Selenia Miglietta | Università degli Studi "La Sapienza" di Roma (original) (raw)

Papers by Selenia Miglietta

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

International Journal of Andrology, Aug 27, 2016

Vitrification is a new method that has been recently introduced in Assisted Reproduction Techniqu... more Vitrification is a new method that has been recently introduced in Assisted Reproduction Technique programs. The aim of this study was to design a new medium similar to normal human seminal fluid (SF), formulation artificial seminal fluid (ASF), and to compare the cryoprotective potency of this medium with SF and human tubal fluid (HTF) medium. Thirty normal ejaculates were processed with the swim-up technique and sperm suspensions were divided into four aliquots: (i) fresh sample (control); (ii) vitrification in HTF medium supplemented with 5 mg/mL human serum albumin and 0.25 mol sucrose (Vit HTF); (iii) vitrification with patients' SF (Vit SF); and (iv) vitrification in ASF (Vit ASF). After warming, sperm parameters of motility, viability, and morphology were analyzed using WHO criteria. Also, sperm pellets were fixed in 2.5% glutaraldehyde and processed for scanning electron microscopy and transmission electron microscopy observations. The results showed that progressive motility (46.09

Biology

Up-to-date in vitro and in vivo preclinical models expressing the patient-specific cancer lineage... more Up-to-date in vitro and in vivo preclinical models expressing the patient-specific cancer lineage responsible for CRC and its metastatic behavior and responsiveness to therapy are needed. Exosomes’ role in tumorigenesis and the metastatic process was demonstrated, and the material content and size of the exosomes are associated with a poor prognosis of CRC. Exosomes are generally imagined after their recovery from blood serum as isolated entities, and our work aims to investigate them “in situ” in their native environment by scanning and transmission electron microscopy to understand their secretion modalities. We studied CRC stem cells in patient-derived multicellular tumor spheroids (MTSs) and in their mouse xenograft to find possible differences in terms of exosome amount, size, and secretion site between in vitro and in vivo models. We observed that MTSs’ exosome secretion patterns depend on their structural complexity: few-layer MTSs show a lesser exosome secretion, limited to ...

Italian journal of anatomy and embryology, 2017

Cryopreservation of human spermatozoa is widely used in many assisted reproduction units to prese... more Cryopreservation of human spermatozoa is widely used in many assisted reproduction units to preserve male fertility [1]. Vitrification is based on the ultrarapid freezing and is routinely assayed for cryopreservation in assisted reproductive technology. Mohamed [2] showed that cryopreservation significantly affects progressive motility, viability and mitochondrial membrane potential of spermatozoa. Pentoxifylline (PX) is a phosphodiesterase considered to be a sperm movement enhancer, hyperactivation agent, inhibitor of reactive oxygen species and acrosome reaction-improving agent. The aim of our study was to evaluate the effect of in-vitro application of PX on sperm parameters and ultrastructure after vitrification. A total of 30 asthenozoospermic semen samples were selected and divided into two groups after vitrification: control (without PX) and experimental (with PX). A significant decrease in sperm motility, morphology and viability was observed post vitrification, but sperm mot...

It is known that exposure to heavy metals such as lead (Pb) and cadmium (Cd) has several adverse ... more It is known that exposure to heavy metals such as lead (Pb) and cadmium (Cd) has several adverse effects, particularly on the human reproductive system. Pb and Cd have been associated with infertility in both men and women. In pregnant women, they have been associated with spontaneous abortion, preterm birth, and impairment of the development of the fetus. Since these heavy metals come from both natural and anthropogenic activities and their harmful effects have been observed even at levels of exposure, their exposure remains a public health issue, especially for the reproductive system. Given this, the present study aimed to investigate the potential reproductive effects of Pb and Cd levels in the follicular fluid (FF) of infertile women and no-smokers exposed to heavy metals for professional reasons or living in rural areas near landfills and waste disposal areas, to correlate the intrafollicular presence of these metals with possible alterations in the ultrastructure of human cum...

Cellular and Molecular Life Sciences, Aug 11, 2023

Heart failure is a major side effect of doxorubicin (DOX) treatment in patients with cancer. Howe... more Heart failure is a major side effect of doxorubicin (DOX) treatment in patients with cancer. However, the mechanisms underlying the development of DOX-induced heart failure need to be addressed. This study aims to test whether the serine/ threonine kinase MST1, a major Hippo pathway component, contributes to the development of DOX-induced myocardial injury. C57BL/6J WT mice and mice with cardiomyocyte-specific dominant-negative MST1 (kinase-dead) overexpression received three weekly injections of DOX, reaching a final cumulative dose of 18 mg/kg. Echocardiographic, histological and biochemical analyses were performed six weeks after the first DOX administration. The effects of MST1 inhibition on DOX-induced cardiomyocyte injury were also tested in vitro. MST1 signaling was significantly activated in cardiomyocytes in response to DOX treatment in vitro and in vivo. Wild-type (WT) mice treated with DOX developed cardiac dysfunction and mitochondrial abnormalities. However, these detrimental effects were abolished in mice with cardiomyocyte-specific overexpression of dominant-negative MST1 (DN-MST1) or treated with XMU-MP-1, a specific MST1 inhibitor, indicating that MST1 inhibition attenuates DOX-induced cardiac dysfunction. DOX treatment led to a significant downregulation of cardiac levels of SIRT3, a deacetylase involved in mitochondrial protection, in WT mice, which was rescued by MST1 inhibition. Pharmacological inhibition of SIRT3 blunted the protective effects of MST1 inhibition, indicating that SIRT3 downregulation mediates the cytotoxic effects of MST1 activation in response to DOX treatment. Finally, we found a significant upregulation of MST1 and downregulation of SIRT3 levels in human myocardial tissue of cancer patients treated with DOX. In summary, MST1 contributes to DOX-induced cardiomyopathy through SIRT3 downregulation.

Cellular and Molecular Life Sciences

The epidermal growth factor receptor (EGFR) is one of the main tumor drivers and is an important ... more The epidermal growth factor receptor (EGFR) is one of the main tumor drivers and is an important therapeutic target for many cancers. Calcium is important in EGFR signaling pathways. Sorcin is one of the most important calcium sensor proteins, overexpressed in many tumors, that promotes cell proliferation, migration, invasion, epithelial-to-mesenchymal transition, malignant progression and resistance to chemotherapeutic drugs. The present work elucidates a functional mechanism that links calcium homeostasis to EGFR signaling in cancer. Sorcin and EGFR expression are significantly correlated and associated with reduced overall survival in cancer patients. Mechanistically, Sorcin directly binds EGFR protein in a calcium-dependent fashion and regulates calcium (dys)homeostasis linked to EGF-dependent EGFR signaling. Moreover, Sorcin controls EGFR proteostasis and signaling and increases its phosphorylation, leading to increased EGF-dependent migration and invasion. Of note, silencing o...

Acute myeloid leukemia (AML) patients bearing the ITD mutation in the tyrosine kinase receptor FL... more Acute myeloid leukemia (AML) patients bearing the ITD mutation in the tyrosine kinase receptor FLT3 (FLT3-ITD) present a poor prognosis and a high risk of relapse. FLT3-ITD is retained in the endoplasmic reticulum (ER) and generates intrinsic proteotoxic stress. We devised a strategy based on proteotoxic stress, generated by the combination of low doses of the differentiating agent retinoic acid (R), the proteasome inhibitor bortezomib (B), and the oxidative stress inducer arsenic trioxide (A). It exerts strong cytotoxic activity on FLT3-ITD+AML cell lines and primary blasts isolated from patients, due to ER homeostasis imbalance and generation of oxidative stress. AML cells become completely resistant to the combination RBA when treated in co-culture with bone marrow stromal cells (BMSC). Nonetheless, we could overcome such protective effects by using high doses of ascorbic acid (Vitamin C) as an adjuvant. Importantly, the combination RBA plus ascorbic acid significantly prolongs t...

The epidermal growth factor receptor (EGFR) is one of the main tumor drivers, and is an important... more The epidermal growth factor receptor (EGFR) is one of the main tumor drivers, and is an important therapeutic target for many cancers. Calcium is important in EGFR internalization and in EGFR signaling pathways. Sorcin is one of the most important calcium sensor proteins, overexpressed in many tumors, that promotes cell proliferation, migration, invasion, epithelial-to-mesenchymal transition, malignant progression and resistance to chemotherapeutic drugs. The present work elucidates an important mechanism that links calcium homeostasis to EGFR signaling in cancer. Sorcin and EGFR overexpression are significantly correlated in cancer patients. Sorcin directly binds EGFR in a calcium-dependent fashion and regulates calcium (dys)homeostasis linked to EGF-dependent EGFR signaling. Sorcin controls EGFR signaling, increases its recycling, activates the PI3K/AKT signaling cascade, and controls the RAS/ERK cascade, participating in the regulation of cellular migration and invasion. Sorcin e...

Cells

The Gravity Force to which living beings are subjected on Earth rules the functionality of most b... more The Gravity Force to which living beings are subjected on Earth rules the functionality of most biological processes in many tissues. It has been reported that a situation of Microgravity (such as that occurring in space) causes negative effects on living beings. Astronauts returning from space shuttle missions or from the International Space Station have been diagnosed with various health problems, such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and vestibular and sensory imbalance, including impaired visual acuity, altered metabolic and nutritional status, and immune system dysregulation. Microgravity has profound effects also on reproductive functions. Female astronauts, in fact, suppress their cycles during space travels, and effects at the cellular level in the early embryo development and on female gamete maturation have also been observed. The opportunities to use space flights to study the effects of gravity variations are limited because of the...

Italian journal of anatomy and embryology, 2016

Mancozeb is an ethylene bis-dithiocarbamate widely used as fungicide, also due to a low reported ... more Mancozeb is an ethylene bis-dithiocarbamate widely used as fungicide, also due to a low reported toxicity in mammals. However, reproductive toxicity has been demonstrated in vivo and in vitro in mouse oocytes, by the alteration of spindle morphology [1] and impairment of fertilizability [2]. Mancozeb exerted on mouse GCs cultured in vitro a premalignant-like status, indicated by reduced p53 expression [3] and a mild oxidative stress [4]. However, presence and extent of ultrastructural alterations induced in vitro by Mancozeb on GCs were not yet studied. To this aim, Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) were applied on mouse GCs cultured with increasing concentration of Mancozeb. GCs were obtained by puncturing antral follicles of PMSG-treated prepubertal CD1 female mice and cultured in vitro in DMEM+5%FBS+pen/strep without (control) or with increasing concentration of Mancozeb (0.001-to-1 µg/ml) for 48hrs, at 37°C and 5%CO2. At the end of the...

International Journal of Molecular Sciences

Before entering human clinical studies to evaluate their safety and effectiveness, new drugs and ... more Before entering human clinical studies to evaluate their safety and effectiveness, new drugs and novel medical treatments are subject to extensive animal testing that are expensive and time-consuming. By contrast, advanced technologies enable the development of animal-free models that allow the efficacy of innovative therapies to be studied without sacrificing animals, while providing helpful information and details. We report on the powerful combination of 3D bioprinting (3DB) and photo-thermal therapy (PTT) applications. To this end, we realize a 3DB construct consisting of glioblastoma U87-MG cells in a 3D geometry, incorporating biomimetic keratin-coated gold nanoparticles (Ker-AuNPs) as a photo-thermal agent. The resulting plasmonic 3DB structures exhibit a homogeneous cell distribution throughout the entire volume while promoting the localization of Ker-AuNPs within the cells. A 3D immunofluorescence assay and transmission electron microscopy (TEM) confirm the uniform distribu...

Uno dei problemi legati alla crioconservazione del liquido seminale è la riduzione dei parametri ... more Uno dei problemi legati alla crioconservazione del liquido seminale è la riduzione dei parametri vitali quali la vitalità e la motilità. La cri preservazione può inoltre indurre modificazioni della normale morfologia della componente nemaspermica. Attualmente la crioconservazione è applicabile attraverso due metodologie: congelamento lento/scongelamento rapido e vitrificazione/riscaldamento. Il primo metodo tende a prevenire la formazione di ghiaccio intracellulare tramite un lento abbassamento della temperatura: in tal modo la cristallizzazione che avviene all’esterno della cellula dovrebbe non disturbare l’ambiente intracellulare; il secondo invece mira ad evitare la formazione di ghiaccio intracellulare attraverso un istantaneo abbassamento della temperatura facendo in modo che il tempo richiesto per la transizione termica non sia tale da permettere il passaggio di stato. Per crioconservare con successo limitando il danno intracellulare si utilizzano delle sostanze dette crioprot...

Environmental Science: Nano

An antibody-functionalized gold nanorod array enables the realization of a reusable early-warning... more An antibody-functionalized gold nanorod array enables the realization of a reusable early-warning system for detecting harmful pathogens dispersed in drinkable water.

ABSTRACTObjectivesextracellular vesicles (EVs) are key biological mediators of several physiologi... more ABSTRACTObjectivesextracellular vesicles (EVs) are key biological mediators of several physiological functions within the cell microenvironment. Platelets are the most abundant source of EVs in the blood. Similarly, platelet lysate (PL), the best platelet derivative and angiogenic performer for regenerative purposes, is enriched of EVs, but their role is still too poorly discovered to be suitably exploited. Here we explored the contribution of the EVs in PL, by investigating the angiogenic features extrapolated from that possessed by PL.Methodswe tested angiogenic ability and molecular cargo in 3D bioprinted models and by RNA sequencing analysis of PL-derived EVs.Resultsa subset of small vesicles is highly represented in PL. The EVs do not retain aggregation ability, preserving a low redox state in HUVEC and increasing the angiogenic tubularly-like structures in 3D endothelial bioprinted constructs. EVs resembled the miRNome profile of PL, mainly enriched of small RNAs and a high am...

Caralluma fimbriata (Apocynaceae) è utilizzata come integratore alimentare per la riduzione del p... more Caralluma fimbriata (Apocynaceae) è utilizzata come integratore alimentare per la riduzione del peso corporeo (Dutt et al., J Med Food, 2012) per la presenza di glucosidi pregnanici, contenuti anche in altre piante, quali ad esempio Hoodia gordonii, utilizzate come dimagranti “naturali”. Dati scientifici sull’efficacia e sulla sicurezza di C. fimbriata sono alquanto carenti. Considerando l’uso del prodotto per lo più sotto forma di automedicazione, scopo del lavoro è stato di indagare la sicurezza d’impiego di un estratto standardizzato di C. fimbriata (Slimaluma), nel ratto normale, analizzando gli effetti del trattamento prolungato su alcuni parametri fisiologici

Andrologia, 2020

Application of nonspecific phosphodiesterases inhibitors, such as pentoxifylline (PTX), is a stra... more Application of nonspecific phosphodiesterases inhibitors, such as pentoxifylline (PTX), is a strategy utilised to aid sperm selection from immotile sperm samples prior to ICSI. No extensive studies have yet been performed to verify the safety of the clinical outcomes of ICSI after PTX administration. In this article, we summarise the data reported in the literature that assess the implication of in vitro usage of PTX on sperm parameters, as well as clinical outcomes during assisted male reproduction programme.

Mancozeb is an ethylene bis-dithiocarbamate widely used as fungicide, also due to a low reported ... more Mancozeb is an ethylene bis-dithiocarbamate widely used as fungicide, also due to a low reported toxicity in mammals. However, reproductive toxicity has been demonstrated in vivo and in vitro in mouse oocytes, by the alteration of spindle morphology [1] and impairment of fertilizability [2]. Mancozeb exerted on mouse GCs cultured in vitro a premalignant-like status, indicated by reduced p53 expression [3] and a mild oxidative stress [4]. However, presence and extent of ultrastructural alterations induced in vitro by Mancozeb on GCs were not yet studied. To this aim, Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) were applied on mouse GCs cultured with increasing concentration of Mancozeb. GCs were obtained by puncturing antral follicles of PMSG-treated prepuber-tal CD1 female mice and cultured in vitro in DMEM+5%FBS+pen/strep without (control) or with increasing concentration of Mancozeb (0.001-to-1 µg/ml) for 48hrs, at 37°C and 5%CO2. At the end of th...

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

International Journal of Andrology, Aug 27, 2016

Vitrification is a new method that has been recently introduced in Assisted Reproduction Techniqu... more Vitrification is a new method that has been recently introduced in Assisted Reproduction Technique programs. The aim of this study was to design a new medium similar to normal human seminal fluid (SF), formulation artificial seminal fluid (ASF), and to compare the cryoprotective potency of this medium with SF and human tubal fluid (HTF) medium. Thirty normal ejaculates were processed with the swim-up technique and sperm suspensions were divided into four aliquots: (i) fresh sample (control); (ii) vitrification in HTF medium supplemented with 5 mg/mL human serum albumin and 0.25 mol sucrose (Vit HTF); (iii) vitrification with patients' SF (Vit SF); and (iv) vitrification in ASF (Vit ASF). After warming, sperm parameters of motility, viability, and morphology were analyzed using WHO criteria. Also, sperm pellets were fixed in 2.5% glutaraldehyde and processed for scanning electron microscopy and transmission electron microscopy observations. The results showed that progressive motility (46.09

Biology

Up-to-date in vitro and in vivo preclinical models expressing the patient-specific cancer lineage... more Up-to-date in vitro and in vivo preclinical models expressing the patient-specific cancer lineage responsible for CRC and its metastatic behavior and responsiveness to therapy are needed. Exosomes’ role in tumorigenesis and the metastatic process was demonstrated, and the material content and size of the exosomes are associated with a poor prognosis of CRC. Exosomes are generally imagined after their recovery from blood serum as isolated entities, and our work aims to investigate them “in situ” in their native environment by scanning and transmission electron microscopy to understand their secretion modalities. We studied CRC stem cells in patient-derived multicellular tumor spheroids (MTSs) and in their mouse xenograft to find possible differences in terms of exosome amount, size, and secretion site between in vitro and in vivo models. We observed that MTSs’ exosome secretion patterns depend on their structural complexity: few-layer MTSs show a lesser exosome secretion, limited to ...

Italian journal of anatomy and embryology, 2017

Cryopreservation of human spermatozoa is widely used in many assisted reproduction units to prese... more Cryopreservation of human spermatozoa is widely used in many assisted reproduction units to preserve male fertility [1]. Vitrification is based on the ultrarapid freezing and is routinely assayed for cryopreservation in assisted reproductive technology. Mohamed [2] showed that cryopreservation significantly affects progressive motility, viability and mitochondrial membrane potential of spermatozoa. Pentoxifylline (PX) is a phosphodiesterase considered to be a sperm movement enhancer, hyperactivation agent, inhibitor of reactive oxygen species and acrosome reaction-improving agent. The aim of our study was to evaluate the effect of in-vitro application of PX on sperm parameters and ultrastructure after vitrification. A total of 30 asthenozoospermic semen samples were selected and divided into two groups after vitrification: control (without PX) and experimental (with PX). A significant decrease in sperm motility, morphology and viability was observed post vitrification, but sperm mot...

It is known that exposure to heavy metals such as lead (Pb) and cadmium (Cd) has several adverse ... more It is known that exposure to heavy metals such as lead (Pb) and cadmium (Cd) has several adverse effects, particularly on the human reproductive system. Pb and Cd have been associated with infertility in both men and women. In pregnant women, they have been associated with spontaneous abortion, preterm birth, and impairment of the development of the fetus. Since these heavy metals come from both natural and anthropogenic activities and their harmful effects have been observed even at levels of exposure, their exposure remains a public health issue, especially for the reproductive system. Given this, the present study aimed to investigate the potential reproductive effects of Pb and Cd levels in the follicular fluid (FF) of infertile women and no-smokers exposed to heavy metals for professional reasons or living in rural areas near landfills and waste disposal areas, to correlate the intrafollicular presence of these metals with possible alterations in the ultrastructure of human cum...

Cellular and Molecular Life Sciences, Aug 11, 2023

Heart failure is a major side effect of doxorubicin (DOX) treatment in patients with cancer. Howe... more Heart failure is a major side effect of doxorubicin (DOX) treatment in patients with cancer. However, the mechanisms underlying the development of DOX-induced heart failure need to be addressed. This study aims to test whether the serine/ threonine kinase MST1, a major Hippo pathway component, contributes to the development of DOX-induced myocardial injury. C57BL/6J WT mice and mice with cardiomyocyte-specific dominant-negative MST1 (kinase-dead) overexpression received three weekly injections of DOX, reaching a final cumulative dose of 18 mg/kg. Echocardiographic, histological and biochemical analyses were performed six weeks after the first DOX administration. The effects of MST1 inhibition on DOX-induced cardiomyocyte injury were also tested in vitro. MST1 signaling was significantly activated in cardiomyocytes in response to DOX treatment in vitro and in vivo. Wild-type (WT) mice treated with DOX developed cardiac dysfunction and mitochondrial abnormalities. However, these detrimental effects were abolished in mice with cardiomyocyte-specific overexpression of dominant-negative MST1 (DN-MST1) or treated with XMU-MP-1, a specific MST1 inhibitor, indicating that MST1 inhibition attenuates DOX-induced cardiac dysfunction. DOX treatment led to a significant downregulation of cardiac levels of SIRT3, a deacetylase involved in mitochondrial protection, in WT mice, which was rescued by MST1 inhibition. Pharmacological inhibition of SIRT3 blunted the protective effects of MST1 inhibition, indicating that SIRT3 downregulation mediates the cytotoxic effects of MST1 activation in response to DOX treatment. Finally, we found a significant upregulation of MST1 and downregulation of SIRT3 levels in human myocardial tissue of cancer patients treated with DOX. In summary, MST1 contributes to DOX-induced cardiomyopathy through SIRT3 downregulation.

Cellular and Molecular Life Sciences

The epidermal growth factor receptor (EGFR) is one of the main tumor drivers and is an important ... more The epidermal growth factor receptor (EGFR) is one of the main tumor drivers and is an important therapeutic target for many cancers. Calcium is important in EGFR signaling pathways. Sorcin is one of the most important calcium sensor proteins, overexpressed in many tumors, that promotes cell proliferation, migration, invasion, epithelial-to-mesenchymal transition, malignant progression and resistance to chemotherapeutic drugs. The present work elucidates a functional mechanism that links calcium homeostasis to EGFR signaling in cancer. Sorcin and EGFR expression are significantly correlated and associated with reduced overall survival in cancer patients. Mechanistically, Sorcin directly binds EGFR protein in a calcium-dependent fashion and regulates calcium (dys)homeostasis linked to EGF-dependent EGFR signaling. Moreover, Sorcin controls EGFR proteostasis and signaling and increases its phosphorylation, leading to increased EGF-dependent migration and invasion. Of note, silencing o...

Acute myeloid leukemia (AML) patients bearing the ITD mutation in the tyrosine kinase receptor FL... more Acute myeloid leukemia (AML) patients bearing the ITD mutation in the tyrosine kinase receptor FLT3 (FLT3-ITD) present a poor prognosis and a high risk of relapse. FLT3-ITD is retained in the endoplasmic reticulum (ER) and generates intrinsic proteotoxic stress. We devised a strategy based on proteotoxic stress, generated by the combination of low doses of the differentiating agent retinoic acid (R), the proteasome inhibitor bortezomib (B), and the oxidative stress inducer arsenic trioxide (A). It exerts strong cytotoxic activity on FLT3-ITD+AML cell lines and primary blasts isolated from patients, due to ER homeostasis imbalance and generation of oxidative stress. AML cells become completely resistant to the combination RBA when treated in co-culture with bone marrow stromal cells (BMSC). Nonetheless, we could overcome such protective effects by using high doses of ascorbic acid (Vitamin C) as an adjuvant. Importantly, the combination RBA plus ascorbic acid significantly prolongs t...

The epidermal growth factor receptor (EGFR) is one of the main tumor drivers, and is an important... more The epidermal growth factor receptor (EGFR) is one of the main tumor drivers, and is an important therapeutic target for many cancers. Calcium is important in EGFR internalization and in EGFR signaling pathways. Sorcin is one of the most important calcium sensor proteins, overexpressed in many tumors, that promotes cell proliferation, migration, invasion, epithelial-to-mesenchymal transition, malignant progression and resistance to chemotherapeutic drugs. The present work elucidates an important mechanism that links calcium homeostasis to EGFR signaling in cancer. Sorcin and EGFR overexpression are significantly correlated in cancer patients. Sorcin directly binds EGFR in a calcium-dependent fashion and regulates calcium (dys)homeostasis linked to EGF-dependent EGFR signaling. Sorcin controls EGFR signaling, increases its recycling, activates the PI3K/AKT signaling cascade, and controls the RAS/ERK cascade, participating in the regulation of cellular migration and invasion. Sorcin e...

Cells

The Gravity Force to which living beings are subjected on Earth rules the functionality of most b... more The Gravity Force to which living beings are subjected on Earth rules the functionality of most biological processes in many tissues. It has been reported that a situation of Microgravity (such as that occurring in space) causes negative effects on living beings. Astronauts returning from space shuttle missions or from the International Space Station have been diagnosed with various health problems, such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and vestibular and sensory imbalance, including impaired visual acuity, altered metabolic and nutritional status, and immune system dysregulation. Microgravity has profound effects also on reproductive functions. Female astronauts, in fact, suppress their cycles during space travels, and effects at the cellular level in the early embryo development and on female gamete maturation have also been observed. The opportunities to use space flights to study the effects of gravity variations are limited because of the...

Italian journal of anatomy and embryology, 2016

Mancozeb is an ethylene bis-dithiocarbamate widely used as fungicide, also due to a low reported ... more Mancozeb is an ethylene bis-dithiocarbamate widely used as fungicide, also due to a low reported toxicity in mammals. However, reproductive toxicity has been demonstrated in vivo and in vitro in mouse oocytes, by the alteration of spindle morphology [1] and impairment of fertilizability [2]. Mancozeb exerted on mouse GCs cultured in vitro a premalignant-like status, indicated by reduced p53 expression [3] and a mild oxidative stress [4]. However, presence and extent of ultrastructural alterations induced in vitro by Mancozeb on GCs were not yet studied. To this aim, Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) were applied on mouse GCs cultured with increasing concentration of Mancozeb. GCs were obtained by puncturing antral follicles of PMSG-treated prepubertal CD1 female mice and cultured in vitro in DMEM+5%FBS+pen/strep without (control) or with increasing concentration of Mancozeb (0.001-to-1 µg/ml) for 48hrs, at 37°C and 5%CO2. At the end of the...

International Journal of Molecular Sciences

Before entering human clinical studies to evaluate their safety and effectiveness, new drugs and ... more Before entering human clinical studies to evaluate their safety and effectiveness, new drugs and novel medical treatments are subject to extensive animal testing that are expensive and time-consuming. By contrast, advanced technologies enable the development of animal-free models that allow the efficacy of innovative therapies to be studied without sacrificing animals, while providing helpful information and details. We report on the powerful combination of 3D bioprinting (3DB) and photo-thermal therapy (PTT) applications. To this end, we realize a 3DB construct consisting of glioblastoma U87-MG cells in a 3D geometry, incorporating biomimetic keratin-coated gold nanoparticles (Ker-AuNPs) as a photo-thermal agent. The resulting plasmonic 3DB structures exhibit a homogeneous cell distribution throughout the entire volume while promoting the localization of Ker-AuNPs within the cells. A 3D immunofluorescence assay and transmission electron microscopy (TEM) confirm the uniform distribu...

Uno dei problemi legati alla crioconservazione del liquido seminale è la riduzione dei parametri ... more Uno dei problemi legati alla crioconservazione del liquido seminale è la riduzione dei parametri vitali quali la vitalità e la motilità. La cri preservazione può inoltre indurre modificazioni della normale morfologia della componente nemaspermica. Attualmente la crioconservazione è applicabile attraverso due metodologie: congelamento lento/scongelamento rapido e vitrificazione/riscaldamento. Il primo metodo tende a prevenire la formazione di ghiaccio intracellulare tramite un lento abbassamento della temperatura: in tal modo la cristallizzazione che avviene all’esterno della cellula dovrebbe non disturbare l’ambiente intracellulare; il secondo invece mira ad evitare la formazione di ghiaccio intracellulare attraverso un istantaneo abbassamento della temperatura facendo in modo che il tempo richiesto per la transizione termica non sia tale da permettere il passaggio di stato. Per crioconservare con successo limitando il danno intracellulare si utilizzano delle sostanze dette crioprot...

Environmental Science: Nano

An antibody-functionalized gold nanorod array enables the realization of a reusable early-warning... more An antibody-functionalized gold nanorod array enables the realization of a reusable early-warning system for detecting harmful pathogens dispersed in drinkable water.

ABSTRACTObjectivesextracellular vesicles (EVs) are key biological mediators of several physiologi... more ABSTRACTObjectivesextracellular vesicles (EVs) are key biological mediators of several physiological functions within the cell microenvironment. Platelets are the most abundant source of EVs in the blood. Similarly, platelet lysate (PL), the best platelet derivative and angiogenic performer for regenerative purposes, is enriched of EVs, but their role is still too poorly discovered to be suitably exploited. Here we explored the contribution of the EVs in PL, by investigating the angiogenic features extrapolated from that possessed by PL.Methodswe tested angiogenic ability and molecular cargo in 3D bioprinted models and by RNA sequencing analysis of PL-derived EVs.Resultsa subset of small vesicles is highly represented in PL. The EVs do not retain aggregation ability, preserving a low redox state in HUVEC and increasing the angiogenic tubularly-like structures in 3D endothelial bioprinted constructs. EVs resembled the miRNome profile of PL, mainly enriched of small RNAs and a high am...

Caralluma fimbriata (Apocynaceae) è utilizzata come integratore alimentare per la riduzione del p... more Caralluma fimbriata (Apocynaceae) è utilizzata come integratore alimentare per la riduzione del peso corporeo (Dutt et al., J Med Food, 2012) per la presenza di glucosidi pregnanici, contenuti anche in altre piante, quali ad esempio Hoodia gordonii, utilizzate come dimagranti “naturali”. Dati scientifici sull’efficacia e sulla sicurezza di C. fimbriata sono alquanto carenti. Considerando l’uso del prodotto per lo più sotto forma di automedicazione, scopo del lavoro è stato di indagare la sicurezza d’impiego di un estratto standardizzato di C. fimbriata (Slimaluma), nel ratto normale, analizzando gli effetti del trattamento prolungato su alcuni parametri fisiologici

Andrologia, 2020

Application of nonspecific phosphodiesterases inhibitors, such as pentoxifylline (PTX), is a stra... more Application of nonspecific phosphodiesterases inhibitors, such as pentoxifylline (PTX), is a strategy utilised to aid sperm selection from immotile sperm samples prior to ICSI. No extensive studies have yet been performed to verify the safety of the clinical outcomes of ICSI after PTX administration. In this article, we summarise the data reported in the literature that assess the implication of in vitro usage of PTX on sperm parameters, as well as clinical outcomes during assisted male reproduction programme.

Mancozeb is an ethylene bis-dithiocarbamate widely used as fungicide, also due to a low reported ... more Mancozeb is an ethylene bis-dithiocarbamate widely used as fungicide, also due to a low reported toxicity in mammals. However, reproductive toxicity has been demonstrated in vivo and in vitro in mouse oocytes, by the alteration of spindle morphology [1] and impairment of fertilizability [2]. Mancozeb exerted on mouse GCs cultured in vitro a premalignant-like status, indicated by reduced p53 expression [3] and a mild oxidative stress [4]. However, presence and extent of ultrastructural alterations induced in vitro by Mancozeb on GCs were not yet studied. To this aim, Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) were applied on mouse GCs cultured with increasing concentration of Mancozeb. GCs were obtained by puncturing antral follicles of PMSG-treated prepuber-tal CD1 female mice and cultured in vitro in DMEM+5%FBS+pen/strep without (control) or with increasing concentration of Mancozeb (0.001-to-1 µg/ml) for 48hrs, at 37°C and 5%CO2. At the end of th...