Ionic conductivity and phase stabilization in Cu- and Tl-substituted CsAg2I3

Samples of general formula CsAg_2−xM_xI₃, x=0–0.4 and M=Cu and Tl, have been prepared and studied by powder X-ray diffraction, DSC and electrical conductivity measurements. X-ray diffractograms and DSC curves showed the possibility of stabilizing the high-temperature -phase at lower temperatures in Tl-substituted samples, while such results were not obtained in Cu-substituted samples. Ionic conductivity measurements showed two regions corresponding to the low- and high-temperature phases. The transition temperature between the two phases was found to remain unchanged with the addition of Cu⁺ and decreased gradually with increasing Tl⁺. The ionic conductivity decreased in Cu-substituted samples and enhanced with the incorporation of Tl⁺ ion in the lattice of CsAg₂I₃. Dielectric constant was found to show behaviour similar to that of the ionic conductivity, and this is an evidence of the predominant effect of ion hopping on this property.     

The Growth Factors and Cytokines of Dental Pulp Mesenchymal Stem Cell Secretome May Potentially Aid in Oral Cancer Proliferation

Background: Growth factors and cytokines responsible for the regenerative potential of the dental pulp mesenchymal stem cell secretome (DPMSC-S) are implicated in oral carcinogenesis. The impact and effects of these secretory factors on cancer cells must be understood in order to ensure their safe application in cancer patients. Objective: We aimed to quantify the growth factors and cytokines in DPMSC-S and assess their effect on oral cancer cell proliferation. Materials and methods: DPMSCs were isolated from patients with healthy teeth (n = 5) that were indicated for extraction for orthodontic reasons. The cells were characterized using flow cytometry and conditioned medium (DPMSC-CM) was prepared. DPMSC-CM was subjected to a bead-based array to quantify the growth factors and cytokines that may affect oral carcinogenesis. The effect of DPMSC-CM (20%, 50%, 100%) on the proliferation of oral cancer cells ({"type":"entrez-nucleotide","attrs":{"text":"AW123516","term_id":"6099046"}}AW123516) was evaluated using a Ki-67-based assay at 48 h. AW13516 cultured in the standard growth medium acted as the control. Results: VEGF, HCF, Ang-2, TGF-α, EPO, SCF, FGF, and PDGF-BB were the growth factors with the highest levels in the DPMSC-CM. The highest measured pro-inflammatory cytokine was TNF-α, followed by CXCL8. The most prevalent anti-inflammatory cytokine in the DPMSC-CM was IL-10, followed by TGF-β1 and IL-4. Concentrations of 50% and 100% DPMSC-CM inhibited Ki-67 expression in AW13516, although the effect was non-significant. Moreover, 20% DPMSC-CM significantly increased Ki-67 expression compared to the control. Conclusions: The increased Ki-67 expression of oral cancer cells in response to 20% DPMSC-CM indicates the potential for cancer progression. Further research is needed to identify their effects on other carcinogenic properties, including apoptosis, stemness, migration, invasion, adhesion, and therapeutic resistance.     

Thymus algeriensis and Artemisia herba-alba Essential Oils: Chemical Analysis,Antioxidant Potential and In Vivo Anti-Inflammatory,Analgesic Activities,and Acute Toxicity

The study of bioactive molecules of natural origin is a focus of current research. Thymus algeriensis and Artemisia herba-alba are two medicinal plants widely used by the Moroccan population in the traditional treatment of several pathologies linked to inflammation. This study aimed to evaluate the single and combined antioxidant, anti-inflammatory and analgesic effects of the essential oils extracted from these two medicinal plants, and also their potential toxicity. Essential oils were extracted using hydro-distillation in a Clevenger-type apparatus. The antioxidant activity was evaluated by two methods: the scavenging of the free radical DPPH, and the reduction in iron. Anti-inflammatory activity was evaluated by evaluating the edema development induced by carrageenan injecting, while the analgesic power was evaluated according to the number of abdominal contortions induced by the intraperitoneal injection of acetic acid (0.7%). The acute oral toxicity was performed to assess the potential toxicity of the studied EOs, followed by an analysis of the blood biochemical parameters. The results of the two antioxidant tests indicated that our extract mixture exhibits good iron reduction capacity and very interesting DPPH free radical scavenging power, with an IC₅₀ of around 4.38 ± 0.98 μg/mL higher than that of the benchmark antioxidant, BHT. The anti-inflammatory test demonstrated that the mixture administered orally at a dose of 150 mg/kg has a better activity, exceeding that of 1% Diclofenac, with a percentage of maximum inhibition of the edema of 89.99 ± 4.08. The number of cramps in the mice treated with the mixture at a dose of 150 mg/kg is significantly lower (29.80 ± 1.92) than those of the group treated with Tramadol (42.00 ± 2.70), respectively. The toxicity results show no signs of toxicity with an LD₅₀ greater than 150 mg/Kg. These interesting results show that the two plants’ EOs had an important anti-inflammatory, analgesic, and antioxidant activity, and also a powerful synergistic effect, which encourages further in-depth investigations on their pharmacological proprieties.     

Synthesis,Antimicrobial, Anticancer,PASS, Molecular Docking,Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs

A series of methyl β-D-galactopyranoside (MGP, 1) analogs were selectively acylated with cinnamoyl chloride in anhydrous N,N-dimethylformamide/triethylamine to yield 6-O-substitution products, which was subsequently converted into 2,3,4-tri-O-acyl analogs with different acyl halides. Analysis of the physicochemical, elemental, and spectroscopic data of these analogs revealed their chemical structures. In vitro antimicrobial testing against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) showed promising antifungal functionality comparing to their antibacterial activities. Minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests were conducted for four compounds (4, 5, 6, and 9) based on their activity. MTT assay showed low antiproliferative activity of compound 9 against Ehrlich’s ascites carcinoma (EAC) cells with an IC₅₀ value of 2961.06 µg/mL. Density functional theory (DFT) was used to calculate the thermodynamic and physicochemical properties whereas molecular docking identified potential inhibitors of the SARS-CoV-2 main protease (6Y84). A 150-ns molecular dynamics simulation study revealed the stable conformation and binding patterns in a stimulating environment. In-silico ADMET study suggested all the designed molecules to be non-carcinogenic, with low aquatic and non-aquatic toxicity. In summary, all these antimicrobial, anticancer and in silico studies revealed that newly synthesized MGP analogs possess promising antiviral activity, to serve as a therapeutic target for COVID-19.     

Elucidation of the Roles of Ionic Liquid in CO2 Electrochemical Reduction to Value-Added Chemicals and Fuels

The electrochemical reduction of carbon dioxide (CO₂ER) is amongst one the most promising technologies to reduce greenhouse gas emissions since carbon dioxide (CO₂) can be converted to value-added products. Moreover, the possibility of using a renewable source of energy makes this process environmentally compelling. CO₂ER in ionic liquids (ILs) has recently attracted attention due to its unique properties in reducing overpotential and raising faradaic efficiency. The current literature on CO₂ER mainly reports on the effect of structures, physical and chemical interactions, acidity, and the electrode–electrolyte interface region on the reaction mechanism. However, in this work, new insights are presented for the CO₂ER reaction mechanism that are based on the molecular interactions of the ILs and their physicochemical properties. This new insight will open possibilities for the utilization of new types of ionic liquids. Additionally, the roles of anions, cations, and the electrodes in the CO₂ER reactions are also reviewed.     

A Review of HER4 (ErbB4) Kinase,Its Impact on Cancer,and Its Inhibitors

HER4 is a receptor tyrosine kinase that is required for the evolution of normal body systems such as cardiovascular, nervous, and endocrine systems, especially the mammary glands. It is activated through ligand binding and activates MAPKs and PI3K/AKT pathways. HER4 is commonly expressed in many human tissues, both adult and fetal. It is important to understand the role of HER4 in the treatment of many disorders. Many studies were also conducted on the role of HER4 in tumors and its tumor suppressor function. Mostly, overexpression of HER4 kinase results in cancer development. In the present article, we reviewed the structure, location, ligands, physiological functions of HER4, and its relationship to different cancer types. HER4 inhibitors reported mainly from 2016 to the present were reviewed as well.     

Phytochemical Analysis,Antispasmodic, Myorelaxant,and Antioxidant Effect of Dysphania ambrosioides (L.) Mosyakin and Clemants Flower Hydroethanolic Extracts and Its Chloroform and Ethyl Acetate Fractions

Dysphania ambrosioides (L.) Mosyakin and Clemants is an annual or ephemeral perennial herb used traditionally in the Mediterranean region in folk medicine to treat various illnesses, including those related to the digestive system. This study aims to assess the antispasmodic, myorelaxant, and antioxidant effects of D. ambrosioides flower hydroethanolic extract and its chloroform and ethyl acetate fractions in a comparative study to evaluate the result of the extraction type on the potential activity of the extract. Both rat and rabbit jejunum were used to evaluate the antispasmodic and myorelaxant effect, while the antioxidant effect was evaluated using DPPH, a ferric reducing power assay, and a beta-carotene bleaching test. LC/MS-MS analysis was carried out to reveal the composition of the different types of extract. Following the results, the hydroethanolic extract showed a significant myorelaxant effect (IC₅₀ = 0.39 ± 0.01 mg/mL). Moreover, it was shown that the hydroethanolic extract demonstrated the best antispasmodic activity (IC₅₀ = 0.51 ± 0.05 mg/mL), followed by the ethyl acetate (IC₅₀ = 4.05 ± 0.32 mg/mL) and chloroform (IC₅₀ = 4.34 ± 0.45 mg/mL) fractions. The antioxidant tests showed that the hydroethanolic extract demonstrated high antioxidant activity, followed by the ethyl acetate and chloroform fractions. The LC/MS-MS analysis indicates that the plant extract was rich in flavonoids, to which the extract activity has been attributed. This study supports the traditional use of this plant to treat digestive problems, especially those with spasms.     

Nano-Structured Lipid Carrier-Based Oral Glutathione Formulation Mediates Renoprotection against Cyclophosphamide-Induced Nephrotoxicity,and Improves Oral Bioavailability of Glutathione Confirmed through RP-HPLC Micellar Liquid Chromatography

The study aimed to develop a new glutathione (GSH) oral formulation to enhance the delivery of GSH and counter the nephrotoxicity of the anticancer drug, cyclophosphamide (CP). A nanostructured lipid carrier glutathione formulation (GSH-NLCs) composed of glutathione (500 mg), stearic and oleic acid (300 mg, each), and Tween^® 80 (2%, w/v) was prepared through the emulsification-solvent-evaporation technique, which exhibited a 452.4 ± 33.19 nm spheroidal-sized particulate material with narrow particle size distributions, −38.5 ± 1.4 mV zeta potential, and an entrapment efficiency of 79.8 ± 1.9%. The GSH formulation was orally delivered, and biologically tested to ameliorate the CP-induced renal toxicity in a rat model. Detailed renal morphology, before and after the GSH-NLCs administration, including the histopathological examinations, confirmed the ameliorating effects of the prepared glutathione formulation together with its safe oral delivery. CP-induced oxidative stress, superoxide dismutase depletion, elevation of malondialdehyde levels, depletion of Bcl-2 concentration levels, and upregulated NF-KB levels were observed and were controlled within the recommended and near normal/control levels. Additionally, the inflammatory mediator marker, IL-1β, serum levels were marginally normalized by delivery of the GHS-NLCs formulation. Oral administration of the pure glutathione did not exhibit any ameliorating effects on the renal tissues, which suggested that the pure glutathione is reactive and is chemically transformed during the oral delivery, which affected its pharmacological action at the renal site. The protective effects of the GSH-NLCs formulation through its antioxidant and anti-inflammatory effects suggested its prominent role in containing CP-induced renal toxicity and renal tissue damage, together with the possibility of administrating higher doses of the anticancer drug, cyclophosphamide, to achieve higher and effective anticancer action in combination with the GSH-NLCs formulation.     

Simultaneous Determination of Caffeine and Paracetamol in Commercial Formulations Using Greener Normal-Phase and Reversed-Phase HPTLC Methods: A Contrast of Validation Parameters

There has been no assessment of the greenness of the described analytical techniques for the simultaneous determination (SMD) of caffeine and paracetamol. As a result, in comparison to the greener normal-phase high-performance thin-layer chromatography (HPTLC) technique, this research was conducted to develop a rapid, sensitive, and greener reversed-phase HPTLC approach for the SMD of caffeine and paracetamol in commercial formulations. The greenness of both techniques was calculated using the AGREE method. For the SMD of caffeine and paracetamol, the greener normal-phase and reversed-phase HPTLC methods were linear in the 50–500 ng/band and 25–800 ng/band ranges, respectively. For the SMD of caffeine and paracetamol, the greener reversed-phase HPTLC approach was more sensitive, accurate, precise, and robust than the greener normal-phase HPTLC technique. For the SMD of caffeine paracetamol in commercial PANEXT and SAFEXT tablets, the greener reversed-phase HPTLC technique was superior to the greener normal-phase HPTLC approach. The AGREE scores for the greener normal-phase and reversed-phase HPTLC approaches were estimated as 0.81 and 0.83, respectively, indicated excellent greenness profiles for both analytical approaches. The greener reversed-phase HPTLC approach is judged superior to the greener normal-phase HPTLC approach based on numerous validation parameters and pharmaceutical assays.     

Chemical Profile of Lipophilic Fractions of Different Parts of Zizyphus lotus L. by GC-MS and Evaluation of Their Antiproliferative and Antibacterial Activities

Zizyphus lotus L. is a perennial shrub particularly used in Algerian folk medicine, but little is known concerning the lipophilic compounds in the most frequently used parts, namely, root bark, pulp, leaves and seeds, which are associated with health benefits. In this vein, the lipophilic fractions of these morphological parts of Z. lotus from Morocco were studied by gas chromatography–mass spectrometry (GC–MS), and their antiproliferative and antimicrobial activities were evaluated. GC–MS analysis allowed the identification and quantification of 99 lipophilic compounds, including fatty acids, long-chain aliphatic alcohols, pentacyclic triterpenic compounds, sterols, monoglycerides, aromatic compounds and other minor components. Lipophilic extracts of pulp, leaves and seeds were revealed to be mainly composed of fatty acids, representing 54.3–88.6% of the total compounds detected. The leaves and seeds were particularly rich in unsaturated fatty acids, namely, (9Z,12Z)-octadeca-9,12-dienoic acid (2431 mg kg⁻¹ of dry weight) and (9Z)-octadec-9-enoic acid (6255 mg kg⁻¹ of dry weight). In contrast, root bark contained a high content of pentacyclic triterpenic compounds, particularly betulinic acid, accounting for 9838 mg kg⁻¹ of dry weight. Root bark extract showed promising antiproliferative activity against a triple-negative breast cancer cell line, MDA-MB-231, with a half-maximal inhibitory concentration (IC₅₀) = 4.23 ± 0.18 µg mL⁻¹ of extract. Leaf extract displayed interesting antimicrobial activity against Escherichia coli, methicillin-sensitive Staphylococcus aureus and Staphylococcus epidermis, presenting minimum inhibitory concentration (MIC) values from 1024 to 2048 µg mL⁻¹ of extract. Our results demonstrate that Zizyphus lotus L. is a source of promising bioactive components, which can be exploited as natural ingredients in pharmaceutical formulations.