Zoledronic acid induces apoptosis via stimulating the expressions of ERN1, TLR2, and IRF5 genes in glioma cells

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor that affects older people. Although the current therapeutic approaches for GBM include surgical resection, radiotherapy, and chemotherapeutic agent temozolomide, the median survival of patients is 14.6 months because of its aggressiveness. Zoledronic acid (ZA) is a nitrogen-containing bisphosphonate that exhibited anticancer activity in different cancers. The purpose of this study was to assess the potential effect of ZA in distinct signal transduction pathways in U87-MG cells. In this study, experiments performed on U87-MG cell line (Human glioblastoma-astrocytoma, epithelial-like cell line) which is an in vitro model of human glioblastoma cells to examine the cytotoxic and apoptotic effects of ZA. IC50 dose of ZA, 25 μM, applied on U87-MG cells during 72 h. ApoDIRECT In Situ DNA Fragmentation Assay was used to investigate apoptosis of U87MG cells. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) (LightCycler480 System) was carried out for 48 gene expression like NF-κB, Toll-like receptors, cytokines, and inteferons. Our results indicated that ZA (IC50 dose) increased apoptosis 1.27-fold in U87MG cells according to control cells. According to qRT-PCR data, expression levels of the endoplasmic reticulum-nuclei-1 (ERN1), Toll-like receptor 2 (TLR2), and human IFN regulatory factor 5 (IRF5) tumor suppressor genes elevated 2.05-, 2.08-, and 2.3-fold by ZA, respectively, in U87MG cells. Our recent results indicated that ZA have a key role in GBM progression and might be considered as a potential agent in glioma treatment. © 2015, International Society of Oncology and BioMarkers (ISOBM)

Tackling ionospheric scintillation threat to GNSS in Latin America

Scintillations are rapid fluctuations in the phase and amplitude of transionospheric radio signals which are caused by small-scale plasma density irregularities in the ionosphere. In the case of the Global Navigation Satellite System (GNSS) receivers, scintillation can cause cycle slips, degrade the positioning accuracy and, when severe enough, can even lead to a complete loss of signal lock. Thus, the required levels of availability, accuracy, integrity and reliability for the GNSS applications may not be met during scintillation occurrence; this poses a major threat to a large number of modern-day GNSS-based applications. The whole of Latin America, Brazil in particular, is located in one of the regions most affected by scintillations. These effects will be exacerbated during solar maxima, the next predicted for 2013. This paper presents initial results from a research work aimed to tackle ionospheric scintillation effects for GNSS users in Latin America. This research is a part of the CIGALA (Concept for Ionospheric Scintillation Mitigation for Professional GNSS in Latin America) project, co-funded by the EC Seventh Framework Program and supervised by the GNSS Supervisory Authority (GSA), which aims to develop and test ionospheric scintillation countermeasures to be implemented in multi-frequency, multi-constellation GNSS receivers

Metabolic Network-Based Identification and Prioritization o f Anticancer Targets Based on Expression Data in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a deadly form of liver cancer with high mortality worldwide. Unfortunately, the large heterogeneity of this disease makes it difficult to develop effective treatment strategies. Cellular network analyses have been employed to study heterogeneity in cancer, and to identify potential therapeutic targets. However, the existing approaches do not consider metabolic growth requirements, i.e., biological network functionality, to rank candidate targets while preventing toxicity to non-cancerous tissues. Here, we developed an algorithm to overcome these issues based on integration of gene expression data, genome-scale metabolic models, network controllability, and dispensability, as well as toxicity analysis. This method thus predicts and ranks potential anticancer non-toxic controlling metabolite and gene targets. Our algorithm encompasses both objective-driven and-independent tasks, and uses network topology to finally rank the predicted therapeutic targets. We employed this algorithm to the analysis of transcriptomic data for 50 HCC patients with both cancerous and non-cancerous samples. We identified several potential targets that would prevent cell growth, including 74 anticancer metabolites, and 3 gene targets (PRKACA, PGS1, and CRLS1). The predicted anticancer metabolites showed good agreement with existing FDA-approved cancer drugs, and the 3 genes were experimentally validated by performing experiments in HepG2 and Hep3B liver cancer cell lines. Our observations indicate that our novel approach successfully identifies therapeutic targets for effective treatment of cancer. This approach may also be applied to any cancer type that has tumor and non-tumor gene or protein expression data

A focusing study on radioprotective and antioxidant effects of Annona muricata leaf extract in the circulation and liver tissue: Clinical and experimental studies

Objectives: This study investigates the effect of Annona muricata (AM) leaf extract against irradiation-induced damage by the evaluation of hepatic tissue and the levels of oxidative and inflammatory stress in the circulation. Methods: An experimental study with 37 female Wistar albino rats randomized into four groups (controls and three intervention groups) was performed. The first interventional group (group 2) received 300 mg/kg of AM leaf extract by oral gavage once a day for 9 days, group 3 received a single dose of whole-body radiation (8.3 Gy) after a 9-day oral gavage treatment with saline, and the last group received the same irradiation of 8.3 Gy after being treated with 300 mg/kg of AM leaf extract by oral gavage once a day for 9 days. Results: Radiation was found to elevate reactive oxygen species parameters, and AM administration before irradiation was found to decrease total oxidant status (TOS), increase caspase 9, and improve hepatic damage when compared with the group that received only irradiation. Conclusion: The damage caused by irradiation may be ameliorated by the use of the AM extract, which appears to be effective in preventing oxidative stress and inflammatory activity. © 2022 Ozlem Elmas et al.Dunarea de Jos” University of GalatiUniversitatea 'Dunărea de Jos' Galați, UDJG, (RF 3621/2021)Funding text 1: Author contributions: O.E., H.H.K.S., H.O.T.: conceptualization and methodologyM.A., W.E., G.A.: validationG.A. and H.M.H.Z.: formal analysisO.E., H.H.K.S., B.G., H.O.T.: writing and reviewO.E., H.H.K.S., B.G., A.E., M.A., W.E.: investigationA.E.: funding acquisition through APC by “Dunarea de Jos” University of Galati, Romania through the grant no. RF 3621/2021.Funding text 2: Funding information: The work of Antoaneta ENE and the APC were supported by Dunarea de Jos University of Galati, Romania through the grant no. RF 3621/2021

Clinical comprehensive and experimental assessment of the radioprotective effect of Annona muricata leaf extract to prevent cellular damage in the ileum tissue

We report the radioprotective attitude of Annona muricata (AM) leaf extract as antioxidant material to prevent cellular damage in the ileum tissue. The protective effects of an ethyl acetate extract of AM leaves are comprehensively investigated against radiation-induced ileal damage in numerous rats. Thirty-two adult female rats were separated into 4 groups (3 intervention groups and 1 control) as follows: controls received 0.01 mL/kg distilled water, the AM group received 300 mg/kg AM leaf extract, the ionizing radiation (IR) group received a single dose of whole body radiation (8.3 Gy) after 0.01 mL/kg saline treatment, and the AM + IR group received 300 mg/kg AM leaf extract treatment and were subjected to whole body radiation (8.3 Gy) 1 h after the last gavage. All treatments are administered by oral gavage once a day for 9 days. At the end of the experiment, biochemical total oxidant status (TOS, interleukin-6, and caspase) and histological examinations are performed on blood samples as well as ileum tissue. TOS levels are found to be significantly high in rats, which received irradiation, and those in the AM group when compared to controls. These findings suggest that AM has radioprotective effects on ileum tissue, likely because of its antioxidative properties. The findings of this research may contribute to the minimizing of major side effects induced by excessive radiation exposure in patients undergoing radiotherapy and may serve as a significant impetus for further assessments. However, future studies are highly recommended to confirm safety and to determine extraction technique and dosage before human use can be considered. © 2022 Ozlem Elmas et al.Dunarea de Jos” University of Galati, (RF 3621/2021)Universitatea 'Dunărea de Jos' Galați, UDJGFunding text 1: Funding information: The work of Antoaneta ENE and the APC were supported by Dunarea de Jos University of Galati, Romania through the grant no. RF 3621/2021.Funding text 2: Author contributions: O.E., H.H.K.S., and H.O.T.: – conceptualization and methodologyE.K., B.G., G.A., and R.U.E.: validationG.A. and H.M.H.Z.: formal analysisO.E., H.H.K.S., E.K., B.G., and H.O.T.: writing and reviewO.E., H.H.K.S., E.K., B.G., and A.E.: investigationA.E.: funding acquisition through APC by “Dunarea de Jos” University of Galati, Romania through the grant no. RF 3621/2021

Five-frequency Galileo long-baseline ambiguity resolution with multipath mitigation

© 2018, The Author(s). For long-baseline over several hundreds of kilometers, the ionospheric delays that cannot be fully removed by differencing observations between receivers hampers rapid ambiguity resolution. Compared with forming ionospheric-free linear combination using dual- or triple-frequency observations, estimating ionospheric delays using uncombined observations keeps all the information of the observations and allows extension of the strategy to any number of frequencies. As the number of frequencies has increased for the various GNSSs, it is possible to study long-baseline ambiguity resolution performance using up to five frequencies with uncombined observations. We make use of real Galileo observations on five frequencies with a sampling interval of 1 s. Two long baselines continuously receiving signals from six Galileo satellites during corresponding test time intervals were processed to study the formal and empirical ambiguity success rates in case of full ambiguity resolution (FAR). The multipath effects are mitigated using the measuremen ts of another day when the constellation repeats. Compared to the results using multipath-uncorrected Galileo observations, it is found that the multipath mitigation plays an important role in improving the empirical ambiguity success rates. A high number of frequencies are also found to be helpful to achieve high ambiguity success rate within a short time. Using multipath-uncorrected observations on two, three, four and five frequencies, the mean empirical success rates are found to be about 73, 88, 91, and 95% at 10 s, respectively, while the values are increased to higher than 86, 95, 98, and 99% after mitigating the multipath effects