Aboul Ella Hassanien (Abo)

BACKGROUND: Bevacizumab (Bev) resistance is hypothesized to be overcome by combination with inhibitors of other signalling pathways.

OBJECTIVE: We aimed to study the effect of combining Bev with knocked down β-catenin (Bev-β-cat-siRNA) on the expression of VEGF-A, Slug, NFКB and its two target genes c-Flip and FasR in HepG2. Expression of VEGF-A and Slug was also studied in Caco-2 cells.

METHODS: Cultured cells were divided into six groups 1) cells treated with Bev only 2) cells treated with β-catenin-siRNA 3) cells treated with Bev-β-cat-siRNA 4) cells treated with negative control 5) cells treated with Bev-negative control and untreated cells. Expressions were assessed using qPCR and western blotting.

RESULTS: Bev-β-cat-siRNA significantly reduced the mRNA level of VEGF-A, which was initially increased in response to Bev alone in HepG2 but not in Caco-2. Additionally, Bev-β-cat-siRNA significantly decreased Slug mRNA level compared to Bev only treated HepG2 cells. In contrast, VEGF-A and Slug mRNA levels in Bev only group were remarkably lower than Bev-β-cat-siRNA in Caco-2 cells. Distinct β-catenin and Slug protein expressions were noticed in HepG2 and Caco-2 cells. On the other hand, Bev-β-cat-siRNA remarkably reduced the level of NFКB, FasR and c-Flip compared to Bev only treated HepG2 cells although the difference was not statistically significant.

CONCLUSION: We conclude that, combining Bevacizumab with knocked down β-catenin reduce the expression of VEGF-A and Slug in HepG2 but not in Caco-2 cells.

Harmonic pollution is one of the challenging problems facing power networks recently due to the widespread non-linear loads and inverter-based renewables. In this regard, this work presents the optimal design of damped and undamped passive filters using a solver called Mixed-Integer Distributed Ant Colony Optimisation (MIDACO). This solver is employed to obtain an optimal design strategy for single-tuned passive power filters by investigating three primary criteria – minimisation of active power losses of the Thevenin’s resistor, maximisation of the true power factor, and maximisation of the transmission efficiency. Several constrictions associated with the designed filters have been considered, in which the global maximum or minimum criterion was attained by retaining the quality factors of the designed filters within a particular range, damping harmonic resonance, achieving a permissible range of the power factor, limiting voltage harmonic distortion by complying with IEEE Std. 519–2014 restrictions. Besides, the performance limits of capacitors operating in distorted systems have been met while complying with IEEE Std. 18–2012. Further, the results obtained using the MIDACO solver in four different case studies are compared to those obtained using particle swarm optimisation and genetic algorithm. In addition, this work depicts the damping resistor of the inductance in the single-tuned filters. The benefits and drawbacks of damping over an undamped filter are discussed. Finally, the results validate the effectiveness of the MIDACO solver employed in this paper.

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Pesticides are viewed as a major wellspring of ecological contamination and causing serious risky consequences for people and animals. Imidacloprid (IM) and hexaflumuron (HFM) are extensively utilized insect poisons for crop assurance on the planet. A few investigations examined IM harmfulness in rodents, but its exact mechanism hasn't been mentioned previously as well as the toxicity of HFM doesn't elucidate yet. For this reason, the present study was designed to explore the mechanism of each IM and HFM-evoked rat liver and kidney toxicity and to understand its molecular mechanism. 21 male Wistar albino rats were divided into 3 groups, as follows: group (1), normal saline; group (2), IM; and group (3), HFM. Both insecticides were orally administered every day for 28 days at a dose equal to 1/10 LD50 from the active ingredient. After 28 days postdosing, rats were anesthetized to collect blood samples then euthanized to collect liver and kidney tissue specimens. The results showed marked changes in walking, body tension, alertness, and head movement with a significant reduction in rats' body weight in both IM and HFM receiving groups. Significant increases in MDA levels and decrease of GHS levels were recorded in liver and kidney homogenates of either IM or HFM groups. Liver and kidney tissues obtained from both pesticide receiving groups showed extensive histopathological alterations with a significant increase in the serum levels of ALT, AST, urea, and creatinine and a decrease in total proteins, albumin, and globulin levels. In addition, there was upregulation of the transcript levels of casp-3, JNK, and HO-1 genes with strong immunopositivity of casp-3, TNF-ὰ, and NF-B protein expressions in the liver and kidneys of rats receiving either IM or HFM compared with the control group. In all studied parameters, HFM caused hepatorenal toxicity more than those induced by IM. We can conclude that each IM and HFM provoked liver and kidneys damage through overproduction of ROS, activation of NF-B signaling pathways and mitochondrial/JNK-dependent apoptosis pathway.