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  • Kenny posted an update 9 months ago

    With an improvement in the survival rate of cancer patients, chemotherapy-induced premature ovarian insufficiency (POI) is increasingly affecting the quality of life of female patients. Currently, there are many relevant studies using mice as an animal model. However, a large coefficient of variation for weight in mice is not appropriate for endocrine-related studies, compared with rats; therefore, it is necessary to identify an appropriate experimental model in rats. In this study, cyclophosphamide combined with busulfan was used to establish an animal model. We compared several common modeling methods using chemotherapeutic drugs, cisplatin, cyclophosphamide, and 4-vinylcyclohexene diepoxide (VCD), and we found that the combination of cyclophosphamide and busulfan was more effective in establishing a POI model in rats with few side effects by analyzing general physical conditions, pathological tissue sections of heart, liver, lung, spleen, kidney, uterus, and ovary, serum hormone levels, and follicle counts; thus, providing a more reliable model basis for subsequent studies.The indispensable role of Beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) in Amyloid beta (Aβ) plaques generation and Aβ-mediated synaptic dysfunctions makes it a crucial target for therapeutic intervention in Alzheimer’s disease (AD). In order to find out the potential inhibitors of BACE1, the present study focused on five phytochemicals from Pueraria tuberosa, namely, daidzin, genistin, mangiferin, puerarin, and tuberosin. A molecular docking study showed that all five phytochemicals presented the strongest BACE1 inhibition. Integrated molecular dynamics simulations and free energy calculations demonstrated that all five natural compounds have stable and favorable energies causing strong binding with the pocket site of BACE1 on 50 ns. All these molecules also passed Lipinski’s rule of five. To validate the molecular modeling based findings, we primarily targeted the cognitive decline associated with BACE1 expression in AD flies with P. tuberosa. Significant improvement in cognitive decline was observed in AD flies in different behavioral assays such as Larval crawling assay (16.38%), Larval light preference assay (26.39%), Climbing assay (32.97%), Cold sensitivity assay (43.6%), and Thermal sensitivity assay (44.42%). The present findings suggest that P. tuberosa may be considered as a promising dietary supplement that can significantly ameliorate cognitive decline caused by BACE1 in Alzheimer’s disease (AD).A nanohybrid formulation of silver‑titanium dioxide nanoparticles/poly(lactic acid) (Ag-TiO2/PLA) was designed for Norfloxacin/Tenoxicam (NOR/TENO) targeted delivery to maximize the bioavailability and minimize the side effects of the drugs. Ag-TiO2 nanoparticles were prepared via Stober method. NOR, TENO and a mixture of NOR/TENO (NT) were loaded onto Ag-TiO2 nanoparticles and coated by PLA via solution casting. The physical interaction between the drugs and carrier was confirmed by Fourier-transform infrared (FTIR) analysis. X-ray diffraction (XRD) demonstrated that Ag-TiO2 consists of a cubic phase of Ag with two phases of TiO2 (anatase and brookite). Ag nanoparticle fine spots coated with TiO2 were collected to form spheres averaging at 100 nm in size. In-vitro release behavior of drugs was studied at different pH (5.4, 7.4) and the release of drug from NT/Ag-TiO2/PLA was faster at pH 7.4. Gram-positive and Gram-negative bacteria were used to investigate antibacterial properties of the nanohybrid. Cytotoxicity of the nanohybrid using an MTT assay was studied against different tumor and normal cell lines. It was found that NT/Ag-TiO2/PLA has an excellent cytotoxic effect against various bacterial cells and tumor cell lines. In addition, antioxidant properties of the nanohybrids were tested using ABTS method and the nanohybrid showed moderate antioxidant activity.In this approach, we assembled AgNps on cotton by using iota-carrageenan as a carbohydrate polymer under ultrasonic waves. UV-Vis spectroscopy revealed that iota-carrageenan free radicals increased the absorbance values of AgNps at 438 nm under ultrasonic vibration. We also observed an effective reduction of AgNps by color hue changes in the colloidal dispersions, ranging from pale to dark yellow. Interestingly, the zeta potential values for the AgNps changed from -8.5 to -45.7 mV after incorporation with iota-carrageenan. selleck kinase inhibitor Moreover, iota-carrageenan reduced the average particle sizes of AgNps/iota-carrageenan nanocomposite particles. Fourier transform infrared (FTIR) spectra proved the successful fabrication of AgNps/iota-carrageenan/cotton nanocomposites by shifting two bands at 3257 and 990 cm-1. Quantum Chemistry and Molecular Dynamics demonstrated strong interactions between AgNps and iota-carrageenan by changes in the bond lengths for CC, CH, CO, SO. Furthermore, new energy levels were generated in iota-carrageenan’s molecules by exciting electrons under ultrasonic vibration. According to the thermal gravimetric analysis (TGA) results, fabrication of AgNps/iota-carrageenan on cotton reduced the thermal stability of the resultant AgNps/iota-carrageenan/cotton nanocomposites. The average friction coefficient values of nanocomposite samples were increased in weft-to-warp direction that can be an advantage for wound healing, antimicrobial treatment and drug delivery applications. We did not observe reduction in the mechanical properties of our AgNps incorporated nanocomposites. Furthermore, the samples were tested for possible cytotoxicity against primary human skin fibroblast cells and no toxicity was observed.Drug-delivery technology is an effective way to promote drug absorption and efficacy. Mesoporous hollow silica material and small-molecule drug ibuprofen were used as a carrier model and as model drug, respectively. By quantum chemical calculation (density functional theory and frontier orbital theory), it was found that the content of geminal silanols on the material surface played a decisive role in the release of the different drugs. The rough hollow materials are easily adsorbed and have a large loading capacity, and so we fabricated a mesoporous hollow silica material (R-nCHMSNs) with a rough surface and rich geminal silanols by using hydroxyl-rich nanocellulose as a template. The content and types of hydroxyl groups on the material surface were studied by 29Si NMR. The loading and delivery of ibuprofen and lysozyme were studied in detail. Materials with rich geminal silanols exhibited excellent delivery properties for different drugs, which shows great potential and research value for drug delivery.

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