Carbamazepine induces a bioenergetics disruption to microvascular endothelial cells from the blood-brain barrier

Carbamazepine (CBZ) is a widely employed anti-seizure medication that crosses the blood-brain barrier (BBB) to exert its anti-convulsant action. The effects of CBZ on components of the BBB have yet to be completely delineated. Hence the current study evaluated the effects of CBZ upon mitochondrial functionality of BBB-derived microvascular endothelial cells isolated from Albino rats. The influence of CBZ on cell viability and barrier functions were evaluated by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), lactate dehydrogenase, and electrophysiological assays over a drug concentration range of 0.1-1000 µM. Bioenergetics effects were measured via ATP production, mitochondrial complexes I an

Green synthesis and photocatalytic dye degradation activity of CuO Nanoparticles

This project was supported by Researchers Supporting Project Number (RSP-2023R7) King Saud University, Riyadh, Saudi Arabia. S.A.C.C. acknowledges support from FCT/MCTES (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through projects UIDB/50006/2020 and UIDP/50006/2020 and for the Scientific Employment Stimulus—Institutional Call (CEECINST/00102/2018). The authors thank The Islamia University of Bahawalpur for providing basic facilities.The degradation of dyes is a difficult task due to their persistent and stable nature; therefore, developing materials with desirable properties to degrade dyes is an important area of research. In the present study, we propose a simple, one-pot mechanochemical approach to synthesize CuO nanoparticles (NPs) using the leaf extract of Seriphidium oliverianum, as a reducing and stabilizing agent. The CuO NPs were characterized via X-ray diffraction (XRD), scanning electron microscopy (SEM), photoluminescence (PL) and Fourier-transform infrared spectroscopy (FTIR). The photocatalytic activity of CuO NPs was monitored using ultraviolet-visible (UV-Vis) spectroscopy. The CuO NPs exhibited high potential for the degradation of water-soluble industrial dyes. The degradation rates for methyl green (MG) and methyl orange (MO) were 65.231% ± 0.242 and 65.078% ± 0.392, respectively. Bio-mechanochemically synthesized CuO NPs proved to be good candidates for efficiently removing dyes from waterpublishersversionpublishe

Ibuprofen-loaded chitosan–lipid nanoconjugate hydrogel with gum arabic: Green synthesis, characterisation, in vitro kinetics mechanistic release study and PGE2 production test

Ibuprofen is a well-known non-steroidal anti-inflammatory (NSAID) medicine that is often used to treat inflammation in general. When given orally, it produces gastrointestinal issues which lead to lower patient compliance. Ibuprofen transdermal administration improves both patient compliance and the efficacy of the drug. Nanoconjugation hydrogels were proposed as a controlled transdermal delivery tool for ibuprofen. Six formulations were prepared using different compositions including chitosan, lipids, gum arabic, and polyvinyl alcohol, through ionic interaction, maturation, and freeze–thaw methods. The formulations were characterised by size, drug conjugation efficiency, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Further analysis of optimised hydrogels was performed, including X-ray diffraction (XRD), rheology, gel fraction and swelling ability, in vitro drug release, and in vitro macrophage prostaglandin E2 (PGE2 ) production testing. The effects of ibuprofen’s electrostatic interaction with a lipid or polymer on the physicochemical and dissolution characterisation of ibuprofen hydrogels were evaluated. The results showed that the S3 (with lipid conjugation) hydrogel provided higher conjugation efficiency and prolonged drug release compared with the S6 hydrogel

A Multifunctional Approach for Methyl Violet Photocatalytic Degradation and the Assessment of Antibacterial, Antioxidant, and Cytotoxicity Properties

Funding Information: M.B.T acknowledges support from HEC (Higher Education Commission) of Pakistan. S.A.C.C. acknowledges support from FCT/MCTES (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through projects UIDB/50006/2020 and UIDP/50006/2020 and for the Scientific Employment Stimulus—Institutional Call (CEECINST/00102/2018). Publisher Copyright: © 2023 by the authors.In this study, bimetallic nanoparticles (NPs) of silver (Ag) and zinc oxide (ZnO) were synthesized using Leptadenia pyrotechnica leaf extract for the first time. Monometallic NPs were also obtained for comparison. The characterization of the prepared NPs was carried out using various techniques, including UV-Visible spectroscopy (UV-Vis), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The latter confirmed the crystalline nature and diameter of the monometallic and bimetallic NPs of Ag and ZnO. The SEM images of the prepared NPs revealed their different shapes. The biological activities of the NPs were evaluated concerning their antibacterial, antioxidant, and cytotoxic properties. The antibacterial activities were measured using the time-killing method. The results demonstrated that both the monometallic and bimetallic NPs inhibited the growth of Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. The antioxidant activities of the NPs were evaluated using the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay and their cytotoxicity was checked using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The results indicated that the controlled quantity of the monometallic and bimetallic NPs did not affect the viability of the cells. However, the decreased cell (L-929) viability suggested that the NPs could have anticancer properties. Furthermore, the photocatalytic degradation of methyl violet and 4-nitrophenol was investigated using the prepared Ag/ZnO NPs, examining the factors affecting the degradation process and conducting a kinetic and thermodynamic study. The prepared Ag/ZnO NPs demonstrated good photocatalytic degradation (88.9%) of the methyl violet (rate constant of 0.0183 min−1) in comparison to 4-nitrophenol (NPh), with a degradation rate of 81.37% and 0.0172 min−1, respectively. Overall, the bimetallic NPs showed superior antibacterial, antioxidant, cytotoxic, and photocatalytic properties compared to the monometallic NPs of Ag and ZnO.publishersversionpublishe

Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids

Little is known about the role of microRNAs (miRNAs) in rewiring the metabolism within tumours and adjacent non-tumour bearing normal tissue and their potential in cancer therapy. This study aimed to investigate the relationship between deregulated miRNAs and metabolic components in murine duodenal polyps and non-polyp-derived organoids (mPOs and mNPOs) from a double-mutant ApcMinFbxw7∆G mouse model of intestinal/colorectal cancer (CRC). We analysed the expression of 373 miRNAs and 12 deregulated metabolic genes in mPOs and mNPOs. Our findings revealed miR-135b might target Spock1. Upregulation of SPOCK1 correlated with advanced stages of CRCs. Knockdown of miR-135b decreased the expression level of SPOCK1, glucose consumption and lactic secretion in CRC patient-derived tumours organoids (CRC tPDOs). Increased SPOCK1 induced by miR-135b overexpression promoted the Warburg effect and consequently antitumour effect of 5-fluorouracil. Thus, combination with miR-135b antisense nucleotides may represent a novel strategy to sensitise CRC to the chemo-reagent based treatment

Genetic Variation in DEAD-Box Helicase 20 as a Putative Marker of Recurrence in Propensity-Matched Colon Cancer Patients

Variants of the DEAD-Box Helicase 20 (DDX20), one of the microRNAs (miRNAs) machinery genes, can modulate miRNA/target gene expressions and, hence, influence cancer susceptibility and prognosis. Here, we aimed to unravel the association of DDX20 rs197412 T/C variant with colon cancer risk and/or prognosis in paired samples of 122 colon cancer and non-cancer tissue specimens by TaqMan allelic discrimination analysis. Structural/functional bioinformatic analyses were carried out, followed by a meta-analysis. We found that the T allele was more frequent in cancer tissues compared to control tissues (60.2% vs. 35.7%, p p p p p p = 0.001) models. Kaplan–Meier survival curves showed the shift in the C > T allele to be associated with poor disease-free survival. After adjusting covariates using a multivariate cox regression model, patients harboring C > T somatic mutation were 3.5 times more likely to develop a recurrence (p DDX20 rs197412 variant is associated with increased colon cancer risk and a higher likelihood of recurrence in the study population

Green-synthesized nanoparticles of the polyherbal extract attenuate the necrosis of pancreatic β-cell in a streptozotocin-induced diabetic model

Plant-based nanoformulation is one of the novel approaches for therapeutic benefits. This research synthesized a silver nanoparticle from the polyherbal combination of four plants/seeds (Momordica charantia, Trigonella foenum-graecum, Nigella sativa, and Ocimum sanctum) and investigated its antidiabetic effects in streptozotocin-induced Wistar albino rat model. The polyherbal extract (PH) was extracted by the Soxhlet-solvent extraction method and the resulting crude extract was undergone for silver nanoparticle synthesis. The PH extract was subjected to a four-week intervention in fructose-fed streptozotocin-induced Wistar Albino rats’ models and in vitro antioxidative tests. Experimental animals (age: 6–7 weeks, male, body weight: 200–220 g), were divided into five groups including normal control (NC), reference control (RC), diabetic control (DC), and treatment groups PH200, PH100, and PHAgNP20. After three weeks of intervention, body weight, weekly blood glucose level, oral glucose tolerance test, AST, ALT, alkaline phosphatase, total cholesterol, triglycerides, uric acid, urea, and creatinine level of PH200 were found to be significantly (P < 0.05) improved compared to the diabetic control. The same dose demonstrated better regeneration of damaged pancreatic and kidney tissues. In vitro antioxidant assay manifested promising IC50 values of 86.17 μg/mL for DPPH, 711.04 μg/mL for superoxide free radical, and 0.48 mg/mL for Iron chelating activity of the polyherbal extract. GC-MS analysis impacted the major volatile compounds of the PH. The data demonstrate that the PH and its nanoparticles could be a novel source of antidiabetic therapeutics through an advanced dose-response study in the type 2 diabetic model

Supplements of an aqueous combination of Justicia adhatoda and Ocimum tenuiflorum boost antioxidative effects and impede hyperlipidemia

Background: Justicia adhatoda and Ocimum tenuiflorum, locally known as bashok and tulsi, are two ethnomedicinally important herbs that have been using as dietary supplements for several therapeutic applications. This study evaluated the combined effect of both the herbs as an antioxidative and antihyperlipidemic agent. Methods: Antihyperlipidemic effect was assessed in a high-fat diet-induced hyperlipidemic model in Wistar albino rats. The rats were treated orally with extracts of bashok (J adhatoda, 200 mg/kg bw), tulshi (O tenuiflorum, 200 mg/kg bw), and a combination of bashok and tulshi (50:50), as well as with a reference drug, atorvastatin (10 mg/kg/day), with or without high-fat diet for 14 days. The antioxidative effect was studied using established in vitro models. The studies were supported by experimentally testing the effects of the extracts on membrane stabilization and inhibition of protein denaturation. Results: The results showed that the serum lipid profile was significantly decreased in the different treatment groups, with bashok having the greatest effect. Body weights, total serum protein, LDH, and relative liver and adipose tissue weights were markedly restored towards baseline values, the lowest atherogenic index being achieved with the combined extract. The combination treatment significantly enhanced total phenolic content and antioxidative capacity and greatly potentiated membrane stabilization, but inhibition of protein denaturation was not significantly affected. Conclusion: The data demonstrate that a combination of Justicia adhatoda and Ocimum tenuiflorum could be developed as a food supplement with antioxidative and antihyperlipidemic benefits

Exploring novel fluorine-rich fuberidazole derivatives as hypoxic cancer inhibitors: Design, synthesis, pharmacokinetics, molecular docking, and DFT evaluations.

Sixteen fuberidazole derivatives as potential new anticancer bioreductive prodrugs were prepared and characterized. The in vitro anticancer potential was examined to explore their cytotoxic properties by employing apoptosis, DNA damage, and proliferation tests on chosen hypoxic cancer cells. Eight substances (Compound 5a, 5c, 5d, 5e, 5g, 5h, 5i, and 5m) showed promising cytotoxicity values compared to the standard control. The potential of compounds was also examined through in silico studies (against human serum albumin), including chem-informatics, to understand the structure-activity relationship (SAR), pharmacochemical strength, and the mode of interactions responsible for their action. The DFT calculations revealed that only the 5b compound showed the lowest ΔET (2.29 eV) while 5i showed relatively highest βtot (69.89 x 10-31 esu), highest αave (3.18 x 10-23 esu), and dipole moment (6.49 Debye). This study presents a novel class of fuberidazole derivatives with selectivity toward hypoxic cancer cells