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RECETTORI KIR NELLA PATOGENESI DELLA NON-CELIAC GLUTEN SENSITIVITY (NCGS)
No full textIntroduzione:La sensibilità al glutine non celiaca (NCGS) è una condizione caratterizzata dalla comparsa di sintomi gastrointestinali ed extraintestinali in seguito all’ingestione di glutine, in assenza di malattia celiaca (CD) e allergia al grano. Nonostante l’ampio interesse per la NCGS, i meccanismi alla base della sua patogenesi restano in gran parte sconosciuti e, ad oggi, non sono stati individuati specifici fattori genetici predisponenti. È noto che, a differenza della CD, la NCGS non è associata a un particolare assetto genotipico o fenotipico HLA. Diversi studi hanno evidenziato il ruolo dell’immunità innata e delle cellule natural killer (NK) nello sviluppo della malattia. I recettori KIR, espressi sulle cellule NK, ne regolano l’attivazione attraverso l’interazione con le molecole HLA.Obiettivo dello studio:Questo studio ha l’obiettivo di analizzare le varianti genetiche dei recettori KIR, suddivise in aplotipi "inibitori" e "attivatori", per comprendere il loro possibile coinvolgimento nello sviluppo e nella progressione della NCGS. In particolare, vogliamo valutare la presenza di specifiche varianti genetiche KIR nei pazienti con NCGS rispetto a un gruppo di controllo costituito da donatori di sangue sani.Materiali e metodi:Abbiamo condotto uno studio retrospettivo caso-controllo su 40 pazienti con diagnosi confermata di NCGS e 32 donatori sani. La tipizzazione dei geni KIR è stata eseguita utilizzando il kit KIR SSO Genotyping Test (One Lambda, Inc., Canoga Park, CA, USA) basato sulla tecnologia Luminex. Questo test consente di rilevare la presenza o l’assenza dei seguenti geni: 2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1, 2DP1, 3DP1, oltre alle varianti comuni di 2DL5, 2DS4 e 3DP1.Risultati:Abbiamo riscontrato che la frequenza dei geni KIR inibitori era significativamente più alta nei soggetti sani rispetto ai pazienti con NCGS per i seguenti geni: KIR2DL1 (96,87% contro 55%, p= .0024, OR= 25.36; 95% CI = 3.15 - 204.35), KIR2DL2 (65,62% contro 32,5%, p = .006; OR = 3.95, 95% CI = 1.48 - 10.6), KIR2DL3 (81,25% contro 22,5%, p < .0001; OR = 14.92, 95% CI = 4.69 - 47.47) e KIR2DL5 (62,5% contro 10%, p < .0001; OR = 15, 95% CI = 4.27 - 52.7). Questi dati suggeriscono un possibile ruolo protettivo di tali geni nella suscettibilità alla NCGS. Inoltre, l’analisi degli aplotipi ha mostrato che l’85% dei pazienti con NCGS possiede un aplotipo di tipo B, mentre nei soggetti sani prevalgono gli aplotipi A e AB, con una frequenza rispettivamente del 31,25% e 56,25%.Conclusione:I nostri risultati indicano che i geni KIR inibitori sono più frequentemente presenti nei soggetti sani, suggerendo un possibile effetto protettivo nei confronti della NCGS. Di conseguenza, il bilanciamento tra i recettori KIR attivatori e inibitori potrebbe giocare un ruolo chiave nella patogenesi della malattia
On the Persian Translations of Avicenna’s Ilāhiyyāt: Part II
No full textThis contribution will take into account the Persian translations of the fourth part concerning Metaphysics (Ilāhiyyāt ([Science of] Divine Things) of the most important philosophical summa by
Ibn Sīnā (Avicenna), i.e. al-Kitāb al-Šifāʾ (Book of the Healing/Cure)
Valorizing Coffee Waste into N-, P-, O-Heteroatom-Doped Carbons for Metal-Free Electrocatalysis
No full textSpent coffee grounds were valorized as a renewable feedstock to prepare N-, P-, and O-codoped activated carbons via pyrolysis, targeting the development of metal-free electrocatalysts for the oxygen reduction reaction (ORR). Hexachlorocyclotriphosphazene (HCCP) was used as a doping agent, and the influence of different porosity activators such as NH4HCO3, KOH, and oxalic acid was studied. This work employs NH4HCO3 as a benign, metal-free activator and secondary nitrogen source compared against conventional porosity agents. Among the mild activators, NH4HCO3 simultaneously provided nitrogen and released NH3 and CO2, while oxalic acid generated a clean CO2 stream, both contributing to mesoporous structure formation. XPS confirmed the successful incorporation of N and P into the carbon matrix, with a high fraction of graphitic nitrogen enhancing the conductivity and catalytic activity. Raman spectroscopy, TEM, and XRD analyses revealed predominantly sp2-hybridized, turbostratic carbon, with higher structural order at 900 degrees C compared to 700 degrees C. The combined effect of pyrolysis temperature, HCCP, and NH4HCO3 produced mesoporous, nitrogen-rich graphitic carbon structures with promising ORR performance, demonstrating a green strategy that maximizes atom economy, minimizes energy input and waste, and transforms low-value biomass into high-performance metal-free electrocatalysts
Halloysite nanotubes interacting with lipid vesicle membranes
No full textHalloysite nanotubes (HNTs), naturally occurring aluminosilicates with a tubular structure, are promising nanocarriers for drug delivery due to their biocompatibility and unique morphology. However, their interaction with lipid membranes remains not fully explored. In this work, we aim at elucidating on the adhesion of HNTs on unilamellar vesicles made of phospholipids used as model of biological membranes. The adhesion was modulated by varying the lipid composition, ionic strength, and the size ratio between HNTs and vesicles. The adhesion mechanism was also studied by trapping a single HNT with optical tweezers and let it interact with a single vesicle. These findings show a preferential adhesion of the HNT tip on the lipid bilayer, which represents an important step toward directional membrane targeting in biomedical applications
Non-canonical σ-hole interactions: halogen, chalcogen, and pnictogen bonds in biomolecular structure and drug design
No full textσ-Hole interactions, including halogen, chalcogen, and pnictogen bonds, are a versatile and directional class of noncovalent forces that expand the molecular design space in chemical biology and medicinal chemistry. Their emerging roles in biological systems and medicinal chemistry are now becoming increasingly intriguing, opening new avenues for exploration and this review focuses on the role of these interactions in biological system. Halogen bonds contribute measurably to binding in desolvated protein pockets. Chalcogen bonds stabilize protein structures, control conformation, enable catalysis, and facilitate redox-responsive drug delivery. Pnictogen bonds (PnB) combine electrostatic and orbital components, supporting supramolecular assembly, anion recognition, and selective catalysis, though careful attention to toxicity and ADME properties is required. Early consideration of developability limitations, such as lipophilicity, metabolism, and toxicity, is critical. Increasing attention to σ-hole interactions, combined with polarizable force fields and machine learning structural analysis allows these interactions to be used as predictive and reproducible tools in molecular design
Una svolta nella storia del contrasto alla mafia
No full textanalisi storica critica e documentata di come e quando nelle istituzioni italiane si sia realizzato un cambiamento significativo nella lotta allo Stato mafioso, passando da un contrasto intermittente a una vera e propria strategia organica di Stat
Sustainable and efficient metal hydroxides as halogen-free flame-retardant additives in polyolefin-based composites for cable sheathing applications
No full textSustainable and efficient metal hydroxides as halogen-free flame-retardant additives in polyolefin-based composites for cable sheathing application