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Article ; Online: Mechanobiology of the Human Intervertebral Disc: Systematic Review of the Literature and Future Perspectives.

Ruffilli, Alberto / Viroli, Giovanni / Neri, Simona / Traversari, Matteo / Barile, Francesca / Manzetti, Marco / Assirelli, Elisa / Ialuna, Marco / Vita, Fabio / Faldini, Cesare

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: Low back pain is an extremely common condition with severe consequences. Among its potential specific causes, degenerative disc disease (DDD) is one of the most frequently observed. Mechanobiology is an emerging science studying the interplay between ... ...

Abstract	Low back pain is an extremely common condition with severe consequences. Among its potential specific causes, degenerative disc disease (DDD) is one of the most frequently observed. Mechanobiology is an emerging science studying the interplay between mechanical stimuli and the biological behavior of cells and tissues. The aim of the presented study is to review, with a systematic approach, the existing literature regarding the mechanobiology of the human intervertebral disc (IVD), define the main pathways involved in DDD and identify novel potential therapeutic targets. The review was carried out in accordance with the Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies were included if they described biological responses of human IVD cells under mechanical stimulation or alterations of mechanical properties of the IVD determined by different gene expression. Fifteen studies were included and showed promising results confirming the mechanobiology of the human IVD as a key element in DDD. The technical advances of the last decade have allowed us to increase our understanding of this topic, enabling us to identify possible therapeutic targets to treat and to prevent DDD. Further research and technological innovations will shed light on the interactions between the mechanics and biology of the human IVD.
MeSH term(s)	Humans ; Biophysics ; Intervertebral Disc/metabolism ; Intervertebral Disc Degeneration/genetics ; Intervertebral Disc Degeneration/metabolism ; Low Back Pain
Language	English
Publishing date	2023-02-01
Publishing country	Switzerland
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24032728
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Epigenetic Factors Related to Low Back Pain: A Systematic Review of the Current Literature.

Ruffilli, Alberto / Neri, Simona / Manzetti, Marco / Barile, Francesca / Viroli, Giovanni / Traversari, Matteo / Assirelli, Elisa / Vita, Fabio / Geraci, Giuseppe / Faldini, Cesare

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: Low back pain (LBP) is one of the most common causes of pain and disability. At present, treatment and interventions for acute and chronic low back pain often fail to provide sufficient levels of pain relief, and full functional restoration can be ... ...

Abstract	Low back pain (LBP) is one of the most common causes of pain and disability. At present, treatment and interventions for acute and chronic low back pain often fail to provide sufficient levels of pain relief, and full functional restoration can be challenging. Considering the significant socio-economic burden and risk-to-benefit ratio of medical and surgical intervention in low back pain patients, the identification of reliable biomarkers such as epigenetic factors associated with low back pain could be useful in clinical practice. The aim of this study was to review the available literature regarding the epigenetic factors associated with low back pain. This review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was carried out in October 2022. Only peer-reviewed articles were considered for inclusion. Fourteen studies were included and showed promising results in terms of reliable markers. Epigenetic markers for LBP have the potential to significantly modify disease management. Most recent evidence suggests that epigenetics is a more promising field for the identification of factors associated with LBP, offering a rationale for further investigation in this field with the long-term goal of finding epigenetic biomarkers that could constitute biological targets for disease management and treatment.
MeSH term(s)	Humans ; Low Back Pain/genetics ; Low Back Pain/therapy ; Pain Management ; Exercise Therapy
Language	English
Publishing date	2023-01-17
Publishing country	Switzerland
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24031854
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Article ; Online: Mechanobiology of the Human Intervertebral Disc

Alberto Ruffilli / Giovanni Viroli / Simona Neri / Matteo Traversari / Francesca Barile / Marco Manzetti / Elisa Assirelli / Marco Ialuna / Fabio Vita / Cesare Faldini

International Journal of Molecular Sciences, Vol 24, Iss 2728, p

Systematic Review of the Literature and Future Perspectives

2023 Volume 2728

Abstract	Low back pain is an extremely common condition with severe consequences. Among its potential specific causes, degenerative disc disease (DDD) is one of the most frequently observed. Mechanobiology is an emerging science studying the interplay between mechanical stimuli and the biological behavior of cells and tissues. The aim of the presented study is to review, with a systematic approach, the existing literature regarding the mechanobiology of the human intervertebral disc (IVD), define the main pathways involved in DDD and identify novel potential therapeutic targets. The review was carried out in accordance with the Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies were included if they described biological responses of human IVD cells under mechanical stimulation or alterations of mechanical properties of the IVD determined by different gene expression. Fifteen studies were included and showed promising results confirming the mechanobiology of the human IVD as a key element in DDD. The technical advances of the last decade have allowed us to increase our understanding of this topic, enabling us to identify possible therapeutic targets to treat and to prevent DDD. Further research and technological innovations will shed light on the interactions between the mechanics and biology of the human IVD.
Keywords	mechanobiology ; mechanotransduction ; degenerative disc disease ; intervertebral disc ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Epigenetic Factors Related to Low Back Pain

Alberto Ruffilli / Simona Neri / Marco Manzetti / Francesca Barile / Giovanni Viroli / Matteo Traversari / Elisa Assirelli / Fabio Vita / Giuseppe Geraci / Cesare Faldini

International Journal of Molecular Sciences, Vol 24, Iss 1854, p

A Systematic Review of the Current Literature

2023 Volume 1854

Abstract	Low back pain (LBP) is one of the most common causes of pain and disability. At present, treatment and interventions for acute and chronic low back pain often fail to provide sufficient levels of pain relief, and full functional restoration can be challenging. Considering the significant socio-economic burden and risk-to-benefit ratio of medical and surgical intervention in low back pain patients, the identification of reliable biomarkers such as epigenetic factors associated with low back pain could be useful in clinical practice. The aim of this study was to review the available literature regarding the epigenetic factors associated with low back pain. This review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was carried out in October 2022. Only peer-reviewed articles were considered for inclusion. Fourteen studies were included and showed promising results in terms of reliable markers. Epigenetic markers for LBP have the potential to significantly modify disease management. Most recent evidence suggests that epigenetics is a more promising field for the identification of factors associated with LBP, offering a rationale for further investigation in this field with the long-term goal of finding epigenetic biomarkers that could constitute biological targets for disease management and treatment.
Keywords	low back pain ; epigenetics ; spine ; therapeutic target ; onset ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: NMR-based approaches for the identification and optimization of inhibitors of protein-protein interactions.

Barile, Elisa / Pellecchia, Maurizio

Chemical reviews

2014 Volume 114, Issue 9, Page(s) 4749–4763

MeSH term(s)	Biophysics ; Drug Design ; Ligands ; Magnetic Resonance Spectroscopy/methods ; Protein Binding/drug effects ; Proteins/antagonists & inhibitors ; Proteins/chemistry
Chemical Substances	Ligands ; Proteins
Language	English
Publishing date	2014-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	207949-5
ISSN	1520-6890 ; 0009-2665
ISSN (online)	1520-6890
ISSN	0009-2665
DOI	10.1021/cr500043b
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Enthalpy-Based Screening of Focused Combinatorial Libraries for the Identification of Potent and Selective Ligands.

Baggio, Carlo / Udompholkul, Parima / Barile, Elisa / Pellecchia, Maurizio

ACS chemical biology

2017

Abstract: In modern drug discovery, the ability of biophysical methods, including nuclear magnetic resonance spectroscopy or surface plasmon resonance, to detect and characterize ligand-protein interactions accurately and unambiguously makes these approaches ... ...

Abstract	In modern drug discovery, the ability of biophysical methods, including nuclear magnetic resonance spectroscopy or surface plasmon resonance, to detect and characterize ligand-protein interactions accurately and unambiguously makes these approaches preferred versus conventional biochemical high-throughput screening of large collections of compounds. Nonetheless, ligand screening strategies that address simultaneously potency and selectivity have not yet been fully developed. In this work, we propose a novel method for screening large collections of combinatorial libraries using enthalpy measurements as a primary screening technique. We demonstrate that selecting binders that are driven by enthalpy (ΔH) results in agents that are not only potent but also more selective for a given target. This general and novel approach, we termed ΔH screening of fPOS (enthalpy screening of focused positional scanning library), combines the principles of focused combinatorial chemistry with rapid calorimetry measurements to efficiently identify potent and selective inhibitors.
Language	English
Publishing date	2017-11-02
Publishing country	United States
Document type	Journal Article
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.7b00717
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming.

Barile, Elisa / Baggio, Carlo / Gambini, Luca / Shiryaev, Sergey A / Strongin, Alex Y / Pellecchia, Maurizio

Molecules (Basel, Switzerland)

2020 Volume 25, Issue 10

Abstract: Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2') cleavage sites that are processed by human host proteases. ...

Abstract	Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2') cleavage sites that are processed by human host proteases. The exact nature of these cleavage sites, and their respective processing proteases, can determine whether the virus can cross species and the level of pathogenicity. Recent comparisons of the genomes of the highly pathogenic SARS-CoV2 and MERS-CoV, with less pathogenic strains (e.g., Bat-RaTG13, the bat homologue of SARS-CoV2) identified possible mutations in the receptor binding domain and in the S1 and S2' cleavage sites of their spike glycoprotein. However, there remains some confusion on the relative roles of the possible serine proteases involved for priming. Using anthrax toxin as a model system, we show that in vivo inhibition of priming by pan-active serine protease inhibitors can be effective at suppressing toxicity. Hence, our studies should encourage further efforts in developing either pan-serine protease inhibitors or inhibitor cocktails to target SARS-CoV2 and potentially ward off future pandemics that could develop because of additional mutations in the S-protein priming sequence in coronaviruses.
MeSH term(s)	Animals ; Antigens, Bacterial/toxicity ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Bacterial Toxins/toxicity ; Betacoronavirus/pathogenicity ; Binding Sites ; COVID-19 ; Coronavirus Infections/drug therapy ; Drug Delivery Systems ; Female ; Furin/pharmacology ; Humans ; Mice ; Mice, Inbred BALB C ; Models, Molecular ; Pandemics ; Pneumonia, Viral/drug therapy ; RAW 264.7 Cells ; SARS-CoV-2 ; Serine Proteases/metabolism ; Serine Proteinase Inhibitors/pharmacology ; Serine Proteinase Inhibitors/therapeutic use ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	Antigens, Bacterial ; Antiviral Agents ; Bacterial Toxins ; Serine Proteinase Inhibitors ; Spike Glycoprotein, Coronavirus ; anthrax toxin ; spike protein, SARS-CoV-2 ; Serine Proteases (EC 3.4.-) ; Furin (EC 3.4.21.75)
Keywords	covid19
Language	English
Publishing date	2020-05-22
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/molecules25102424
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Article ; Online: Cyparissins A and B, jatrophane diterpenes from Euphorbia cyparissias as Pgp inhibitors and cytotoxic agents against ovarian cancer cell lines.

Lanzotti, Virginia / Barile, Elisa / Scambia, Giovanni / Ferlini, Cristiano

Fitoterapia

2015 Volume 104, Page(s) 75–79

Abstract: From the whole plant of Euphorbia cyparissias, two new diterpenes based on jatrophane skeleton, named cyparissins A and B (1 and 2) were isolated. Their chemical structures were established through a combination of nuclear magnetic resonance spectroscopy ...

Abstract	From the whole plant of Euphorbia cyparissias, two new diterpenes based on jatrophane skeleton, named cyparissins A and B (1 and 2) were isolated. Their chemical structures were established through a combination of nuclear magnetic resonance spectroscopy and mass spectrometric methods. The new cyparissins A and B were tested to evaluate their ability to inhibit P-glycoprotein-mediated multidrug resistance and their cytotoxic activity against A2780 human ovarian cancer cells, both WT and ADR. Compounds 1 and 2 showed moderate inhibitory effects on P-glycoprotein while showing a significant concentration-depending cytotoxic activity for both cancer cell lines. These isolated compounds are based on a new chemical structure that expands the knowledge base for this class of bioactive metabolites.
MeSH term(s)	ATP-Binding Cassette, Sub-Family B, Member 1/antagonists & inhibitors ; ATP-Binding Cassette, Sub-Family B, Member 1/metabolism ; Antineoplastic Agents, Phytogenic/pharmacology ; Cell Line, Tumor/drug effects ; Diterpenes/pharmacology ; Drug Resistance, Multiple/drug effects ; Drug Resistance, Neoplasm/drug effects ; Euphorbia/chemistry ; Female ; Humans ; Molecular Structure ; Ovarian Neoplasms/pathology
Chemical Substances	ATP-Binding Cassette, Sub-Family B, Member 1 ; Antineoplastic Agents, Phytogenic ; Diterpenes ; cyparissin A ; cyparissin B ; jatrophane
Language	English
Publishing date	2015-07
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	412385-2
ISSN	1873-6971 ; 0367-326X
ISSN (online)	1873-6971
ISSN	0367-326X
DOI	10.1016/j.fitote.2015.05.012
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Article: Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming

Barile, Elisa / Baggio, Carlo / Gambini, Luca / Shiryaev, Sergey A / Strongin, Alex Y / Pellecchia, Maurizio

Molecules (Basel)

Abstract	Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2') cleavage sites that are processed by human host proteases. The exact nature of these cleavage sites, and their respective processing proteases, can determine whether the virus can cross species and the level of pathogenicity. Recent comparisons of the genomes of the highly pathogenic SARS-CoV2 and MERS-CoV, with less pathogenic strains (e.g., Bat-RaTG13, the bat homologue of SARS-CoV2) identified possible mutations in the receptor binding domain and in the S1 and S2' cleavage sites of their spike glycoprotein. However, there remains some confusion on the relative roles of the possible serine proteases involved for priming. Using anthrax toxin as a model system, we show that in vivo inhibition of priming by pan-active serine protease inhibitors can be effective at suppressing toxicity. Hence, our studies should encourage further efforts in developing either pan-serine protease inhibitors or inhibitor cocktails to target SARS-CoV2 and potentially ward off future pandemics that could develop because of additional mutations in the S-protein priming sequence in coronaviruses.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #343433
Database	COVID19

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Book ; Online: Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming

Elisa Barile / Carlo Baggio / Luca Gambini / Sergey A. Shiryaev / Alex Y. Strongin and Maurizio Pellecchia

Molecules ; Volume 25 ; Issue 10

2020

Abstract: Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2′ ... cleavage sites that are processed by human host ... ...

Abstract	Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2′ ) cleavage sites that are processed by human host proteases. The exact nature of these cleavage sites, and their respective processing proteases, can determine whether the virus can cross species and the level of pathogenicity. Recent comparisons of the genomes of the highly pathogenic SARS-CoV2 and MERS-CoV, with less pathogenic strains (e.g., Bat-RaTG13, the bat homologue of SARS-CoV2) identified possible mutations in the receptor binding domain and in the S1 and S2′ cleavage sites of their spike glycoprotein. However, there remains some confusion on the relative roles of the possible serine proteases involved for priming. Using anthrax toxin as a model system, we show that in vivo inhibition of priming by pan-active serine protease inhibitors can be effective at suppressing toxicity. Hence, our studies should encourage further efforts in developing either pan-serine protease inhibitors or inhibitor cocktails to target SARS-CoV2 and potentially ward off future pandemics that could develop because of additional mutations in the S-protein priming sequence in coronaviruses.
Keywords	COVID19 ; SARS-COV2 ; Anthrax toxin ; protecting antigen ; furin ; TMPRSS2 ; covid19
Subject code	570
Language	English
Publishing date	2020-05-22
Publisher	Multidisciplinary Digital Publishing Institute
Publishing country	ch
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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