1,721,063 research outputs found
Sequence conservation of schistosome cyclophilins
No full textSequence conservation of schistosome cyclophilin
Expression Cloning and Biochemical Characterizations of Recombinant Cyclophilin Proteins from Schistosoma mansoni
No full textRecombinant Schistosoma mansoni cyclophilin proteins of the A and the B subtypes (SmCYP A and B) were expressed in bacterial cells as histidine- and maltose-binding fusion proteins and also as nonfused proteins. In addition, S. mansoni CYPs were produced in Sf9 insect cells in their natural forms. Purified recombinant SmCYP B was found to possess a peptidyl-prolyl cis-trans isomerase (PPIase) activity, with a kcat/Km value of 8.2 x 10(5) M-1 s-1. The SmCYP B isoform is approximately two to three times more active than SmCYP A. SmCYP B-specific RNA appears to be more abundant in adult schistosomes than SmCYP A RNA in Northern blots. These results support the conclusion that SmCYP B represents the major schistosomal CYP. The PPIase-associated activity of both CYPs was inhibitable by the immunosuppressive drug cyclosporin A (CsA). We attempt to explain differences in PPIase activities and in CsA inhibition by examining models of the two CYPs complexed to Cs
Bioinspired oriented calcium phosphate nanocrystal arrays with bactericidal and osteogenic properties
Full text linkThe global diffusion of antibiotic resistance poses a severe threat to public health. Addressing antibiotic-resistant infections requires innovative approaches, such as antibacterial nanostructured surfaces (ANSs). These surfaces, featuring ordered arrays of nanostructures, exhibit the ability to kill bacteria upon contact. However, most currently developed ANSs utilize bioinert materials, lacking bioactivity crucial for promoting tissue regeneration, particularly in the context of bone infections. This study introduces ANSs composed of bioactive calcium phosphate nanocrystals. Two distinct ANSs were created through a biomineralization-inspired growth of amorphous calcium phosphate (ACP) precursors. The ANSs demonstrated efficient antibacterial properties against both Gram-negative (P. aeruginosa) and Gram-positive (S. aureus) antibiotic resistant bacteria, with up to 75 % mortality in adhered bacteria after only 4 h of contact. Notably, the ANS featuring thinner and less oriented nano-needles exhibited superior efficacy attributed to simultaneous membrane rupturing and oxidative stress induction. Moreover, the ANSs facilitate the proliferation of mammalian cells, enhancing adhesion, spreading, and reducing oxidative stress. The ANSs displayed also significant bioactivity towards human mesenchymal stem cells, promoting colonization and inducing osteogenic differentiation. Specifically, the ANS with thicker and more ordered nano-needles demonstrated heightened effects. In conclusion, ANSs introduced in this work have the potential to serve as foundation for developing bone graft materials capable of eradicate site infections while concurrently stimulating bone regeneration. Statement of significance: Nanostructured surfaces with antibacterial properties through a mechano-bactericidal mechanism have shown significant potential in fighting antibiotic resistance. However, these surfaces have not been fabricated with bioactive materials necessary for developing devices that are both antibacterial and able to stimulate tissue regeneration. This study demonstrates the feasibility of creating nanostructured surfaces of ordered calcium phosphate nano-needles through a biomineralization-inspired growth. These surfaces exhibit dual functionality, serving as effective bactericidal agents against Gram-negative and Gram-positive antibiotic-resistant bacteria while also promoting the proliferation of mammalian cells and inducing osteogenic differentiation of human mesenchymal stem cells. Consequently, this approach holds promise in the context of bone infections, introducing innovative nanostructured surfaces that could be utilized in the development of antimicrobial and osteogenic grafts
Test domiciliare per la diagnosi integrata di infezione da SARS-CoV-2
No full textLa diffusione pandemica della malattia Covid-19 impone un enorme sforzo di identificazione degli individui già entrati in contatto con il virus o tuttora portatori dell’infezione anche tra gli individui pauci- o asintomatici. A fronte di questa esigenza le attuali capacità diagnostiche appaiono su scala mondiale fortemente sottodimensionate1.
L’invenzione prevede la messa a punto di un test diagnostico rapido e semplice capace di rivelare la presenza del virus SARS-CoV-2 e delle immunoglobuline secretorie specifiche di classe IgA (sIgA) nella saliva/escreato del probando. Il test deve essere concepito come un test domiciliare (home testing) operato direttamente dal probando ed interpretato dal medico tramite semplice documentazione fotografica o App dedicata.
L’evidenziazione del virus si basa su un test di agglutinazione nel liquido salivare di particelle di latex (Latex Agglutination Test) colorate, precedentemente sensibilizzate con un anticorpo (monoclonale) rivolto contro la Spike Protein (S1) virale, su una superfice di vetro o carta; la rivelazione potrà avvenire entro pochi minuti ad occhio nudo. La abbondanza e ripetitività dell’antigene bersaglio sulla superficie di SARS-CoV-2 rendono questo virus particolarmente efficace come agente agglutinante.
Per la rilevazione delle sIgA anti SARS-CoV-2 nello stesso tipo di campione viene utilizzata una reazione immunocromatografica su striscetta (Lateral flow test) simile a quella comunemente utilizzata per la rivelazione qualitativa di IgG ed IgM specifiche in campioni di sangue; in questo caso immunoglobuline anti-IgA vengono immobilizzate sulla “linea di cattura”
Copper-functionalized hydroxyapatite nanoparticles to counteract fungal infections
Full text linkDrug-resistant fungal pathogens pose an increasing threat to human health. Nanoparticles are promising tools for treating and limiting fungal resistance due to their ability to attack microorganisms via multiple mechanisms. In this work, hydroxyapatite (HA) nanoparticles were synthesized and functionalized with copper by ionic exchange at different solution concentrations (from 0.01 to 0.2 M). The physico-chemical properties of the samples were studied using low-temperature N2 adsorption volumetry, elemental analysis, X-ray diffraction, electron microscopy and IR spectroscopy of adsorbed CO. All the obtained HA particles were poorly crystalline, elongated in the c-axis direction, and had a high specific surface area (ca. 200 m2/g). Copper was incorporated into HA surface layers with a Cu2+ doping content proportional to the initial concentration, reaching a maximum value of 14 %wt. The antifungal activity of the samples was tested against drug-resistant clinical isolates of Cryptococcus neoformans and several Candida species strains (C. parapsilosis, C. krusei, C. tropicalis, C. albicans, C. glabrata, C. auris). Minimal inhibitory concentrations and fungal growth curves were determined. Cytocompatibility evaluation showed that both undoped and Cu-doped HA samples were not toxic to mammalian cells. The Cu-containing HA samples demonstrated potential as effective and safe antifungal agents with wide-spectrum activity, representing a promising candidate for therapeutic approaches against diverse fungal infections
DDX3X inhibitors, an effective way to overcome HIV-1 resistance targeting host proteins
Full text linkThe huge resources that had gone into Human Immunodeficiency virus (HIV) research led to the development of potent antivirals able to suppress viral load in the majority of treated patients, thus dramatically increasing the life expectancy of people living with HIV. However, life-long treatments could result in the emergence of drug-resistant viruses that can progressively reduce the number of therapeutic options, facilitating the progression of the disease. In this scenario, we previously demonstrated that inhibitors of the human DDX3X helicase can represent an innovative approach for the simultaneous treatment of HIV and other viral infections such as Hepatitis c virus (HCV). We reported herein 6b, a novel DDX3X inhibitor that thanks to its distinct target of action is effective against HIV-1 strains resistant to currently approved drugs. Its improved in vitro ADME properties allowed us to perform preliminary in vivo studies in mice, which highlighted optimal biocompatibility and an improved bioavailability. These results represent a significant advancement in the development of DDX3X inhibitors as a novel class of broad spectrum and safe anti-HIV-1 drugs
Graphene Oxide Coatings as Tools to Prevent Microbial Biofilm Formation on Medical Device
No full textThe clinical challenge on surface engineering of medical devices to prevent microorganisms adhesion and biofilm formation, has become an essential aspect for medical implants. Antibacterial properties of Graphene Oxide (GO) have been demonstrated across a broad spectrum of bacteria, and the different mechanisms of action with which this nanomaterial interacts with the microbial surface have been elucidated in detail. Innovative protective coatings based on graphene film and hydrogel could represent an innovative solution for the prevention of nosocomial pathogens colonization on implantable device. This brief review mainly focuses on the applications of graphene in nanomedicine with a particular deepening on the antibacterial properties of GO and GO-based nanomaterials. In order to evaluate the possible future applications of GO as an anti-biofilm coating material for medical devices, studies on the ability of graphene coated surface to prevent microbial adhesion are also discussed. A concise review on in vitro toxicity and in vivo safety is also presented
Human monoclonal antibody fragment specific for glycoprotein G in Herpes simplex type 2 with applications for serotype-specific diagnosis
No full textA combinatorial library was used to select a human monoclonal antibody fragment (Fab) with high affinity for G glycoprotein in herpes simplex virus type 2 (HSV-2). Tests with 112 clinical specimens demonstrated successful discrimination between HSV-2 and HSV-1, showing the potential of Fab as a low-cost tool for HSV subtyping in clinical diagnosis
Multiple malaria infection in a pregnant woman from Nigeria: detection by multiplex PCR
No full textFor the last 100 years, diagnosis of malaria has been based on examination of Giemsa-stained thick and thin blood films under the microscope. This is a time-consuming procedure which often fails to correctly diagnose the infecting species especially when carried out by inexperienced technicians or when blood levels of parasite are low. Rapid Diagnostic Tests (RDTs) for antigen detection can distinguish between Plasmodium falciparum and Plasmodium vivax but cannot identify the species present in mixed infections. In the case reported here we used multiplex PCR to investigate suspected mixed infection in a pregnant woman from Nigeria. The results suggest that the method used is highly specific and can be very sensitive and that it has several advantages with respect to microscopy and RTD
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