The beneficial role of SIRT1 activator on chemo- and radiosensitization of breast cancer cells in response to IL-6.

Tumor environmental cytokines, such as IL-6, has a major role in the outcome of radiation and chemotherapy. In this study, we hypothesized that IL-6 mediates its effects via SIRT1 as a protein deacetylase and activator of phosphatidylinositol-3 kinase pathways. In the present study, we evaluated the effects of the novel dual inhibitor of phosphatidylinositol-3 kinase/mammalian target of rapamycin, NVP-BEZ235, and SIRT1 inhibitor and activator plus radiotherapy in breast cancer cells treated with IL-6. Here, IL-6 untreated/pretreated human breast cancer cells were cultured with single or combination of NVP-BEZ235 and/or SIRT1 activator (SRT1720)/inhibitor (EX-527) under radiotherapy condition. After all treatments, the MTT assay and flow cytometry assay were used to explore cell viability and the ability of our treatments in altering cancer stem cells (CSCs) population or cellular death (apoptosis + necrosis) induction. Simultaneous exposure to NVP-BEZ235 and SRT1720 sensitized breast cancer cells to radiotherapy but elevated CSCs. Treatment with IL-6 for 2 weeks significantly decreased CSCs population. Activation of SIRT1 via SRT1720 in combination with NVP-BEZ235 significantly decreased breast cancer cells viability in IL-6 pretreatment cultures. Inhibition of SIRT1 via EX-527 diminished the beneficial effects of IL-6 pretreatment. The combination of NVP-BEZ235 and SRT1720 as a SIRT1 activation could effectively decrease breast cancer cells population and augments the efficacy of radiotherapy.

Molecular detection of six virulence genes in Pseudomonas aeruginosa isolates detected in children with urinary tract infection.

Although a vast majority of Urinary tract infections (UTIs) are caused by E. coli, epidemiological reports have indicated an increasing rate of such infections caused by some other opportunistic organisms including Pseudomonas aeruginosa. Antimicrobial susceptibility and pathogenesis mechanisms of P. aeruginosa are poorly understood. The aim of this study was to detect some virulence factor genes and antimicrobial susceptibility patterns of P. aeruginosa isolates detected in patients with UTI, in children hospital of Tehran, Tehran, Iran. Eighty-four Pseudomonas aeruginosa were isolated. Then, the presence of six virulence genes, in the genome of the isolates was evaluated using PCR amplifications techniques. Finally, antimicrobial susceptibility pattern of the isolates was determined by disk diffusion method. According to the results, lasB was the most prevalent virulence gene that could be detected in the P. aeruginosa isolates (92.9%) used in this study. This was followed by aprA (81.2%), toxA (69.4%), and algD (60%) genes. Two genes, plcH and plcN, were detected in about 38.8% of the isolates. Additionally, Imipenem was found as the most active agent against the P. aeruginosa isolates used in this research. However, Cefotaxime resistance was observed in most of the isolates. Our P. aeruginosa isolates exhibited a great degree of heterogeneity not only in their virulence genes but also in their antimicrobial susceptibility profiles. Imipenem therapies tend to be among the best choices in the management of UTI caused by P. aeruginosa. As a conclusion, assessment of antimicrobial susceptibility pattern and also analyzing the virulence factors can be highly helpful to develop effective treatment strategies against P. aeruginosa urinary infections.

Electrochemical study of 2-amino-5-mercapto-1,3,4-thiadiazole in the absence and presence of p-benzoquinone: an efficient strategy for the electrosynthesis of new 1,3,4-thiadiazole derivatives.

In this study, first, the electrochemical behavior of 2-amino-5-mercapto-1,3,4-thiadiazole (AMT) was fully investigated in the absence and presence of electrochemically generated p-benzoquinone (p-BQ, which is the oxidized form of hydroquinone), as an electrophile, via cyclic voltammetry (CV) at a glassy carbon electrode (GCE) and in an acetic acid buffer (0.2 M)/ethanol solution mixture. Then, an E-pH diagram was proposed for different structures of AMT at various pH values. The obtained voltammograms also exhibited an "electron transfer + chemical reaction" (EC) mechanism. Besides the voltammetric exploration, electrosynthesis of new 1,3,4-thiadiazole derivatives was conducted by constant current electrolysis (CCE) as a facile and cost-effective method for the formation of S-S and S-C bonds. Finally, the biological activity of products was also analyzed via an in silico method.

Green electrochemical method for the synthesis of nitro and azo derivatives based on mefenamic acid.

Electrochemical study of mefenamic acid (MFA) was carried out with details in water/ethanol mixture by the various voltammetric techniques. The results showed that the oxidation of MFA is highly dependent on pH and follows the Eir mechanism. The EpA1-pH diagram plotted based on the differential pulse voltammograms shows two linear segments, 66 and 26 mV/pH slope. Also, the diffusion coefficient and the surface excess, Ó¶* of MFA in aqueous buffered solution, determined by using the single potential-step chronoamperometry and chronocoulometry methods. Electrochemical nitration of MFA in an aqueous solution and the presence of nitrite ion (1) were both investigated by the cyclic voltammetry and controlled-potential coulometry techniques. Our results indicate that the oxidized form of MFA participates in a Michael-type addition reaction with nitrite ion (1) to form the corresponding Nitromefenamic acids (MFA-4-NO2 and MFA-5-NO2). Also, in another part, a computational study based on the density functional theory (DFT/B3LYP) was performed for the prediction of the best possible pathway in the nucleophilic addition of nitrite ion (1). The electrochemical reduction of produced nitromefenamic acids was investigated using cyclic voltammetry and controlled-potential coulometry techniques. Eventually, two new azo derivatives have been generated via electroreduction of produced nitromefenamic acids and conduction of diazotization reaction, respectively. Both nitro and azo products are approved as paints.

Automatic generation of structural geometric digital twins from point clouds.

A geometric digital twin (gDT) model capable of leveraging acquired 3D geometric data plays a vital role in digitizing the process of structural health monitoring. This study presents a framework for generating and updating digital twins of existing buildings by inferring semantic information from as-is point clouds (gDT's data) acquired regularly from laser scanners (gDT's connection). The information is stored in updatable Building Information Models (BIMs) as gDT's virtual model, and dimensional outputs are extracted for structural health monitoring (gDT's service) of different structural members and shapes (gDT's physical part). First, geometric information, including position and section shape, is obtained from the acquired point cloud using domain-specific contextual knowledge and supervised classification. Then, structural members' function and section family type is inferred from geometric information. Finally, a BIM is automatically generated or updated as the virtual model of an existing facility and incorporated within the gDT for structural health monitoring. Experiments on real-world construction data are performed to illustrate the efficiency and precision of the proposed model for creating as-is gDT of building structural members.

Determine the Dose Distribution Using Ultrasound Parameters in MAGIC-f Polymer Gels.

In this study, using methacrylic and ascorbic acid in gelatin initiated by copper (MAGIC-f) polymer gel after megavoltage energy exposure, the sensitivity of the ultrasound velocity and attenuation coefficient dose-dependent parameters was evaluated. The MAGIC-f polymer gel was irradiated under 1.25 MeV cobalt-60, ranging from 0 to 60 Gy in 2-Gy steps, and received dose uniformity and accuracy of ±2%. After calibration of the ultrasonic systems with a frequency of 500 kHz, the parameters of ultrasound velocity and attenuation coefficient of the irradiated gel samples were measured. According to the dose-response curve, the ability of ultrasonic parameters was evaluated in dose rate readings. Based on a 4-order polynomial curve, fitted on the dose-response parameters of ultrasound velocity and attenuation coefficient and observed at 24 hours after irradiation, ultrasonic parameters had more sensitivity. The sensitivity of the dose-velocity and dose-attenuation coefficient curves was observed as 50 m/s/Gy and 0.06 dB/MHz/Gy over the linear range of 4 to 44 Gy, respectively. The ultrasonic parameters at 5°C, 15°C, and 25°C on the gel dosimeter after 0 to 60 Gy irradiation showed that readings at 25°C have higher sensitivity compared to 15°C and 5°C. Maximum sensitivity time and temperature readings of the MAGIC-f ultrasonic parameters were concluded 24 hours after irradiation and at a temperature of 25°C.