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  1. Article ; Online: Targeting the LPS export pathway for the development of novel therapeutics.

    Sperandeo, Paola / Martorana, Alessandra M / Zaccaria, Marta / Polissi, Alessandra

    Biochimica et biophysica acta. Molecular cell research

    2022  Volume 1870, Issue 2, Page(s) 119406

    Abstract: The rapid rise of multi-resistant bacteria is a global health threat. This is especially serious for Gram-negative bacteria in which the impermeable outer membrane (OM) acts as a shield against antibiotics. The development of new drugs with novel modes ... ...

    Abstract The rapid rise of multi-resistant bacteria is a global health threat. This is especially serious for Gram-negative bacteria in which the impermeable outer membrane (OM) acts as a shield against antibiotics. The development of new drugs with novel modes of actions to combat multi-drug resistant pathogens requires the selection of suitable processes to be targeted. The LPS export pathway is an excellent under exploited target for drug development. Indeed, LPS is the major determinant of the OM permeability barrier, and its biogenetic pathway is conserved in most Gram-negatives. Here we describe efforts to identify inhibitors of the multiprotein Lpt system that transports LPS to the cell surface. Despite none of these molecules has been approved for clinical use, they may represent valuable compounds for optimization. Finally, the recent discovery of a link between inhibition of LPS biogenesis and changes in peptidoglycan structure uncovers additional targets to develop novel therapeutic strategies.
    MeSH term(s) Lipopolysaccharides ; Bacterial Outer Membrane Proteins/chemistry ; Bacterial Outer Membrane Proteins/metabolism ; Biological Transport ; Cell Membrane/metabolism ; Cell Membrane Permeability
    Chemical Substances Lipopolysaccharides ; Bacterial Outer Membrane Proteins
    Language English
    Publishing date 2022-12-05
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbamcr.2022.119406
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Solid Forms of The New Antitrypanosomal 1-(4-Acetamide-Benzenesulfonyl)-Benzimidazole: Preparation and Physicochemical Characterization.

    Marcos Valdez, Marina M / Fandiño, Octavio E / Faudone, Sonia N / Ayala, Alejandro P / Caira, Mino R / Sperandeo, Norma R

    Journal of pharmaceutical sciences

    2023  Volume 112, Issue 12, Page(s) 3233–3239

    Abstract: This study aimed to investigate the polymorphism of 1-(4-acetamide-benzenesulfonyl)-benzimidazole (PABZI), a newly developed compound with significant activity against Trypanosoma cruzi, the parasite which causes American trypanosomiasis (Chagas disease). ...

    Abstract This study aimed to investigate the polymorphism of 1-(4-acetamide-benzenesulfonyl)-benzimidazole (PABZI), a newly developed compound with significant activity against Trypanosoma cruzi, the parasite which causes American trypanosomiasis (Chagas disease). Three different crystalline forms of PABZI [a solvent-free form (form I), three isostructural solvates (from isopropanol; acetonitrile-dichloromethane, and methanol-benzene) and a non-isostructural solvate from methanol] were isolated and characterized. The crystal structure of form I was resolved at 173 K and 300 K by single crystal X-ray diffraction. Physicochemical properties, including solubility, dissolution rate, wettability, and solid-state stability were assessed for the two most viable solid forms of PABZI, viz. form I and the isopropanol solvate (PABZI-isoOH). Form I exhibited a higher solubility and dissolution rate, and superior stability towards moisture (40 °C/75 % relative humidity) and UV-Visible light than PABZI-isoOH. Based on the solid-state stability results, form I was selected over PABZI-isoOH for further preclinical studies.
    MeSH term(s) 2-Propanol ; Methanol ; Crystallization ; Solvents/chemistry ; Solubility ; Acetamides ; Benzimidazoles ; X-Ray Diffraction ; Calorimetry, Differential Scanning
    Chemical Substances 2-Propanol (ND2M416302) ; Methanol (Y4S76JWI15) ; Solvents ; Acetamides ; Benzimidazoles
    Language English
    Publishing date 2023-09-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3151-3
    ISSN 1520-6017 ; 0022-3549
    ISSN (online) 1520-6017
    ISSN 0022-3549
    DOI 10.1016/j.xphs.2023.09.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: The Unveiled Triad: Clinical, Radiological and Pathological Insights into Hypersensitivity Pneumonitis.

    Rea, Gaetano / Bocchino, Marialuisa / Lieto, Roberta / Ledda, Roberta Eufrasia / D'Alto, Michele / Sperandeo, Marco / Lucci, Raffaella / Pasquinelli, Patrizio / Sanduzzi Zamparelli, Stefano / Bocchini, Giorgio / Valente, Tullio / Sica, Giacomo

    Journal of clinical medicine

    2024  Volume 13, Issue 3

    Abstract: Hypersensitivity pneumonitis (HP) is a diffuse parenchymal lung disease (DLPD) characterized by complex interstitial lung damage with polymorphic and protean inflammatory aspects affecting lung tissue targets including small airways, the interstitium, ... ...

    Abstract Hypersensitivity pneumonitis (HP) is a diffuse parenchymal lung disease (DLPD) characterized by complex interstitial lung damage with polymorphic and protean inflammatory aspects affecting lung tissue targets including small airways, the interstitium, alveolar compartments and vascular structures. HP shares clinical and often radiological features with other lung diseases in acute or chronic forms. In its natural temporal evolution, if specific therapy is not initiated promptly, HP leads to progressive fibrotic damage with reduced lung volumes and impaired gas exchange. The prevalence of HP varies considerably worldwide, influenced by factors like imprecise disease classification, diagnostic method limitations for obtaining a confident diagnosis, diagnostic limitations in the correct processing of high-resolution computed tomography (HRCT) radiological parameters, unreliable medical history, diverse geographical conditions, heterogeneous agricultural and industrial practices and occasionally ineffective individual protections regarding occupational exposures and host risk factors. The aim of this review is to present an accurate and detailed 360-degree analysis of HP considering HRCT patterns and the role of the broncho-alveolar lavage (BAL), without neglecting biopsy and anatomopathological aspects and future technological developments that could make the diagnosis of this disease less challenging.
    Language English
    Publishing date 2024-01-30
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm13030797
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Redundant essentiality of AsmA-like proteins in

    Sposato, Davide / Mercolino, Jessica / Torrini, Luisa / Sperandeo, Paola / Lucidi, Massimiliano / Alegiani, Riccardo / Varone, Ilaria / Molesini, Giorgia / Leoni, Livia / Rampioni, Giordano / Visca, Paolo / Imperi, Francesco

    mSphere

    2024  Volume 9, Issue 2, Page(s) e0067723

    Abstract: The outer membrane (OM) is an essential structure of Gram-negative bacteria that provides mechanical strength and protection from large and/or hydrophobic toxic molecules, including many antibiotics. The OM is composed of glycerophospholipids (GPLs) and ... ...

    Abstract The outer membrane (OM) is an essential structure of Gram-negative bacteria that provides mechanical strength and protection from large and/or hydrophobic toxic molecules, including many antibiotics. The OM is composed of glycerophospholipids (GPLs) and lipopolysaccharide (LPS) in the inner and outer leaflets, respectively, and hosts integral β-barrel proteins and lipoproteins. While the systems responsible for translocation and insertion of LPS and OM proteins have been elucidated, the mechanism(s) mediating transport of GPLs from the inner membrane to the OM has remained elusive for decades. Very recently, studies performed in
    Importance: Given the importance of the outer membrane (OM) for viability and antibiotic resistance in Gram-negative bacteria, in the last decades, several studies have focused on the characterization of the systems involved in OM biogenesis, which have also been explored as targets for antibacterial drug development. However, the mechanism mediating translocation of glycerophospholipids (GPLs) to the OM remained unknown until recent studies provided evidence that AsmA-like proteins could be responsible for this process. Here, we demonstrate for the first time that AsmA-like proteins are essential and redundant for growth and OM integrity in a Gram-negative bacterium other than the model organism
    MeSH term(s) Humans ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Pseudomonas aeruginosa/genetics ; Pseudomonas aeruginosa/metabolism ; Lipopolysaccharides/metabolism ; Bacterial Outer Membrane Proteins/genetics ; Bacterial Outer Membrane Proteins/metabolism ; Anti-Bacterial Agents/metabolism ; Glycerophospholipids/metabolism
    Chemical Substances Lipopolysaccharides ; Bacterial Outer Membrane Proteins ; Anti-Bacterial Agents ; Glycerophospholipids
    Language English
    Publishing date 2024-02-02
    Publishing country United States
    Document type Journal Article
    ISSN 2379-5042
    ISSN (online) 2379-5042
    DOI 10.1128/msphere.00677-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Lipopolysaccharide Biosynthesis and Transport to the Outer Membrane of Gram-Negative Bacteria.

    Sperandeo, Paola / Martorana, Alessandra M / Polissi, Alessandra

    Sub-cellular biochemistry

    2019  Volume 92, Page(s) 9–37

    Abstract: Gram-negative bacteria have an outer membrane that is positioned at the frontline of the cell's interaction with the environment and that serves as a barrier against noxious molecules including many antibiotics. This protective function mainly relies on ... ...

    Abstract Gram-negative bacteria have an outer membrane that is positioned at the frontline of the cell's interaction with the environment and that serves as a barrier against noxious molecules including many antibiotics. This protective function mainly relies on lipopolysaccharide, a complex glycolipid located in the outer leaflet of the outer membrane. In this chapter we will first summarize lipopolysaccharide structure, functions and biosynthetic pathway and then we will discuss how it is transported and assembled to the cell surface. This is a remarkably complex process, as amphipathic lipopolysaccharide molecules must traverse three different cellular compartments to reach their final destination.
    MeSH term(s) Biological Transport ; Cell Membrane/metabolism ; Gram-Negative Bacteria/cytology ; Gram-Negative Bacteria/metabolism ; Lipopolysaccharides/biosynthesis ; Lipopolysaccharides/metabolism
    Chemical Substances Lipopolysaccharides
    Language English
    Publishing date 2019-06-18
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 0306-0225 ; 0096-8757
    ISSN 0306-0225 ; 0096-8757
    DOI 10.1007/978-3-030-18768-2_2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The Lpt ABC transporter for lipopolysaccharide export to the cell surface.

    Sperandeo, Paola / Martorana, Alessandra M / Polissi, Alessandra

    Research in microbiology

    2019  Volume 170, Issue 8, Page(s) 366–373

    Abstract: The surface of the outer membrane of Gram-negative bacteria is covered by a tightly packed layer of lipopolysaccharide molecules which provide a barrier against many toxic compounds and antibiotics. Lipopolysaccharide, synthesized in the cytoplasm, is ... ...

    Abstract The surface of the outer membrane of Gram-negative bacteria is covered by a tightly packed layer of lipopolysaccharide molecules which provide a barrier against many toxic compounds and antibiotics. Lipopolysaccharide, synthesized in the cytoplasm, is assembled in the periplasmic leaflet of the inner membrane where the intermembrane Lpt system mediates its transport to the cell surface. The first step of lipopolysaccharide transport is its extraction from the outer leaflet of inner membrane powered by the atypical LptB
    MeSH term(s) ATP-Binding Cassette Transporters/metabolism ; Bacterial Outer Membrane Proteins/metabolism ; Biological Transport/physiology ; Cell Membrane/metabolism ; Escherichia coli/metabolism ; Lipopolysaccharides/metabolism ; Protein Conformation
    Chemical Substances ATP-Binding Cassette Transporters ; Bacterial Outer Membrane Proteins ; Lipopolysaccharides
    Language English
    Publishing date 2019-08-01
    Publishing country France
    Document type Journal Article
    ZDB-ID 1004220-9
    ISSN 1769-7123 ; 0923-2508
    ISSN (online) 1769-7123
    ISSN 0923-2508
    DOI 10.1016/j.resmic.2019.07.005
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  7. Article: The Lpt ABC transporter for lipopolysaccharide export to the cell surface

    Sperandeo, Paola / Martorana, Alessandra M / Polissi, Alessandra

    Institut Pasteur Research in microbiology. 2019 July 13,

    2019  

    Abstract: The surface of the outer membrane of Gram-negative bacteria is covered by a tightly packed layer of lipopolysaccharide molecules which provide a barrier against many toxic compounds and antibiotics. Lipopolysaccharide, synthesized in the cytoplasm, is ... ...

    Abstract The surface of the outer membrane of Gram-negative bacteria is covered by a tightly packed layer of lipopolysaccharide molecules which provide a barrier against many toxic compounds and antibiotics. Lipopolysaccharide, synthesized in the cytoplasm, is assembled in the periplasmic leaflet of the inner membrane where the intermembrane Lpt system mediates its transport to the cell surface. The first step of lipopolysaccharide transport is its extraction from the outer leaflet of inner membrane powered by the atypical LptB2FGC ABC transporter. Here we review latest advances leading to understanding at molecular level how lipopolysaccharide is transported irreversibly to the outer membrane.
    Keywords ABC transporters ; antibiotics ; cytoplasm ; Gram-negative bacteria ; lipopolysaccharides ; physiological transport ; toxic substances
    Language English
    Dates of publication 2019-0713
    Publishing place Elsevier Masson SAS
    Document type Article
    Note Pre-press version
    ZDB-ID 1004220-9
    ISSN 1769-7123 ; 0923-2508
    ISSN (online) 1769-7123
    ISSN 0923-2508
    DOI 10.1016/j.resmic.2019.07.005
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Diaphragm ultrasound in infants with bronchiolitis.

    Tomà, Paolo / Granata, Claudio / Sperandeo, Marco

    Pediatric pulmonology

    2018  Volume 53, Issue 9, Page(s) 1177–1178

    MeSH term(s) Bronchiolitis ; Diaphragm ; Humans ; Infant ; Point-of-Care Systems ; Prospective Studies ; Ultrasonography
    Language English
    Publishing date 2018-05-27
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 632784-9
    ISSN 1099-0496 ; 8755-6863
    ISSN (online) 1099-0496
    ISSN 8755-6863
    DOI 10.1002/ppul.24060
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Ultrasound-guided fine needle aspiration biopsy (FNAB) demonstrating upper distal extremity metastasis of lung adenocarcinoma: a case report and review of the literature.

    La Marca, A / Graziano, P / Simeone, A / Maiello, E / Serviddio, G / Vendemiale, G / Sperandeo, M

    European review for medical and pharmacological sciences

    2021  Volume 25, Issue 8, Page(s) 3221–3225

    Abstract: Due to early metastasis and delayed diagnosis, lung cancer is the leading cause of cancer-related deaths. Although the most common metastasis sites are brain, bone, lung, adrenal glands, liver, and extra-thoracic lymph node, soft tissues, such as ... ...

    Abstract Due to early metastasis and delayed diagnosis, lung cancer is the leading cause of cancer-related deaths. Although the most common metastasis sites are brain, bone, lung, adrenal glands, liver, and extra-thoracic lymph node, soft tissues, such as skeletal muscles, skin, and subcutaneous tissues, can also be undermined. This article aims to report the first case of an asymptomatic radial extensor muscle metastasis generating from a lung adenocarcinoma that was diagnosed by ultrasound-guided fine-needle aspiration biopsy (FNAB).
    MeSH term(s) Adenocarcinoma of Lung/diagnosis ; Aged ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Humans ; Lung Neoplasms/diagnosis ; Male ; Upper Extremity/pathology
    Language English
    Publishing date 2021-04-27
    Publishing country Italy
    Document type Case Reports ; Journal Article
    ZDB-ID 605550-3
    ISSN 2284-0729 ; 1128-3602 ; 0392-291X
    ISSN (online) 2284-0729
    ISSN 1128-3602 ; 0392-291X
    DOI 10.26355/eurrev_202104_25730
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Could transthoracic ultrasound be useful to suggest a small airways disease in severe uncontrolled asthma?

    Scioscia, Giulia / Lacedonia, Donato / Quarato, Carla Maria Irene / Tondo, Pasquale / Del Colle, Anna / Sperandeo, Marco / Carpagnano, Giovanna Elisiana / Foschino Barbaro, Maria Pia

    Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology

    2022  Volume 129, Issue 4, Page(s) 461–466

    Abstract: Background: Transthoracic ultrasound (TUS) is an accepted complementary tool in the diagnostic process of several pleuro-pulmonary diseases. However, to the best of our knowledge, TUS findings in patients with severe asthma have never been ... ...

    Abstract Background: Transthoracic ultrasound (TUS) is an accepted complementary tool in the diagnostic process of several pleuro-pulmonary diseases. However, to the best of our knowledge, TUS findings in patients with severe asthma have never been systematically described.
    Objective: To explore if TUS examination is a useful imaging method in suggesting the presence of a "small airways disease" in patients with severe uncontrolled asthma.
    Methods: Seventy-two consecutive subjects with a diagnosis of severe uncontrolled asthma were enrolled. The presence of a "small airways disease" was assessed through the execution of pulmonary function tests. All the patients underwent a complete TUS examination and a chest high resolution computed tomography (HRCT), which was regarded as the reference standard for comparison with TUS findings.
    Results: Pulmonary function tests results have confirmed a reduction in expiratory flows relative to the small airways and a condition of hyperinflation in 78% and 82% of our patients, respectively. The main signs observed in the TUS examination were a thickened and/or irregular pleural line and the lack or reduction of the "gliding sign." TUS showed high sensitivity and specificity in suggesting the presence of hyperinflation and distal airways inflammation according to the HRCT scan. K Cohen's coefficients showed substantial agreement between the 2 diagnostic tests.
    Conclusion: TUS in patients with severe uncontrolled asthma can provide useful information on the state of the peripheral lung, suggesting the execution of a second-line HRCT scan for better assessment of eventual alterations that may represent the underlying causes of nonresponse to treatment.
    MeSH term(s) Asthma/diagnostic imaging ; Humans ; Lung/diagnostic imaging ; Lung Diseases ; Pulmonary Disease, Chronic Obstructive ; Tomography, X-Ray Computed ; Ultrasonography
    Language English
    Publishing date 2022-05-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1228189-x
    ISSN 1534-4436 ; 0003-4738 ; 1081-1206
    ISSN (online) 1534-4436
    ISSN 0003-4738 ; 1081-1206
    DOI 10.1016/j.anai.2022.05.024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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