Identifying the specific-targeted marine cerebrosides against SARS-CoV-2: an integrated computational approach

Cerebrosides are a group of metabolites belonging to the glycosphingolipids class of natural products. So far, 167 cerebrosides, compounds 1–167, have been isolated from diverse marine organisms or microorganisms. The as yet smaller number of compounds that have been studied more in depth proves a potential against challenging diseases, such as cancer, a range of viral and bacterial diseases, as well as inflammation. This review provides a comprehensive summary on this so far under-explored class of compounds, their chemical structures, bioactivities, and their marine sources, with a full coverage to the end of 2020. Today, the global pandemic concern, COVID-19, has claimed millions of death cases around the world, making the development of anti-SARS-CoV-2 drugs urgently needed for such a battle. Accordingly, selected examples from all subclasses of cerebrosides were virtually screened for potential inhibition of SARS-CoV-2 proteins that are crucially involved in the viral–host interaction, viral replication, or in disease progression. The results highlight five cerebrosides that could preferentially bind to the hACE2 protein, with binding scores between −7.1 and −7.6 kcal mol⁻¹ and with the docking poses determined underneath the first α₁-helix of the protein. Moreover, the molecular interaction determined by molecular dynamic (MD) simulation revealed that renieroside C1 (60) is more conveniently involved in key hydrophobic interactions with the best stability, least deviation, least ΔG (−6.9 kcal mol⁻¹) and an RMSD value of 3.6 Å. Thus, the structural insights assure better binding affinity and favorable molecular interaction of renieroside C1 (60) towards the hACE2 protein, which plays a crucial role in the biology and pathogenesis of SARS-CoV-2.

Cerebrosides are a group of metabolites belonging to the glycosphingolipids class of natural products.     

Interferon‐gamma serum level and immunohistochemical expression of CD8 cells in tissue biopsies in patients with alopecia areata in correlation with trichoscopic findings

Alopecia areata (AA) is an autoimmune form of nonscarring hair loss. The aim of the study was to assess the serum concentration of interferon gamma (IFN‐γ) and CD8 cell expression in lesional skin biopsies in correlation with the disease severity, activity, duration, and trichoscopic findings in patients with AA. The study included 30 patients with AA and 15 age‐ and sex‐matched healthy controls. Trichoscopy was performed and photographs were captured for the alopecic areas, and the enzyme‐linked immunosorbent assay technique was used for serum level of IFN‐γ assessment and immunohistochemistry for CD8 cells. The results obtained indicate that IFN‐γ serum level in patients was significantly higher than that of control subjects, and significantly correlated with the activity status and the duration of the disease. CD8+ T cells infiltrate intensity significantly correlated with severity. Yellow dots (YDs), vellus hair, black dot, and exclamation marks were the most common trichoscopic findings. The presence of black dots significantly correlated to the disease activity, duration, serum IFN‐γ, and CD8+ infiltrate intensity. The presence of YDs significantly correlated with the mean serum IFN‐γ level. Exclamation marks significantly correlated with the disease activity and the degree of CD8+ infiltrate. In conclusion, trichoscopy could be a reliable indicator of the IFN‐γ serum level and CD8+ T cell infiltrate intensity in AA patient.     

UV-selective organic absorbers for the cosensitization of greenhouse-integrated dye-sensitized solar cells: synthesis and computational study

Molecular cosensitization is favorable for manipulating solar radiation through the judicious choice of cosensitizers having complementary absorption spectra. For greenhouse-integrated dye-sensitized solar cells (DSCs), the manipulation of solar radiation is crucial in order to maximize the flow of photosynthetically active radiation (PAR) for the effectual photosynthetic activity of plants; meanwhile, non-PAR is utilized in agrivoltaics for generating electricity. In this study, we report the synthesis of novel four UV-selective absorbers, based on the diimide scaffold, functionalized with carboxylate and pyridyl anchoring groups, for adequate adsorption onto the TiO₂ electrode in DSC. The UV/Vis absorption spectra of the DMF solution-based free dyes were measured experimentally. Basic photophysical and energetics requirements for operating greenhouse-integrated DSCs were examined at the molecular level via (time-dependent) density functional theory-based calculations. The computational results revealed the outperformance of the biphenyldiimide-structured DI-CA1 dye, especially for maximum charge transferred to its anchor, lower thermodynamic barrier for dissociating the photogenerated exciton, largest Stokes'' shift, strong electronic coupling with TiO₂ nanoparticles, and higher degree of charge separation at the DI-CA1/TiO₂ interface. PDOS showed deeper existence for the LUMO level in the CB of TiO₂, which expedites the electron injection process. The chemical and optical compatibility of DI-CA1 were then investigated as a potential cosensitizer of a reference BTD–DTP1, a green light-absorbing dye. Considerable overlap between the fluorescence spectrum of DI-CA1 and absorption spectrum of the reference BTD–DTP1 advocated the opportunity of excitation energy transfer via the radiative trivial reabsorption mechanism, which confirms the cosensitization functionality. Energy decomposition analysis and reduced density gradient maps estimated the chemical compatibility owing to weak dispersion interactions as the dominant stabilizing attractive force. This noncovalent functionalization retains the chemical compatibility without distorting the π–π conjugation and the associated physicochemical properties of the individual dye molecules. Along with the expanded consumption of non-photosynthetically active solar radiation, an improved power conversion efficiency of greenhouse-integrated DSC is accordingly expected.

Molecular cosensitization is favorable for manipulating solar radiation through the judicious choice of cosensitizers having complementary absorption spectra.     

Chitosan-coated bovine serum albumin nanoparticles for topical tetrandrine delivery in glaucoma: in vitro and in vivo assessment

Glaucoma is one of the leading causes of blindness. Therapies available suffer from several drawbacks including low bioavailability, repeated administration and poor patient compliance with adverse effects thereafter. In this study, bovine serum albumin nanoparticles (BSA-NPs) coated with chitosan(CS) were developed for the topical delivery of tetrandrine (TET) for glaucoma management. Optimized nanoparticles were prepared by desolvation. pH, BSA, CS and cross-linking agent concentrations effects on BSA-NPs colloidal properties were investigated. CS-BSA-NPs with particle size 237.9 nm and zeta potential 24 mV was selected for further evaluation. EE% exceeded 95% with sustained release profile. In vitro mucoadhesion was evaluated based on changes in viscosity and zeta potential upon incubation with mucin. Ex vivo transcorneal permeation was significantly enhanced for CS coated formulation. In vitro cell culture studies on corneal stromal fibroblasts revealed NPs biocompatibility with enhanced cellular uptake and improved antioxidant and anti-proliferative properties for the CS-coated formulation. Moreover, BSA-NPs were nonirritant as shown by HET-CAM test. Also, bioavailability in rabbit aqueous humor showed 2-fold increase for CS-TET-BSA-NPs compared to TET with a sustained reduction in intraocular pressure in a rabbit glaucoma model. Overall, results suggest CS-BSA-NPs as a promising platform for topical ocular TET delivery in the management of glaucoma.     

A simple single jar “on–off fluorescence” designed system for the determination of mitoxantrone using an eosin Y dye in raw powder,vial, and human biofluids

In this work, a direct, simple, one-pot, and green spectrofluorimetric approach was applied to measure mitoxantrone, a chemotherapeutic agent, through a green validated method. The suggested approach focused on establishing an easy association complex combining mitoxantrone and the eosin Y reagent in a slightly acidic solution. The fluorometric analysis was dependent on off-mitoxantrone action on the emission intensity of the dye (eosin Y) at 544.5 nm (excitation = 301 nm). The devised system has a linear range of 0.07–2.5 μg mL⁻¹ and a detection limit of 0.016 μg mL⁻¹. All system parameters for the formation of mitoxantrone–eosin Y complexes were modulated analytically. Also, the system was reviewed in agreement with ICH criteria. Furthermore, the proposed model was approached to quantify mitoxantrone in its pharmaceutical vial dosage form with high recoveries. Also, the proposed spectroscopic design was efficiently employed to detect the investigated drug in body fluids (blood and urine). Lastly, the designed method was evaluated from a greenness point of view according to eco-scale.

This work describes a green fluorescence on–off system that relies on establishing a simple ion association complex pairing the mitoxantrone antineoplastic drug with the eosin Y reagent in a slightly acidic solution.     

Differentiation malignant from benign parotid tumors in children with diffusion-weighted MR imaging

Purpose

To differentiate pediatric solid malignant from the benign parotid tumors with diffusion-weighted MR imaging (DWI).

Materials and methods

A retrospective study comprising 38 children with parotid tumors (21 boys and 17 girls aged from 2 months to 17 years) was conducted using (DWI) of the parotid gland. Apparent diffusion coefficient (ADC) maps were generated. The ADC value of the parotid tumors was calculated.

Results

The mean ADC value of malignant parotid tumors (1.08?±?0.1, 1.04?±?0.1?×?10^?3mm²/s) was significantly lower [P?=?0.001] than that of benign lesions (1.69?±?0.2, 1.72?±?0.3?×?10^?3mm²/s). A threshold of ADC of 1.40, 1.33?×?10^?3mm²/s was used for differentiating malignant parotid tumors from benign lesions and led to the best results of the area under the curve of 0.940, 0.929, accuracy of 86, 89%, sensitivity of 94, 94%, specificity of 80, 85%, negative predictive value of 94.1, 94.4%, and positive predictive value of 81, 85%. There was insignificant difference in ADC values of malignant lesions (P?=?0.23, 0.30) as well as within benign lesions (P?=?0.25, 0.08).

Conclusion

DWI is an innovative anticipating imaging technique that can be used in the differentiation of pediatric solid malignant parotid tumors from benign lesions.