Protein Adsorption on Solid Surfaces: Data Mining, Database, Molecular Surface-Derived Properties, and Semiempirical Relationships.

Protein adsorption on solid surfaces is a process relevant to biological, medical, industrial, and environmental applications. Despite this wide interest and advancement in measurement techniques, the complexity of protein adsorption has frustrated its accurate prediction. To address this challenge, here, data regarding protein adsorption reported in the last four decades was collected, checked for completeness and correctness, organized, and archived in an upgraded, freely accessible Biomolecular Adsorption Database, which is equivalent to a large-scale, ad hoc, crowd-sourced multifactorial experiment. The shape and physicochemical properties of the proteins present in the database were quantified on their molecular surfaces using an in-house program (ProMS) operating as an add-on to the PyMol software. Machine learning-based analysis indicated that protein adsorption on hydrophobic and hydrophilic surfaces is modulated by different sets of operational, structural, and molecular surface-based physicochemical parameters. Separately, the adsorption data regarding four "benchmark" proteins, i.e., lysozyme, albumin, IgG, and fibrinogen, was processed by piecewise linear regression with the protein monolayer acting as breakpoint, using the linearization of the Langmuir isotherm formalism, resulting in semiempirical relationships predicting protein adsorption. These relationships, derived separately for hydrophilic and hydrophobic surfaces, described well the protein concentration on the surface as a function of the protein concentration in solution, adsorbing surface contact angle, ionic strength, pH, and temperature of the carrying fluid, and the difference between pH and the isoelectric point of the protein. When applying the semiempirical relationships derived for benchmark proteins to two other "test" proteins with known PDB structure, i.e., ß-lactoglobulin and α-lactalbumin, the errors of this extrapolation were found to be in a linear relationship with the dissimilarity between the benchmark and the test proteins. The work presented here can be used for the estimation of operational parameters modulating protein adsorption for various applications such as diagnostic devices, pharmaceuticals, biomaterials, or the food industry.

Direct Interaction of Minocycline to p47phox Contributes to its Attenuation of TNF-α-Mediated Neuronal PC12 Cell Death: Experimental and Simulation Validation.

Kaempferol illustrates an example of attempting to discover new treatments for neurodegeneration by investigating the potential efficacy of natural products. Despite the identification of several molecular targets for this bio-active compound, the precise underlying pathways are not well elucidated yet. Recently, it has been shown through pulldown assay that kaemferol directly interacts with p47phox, the organizer subunit of NADPH oxidase-2 (NOX2) complex. Hence, in this study, we used homology modelling, computational docking, mutation analysis, molecular dynamics simulations and free energy calculations to determine how kaempferol interacts with p47phox. Firstly, 3D structure of p47phox was generated using x-ray structures of its domains. Then, it was docked with kaempferol, and finally 100-ns molecular dynamics (MD) simulations were performed and the global properties like root-mean square deviation (RMSD) and root-mean square fluctuations (RMSF) were calculated. Literature survey and computational analysis of key interacting amino acid residues of p47phox provided insights into a possible binding site for kaempferol, approximately around Trp193 and Cys196 located within the N-terminal SH3 domain of p47phox. Moreover, free energy calculations indicated that in silico substitution of Trp193 and Cys196 with arginine and alanine, respectively, results in less favorable interaction corroborating their importance in binding with kaempferol. Taken together, these findings suggest that kaempferol directly attaches to N-SH3 domain p47 phox, with a subsequent diminution of p47phox protein-protein interaction and possibly attenuation of NOX2 complex assembly, which reduces reactive oxygen species (ROS) generation. These observations will be beneficial for researchers exploring neuroprotection and for the development of p47phox inhibitors.

Investigation of air bubble behaviour after gas embolism events induced in a microfluidic network mimicking microvasculature.

Gas embolism is a medical condition that occurs when gas bubbles are present in veins or arteries, decreasing blood flow and potentially reducing oxygen delivery to vital organs, such as the brain. Although usually reported as rare, gas embolism can lead to severe neurological damage or death. However, presently, only limited understanding exists regarding the microscale processes leading to the formation, persistence, movement, and resolution of gas emboli, as modulated by microvasculature geometrical features and blood properties. Because gas embolism is initially a physico-chemical-only process, with biological responses starting later, the opportunity exists to fully study the genesis and evolution of gas emboli using in vitro microfluidic networks mimicking small regions of microvasculature. The microfluidics networks used in this study, which aim to mimic microvasculature geometry, comprise linear channels with T-, or Y-junction air inlets, with 20, 40, and 60 µm widths (arterial or venous), and a 30 µm width honeycombed network (arterial) with three bifurcation angles (30°, 60°, and 90°). Synthetic blood, equivalent to 46% haematocrit concentrations, and water were used to study the modulation of gas embolism-like events by liquid viscosity. Our study shows that (i) longer bubbles with lower velocity occur in narrower channels, e.g., with 20 µm width; (ii) the resistance of air bubbles to the flow increases with the higher haematocrit concentration; and lastly (iii) the propensity of gas embolism-like events in honeycomb architectures increases for more acute, e.g., 30°, bifurcation angles. A dimensionless analysis using Euler, Weber, and capillary numbers demarcated the conditions conducive to gas embolism. This work suggests that in vitro experimentation using microfluidic devices with microvascular tissue-like structures could assist medical guidelines and management in preventing and mitigating the effects of gas embolism.

The association between vitamin D intake with inflammatory and biochemical indices and mortality in critically ill patients with COVID-19: A case-control study.

BACKGROUND: The coronavirus disease-2019 (COVID-19) has become a worldwide health issue with widespread hospitalization and dependence on the intensive care unit (ICU). Vitamin D has a key role in modulating immune cells and modulating the inflammatory responses. This study aimed to investigate the association of vitamin D supplementation with inflammatory, biochemical, and mortality indices in critically ill patients with COVID-19. METHODS: This case-control study was conducted on critically ill COVID-19 patients hospitalized in the ICU including the survived >30 day patients as the case group and dead patients as the control group. The status of vitamin D supplementation and inflammatory and biochemical indices of the patients were retrieved from the medical records. Logistic regression method was used to assess the association between 30 days survival and vitamin D supplement intake. RESULTS: Compared to the group of COVID-19 patients who died in <30 day, the survived patients had a lower eosinophile level (2.2 ± 0.5 vs. 6 ± 0.0, p < .001) and higher vitamin D supplementation duration (9 ± 4.4 vs. 3.3 ± 1.9 day, p = .001). Vitamin D supplementation had a positive association with survival in COVID-19 patients (OR: 1.98, 95% CI: 1.15-3.40, p < .05). The association remained significant after adjustments fot age, sex, underlying diseases, and smoking. CONCLUSION: Vitamin D supplementation in critically ill patients with COVID-19 has the potential to increase survivability within the first 30 days of hospitalization.

Structural, Electronic, Reactivity, and Conformational Features of 2,5,5-Trimethyl-1,3,2-diheterophosphinane-2-sulfide, and Its Derivatives: DFT, MEP, and NBO Calculations.

In this study, we used density functional theory (DFT) and natural bond orbital (NBO) analysis to determine the structural, electronic, reactivity, and conformational features of 2,5,5-trimethyl-1,3,2-di-heteroatom (X) phosphinane-2-sulfide derivatives (X = O (compound 1), S (compound 2), and Se (compound 3)). We discovered that the features improve dramatically at 6-31G** and B3LYP/6-311+G** levels. The level of theory for the molecular structure was optimized first, followed by the frontier molecular orbital theory development to assess molecular stability and reactivity. Molecular orbital calculations, such as the HOMO-LUMO energy gap and the mapping of molecular electrostatic potential surfaces (MEP), were performed similarly to DFT calculations. In addition, the electrostatic potential of the molecule was used to map the electron density on a surface. In addition to revealing molecules' size and shape distribution, this study also shows the sites on the surface where molecules are most chemically reactive.

A simple coating method of PDMS microchip with PTFE for synthesis of dexamethasone-encapsulated PLGA nanoparticles.

Dexamethasone is a widely used drug in medical and biological applications. Since the systematic and controllable release of this drug is of significant importance, encapsulation of this anti-inflammatory drug in poly(lactic-co-glycolic acid) (PLGA) nanoparticles can minimize uncontrolled issues. As dexamethasone-encapsulated PLGA nanoparticles are synthesized in the presence of organic solvents, poly(dimethylsiloxane) (PDMS)-based microchannels collapse due to the swelling problem. In present study, PTFE nanoparticles were used for the surface modification of the microchannels to prevent absorption and adhesion of solvents into the microchannels' wall. The contact angle analysis of microchips after coating showed that the surface of microchannels bear the superhydrophobicity feature (140.30°) and SEM images revealed that PTFE covered the surface of PDMS, favorably. Then, the prepared microchip was tested for the synthesis of dexamethasone-loaded nanoparticles. SEM and atomic force microscopy (AFM) images of the synthesized nanoparticles represented that there was not any evidence of adhesion or absorption of nanoparticles. Furthermore, the monodispersity of nanoparticles was discernible. As AFM results revealed, the average diameters of 47, 63, and 82 nm were achieved for flow ratios of 0.01, 0.05, and 0.1, respectively. To evaluate the drug efficiency, cumulative release and encapsulation efficiency were analyzed which showed much more efficiency than the synthesized nanoparticles in the bulk mode. In addition, MTT test revealed that nanoparticles could be considered as a non-toxic material. Since the synthesis of drug-loaded nanoparticles is ubiquitous in laboratory experiments, the approach presented in this study can render more versatility in this regard.