A radioanalytical technique to study the behavior of organic toxicants applied to a study of the photodegradation of 2,3,7,8-tetrachlorodibenzo-p-dioxin

A general method for tritium labeling of organic compounds by the use of thermal activation of tritium is described. It allows obtaining uniformly tritium-labeled organic compounds with high specific activity (up to 50 Ci/mmol) which permits tracing the majority of the biodegradation products of compounds studied. More than 40 compounds were labeled using this simple, rapid and inexpensive method. Separation of the biodegradation products is performed by thin layer chromatography. Quantification is performed by direct measurement of the radioactivity by liquid scintillation counting after transfer of the layer from TLC plates into scintillation vials, or by densitometry of autoradiographs. The technique is useful for a wide range of organic compounds, including ones with unknown structure, and can be applied to various in vivo and in vitro studies.     

Sustainable biorefinery processes using renewable deep eutectic solvents

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Exploring the Role of Surface States in Emissive Carbon Nanodots: Analysis at Single-Particle Level

Fluorescent carbon nanodots (CDs) have been highlighted as promising semiconducting materials due to their outstanding chemical and optical properties. However, the intrinsic heterogeneity of CDs has impeded a clear understanding of the mechanisms behind their photophysical properties. In this study, as-prepared CDs are fractionated via chromatography to reduce their structural and chemical heterogeneity and analyzed through ensemble and single-particle spectroscopies. Many single particles reveal fluorescence intensity fluctuations between two or more discrete levels with bi-exponential decays. While the intrinsic τ₁ components are uniform among single particles, the τ₂ components from molecule-like emissions spans a wider range of lifetimes, reflecting the inhomogeneity of the surface states. Furthermore, it is concluded that the relative population and chemical states of surface functional groups in CDs have a significant impact on emissive states, brightness, blinking, stability, and lifetime distribution of photoluminescence.     

Computational Approaches to Discover Novel Natural Compounds for SARS-CoV-2 Therapeutics

Scientists all over the world are facing a challenging task of finding effective therapeutics for the coronavirus disease (COVID-19). One of the fastest ways of finding putative drug candidates is the use of computational drug discovery approaches. The purpose of the current study is to retrieve natural compounds that have obeyed to drug-like properties as potential inhibitors. Computational molecular modelling techniques were employed to discover compounds with potential SARS-CoV-2 inhibition properties. Accordingly, the InterBioScreen (IBS) database was obtained and was prepared by minimizing the compounds. To the resultant compounds, the absorption, distribution, metabolism, excretion and toxicity (ADMET) and Lipinski's Rule of Five was applied to yield drug-like compounds. The obtained compounds were subjected to molecular dynamics simulation studies to evaluate their stabilities. In the current article, we have employed the docking based virtual screening method using InterBioScreen (IBS) natural compound database yielding two compounds has potential hits. These compounds have demonstrated higher binding affinity scores than the reference compound together with good pharmacokinetic properties. Additionally, the identified hits have displayed stable interaction results inferred by molecular dynamics simulation results. Taken together, we advocate the use of two natural compounds, STOCK1N-71493 and STOCK1N-45683 as SARS-CoV-2 treatment regime.     

Ion transport in polymerized lyotropic liquid crystals containing ionic liquid

In this work, we investigate the effect of morphology and segmental dynamics on ion transport in polymerized lyotropic liquid crystals (polyLLCs) containing 1-butyl-3-methylimidazolium tetrafluoroborate as ionic liquid (IL). We demonstrate that two important factors, which affect ion conduction in polyLLCs, are grain size and chain density at the interface. The polyLLC with large grain size (70 nm) shows significant reduction in ion conductivity (one order of magnitude) compared to its homopolymer/IL mixture. However, the polyLLC with small grain size (20 nm) has little difference in ion conductivity compared to its homopolymer/IL mixture. It is observed that decreasing the chain density enhances the interaction of IL with polymer chains and consequently slows the relaxation of polymer chains. In addition, comparing the dynamics of polymer chains in mixtures of homopolymer/IL and templated LLC mesophases shows that the confinement in LLC structure prolongs the relaxation of polymer chains.     

Chemical Composition of a Novel Distillate from Fermented Mixture of Nine Anti-Inflammatory Herbs and Its UVB-Protective Efficacy in Mouse Dorsal Skin via Attenuating Collagen Disruption and Inflammation

Since ancient times, various herbs have been used in Asia, including Korea, China, and Japan, for wound healing and antiaging of the skin. In this study, we manufactured and chemically analyzed a novel distillate obtained from a fermented mixture of nine anti-inflammatory herbs (Angelica gigas, Lonicera japonica, Dictamnus dasycarpus Turcz., D. opposita Thunb., Ulmus davidiana var. japonica, Hordeum vulgare var. hexastichon Aschers., Xanthium strumarium L., Cnidium officinale, and Houttuynia cordata Thunb.). The fermentation of natural plants possesses beneficial effects in living systems. These activities are attributed to the chemical conversion of the parent plants to functional constituents which show more potent biological activities. In our current study, the distillate has been manufactured after fermenting the nine oriental medical plants with Lactobacillus fermentum, followed by distilling. We analyzed the chemical ingredients involved in the distillate and evaluated the effects of topical application of the distillate on ultraviolet B (UVB)-induced skin damage in Institute of Cancer Research (ICR) mice. Topical application of the distillate significantly ameliorated the macroscopic and microscopic morphology of the dorsal skin against photodamage induced by UVB radiation. Additionally, our current results showed that topical application of the distillate alleviated collagen disruption and reduced levels of proinflammatory cytokines (tumor necrosis factor alpha and interleukin 1 β expressions) in the dorsal skin against UVB radiation. Taken together, our current findings suggest that the distillate has a potential to be used as a material to develop a photoprotective adjuvant.     

Combinatorial Therapeutic Effect of Inhibitors of Aldehyde Dehydrogenase and Mitochondrial Complex I,and the Chemotherapeutic Drug,Temozolomide against Glioblastoma Tumorspheres

Resident cancer cells with stem cell-like features induce drug tolerance, facilitating survival of glioblastoma (GBM). We previously showed that strategies targeting tumor bioenergetics present a novel emerging avenue for treatment of GBM. The objective of this study was to enhance the therapeutic effects of dual inhibition of tumor bioenergetics by combination of gossypol, an aldehyde dehydrogenase inhibitor, and phenformin, a biguanide compound that depletes oxidative phosphorylation, with the chemotherapeutic drug, temozolomide (TMZ), to block proliferation, stemness, and invasiveness of GBM tumorspheres (TSs). Combination therapy with gossypol, phenformin, and TMZ induced a significant reduction in ATP levels, cell viability, stemness, and invasiveness compared to TMZ monotherapy and dual therapy with gossypol and phenformin. Analysis of differentially expressed genes revealed up-regulation of genes involved in programmed cell death, autophagy, and protein metabolism and down-regulation of those associated with cell metabolism, cycle, and adhesion. Combination of TMZ with dual inhibitors of tumor bioenergetics may, therefore, present an effective strategy against GBM by enhancing therapeutic effects through multiple mechanisms of action.     

Effect of Penetration Enhancers on Toenail Delivery of Efinaconazole from Hydroalcoholic Preparations

The incorporation of permeation enhancers in topical preparations has been recognized as a simple and valuable approach to improve the penetration of antifungal agents into toenails. In this study, to improve the toenail delivery of efinaconazole (EFN), a triazole derivative for onychomycosis treatment, topical solutions containing different penetration enhancers were designed, and the permeation profiles were evaluated using bovine hoof models. In an in vitro permeation study in a Franz diffusion cell, hydroalcoholic solutions (HSs) containing lipophilic enhancers, particularly prepared with propylene glycol dicaprylocaprate (Labrafac PG), had 41% higher penetration than the HS base. Moreover, the combination of hydroxypropyl-β-cyclodextrin with Labrafac PG further facilitated the penetration of EFN across the hoof membrane. In addition, this novel topical solution prepared with both lipophilic and hydrophilic enhancers was physicochemically stable, with no drug degradation under ambient conditions (25 °C, for 10 months). Therefore, this HS system can be a promising tool for enhancing the toenail permeability and therapeutic efficacy of EFN.     

The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure–Activity Relationship

The main protease (M^pro) is a major protease having an important role in viral replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that caused the pandemic of 2020. Here, active M^pro was obtained as a 34.5 kDa protein by overexpression in E. coli BL21 (DE3). The optimal pH and temperature of M^pro were 7.5 and 37 °C, respectively. M^pro displayed a K_m value of 16 μM with Dabcyl-KTSAVLQ↓SGFRKME-Edans. Black garlic extract and 49 polyphenols were studied for their inhibitory effects on purified M^pro. The IC₅₀ values were 137 μg/mL for black garlic extract and 9–197 μM for 15 polyphenols. The mixtures of tannic acid with puerarin, daidzein, and/or myricetin enhanced the inhibitory effects on M^pro. The structure–activity relationship of these polyphenols revealed that the hydroxyl group in C3′, C4′, C5′ in the B-ring, C3 in the C-ring, C7 in A-ring, the double bond between C2 and C3 in the C-ring, and glycosylation at C8 in the A-ring contributed to inhibitory effects of flavonoids on M^pro.