Bacterial biofilms exhibit remarkable resistance against conventional antibiotics and are capable of evading the humoral immune response. They account for nearly 80% of chronic infections in humans. Development of bacterial biofilms on medical implants results in their malfunctioning and subsequently leads to high mortality rates worldwide. Therefore, early and precise diagnosis of bacterial biofilms on implanted medical devices is essential to prevent their failure and associated complications. Culture-based methods are time consuming, more prone to contamination and often exhibit low sensitivity. Different molecular, imaging, and physical methods can aid in more accurate and faster detection of implant-associated bacterial biofilms. Biofilm growth on implant surface can be prevented either through modification of the implant material or by application of different antibacterial coatings on implant surface. Experimental studies have shown that pre-existing biofilms from medical implants can be removed by breaking down biofilm matrix, utilizing physical methods, nanomaterials and antimicrobial peptides. The current review delves into mechanism of biofilm formation on implanted medical devices and the subsequent host immune response. Much emphasis has been laid on different ongoing diagnostic and therapeutic strategies to achieve improved patient outcomes and reduced socio-economic burden.

• Klíčová slova
• Antibiotics, Antimicrobial resistance, Bacterial drug resistance, Medical implants, Theranostics,
• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• Bacteria účinky léků   izolace a purifikace   růst a vývoj   MeSH
• bakteriální infekce * diagnóza   farmakoterapie   mikrobiologie   MeSH
• biofilmy * účinky léků   růst a vývoj   MeSH
• infekce spojené s protézou * diagnóza   mikrobiologie   farmakoterapie   prevence a kontrola   terapie   MeSH
• lidé MeSH
• protézy a implantáty * mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antibakteriální látky MeSH

• Klíčová slova
• diseases, extracellular matrix, matrix metalloproteinases, molecular modeling & simulation, therapeutics,
• Publikační typ
• úvodníky MeSH

Several therapeutic monoclonal antibodies approved by the FDA are available against the PD-1/PD-L1 (programmed death 1/programmed death ligand 1) immune checkpoint axis, which has been an unprecedented success in cancer treatment. However, existing therapeutics against PD-L1, including small molecule inhibitors, have certain drawbacks such as high cost and drug resistance that challenge the currently available anti-PD-L1 therapy. Therefore, this study presents the screening of 32,552 compounds from the Natural Product Atlas database against PD-L1, including three steps of structure-based virtual screening followed by binding free energy to refine the ideal conformation of potent PD-L1 inhibitors. Subsequently, five natural compounds, i.e., Neoenactin B1, Actinofuranone I, Cosmosporin, Ganocapenoid A, and 3-[3-hydroxy-4-(3-methylbut-2-enyl)phenyl]-5-(4-hydroxybenzyl)-4-methyldihydrofuran-2(3H)-one, were collected based on the ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling and binding free energy (>−60 kcal/mol) for further computational investigation in comparison to co-crystallized ligand, i.e., JQT inhibitor. Based on interaction mapping, explicit 100 ns molecular dynamics simulation, and end-point binding free energy calculations, the selected natural compounds were marked for substantial stability with PD-L1 via intermolecular interactions (hydrogen and hydrophobic) with essential residues in comparison to the JQT inhibitor. Collectively, the calculated results advocate the selected natural compounds as the putative potent inhibitors of PD-L1 and, therefore, can be considered for further development of PD-L1 immune checkpoint inhibitors in cancer immunotherapy.

• Klíčová slova
• Neoenactin B1, immunotherapy, molecular dynamics simulation, natural products, programmed death ligand 1,
• Publikační typ
• časopisecké články MeSH

Tyrosinase, exquisitely catalyzes the phenolic compounds into brown or black pigment, inhibition is used as a treatment for dermatological or neurodegenerative disorders. Natural products, such as cyanidin-3-O-glucoside and (-/+)-catechin, are considered safe and non-toxic food additives in tyrosinase inhibition but their ambiguous inhibitory mechanism against tyrosinase is still elusive. Thus, we presented the mechanistic insights into tyrosinase with cyanidin-3-O-glucoside and (-/+)-catechin using computational simulations and in vitro assessment. Initial molecular docking results predicted ideal docked poses (- 9.346 to - 5.795 kcal/mol) for tyrosinase with selected flavonoids. Furthermore, 100 ns molecular dynamics simulations and post-simulation analysis of docked poses established their stability and oxidation of flavonoids as substrate by tyrosinase. Particularly, metal chelation via catechol group linked with the free 3-OH group on the unconjugated dihydropyran heterocycle chain was elucidated to contribute to tyrosinase inhibition by (-/+)-catechin against cyanidin-3-O-glucoside. Also, predicted binding free energy using molecular mechanics/generalized Born surface area for each docked pose was consistent with in vitro enzyme inhibition for both mushroom and murine tyrosinases. Conclusively, (-/+)-catechin was observed for substantial tyrosinase inhibition and advocated for further investigation for drug development against tyrosinase-associated diseases.

• MeSH
• Agaricus enzymologie   MeSH
• anthokyaniny farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• termodynamika MeSH
• tyrosinasa antagonisté a inhibitory   chemie   metabolismus   MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anthokyaniny MeSH
• cyanidin-3-O-beta-glucopyranoside MeSH Prohlížeč
• inhibitory enzymů MeSH
• tyrosinasa MeSH