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Article ; Online: Geotechnical characterization of natural clays for the prediction of clogging risk for TBM

Sebastiani, Diego / Spagnoli, Giovanni / Amici, Marco / Mangifesta, Sara

Environ Earth Sci. 2022 Oct., v. 81, no. 20 p.500-500

2022

Abstract: During mechanical tunnel driving it is known that the excavated soils can stick to the metallic part of the tunnel boring machine (TBM). Despite the fact that several test methodologies have been developed during the last 15 years to provide an ... ...

Abstract	During mechanical tunnel driving it is known that the excavated soils can stick to the metallic part of the tunnel boring machine (TBM). Despite the fact that several test methodologies have been developed during the last 15 years to provide an assessment or quantification of the clogging risk, no standardized method is available yet. This study evaluated three natural clay samples with different grain size distribution and mineralogical content considering two widespread test set ups for the evaluation of the clogging tendency: the Hobart mixing and the plate pull-out test. After a comprehensive geotechnical characterization of the three clay samples, adherence and plate pull-out force have been measured at different water content/consistency index. Results show that adherence and plate pull-out force in terms of water content [Formula: see text] and consistency index [Formula: see text] follow normal distribution curves which, as the percentage of clay, the content of clay minerals and the plasticity increases, have higher amplitudes and higher peak values. In general, the existence of a correlation between geotechnical classifications parameters and the behavior in terms of potential clogging risk for natural clays makes it possible to predict these risks in the design phase of the tunnel excavation and to plan appropriate mitigation actions.
Keywords	clay ; normal distribution ; particle size distribution ; plasticity ; prediction ; risk ; water content
Language	English
Dates of publication	2022-10
Size	p. 500.
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	2493699-6
ISSN	1866-6299 ; 1866-6280
ISSN (online)	1866-6299
ISSN	1866-6280
DOI	10.1007/s12665-022-10630-3
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Advances in small molecule selective ligands for heteromeric nicotinic acetylcholine receptors.

Matera, Carlo / Papotto, Claudio / Dallanoce, Clelia / De Amici, Marco

Pharmacological research

2023 Volume 194, Page(s) 106813

Abstract: The study of nicotinic acetylcholine receptors (nAChRs) has significantly progressed in the last decade, due to a) the improved techniques available for structural studies; b) the identification of ligands interacting at orthosteric and allosteric ... ...

Abstract	The study of nicotinic acetylcholine receptors (nAChRs) has significantly progressed in the last decade, due to a) the improved techniques available for structural studies; b) the identification of ligands interacting at orthosteric and allosteric recognition sites on the nAChR proteins, able to tune channel conformational states; c) the better functional characterization of receptor subtypes/subunits and their therapeutic potential; d) the availability of novel pharmacological agents able to activate or block nicotinic-mediated cholinergic responses with subtype or stoichiometry selectivity. The copious literature on nAChRs is related to the pharmacological profile of new, promising subtype selective derivatives as well as the encouraging preclinical and early clinical evaluation of known ligands. However, recently approved therapeutic derivatives are still missing, and examples of ligands discontinued in advanced CNS clinical trials include drug candidates acting at both neuronal homomeric and heteromeric receptors. In this review, we have selected heteromeric nAChRs as the target and comment on literature reports of the past five years dealing with the discovery of new small molecule ligands or the advanced pharmacological/preclinical investigation of more promising compounds. The results obtained with bifunctional nicotinic ligands and a light-activated ligand as well as the applications of promising radiopharmaceuticals for heteromeric subtypes are also discussed.
MeSH term(s)	Receptors, Nicotinic/metabolism ; Ligands ; Allosteric Regulation ; Neurons/metabolism ; Synaptic Transmission ; Nicotine ; Nicotinic Antagonists/metabolism ; Nicotinic Antagonists/pharmacology
Chemical Substances	Receptors, Nicotinic ; Ligands ; Nicotine (6M3C89ZY6R) ; Nicotinic Antagonists
Language	English
Publishing date	2023-06-10
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2023.106813
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Article ; Online: 2020 Italian Special Anniversary Collection: Celebrating NMMC 2019 and 40 Years of the DCF-SCI.

Carini, Marina / De Amici, Marco

ChemMedChem

2020 Volume 16, Issue 2, Page(s) 303–308

Abstract: Marina Carini and Marco De Amici, Guest Editors of this Special Collection dedicated to NMMC 2019 and the ... ...

Abstract	Marina Carini and Marco De Amici, Guest Editors of this Special Collection dedicated to NMMC 2019 and the 40
MeSH term(s)	Anniversaries and Special Events ; Chemistry, Pharmaceutical ; Humans ; Italy ; Societies, Scientific
Language	English
Publishing date	2020-12-23
Publishing country	Germany
Document type	Editorial
ZDB-ID	2218496-X
ISSN	1860-7187 ; 1860-7179
ISSN (online)	1860-7187
ISSN	1860-7179
DOI	10.1002/cmdc.202000926
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Article: Use of acridinium-based photocatalyst in the Giese-type coupling of arylboronic acids with electron poor olefins

Caldarelli, Marina / Laze, Loris / Piazza, Lavinia / Caputo, Giulia / De Amici, Marco / Papeo, Gianluca

Tetrahedron letters. 2022 Aug. 03, v. 103

2022

Abstract: The development of a visible light-mediated Giese-type reaction using arylboronic acids as aryl radical source is described. The synthetic protocol capitalizes on the employment of environmentally benign metal-free catalyst to forge Csp²–Csp³ bonds. ... ...

Abstract	The development of a visible light-mediated Giese-type reaction using arylboronic acids as aryl radical source is described. The synthetic protocol capitalizes on the employment of environmentally benign metal-free catalyst to forge Csp²–Csp³ bonds. Applications of the methodology to the synthesis of aminoesters and the anti-inflammatory drug nabumetone, either in batch or in flow, are also reported.
Keywords	acids ; anti-inflammatory agents ; couplings ; electrons ; olefin ; photocatalysts
Language	English
Dates of publication	2022-0803
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	204287-3
ISSN	1873-3581 ; 0040-4039
ISSN (online)	1873-3581
ISSN	0040-4039
DOI	10.1016/j.tetlet.2022.153978
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Article: M2 Muscarinic Receptor Stimulation Induces Autophagy in Human Glioblastoma Cancer Stem Cells via mTOR Complex-1 Inhibition.

Guerriero, Claudia / Manfredelli, Marianna / Matera, Carlo / Iuzzolino, Angela / Conti, Luciano / Dallanoce, Clelia / De Amici, Marco / Trisciuoglio, Daniela / Tata, Ada Maria

Cancers

2023 Volume 16, Issue 1

Abstract: Background: Although autophagy is a pro-survival process of tumor cells, it can stimulate cell death in particular conditions and when differently regulated by specific signals. We previously demonstrated that the selective stimulation of the M2 ... ...

Abstract	Background: Although autophagy is a pro-survival process of tumor cells, it can stimulate cell death in particular conditions and when differently regulated by specific signals. We previously demonstrated that the selective stimulation of the M2 muscarinic receptor subtype (mAChR) negatively controls cell proliferation and survival and causes oxidative stress and cytotoxic and genotoxic effects in both GBM cell lines and GBM stem cells (GSCs). In this work, we have evaluated whether autophagy was induced as a downstream mechanism of the observed cytotoxic processes induced by M2 mAChR activation by the orthosteric agonist APE or the dualsteric agonist N8-Iper (N8). Methods: To assess the activation of autophagy, we analyzed the expression of LC3B using Western blot analysis and in LC3B-EGFP transfected cell lines. Apoptosis was assessed by measuring the protein expression of Caspases 3 and 9. Results: Our data indicate that activation of M2 mAChR by N8 promotes autophagy in both U251 and GB7 cell lines as suggested by the LC3B-II expression level and analysis of the transfected cells by fluorescence microscopy. Autophagy induction by M2 mAChRs is regulated by the decreased activity of the PI3K/AKT/mTORC1 pathway and upregulated by pAMPK expression. Downstream of autophagy activation, an increase in apoptosis was also observed in both cell lines after treatment with the two M2 agonists. Conclusions: N8 treatment causes autophagy via pAMPK upregulation, followed by apoptosis in both investigated cell lines. In contrast, the absence of autophagy in APE-treated GSC cells seems to indicate that cell death could be triggered by mechanisms alternative to those observed for N8.
Language	English
Publishing date	2023-12-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16010025
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Article ; Online: α7 Nicotinic Acetylcholine Receptors May Improve Schwann Cell Regenerating Potential via Metabotropic Signaling Pathways.

Botticelli, Elisabetta / Guerriero, Claudia / Fucile, Sergio / De Stefano, Maria Egle / Matera, Carlo / Dallanoce, Clelia / De Amici, Marco / Tata, Ada Maria

Cells

2023 Volume 12, Issue 11

Abstract: Background: Schwann cells (SCs) are glial cells involved in peripheral axon myelination. SCs also play a strategic role after peripheral nerve injury, regulating local inflammation and axon regeneration. Our previous studies demonstrated the presence of ...

Abstract	Background: Schwann cells (SCs) are glial cells involved in peripheral axon myelination. SCs also play a strategic role after peripheral nerve injury, regulating local inflammation and axon regeneration. Our previous studies demonstrated the presence of cholinergic receptors in SCs. In particular, the α7 nicotinic acetylcholine receptors (nAChRs) are expressed in SCs after peripheral axotomy, suggesting their involvement in the regulation of SC-regenerating properties. To clarify the role that α7 nAChRs may play after peripheral axon damage, in this study we investigated the signal transduction pathways triggered by receptor activation and the effects produced by their activation. Methods: Both ionotropic and metabotropic cholinergic signaling were analyzed by calcium imaging and Western blot analysis, respectively, following α7 nAChR activation. In addition, the expression of c-Jun and α7 nAChRs was evaluated by immunocytochemistry and Western blot analysis. Finally, the cell migration was studied by a wound healing assay. Results: Activation of α7 nAChRs, activated by the selective partial agonist ICH3, did not induce calcium mobilization but positively modulated the PI3K/AKT/mTORC1 axis. Activation of the mTORC1 complex was also supported by the up-regulated expression of its specific p-p70 S6K Conclusions: Our data demonstrate that α7 nAChRs, expressed by SCs only after peripheral axon damage and/or in an inflammatory microenvironment, contribute to improve the SCs regenerating properties. Indeed, α7 nAChR stimulation leads to an upregulation of c-Jun expression and promotes Schwann cell migration by non-canonical pathways involving the mTORC1 activity.
MeSH term(s)	alpha7 Nicotinic Acetylcholine Receptor/metabolism ; Axons/metabolism ; Calcium/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Nerve Regeneration ; Signal Transduction/physiology ; Schwann Cells/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism
Chemical Substances	alpha7 Nicotinic Acetylcholine Receptor ; Calcium (SY7Q814VUP) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1)
Language	English
Publishing date	2023-05-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12111494
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Article ; Online: Gaucher Disease: A Glance from a Medicinal Chemistry Perspective.

Prencipe, Filippo / Barzan, Chiara / Savian, Chiara / Spalluto, Giampiero / Carosati, Emanuele / De Amici, Marco / Mosconi, Giorgio / Gianferrara, Teresa / Federico, Stephanie / Da Ros, Tatiana

ChemMedChem

2024 , Page(s) e202300641

Abstract: Rare diseases are particular pathological conditions affecting a limited number of people and few drugs are known to be effective as therapeutic treatment. Gaucher disease, caused by a deficiency of the lysosomal enzyme glucocerebrosidase, belongs to ... ...

Abstract	Rare diseases are particular pathological conditions affecting a limited number of people and few drugs are known to be effective as therapeutic treatment. Gaucher disease, caused by a deficiency of the lysosomal enzyme glucocerebrosidase, belongs to this class of disorders, and it is considered the most common among the Lysosomal Storage Diseases. The two main therapeutic approaches are the Enzyme Replacement Therapy (ERT) and the Substrate Reduction Therapy (SRT). ERT, consisting in replacing the defective enzyme by administering a recombinant enzyme, is effective in alleviating the visceral symptoms, hallmarks of the most common subtype of the disease whereas it has no effects when symptoms involve CNS, since the recombinant protein is unable to significantly cross the Blood Brain Barrier. The SRT strategy involves inhibiting glucosylceramide synthase (GCS), the enzyme responsible for the production of the associated storage molecule. The rational design of new inhibitors of GCS has been hampered by the lack of either the crystal structure of the enzyme or an in-silico model of the active site which could provide important information regarding the interactions of potential inhibitors with the target, but, despite this, interesting results have been obtained and are herein reviewed.
Language	English
Publishing date	2024-02-08
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2218496-X
ISSN	1860-7187 ; 1860-7179
ISSN (online)	1860-7187
ISSN	1860-7179
DOI	10.1002/cmdc.202300641
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Article ; Online: Novel Xanomeline-Containing Bitopic Ligands of Muscarinic Acetylcholine Receptors: Design, Synthesis and FRET Investigation.

Matera, Carlo / Kauk, Michael / Cirillo, Davide / Maspero, Marco / Papotto, Claudio / Volpato, Daniela / Holzgrabe, Ulrike / De Amici, Marco / Hoffmann, Carsten / Dallanoce, Clelia

Molecules (Basel, Switzerland)

2023 Volume 28, Issue 5

Abstract: In the last few years, fluorescence resonance energy transfer (FRET) receptor sensors have contributed to the understanding of GPCR ligand binding and functional activation. FRET sensors based on muscarinic acetylcholine receptors (mAChRs) have been ... ...

Abstract	In the last few years, fluorescence resonance energy transfer (FRET) receptor sensors have contributed to the understanding of GPCR ligand binding and functional activation. FRET sensors based on muscarinic acetylcholine receptors (mAChRs) have been employed to study dual-steric ligands, allowing for the detection of different kinetics and distinguishing between partial, full, and super agonism. Herein, we report the synthesis of the two series of bitopic ligands,
MeSH term(s)	Cricetinae ; Animals ; Ligands ; Fluorescence Resonance Energy Transfer ; Receptors, G-Protein-Coupled ; Receptors, Muscarinic ; Receptor, Muscarinic M1/agonists ; Receptor, Muscarinic M1/metabolism ; CHO Cells
Chemical Substances	xanomeline (9ORI6L73CJ) ; Ligands ; Receptors, G-Protein-Coupled ; Receptors, Muscarinic ; Receptor, Muscarinic M1
Language	English
Publishing date	2023-03-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28052407
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Article: Insight into the Mechanism of Hydrolysis of Meropenem by OXA-23 Serine-Î²-lactamase Gained by Quantum Mechanics/Molecular Mechanics Calculations

Sgrignani, Jacopo / Grazioso Giovanni / De Amici Marco

Biochemistry. 2016 Sept. 13, v. 55, no. 36

2016

Abstract: The fast and constant development of drug resistant bacteria represents a serious medical emergency. To overcome this problem, the development of drugs with new structures and modes of action is urgently needed. In this work, we investigated, at the ... ...

Abstract	The fast and constant development of drug resistant bacteria represents a serious medical emergency. To overcome this problem, the development of drugs with new structures and modes of action is urgently needed. In this work, we investigated, at the atomistic level, the mechanisms of hydrolysis of Meropenem by OXA-23, a class D Î²-lactamase, combining unbiased classical molecular dynamics and umbrella sampling simulations with classical force field-based and quantum mechanics/molecular mechanics potentials. Our calculations provide a detailed structural and dynamic picture of the molecular steps leading to the formation of the MeropenemâOXA-23 covalent adduct, the subsequent hydrolysis, and the final release of the inactive antibiotic. In this mechanistic framework, the predicted activation energy is in good agreement with experimental kinetic measurements, validating the expected reaction path.
Keywords	activation energy ; bacteria ; beta-lactamase ; drug resistance ; hydrolysis ; mechanism of action ; meropenem ; molecular dynamics ; new drugs ; quantum mechanics
Language	English
Dates of publication	2016-0913
Size	p. 5191-5200.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021%2Facs.biochem.6b00461
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Zs.A 217: Show issues

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Article ; Online: The Combined Treatment with Chemotherapeutic Agents and the Dualsteric Muscarinic Agonist Iper-8-Naphthalimide Affects Drug Resistance in Glioblastoma Stem Cells.

Guerriero, Claudia / Matera, Carlo / Del Bufalo, Donatella / De Amici, Marco / Conti, Luciano / Dallanoce, Clelia / Tata, Ada Maria

Cells

2021 Volume 10, Issue 8

Abstract: Background: Glioblastoma multiforme (GBM) is characterized by heterogeneous cell populations. Among these, the Glioblastoma Stem Cells (GSCs) fraction shares some similarities with Neural Stem Cells. GSCs exhibit enhanced resistance to conventional ... ...

Abstract	Background: Glioblastoma multiforme (GBM) is characterized by heterogeneous cell populations. Among these, the Glioblastoma Stem Cells (GSCs) fraction shares some similarities with Neural Stem Cells. GSCs exhibit enhanced resistance to conventional chemotherapy drugs. Our previous studies demonstrated that the activation of M2 muscarinic acetylcholine receptors (mAChRs) negatively modulates GSCs proliferation and survival. The aim of the present study was to analyze the ability of the M2 dualsteric agonist Iper-8-naphthalimide (N-8-Iper) to counteract GSCs drug resistance. Methods: Chemosensitivity to M2 dualsteric agonist N-8-Iper and chemotherapy drugs such as temozolomide, doxorubicin, or cisplatin was evaluated in vitro by MTT assay in two different GSC lines. Drug efflux pumps expression was evaluated by RT-PCR and qRT-PCR. Results: By using sub-toxic concentrations of N-8-Iper combined with the individual chemotherapeutic agents, we found that only low doses of the M2 agonist combined with doxorubicin or cisplatin or temozolomide were significantly able to counteract cell growth in both GSC lines. Moreover, we evaluated as the exposure to high and low doses of N-8-Iper downregulated the ATP-binding cassette (ABC) drug efflux pumps expression levels. Conclusions: Our results revealed the ability of the investigated M2 agonist to counteract drug resistance in two GSC lines, at least partially by downregulating the ABC drug efflux pumps expression. The combined effects of low doses of conventional chemotherapy and M2 agonists may thus represent a novel promising pharmacological approach to impair the GSC-drug resistance in the GBM therapy.
MeSH term(s)	ATP-Binding Cassette Transporters/genetics ; ATP-Binding Cassette Transporters/metabolism ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Brain Neoplasms/drug therapy ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cisplatin/pharmacology ; Doxorubicin/pharmacology ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic ; Glioblastoma/drug therapy ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Glioblastoma/pathology ; Humans ; Muscarinic Agonists/pharmacology ; Naphthalimides/pharmacology ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Receptor, Muscarinic M2/agonists ; Receptor, Muscarinic M2/genetics ; Receptor, Muscarinic M2/metabolism ; Signal Transduction ; Temozolomide/pharmacology
Chemical Substances	ATP-Binding Cassette Transporters ; CHRM2 protein, human ; Muscarinic Agonists ; Naphthalimides ; Receptor, Muscarinic M2 ; Doxorubicin (80168379AG) ; Cisplatin (Q20Q21Q62J) ; Temozolomide (YF1K15M17Y)
Language	English
Publishing date	2021-07-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10081877
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