Normal Lung Cell Line Research Articles

New antibacterial hydrogels based on sodium alginate

Nowadays, the combined knowledge and experience in biomedical research and material sciences results in the innovation of smart materials that could efficiently overcome the problems of microbial contaminations. Herein, a new drug delivery platform prepared by grafting sodium alginate with β-carboxyethyl acrylate and acrylamide was described and characterized. 9-Aminoacridine (9-AA), and kanamycin sulfate (KS) were separately loaded into the hydrogel in situ during graft polymerization. The grafting efficiency for the resulting hydrogels was 70.01–78.08 %. The chemical structure of the hydrogels, thermogravimetric analysis, and morphological features were investigated. The swelling study revealed that the hydrogel without drugs achieved a superior swelling rate compared to drug-loaded hydrogels. The hydrogel tuned the drug-release rate in a pH-dependent manner.Furthermore, the antibacterial study suggested that the hydrogels encapsulating 9-AA (88.6 %) or KS (89.3 %) exhibited comparable antibacterial activity against Gram-positive and Gram-negative bacterial strains. Finally, the cytocompatibility study conducted on normal lung cell line (Vero cells) demonstrated neglectable to tolerable toxicity for the drug-loaded hydrogel. More interestingly, the cell viability for the blank hydrogel was 92.5 %, implying its suitability for biomedical applications.

Identification of ALX3 Gene Promoter Hypermethylation as a Potential Biomarker for Lung Cancer.

Recent studies imply the significance of promoter CpG methylation as a biomarker for various cancer types in different genes. ALX3 is one of the candidate genes with prominent promoter methylation status change. In this study, the methylation status of ALX3 gene promoter and its expression was analyzed in lung cancer cell lines and clinical samples from The Cancer Genome Atlas Program (TCGA) program. Methylation status was screened using the COBRA Assay, and gene expression in two cancer (A549 & H1299) and one normal (Beas 2B) lung cell lines was determined using RT-PCR. ALX3 gene promoter was found to be hypermethylated in both lung cancer cell lines compared to normal cells. However, no difference in the expression of this gene was observed. In addition to our in vitro findings, DNA Methylation and RNA-seq data of 413 adenocarcinoma samples from TCGA-LUAD dataset were analyzed. ALX3 gene was found to be hypermethylated in tumor compared to normal samples. Interestingly, the expression level of ALX3 gene in tumors was found to be higher than that in normal samples. ALX3 gene promoter hypermethylation could serve as a biomarker in lung cancer.

Artemisinin-inspired novel functionalized aryloxy-arylvinyl-1,2,4-trioxanes as potent anticancer agents: Design, synthesis, bioevaluation, SAR and in silico studies

Herein, a range of substituted aryloxy-arylvinyl-1,2,4-trioxanes (8a-8i), inspired from naturally occurring artemisinin, has been synthesized and then evaluated for their in vitro anticancer activity against human lung (A549) and liver (HepG2) cancer cell lines along with immortalized normal lung (BEAS-2B) and liver (LO2) cell lines. Out of the 34 synthesized aryloxy-arylvinyl-1,2,4-trioxanes, six compounds (8b2, 8d1, 8f2, 8f3, 8g1, 8h1) (IC50=11-37.73 µM; SI=1.7-9.6) displays promising in vitro anticancer activity. While these six compounds were proven to be more efficient and selective than those of reference standards such as artemisinin (IC50 = 100 µM) and chloroquine (IC50 = 100 µM), at the same time these were showing comparable in vitro anticancer activity with respect to one of standard reference compound artesunic acid (IC50 = 9.85 µM; SI = 0.76) against (A549) lung cancer cell line. Compound 8d1 from the series of synthesized aryloxy-arylvinyl-1,2,4-trioxanes was found out to be equipotent (IC50 = 11 µM; SI > 9) with respect to standard reference compound artesunic acid and likewise compound 8g1 (IC50 = 17.7 µM; SI > 2.4) also showed promising anticancer activity. In silico molecular docking studies of potent aryloxy-arylvinyl-1,2,4-trioxanes (8d1 & 8g1) along with standard drug molecules against the epidermal growth factor receptor (EGFR; PDB ID: 1M17) revealed a strong virtual interaction.

PLCG2 can exist in eccDNA and contribute to the metastasis of non-small cell lung cancer by regulating mitochondrial respiration

Extrachromosomal circular DNAs (eccDNAs) participate in tumorigenesis and tumor progression. However, the role and mechanism of eccDNAs have yet to be elucidated in non-small cell lung cancer (NSCLC). In our research, three surgically matched NSCLC tissue samples, NSCLC cell lines (H1299, A549, and H460), and a normal lung cell line (MRC-5) were used as study objects. High-throughput eccDNA sequencing and bioinformatics analysis were performed to study the distribution pattern and level of eccDNA expression. The upregulated candidate eccDNA-encoding PLCG2 was validated by routine PCR. Plasmid transfection, RNA interference, qRT‒PCR and western blotting experiments were used to verify the expression level of PLCG2. Our results showed that the chromosome distribution, length distribution, and genomic annotation of the eccDNAs were comparable between the NSCLC and normal groups. Nevertheless, there were no significant differences in eccDNAs between NSCLC tissues and matched normal lung tissues. The eccDNA derived from PLCG2 was upregulated in NSCLC cells. TCGA analysis and immunohistochemistry showed that PLCG2 was highly expressed in lung cancer tissues and tended to be associated with poor outcome. We also demonstrated that PLCG2 can promote metastasis through the regulation of mitochondrial respiration. These results suggested that PLCG2 identified by eccDNA sequencing acts as an oncogene and might be a new biomarker for NSCLC diagnosis and prognosis evaluation.

Flavonol-Glycoside and Rare Triterpenoid Derivatives Isolated from Leaves of Combretum glutinosum Perr. Ex Dc. with In Vitro Cytotoxic Activity

Combretaceae plants are used traditionally by many cultures, especially in Sudanese patients for the treatment of diverse ailments such as anti-inflammatory, antimicrobial, antitumor, and antioxidant disorders. Of these plants, the genus Combretum are traditional medicinal plants. Thus, they are formed from the non-polar or polar extracts of many isolated phytochemicals. Of these necessities, the use of Combretum extracts for their medicinal properties can be found in the earliest of myths and traditions used to document the plants’ ability to treat diseases. Combretum glutinosum Perr. Ex Dc. is a common shrub native to the African continent, especially Sudan. Currently, there are no published data regarding its cytotoxic activity. Additionally, there are few chemical and biological reports of C. glutinosum. Therefore, the current study aimed to isolate the chemical bioactive compounds (1–6) from the ethyl acetate (EtOAc) extract of C. glutinosum. A new flavonoid compound, namely, glutosinumoside (4), was afforded, and five known compounds were obtained: three oleanane-glycosides (1–3) and two phenolic acids (5,6). The structures of the six compounds were determined by spectroscopic analysis, including one- and two-dimensional (1D and 2D) NMR, mass spectrometry, and chromatographic analysis. Moreover, an in vitro cytotoxic evaluation of the successive extracts and the bioactive EtOAc fractions of C. glutinosum against MCF7 (breast), HT29 (colon), HepG2 (liver), and MRC5 (normal lung) cell lines was performed. The isolated compounds showed comparable cytotoxic activities with the crude EtOH extract and doxorubicin against the tested cell lines. Compounds (1) and (6) exhibited the highest cytotoxicity against MCF7 (1.37 ± 0.21 and 1.48 ± 0.34 µg/mL, respectively) and HepG2 (3.30 ± 0.02 and 2.10 ± 0.22 µg/mL, respectively) in the MTT assay. In addition, compounds (1) and (3) demonstrated a significant upregulation of cancer’s two important hallmarks (caspase 3 and bax genes) by inducing apoptosis and perturbing the MCF7 cell cycle.

Dimeric Benzodiazepines as Peptide Mimetics to Overcome p53-Dependent Drug Resistance of Tumors.

Benzodiazepines that consist of one α- and one β-amino acid residues linked together in a seven-membered heterocyclic ring could be treated as small, rigid, cyclic dipeptides capable of exhibiting a wide range of biological activities. During our research on novel analogues of anthramycin, a tricyclic antibiotic benzodiazepine, we developed the synthesis of two benzodiazepine dimers, obtained through the cyclization of appropriate linear tripeptides. The synthesized compounds were tested on a panel of seven cancer and normal cell lines. The developed molecules exhibited promising cytotoxic activity against the lung cancer cell lines A549 and NCI-H1299 and the epidermoid carcinoma cell line A-431. Moreover, they showed significant selectivity compared to the reference cell lines (BJ-human normal skin fibroblasts and MRC-5-human normal lung cell line). When tested on two isogenic cell lines, HCT116 and HCT116p53-/- (colon cancer), contrary to cisplatin being used as a positive control, the obtained compounds showed a cytotoxic effect independent of the p53 protein status. For the above reasons, the obtained compounds can be considered a new group of promising anticancer agents, useful in the fight against p53-dependent drug resistance in cancers. They can also be treated as convenient, leading structures suitable for further optimization and searching for more active and selective molecules.

One-pot green synthesis of chitosan biguanidine nanoparticles for targeting M. tuberculosis

Tuberculosis (TB) is considered as one of the most fatal infectious diseases nowadays. Several traditional anti-tuberculosis drugs like isoniazid have been largely applied; however, they are associated with toxicity and poor anti-TB treatment. So, the fabrication of new alternative anti-TB drugs containing natural biopolymers for TB treatment has attracted great attention in recent years because of their remarkable features: biodegradability, biocompatibility and non-toxicity. Therefore, their medicine is very effective with low side effects compared with synthetic drugs. Our current work intends to engineer chitosan biguanidine (ChBG) nanoparticles as a new safe and high-efficient anti-TB drug using one-pot, green, cost-effective ionic gelation method. The chemical structure of as-formed materials was chemically confirmed using various analysis techniques: H-NMR, FTIR, SEM, and TEM. TEM results have proved the formation of uniformly well-distributed ChBG nanoparticles with a small particle size of ~38 nm. The inhibitory activity of these prepared nanoparticles was investigated against the growth of three different M. tuberculosis pathogens such as sensitive, MDR, and XDR, and in a comparison with the isoniazid drug as a standard anti-tuberculosis drug. The antituberculosis assay results showed that ChBG NPs attained MIC values of 0.48, 3.9, 7.81 μg/mL for inhibiting the growth of sensitive, MDR, and XDR M. tuberculosis pathogens compared to bare Ch NPs (15.63, 62.5 > 125 μg/mL) and the isoniazid drug (0.24, 0, 0 μg/mL), respectively. Moreover, cytotoxicity of the ChBG NPs was examined against normal lung cell lines (Wi38) and was found to have cell viability of 100 % with the concentration range of 0.48–7.81 μg/mL.

Green synthesis of nanostructured zinc oxide by Ocimum tenuiflorum extract: characterization, adsorption modeling, cytotoxic screening, and metal ions adsorption applications

Nano-ZnO was synthesized by the reduction of Zn (CH3COO)2.2H2O salt using the extract of Ocimum tenuiflorum leaves. The generated ZnO NPs were characterized by FT-IR, XRD, SEM, and EDX techniques. FT-IR results approved the characteristic peaks, the formation of ZnO bonds, and the morphology changes after the adsorption of Cd2+ and Pb2+ from solutions. The outlined data of the XRD pointed to the formation of a hexagonal wurtzite structure. SEM images showed the spherical nature of the synthesized particles with an average diameter of 19 nm. Moreover, the best conditions for the adsorption of Cd2+ and Pb2+ by ZnO NPs were evaluated and fitted to isotherm and kinetic models. Short contact time of ~ 20 min and a small sorbent dosage of 40 mg were sufficient conditions for attaining maximum Pb2+ adsorption capacity. Based on the modeling parameters, the adsorption follows pseudo-second-order kinetics where ZnO and metal ions are involved in the rate-determining step. Two important applications were thoroughly studied. The nanoparticles significantly removed Pb2+ and Cd2+ contaminants from real environmental water samples collected from different locations in Egypt. Additionally, the cytotoxic activity results provided perfect evidence for the higher efficacy of the synthesized ZnO NPs as an anticancer agent against Panc-1, PC-3, and CACO-2 cell lines with IC50 of 1.70, 3.67, and 5.70 μgml−1, respectively, compared to cisplatin (IC50 = 3.57, 5.09, and 7.75 μgml−1). Furthermore, a low cytotoxic effect was observed on the normal human lung cell line (MRC-5, IC50 = 22.40 μgml−1). The data can be used as a preliminary study for anticancer drug design after further clinical investigations.Graphical

Green engineering of TMC-CMS nanoparticles decorated graphene sheets for targeting M. tuberculosis

Our current work intends to primarily engineer a new type of antibacterial composite by preparing a highly biocompatible graphene sheet decorated with TMC-CMS IPNs nanoparticles utilizing one-pot, green, cost-effective ultrasonication approach. The microstructure of as-formed materials was chemically confirmed using various analytical techniques such as 1H-NMR, FTIR, UV/vis, SEM, and TEM. TEM data has proved the formation of uniformly distributed TCNPs on graphene surfaces with a small particle size of ~22 nm compared with that of pure nanoparticles (~30 nm). The inhibitory activity of these developed materials was examined against the growth of three different M. tuberculosis pathogens and in a comparison with the isoniazid drug as a standard anti-tuberculosis drug. The TCNPs@GRP composite attained MIC values of 0.98, 3.9, and 7.81 μg/mL for inhibiting the growth of sensitive, MDR, and XDR M. tuberculosis pathogens compared to the bare TCNPs (7.81, 31.25, >125 μg/mL) and the isoniazid drug (0.24, 0, 0 μg/mL), respectively. This reveals a considerable synergism in the antituberculosis activity between TCNPs and graphene nanosheets. Cytotoxicity of the TCNPs@GRP was examined against normal lung cell lines (WI38) and was found to have cell viability of 100% with the concentration range of 0.98–7.81 μg/mL.

Design, synthesis and evaluation of novel substituted fused pyrido diazepine and pyrimido piperazine derivatives: In vitro cytotoxicity study over various cancer cell lines

The current study describes, a novel combinatorial library of substituted fused pyrimido[3,2–e]pyrrolo[1,2-a]piperazine and pyrido[3,2-b]pyrrolo[1,2-d][1,4]diazepin heterocycles procured via utilization of suzuki coupling and acid amine coupling protocols. The synthesized compounds were screened for their in vitro cytotoxic activity over nine different cancer cell lines such as U-251, Panc-1, MCF-7, HepG2, DU-145, A549, 786-O, OVCAR3 and HCT-116 as well as on non-cancerous cell lines like normal human lung cell line WI38 and Mouse embryonic normal cell line NIH3T3 to evaluate safety profile of synthesized compounds. The bioassay results indicates that compound Cpd-J2 to be most potent among all the synthesized compounds towards ovary cancer cell lines (OVCAR-3) with promising activity value (EC50: 6.3 μM) relative to standard doxorubicin (EC50: 0.2 μM).

A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II.

Computational chemistry, molecular docking, and drug design approaches, combined with the biochemical evaluation of the antitumor activity of selected derivatives of the thiouracil-based dihydroindeno pyrido pyrimidines against topoisomerase I and II. The IC50 of other cell lines including the normal human lung cell line W138, lung cancer cell line, A549, breast cancer cell line, MCF-7, cervical cancer, HeLa, and liver cancer cell line HepG2 was evaluated using biochemical methods. The global reactivity descriptors and physicochemical parameters were computed, showing good agreement with the Lipinski and Veber’s rules of the drug criteria. The molecular docking study of the ligands with the topoisomerase protein provides the binding sites, binding energies, and deactivation constant for the inhibition pocket. Various biochemical methods were used to evaluate the IC50 of the cell lines. The QSAR model was developed for colorectal cell line HCT as a case study. Four QSAR statistical models were predicted between the IC50 of the colorectal cell line HCT to correlate the anticancer activity and the computed physicochemical and quantum chemical global reactivity descriptors. The predictive power of the models indicates a good correlation between the observed and the predicted activity.

Evaluation of Green Silver Nanoparticles Fabricated by Spirulina platensis Phycocyanin as Anticancer and Antimicrobial Agents.

Green nanotechnology has attracted attention worldwide, especially in treating cancer and drug-resistant section 6 microbes. This work aims to investigate the anticancer activity of green silver nanoparticles synthesized by Spirulina platensis phycocyanin (SPAgNPs) on two cancer cell lines: Lung cancer cell line (A-549) and breast cancer cell line (MCF-7), compared to the normal human lung cell line (A138). We also aimed to investigate the bactericidal activity against Staphylococcus aureus ATCC29737, Bacillus cereus ATCC11778, Escherichia coli ATCC8379, and Klebsiella pneumonia, as well as the fungicidal activity against Candida albicans (ATCC6019) and Aspergillus niger. The obtained SPAgNPs were spherical and crystalline with a size of 30 nm and a net charge of −26.32 mV. Furthermore, they were surrounded by active groups responsible for stability. The SPAgNPs scavenged 85% of the DPPH radical with a relative increase of approximately 30% over the extract. The proliferation of cancer cells using the MTT assay clarified that both cancer cells (A-549 and MCF-7) are regularly inhibited as they grow on different concentrations of SPAgNPs. The maximum inhibitory effect of SPAgNPs (50 ppm) reached 90.99 and 89.51% against A-549 and MCF7, respectively. Regarding antimicrobial activity, no inhibition zones occurred in bacterial or fungal strains at low concentrations of SPAgNPs and the aqueous Spirulina platensis extract. However, at high concentrations, inhibition zones, especially SPAgNPs, were more potent for all tested microorganisms than their positive controls, with particular reference to Staphylococcus aureus, since the inhibition zones were 3.2, 3.8, and 4.3 mm, and Bacillus cereus was 2.37 mm when compared to tetracycline (2.33 mm). SPAgNPs have more potent antifungal activity, especially against Aspergillus niger, compared to their positive controls. We concluded that SPAgNPs are powerful agents against oxidative stress and microbial infection.

Antimalarial and Anticancer Activity Evaluation of Bridged Ozonides, Aminoperoxides, and Tetraoxanes.

Bridged aminoperoxides, for the first time, were investigated for the in vitro antimalarial activity against the chloroquine-resistant Plasmodium falciparum strain K1 and for their cytotoxic activities against immortalized human normal liver (LO2) and lung (BEAS-2B) cell lines as well as human liver (HepG2) and lung (A549) cancer cell lines. Aminoperoxides exhibit good cytotoxicity against lung A549 cancer cell line. Synthetic ozonides were shown to have high activity against the chloroquine-resistant P. falciparum. A cyclic voltammetry study of peroxides was performed, and most of the compounds did not show a direct correlation in oxidative capacity-activity. Peroxides were analyzed for ROS production to understand their mechanism of action. However, none of the compounds has an impact on ROS generation, suggesting that ozonides induce apoptosis in HepG2 cells through ROS-independent dysfunction pathway.

Lab-scale Preparation of Recombinant Human Insulin-like Growth Factor-1 in Escherichia coli and its Potential Safety on Normal Human Lung Cell Line.

Insulin-like growth factor-1 (IGF-1) is structurally similar to insulin and acts as an endocrine hormone secreted by the liver. Production of recombinant human IGF-1 (rhIGF-1) in Escherichia coli (E.coli) and evaluation of its proliferation stimulatory activity. hIGF-1 gene cloned into pBSK (+) simple vector was transformed into TOP 10 chemically competent cells of E. coli. Polymerase chain reaction (PCR) was achieved using specific hIGF-1 gene primers to confirm the successful transformation. To express the rhIGF-1 in E. coli (Rosetta (DE3) pLysS); the hIGF-1 gene was cloned into the pET-15b expression vector and then the recombinant pET-15b/IGF-1 vector was transformed into a chemically prepared competent expression bacterial cells; Rosetta (DE3) pLysS. The rhIGF-1 was expressed as insoluble aggregates called inclusion bodies (IBs) using a 2 mM Isopropyl β-D-1-thiogalactopyranoside (IPTG) inducer. IBs were solubilized in a denatured form using 6 M guanidinium hydrochloride (GdmCl), followed by in vitro protein refolding using the rapid dilution method. The refolded hIGF-1 was purified using the HiTrap- ANX anion exchange column. Western blot and ELISA using rabbit polyvalent anti-hIGF- 1 were performed to confirm the protein antigenic identity. Cell proliferation activity of rhIGF-1 was testified on normal human lung cell line (WI-38). rhIGF-1 was purified from the HiTrap-ANX column at a concentration of 300 μg/ml. Western blot showed a single 7.6 kDa band obtained in the induced Rosetta (DE3) pLYsS. ELISA confirmed the molecular identity of the rhIGF-1 epitope, the concentration of purified rhIGF-1 obtained from the ELISA standard curve using rhIGF-1 reference protein as a standard was 300 μg/ml, and activity on WI-38 cells was 2604.17I U/mg. Biologically active native rhIGF-1 protein was successfully expressed. Patents related to the preparation of IGF-1 were mentioned along the text.

FUBP1 promotes the proliferation of lung squamous carcinoma cells and regulates tumor immunity through PD-L1.

Lung cancer is a common malignancy. Non-small cell lung cancer (NSCLC) is divided into lung squamous cancer (LUSC), large cell carcinoma, and adenocarcinoma. More than 85% of lung cancer cases are NSCLC patients. Further exploration of the pathogenesis of lung cancer is of great significance. In this study, functions of far upstream element-binding protein 1 (FUBP1) on the proliferation and tumor immunity of LUSC cells were evaluated. The Cancer Genome Atlas (TCGA) database, Western blot analysis, and immunohistochemistry (IHC) analysis were used to examine the overexpression levels of FUBP1 in LUSC and paracancerous tissues, LUSC cell line, and human normal lung cell line. Then, Western blot assay was employed to validate the transfection efficiency of FUBP1 knockdown in SK-MES-1 cells. Cell counting kit-8 and colony formation assays were used to detect the viability and proliferation of SK-MES-1 cells. Transwell assay was used to examine the migrative and invasive abilities of SK-MES-1 cells. Finally, the xenograft tumor mice model was applied to explore the role of FUBP1 in vivo. IHC assay was used to determine the expression levels FUBP1, PD-L1, and Ki-67. Flow cytometry technology was employed to detect the proportion of CD4+ and CD8+ cells in short sequence negative control (sh-NC) and sh-FUBP1 groups. Collectively, the results first indicated that FUBP1 was up-regulated in LUSC tissues and cells. It was also demonstrated that knockdown of FUBP1 suppressed cell migration, invasion, and proliferation in lung squamous carcinoma cells. Finally, knockdown of FUBP1 regulated tumor immunity in vivo. This research suggested that FUBP1 promotes the proliferation of LUSC cells and regulates tumor immunity through programmed death-ligand 1 (PD-L1).

DNA double-strand break repair and adaptive responses of low-dose radiation in normal and tumor lung cell lines

The adaptive response (AR), which can be induced by low-dose ionizing radiation (LD), may influence the therapeutic ratio of cancer treatment. We investigated the AR and the DNA double-strand break (DSB) repair pathway in human lung tumor cells and normal cells. We measured viability and proliferation of normal lung cells (MRC-5) and lung cancer cells (QU-DB) using the MTT and colony formation assays. Flow cytometric analysis of γ-H2AX was used to measure DNA-DSBs induction, repair, and residual damages. AR was seen in the normal cells but not in the cancer cells. Our findings suggest that LD stimulates DSB repair and that this may contribute to distinctive AR in normal vs. cancer cells.

Novel 1,2,3-Triazole-sulphadiazine-ZnO Hybrids as Potent Antimicrobial Agents against Carbapenem Resistant Bacteria.

Bacterial pneumonia is considered one of the most virulent diseases with high morbidity and mortality rates, especially in hospitalized patients. Moreover, bacterial resistance increased over the last decades which limited the therapy options to carbapenem antibiotics. Hence, the metallo-β-lactamase-producing bacteria were deliberated as the most deadly and ferocious infectious agents. Sulphadiazine-ZnO hybrids biological activity was explored in vitro and in vivo against metallo-β-lactamases (MBLs) producing Klebsiella pneumoniae. Docking studies against NDM-1 and IMP-1 MBLs revealed the superior activity of the 3a compound in inhibiting both MBLs enzymes in a valid reliable docking approach. The MBLs inhibition enzyme assay revealed the remarkable sulphadiazine-ZnO hybrids inhibitory effect against NDM-1 and IMP-1 MBLs. The tested compounds inhibited the enzymes both competitively and noncompetitively. Compound 3b-ZnO showed the highest antibacterial activity against the tested metallo-β-lactamase producers with an inhibition zone (IZ) diameter reaching 43 mm and a minimum inhibitory concentration (MIC) reaching 2 µg/mL. Sulphadiazine-ZnO hybrids were tested for their in vitro cytotoxicity in a normal lung cell line (BEAS-2Bs cell line). Higher cell viability was observed with 3b-ZnO. Biodistribution of the sulphadiazine-ZnO hybrids in the lungs of uninfected rats revealed that both [124I]3a-ZnO and [124I]3b-ZnO hybrids remained detectable within the rats’ lungs after 24 h of endotracheal aerosolization. Moreover, the residence duration in the lungs of [124I]3b-ZnO (t1/2 4.91 h) was 85.3%. The histopathological investigations confirmed that compound 3b-ZnO has significant activity in controlling bacterial pneumonia infection in rats.

Expression of Deubiquitinating Enzymes in Lung Cancer Cells with Different REST Status

he aims of this study were: (1) to screen a panel of lung cell lines for expression of the proteins UCHL1, USP49, USP15, USP4, and USP11. (2) To investigate the correlation of transcript and protein expression level of these DUBs. (3) To find any proteins that discriminate non-small cell lung cancer (NSCLC) from neuroendocrine (NE) SCLC or benign lung carcinoid. (4) To investigate any correlation of DUB proteins expression with lung cancer sub-types that has different amounts of REST protein. Method: Western blots were performed to detect the expression of DUB expression (USP4, USP11, USP15, USP49, and UCHL1) and REST protein in extracts from normal lung cell lines, SCLC, carcinoid, and NSCLC Results: we found that the transcript level was in general not a good indicator of DUB protein level. There was a significant positive correlation of REST with DUB proteins from whole-cell extracts for USP15, USP11, USP4, and USP49 in normal lung cell lines. The P values were 0.016, 0.002, 0 .018 and 0 .034 respectively. Also in both normal and NSCLC cell lines total USP15, USP11 and USP49 showed a positive correlation with REST. P values were 0.007, 0.029 and 0.001 respectively. However USP11 protein was highly abundant in REST-deficient SCLC. In contrast, both USP11 and USP15 showed a positive correlation with REST in SCLC and NSCLC nuclear extracts. P values were 0.001 and 0.005 respectively. A positive correlation of DUBs with REST would be consistent with their putative role in stabilizing REST.

Inflammatory Signaling and DNA Damage Responses after Local Exposure to an Insoluble Radioactive Microparticle.

Simple SummaryA cesium-bearing microparticle (Cs-BMP) is an insoluble radioactive microparticle possessing high specific radioactivity, which was discovered after the incident at the Fukushima nuclear power plant. Due to their insoluble nature, such Cs-BMPs are assumed to adhere in the long term to normal tissue, leading to chronic local exposure. However, radiation risk due to the intake of internal exposure to radioactive cesium is conventionally estimated from the organ dose given by uniform exposure to soluble cesium. As such, it is critical to clarify the normal tissue effects posed by heterogeneous exposure to Cs-BMPs. This in vitro study reports on the relationship between the inflammatory responses and DNA damage induction during local exposure to a Cs-BMP.Cesium-bearing microparticles (Cs-BMPs) can reach the human respiratory system after inhalation, resulting in chronic local internal exposure. We previously investigated the spatial distribution of DNA damage induced in areas around a Cs-BMP; however, the biological impacts have not been fully clarified due to the limited amount of data. Here, we investigated the inflammatory signaling and DNA damage responses after local exposure to a Cs-BMP in vitro. We used two normal human lung cell lines, i.e., lung fibroblast cells (WI-38) and bronchial epithelial cells (HBEC3-KT). After 24 h exposure to a Cs-BMP, inflammation was evaluated by immunofluorescent staining for nuclear factor κB (NF-κB) p65 and cyclooxygenase 2 (COX-2). The number of DNA double-strand breaks (DSBs) was also detected by means of phospholylated histone H2AX (γ-H2AX) focus formation assay. Cs-BMP exposure significantly increased NF-κB p65 and COX-2 expressions, which were related to the number of γ-H2AX foci in the cell nuclei. Compared to the uniform (external) exposure to 137Cs γ-rays, NF-κB tended to be more activated in the cells proximal to the Cs-BMP, while both NF-κB p65 and COX-2 were significantly activated in the distal cells. Experiments with chemical inhibitors for NF-κB p65 and COX-2 suggested the involvement of such inflammatory responses both in the reduced radiosensitivity of the cells proximal to Cs-BMP and the enhanced radiosensitivity of the cells distal from Cs-BMP. The data show that local exposure to Cs-BMP leads to biological effects modified by the NF-κB pathway, suggesting that the radiation risk for Cs-BMP exposure can differ from that estimated based on conventional uniform exposure to normal tissues.

MiR-129-2 upregulation induces apoptosis and promotes NSCLC chemosensitivity by targeting SOX4.

BackgroundAs one of the main causes of death worldwide, the treatment of non‐small‐cell lung cancer (NSCLC) is still unsatisfactory. This study aimed to explore the role of miR‐129‐2 in cell apoptosis and NSCLC chemosensitivity.MethodsThe effect of miR‐129‐2 on NSCLC was investigated using lung cancer cell lines (A549, NCl‐H23, and HCC827), a normal lung cell line (BEAS‐2B), and NSCLC tissues and adjacent healthy tissues. The oncogene SOX4 was verified as the target gene of miR‐129‐2 by luciferase reporter assay and real‐time polymerase chain reaction.ResultsmiR‐129‐2 expression was downregulated in NSCLC tissues, NCl‐H23 cells, and A549 cells. miR‐129‐2 upregulation induced apoptosis in NCl‐H23 and A549 cells. miR‐129‐2 upregulation also inhibited NSCLC in a xenograft mouse model, which was related to downregulation of SOX4 expression. Furthermore, miR‐129‐2 and SOX4 were aberrantly expressed in the cisplatin‐resistant lung cancer cell line A549/DDP, and upregulation of miR‐129‐2 expression promoted cisplatin sensitivity in A549/DDP cells.ConclusionsIn conclusion, miR‐129‐2 expression was downregulated in NSCLC tissues and cell lines, and its upregulation induced cell apoptosis and promoted NSCLC chemosensitivity by regulating SOX4. Therefore, miR‐129‐2 can serve as a potential diagnostic and therapeutic target in NSCLC.