New Approach for Medical Student’s Learning

Anna Bartoletti-Stella / Valentina Gatta / Giulia Adalgisa Mariani / Pietro Gobbi / Mirella Falconi / Lucia Manzoli / Irene Faenza / Sara Salucci

International Journal of Environmental Research and Public Health, Vol 18, Iss 13247, p

2021 Volume 13247

Abstract: Most medical and health science schools adopt innovative tools to implement the teaching of anatomy to their undergraduate students. The increase in technological resources for educational purposes allows the use of virtual systems in the field of ... ...

Abstract	Most medical and health science schools adopt innovative tools to implement the teaching of anatomy to their undergraduate students. The increase in technological resources for educational purposes allows the use of virtual systems in the field of medicine, which can be considered decisive for improving anatomical knowledge, a requisite for safe and competent medical practice. Among these virtual tools, the Anatomage Table 7.0 represents, to date, a pivotal anatomical device for student education and training medical professionals. This review focuses attention on the potential of the Anatomage Table in the anatomical learning process and clinical practice by discussing these topics based on recent publication findings and describing their trends during the COVID-19 pandemic period. The reports documented a great interest in and a positive impact of the use of this technological table by medical students for teaching gross anatomy. Anatomage allows to describe, with accuracy and at high resolution, organ structure, vascularization, and innervation, as well as enables to familiarize with radiological images of real patients by improving knowledge in the radiological and surgical fields. Furthermore, its use can be considered strategic in a pandemic period, since it ensures, through an online platform, the continuation of anatomical and surgical training on dissecting cadavers.
Keywords	virtual gross anatomy ; medical student learning ; radiologist and surgical training ; virtual cadaveric dissection ; DICOM images ; Medicine ; R
Subject code	629
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Age-Related Alterations Affecting the Chondrogenic Differentiation of Synovial Fluid Mesenchymal Stromal Cells in an Equine Model

Eleonora Mazzotti / Gabriella Teti / Mirella Falconi / Francesca Chiarini / Barbara Barboni / Antonio Mazzotti / Aurelio Muttini

Cells, Vol 8, Iss 10, p

2019 Volume 1116

Abstract: Osteoarthritis is a degenerative disease that strongly correlates with age and promotes the breakdown of joint cartilage and subchondral bone. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of ... ...

Abstract	Osteoarthritis is a degenerative disease that strongly correlates with age and promotes the breakdown of joint cartilage and subchondral bone. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stromal cells (MSCs) isolated from adult tissues. It seems that MSCs derived from synovial joint tissues exhibit superior chondrogenic ability, but their unclear distribution and low frequency actually limit their clinical application. To date, the influence of aging on synovial joint derived MSCs’ biological characteristics and differentiation abilities remains unknown, and a full understanding of the mechanisms involved in cellular aging is lacking. The aim of this study was therefore to investigate the presence of age-related alterations in synovial fluid MSCs and their influence on the potential ability of MSCs to differentiate toward chondrogenic phenotypes. Synovial fluid MSCs, isolated from healthy equine donors from 3 to 40 years old, were cultured in vitro and stimulated towards chondrogenic differentiation for up to 21 days. An equine model was chosen due to the high degree of similarity of the anatomy of the knee joint to the human knee joint and as spontaneous disorders develop that are clinically relevant to similar human disorders. The results showed a reduction in cell proliferation correlated with age and the presence of age-related tetraploid cells. Ultrastructural analysis demonstrated the presence of morphological features correlated with aging such as endoplasmic reticulum stress, autophagy, and mitophagy. Alcian blue assay and real-time PCR data showed a reduction of efficiency in the chondrogenic differentiation of aged synovial fluid MSCs compared to young MSCs. All these data highlighted the influence of aging on MSCs’ characteristics and ability to differentiate towards chondrogenic differentiation and emphasize the importance of considering age-related alterations of MSCs in clinical applications.
Keywords	aging ; senescence ; MSCs ; chondrogenic differentiation ; osteoarthritis ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Hypoxia-Mimetic Agent Cobalt Chloride Differently Affects Human Mesenchymal Stem Cells in Their Chondrogenic Potential

Gabriella Teti / Stefano Focaroli / Viviana Salvatore / Eleonora Mazzotti / Laura Ingra’ / Antonio Mazzotti / Mirella Falconi

Stem Cells International, Vol

2018 Volume 2018

Abstract: Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl2) imitates hypoxia in vitro ...

Abstract	Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl2) imitates hypoxia in vitro by stabilizing hypoxia-inducible factor-alpha (HIF-1α), which is the master regulator in the cellular adaptive response to hypoxia. In this study, the influence of CoCl2 on the chondrogenic potential of human MSCs, isolated from dental pulp, umbilical cord, and adipose tissue, was investigated. Cells were treated with concentrations of CoCl2 ranging from 50 to 400 μM. Cell viability, HIF-1α protein synthesis, and the expression of the chondrogenic markers were analyzed. The results showed that the CoCl2 supplementation had no effect on cell viability, while the upregulation of chondrogenic markers such as SOX9, COL2A1, VCAN, and ACAN was dependent on the cellular source. This study shows that hypoxia, induced by CoCl2 treatment, can differently influence the behavior of MSCs, isolated from different sources, in their chondrogenic potential. These findings should be taken into consideration in the treatment of cartilage repair and regeneration based on stem cell therapies.
Keywords	Internal medicine ; RC31-1245
Subject code	610
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Calcium/Cobalt Alginate Beads as Functional Scaffolds for Cartilage Tissue Engineering

Stefano Focaroli / Gabriella Teti / Viviana Salvatore / Isabella Orienti / Mirella Falconi

Stem Cells International, Vol

2016 Volume 2016

Abstract: Articular cartilage is a highly organized tissue with complex biomechanical properties. However, injuries to the cartilage usually lead to numerous health concerns and often culminate in disabling symptoms, due to the poor intrinsic capacity of this ... ...

Abstract	Articular cartilage is a highly organized tissue with complex biomechanical properties. However, injuries to the cartilage usually lead to numerous health concerns and often culminate in disabling symptoms, due to the poor intrinsic capacity of this tissue for self-healing. Although various approaches are proposed for the regeneration of cartilage, its repair still represents an enormous challenge for orthopedic surgeons. The field of tissue engineering currently offers some of the most promising strategies for cartilage restoration, in which assorted biomaterials and cell-based therapies are combined to develop new therapeutic regimens for tissue replacement. The current study describes the in vitro behavior of human adipose-derived mesenchymal stem cells (hADSCs) encapsulated within calcium/cobalt (Ca/Co) alginate beads. These novel chondrogenesis-promoting scaffolds take advantage of the synergy between the alginate matrix and Co+2 ions, without employing costly growth factors (e.g., transforming growth factor betas (TGF-βs) or bone morphogenetic proteins (BMPs)) to direct hADSC differentiation into cartilage-producing chondrocytes.
Keywords	Internal medicine ; RC31-1245
Subject code	616
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Thixotropic Peptide-Based Physical Hydrogels Applied to Three-Dimensional Cell Culture

Nicola Zanna / Stefano Focaroli / Andrea Merlettini / Luca Gentilucci / Gabriella Teti / Mirella Falconi / Claudia Tomasini

ACS Omega, Vol 2, Iss 5, Pp 2374-

2017 Volume 2381

Keywords	Chemistry ; QD1-999
Language	English
Publishing date	2017-05-01T00:00:00Z
Publisher	American Chemical Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: 17β-Estradiol enhances sulforaphane cardioprotection against oxidative stress

Angeloni, Cristina / Gabriella Teti / Marco Malaguti / Maria Cristina Barbalace / Mirella Falconi / Silvana Hrelia

Journal of nutritional biochemistry. 2017 Apr., v. 42

2017

Abstract: The lower incidence of ischemic heart disease in female with respect to male gender suggests the possibility that female sex hormones could have specific effects in cardiovascular protection. 17β-Estradiol is the predominant premenopausal circulating ... ...

Abstract	The lower incidence of ischemic heart disease in female with respect to male gender suggests the possibility that female sex hormones could have specific effects in cardiovascular protection. 17β-Estradiol is the predominant premenopausal circulating form of estrogen and has a protective role on the cardiovascular system. Recent evidences suggest that gender can influence the response to cardiovascular medications; therefore, we hypothesized that sex hormones could also modulate the cardioprotective effects of nutraceutical compounds, such as the isothiocyanate sulforaphane, present in Brassica vegetables. This study was designed to explore the protective effects of sulforaphane in the presence of 17β-estradiol against H2O2-induced oxidative stress in primary cultures of rat cardiomyocytes. Interestingly, 17β-estradiol enhanced sulforaphane protective activity against H2O2-induced cell death with respect to sulforaphane or 17β-estradiol alone as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl-tetrazolium bromide and lactate dehydrogenase assays. Moreover, 17β-estradiol boosted sulforaphane ability to counteract oxidative stress, reducing intracellular reactive oxygen species and 8-hydroxy-2′-deoxyguanosine levels and increasing the expression of phase II enzymes. Using specific antagonists of estrogen receptor α and β, we observed that these effects are not mediated by estrogen receptors. Otherwise, ERK1/2 and Akt signaling pathways seem to be involved, as the presence of specific inhibitors of these kinases reduced the protective effect of sulforaphane in the presence of 17β-estradiol. Sulforaphane and 17β-estradiol co-treatment counteracted cell morphology alterations induced by H2O2 as evidenced by transmission electron microscopy. Our results demonstrated, for the first time, that estrogens could enhance sulforaphane protective effects, suggesting that nutraceutical efficacy might be modulated by sex hormones.
Keywords	antagonists ; Brassica ; cardiomyocytes ; cardioprotective effect ; cell death ; estradiol ; estrogen receptors ; females ; functional foods ; hydrogen peroxide ; lactate dehydrogenase ; males ; myocardial ischemia ; oxidative stress ; phosphotransferases (kinases) ; premenopause ; rats ; signal transduction ; transmission electron microscopy ; vegetables
Language	English
Dates of publication	2017-04
Size	p. 26-36.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1014929-6
ISSN	1873-4847 ; 0955-2863
ISSN (online)	1873-4847
ISSN	0955-2863
DOI	10.1016/j.jnutbio.2016.12.017
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Osteoblastic Differentiation on Graphene Oxide-Functionalized Titanium Surfaces

Roberta Di Carlo / Antonello Di Crescenzo / Serena Pilato / Alessia Ventrella / Adriano Piattelli / Lucia Recinella / Annalisa Chiavaroli / Silvia Giordani / Michele Baldrighi / Adalberto Camisasca / Barbara Zavan / Mirella Falconi / Amelia Cataldi / Antonella Fontana / Susi Zara

Nanomaterials, Vol 10, Iss 654, p

An In Vitro Study

2020 Volume 654

Abstract: Background: Titanium implant surfaces are continuously modified to improve biocompatibility and to promote osteointegration. Graphene oxide (GO) has been successfully used to ameliorate biomaterial performances, in terms of implant integration with host ... ...

Abstract	Background: Titanium implant surfaces are continuously modified to improve biocompatibility and to promote osteointegration. Graphene oxide (GO) has been successfully used to ameliorate biomaterial performances, in terms of implant integration with host tissue. The aim of this study is to evaluate the Dental Pulp Stem Cells (DPSCs) viability, cytotoxic response, and osteogenic differentiation capability in the presence of GO-coated titanium surfaces. Methods: Two titanium discs types, machined (control, Crtl) and sandblasted and acid-etched (test, Test) discs, were covalently functionalized with GO. The ability of the GO-functionalized substrates to allow the proliferation and differentiation of DPSCs, as well as their cytotoxic potential, were assessed. Results: The functionalization procedures provide a homogeneous coating with GO of the titanium surface in both control and test substrates, with unchanged surface roughness with respect to the untreated surfaces. All samples show the deposition of extracellular matrix, more pronounced in the test and GO-functionalized test discs. GO-functionalized test samples evidenced a significant viability, with no cytotoxic response and a remarkable early stage proliferation of DPSCs cells, followed by their successful differentiation into osteoblasts. Conclusions: The described protocol of GO-functionalization provides a novel not cytotoxic biomaterial that is able to stimulate cell viability and that better and more quickly induces osteogenic differentiation with respect to simple titanium discs. Our findings pave the way to exploit this GO-functionalization protocol for the production of novel dental implant materials that display improved integration with the host tissue.
Keywords	titanium disc ; surface functionalization ; graphene oxide ; dental pulp stem cells ; osteoblastic differentiation ; Chemistry ; QD1-999
Subject code	600
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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