Staphylococcus aureus enterotoxin b down-regulates the expression of transforming growth factor-beta (TGF-β) signaling transducers in human glioblastoma

Background: It has been revealed that Staphylococcus aureus enterotoxin B (SEB) may feature anti-cancer and anti-metastatic advantages due to its ability to modify cell immunity processes and signaling pathways. Glioblastoma is one of the most aggressive human cancers; it has a high mortality nature, which makes it an attractive area for the development of novel therapies. Objectives: We examined whether the SEB could exert its growth inhibitory effects on glioblastoma cells partially through the manipulation of a key tumor growth factor termed transforming growth factor-beta (TGF-β). Materials and Methods: A human primary glioblastoma cell line, U87, was treated with different concentrations of SEB. The cell quantity was measured by the MTT assay at different exposure times. For molecular assessments, total ribonucleic acid (RNA) was extracted from either non-treated or SEB-treated cells. Subsequently, the gene expression of TGF-β transducers, smad2/3, at the messenger RNA (mRNA) level, was analyzed via a quantitative real-time polymerase chain reaction (qPCR) using the SYBR Green method. Significant differences between cell viability and gene expression levels were determined (Prism 5.0 software) using a one-way analysis of variance (ANOVA) test. Results: We reported that SEB could effectively down-regulate smad2/3 expression in glioblastoma cells at concentrations as quantity as 1 µg/mL and 2 µg/mL (P < 0.05 and P < 0.01, respectively). The SEB concentrations effective at regulating smad2/3 expression were correlated with those used to inhibit the proliferation of glioblastoma cells. Our results also showed that SEB was able to decrease smad2/3 expression at the mRNA level in a concentration- and time-dependent manner. Conclusions: We suggested that SEB could represent an agent that can significantly decrease smad2/3 expression in glioblastoma cells, leading to moderate TGF-β growth signaling and the reduction of tumor cell proliferation. © 2016, Ahvaz Jundishapur University of Medical Sciences

Large-scale magnetic fields from inflation due to a CPTCPT-even Chern-Simons-like term with Kalb-Ramond and scalar fields

We investigate the generation of large-scale magnetic fields due to the breaking of the conformal invariance in the electromagnetic field through the $CPT$-even dimension-six Chern-Simons-like effective interaction with a fermion current by taking account of the dynamical Kalb-Ramond and scalar fields in inflationary cosmology. It is explicitly demonstrated that the magnetic fields on 1Mpc scale with the field strength of $\sim 10^{-9}$G at the present time can be induced.Comment: 18 pages, 6 figures, version accepted for publication in Eur. Phys. J.

Business analytics in industry 4.0: a systematic review

Recently, the term “Industry 4.0” has emerged to characterize several Information Technology and Communication (ICT) adoptions in production processes (e.g., Internet-of-Things, implementation of digital production support information technologies). Business Analytics is often used within the Industry 4.0, thus incorporating its data intelligence (e.g., statistical analysis, predictive modelling, optimization) expert system component. In this paper, we perform a Systematic Literature Review (SLR) on the usage of Business Analytics within the Industry 4.0 concept, covering a selection of 169 papers obtained from six major scientific publication sources from 2010 to March 2020. The selected papers were first classified in three major types, namely, Practical Application, Reviews and Framework Proposal. Then, we analysed with more detail the practical application studies which were further divided into three main categories of the Gartner analytical maturity model, Descriptive Analytics, Predictive Analytics and Prescriptive Analytics. In particular, we characterized the distinct analytics studies in terms of the industry application and data context used, impact (in terms of their Technology Readiness Level) and selected data modelling method. Our SLR analysis provides a mapping of how data-based Industry 4.0 expert systems are currently used, disclosing also research gaps and future research opportunities.The work of P. Cortez was supported by FCT - Fundação para a Ciência e Tecnologia within the R&D Units Project Scope: UIDB/00319/2020. We would like to thank to the three anonymous reviewers for their helpful suggestions

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Peer reviewe

The comparison of fennel infusion plus dry cupping versus metformin in management of oligomenorrhoea in patients with polycystic ovary syndrome: a randomised clinical trial

Oligomenorrhoea treatment with hormone therapy and Metformin is not usually well tolerated and is associated with a broad range of side effects. In Persian medicine, the management of oligomenorrhoea can be done with fennel and dry cupping. A clinical trial was conducted on 61 patients with oligomenorrhoea. The patients randomly received treatment for 6 months in two groups: fennel infusion plus dry cupping (Group A); versus treatment with Metformin (Group B). On the days between the two periods, the patients� BMI, pain levels and side effects were assessed. Thirty-one patients (mean age: 26.68) in Group A, and 30 patients (mean age: 28.90) in Group B were enrolled. The mean numbers of days between the two periods after 3 and 6 months in Group A was, respectively, 32.59 and 30.69, versus 40.66 and 431.22 in Group B. The mean pain severity dropped significantly in Group A. Fennel seed infusion plus a dry cupping uses a safe and effective therapeutic intervention in the management of oligomenorrhoea.IMPACT STATEMENTWhat is already known on this subject? Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women. Some common clinical manifestations of this syndrome include menstrual disorders such as oligomenorrhoea and amenorrhoea. The recommended therapeutic interventions include oral intervention, as well as metformin, which are associated with an increased risk of vascular thromboembolism, digestive complications such as nausea, and dizziness, and vitamin B12 deficiency. Therefore, the use of complementary medicine in controlling and treating PCOS is considered a valuable intervention in conventional medicine. In Persian traditional medicine, medicinal fennel (with the scientific name of Foeniculum Vulgare Mill) is commonly used in this regard. The practice of dry cupping during the monthly period that ends with ovulation is also recommended. What do the results of this study add? The present study concludes that fennel seed infusion plus a dry cupping therapy is effective and safe in reducing the days between two menstrual periods and manages oligomenorrhoea. What are the implications of these findings for clinical practice and/or further research? A clinical study is suggested for assessing the effect of fennel seed infusion plus dry cupping on oligomenorrhoea, with a large sample size and a longer follow up time. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group

Silybin as a potent inhibitor of a-synuclein aggregation and associated cytotoxicity against neuroblastoma cells induced by zinc oxide nanoparticles

a-synuclein (a-syn) amyloid fibrils, the leading neurotoxic types, are predominately formed through interaction with nanoparticles (NPs). However, some natural compounds like silybin can reduce the formation of NPs-induced amyloid fibrils and related cytotoxicity. Herein, we assayed the ZnO-induced a-syn amyloid fibril formation and underlying cytotoxicity in the absence and presence of silybin using a wide range of multispectroscopic (ThT fluorescence, Congo red absorbance, and CD), TEM, and cellular (MTT, LDH, ROS, and caspase-3) approaches. Spectroscopy data and TEM investigation showed that ZnO NPs accelerate the induction of a-syn amyloid fibrils in the amyloidogenic conditions. However, silybin as a bioactive compound can result in inhibition of a-syn fibrillogenesis induced by ZnO NPs. The potent inhibitory impact of silybin on cytotoxicity of a-syn amyloid fibrils induced by ZnO NPs was also assessed by cellular assays. It was depicted that the mortality, LDH release, ROS production, and caspase-3 activity upon addition of silybin were less than those reported in absence of this small molecule. These outcomes revealed that silybin is of great importance as neuroprotective and therapeutic small molecules for NP-induced protein aggregation and related cytotoxicity.Scopu

Hydrothermal method-based synthesized tin oxide nanoparticles: Albumin binding and antiproliferative activity against K562 cells

The interaction of nanoparticles with protein and cells may provide important information regarding their biomedical implementations. Herein, after synthesis of tin oxide (SnO2) nanoparticles by hydrothermal method, their interaction with human serum albumin (HSA) was evaluated by multispectroscopic and molecular docking (MD) approaches. Furthermore, the selective antiproliferative impact of SnO2 nanoparticles against leukemia K562 cells was assessed by different cellular assays, whereas lymphocytes were used as control cells. TEM, DLS, zeta potential and XRD techniques showed that crystalline SnO2 nanoparticles have a size of less than 50 nm with a good colloidal stability. Fluorescence and CD spectroscopy analysis indicated that the HSA undergoes some slight conformational changes after interaction with SnO2 nanoparticles, whereas the secondary structure of HSA remains intact. Moreover, MD outcomes revealed that the charged residues of HSA preferentially bind to SnO2 nanoclusters in the binding pocket. Antiproliferative examinations displayed that SnO2 nanoparticles can selectively cause the mortality of K562 cells through induction of cell membrane leakage, activation of caspase-9, -8, -3, down regulation of Bcl-2 mRNA, the elevation of ROS level, S phase arrest, and apoptosis. In conclusion, this data may indicate that SnO2 nanoparticles can be used as promising particles to be integrated into therapeutic platforms.Scopu

Exploring the interaction of quercetin-3-O-sophoroside with SARS-CoV-2 main proteins by theoretical studies: A probable prelude to control some variants of coronavirus including Delta

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2?s proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variantsScopu