The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review

Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi’s sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to approve the use of retinoids for NMSC management. Acceptable off-label uses of these compounds as drugs for skin cancers are also described. This review is a comprehensive outline on the biochemistry of retinoids, their activities in the skin, their effects on cancer cells and their adoption in clinical practice.     

Corrosion inhibition and Biocidal effect of some cationic surfactants based on Schiff base

The three cationic surfactants based on Schiff base were laboratory prepared, (E)-decyl-4-[(2-hydroxyethylamino) methyl]-N,N-dimethyl benzenaminium bromide (I), (E)-dodecyl-4-[(2-hydroxyethylamino)methyl]-N,N-dimethyl benzenaminium bromide (II) and (E)-hexadecyl-4-[(2-hydroxyethylamino)methyl]-N,N-dimethyl benzenaminium bromide (III) were evaluated as corrosion inhibitors for carbon steel in acid medium and antimicrobial agents against sulfate reducing bacteria, SRB. Three techniques were used for the corrosion inhibition evaluation, namely; weight loss, polarization and electrochemical impedance. The serial dilution method was used to evaluate the inhibiting effect of these compounds on the sulfate reducing bacteria growth. The results showed that the prepared compounds have good antimicrobial activities against the SRB as well as they have high efficiency as corrosion inhibitors for carbon steel in 1 M HCl.     

Optimal economic study of hybrid PV-wind-fuel cell system integrated to unreliable electric utility using hybrid search optimization technique

This study addresses the problem of power outages in distant districts by taking advantage of the available renewable energy resources in the surrounding environment. This was done by proposing connecting the utility to a hybrid system constituting from photovoltaic (PV), wind turbine (WT), and fuel cell (FC) systems where this hybrid system is considered as a backup system that works when the grid is unavailable. This hybrid system proposed is used for feeding the load to a tourist resort in Hurghada, Egypt.The design of the introduced system has taken into consideration the cost of purchasing electric energy and the profit from selling it to the utility network. Component scaling was implemented to improve the net present cost of the proposed system using two grouped meta-heuristic techniques, which are the Hybrid Firefly and Harmony Search optimization technique (HFA/HS) and compared to the particle swarm optimization (PSO) technique.Simulation results have shown that the optimal system for solving the grid unavailability consists of eighty PVs, two WTs, twenty FCs, forty-one electrolyzers, and one hundred eighteen hydrogen tanks. The results also showed that the volume of exchange with the grid has reached 4 GW of purchase and 3 GW of sale. It is manifest from the results that the suggested system is economically viable with an LCOE of 0.0628 $/kWh, which is less than the purchase of electricity from the grid for commercial users in Egypt, which is 0.1 $/kWh.     

Inhibitive Action of New Synthesized Cationic Surfactant with Free Hydroxyl Group on the C1018 Steel Corrosion: Experimental and Theoretical Investigations

Protection of Metals and Physical Chemistry of Surfaces - A new cationic surfactant namely, N-(2-(2-hydroxyethoxy)ethyl)-N,N-dimethylhexadecan-1-ammonium bromide (HEDHB) was prepared and its...     

Assessment of formulation parameters needed for successful vitamin C entrapped polycaprolactone nanoparticles

Vitamin C (Vit.C)-entrapped polycaprolactone (PCL) nanoparticles (Vit.C–PCNs) were prepared by encapsulation of Vit.C into PCL-based nanoparticles (PCNs) which were prepared using double emulsion method with two steps. First, the inner aqueous phase (W₁) was added to dichloromethane solution containing PCL with homogenization to form primary emulsion (W₁/O) which was emulsified with the outer aqueous phase (W₂) containing polyvinyl alcohol as stabilizer to attain the double emulsion (W₁/O/W₂). Versatile parameters were investigated to reach to the most successful formulation for Vit.C–PCNs, such as time, effect of speed of homogenization on drug encapsulation efficiency, etc.     

Chemical Space Overlap with Critical Protein–Protein Interface Residues in Commercial and Specialized Small-Molecule Libraries

There is growing interest in the use of structure-based virtual screening to identify small molecules that inhibit challenging protein–protein interactions (PPIs). In this study, we investigated how effectively chemical library members docked at the PPI interface mimic the position of critical side-chain residues known as “hot spots”. Three compound collections were considered, a commercially available screening collection (ChemDiv), a collection of diversity-oriented synthesis (DOS) compounds that contains natural-product-like small molecules, and a library constructed using established reactions (the “screenable chemical universe based on intuitive data organization”, SCUBIDOO). Three different tight PPIs for which hot-spot residues have been identified were selected for analysis: uPAR⋅uPA, TEAD4⋅Yap1, and Ca_Vα⋅Ca_Vβ. Analysis of library physicochemical properties was followed by docking to the PPI receptors. A pharmacophore method was used to measure overlap between small-molecule substituents and hot-spot side chains. Fragment-like conformationally restricted small molecules showed better hot-spot overlap for interfaces with well-defined pockets such as uPAR⋅uPA, whereas better overlap was observed for more complex DOS compounds in interfaces lacking a well-defined binding site such as TEAD4⋅Yap1. Virtual screening of conformationally restricted compounds targeting uPAR⋅uPA and TEAD4⋅Yap1 followed by experimental validation reinforce these findings, as the best hits were fragment-like and had few rotatable bonds for the former, while no hits were identified for the latter. Overall, such studies provide a framework for understanding PPIs in the context of additional chemical matter and new PPI definitions.     

Effect of waste-derived MA spinel on sintering and stabilization behavior of partially stabilized double phase zirconia

Cubic-stabilized zirconia ceramic composites have been synthesized by conventional sintering, starting from commercial m-ZrO₂, Y₂O₃, and waste-derived magnesium aluminate spinel (MA) powders. In this work, the effect of sintering temperature and MA content on stabilization and densification properties of YSZ have been duly considered. MA-free YSZ0 composite sintered at 1600°C-1700°C revealed m- and t-ZrO₂ dual-phase structure where its m-ZrO₂ was partially stabilized upon temperature rising into tetragonal phase by Y³⁺ diffusion inside zirconia structure. YSZ10-50 composites containing 10-50 wt% MA demonstrated dissimilar behavior where their m-ZrO₂ was transformed and stabilized into a cubic form by diffusion of Y³⁺, Mg⁺², and Al⁺³ inside zirconia lattice. Furthermore, densification of YSZ10-50 powder mixtures by conventional sintering at 1600°C for 2 hours resulted in fully dense compacts with micrometer-sized grains. The outcomes indicate that MA has a significant effect on m-ZrO₂ stabilization into the cubic phase structure at room temperature. In this respect, this study offers huge potentials for developing fully stabilized c-ZrO₂ ceramics that could be possibly used as industrial ceramics for structural applications of harsh chemical and thermal environmental conditions.     

Covalent Fragment Screening Identifies Rgl2 RalGEF Cysteine for Targeted Covalent Inhibition of Ral GTPase Activation

Ral GTPases belong to the RAS superfamily, and they are directly activated by K-RAS. The RalGEF pathway is one of the three major K-RAS signaling pathways. Ral GTPases do not possess a cysteine nucleophile to develop a covalent inhibitor following the strategy that led to a K-RAS G12C therapeutic agent. However, several cysteine amino acids exist on the surface of guanine exchange factors that activate Ral GTPases, such as Rgl2. Here, we screen a library of cysteine electrophile fragments to determine if covalent bond formation at one of the Rgl2 surface cysteines could inhibit Ral GTPase activation. We found several chloroacetamide and acrylamide fragments that inhibited Ral GTPase exchange by Rgl2. Site-directed mutagenesis showed that covalent bond formation at Cys-284, but not other cysteines, leads to inhibition of Ral activation by Rgl2. Follow-up time- and concentration-dependent studies of derivatives identified by substructure search of commercial libraries further confirmed Cys-284 as the reaction site and identified the indoline fragments as the most promising series for further development. Cys-284 is located outside of the Ral ⋅ Rgl2 interface on a loop that has several residues that come in direct contact with Ral GTPases. Our allosteric covalent fragment inhibitors provide a starting point for the development of small-molecule covalent inhibitors to probe Ral GTPases in animal models.