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Lung ischemia-reperfusion injury (LIRI) causes oxidative stress, inflammation, and immune system activation. The Nrf2/Keap1/HO-1 pathway is important in cellular defense against these effects. Quercetin, a flavonoid with antioxidant, anti-inflammatory, and anti-cancer properties, has been investigated. Our aim in this study was to investigate the effect of quercetin on preventing lung ischemia-reperfusion injury and the role of the Nrf2/Keap1/HO-1 pathway. Sixty-four male Wistar rats were divided into four distinct groups(n = 16). Sham, lung ischemia-reperfusion (LIR), Saline + LIR, Quercetin + LIR (30 mg/kg i.p for a week before LIR). LIR groups were subjected to 60 min of ischemia (left pulmonary artery, vein, and bronchus) and 120 min of reperfusion. Our assessment encompassed a comprehensive analysis of various factors, including the evaluation of expression Nrf2, Keap1, and Heme Oxygenase-1 (HO-1) levels and NF-κB protein. Furthermore, we examined markers related to inflammation (interleukin-1β and tumor necrosis factor alpha), oxidative stress (malondialdehyde, total oxidant status, superoxide dismutase, glutathione peroxidase, total antioxidant capacity), lung edema (Wet/dry lung weight ratio and total protein concentration), apoptosis (Bax and Bcl2 protein), and histopathological alterations (intra-alveolar edema, alveolar hemorrhage, and neutrophil infiltration). Our results show that ischemia-reperfusion results in heightened inflammation, oxidative stress, apoptosis, lung edema, and histopathological damage. Quercetin showed preventive effects by reducing these markers, acting through modulation of the Nrf2/Keap1 pathway and inhibiting the NF-κB pathway. This anti-inflammatory effect, complementary to the antioxidant effects of quercetin, provides a multifaceted approach to cell protection that is important for developing therapeutic strategies against ischemia-reperfusion injury and could be helpful in preventive strategies against ischemia-reperfusion. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) play various roles in gene regulation. GATA3 antisense RNA 1 (GATA3-AS1) is an lncRNA gene neighboring GATA binding protein 3 (GATA3). The current study aims to quantitatively compare the levels of the expression of GATA3-AS1, GATA3, and Interleukin-4 (IL-4) in peripheral blood mononuclear cells (PBMC) samples of MS patients and healthy individuals under the hypothesis of regulation of GATA3 and IL-4 expression orchestrated by GATA3-AS1. Methods and results: In this case-control study, the GATA3-AS1, GATA3 and IL-4 expression profiles were assessed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Also, we assessed the IL-4 levels in the serum. The median fold changes in MS patients vs. controls were (4.39 ± 0.38 vs. 2.44 ± 0.20) for GATA3-AS1, (5.22 ± 0.51 vs. 2.86 ± 0.30) for GATA3, and (6.16 ± 0.52 vs. 3.57 ± 0.38) for IL-4, (P < 0.001). Furthermore, the mean serum levels of IL-4 were 30.85 ± 1.53 pg/ml in MS patients and 11.15 ± 4.23 pg/ml in healthy controls (P < 0.001). ROC curve analysis showed that the level of GATA3-AS1 might serve as a biomarker for diagnosing MS patients with the area under the curve (AUC = 0.918, P < 0.0001). Based on our results, this GATA3-AS1/GATA3/IL-4 pathway may increase IL-4 expression in MS patients. Conclusions: Our results indicate a probably regulatory function for GATA3-AS1and the levels of GATA3-AS1 in blood could be important biomarkers for MS diagnosis. To confirm and be more certain of these results, it is necessary to study neuromyelitis optica (NMO) and asthma patients in future studies. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common and deadly cancers worldwide. Different factors, such as environmental and genetic factors and lifestyle, affect it. Owing to the presence of phenolic, alkaloid, antioxidant, and terpenoid compounds, herbal compounds can be effective in the treatment of various cancers. Thymol is a natural monoterpene phenol that is abundant in some plants and exerts several biological effects. The aim of this study was to investigate the apoptotic, anti-proliferative effect and EGFR gene expression under the influence of thymol-loaded nanoliposome in SW84 and SW111 cell lines derived from colorectal cancer. Materials and methods: The lipid thin-film hydration method was used to synthesize thymol-loaded liposomes, and their characterization was performed using TEM, DLS, and HPLC analyses. SW84 and SW1111 cells were treated with thymol- and thymol-loaded liposomes at different doses, the inhibition of cell proliferation was evaluated using an MTT assay, the rate of apoptosis induction was assessed using flow cytometry, and EGFR gene expression was measured using real-time PCR. Results: The nanoparticles produced were spherical, uniform, and 200 ± 10 nm in size. HPLC analysis showed that approximately 98% thymol was loaded into the nanoliposome. The results of the MTT assay showed that thymol and thymol-nanoliposomes decreased the proliferation of SW84 and SW1111 cells in a concentration-dependent manner. The IC50 of thymol and thymol-nanoliposomes were 18 and 14.2 µg/ml for the SW48 cell line (P = 0.04) and 10.5 and 6.4 µg/ml for the SW1116 cell line (P = 0.001). Thymol-nanoliposomes significantly inhibited the proliferation of cancer cells compared to free thymol. Flow cytometry showed an increase in the percentage of apoptotic cells, especially in the thymol-nanoliposome group in the treated cells. Real-time PCR results also showed that thymol and thymol-nanoliposome both caused a decrease in the expression of EGFR genes in both cell lines, but this effect of decreasing gene expression was significantly higher in the thymol-nanoliposome group. Conclusions: Our results showed that thymol-nanoliposomes reduced proliferation, increased apoptosis, and decreased EGFR expression in colorectal cancer-derived cell lines. [ABSTRACT FROM AUTHOR]

B lymphocytes play a vital role in the human defense against viral infections by producing specific antibodies. They are also critical for the prevention of infectious diseases by vaccination, and their activation influences the efficacy of the vaccination. Since the beginning of coronavirus disease 2019 (COVID-19), which became the main concern of the world health system, many efforts have been made to treat and prevent the disease. However, for the development of successful therapeutics and vaccines, it is necessary to understand the interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, and the immune system. The innate immune system provides primary and nonspecific defense against the virus, but within several days after infection, a virus-specific immune response is provided first by antibody-producing B cells, which are converted after the resolution of disease to memory B cells, which provide long-term immunity. Although a failure in B cell activation or B cell dysfunction can cause a severe form of the disease and also lead to vaccination inefficiency, some individuals with B cell immunodeficiency have shown less production of the cytokine IL-6, resulting in a better disease outcome. In this review, we present the latest findings on the interaction between SARS-CoV-2 and B lymphocytes during COVID-19 infection. [ABSTRACT FROM AUTHOR]

Quasi-classical trajectory calculations and stochastic one-dimensional chemical master equation simulation methods are used to study the dynamics of the reaction of amidogen radical [NH(B)] with hydroperoxyl radical [HO(A″)] on the lowest singlet electronic state. The title complex reaction takes place on a multi-well multichannel potential energy surface consisting of three deep potential wells and one van der Waals complex. In quasi-classical trajectory calculations a new analytical potential energy surface based on CCSD(T)/aug-cc-pVTZ//MPW1K/6-31+G(d,p) ab initio method was driven and used to study the dynamics of the title reaction. In quasi-classical trajectory calculations, the reactive cross sections and reaction probabilities are determined for 200-2000 K relative translational energies to calculate the rate constants. The same ab initio method was used to have the necessary data for solving the one-dimensional chemical master equation to calculate the rate constants of different channels. In solving the master equation, the Lennard-Jones potential model was used to form the collision between the collider gases. The fractional populations of different intermediates and products in the early stages of the reaction were examined to determine the role of the energized intermediates and the van der Waals complex on the dynamics of the title reaction. Although the calculated total rate constants from both methods are in good agreement with the reported experimental values in the literature, the quasi-classical trajectory simulation predicts the formation of NHO + OH as the major channel in the title reaction in accordance with the previous studies (Sumathi and Peyerimhoff, Chem. Phys. Lett., 263:742-748, 1996), while the stochastic master equation simulation predicts the formation of HNO + HO as the major products. [ABSTRACT FROM AUTHOR]

In this study, we used molecular docking and molecular dynamics (MD) simulation studies to analyze the interactions of a series of naphthalene and non-naphthalene derivatives ( n = 38) as potent inhibitors of cytochrome P450 2A6 (CYP2A6) and to construct a structure-based quantitative structure activity relationship (QSAR) model. A 6000 ps MD simulation in a cubic water box were employed to build 3D structure of the CYP2A6 in a water environment. After reaching the equilibrium, the most potent inhibitor (2-bromonaphthalene) was docked into the CYP2A6 to realize the binding site of the enzyme. The docking analysis showed that π- π interaction of the inhibitors with four phenylalanine residues at positions of 107, 111, 118, and 480 plays an important role in the activities of the inhibitors. Then, an additional 6000 ps MD simulation was performed on the complex of the CYP2A6-2-bromonaphthalene to explore the effect of the inhibitor on the stability of the protein-inhibitor complex. Radius of gyration values for CYP2A6 and CYP2A6-2-bromonaphthalene complex were 2.23 ± 0.01 and 2.21 ± 0.01 nm, respectively, which revealed that the structure of the CYP2A6 in the presence of 2-bromonaphthalene has not changed. Finally, all the inhibitors docked into the enzyme and the docked configuration of the inhibitors with the lowest free energy was used to calculate the most feasible descriptors. The selected descriptors were related to the inhibitory activities using multiple linear regression (MLR) and least squares support vector regression (LS-SVR) models. The Q values for MLR and LS-SVR were 0.695 and 0.728, respectively. [ABSTRACT FROM AUTHOR]

Human serum albumin (HSA) primarily functions as a transport carrier for a vast variety of natural ligands and pharmaceutical drugs. In the present study, three structurally related cationic Pt(II) complexes ([Pt(ppy)(dppe)]CFCO: 1, Pt(bhq)(dppe)]CFCO: 2, and [Pt(bhq)(dppf)]CFCO: 3) were used to evaluate their interaction with HSA under different experimental setups, using UV-Vis absorption spectroscopy, fluorescence and circular dichroism techniques. The spectroscopic results suggest that upon binding to HSA, the Pt(II) complexes could effectively induce structural alteration of the protein. The complexes can bind to HSA with the binding affinities of the following order: 3 > 2 > 1. Also, thermodynamic parameters of binding between these complexes and HSA indicated the existence of entropy-driven spontaneous interaction which primarily dominated with the hydrophobic forces. Also, docking simulation study revealed the binding details of these complexes on HSA. Complex 3 with highest binding affinity for HSA indicates lowest denaturing effect on this protein. The low denaturation properties of 3 appear important in the terms of lower susceptibility of this platinum complex for possible development of deleterious side effects. [ABSTRACT FROM AUTHOR]