Human Lung Carcinoma Research Articles

Madecassic acid analogues with a five-membered A-ring and their cytotoxic activity

The structural modification of madecassic acid focused on the contraction of the six-membered A-ring to a five-membered ring, combined with the dehydration of 6-OH to form a new double bond and formation of the esterification or amidation at C-28. The synthesised structures were identified based on the analysis of their NMR and EIS-MS data. Eighteen new madecassic acid analogues were tested in vitro for their cytotoxicity against three cancer cell lines, including human mouth carcinoma (KB), human hepatocellular carcinoma (HepG2), and human lung carcinoma (A549) using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Among them, compounds 5 and 12 exhibited potent and selective cytotoxic activity in KB and HepG2 cell lines, with IC50 values ranging from 3.57 to 6.32 µM. The results also indicated that analogues with a 5-membered A-ring containing an α,β-unsaturated aldehyde esterified at C-23 showed a decrease in their cytotoxic activity compared to precursors in the tested cancer cells.

Design, Synthesis, and Biological Evaluation of Some Novel Retinoid Derivatives

Background: As cancer stands as a significant global health concern, many heterocyclic compounds that are more effective in cancer cells than healthy cells are being investigated for their selective anticancer potentials. One such compound is fenretinide, a synthetic derivative of retinoic acid that has a broad spectrum of cytotoxic activity against primary tumor cells, cell lines, and/or xenografts of various cancers. In this context, bexarotene and its derivatives, synthesized from hybridization of the fenretinide, are expected to possess a potential anticancer activity. Objective: The objective of the present study was to investigate the synthesis of novel amid-derived and bexarotene-based compounds, as well as to assess their cytotoxic effects in different cancer cell lines. Methods: This study involved the synthesis of twelve novel retinoid derivatives (6-17) in a six-step process. The cytotoxic activities of these compounds were assessed against various cancer cell lines, such as A549 (human lung carcinoma), HeLa (human cervical cancer), MCF7 (human breast adenocarcinoma), and WiDr (human colon adenocarcinoma). The chemical structures of these compounds were elucidated through their elemental analysis, mass spectrometry (ESI+, ESI-), as well as 1H-NMR and 13C-NMR spectroscopic data. Results: The obtained cell toxicity results indicated that compounds 6, 8, 11, 12, 13, 14, and 17 were found to exhibit the strongest cytotoxic activity in above mentioned cancer cell lines. The IC50 values for active compounds, 11 and 12, were determined as 2.38μM and 2.29μM, respectively. Remarkably, these compounds displayed higher cytotoxic activity in the WiDr cell line related to positive control, camptothecin (CPT). Moreover, compounds 14 and 17 demonstrated very similar level of cytotoxic activity to CPT, indicating their potential for antitumoral applications upon further studies. Conclusion: While compounds 11, 12, 14, and 17 indicated a very comparable anticancer activity to CPT, compounds 6, 8, 11 and 12 showed more selective anticancer effect against cancer cells than noncancerous cells. In accordance with the findings of the present study, they can be evaluated as primary candidates for further studies, specifically as RXRα-targeted anticancer agents.

Homology modelling, molecular docking studies and synthesis of aminopyrimidines as inhibitors for deoxynucleoside kinase analogues in cancer chemoprevention

The development of alternative anticancer agents with minimal side effects has become more critical due to the rising recurrence of mammalian malignancies and the severe side effects of chemotherapeutic treatments. Kinases are an essential target for neostatic impact as they play an important role in the modulation of growth factor signalling. Our work aims to screen novel nine-series of thiazole-based aminopyrimidines and sulphaminopyrimidines against the enzymes mitochondrial thymidine kinase 2, deoxyguanosine kinase (2OCP), deoxycytidine kinase (2QRN) and thymidylate kinase (1E2Q) by molecular docking, synthesise and to study their in vitro inhibitory studies. The synthesised compounds were characterised by Infrared, Nuclear magnetic resonance and Mass spectroscopy. In silico studies, compound 4c stands out among the series, with a reported docking score ranging from −6 to −8 Kcal/mol against all the analogue kinases. The in vitro cytotoxicity assay against human small-cell lung carcinoma (A-549) has shown that 5c (IC50 = 53.9 µM) has an excellent cytotoxic effect over 4c (IC50= 68.68 µM). The reason might be the presence of the benzene sulphonamide group, which enhances their anticancer action. To conclude, the compounds 4c and 5c were found to be potent inhibitors of the deoxynucleoside kinases. In vivo studies must further verify these to prove their potent neostatic effect.

Effect of N-substituted aliphatic glycine presence on bioactivity, cytotoxicity, and selectivity of Pt(II) and Pd(II) complexes in cancer treatment

In this study, four new platinum (II) and palladium(II) complexes were synthesized to develop metallo-drugs that can attach to DNA and prevent the division of cancer cells. The complexes, 1: [Pt(bipy)(LP)]NO3, 2: [Pt(bipy)(LA)]NO3, 3: [Pd(bipy)(LP)]NO3, and 4: [Pd(phen)(LP)]NO3 (where LP is propylglycine, LA is 2-heptyl glycine, bipy is 2,2-bipyridine, and phen is 1,10-phenanthroline), were structurally characterized using computational and experimental analysis. Their stability, solubility, and lipophilicity were evaluated. Single-crystal X-ray and powder X-ray crystallographic analyses were performed for [Pt(bipy)(LA)]NO3. Density functional theory calculations were performed to investigate the reactivity, stability descriptors, and natural bond orbital analysis of these complexes. The in vitro cytotoxicity of these substances was examined against the human colorectal carcinoma (HCT116), A549 (Human Caucasian lung carcinoma), MCF7 (breast cancer), and HFF (Human Freskin Fibroblast) cell lines. According to the findings, complexes 4 and 3 had near oxaliplatin concentrations and more than carboplatin due to lipophilic ligands in their structure. Also, regarding IC50 values on normal HFF cell line, 4 is selectively toxic against the A549 cancer cell line with SI=5.6. Fluorescence, electronic absorption spectroscopy, and CD spectroscopy were used to investigate the binding affinities of compounds to CT-DNA and HSA. The results revealed that they could interact with CT-DNA through groove mode and with HSA via hydrogen bond and van der Waals forces. Electronic absorption and CD spectra indicated that compounds changed the way the HSA folded by increasing the proportion of a-helix. The binding posture of the metal complex to both biomolecules was predicted using docking simulation, which also verified the groove binding for DNA-complex. The findings indicated that complex 4 had a greater negative docking energy and a higher propensity for CT-DNA and HSA interaction.

Enhanced Photodynamic Therapy Efficacy through Solid Lipid Nanoparticle of Purpurin-18-N-Propylimide Methyl Ester for Cancer Treatment.

Photodynamic therapy (PDT) is an innovative cancer treatment that utilizes light. When light irradiates, purpurin-18-N-propylimide methyl ester (P18 N PI ME) generates reactive oxygen species that destroy cancer cells. The hydrophobic nature of P18 N PI ME presents challenges regarding its aggregation in the body, which can affect its effectiveness. This study aimed to enhance the bioavailability and effectiveness of cancer treatment by synthesizing P18 N PI ME and formulating P18 N PI ME-loaded solid lipid nanoparticles (SLNs). The efficacy of PDT was estimated using the 1,3-diphenylisobenzofuran (DPBF) assay and photocytotoxicity tests on the HeLa (human cervical carcinoma) and A549 (human lung carcinoma) cell lines. The P18 N PI ME-loaded SLNs demonstrated particle sizes in the range of 158.59 nm to 248.43 nm and zeta potentials in the range of -15.97 mV to -28.73 mV. These SLNs exhibited sustained release of P18 N PI ME. DPBF analysis revealed enhanced PDT effects with SLNs containing P18 N PI ME compared with standalone P18 N PI MEs. Photocytotoxicity assays indicated toxicity under light irradiation but no toxicity in the dark. Furthermore, the smallest-sized formulation exhibited the most effective photodynamic activity. These findings indicate the potential of P18 N PI ME-loaded SLNs as promising strategies for PDT in cancer therapy.

Concanavalin: A Loaded Chitosan Nanoparticles Synthesis and Characterization to Inhibit the Proliferation of Lung Cancer

Background Non-small-cell lung cancer is the most ubiquitous malignancy, and the present treatments do not offer the most effective outcomes for therapy. Natural drug therapy, which directly targets tumor cells, is now recognized as a safe technique for cancer treatment. The use of tailored nanoparticles also improves the efficacy of cancer therapy. Purpose To synthesize, characterize, and evaluate the natural drug concanavalin A (ConA) coated with chitosan nanoparticles (ConA-CS NPs) for cytotoxicity against lung cancer cell line (NCI-H358). Methods The current study demonstrates the development of ConA-CS NPs as well as their unique characteristics, anticancer processes, and possible applications in treatment. Using UV–Vis, Fourier transform infrared, X-ray diffraction, field emission scanning electron microscopy, and dynamic light scattering studies, ConA-CS NPs were generated and evaluated. The mitochondrial toxicity test assay was used to examine ConA-CS NP-induced cytotoxicity. Dual (acridine orange/ethidium bromide) staining was performed to examine apoptotic modifications, and mitochondrial membrane potential levels in NCI-H358 cells were examined using the appropriate fluorescence staining assays. Results and Conclusion The use of ConA-CS NPs for enhanced tumor treatment, which combines natural drugs to eradicate the tumor and prevent relapses, is supported by in vitro investigations. The ability of ConA-encapsulated CS NPs to impede human lung carcinoma cell growth has not yet been investigated. Therefore, this investigation may provide a new paradigm for cancer detection and therapy, and the results may surely help to enhance the quality of life for cancer patients.

Real time monitoring of heavy metal adulteration in biodiesel using Arduino UNO platform@A promising multi-purpose stimuli-responsive azomethine based chemoreceptor for hierarchical tri-ionic sensing

The presence of metallic adulteration even in very trace level may lead to deleterious impact on the biodiesel quality and ultimately may be responsible for the dropping down of system efficiency, which necessitates the trace level recognition of heavy metal adulteration from biodiesel. In this context, herein using an azomethine functionalized chromogenic chemoreceptor, 1-((E)-(4-hydroxyphenylimino) methyl) napthalen-2-ol (HMN) has been reported for the selective chemodosimetric recognition of Cu2+ with a lower detection threshold of 7.8 ppb via distinct chromogenic variation of HMN. In addition to this, it has also exhibited selective and reversible naked eye chromogenic sensing behaviour towards F− (LOD=160 ppb) and Al3+ (LOD=48 ppb) at very trace level, which is quite lower than the WHO permissible limit. Distinct chromogenic recognition of F− by HMN proceeds via strong intermolecular hydrogen bonding mediated improved intramolecular charge transfer. The spectroscopic response of HMN in alternate presence and absence of the targeted analytes made it suitable to formulate AND-NOT-XNOR-NAND-OR gate based ‘Castle-like’ complicated logic circuitry. In-vitro cell imaging study using A549, human lung carcinoma cell line attests intracellular recognition capability of HMN, demonstrating its effectual bio-medicinal applications. Interestingly, inspired by the capability of HMN towards recognition of copper from biodiesel specimen, an RGB-assisted device comprised of TCS color sensor and an Arduino UNO 8-bit microcontroller has been developed for real-time quantitative analysis of the biodiesel adulteration. Going one step further, utilization of lab-on-a-box based prototype to monitor the concentration-dependent chromogenic fluctuation via RGB analysis is undoubtedly beneficial for the determination of copper adulteration in biodiesel sample. The presently developed chemoreceptor can thus be regarded as a valuable addition in the field of supramolecular chemistry as well as a significant initiative towards regular monitoring of the biodiesel quality control parameters as a part of sustainable environment.

From 2D to 3D In Vitro World: Sonodynamically-Induced Prooxidant Proapoptotic Effects of C60-Berberine Nanocomplex on Cancer Cells.

The primary objective of this research targeted the biochemical effects of SDT on human cervix carcinoma (HeLa) and mouse Lewis lung carcinoma (LLC) cells grown in 2D monolayer and 3D spheroid cell culture. HeLa and LLC monolayers and spheroids were treated with a 20 µM C60-Ber for 24 h, followed by irradiation with 1 MHz, 1 W/cm2 US. To evaluate the efficacy of the proposed treatment on cancer cells, assessments of cell viability, caspase 3/7 activity, ATP levels, and ROS levels were conducted. Our results revealed that US irradiation alone had negligible effects on LLC and HeLa cancer cells. However, both monolayers and spheroids irradiated with US in the presence of the C60-Ber exhibited a significant decrease in viability (32% and 37%) and ATP levels (42% and 64%), along with a notable increase in ROS levels (398% and 396%) and caspase 3/7 activity (437% and 246%), for HeLa monolayers and spheroids, respectively. Similar tendencies were observed with LLC cells. In addition, the anticancer effects of C60-Ber surpassed those of C60, Ber, or their mixture (C60 + Ber) in both cell lines. The detected intensified ROS generation and ATP level drop point to mitochondria dysfunction, while increased caspase 3/7 activity points on the apoptotic pathway induction. The combination of 1 W/cm2 US with C60-Ber showcased a promising platform for synergistic sonodynamic chemotherapy for cancer treatment.

Gossypol Inhibits Metastasis of Lung Cell Carcinoma by Reversing Epithelial to Mesenchymal Transition and Suppressing Proteases Activity.

Gossypol, a natural polyphenolic compound, possesses antivirus activity and induces cell death of different types of tumors. However, the efficacy of gossypol on lung carcinoma metastases and epithelial to mesenchymal transition remains unknown. The aim of the present work was to determine the cellular and molecular mechanism of the anti-cancer and anti-metastatic efficacies of gossypol on human lung carcinoma cells. Gossypol showed a marked suppression of the viability, motility, and invasion in H1299 and A549 cells. Zymography assay showed that gossypol was sufficient to suppress the activities of urokinase-type plasminogen activator and matrix metalloproteinase-2. Gossypol reversed TGF-β-induced epithelial to mesenchymal transition. Gossypol reduced vimentin, p-FAK, p-Src and p-paxillin. In vivo studies of gossypol were performed using subcutaneous inoculation and tail vein injection of A549 into immunodeficient BALB/c nude mice and severe combined immunodeficient mice.

Stable Cyclometallated Palladium Complexes of Arylamides: Synthesis, Redox and Anticancer Activities

AbstractAir‐stable cyclometalated palladium(II) complexes with benzamide ligands were synthesized in high yields and characterized by X‐ray diffraction analysis, CVA, 1H NMR, 13C NMR spectroscopy, MALDI‐MS, and ESI‐MS. The electrochemical oxidation of the complexes is reversible in the presence of a quinoline substituent in the ligand and gives Pd (III) species that do not undergo reductive elimination and are detectable by ESR spectroscopy. The complexes showed high cytotoxicity against cervical cancer (M‐HeLa) and duodenal adenocarcinoma (HuTu 80), a human mammary ductal adenocarcinoma line (MCF‐7) and a human lung carcinoma cell line (A549). The possibility of generating reactive oxygen species in solution (such as OH−radicals), which can be responsible for the antitumor activity of the studied complexes, using the ESR method was shown.

Temporal and spatial resolution of magnetosome degradation at the subcellular level in a 3D lung carcinoma model

Magnetic nanoparticles offer many exciting possibilities in biomedicine, from cell imaging to cancer treatment. One of the currently researched nanoparticles are magnetosomes, magnetite nanoparticles of high chemical purity synthesized by magnetotactic bacteria. Despite their therapeutic potential, very little is known about their degradation in human cells, and even less so of their degradation within tumours. In an effort to explore the potential of magnetosomes for cancer treatment, we have explored their degradation process in a 3D human lung carcinoma model at the subcellular level and with nanometre scale resolution. We have used state of the art hard X-ray probes (nano-XANES and nano-XRF), which allow for identification of distinct iron phases in each region of the cell. Our results reveal the progression of magnetite oxidation to maghemite within magnetosomes, and the biosynthesis of magnetite and ferrihydrite by ferritin.Graphical

Comparative Analysis of Structural Analogs of Dipyridothiazines with m-Xylene and a Lutidine Moiety—In Silico, In Vitro, and Docking Studies

Dimers of dipyridothiazines with an m-xylene moiety are presented in terms of a comparative analysis with anticancer active structural analogs containing a lutidine system. The synthesis of new isomeric dimers was described, the structure of which was confirmed by 1H, 13C and 2D NMR, and HR MS spectroscopic methods. The preliminary prediction of the pharmacological profile using the Way2Drug server indicated the anticancer potential of the tested derivatives. In vitro biological activity tests were performed on a normal skin cell line (HaCaT) and five cancer cell lines, including human primary colon cancer (SW480), human metastatic colon cancer (SW620), human breast adenocarcinoma (MDA-MB-231), human lung carcinoma (A-549), and human glioblastoma (LN-229), which indicated low cytotoxic activity. In order to explain the surprisingly low activity, a comparative structural analysis of the tested analogs compared to the dimers with the lutidine system was performed using quantum mechanics and molecular docking in relation to histone deacetylase. Molecular docking indicated the different binding sites of the analyzed dimers, which explained the differences in the activity.

Inducing Immunogenic Cancer Cell Death through Oxygen‐Economized Photodynamic Therapy with Nitric Oxide‐Releasing Photosensitizers

AbstractPhotodynamic therapy (PDT) utilizes reactive oxygen species (ROS) for eradication of cancer cells. Its effectiveness is governed by the oxygen content, which is scarce in the hypoxic tumor microenvironment. We report herein two zinc(II) phthalocyanines substituted with two or four nitric oxide (NO)‐releasing moieties, namely ZnPc‐2NO and ZnPc‐4NO, which can suppress the mitochondrial respiration, thereby sparing more intracellular oxygen for PDT. Using HT29 human colorectal adenocarcinoma cells and A549 human lung carcinoma cells, we have demonstrated that both conjugates release NO upon interaction with the intracellular glutathione, which can reduce the cellular oxygen consumption rate and adenosine triphosphate generation and alter the mitochondrial membrane potential. They can also relieve the hypoxic status of cancer cells and decrease the expression of hypoxia‐inducible factor protein HIF‐1α. Upon light irradiation, both conjugates can generate ROS and induce cytotoxicity even under a hypoxic condition, overcoming the oxygen‐dependent nature of PDT. Interestingly, the photodynamic action of ZnPc‐2NO elicits the release of damage‐associated molecular patterns, inducing the maturation of dendritic cells and triggering an antitumor immune response. The immunogenic cell death caused by this oxygen‐economized PDT has been demonstrated through a series of in vitro and in vivo experiments.

Inducing Immunogenic Cancer Cell Death through Oxygen-Economized Photodynamic Therapy with Nitric Oxide-Releasing Photosensitizers.

Photodynamic therapy (PDT) utilizes reactive oxygen species (ROS) for eradication of cancer cells. Its effectiveness is governed by the oxygen content, which is scarce in the hypoxic tumor microenvironment. We report herein two zinc(II) phthalocyanines substituted with two or four nitric oxide (NO)-releasing moieties, namely ZnPc-2NO and ZnPc-4NO, which can suppress the mitochondrial respiration, thereby sparing more intracellular oxygen for PDT. Using HT29 human colorectal adenocarcinoma cells and A549 human lung carcinoma cells, we have demonstrated that both conjugates release NO upon interaction with the intracellular glutathione, which can reduce the cellular oxygen consumption rate and adenosine triphosphate generation and alter the mitochondrial membrane potential. They can also relieve the hypoxic status of cancer cells and decrease the expression of hypoxia-inducible factor protein HIF-1α. Upon light irradiation, both conjugates can generate ROS and induce cytotoxicity even under a hypoxic condition, overcoming the oxygen-dependent nature of PDT. Interestingly, the photodynamic action of ZnPc-2NO elicits the release of damage-associated molecular patterns, inducing the maturation of dendritic cells and triggering an antitumor immune response. The immunogenic cell death caused by this oxygen-economized PDT has been demonstrated through a series of in vitro and in vivo experiments.

2D TiO2 Nanosheets Decorated Via Sphere-Like BiVO4: A Promising Non-Toxic Material for Liquid Phase Photocatalysis and Bacterial Eradication.

An in-depth investigation was conducted on a promising composite material (BiVO4/TiO2), focusing on its potential toxicity, photoinduced catalytic properties, as well as its antibiofilm and antimicrobial functionalities. The preparation process involved the synthesis of 2D TiO2 using the lyophilization method, which was subsequently functionalized with sphere-like BiVO4 through wet impregnation. Finally, we developed BiVO4/TiO2 S-scheme heterojunctions which can greatly promote the separation of electron-hole pairs to achieve high photocatalytic performance. The evaluation of concentration- and time-dependent viability inhibition was performed on human lung carcinoma epithelial A549 cells. This assessment included the estimation of glutathione levels and mitochondrial dehydrogenase activity. Significantly, the BiVO4/TiO2 composite demonstrated minimal toxicity towards A549 cells. Impressively, the BiVO4/TiO2 composite exhibited notable photocatalytic performance in the degradation of rhodamine B (k=0.135 min-1) and phenol (k=0.016 min-1). In terms of photoinduced antimicrobial performance, the composite effectively inactivated both gram-negative E. coli and gram-positive E. faecalis bacteria upon 60 minutes of UV-A light exposure, resulting in a significant log 6 (log 10 CFU/mL) reduction in bacterial count. In addition, a 49 % reduction of E. faecalis biofilm was observed. These promising results can be attributed to the unique 2D morphology of TiO2 modified by sphere-like BiVO4, leading to an increased generation of (intracellular) hydroxyl radicals, which plays a crucial role in the treatments of both organic pollutants and bacteria. This research has significant potential for various applications, particularly in addressing environmental contamination and microbial infections.

Polyallylamine antiviral activity against influenza and acute respiratory viral infection in various cell cultures

Acute respiratory viral infections, including influenza, comprise the most common group of seasonal viral infections. Influenza is the most common and dangerous viral infection. The only way to control it is influenza vaccination. Regarding infections caused by parainfluenza and respiratory syncytial virus, only symptomatic treatment is available. Influenza virus quickly bypasses post-vaccination immunity due to its ability to antigenic drift and genetic reassortment. Available antiviral drugs quickly lose effectiveness, especially in relation to highly contagious influenza virus strains. The aim of the study was to create chemotherapeutic agent with a multi-layered effect on all viral structures: surface proteins, lipid membrane and ribonucleoprotein. Such drugs include polyelectrolytes (PE), particularly, polyallylamine (PAA), which showed strong virus-inhibiting effect in combination with low cytotoxicity against several influenza strains in MDCK cell culture and as well as measles virus in Vero cell culture. Materials and methods. In this work, an extended study on PAA antiviral activity and cytotoxicity was carried out using three influenza virus strains in A549 cell line, parainfluenza virus type 3 (HPIV-3) and respiratory syncytial virus (RSV) in A549, HEp-2, Vero, L-41, MA-104 cell lines. Results. It was shown that influenza and RSV were the most sensitive to PAA,so that virus activity decreased by 3 orders of magnitude in human lung carcinoma cells A549. The lowest antiviral activity was registered in Vero cells, which may be because it lacks interferon production system. Based on the results of in vitro experiments, PAA can be considered as a broad-spectrum antiviral drug not only against influenza, but also other human respiratory viruses.

Antioxidant properties and bioactivity of three marine microalgae on human cancer cell lines

ABSTRACT Marine microalgae offer significant potential as sustainably cultivable microorganisms for the biorefining of a diverse array of functional metabolites. In this study, three species of marine microalgae, Tetraselmis chuii Butcher CCAP 66/21B (Chlorophyte), Phaeodactylum tricornutum Bohlin CCAP 1052/1 (Diatom) and Amphidinium carterae Hulburt CCAP 1102/8 (Dinoflagellate), were batch cultivated and their biomass retrieved for analysis in terms of pigment and fatty acid composition as well as bioactivity potential. Sequential solvent maceration of the biomass returned extracts was used to determine antioxidant capacity and assess their growth inhibition potential against A549 (a human lung carcinoma) and MCF-7 (a breast carcinoma) cell lines. The extracts of A. carterae showed higher antioxidant capacity (≤ 33.5 μmol Trolox Equivalent mg Recovered Dried Material‒1) compared to the other extracts. No major cytotoxic activity nor production of reactive oxygen species was observed using the extracts of T. chuii and P. tricornutum. However, the methanolic extraction of A. carterae inhibited the growth of both A549 and MCF-7 cells (< 4%) at 25, 50 and 100 µg ml−1 concentrations, as determined using the MTS assay and AO/PI cell staining. Microalgal metabolites have the potential for practical applications in a variety of industrial sectors. The absence of toxicity and substantial antioxidant potential of extracts of T. chuii and P. tricornutum confirm their suitability for incorporation into animal feeds or human nutrition supplements. A. carterae also appears to be a promising source of bioactives that can be further valorized via multi-compound biorefinery pipelines.

G-Banding and Molecular Cytogenetics Detect Novel Translocations and Cryptic Aberrations in Human Immortal Endothelial Cells.

Endothelial cells (ECs) maintain vessel tone and barrier integrity, regulate blood homeostasis, and prevent the extravasation of leukocytes under normal physiological conditions. Because of the limited lifespans and batch-to-batch differences with respect to the genetic make-up of primary ECs, established immortal EC lines are extensively used for studying endothelial biology. To address this issue, the immortal endothelial cell line EA.hy926 was developed by fusing primary human umbilical vein endothelial cells (HUVECs) with human lung carcinoma A549 cells. EA.hy926 cells share a number of similar endothelial properties with HUVECs and are considered the immortal counterpart to primary HUVECs. However, the cytogenetic integrity of EA.hy926 cells is not fully elucidated. We characterized EA.hy926 cells with conventional G-banding and molecular cytogenetic techniques such as spectral karyotyping and subtelomeric fluorescence in situ hybridization. Cytogenetic analysis revealed an array of numerical and stable structural chromosomal rearrangements including one deletion, one duplication, one isochromosome, seven simple translocations, and five complex translocations in Ea.hy926 cells. These findings will advance comprehension of EA.hy926 cell biology and augment future endothelial studies, specifically in comparison studies between HUVECs and EA.hy926 cells.

Optimization of Enzyme-Assisted Extraction of Rosemary Essential Oil Using Response Surface Methodology and Its Antioxidant Activity by Activating Nrf2 Signaling Pathway.

Rosemary essential oil (REO) is widely recognized as a food flavoring and traditional herb and possesses potential antioxidant activity. However, its low yield rate and unclarified antioxidant mechanism warrant further investigation. In this study, an enzyme pretreatment-assisted extraction method with Box-Behnken design (BBD) and response surface methodology (RSM) models was employed to optimize the main factors of REO, and its antioxidant molecular mechanism under oxidative stress was elucidated in hydrogen peroxide-induced human lung carcinoma (A549) cells. The optimized yield (4.10%) of REO was recorded with the following optimum conditions: enzyme amount 1.60%, enzyme digestion pH 5.0, enzyme digestion temperature 46.50 °C, and enzyme digestion time 1.7 h. Meanwhile, 1.8-cineole (53.48%) and β-pinene (20.23%) exhibited radical scavenging activity higher than that of BHA and BHT. At the cellular level, REO (12.5-50 µg/mL) increased the levels of cell viability, CAT, SOD, and GSH significantly while reducing the contents of ROS, MDA, and GSSG, when compared to H2O2 exposure. Mechanically, REO relieved oxidative stress via activating the Nrf2 signaling pathway and enhancing the protein expression of Nrf2, NQO-1, and HO-1, which was further verified by molecular docking between the main component 1.8-cineole and the Kelch domain of KEAP1. Therefore, REO could be considered as a potent natural antioxidant with a potential strategy in the food and pharmaceutical industries.

Role of Ciminalum-4-thiazolidinone Hybrids in Molecular NF-κB Dependent Pathways.

A range of hybrid molecules incorporating the ciminalum moiety in the thiazolidinone ring demonstrate significant anticancer and antimicrobial properties. Therefore, the aim of our study was to evaluate the properties and mechanism of action of two 4-thiazolidinone-based derivatives, i.e., 3-{5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}propanoic acid (Les-45) and 5-[2-chloro-3-(4-nitrophenyl)-2-propenylidene]-2-(3-hydroxyphenylamino)thiazol-4(5H)-one (Les-247). In our study, we analyzed the impact of Les-45 and Les-247 on metabolic activity, caspase-3 activity, and the expression of genes and proteins related to inflammatory and antioxidant defenses and cytoskeleton rearrangement in healthy human fibroblasts (BJ) and a human lung carcinoma cell line (A549). The cells were exposed to increasing concentrations (1 nM to 100 μM) of the studied compounds for 24 h and 48 h. A decrease in the metabolic activity in the BJ and A549 cell lines was induced by both compounds at a concentration range from 10 to 100 µM. Both compounds decreased the mRNA expression of NRF2 (nuclear factor erythroid 2-related factor 2) and β-actin in the BJ cells. Interestingly, a significant decrease in the level of NF-κB gene and protein expression was detected in the BJ cell line, suggesting a direct impact of the studied compounds on the inhibition of inflammation. However, more studies are needed due to the ability of Les-45 and Les-247 to interfere with the tubulin/actin cytoskeleton, i.e., a critical system existing in eukaryotic cells.