Molecular interactions of the Omicron, Kappa, and Delta SARS-CoV-2 spike proteins with quantum dots of graphene oxide.

CONTEXT: The Omicron, Kappa, and Delta variants are different strains of the SARS-CoV-2 virus. Graphene oxide quantum dots (GOQDs) represent a burgeoning class of oxygen-enriched, zero-dimensional materials characterized by their sub-20-nm dimensions. Exhibiting pronounced quantum confinement and edge effects, GOQDs manifest exceptional physical-chemical attributes. This study delves into the potential of graphene oxide quantum dots, elucidating their inherent properties pertinent to the surface structures of SARS-CoV-2, employing an integrated computational approach for the repositioning of inhibitory agents. METHODS: Following rigorous adjustment tests, a spectrum of divergent bonding conformations emerged, with particular emphasis placed on identifying the conformation exhibiting optimal adjustment scores and interactions. The investigation employed molecular docking simulations integrating affinity energy evaluations, electrostatic potential clouds, molecular dynamics encompassing average square root calculations, and the computation of Gibbs-free energy. These values quantify the strength of interaction between GOQDs and SARS-CoV-2 spike protein variants. The receptor structures were optimized using the CHARM-GUI server employing force field AMBERFF14SB. The algorithm embedded in CHARMM offers an efficient interpolation scheme and automatic step size selection, enhancing the efficiency of the optimization process. The 3D structures of the ligands are constructed and optimized with density functional theory (DFT) method based on the most stable conformer of each binder. Autodock Vina Software (ADV) was utilized, where essential parameters were specified. Electrostatic potential maps (MEPs) provide a visual depiction of molecules' charge distributions and related properties. After this, molecular dynamics simulations employing the CHARM36 force field in Gromacs 2022.2 were conducted to investigate GOs' interactions with surface macromolecules of SARS-CoV-2 in an explicit aqueous environment. Furthermore, our investigation suggests that lower values indicate stronger binding. Notably, GO-E consistently showed the most negative values across interactions with different variants, suggesting a higher affinity compared to other GOQDs (GO-A to GO-D).

Euterpe oleracea fruit (Açai)-enriched diet suppresses the development of experimental cerebral malaria induced by Plasmodium berghei (ANKA) infection.

BACKGROUND: Cerebral malaria is one of the most severe complications attributed to protozoal infection by Plasmodium falciparum, gaining prominence in children mortality rates in endemic areas. This condition has a complex pathogenesis associated with behavioral, cognitive and motor sequels in humans and current antimalarial therapies have shown little effect in those aspects. Natural products with antioxidant and anti-inflammatory properties have become a valuable alternative therapeutic option in the treatment of distinct conditions. In this context, this study investigated the neuroprotective effect of Euterpe oleracea (açai) enriched diet during the development of experimental cerebral malaria induced by the inoculation of Swiss albino mice with Plasmodium berghei ANKA strain. METHODS: After Plasmodium infection, animals were maintained on a feeding with Euterpe oleracea enriched ration and parameters such as survival curve, parasitemia and body weight were routinely monitored. The present study has also evaluated the effect of açai-enriched diet on the blood-brain barrier leakage, histological alterations and neurocognitive impairments in mice developing cerebral malaria. RESULTS: Our results demonstrate that between 7th-19th day post infection the survival rate of the group treated with açai enriched ration was higher when compared with Plasmodium-infected mice in which 100% of mice died until the 11th days post-infection, demonstrating that açai diet has a protective effect on the survival of infected treated animals. The same was observed in the brain vascular extravasation, where Evans blue dye assays showed significantly less dye extravasation in the brains of Plasmodium-infected mice treated with açai enriched ration, demonstrating more preserved blood-brain barrier integrity. Açai-enriched diet also attenuate the histopathological alterations elicited by Plasmodium berghei infection. We also showed a decrease of the neurological impairments arising from the exposure of cerebral parenchyma in the group treated with açai diet, ameliorating motor and neuropsychiatric changes, analyzed through the SHIRPA protocol. CONCLUSION: With these results, we conclude that the treatment with açai enriched ration decreased the mortality of infected animals, as well as protected the blood-brain barrier and the neurocognitive deficits in Plasmodium-infected animals.

Hormones Nanofiltration in Carbon Nanotubes and Boron Nitride Nanotubes Using Uniform External Electric Field Through Molecular Dynamics.

Hormones are a dangerous group of molecules that can cause harm to humans. This study based on classical molecular dynamics proposes the nanofiltration of wastewater contaminated by hormones from a computer simulation study, in which the water and the hormone were filtered in two single-walled nanotube compositions. The calculations were carried out by changing the intensities of the electric field that acted as a force exerting pressure on the filtration along the nanotube, in the simulation time of 100 ps. The hormones studied were estrone, estradiol, estriol, progesterone, ethinylestradiol, diethylbestrol, and levonorgestrel in carbon nanotubes (CNTs) and boron nitride (BNNTs). The most efficient nanofiltrations were for fields with low intensities in the order of 10-8 au and 10-7 au. The studied nanotubes can be used in membranes for nanofiltration in water treatment plants due to the evanescent field potential caused by the action of the electric field inside. Our data showed that the action of EF in conjunction with the van der Walls forces of the nanotubes is sufficient to generate the attractive potential. Evaluating the transport of water molecules in CNTs and BNNTs, under the influence of the electric field, a sequence of simulations with the same boundary conditions was carried out, seeking to know the percentage of water molecules filtered in the nanotubes.

Mechanisms underlying the vasorelaxant effect of trans-4-methoxy-ß-nitrostyrene in the rat mesenteric resistance arteries.

Mechanisms underlying the vasorelaxant effects of the synthetic nitro compound, trans-4-methoxy-ß-nitrostyrene (T4MN) were studied in isolated small resistance arteries from spontaneously hypertensive rats (SHRs). T4MN caused vasorelaxation in endothelium-intact third-order branches of the mesenteric artery pre-contracted with noradrenaline (NA). This effect was unchanged by indomethacin and atropine but was significantly reduced by endothelium removal, L-NAME, LY294002, glybenclamide, TEA, apamin, TRAM 34, or by the association of apamin and TRAM 34. Pretreatment with the sGC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reduced the T4MN-induced relaxation in endothelium-intact, but not in denuded preparations. Incubation of small resistance arteries with T4MN increased nitric oxide (NO) production, an effect that was blocked by L-NAME. In Ca2+-free medium, T4MN inhibits the contractions induced by (i) NA, (ii) exogenous calcium through receptor- or voltage-operated Ca2+ channels and (iii) those evoked by Ca2+ influx through stores-operated Ca2+ channels activated by thapsigargin-induced Ca2+ store depletion. In contrast, T4MN was inert against the transient contraction induced by caffeine in Ca2+-free medium. In conclusion, T4MN induced effective vasorelaxant effects in isolated small resistance arteries from SHRs. This vasorelaxation seems to be mediated partly by an endothelium-dependent mechanism involving activation of Akt/eNOS/NO pathway and partly by an endothelium-independent mechanism through activation of sGC/cGMP/PKG pathway in vascular smooth muscle, leading to inhibition of Ca2+ influx from the extracellular milieu and IP3-sensitive intracellular Ca2+ release as well as activation of potassium channels.

Anti-Inflammatory Potential of 1-Nitro-2-Phenylethylene.

Inflammation is a reaction of the host to infectious or sterile stimuli and has the physiological purpose of restoring tissue homeostasis. However, uncontrolled or unresolved inflammation can lead to tissue damage, giving rise to a plethora of chronic inflammatory diseases, including metabolic syndrome and autoimmunity pathologies with eventual loss of organ function. Beta-nitrostyrene and its derivatives are known to have several biological activities, including anti-edema, vasorelaxant, antiplatelet, anti-inflammatory, and anticancer. However, few studies have been carried out regarding the anti-inflammatory effects of this class of compounds. Thereby, the aim of this study was to evaluate the anti-inflammatory activity of 1-nitro-2-phenylethene (NPe) using in vitro and in vivo assays. Firstly, the potential anti-inflammatory activity of NPe was evaluated by measuring TNF-α produced by human macrophages stimulated with lipopolysaccharide (LPS). NPe at non-toxic doses opposed the inflammatory effects induced by LPS stimulation, namely production of the inflammatory cytokine TNF-α and activation of NF-κB and ERK pathways (evaluated by phosphorylation of inhibitor of kappa B-alpha [IκB-α] and extracellular signal-regulated kinase 1/2 [ERK1/2], respectively). In a well-established model of acute pleurisy, pretreatment of LPS-challenged mice with NPe reduced neutrophil accumulation in the pleural cavity. This anti-inflammatory effect was associated with reduced activation of NF-κB and ERK1/2 pathways in NPe treated mice as compared to untreated animals. Notably, NPe was as effective as dexamethasone in both, reducing neutrophil accumulation and inhibiting ERK1/2 and IκB-α phosphorylation. Taken together, the results suggest a potential anti-inflammatory activity for NPe via inhibition of ERK1/2 and NF-κB pathways on leukocytes.