WI-38 Cells Research Articles

Evaluation of the synergistic effect of chitosan metal ions (Cu2+/Co2+) in combination with antibiotics to counteract the effects on antibiotic resistant bacteria.

The effectiveness of antibiotics that save millions of lives is in danger due to the increasing rise of resistant bacteria around the world. We proposed chitosan-copper ions (CSNP-Cu2+) and chitosan-cobalt ion nanoparticles (CSNP-Co2+) as biodegradable nanoparticles loaded with metal ions synthesized via an ionic gelation method for treatment of antibiotic resistant bacteria. The nanoparticles were characterized using TEM, FT-IR, zeta potential and ICP-OES. The MIC was evaluated for the NPs in addition to evaluating the synergetic effect of the nanoparticles in combination with cefepime or penicillin for five different antibiotic resistant bacterial strains. In order to investigate the mode of action, MRSA, DSMZ 28766 and Escherichia coli E0157:H7 were selected for further evaluation of antibiotic resistant genes expression upon treatment with NPs. Finally, the cytotoxic activities were investigated using MCF7, HEPG2 and A549 and WI-38 cell lines. The results showed quasi spherical shape and mean particle size of 19.9 ± 5 nm, 21 ± 5 nm and 22.27 ± 5 for CSNP, CSNP-Cu2+ and CSNP-Co2+ respectively. FT-IR showed slight shifting of the hydroxyl and amine group's peaks of chitosan indicating the adsorption of metal ions. Both nanoparticles had antibacterial activity with MIC ranging between 125 and 62 μg ml-1 for the used standard bacterial strains. Moreover, the combination of each of the synthesized NP with either cefepime or penicillin not only showed a synergetic effect as antibacterial activity of each NP or antibiotics alone, but also decreased the fold of antibiotic resistance genes expression. The NPs showed potent cytotoxic activities for MCF-7, HepG2 and A549 cancer cell lines with lower cytotoxic values for the WI-38 normal cell line. The NPs' antibacterial activity may be due to penetration and rupture of the cell membrane and the outer membrane of Gram negative and Gram positive bacteria causing bacterial cell death, in addition to, penetration into the bacterial genes and blocking gene expression that is vital to bacterial growth. The fabricated nanoparticles can be an effective, affordable and biodegradable solution to challenge antibiotic resistant bacteria.

Design of N-heterocycle based-phthalonitrile/metal phthalocyanine-silver nanoconjugates for cancer therapies.

This study reports the anticancer properties of carbazole-containing phthalonitrile/phthalocyanine-modified silver nanoparticles for the first time. In this study, a new mono-substituted phthalonitrile namely 3-[9H-carbazole-9-ethoxy]phthalonitrile and its metal phthalocyanines {M = Zn, Co, and Mn(Cl)} were synthesized by template cyclotetramerization of phthalonitrile derivatives. The newly synthesized compounds were characterized using UV-vis, FT-IR, 1H NMR, 13C NMR, and mass spectroscopy. The resultant compounds were successfully linked to the surface of silver nanoparticles. The characterization of the surficial modification was carried out by applying the TEM technique. The cytotoxic activities of the studied nanoconjugates were tested against A549, DLD-1, and Wi38 cell lines by performing a (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay with/without irradiation. Although the functionalization of silver nanoparticles increased the solubility of phthalocyanines in aqueous media, the presence of phthalonitrile/phthalocyanine derivatives on the silver nanoparticles' surface improved their biological properties. All the studied biological candidates exhibited antiproliferative activities against the cell lines. The IC50 values calculated were between 6.80 and 97.99 μM against the studied cell lines in the dark. However, the IC50 values determined were between 3.11 and 88.90 μM with irradiation. The highest IC50 values obtained were 3.11 and 3.52 μM against the DLD-1 cell line for nanoconjugates 1-AgNP and 3-AgNP, respectively. The findings indicated that the compounds may be utilized as anticancer agents after further studies.

Investigation of Antimicrobial and Cytotoxic Activities of Palmarosa (Cymbopogon martinii) Essential Oil

In this study; It was aimed to investigate the cytotoxic activities and antimicrobial effects of Palmarosa essential oil obtained from Cymbopogon martinii plant. Content analyzes of Palmarosa essential oil were made by Gas Chromatopraphy-Mess Spectrometry (GS-MS). The antimicrobial effects of Palmarosa essential oil were investigated using Disk Diffusion and Minimum Inhibition Concentration (MIC) methods. Cytotoxic effects of essential oil at different concentrations in breast cancer (MCF-7), prostate cancer (DU-145) and healthy human fibroblast (WI-38) cell lines XTT (2,3-bis-(2-methoxy-4-nitro-5) -sulfophenyl)-2H-tetrazolium-5-carboxanilide) test. In the disc diffusion method of Palmarosa; against K. pneumoniae, S. aureus, and E. coli, it was observed that the first concentrations formed zone diameters very close to the standard. It has been determined that the antifungal effect against C. albicans is present in the first two concentrations (200-100 µg/mL). Palmarosa, in the MIC method; Showed the highest antibacterial effect against B. cereus (MIC: <1.56 µg/mL). It has reached effective MIC values against other bacteria and fungi. In our cytotoxic activity studies; The IC50 value for DU-145 cells was 3.14 ±0.126, 6.29 ±0.56 for MCF-7 and 20.06 ±1.02 for WI-38. The antitumor activity of Palmarosa essential oil was found to be more effective in DU-145 cells, but it was observed that there was no toxicity in WI-38 cell line.

Suppressive effects of pterostilbene on human cytomegalovirus (HCMV) infection and HCMV-induced cellular senescence

BackgroundHuman cytomegalovirus (HCMV), a member of the β-herpesvirus family, causes the establishment of a latent infection that persists throughout the life of the host and can be reactivated when immunity is weakened. To date, there is no vaccine to prevent HCMV infection, and clinically approved drugs target the stage of viral replication and have obvious adverse reactions. Thus, development of novel therapeutics is urgently needed.MethodsIn the current study, we identified a naturally occurring pterostilbene that inhibits HCMV Towne strain replication in human diploid fibroblast WI-38 cells through Western blotting, qPCR, indirect immunofluorescence assay, tissue culture infective dose assays. The time-of-addition experiment was carried out to identify the stage at which pterostilbene acted. Finally, the changes of cellular senescence biomarkers and reactive oxygen species production brought by pterostilbene supplementation were used to partly elucidate the mechanism of anti-HCMV activity.ResultsOur findings revealed that pterostilbene prevented lytic cytopathic changes, inhibited the expression of viral proteins, suppressed the replication of HCMV DNA, and significantly reduced the viral titre in WI-38 cells. Furthermore, our data showed that pterostilbene predominantly acted after virus cell entry and membrane fusion. The half-maximal inhibitory concentration was determined to be 1.315 μM and the selectivity index of pterostilbene was calculated as 26.73. Moreover, cell senescence induced by HCMV infection was suppressed by pterostilbene supplementation, as shown by a decline in senescence-associated β-galactosidase activity, decreased production of reactive oxygen species and reduced expression of p16, p21 and p53, which are considered biomarkers of cellular senescence.ConclusionTogether, our findings identify pterostilbene as a novel anti-HCMV agent that may prove useful in the treatment of HCMV replication.

Synthesis, Cytotoxic Activity, Crystal Structure, DFT, Molecular Docking Study of β-Enaminonitrile Incorporating 1H-Benzo[f]Chromene Moiety

In this work, we used microwave irradiation conditions to synthesize β-enaminonitrile (4), which was affirmed using single crystal X-ray diffraction and the different spectral data. Two tumor cell lines, MCF-7 and MCF-7/ADR, as well as two normal cell lines, HFL-1 and WI-38, were used to assess the anticancer activity of compound 4. The studied molecule exhibited potent efficacy against the MCF-7 and MCF-7/ADR cell lines compared with the reference drugs. Furthermore, target compound 4 had feeble activity against HFL-1 and WI-38. The chemical reactivity was discussed using DFT and QTAIM analysis to study the intrinsic electronic properties of compound 4. A molecular docking study was also conducted to examine their binding affinity to the EGFR. Compound 4 revealed a stable binding mode at the enzyme active pocket more than the reference inhibitor. The docking analysis was performed for molecule (4).

Synthesis of 9-Hydroxy-1H-Benzo[f]chromene Derivatives with Effective Cytotoxic Activity on MCF7/ADR, P-Glycoprotein Inhibitors, Cell Cycle Arrest and Apoptosis Effects

β-Enaminonitriles bearing 9-hydroxy-1H-benzo[f]chromene moiety was synthesized. The targeted compounds were evaluated for their anti-proliferative activity against three human tumor cell lines, PC-3, SKOV-3 and HeLa, and the active cytotoxic compounds were further evaluated against cancer cells, MCF-7/ADR, and two normal cell lines, HFL-1 and WI-38. Few compounds were assigned to be the most potent derivatives against PC-3, SKOV-3 and HeLa cell lines in comparison with Vinblastine and Doxorubicin. Several compounds possessed a relatively good potency against MCF-7/ADR cells as compared with Doxorubicin and were tested as a P-gp inhibitor. Moreover, the halogenated substituents, 2,4-F2, 2,3-Cl2, 2,5-Cl2 and 3,4-Cl2; have good potency against P-gp-mediated MDR in MCF-7/ADR as compared with Doxorubicin. Meanwhile, Rho123 accumulation assays revealed that few compounds effectively inhibited P-pg and efflux function. In addition, certain derivatives induced apoptosis and an accumulation of the treated MCF-7/ADR cells in the G1, S and G1/S phases.

Antidiabetic Potential of Novel 1,3,5-Trisubstituted-2-Thioxoimidazloidin-4-One Analogues: Insights into α-Glucosidase, α-Amylase, and Antioxidant Activities.

As the ninth leading cause of death globally, diabetes mellitus (DM) is considered to be the worst chronic metabolic disease requiring an enormous need for healthcare with over 578 million expected cases by 2023. Several recent findings have demonstrated that mediating the activity of carbohydrate-hydrolyzing enzymes, including α-amylase and α-glucosidase, could be a potential strategy for managing the development of DM. In the presented study, a novel set of 1,3,5-trisubstituted-2-thioxoimidazolidin-4-ones was designed, synthesized, and characterized. The antidiabetic activity of the synthesized compounds was explored by assessing their inhibitory activity toward α-amylase and α-glucosidase enzymes. The results demonstrated that this class of compounds exhibits considerable inhibitory activity toward both α-amylase and α-glucosidase enzymes. Among the synthesized compounds, compound 5a demonstrated the most inhibitory activity with IC50 of 5.08 and µg/mL and 0.21 µg/mL toward α-glucosidase and α-amylase activities, respectively, as compared to the drug Acarbose (IC50 = 5.76 µg/mL and 0.39 µg/mL, respectively). To gain insights into the antidiabetic potential of compound 5a, we assessed the cytotoxic and antioxidant activities. Our findings indicated that compound 5a displays considerable cytotoxicity toward WI-38 cells with an IC50 of 88.54 µg/mL, as compared to the drug Celecoxib (IC50 = 93.05 µg/mL). Further, compound 5a exhibited a high scavenging activity toward 2,2-Diphenyl1-picrylhydrazyl (DPPH) free radicals (IC50 = 51.75 µg/mL) and showed a low potential to produce ROS as indicated by the monitoring of the generated H2O2 (132.4 pg/mL), as compared to Trolox (IC50 = 58.09 µg/mL) and Celecoxib (171.6 pg/mL). Finally, we performed extensive molecular modeling studies to affirm the binding affinity of this class of compounds to the binding pocket of α-amylase and α-glucosidase enzymes. Collectively, our findings indicate that this class of compounds, particularly compound 5a, could be utilized as a lead structure for the development of novel compounds with potential antidiabetic and antioxidant activities.

New benzimidazole derivatives: Design, synthesis, docking, and biological evaluation

The aim of this study was to synthesize novel enaminonitrile derivatives starting from 2-aminobenzimidazole and utilize this derivative for the preparation of novel heterocyclic compounds and assess their function for biological activity screening. The key precursor N-(1H-benzo[d]imidazol-2-yl)carbonohydrazonoyl dicyanide (2) was prepared in pyridine by coupling of diazotized 2-aminobenzimidazole (1) with malononitrile. Compound 2 was subjected to react with various secondary amines such as piperidine, morpholine, piperazine, diphenylamine, N-methylglucamine, and diethanolamine in boiling ethanol to give the acrylonitriles (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(piperidin-1-yl)acrylonitrile (3), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-morpholinoacrylonitrile (4), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(piperazin-1-yl)acrylonitrile (5), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(diphenylamino)acrylonitrile (6), (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(methyl((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)acrylonitrile (7), and (2Z)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-3-amino-3-(bis(2-hydroxyethyl)amino)acrylonitrile (8), respectively. It has been found that the behaviour of nitrile derivative 2 towards hydrazine hydrate to the creation of 4-((1H-benzo[d]imidazol-2-yl)diazenyl)-1H-pyrazole-3,5-diamine (9). The reaction of malononitrile with compound 2 in an ethanolic solution catalyzed with sodium ethoxide afforded 4-amino-1-(1H-benzo[d]imidazol-2-yl)-6-imino-1,6-dihydropyridazine-3,5-dicarbonitrile (11). Moreover, malononitrile reacted with 7 in a boiling ethanolic sodium ethoxide solution to give 2-(5-((1H-benzo[d]imidazol-2-yl)diazenyl)-4-amino-6-(methyl((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)pyrimidin-2-yl)acetonitrile (14). Heating 7 in boiling acetic anhydride and pyridine afforded (2R,3R,4R,5S)-6-(((1E)-2-((1-acetyl-1H-benzo[d]imidazol-2-yl)diazenyl)-1-(N-acetylacetamido)-2-cyanovinyl)(methyl)amino)hexane-1,2,3,4,5-pentayl pentaacetate (15). When compound 15 is heated for a long time in refluxing DMF including a catalytic of TEA, cyclization occurs to give the corresponding (2R,3R,4R,5S)-6-((1-acetyl-3-((1-acetyl-1H-benzo[d]imidazol-2-yl)diazenyl)-4-amino-6-oxo-1,6-dihydropyridin-2-yl)(methyl)amino)hexane-1,2,3,4,5-pentayl pentaacetate (16). In addition, triethyl orthoformate was reacted with compound 7 in the presence of acetic anhydride to afford the corresponding ethoxymethyleneamino derivative (2R,3R,4R,5S)-6-(((1E)-2-((1-acetyl-1H-benzo[d]imidazol-2-yl)diazenyl)-2-cyano-1-(((E) ethoxymethylene)amino)vinyl)(methyl)amino)hexane-1,2,3,4,5-pentayl pentaacetate (17). Also, it has been found that heating a mixture of 7 with DMF/DMA in anhydrous xylene yielded compound (1E)-N'-((1E)-2-((1H-benzo[d]imidazol-2-yl)diazenyl)-2-cyano-1-(methyl((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)vinyl)-N,N-dimethylformimidamide (18). In addition, compound 7, when reacted with several acid anhydrides, allowed the matching phthalimide derivatives 19–26. The results showed that compound 14 has significantly higher ABTS and antitumor activities than the other compounds. Molecular modelling was also studied for compounds 22 and 24. The viability of four many cell lines—the African green monkey kidney epithelial cells (VERO), human breast adenocarcinoma cell line (MCF-7), human lung fibroblast cell line (WI-38), and human hepatocellular liver carcinoma cell line (HepG2) was examined to determine the antitumor activities of the newly synthesized compounds. Also, it was found that compounds 9, 11, 15, 16, 22, 23, 24 and 25 are strong against HepG2 cell lines, while 16, 22, and 25 are strong against WI-38 cell lines. Moreover, it was also found that compounds 16 and 22 are strong against VERO cell lines. On the other hand, compounds 7, 14, 15, 16, and 22 are strong while the rest of the other compounds are moderate against the MCF-7 cell line. The result of docking showed that compound 24 got stabilized inside the pocket with a very promising binding score of − 8.12 through hydrogen bonds with Arg184 and Lys179, respectively.

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).

Arc discharge rapid synthesis of engineered copper oxides nano shapes with potent antibacterial activity against multi-drug resistant bacteria

Nowadays Nano metals have received an eminent compromise of attention. Even though different nanostructure of same metal maybe gives different results in wide range applications. Copper oxide (CuO-NPs) and Copper Nano wires (CuO-NWs) were prepared in controlled size via the alternating current Arc discharge process. Deionized water and argon gas were the chosen dielectric medium during the process to obtain 2 different forms of copper oxides. By changing the dielectric material from deionized water to argon gas the shape of CuO nanoparticles changed from spherical (CuO-NPs) to wires (CuO-NWS). The yield prepared depicted the purity of the prepared CuO, and their diameters were about 10 ± 5 nm and 30 ± 3 nm for CuO-NWs and CuO-NPs respectively. In vitro cytotoxic effect of the prepared CuO-NWs & CuO-NPs using human normal lung fibroblast cell line (WI-38 cells) revealed that CuO-NWs & CuO-NPs CC50 values were 458.8 and 155.6 µg/mL respectively. Both yields showed potent antibacterial activity against different multi-drug resistant Acinetobacter baumannii strains. A complete eradication of the bacterial growth was noticed after 4 Hrs incubation with CuO-NWs. Moreover, CuO-NWs showed superior antibacterial activity (with minimum inhibitory concentration reached 1.8 µg/mL) over CuO-NPs. The detailed antibacterial activity mechanism of CuO-NWs was further investigated; data proved the precipitation and adsorption of the nanoparticles on the bacterial cell surface leading to cell deformation with reactive oxygen species increment. The results explicated that the nanoparticles shape plays an essential role in the antibacterial activity. Rotational Arc discharge machine might be a promising tool to obtain various metal nanostructures with low cost and environmentally friendly with potent activity.

Sinomenine attenuates lipopolysaccharide-induced inflammation and apoptosis of WI-38 cells by reducing glutathione S-transferase M1 expression.

Pediatric pneumonia is an infectious lung disease with high morbidity and mortality. Sinomenine, an alkaloid extracted from Caulis Sinomenii, exerts anti-inflammatory and anti-apoptotic activities. Lipopolysaccharide (LPS) is widely used for the establishment of an inflammatory model. This research aimed to explore the influences of sinomenine on LPS-caused inflammatory injuries in fetal lung WI-38 cells. WI-38 cells were treated with LPS to establish a cellular model of pediatric pneumonia. Cell viability was evaluated using CCK-8 assay. Apoptosis was evaluated using TUNEL staining and caspase-3 activity assays. Inflammatory cytokines and NF-κB p65 phosphorylation levels were measured by Enzyme-Linked Immunosorbent Assay. Glutathione S-transferase M1 (GSTM1) expression was detected by western blotting. Results showed that LPS reduced WI-38 cell viability, and sinomenine protected cells against LPS-induced viability reduction. Sinomenine concentration-dependently attenuated LPS-induced inflammation by reducing TNF-α, IL-1β and MCP-1, and increasing IL-10 levels. Sinomenine mitigated LPS-induced apoptosis. GSTM1 was screened by matching the targets of sinomenine and pediatric pneumonia. GSTM1 was upregulated in LPS-treated WI-38 cells, and this effect was attenuated after sinomenine treatment. GSTM1 was upstream of NF-κB pathway. Overexpression of GSTM1 reversed the suppressive functions of sinomenine on LPS-stimulated inflammation and apoptosis. Overall, sinomenine attenuates inflammation and apoptosis in WI-38 cells stimulated by LPS via inhibiting GSTM1 expression, indicating the therapeutic potential of sinomenine in pediatric pneumonia.

Construction and stable gene expression of AGR2xPD1 bi-specific antibody that enhances attachment between T-Cells and lung tumor cells, suppress tumor cell migration and promoting CD8 expression in cytotoxic T-cells

There has been a substantial and consistent rise in the number of clinical trials to develop advanced and potent bispecific antibodies (BsAb) over the past two decades with multiple targets to improve the efficacy or tissue specificity of monoclonal antibodies (mAb) treatment for diseases with multiple determining factors or widely-expressed targets. In this study, we designed and synthesized BsAb AGR2xPD1 targeting extracellular AGR2, a paracrine signal, and PD1, an immune checkpoint protein. Our design is intended to use AGR2 binding to guide PD1 targeting for AGR2+cancer. We used this construction to produce AGR2xPD1 BsAb by generating clonally selected stable 293F cell line with high expression. Applying this BsAb in a T cell-Tumor cell co-culture system showed that targeting both PD1 and AGR2 with this BsAb induces the attachment of TALL-104 (CD8+T-lymphocytes) cells onto co-cultured H460 AGR2+ Lung tumor cells and significantly reduces migration of H460 cells. T-cell expression of CD8 and IFNγ is also synergistically enhanced by the AGR2xPD1 BsAb treatment in the AGR2+H460 co-culture system. These effects are significantly reduced with AGR2 expression negative WI38 cells. Our results demonstrate that the AGR2xPD1 BsAb could be a potential therapeutic agent to provide better solid tumor targeting and synergetic efficacy for treating AGR2+ cancer by blocking AGR2 paracrine signaling to reduce tumor survival, and redirecting cytotoxic T-cells into AGR2+ cancer cells.

Novel pyrazole-based COX-2 inhibitors as potential anticancer agents: Design, synthesis, cytotoxic effect against resistant cancer cells, cell cycle arrest, apoptosis induction and dual EGFR/Topo-1 inhibition

Novel differently substituted pyrazole derivatives were designed, synthesized and evaluated for their anticancer activity. All compounds selectively inhibited COX-2 enzyme (IC50 = 0.043–0.56 μM). Compounds 11, 12 and 15 showed superior potency (IC50 = 0.043–0.049 μM) and screened for their antiproliferative effect against MCF-7 and HT-29 cancer cell lines using doxorubicin and 5-FU as reference drugs. Compounds 11, 12 and 15 showed good potency against MCF-7 (IC50 = 2.85–23.99 μM) and HT-29 (IC50 = 2.12–69.37 μM) cell lines. Also, compounds 11, 12 and 15 displayed (IC50 = 56.61–115.75 μM) against non-cancerous WI-38 cells compared to doxorubicin (IC50 = 13.32 μM). Compound 11 showed superior cytotoxicity against both MCF-7 (IC50 = 2.85) and HT-29 (IC50 = 2.12 μM) and was more potent than 5-FU (HT-29: IC50 = 8.77 μM). Besides, it displayed IC50 of 115.75 μM against normal WI-38 cells regarding it as a safe cytotoxic agent. In addition, compound 11 displayed IC50 values of 63.44 μM and 98.60 μM against resistant HT-29 and resistant MCF-7 cancer cell lines sequentially. The most potent compound arrested cell cycle at G1/S phase in HT-29 treated cells displaying accumulation of cells in G0 phase and increase in percentage of cells in both early and late apoptotic stages. Apoptotic induction ability was confirmed via up-regulation of BAX, down-regulation of Bcl-2 and activation of caspase-3/9 protein levels. Compound 11 inhibited both EGFR (IC50 = 0.083 μM) and Topo-1 (IC50 = 0.020 μM) enzymes. Also, compound 11 decreased both total and phosphorylated EGFR concentration in HT-29 cells. Finally, molecular docking study showed good binding interactions between novel compounds and target receptors.

In Vitro of Melaleuca viridiflora Sol. ex Gaertn Plant Investigation of Antimicrobial, Anticancer and Cytotoxic Activities

In this study; it was aimed to investigate the anticancer and cytotoxic activities on DU-145 prostate cancer and MCF-7 breast cancer cell lines and WI-38 human fibroblast cell line of essential oil (Nioli) obtained from Melaleuca viridiflora Sol. ex Gaertn. plant and its antimicrobial effects on various bacteria and yeast cells. Content analyzes of Nioli essential oil were made by Gas Chromatography-Mass Spectrometry (GK-KS). The antimicrobial effects of the essential oil were determined using Disk Diffusion and Minimum Inhibition Concentration (MIC) tests. Its cytotoxic effects were determined by the XTT (2,3-bis-(2-methoxy-4-) nitro-5)-sulfophenyl)-2H-tetrazolium-5-carboxanilide) test; were investigated at different concentrations in breast cancer (MCF-7), prostate cancer (DU-145) and healthy human fibroblast (WI-38) cell lines. In the disc diffusion method of essential oil; It was determined that it formed an inhibition zone against Klebsiella pneumoniae bacteria at 200, 100, 50, 25 and 12.5 µg/mL concentrations, and against Candida albicans yeast at 200 and 100 µg/mL concentrations. Nioli essential oil showed the highest antibacterial effect against Bacillus cereus. While it was moderately effective against Pseudomonas aeruginosa and Candida albicans, it reached MIC values effective against other bacteria. It was observed that the anticancer activity of Nioli essential oil was more effective in DU-145 prostate cancer cells compared to MCF-7 breast cancer cells, and it had no toxicity in WI-38 healthy human fibroblast cells.

Biological activities and antioxidant potential of different biosynthesized nanoparticles of Moringa oleifera

The science of nanotechnology is expanding daily and has the potential to benefit people. Moringa oleifera is an abundant source of phenolic compounds, which are bioactive substances. It is recognised as a necessary plant because of its medicinal potential and a wide variety of health benefits. The aim of the current study is to examine the antioxidant, antibacterial, and cytotoxicity effects of five nanoparticles (La2O3, CuO, Fe2O3, Ag, and ZnO) made using bioactive chemicals in the aqueous extract of Moringa oleifera leaves on four human cell lines (T47D, HepG2, A549, and Wi38). The UV–visible spectroscopy analysis with a surface plasmon peak in the 300–490 nm range and the value of the zeta potential of the various biosynthesized nanoparticles ranged from + 31 to + 37 mV, indicated the repulsion between the particles and the stability of the formulation nanoparticles confirmed the formation of all nanoparticles. Additionally, the DPPH method was used to assess the antioxidant activity of five distinct metal nanoparticles. The results show that this method works in parallel and is dependent on both the concentration of NPs and the incubation time. The anticancer effect of synthesized nanoparticles against four different cell lines has been tested. The cytotoxicity assay showed a dose-dependent and time-dependent effect of nanoparticles. The obtained results conclude that acceptable potency against T47D and A549 cell lines with IC50 ranged from 38 to 210 μg/mL and 26 to 115 μg/mL, respectively. However, HepG2 and Wi38 cell lines showed relatively higher resistance against all tested nanoparticles when compared with Doxorubicin. Moreover, the antibacterial results revealed that silver nanoparticles exhibited the highest antibacterial activity against both Enterococcus faecalis and Staphylococcus aureus. Nanoparticles' high therapeutic activity at low concentrations opens up new avenues for the development of novel therapeutic approaches against human pathogens.

Retraction.

Zang, L , Song, Y , Yu, F , Liu, X . Emodin relieved lipopolysaccharide-evoked inflammatory damage in WI-38 cells by up-regulating taurine up-regulated gene 1. BioFactors. 2020;46:860-868. https://doi.org/10.1002/biof.1609 The above article, published online on 7 January 2020 in Wiley Online Library (https://doi.org/10.1002/biof.1609), has been retracted by agreement between the International Union of Biochemistry and Molecular Biology, the Editor in Chief (Dr. Angelo Azzi), and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Evidence for image manipulation was found in figures 2, 3, and 5. As a result, the conclusions of this article are considered to be invalid.

Retraction.

Yang, P, Gao, R, Zhou, W, Han, A. Protective impacts of circular RNA VMA21 on lipopolysaccharide-engendered WI-38 cells injury via mediating microRNA-142-3p. BioFactors. 2020; 46: 381-390. https://doi.org/10.1002/biof.1593 The above article, published online on 3 December 2019 in Wiley Online Library (https://doi.org/10.1002/biof.1593), has been retracted by agreement between the International Union of Biochemistry and Molecular Biology, the Editor in Chief (Dr. Angelo Azzi), and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Evidence for image manipulation was found in figures 1, 2, 3, 4, and 6. As a result, the conclusions of this article are considered to be invalid.

Structure based design and synthesis of 3-(7-nitro-3-oxo-3,4-dihydroquinoxalin-2-yl)propanehydrazide derivatives as novel bacterial DNA-gyrase inhibitors: In-vitro, In-vivo, In-silico and SAR studies

Antimicrobial resistance (AMR) is one of the critical challenges that have been encountered over the past years. On the other hand, bacterial DNA gyrase is regarded as one of the most outstanding biological targets that quinolones can extensively inhibit, improving AMR. Hence, a novel series of 3-(7-nitro-3-oxo-3,4-dihydroquinoxalin-2-yl)propanehydrazide derivatives (3-6j) were designed and synthesized employing the quinoxaline-2-one scaffold and relying on the pharmacophoric features experienced by the quinolone antibiotic; ciprofloxacin. The antibacterial activity of the synthesized compounds was assessed via in-vitro approaches using eight different Gram-positive and Gram-negative bacterial species. Most of the synthesized compounds revealed eligible antibacterial activities. In particular, compounds 6d and 6e displayed promising antibacterial activity among the investigated compounds. For example, compounds 6d and 6e displayed MIC values of 9.40 and 9.00 µM, respectively, regarding S. aureus, and 4.70 and 4.50 µM, respectively, regarding S. pneumonia in comparison to ciprofloxacin (12.07 µM). The cytotoxicity of compounds 6d and 6e were performed on normal human WI-38 cell lines with IC50 values of 288.69 and 227.64 μM, respectively assuring their safety and selectivity. Besides, DNA gyrase inhibition assay of compounds 6d and 6e was carried out in comparison to ciprofloxacin, and interestingly, compounds 6d and 6e disclosed promising IC50 values of 0.242 and 0.177 μM, respectively, whereas ciprofloxacin displayed an IC50 value of 0.768 μM, assuring the proposed mechanism of action for the afforded compounds. Consequently, compounds 6d and 6e were further assessed via in-vivo approaches by evaluating blood counts, liver and kidney functions, and histopathological examination. Both compounds were found to be safer on the liver and kidney than the reference ciprofloxacin. Moreover, in-silico molecular docking studies were established and revealed reasonable binding affinities for all afforded compounds, particularly compound 6d which exhibited a binding score of −7.51 kcal/mol, surpassing the reference ciprofloxacin (−7.29 kcal/mol) with better anticipated stability at the DNA gyrase binding pocket. Moreover, ADME studies were conducted, disclosing an eligible bioavailability score of >0.55 for all afforded compounds, and reasonable GIT absorption without passing the blood brain barrier was attained for most investigated compounds, ensuring their efficacy and safety. Lastly, a structure activity relationship study for the synthesized compounds was established and unveiled that not only the main pharmacophores required for DNA gyrase inhibition are enough for exerting promising antimicrobial activities, but also derivatization with diverse aryl/hetero aryl aldehydes is essential for their enhanced antimicrobial potential.

CircVMA21 combining with TAF15 stabilizes SOCS3 mRNA to relieve septic lung injury through regulating NF-κB activation

BackgroundLung injury is a severe complication of sepsis, which brings great threats and challenges to human health. CircVMA21 has exhibited powerful anti- inflammation capacity. However, its underlying molecule mechanism remains blurry. MethodsLipopolysaccharide (LPS) was used to treat mice and WI-38 cells to establish models of lung injury caused by sepsis. Lung injury was evaluated using HE staining. Cell apoptosis was tested by TUNEL and flow cytometry. Levels of inflammatory cytokines were detected using ELISA assay. CircVMA21 and SOCS3 expression was measured using RT-qPCR. The ROS, MDA, SOD and GSH production were monitored by commercial kits. The protein expression was examined with western blot. The correlations among circVMA21, SOCS3 and TAF15 were confirmed using RIP and RNA-pull down. ResultsThe expression of circVMA21 and SOCS3 was downregulated in LPS-induced lung injury of mice and WI-38 cells. Overexpressing circVMA21 or SOCS3 assuaged LPS-induced cell injury through repressing the levels of inflammatory factors, oxidative stress and cell apoptosis. NF-κB signaling pathway was inactivated by circVMA21 or SOCS3 overexpression. circVMA21 enhanced the stabilization of SOCS3 mRNA via interplaying with TAF15. SOCS3 knockdown destroyed the beneficial impacts of circVMA21 overexpression on LPS-induced cell injury. ConclusionCircVMA21 suppressed LPS-induced the levels of inflammatory factors, oxidative stress and cell apoptosis and improved LPS-induced lung injury by mediating TAF15/SOCS3/NF-κB axis.

Etanercept and Infliximab, Two Tumor Necrosis Factor-α (TNF-α) Inhibitors With Different Action Profiles: An In vitro and In Vivo Study in the Context of Reviewed Therapeutic Applications

Tumor necrosis factor-α (TNF-α) is a cytotoxic cytokine in vitro. It mediates septic shock, apoptosis, and inflammation in vivo. The in vitro work was used for testing the effect of Etanercept (ETA) and Infliximab (INF) against cell cytotoxicity caused by TNF-α. At the same time, the in vivo work was used to test the effect of the two tested agents on TNF-α serum levels in rats induced by lipopolysaccharides (LPS). Upon in vitro testing of the protective effect of both agents on the WI38 cells, it was found that ETA was superior to INF for antagonizing the effect of TNF-α whether the tested agent and TNF-α were simultaneously added to the cell line or the antibody addition proceeded TNF-α addition. In vivo testing of the effect of both agents showed that they significantly antagonized the effect of TNF-α with superior effect in case of ETA whether each tested agent was administered at four doses separated by one-week interval before LPS injection or it was administered once 24 hours after LPS administration. This study gave evidence for a differential antagonizing effect of ETA and INF against TNF-α with superior action in the case of ETA when they were assessed both in vitro and in vivo.