Enhancing endothelial differentiation of human mesenchymal stem cells by culture on a nanofibrous polycaprolactone/(poly-glycerol sebacate)/gelatin scaffold

Cardiovascular diseases have always been one of the main causes of death worldwide and eventually one of the major medical concerns. Tissue engineering is promising strategies of treating cardiovascular, which can be an effective approach with the design of appropriate scaffold. In this study, to develop engineering basement membrane for endothelial differentiation with good cell attachment, we produced polycaprolactone (PCL)/poly (glycerol sebacate) (PGS)/gelatin nanofibrous scaffold via electrospinning. Attenuated total reflectance-Fourier transform infrared and the proton nuclear magnetic resonance results confirmed the chemical structure of synthesized PGS. Scanning electron microscope images of the electrospun scaffold revealed that the nanofibers are smooth, continues and uniform. Moreover, due to the presence of hydrophilic functional groups in the scaffold, the contact angle is in the appropriate range for cell adhesion especially endothelial cells. The elastic modulus and ultimate tensile stress of electrospun scaffold were calculated 1.32 ± 0.27 MPa and 1.23 ± 0.18 MPa respectively. Quantitative polymerase chain reaction was performed for evaluation of endothelial differentiation of mesenchymal stem cells cultured on standard plate and fibrous scaffold under chemical stimulation with growth factor. Specific endothelial gene expression results postulated that our modified scaffold could support and significantly promote endothelial differentiation of MSCs.     

Porous and Water Stable 2D Hybrid Metal Halide with Broad Light Emission and Selective H2O Vapor Sorption

In this work we report a strategy for generating porosity in hybrid metal halide materials using molecular cages that serve as both structure-directing agents and counter-cations. Reaction of the [2.2.2] cryptand (DHS) linker with Pb^II in acidic media gave rise to the first porous and water-stable 2D metal halide semiconductor (DHS)₂Pb₅Br₁₄. The corresponding material is stable in water for a year, while gas and vapor-sorption studies revealed that it can selectively and reversibly adsorb H₂O and D₂O at room temperature (RT). Solid-state NMR measurements and DFT calculations verified the incorporation of H₂O and D₂O in the organic linker cavities and shed light on their molecular configuration. In addition to porosity, the material exhibits broad light emission centered at 617 nm with a full width at half-maximum (FWHM) of 284 nm (0.96 eV). The recorded water stability is unparalleled for hybrid metal halide and perovskite materials, while the generation of porosity opens new pathways towards unexplored applications (e.g. solid-state batteries) for this class of hybrid semiconductors.     

High-throughput Synthesis of Solution-Processable van der Waals Heterostructures through Electrochemistry

Two-dimensional van der Waals heterostructures (2D vdWHs) have recently gained widespread attention because of their abundant and exotic properties, which open up many new possibilities for next-generation nanoelectronics. However, practical applications remain challenging due to the lack of high-throughput techniques for fabricating high-quality vdWHs. Here, we demonstrate a general electrochemical strategy to prepare solution-processable high-quality vdWHs, in which electrostatic forces drive the stacking of electrochemically exfoliated individual assemblies with intact structures and clean interfaces into vdWHs with strong interlayer interactions. Thanks to the excellent combination of strong light absorption, interfacial charge transfer, and decent charge transport properties in individual layers, thin-film photodetectors based on graphene/In₂Se₃ vdWHs exhibit great promise for near-infrared (NIR) photodetection, owing to a high responsivity (267 mA W⁻¹), fast rise (72 ms) and decay (426 ms) times under NIR illumination. This approach enables various hybrid systems, including graphene/In₂Se₃, graphene/MoS₂ and graphene/MoSe₂ vdWHs, providing a broad avenue for exploring emerging electronic, photonic, and exotic quantum phenomena.     

Nitazoxanide and azithromycin for the early treatment of COVID-19: A multi-spectroscopic,biochemical and computational drug–drug interaction study

Herein, we present an experimental and theoretical drug–drug interaction study between nitazoxanide (NTZ) and azithromycin (AZT) in an aqueous solution. Interaction was studied by using UV/Vis, fluorescence, attenuated total reflectance-fourier transform infrared (ATR-FTIR), and circular dichroism (CD) spectroscopy, while molecular docking studies were performed to establish the interaction computationally. A bright yellow color was observed when the two drugs interacted, giving a hyperchromic band at 420 nm. The rate of absorbance was linearly increased by increasing drug concentrations and in a time-dependent manner. Stability of the interaction complex (i.e., NTZ: AZT) was measured at variable temperatures (25–80°C), pH (5.0–10.0) and ionic strength (0.05–2.0 M NaCl), and not only proved stable but also retained antimicrobial potential with reduced cellular toxicity. Mole ratio and Job's method of continuous variations were used to establish the binding stoichiometry and found to be 2:1. The calculated binding constant (k_b = 8,400 M⁻¹) and Gibb's free energy (ΔG° = −22.4 KJ/mol) also suggested an energetically favorable interaction. FTIR spectra of NTZ: AZT complex in comparison with two drugs alone revealed significant interaction which was nicely complemented by molecular docking studies. Interaction was also successfully demonstrated in presence of carrier protein HSA and by spiking the two drugs in real samples of human plasma and urine.     

Front Cover: Katritzky Salts for the Synthesis of Unnatural Amino Acids and Late-Stage Functionalization of Peptides (Eur. J. Org. Chem. 12/2023)

Peptide drug discovery often benefits from the large structural diversity permitted by unnatural amino acids (UAAs). Indeed, numerous approved peptide drugs include UAAs in their sequences. Therefore, innovative chemical approaches either to synthesize UAAs or to allow late-stage functionalization of peptides are emerging themes in peptide drug discovery. Thanks to the recent advances in deaminative strategies using alkylpyridiniums salts, often referred to as Katritzky salts, a variety of radical alkylation methods have been developed. In recent years the use of Katritzky salts have become popular in peptide chemistry due to their ease of preparation from a primary amine, which is a predominant functional group in amino acids. This review highlights the progress that has been made by using Katritzky salts in the synthesis of UAAs, late-stage peptide functionalization, and peptide macrocyclization.     

Electrochemical Sensing Platform Based on Graphene Oxide-chitosan for Simultaneous Determination of some Antihypertensive Drugs

The development of selective and simple methods for the determination of different analytes is of great interest. This is the first time to show the applicability of graphene oxide-chitosan (GO-CS) nanocomposite for designing an electrochemical nanosensor for determination of Amlodipine, Valsartan, and Hydrochlorothiazide, simultaneously. Differential pulse voltammetrics current of AML, HCT, and VAL increased linearly in the ranges of 0.1–110, 0.1–110, and 1–230 μM with LOD of 5.5×10⁻², 3.5×10⁻² and 8.6×10⁻² μM, respectively. Finally, GO-CS/GCE was used for the detection of these drugs in commercial tablets and compared with the reference method (HPLC).     

Dispersive solid phase extraction of metronidazole and clarithromycin from human plasma using a β-cyclodextrin grafted polyethylene polymer composite

In this work, for the first time, a polymeric composite based on β-cyclodextrin grafted with polyethylene has been prepared through ball milling and used as an efficient sorbent for dispersive solid phase extraction of metronidazole and clarithromycin from plasma samples. The prepared sorbent was characterized using Fourier transform infrared spectrophotometry, X-ray diffraction, and scanning electron microscopy. In the extraction process, after precipitating the proteins, the sorbent was added into the sample solution, and the mixture was vortexed to facilitate and speed up the sorption of the analytes onto the sorbent surface. After centrifuging, the sorbent particles were contacted with methanol to elute the analytes under the vortexing process. After this step, an aliquot of the eluate was taken and injected into high-performance liquid chromatography–diode array detector for quantitative analysis. Under the optimum extraction conditions, the extraction recoveries for metronidazole and clarithromycin were 76 and 83%, respectively. The limits of detection were 2.6 and 2.2 ng/ml for metronidazole and clarithromycin, respectively. The repeatability of the offered approach, expressed as relative standard deviation, was equal to or less than 4.7%. Finally, the method was successfully applied to plasma samples of the patients treated with metronidazole and clarithromycin.     

Generation of Haploid Spermatids on Silk Fibroin-Alginate-Laminin-Based Porous 3D Scaffolds

In vitro production of sperm is a desirable idea for fertility preservation in azoospermic men and prepubertal boys suffering from cancer. In this study, a biocompatible porous scaffold based on a triad mixture of silk fibroin (SF), alginate (Alg), and laminin (LM) is developed to facilitate the differentiation of mouse spermatogonia stem cells (SSCs). Following SF extraction, the content is analyzed by SDS-PAGE and stable porous 3D scaffolds are successfully prepared by merely Alg, SF, and a combination of Alg-SF, or Alg-SF-LM through freeze-drying. Then, the biomimetic scaffolds are characterized regarding the structural and biological properties, water absorption capacity, biocompatibility, biodegradability, and mechanical behavior. Neonatal mice testicular cells are seeded on three-dimensional scaffolds and their differentiation efficiency is evaluated using real-time PCR, flow cytometry, immunohistochemistry. Blend matrices showed uniform porous microstructures with interconnected networks, which maintained long-term stability and mechanical properties better than homogenous structures. Molecular analysis of the cells after 21 days of culture showed that the expression of differentiation-related proteins in cells that are developed in composite scaffolds is significantly higher than in other groups. The application of a composite system can lead to the differentiation of SSCs, paving the way for a novel infertility treatment landscape in the future.     

Targeted Delivery of Anticancer Drug Loaded Charged PLGA Polymeric Nanoparticles Using Electrostatic Field

Pure positive electrostatic charges (PPECs) show suppressive effect on the proliferation and metabolism of invasive cancer cells without affecting normal tissues. PPECs are used for the delivery of drug-loaded polymeric nanoparticles (DLNs) capped with negatively charged poly(lactide-co-glycolide) (PLGA) and Poly(vinyl-alcohol) PVA into the tumor site of mouse models. The charged patch is installed on top of the skin in the mouse models' tumor region, and the controlled selective release of the drug is assayed by biochemical, radiological, and histological experiments on both tumorized models and normal rats' livers. It is found that DLNs synthesized by PLGA show great attraction to PPECs due to their stable negative charges, which would not degrade immediately in blood. The burst and drug release after less than 48h of this synthesized DLNs are 10% and 50%, respectively. These compounds can deliver the loaded-drug into the tumor site with the assistance of PPECs, and the targeted-retarded release will take place. Hence, local therapy can be achieved with much lower drug concentration (conventional chemotherapy [2 mg kg⁻¹] versus DLNs-based chemotherapy [0.75 mg kg⁻¹]) with negligible side effects in non-targeted organs. PPECs have many potential clinical applications for advanced-targeted chemotherapy with the lowest discernible side effects.     

Recent Advances in the Support Layer,Interlayer and Active Layer of TFC and TFN Organic Solvent Nanofiltration (OSN) Membranes: A Review

Although separation of solutes from organic solutions is considered a challenging process, it is inevitable in various chemical, petrochemical and pharmaceutical industries. OSN membranes are the heart of OSN technology that are widely utilized to separate various solutes and contaminants from organic solvents, which is now considered an emerging field. Hence, numerous studies have been attracted to this field to manufacture novel membranes with outstanding properties. Thin-film composite (TFC) and nanocomposite (TFN) membranes are two different classes of membranes that have been recently utilized for this purpose. TFC and TFN membranes are made up of similar layers, and the difference is the use of various nanoparticles in TFN membranes, which are classified into two types of porous and nonporous ones, for enhancing the permeate flux. This study aims to review recent advances in TFC and TFN membranes fabricated for organic solvent nanofiltration (OSN) applications. Here, we will first study the materials used to fabricate the support layer, not only the membranes which are not stable in organic solvents and require to be cross-linked, but also those which are inherently stable in harsh media and do not need any cross-linking step, and all of their advantages and disadvantages. Then, we will study the effects of fabricating different interlayers on the performance of the membranes, and the mechanisms of introducing an interlayer in the regulation of the PA structure. At the final step, we will study the type of monomers utilized for the fabrication of the active layer, the effect of surfactants in reducing the tension between the monomers and the membrane surface, and the type of nanoparticles used in the active layer of TFN membranes and their effects in enhancing the membrane separation performance.