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This study provides a theoretical basis for the treatment of relapsed refractory MM with ibrutinib combined with DXMS, and a potential therapeutic target for MM clinical treatment.Context Daidzein is a secondary metabolite derived from plants, has a flavonoid structure and is known for its protective activity in gastrointestinal disorders. Objective The current work determines the preventive effect of daidzein against injury in the esophagus mucosa induced by esophageal reflux (RE) in an animal model. Methods Adult male Wistar rats were classified into six groups normal control, ER + different doses of daidzein and ER + omeprazole. RE was induced in all animals except controls and supplemented with daidzein and standard drugs orally for 6 hours. Serum and tissue were used for further biochemical parameters. Results Daidzein as a flavonoid has antioxidant properties and shows in vitro antioxidant activity. The outcomes also reveal an elevation in lipid peroxidation and a decline in the levels of sulphhydryl groups and glutathione, along with the depletion in the activities of enzymatic antioxidants in the oxidative stress state. In a dose-dependent manner daidzein and omeprazole amended all macroscopic and biochemical variations and protected against the raised level of hydrogen peroxide (H₂O₂), calcium and free iron levels in esophageal tissue induced during RE. It also improved the expression and level of proinflammatory cytokines. Conclusion The finding reports that daidzein has a potential to show a shielding effect against esophagus damage induced by RE in rats, at least in part via alteration of inflammatory cytokines.Nevirapine (NVP) is used for the management of HIV/AIDS but must be dosed frequently, exhibits unpredictable bioavailability and a side effect profile that includes hepato- and dermo-toxicity. Niosomes are a colloidal drug delivery system that may be used to overcome the low bioavailability, side effect profile and frequent dosing needed when using conventional drug delivery systems. The compatibility of NVP with sorbitan esters, polysorbate, cholesterol and dihexadecyl phosphate (DCP) was investigated using Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), Fourier Transform Infra-red Spectroscopy (FTIR) and X-ray Powder Diffraction (XRPD). Screening studies were undertaken to identify potential excipients that would produce niosomes with target critical quality attributes (CQA) viz, a particle size (PS) 78% without cholesterol. The addition of cholesterol and DCP was essential to form niosomes with target CQA.Ocular toxoplasmosis is the major cause of infectious posterior uveitis worldwide, inducing visual field defect and/or blindness. Despite the severity of this disease, an effective treatment is still lacking. In this study, spiramycin-loaded PLGA implants were developed aiming at the treatment of ocular toxoplasmosis. Implants were manufactured by a hot-molding technique, characterized by Fourier Transform Infrared Spectroscopy, X-Ray Diffraction, Differential Scanning Calorimetry, Scanning Electron Microscopy; evaluated in terms of ocular biocompatibility by immunofluorescence, flow cytometry, cell migration, Hen's egg test-chorioallantoic membrane (HET-CAM) irritation test; and investigated in terms of in vitro efficacy against Toxoplasma gondii . click here Characterization techniques indicated that spiramycin was dispersed into the polymeric chains and both substances preserved their physical structures in implants. The HET-CAM test indicated that implants did not induce hemorrhage or coagulation, being non-irritant to the CAM. ARPE-19 cells showed viability by MTT assay, and normality in cell cycle kinetics and morphology, without stimulating cell death by apoptosis. Finally, they were highly effective against intracellular parasites without inducing human retinal pigment epithelial cell death. In conclusion, spiramycin-loaded PLGA implants represent a promising therapeutic alternative for the local treatment of ocular toxoplasmosis.Exosomes are bilayer membrane-coated extracellular vesicles measuring between 40 and 100 nm in diameter. As a natural carrier, exosomes have the advantages of low immunogenicity, high stability in blood, and direct delivery of drugs to cells. Exosomes can be transported between cells and thus are conducive to the exchange of substances and information between cells. They change the functional state of recipient cells by loading exogenous drugs (e.g., small-molecule drugs, transmembrane proteins, and nucleic acid drugs). The key to using exosomes as drug carriers is the effective loading of exogenous drugs into exosomes; however, this task poses a challenge in studying the functionalization of exosomes as drug carriers. Currently, sonication, electroporation, transfection, incubation, extrusion, saponin-assisted loading, transgenesis, freeze-thaw cycles, thermal shock, pH gradient method, and hypotonic dialysis have been applied to load these drugs into exosomes. This review aims to provide an overview of the advantages and disadvantages of various drug loading technologies for exosomes.Ferulic acid, a hydroxyl derivative extracted from plants, is abundant in free state in seeds and leaves, or covalently linked with cell wall polysaccharides, lignin and different polymers. It has various pharmacological activities, including antioxidant and anti-inflammatory effects, regulates immunity, protects the cardiovascular system, and contributes to the prevention of tumors and diabetes. The protective effect on cardiovascular system is the most valuable one in view of clinical application. Here, we are reviewing the research progress concerning the pharmacological effects of ferulic acid and its derivatives on cardiovascular diseases in the past five years, mainly focusing on mechanisms of action and clinical application. This should provide guidance for clinical applications of ferulic acid and its derivatives in the treatment of cardiovascular diseases.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has paralysed the livelihood of the global population by inflicting higher mortality among the affected patients. Nearly the entire human physiological system can get disrupted by the virulence of SARS-CoV-2, which exemplifies the significance of discovering a potential drug target. Similar to angiotensin-converting enzyme 2 (ACE2), bitter taste receptors (T2Rs) unequivocally expressed on all vital human organs, particularly on nasal/oral respiratory tract, gastrointestinal organs, innate immune cells, heart, brain and urogenital cells are susceptible to SARS-CoV-2 virulence. Activation of T2Rs by bitter agonists restores vital functions to these organs via activation of large conductance, Ca2+-dependent potassium (K+) channels (BKca), and inducible nitric oxide synthase. T2R activation in the gustatory system can act as the first defence mechanism, primarily preventing or mitigating SARS-CoV-2 entry to the respiratory tract. Moreover, T2R activation is crucial for the improved vasodilation accompanied by the attenuation of systemic inflammation; hyper-innate immune responses; gastrointestinal disorders; defective neurological functions; acute kidney injury; and impotency witnessed in severe SARS-CoV-2 cases.
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