Hanan Hassan Fouad

Hepatic fibrosis is one of the major worldwide health concerns which requires tremendous research due to the limited outcomes of the current therapies. The present study was designed to assess, for the first time, the potential therapeutic effect of rupatadine (RUP) in diethylnitrosamine (DEN)-induced liver fibrosis and to explore its possible mechanistic actions. For the induction of hepatic fibrosis, rats were treated with DEN (100 mg/kg, i.p.) once weekly for 6 consecutive weeks, and on the 6th week, RUP (4 mg/kg/day, p.o.) was administered for 4 weeks. Treatment with RUP ameliorated changes in body weights, liver indices, liver function enzymes, and histopathological alterations induced by DEN. Besides, RUP amended oxidative stress, which led to the inhibition of PAF/NF-κB p65-induced inflammation, and, subsequently, prevention of TGF-β1 elevation and HSCs activation as indicated by reduced α-SMA expression and collagen deposition. Moreover, RUP exerted significant anti-fibrotic and anti-angiogenic effects by suppressing Hh and HIF-1α/VEGF signaling pathways. Our results highlight, for the first time, a promising anti-fibrotic potential of RUP in rat liver. The molecular mechanisms underlying this effect involve the attenuation of PAF/NF-κB p65/TGF-β1 and Hh pathways and, subsequently, the pathological angiogenesis (HIF-1α/VEGF).

Oral squamous-cell carcinoma (OSCC) is a widespread health problem. Myeloid-derived suppressor cells (MDSCs) are major tumor microenvironment (TME) population that govern many carcinogenesis aspects by establishing immunosuppressive milieu favoring tumor aggressiveness and treatment resistance. Cyclooxygenase-2 (COX-2) regulates MDSCs activity, hence, COX-2-selective inhibition by celecoxib (CXB) showed good anticancer effect at relatively high doses with possible subsequent cardiovascular complications. Therefore, targeted CXB delivery to MDSCs may represent a promising OSCC treatment strategy. Novel mucoadhesive-cubosomal buccal sponges were prepared for MDSCs targeting and were evaluated for their in-vitro quality attributes, ex-vivo mucoadhesion using buccal chicken-mucosa. Optimally-selected formulation showed considerable uptake by CD33/11bMDSCs in human OSCC cell-line (SCC-4) when quantitatively analyzed by flow-cytometry and examined using confocal-laser microscope. Optimum formulations loaded with low CXB doses (12 mg) were promoted to in-vivo studies via local application, using 4-nitroquinoline-1-oxide-induced OSCC in rats, and compared to their corresponding CXB gels. SP16 revealed the highest ability to decrease MDSC activation, recruitment and TME-immunosuppression in the isolated tumors. Consequently, SP16 exerted the greatest capacity to reduce histologic tumor grade, the OSCC-specific serum tumor markers levels, cancer hallmarks and stemness markers. CXB-loaded cubosomal sponges preferentially target MDSCs with noticeable anticancer potential and may exemplify novel mucoadhesive nanocarriers for OSCC treatment.

In this study, a novel technique for enhancing the output power of Vertical Axis Wind Turbines (VAWTs) is introduced through the integration of a cross-flow fan (CFF) for active flow control, a first-of-its-kind approach. The CFF, positioned on the airfoil's trailing edge, employs suction to regulate flow separation. A thick airfoil with a 35% thickness-to-chord ratio is utilized to accommodate the CFF. A VAWT, featuring a diameter of 1 m and a height of 0.5 m, is designed, fabricated, and subjected to experimental testing in a wind tunnel. Additionally, a standard NACA 0018 wind turbine with identical dimensions and solidity is manufactured for performance comparison purposes. A custom test rig is developed to measure turbine output, encompassing a fixation mechanism, torque measurement system, and a mechanical brake mechanism for load variation. The impact of the CFF on the wind turbine performance is investigated by measuring turbine static torque due to the fan, fan motor power consumption, turbine torque, and rotational speed across various wind speeds. Power assessments are conducted to estimate the real turbine power increase, taking into account the power consumed by the fans. A fan map is generated to determine the optimal conditions and rotational speeds for fan operation.

The large popularity and rapid technology of smartphones have opened new avenues for their integration into different analytical methodologies and drug quality monitoring as a portable, easily accessible, and user-friendly detector. Herein, a novel and portable smartphone-based high-performance thin layer chromatographic (HPTLC) approach is proposed for the simultaneous analysis of two urological drugs, alfuzosin and solifenacin, which treat benign prostatic hyperplasia accompanied by overactive bladder syndrome. First, chromatographic separation was accomplished using an ecofriendly mobile phase, then the developed plates were visualized using Dragendorff's reagent and photographed a smartphone's rear-facing camera fixed on a fabricated two-illumination-source chamber. The intensities of the drug spots were quantified using open-source image analysis software ImageJ over the concentration ranges of 2.0 to 30.0 μg per band for both drugs with acceptable results in ICH validation parameters. To improve the method's accuracy and reproducibility, various construction and shooting key parameters were investigated and optimized. Moreover, the study was extended to compare the obtained results with those of a benchtop densitometric method using a Camag TLC Scanner 3 at 215.0 nm; the densitometric method provided an additional assessment tool for peak purity and was capable of assaying lower drug concentrations over a linearity range of 0.2-8.0 μg per band for alfuzosin and 0.1-6.0 μg per band for solifenacin. The fast, simple, reliable, green merits of the proposed HPTLC/smartphone method suggest that it is an excellent platform for assaying marketed combined capsules and assuring their content uniformity. Moreover, the high sensitivity of the densitometric method was used, for the first time, to determine the residual content of the cited drugs on manufacturing equipment surfaces for cleaning validation. Finally, the environmental impact of the developed methods was evaluated based on green analytical chemistry principles.