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Article ; Online: The fallacy of functional nomenclature in the kingdom of biological multifunctionality: physiological and evolutionary considerations on ion channels.

Munaron, Luca / Chinigò, Giorgia / Scarpellino, Giorgia / Ruffinatti, Federico Alessandro

2023

Abstract: Living organisms are multiscale complex systems that have evolved high degrees of multifunctionality and redundancy in the structure-function relationship. A number of factors, only in part determined genetically, affect the jobs of proteins. The overall ...

Abstract	Living organisms are multiscale complex systems that have evolved high degrees of multifunctionality and redundancy in the structure-function relationship. A number of factors, only in part determined genetically, affect the jobs of proteins. The overall structural organization confers unique molecular properties that provide the potential to perform a pattern of activities, some of which are co-opted by specific environments. The variety of multifunctional proteins is expanding, but most cases are handled individually and according to the still dominant 'one structure-one function' approach, which relies on the attribution of canonical names typically referring to the first task identified for a given protein. The present topical review focuses on the multifunctionality of ion channels as a paradigmatic example. Mounting evidence reports the ability of many ion channels (including members of voltage-dependent, ligand-gated and transient receptor potential families) to exert biological effects independently of their ion conductivity. 'Functionally based' nomenclature (the practice of naming a protein or family of proteins based on a single purpose) is a conceptual bias for three main reasons: (i) it increases the amount of ambiguity, deceiving our understanding of the multiple contributions of biomolecules that is the heart of the complexity; (ii) it is in stark contrast to protein evolution dynamics, largely based on multidomain arrangement; and (iii) it overlooks the crucial role played by the microenvironment in adjusting the actions of cell structures and in tuning protein isoform diversity to accomplish adaptational requirements. Biological information in protein physiology is distributed among different entwined layers working as the primary 'locus' of natural selection and of evolutionary constraints.
Language	English
Publishing date	2023-08-28
Publishing country	England
Document type	Journal Article
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP284422
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Article ; Online: Vacuum Plasma Treatment Device for Enhancing Fibroblast Activity on Machined and Rough Titanium Surfaces.

Canullo, Luigi / Genova, Tullio / Chinigò, Giorgia / Iacono, Roberta / Pesce, Paolo / Menini, Maria / Mussano, Federico

Dentistry journal

2024 Volume 12, Issue 3

Abstract: This study was conducted to compare the effects of an innovative plasma surface treatment device that does not need a gas supply for titanium disks with two different surface topographies: the prototypical machined surface (MAC) and one of the most ... ...

Abstract	This study was conducted to compare the effects of an innovative plasma surface treatment device that does not need a gas supply for titanium disks with two different surface topographies: the prototypical machined surface (MAC) and one of the most diffused roughened ones (SL) obtained through grit blasting and acid etching. A total of 200-MAC and 200-SL titanium disks were used. Each group of disks was divided into four sub-groups of 40 samples each that were subjected to five different tests. Among these, 150-MAC and 150-SL were considered the test group, and they were treated with plasma for 15, 30, and 60 s after being removed from the sterile packaging. On the other hand, 50-MAC and 50-SL were considered the control group, and they were only removed from sterile plastic vials. The samples were analyzed to evaluate the capability of the plasma treatment in influencing protein adsorption, cell adhesion, proliferation, and microbial growth on the test group disks when compared to the untreated disks. Protein adsorption was significantly enhanced after 20 min of plasma treatment for 15 and 30 s on the MAC and SL disks. Plasma treatment for 15 and 30 s significantly increased the level of adhesion in both treated samples after 30 min. Furthermore, the MAC samples showed a significant increase in cell adhesion 4 h after plasma treatment for 15 s. The SEM analysis highlighted that, on the treated samples (especially on the MAC disks), the cells with a polygonal and flat shape prevailed, while the fusiform- and globular-shaped cells were rare. The encouraging results obtained further confirm the effectiveness of plasma treatments on cell adhesion and fibroblast activity.
Language	English
Publishing date	2024-03-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2681351-8
ISSN	2304-6767 ; 2304-6767
ISSN (online)	2304-6767
ISSN	2304-6767
DOI	10.3390/dj12030071
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Article: The Impact of Plasma Membrane Ion Channels on Bone Remodeling in Response to Mechanical Stress, Oxidative Imbalance, and Acidosis.

Perin, Martina / Chinigò, Giorgia / Genova, Tullio / Mussano, Federico / Munaron, Luca

Antioxidants (Basel, Switzerland)

2023 Volume 12, Issue 3

Abstract: The extracellular milieu is a rich source of different stimuli and stressors. Some of them depend on the chemical-physical features of the matrix, while others may come from the 'outer' environment, as in the case of mechanical loading applied on the ... ...

Abstract	The extracellular milieu is a rich source of different stimuli and stressors. Some of them depend on the chemical-physical features of the matrix, while others may come from the 'outer' environment, as in the case of mechanical loading applied on the bones. In addition to these forces, a plethora of chemical signals drives cell physiology and fate, possibly leading to dysfunctions when the homeostasis is disrupted. This variety of stimuli triggers different responses among the tissues: bones represent a particular milieu in which a fragile balance between mechanical and metabolic demands should be tuned and maintained by the concerted activity of cell biomolecules located at the interface between external and internal environments. Plasma membrane ion channels can be viewed as multifunctional protein machines that act as rapid and selective dual-nature hubs, sensors, and transducers. Here we focus on some multisensory ion channels (belonging to Piezo, TRP, ASIC/EnaC, P2XR, Connexin, and Pannexin families) actually or potentially playing a significant role in bone adaptation to three main stressors, mechanical forces, oxidative stress, and acidosis, through their effects on bone cells including mesenchymal stem cells, osteoblasts, osteoclasts, and osteocytes. Ion channel-mediated bone remodeling occurs in physiological processes, aging, and human diseases such as osteoporosis, cancer, and traumatic events.
Language	English
Publishing date	2023-03-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12030689
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Article ; Online: The Emerging Concept of Transportome: State of the Art.

Ruffinatti, Federico Alessandro / Scarpellino, Giorgia / Chinigò, Giorgia / Visentin, Luca / Munaron, Luca

Physiology (Bethesda, Md.)

2023 Volume 38, Issue 6

Abstract: The array of ion channels and transporters expressed in cell membranes, collectively referred to as the transportome, is a complex and multifunctional molecular machinery; in particular, at the plasma membrane level it finely tunes the exchange of ... ...

Abstract	The array of ion channels and transporters expressed in cell membranes, collectively referred to as the transportome, is a complex and multifunctional molecular machinery; in particular, at the plasma membrane level it finely tunes the exchange of biomolecules and ions, acting as a functionally adaptive interface that accounts for dynamic plasticity in the response to environmental fluctuations and stressors. The transportome is responsible for the definition of membrane potential and its variations, participates in the transduction of extracellular signals, and acts as a filter for most of the substances entering and leaving the cell, thus enabling the homeostasis of many cellular parameters. For all these reasons, physiologists have long been interested in the expression and functionality of ion channels and transporters, in both physiological and pathological settings and across the different domains of life. Today, thanks to the high-throughput technologies of the postgenomic era, the omics approach to the study of the transportome is becoming increasingly popular in different areas of biomedical research, allowing for a more comprehensive, integrated, and functional perspective of this complex cellular apparatus. This article represents a first effort for a systematic review of the scientific literature on this topic. Here we provide a brief overview of all those studies, both primary and meta-analyses, that looked at the transportome as a whole, regardless of the biological problem or the models they used. A subsequent section is devoted to the methodological aspect by reviewing the most important public databases annotating ion channels and transporters, along with the tools they provide to retrieve such information. Before conclusions, limitations and future perspectives are also discussed.
MeSH term(s)	Humans ; Biomedical Research ; Homeostasis ; Membrane Potentials
Language	English
Publishing date	2023-09-05
Publishing country	United States
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	2158667-6
ISSN	1548-9221 ; 1548-9213
ISSN (online)	1548-9221
ISSN	1548-9213
DOI	10.1152/physiol.00010.2023
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Article: TRP Channels in Brain Tumors.

Chinigò, Giorgia / Castel, Hélène / Chever, Oana / Gkika, Dimitra

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 617801

Abstract: Malignant glioma including glioblastoma (GBM) is the most common group of primary brain tumors. Despite standard optimized treatment consisting of extensive resection followed by radiotherapy/concomitant and adjuvant therapy, GBM remains one of the most ... ...

Abstract	Malignant glioma including glioblastoma (GBM) is the most common group of primary brain tumors. Despite standard optimized treatment consisting of extensive resection followed by radiotherapy/concomitant and adjuvant therapy, GBM remains one of the most aggressive human cancers. GBM is a typical example of intra-heterogeneity modeled by different micro-environmental situations, one of the main causes of resistance to conventional treatments. The resistance to treatment is associated with angiogenesis, hypoxic and necrotic tumor areas while heterogeneity would accumulate during glioma cell invasion, supporting recurrence. These complex mechanisms require a focus on potential new molecular actors to consider new treatment options for gliomas. Among emerging and underexplored targets, transient receptor potential (TRP) channels belonging to a superfamily of non-selective cation channels which play critical roles in the responses to a number of external stimuli from the external environment were found to be related to cancer development, including glioma. Here, we discuss the potential as biological markers of diagnosis and prognosis of TRPC6, TRPM8, TRPV4, or TRPV1/V2 being associated with glioma patient overall survival. TRPs-inducing common or distinct mechanisms associated with their Ca
Language	English
Publishing date	2021-04-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.617801
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Article: BioTEA: Containerized Methods of Analysis for Microarray-Based Transcriptomics Data.

Visentin, Luca / Scarpellino, Giorgia / Chinigò, Giorgia / Munaron, Luca / Ruffinatti, Federico Alessandro

Biology

2022 Volume 11, Issue 9

Abstract: Tens of thousands of gene expression data sets describing a variety of model organisms in many different pathophysiological conditions are currently stored in publicly available databases such as the Gene Expression Omnibus (GEO) and ArrayExpress (AE). ... ...

Abstract	Tens of thousands of gene expression data sets describing a variety of model organisms in many different pathophysiological conditions are currently stored in publicly available databases such as the Gene Expression Omnibus (GEO) and ArrayExpress (AE). As microarray technology is giving way to RNA-seq, it becomes strategic to develop high-level tools of analysis to preserve access to this huge amount of information through the most sophisticated methods of data preparation and processing developed over the years, while ensuring, at the same time, the reproducibility of the results. To meet this need, here we present bioTEA (biological Transcript Expression Analyzer), a novel software tool that combines ease of use with the versatility and power of an R/Bioconductor-based differential expression analysis, starting from raw data retrieval and preparation to gene annotation. BioTEA is an R-coded pipeline, wrapped in a Python-based command line interface and containerized with Docker technology. The user can choose among multiple options-including gene filtering, batch effect handling, sample pairing, statistical test type-to adapt the algorithm flow to the structure of the particular data set. All these options are saved in a single text file, which can be easily shared between different laboratories to deterministically reproduce the results. In addition, a detailed log file provides accurate information about each step of the analysis. Overall, these features make bioTEA an invaluable tool for both bioinformaticians and wet-lab biologists interested in transcriptomics. BioTEA is free and open-source.
Language	English
Publishing date	2022-09-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology11091346
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Article: TRP Channels and Small GTPases Interplay in the Main Hallmarks of Metastatic Cancer.

Chinigò, Giorgia / Fiorio Pla, Alessandra / Gkika, Dimitra

Frontiers in pharmacology

2020 Volume 11, Page(s) 581455

Abstract: Transient Receptor Potential (TRP) cations channels, as key regulators of intracellular calcium homeostasis, play a central role in the essential hallmarks of cancer. Among the multiple pathways in which TRPs may be involved, here we focus our attention ... ...

Abstract	Transient Receptor Potential (TRP) cations channels, as key regulators of intracellular calcium homeostasis, play a central role in the essential hallmarks of cancer. Among the multiple pathways in which TRPs may be involved, here we focus our attention on the ones involving small guanosine triphosphatases (GTPases), summarizing the main processes associated with the metastatic cascade, such as migration, invasion and tumor vascularization. In the last decade, several studies have highlighted a bidirectional interplay between TRPs and small GTPases in cancer progression: TRP channels may affect small GTPases activity
Language	English
Publishing date	2020-09-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.581455
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Article: Oral Cavity as a Source of Mesenchymal Stem Cells Useful for Regenerative Medicine in Dentistry.

Roato, Ilaria / Chinigò, Giorgia / Genova, Tullio / Munaron, Luca / Mussano, Federico

Biomedicines

2021 Volume 9, Issue 9

Abstract: The use of mesenchymal stem cells (MSCs) for regenerative purposes has become common in a large variety of diseases. In the dental and maxillofacial field, there are emerging clinical needs that could benefit from MSC-based therapeutic approaches. Even ... ...

Abstract	The use of mesenchymal stem cells (MSCs) for regenerative purposes has become common in a large variety of diseases. In the dental and maxillofacial field, there are emerging clinical needs that could benefit from MSC-based therapeutic approaches. Even though MSCs can be isolated from different tissues, such as bone marrow, adipose tissue, etc., and are known for their multilineage differentiation, their different anatomical origin can affect the capability to differentiate into a specific tissue. For instance, MSCs isolated from the oral cavity might be more effective than adipose-derived stem cells (ASCs) for the treatment of dental defects. Indeed, in the oral cavity, there are different sources of MSCs that have been individually proposed as promising candidates for tissue engineering protocols. The therapeutic strategy based on MSCs can be direct, by using cells as components of the tissue to be regenerated, or indirect, aimed at delivering local growth factors, cytokines, and chemokines produced by the MSCs. Here, the authors outline the major sources of mesenchymal stem cells attainable from the oral cavity and discuss their possible usage in some of the most compelling therapeutic frontiers, such as periodontal disease and dental pulp regeneration.
Language	English
Publishing date	2021-08-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines9091085
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Article ; Online: TRP Channels in Brain Tumors

Giorgia Chinigò / Hélène Castel / Oana Chever / Dimitra Gkika

Frontiers in Cell and Developmental Biology, Vol

2021 Volume 9

Abstract	Malignant glioma including glioblastoma (GBM) is the most common group of primary brain tumors. Despite standard optimized treatment consisting of extensive resection followed by radiotherapy/concomitant and adjuvant therapy, GBM remains one of the most aggressive human cancers. GBM is a typical example of intra-heterogeneity modeled by different micro-environmental situations, one of the main causes of resistance to conventional treatments. The resistance to treatment is associated with angiogenesis, hypoxic and necrotic tumor areas while heterogeneity would accumulate during glioma cell invasion, supporting recurrence. These complex mechanisms require a focus on potential new molecular actors to consider new treatment options for gliomas. Among emerging and underexplored targets, transient receptor potential (TRP) channels belonging to a superfamily of non-selective cation channels which play critical roles in the responses to a number of external stimuli from the external environment were found to be related to cancer development, including glioma. Here, we discuss the potential as biological markers of diagnosis and prognosis of TRPC6, TRPM8, TRPV4, or TRPV1/V2 being associated with glioma patient overall survival. TRPs-inducing common or distinct mechanisms associated with their Ca2+-channel permeability and/or kinase function were detailed as involving miRNA or secondary effector signaling cascades in turn controlling proliferation, cell cycle, apoptotic pathways, DNA repair, resistance to treatment as well as migration/invasion. These recent observations of the key role played by TRPs such as TRPC6 in GBM growth and invasiveness, TRPV2 in proliferation and glioma-stem cell differentiation and TRPM2 as channel carriers of cytotoxic chemotherapy within glioma cells, should offer new directions for innovation in treatment strategies of high-grade glioma as GBM to overcome high resistance and recurrence.
Keywords	ion channel ; TRP channel ; brain tumor ; glioma ; glioblastoma ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: The Impact of Plasma Membrane Ion Channels on Bone Remodeling in Response to Mechanical Stress, Oxidative Imbalance, and Acidosis

Perin, Martina / Chinigò, Giorgia / Genova, Tullio / Mussano, Federico / Munaron, Luca

Antioxidants. 2023 Mar. 10, v. 12, no. 3

2023

Abstract: The extracellular milieu is a rich source of different stimuli and stressors. Some of them depend on the chemical–physical features of the matrix, while others may come from the ‘outer’ environment, as in the case of mechanical loading applied on the ... ...

Abstract	The extracellular milieu is a rich source of different stimuli and stressors. Some of them depend on the chemical–physical features of the matrix, while others may come from the ‘outer’ environment, as in the case of mechanical loading applied on the bones. In addition to these forces, a plethora of chemical signals drives cell physiology and fate, possibly leading to dysfunctions when the homeostasis is disrupted. This variety of stimuli triggers different responses among the tissues: bones represent a particular milieu in which a fragile balance between mechanical and metabolic demands should be tuned and maintained by the concerted activity of cell biomolecules located at the interface between external and internal environments. Plasma membrane ion channels can be viewed as multifunctional protein machines that act as rapid and selective dual-nature hubs, sensors, and transducers. Here we focus on some multisensory ion channels (belonging to Piezo, TRP, ASIC/EnaC, P2XR, Connexin, and Pannexin families) actually or potentially playing a significant role in bone adaptation to three main stressors, mechanical forces, oxidative stress, and acidosis, through their effects on bone cells including mesenchymal stem cells, osteoblasts, osteoclasts, and osteocytes. Ion channel-mediated bone remodeling occurs in physiological processes, aging, and human diseases such as osteoporosis, cancer, and traumatic events.
Keywords	acidosis ; cell physiology ; connexins ; homeostasis ; humans ; mechanical stress ; osteoblasts ; osteoclasts ; osteoporosis ; oxidative stress ; pannexins ; plasma membrane
Language	English
Dates of publication	2023-0310
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12030689
Database	NAL-Catalogue (AGRICOLA)

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