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Article ; Online: Novel Small Molecule Inhibitors That Prevent the Neuroparalysis of Tetanus Neurotoxin

Giulia Zanetti / Andrea Mattarei / Florigio Lista / Ornella Rossetto / Cesare Montecucco / Marco Pirazzini

Pharmaceuticals, Vol 14, Iss 1134, p

2021 Volume 1134

Abstract: Tetanus neurotoxin (TeNT) is a protein exotoxin produced by Clostridium tetani that causes the deadly spastic neuroparalysis of tetanus. It consists of a metalloprotease light chain and of a heavy chain linked via a disulphide bond. TeNT binds to the ... ...

Abstract	Tetanus neurotoxin (TeNT) is a protein exotoxin produced by Clostridium tetani that causes the deadly spastic neuroparalysis of tetanus. It consists of a metalloprotease light chain and of a heavy chain linked via a disulphide bond. TeNT binds to the neuromuscular junction (NMJ) and it is retro-axonally transported into vesicular compartments to the spinal cord, where it is released and taken up by inhibitory interneuron. Therein, the catalytic subunit is translocated into the cytoplasm where it cleaves its target protein VAMP-1/2 with consequent blockage of the release of inhibitory neurotransmitters. Vaccination with formaldehyde inactivated TeNT prevents the disease, but tetanus is still present in countries where vaccination coverage is partial. Here, we show that small molecule inhibitors interfering with TeNT trafficking or with the reduction of the interchain disulphide bond block the activity of the toxin in neuronal cultures and attenuate tetanus symptoms in vivo. These findings are relevant for the development of therapeutics against tetanus based on the inhibition of toxin molecules that are being retro-transported to or are already within the spinal cord and are, thus, not accessible to anti-TeNT immunoglobulins.
Keywords	tetanus neurotoxin ; trafficking ; disulfide reduction ; thioredoxin system inhibitors ; EGA ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Controlled Liposome Delivery from Chitosan-Based Thermosensitive Hydrogel for Regenerative Medicine

Franco Furlani / Arianna Rossi / Maria Aurora Grimaudo / Giada Bassi / Elena Giusto / Filippo Molinari / Florigio Lista / Monica Montesi / Silvia Panseri

International Journal of Molecular Sciences, Vol 23, Iss 894, p

2022 Volume 894

Abstract: This work describes the development of an injectable nanocomposite system based on a chitosan thermosensitive hydrogel combined with liposomes for regenerative medicine applications. Liposomes with good physicochemical properties are prepared and ... ...

Abstract	This work describes the development of an injectable nanocomposite system based on a chitosan thermosensitive hydrogel combined with liposomes for regenerative medicine applications. Liposomes with good physicochemical properties are prepared and embedded within the chitosan network. The resulting nanocomposite hydrogel is able to provide a controlled release of the content from liposomes, which are able to interact with cells and be internalized. The cellular uptake is enhanced by the presence of a chitosan coating, and cells incubated with liposomes embedded within thermosensitive hydrogels displayed a higher cell uptake compared to cells incubated with liposomes alone. Furthermore, the gelation temperature of the system resulted to be equal to 32.6 °C; thus, the system can be easily injected in the target site to form a hydrogel at physiological temperature. Given the peculiar performance of the selected systems, the resulting thermosensitive hydrogels are a versatile platform and display potential applications as controlled delivery systems of liposomes for tissue regeneration.
Keywords	thermosensitive hydrogel ; regenerative medicine ; liposome ; controlled delivery ; extracellular vesicles ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Latrotoxin-Induced Neuromuscular Junction Degeneration Reveals Urocortin 2 as a Critical Contributor to Motor Axon Terminal Regeneration

Giorgia D’Este / Marco Stazi / Samuele Negro / Aram Megighian / Florigio Lista / Ornella Rossetto / Cesare Montecucco / Michela Rigoni / Marco Pirazzini

International Journal of Molecular Sciences, Vol 23, Iss 1186, p

2022 Volume 1186

Abstract: We used α-Latrotoxin (α-LTx), the main neurotoxic component of the black widow spider venom, which causes degeneration of the neuromuscular junction (NMJ) followed by a rapid and complete regeneration, as a molecular tool to identify by RNA ... ...

Abstract	We used α-Latrotoxin (α-LTx), the main neurotoxic component of the black widow spider venom, which causes degeneration of the neuromuscular junction (NMJ) followed by a rapid and complete regeneration, as a molecular tool to identify by RNA transcriptomics factors contributing to the structural and functional recovery of the NMJ. We found that Urocortin 2 (UCN2), a neuropeptide involved in the stress response, is rapidly expressed at the NMJ after acute damage and that inhibition of CRHR2, the specific receptor of UCN2, delays neuromuscular transmission rescue. Experiments in neuronal cultures show that CRHR2 localises at the axonal tips of growing spinal motor neurons and that its expression inversely correlates with synaptic maturation. Moreover, exogenous UCN2 enhances the growth of axonal sprouts in cultured neurons in a CRHR2-dependent manner, pointing to a role of the UCN2-CRHR2 axis in the regulation of axonal growth and synaptogenesis. Consistently, exogenous administration of UCN2 strongly accelerates the regrowth of motor axon terminals degenerated by α-LTx, thereby contributing to the functional recovery of neuromuscular transmission after damage. Taken together, our results posit a novel role for UCN2 and CRHR2 as a signalling axis involved in NMJ regeneration.
Keywords	α-Latrotoxin ; neuromuscular junction ; nerve degeneration ; nerve regeneration ; Urocortin 2 ; CRHR2 receptor ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genetic Diversity of Antimicrobial Resistance and Key Virulence Features in Two Extensively Drug-Resistant Acinetobacter baumannii Isolates

Massimiliano Marazzato / Daniela Scribano / Meysam Sarshar / Francesca Brunetti / Silvia Fillo / Antonella Fortunato / Florigio Lista / Anna Teresa Palamara / Carlo Zagaglia / Cecilia Ambrosi

International Journal of Environmental Research and Public Health, Vol 19, Iss 2870, p

2022 Volume 2870

Abstract: In recent decades, Acinetobacter baumannii emerged as a major infective menace in healthcare settings due to scarce therapeutic options to treat infections. Therefore, undertaking genome comparison analyses of multi-resistant A. baumannii strains could ... ...

Abstract	In recent decades, Acinetobacter baumannii emerged as a major infective menace in healthcare settings due to scarce therapeutic options to treat infections. Therefore, undertaking genome comparison analyses of multi-resistant A. baumannii strains could aid the identification of key bacterial determinants to develop innovative anti-virulence approaches. Following genome sequencing, we performed a molecular characterization of key genes and genomic comparison of two A. baumannii strains, #36 and #150, with selected reference genomes. Despite a different antibiotic resistance gene content, the analyzed strains showed a very similar antibiogram profile. Interestingly, the lack of some important virulence determinants (i.e., bap , ata and omp33 – 36 ) did not abrogate their adhesive abilities to abiotic and biotic surfaces, as reported before; indeed, strains retained these capacities, although to a different extent, suggesting the presence of distinct vicarious genes. Conversely, secretion systems, lipopolysaccharide (LPS), capsule and iron acquisition systems were highly similar to A. baumannii reference strains. Overall, our analyses increased our knowledge on A. baumannii genomic content and organization as well as the genomic events occurring in nosocomial isolates to better fit into changing healthcare environments.
Keywords	Acinetobacter baumannii ; microbial genomics ; multidrug resistance ; healthcare infections ; Medicine ; R
Subject code	630
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: An agonist of the CXCR4 receptor is therapeutic for the neuroparalysis induced by Bungarus snakes envenoming

Marco Stazi / Federico Fabris / Kae Yi Tan / Aram Megighian / Alessandro Rubini / Andrea Mattarei / Samuele Negro / Giorgia D'Este / Florigio Lista / Ornella Rossetto / Choo Hock Tan / Cesare Montecucco

Clinical and Translational Medicine, Vol 12, Iss 1, Pp n/a-n/a (2022)

2022

Keywords	Medicine (General) ; R5-920
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Meningococcal B vaccine antigen FHbp variants among disease-causing Neisseria meningitidis B isolates, Italy, 2014-2017.

Anna Carannante / Cecilia Fazio / Arianna Neri / Florigio Lista / Silvia Fillo / Andrea Ciammaruconi / Paola Vacca / Paola Stefanelli

PLoS ONE, Vol 15, Iss 11, p e

2020 Volume 0241793

Abstract: Background Typing of Neisseria meningitidis isolates is crucial for the surveillance of invasive meningococcal disease (IMD). We performed a molecular epidemiology study of N. meningitidis serogroup B (MenB) causing IMD in Italy between 2014 and 2017 to ... ...

Abstract	Background Typing of Neisseria meningitidis isolates is crucial for the surveillance of invasive meningococcal disease (IMD). We performed a molecular epidemiology study of N. meningitidis serogroup B (MenB) causing IMD in Italy between 2014 and 2017 to describe circulating strains belonging to this serogroup, with particular regards to the two factor H-binding protein (FHbp) subfamilies present in the bivalent MenB vaccine. Materials and methods A total of 109 culture positive and 46 culture negative MenB samples were collected within the National Surveillance System (NSS) of IMD in Italy and molecularly analyzed by conventional methods. Results Overall, 71 MenB samples showed the FHbp subfamily A and 83 the subfamily B. The subfamily variants were differently distributed by age. The most frequent variants, A05 and B231, were associated with cc213 and cc162, respectively. All MenB with the FHbp A05 variant displayed the PorA P1.22,14 and 85.7% of them the FetA F5-5. The majority of MenB with the FHbp B231 variant showed the PorA P1.22,14 (65.4%) and 84.6%, the FetA F3-6. Conclusion MenB circulating in Italy were characterized by a remarkable association between clonal complex and FHbp variants, although a high degree of genetic diversity observed over time. A dynamic trend in clonal complexes distribution within MenB was detected. Our results stress the importance of continued meningococcal molecular surveillance to evaluate the potential vaccine coverage of the available MenB vaccines.
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: An agonist of the CXCR4 receptor accelerates the recovery from the peripheral neuroparalysis induced by Taipan snake envenomation.

Marco Stazi / Giorgia D'Este / Andrea Mattarei / Samuele Negro / Florigio Lista / Michela Rigoni / Aram Megighian / Cesare Montecucco

PLoS Neglected Tropical Diseases, Vol 14, Iss 9, p e

2020 Volume 0008547

Abstract: Envenomation by snakes is a major neglected human disease. Hospitalization and use of animal-derived antivenom are the primary therapeutic supports currently available. There is consensus that additional, not expensive, treatments that can be delivered ... ...

Abstract	Envenomation by snakes is a major neglected human disease. Hospitalization and use of animal-derived antivenom are the primary therapeutic supports currently available. There is consensus that additional, not expensive, treatments that can be delivered even long after the snake bite are needed. We recently showed that the drug dubbed NUCC-390 shortens the time of recovery from the neuroparalysis caused by traumatic or toxic degeneration of peripheral motor neurons. These syndromes are characterized by the activation of a pro-regenerative molecular axis, consisting of the CXCR4 receptor expressed at the damaged site in neuronal axons and by the release of its ligand CXCL12α, produced by surrounding Schwann cells. This intercellular signaling axis promotes axonal growth and functional recovery from paralysis. NUCC-390 is an agonist of CXCR4 acting similarly to CXCL12α. Here, we have tested its efficacy in a murine model of neuroparalytic envenoming by a Papuan Taipan (Oxyuranus scutellatus) where a degeneration of the motor axon terminals caused by the presynaptic PLA2 toxin Taipoxin, contained in the venom, occurs. Using imaging of the neuromuscular junction and electrophysiological analysis, we found that NUCC-390 administration after injection of either the purified neuroparalytic Taipoxin or the whole Taipan venom, significantly accelerates the recovery from paralysis. These results indicate that NUCC-390, which is non-toxic in mice, should be considered for trials in humans to test its efficacy in accelerating the recovery from the peripheral neuroparalysis induced by Taipans. NUCC-390 should be tested as well in the envenomation by other snakes that cause neuroparalytic syndromes in humans. NUCC-390 could become an additional treatment, common to many snake envenomings, that can be delivered after the bite to reduce death by respiratory deficits and to shorten and improve functional recovery.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Historical evolution of human anthrax from occupational disease to potentially global threat as bioweapon

Enrico D'Amelio / Bernardina Gentile / Florigio Lista / Raffaele D'Amelio

Environment International, Vol 85, Iss , Pp 133-

2015 Volume 146

Abstract: Purpose: Anthrax is caused by Bacillus anthracis, which can naturally infect livestock, wildlife and occupationally exposed humans. However, for its resistance due to spore formation, ease of dissemination, persistence in the environment and high ... ...

Abstract	Purpose: Anthrax is caused by Bacillus anthracis, which can naturally infect livestock, wildlife and occupationally exposed humans. However, for its resistance due to spore formation, ease of dissemination, persistence in the environment and high virulence, B. anthracis has been considered the most serious bioterrorism agent for a long time. During the last century anthrax evolved from limited natural disease to potentially global threat if used as bioweapon. Several factors may mitigate the consequences of an anthrax attack, including 1. the capability to promptly recognize and manage the illness and its public health consequences; 2. the limitation of secondary contamination risk through an appropriate decontamination; and 3. the evolution of genotyping methods (for microbes characterization at high resolution level) that can influence the course and/or focus of investigations, impacting the response of the government to an attack. Methods: A PubMed search has been done using the key words “bioterrorism anthrax”. Results: Over one thousand papers have been screened and the most significant examined to present a comprehensive literature review in order to discuss the current knowledge and strategies in preparedness for a possible deliberate release of B. anthracis spores and to indicate the most current and complete documents in which to deepen. Conclusions: The comprehensive analysis of the two most relevant unnatural anthrax release events, Sverdlovsk in the former Soviet Union (1979) and the contaminated letters in the USA (2001), shows that inhalational anthrax may easily and cheaply be spread resulting in serious consequences. The damage caused by an anthrax attack can be limited if public health organization, first responders, researchers and investigators will be able to promptly manage anthrax cases and use new technologies for decontamination methods and in forensic microbiology. Keywords: Anthrax history, Bioweapon, Disease, Decontamination, Microbial forensics
Keywords	Environmental sciences ; GE1-350
Subject code	333
Language	English
Publishing date	2015-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Human Fibroblasts In Vitro Exposed to 2.45 GHz Continuous and Pulsed Wave Signals

Elisa Regalbuto / Anna Anselmo / Stefania De Sanctis / Valeria Franchini / Florigio Lista / Monica Benvenuto / Roberto Bei / Laura Masuelli / Guglielmo D’Inzeo / Alessandra Paffi / Eugenio Trodella / Antonella Sgura

International Journal of Molecular Sciences, Vol 21, Iss 7069, p

Evaluation of Biological Effects with a Multimethodological Approach

2020 Volume 7069

Abstract: The increasing exposure to radiofrequency electromagnetic fields (RF-EMF), especially from wireless communication devices, raises questions about their possible adverse health effects. So far, several in vitro studies evaluating RF-EMF genotoxic and ... ...

Abstract	The increasing exposure to radiofrequency electromagnetic fields (RF-EMF), especially from wireless communication devices, raises questions about their possible adverse health effects. So far, several in vitro studies evaluating RF-EMF genotoxic and cytotoxic non-thermal effects have reported contradictory results that could be mainly due to inadequate experimental design and lack of well-characterized exposure systems and conditions. Moreover, a topic poorly investigated is related to signal modulation induced by electromagnetic fields. The aim of this study was to perform an analysis of the potential non-thermal biological effects induced by 2.45 GHz exposures through a characterized exposure system and a multimethodological approach. Human fibroblasts were exposed to continuous (CW) and pulsed (PW) signals for 2 h in a wire patch cell-based exposure system at the specific absorption rate (SAR) of 0.7 W/kg. The evaluation of the potential biological effects was carried out through a multimethodological approach, including classical biological markers (genotoxic, cell cycle, and ultrastructural) and the evaluation of gene expression profile through the powerful high-throughput next generation sequencing (NGS) RNA sequencing (RNA-seq) approach. Our results suggest that 2.45 GHz radiofrequency fields did not induce significant biological effects at a cellular or molecular level for the evaluated exposure parameters and conditions.
Keywords	2.45 GHz ; Wi-Fi ; genotoxic effect ; gene expression ; RNA sequencing (RNA-seq) ; RT-PCR ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	600
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Historical evolution of human anthrax from occupational disease to potentially global threat as bioweapon

D'Amelio, Enrico / Bernardina Gentile / Florigio Lista / Raffaele D'Amelio

Environment international. 2015 Dec., v. 85

2015

Abstract: Anthrax is caused by Bacillus anthracis, which can naturally infect livestock, wildlife and occupationally exposed humans. However, for its resistance due to spore formation, ease of dissemination, persistence in the environment and high virulence, B. ... ...

Abstract	Anthrax is caused by Bacillus anthracis, which can naturally infect livestock, wildlife and occupationally exposed humans. However, for its resistance due to spore formation, ease of dissemination, persistence in the environment and high virulence, B. anthracis has been considered the most serious bioterrorism agent for a long time. During the last century anthrax evolved from limited natural disease to potentially global threat if used as bioweapon. Several factors may mitigate the consequences of an anthrax attack, including 1. the capability to promptly recognize and manage the illness and its public health consequences; 2. the limitation of secondary contamination risk through an appropriate decontamination; and 3. the evolution of genotyping methods (for microbes characterization at high resolution level) that can influence the course and/or focus of investigations, impacting the response of the government to an attack.A PubMed search has been done using the key words âbioterrorism anthraxâ.Over one thousand papers have been screened and the most significant examined to present a comprehensive literature review in order to discuss the current knowledge and strategies in preparedness for a possible deliberate release of B. anthracis spores and to indicate the most current and complete documents in which to deepen.The comprehensive analysis of the two most relevant unnatural anthrax release events, Sverdlovsk in the former Soviet Union (1979) and the contaminated letters in the USA (2001), shows that inhalational anthrax may easily and cheaply be spread resulting in serious consequences. The damage caused by an anthrax attack can be limited if public health organization, first responders, researchers and investigators will be able to promptly manage anthrax cases and use new technologies for decontamination methods and in forensic microbiology.
Keywords	anthrax ; Bacillus anthracis ; bioterrorism ; decontamination ; forensic sciences ; genotyping ; humans ; livestock ; microorganisms ; public health ; researchers ; risk ; spores ; virulence ; wildlife ; United States ; USSR
Language	English
Dates of publication	2015-12
Size	p. 133-146.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2015.09.009
Database	NAL-Catalogue (AGRICOLA)

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