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Sorafenib (SFB) is an anticancer drug with sparingly water solubility and reduced bioavailability. Nanoformulation of SFB can increase its dissolution rate and solubility. The current study aimed to formulate SFB in nanoparticles to improve their solubility. The sorafenib nanoparticles (SFB-PNs) were synthesized using the solvent evaporation method, then evaluated for their particle size, polydispersity index (PDI), zeta-potential, morphological structure, and entrapment efficiency (EE%). Further, the anticancer efficacy in A549 and Michigan Cancer Foundation-7 (MCF-7) cancer cell lines was evaluated. The SFB-NPs were uniform in size, which have 389.7 ± 16.49 nm, PDI of 0.703 ± 0.12, and zeta-potential of −13.5 ± 12.1 mV, whereas transmission electron microscopy showed a well-identified spherical particle. The EE% was found to be 73.7 ± 0.8%. SFB-NPs inhibited the cell growth by 50% after 48 h incubation, with IC50 of 2.26 and 1.28 µg/mL in A549 and MCF-7, respectively. Additionally, SFB-NPs showed a significant decrease (P < 0.05) in p21, and stathmin-1 gene expression levels in both cell lines. Moreover, SFB-NPs showed a significant increase in DNA damage of 25.50 and 26.75% in A549 and MCF-7, respectively. The results indicate that SFB-NPs are a potential candidate with an effective anticancer agent compared with free drugs.

Drug uptake and distribution through cell–receptor interactions are of prime interest in reducing the adverse effects and increasing the therapeutic effectiveness of delivered formulations. This study aimed to formulate silver nanoparticles (AgNPs) conjugated to somatostatin analogs for specific delivery through somatostatin receptors (SSTRs) expressed on cells and by nebulizing the prepared AgNPs formulations into lung cells for in vivo application. AgNPs were prepared using the citrate reduction method, yielding AgNPs–CTT, which was further chemically conjugated to octreotide (OCT) to form AgNPs–OCT through an amide linkage. The AgNPs–OCT formulation was coated using alginate to yield a carrier, AgNPs–OCT–Alg, feasible for drug delivery through nebulization. AgNPs were uniform in size with an acceptable range of zeta potential. Furthermore, the concentrations of AgNP formulations were found safe for the model cell lines used, and cell proliferation was significantly reduced in a dose-dependent manner (p < 0.05). In the healthy lung tissues, AgNPs–OCT–Alg accumulated at a concentration of 0.416 ± 5.7 mg/kgtissue, as determined via inductively coupled plasma optical emission spectrometry. This study established the accumulation of AgNPs, specifically the AgNPs–OCT–Alg, in lung tissues, and substantiated the active, specific, and selective targeting of SSTRs at pulmonary sites. The anticancer efficacy of the formulations was in vitro tested and confirmed in the MCF-7 cell lines. Owing to the delivery suitability and cytotoxic effects of the AgNPs–OCT–Alg formulation, it is a potential drug delivery formulation for lung cancer therapy in the future.

Background: We studied the potential of human bone marrow–derived mesenchymal stem cell conditioned media (hBMSC CM) in protecting endothelial cell properties (viability, proliferation, and migrations) from the deleterious effects produced by the inflammatory environment of H2O2. Additionally, we investigated their impact on the endothelial cells' gene expression of some inflammatory‐related genes, namely, TGF‐β1, FOS, ATF3, RAF‐1, and SMAD3. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured individually under three conditions: alone, with varying concentrations of H2O2, or with varying concentrations of H2O2 and hBMSC CM. HUVEC adhesion, proliferation, and migration were evaluated using the xCELLigence system. The HUVECs' gene expressions were evaluated by real‐time polymerase chain reaction (RT–PCR). Results: Generally, we observed enhanced HUVEC viability, proliferation, and migration when cultured in media supplemented with H2O2 and hBMSC CM. Furthermore, the CM modulated the expressions of the studied inflammatory‐related genes in HUVECs, promoting a more robust cellular response. Conclusion: This study has illuminated the protective role of hBMSC CM in mitigating the damaging effects of H2O2 on endothelial cell function. Our data demonstrate that hBMSC CM enhances the viability, proliferation, and migration of HUVECs even under oxidative stress conditions. Additionally, the conditioned medium was found to modulate the gene expression of pivotal markers related to inflammation, suggesting a favorable influence on cellular response mechanisms. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic multifactorial inflammatory disease that affects 3% of people worldwide. Ustekinumab is a selective anti-IL-12/23 biologic that alleviates psoriasis, and curcumin is a natural, effective dietary turmeric extract applied to treat numerous diseases through its antioxidant and anti-inflammatory effects. The current study evaluated the therapeutic effects of curcumin and ustekinumab cotherapy (CUC) on imiquimod (IQ)-induced psoriasis in a rat model. Twenty rats were divided into four groups, G1 (control group), G2 (IQ-treated group), G3 (IQ + ustekinumab), and G4 (IQ + CUC). Clinical, histopathological (HP), immunohistochemical (IHC), antioxidant, and biochemical investigations evaluated the efficacy of these drugs for treating IQ induced-psoriasis. Rats of G2 exhibited clinical signs of psoriatic skin lesions (erythema, scaling, and skin thickening) with epidermal changes (acanthosis and parakeratosis). Additionally, the biochemical analysis revealed significant (p < 0.05) reductions in the levels of antioxidant biomarkers (SOD, GPx, and CAT) with significant (p < 0.05) elevations in psoriasis-related cytokines (TNF-α, IL-17A, IL-12P40, and IL-23). In contrast, CUC alleviated the psoriatic changes in G4 better than ustekinumab monotherapy in G3. Ustekinumab inhibits the inflammatory cytokines IL-12P40 and IL-23, while curcumin has antioxidant effects (increasing SOD, GPx, and CAT levels) with anti-inflammatory effects (decreasing the proinflammatory cytokine TNF-α and IL-17). Therefore, CUC could be an excellent cost-effective regimen that can improve the treatment of psoriasis by the synergistic effects of CUC. IQ-induces psoriasis by elevating TNF-α, IL-17A, IL-12, and IL-23 and decreasing GPx, SOD, and CAT Ustekinumab exhibits anti-inflammatory effects by inhibiting IL-12 and IL-23 Curcumin inhibits TNF-α and IL-17A, and increases GPx, SOD, and CAT levels CUC mitigates psoriasis by synergistic antioxidant and anti-inflammatory effects CUC inhibits TNF-α, IL-17A, IL-12, and IL-23 and increases GPx, SOD, and CAT levels [ABSTRACT FROM AUTHOR]

Background: We studied the potential of human bone marrow-derived mesenchymal stem cell conditioned media (hBMSC CM) in protecting endothelial cell properties (viability, proliferation, and migrations) from the deleterious effects produced by the inflammatory environment of H 2 O 2 . Additionally, we investigated their impact on the endothelial cells' gene expression of some inflammatory-related genes, namely, TGF- β 1, FOS, ATF3, RAF-1, and SMAD3. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured individually under three conditions: alone, with varying concentrations of H 2 O 2 , or with varying concentrations of H 2 O 2 and hBMSC CM. HUVEC adhesion, proliferation, and migration were evaluated using the xCELLigence system. The HUVECs' gene expressions were evaluated by real-time polymerase chain reaction (RT-PCR). Results: Generally, we observed enhanced HUVEC viability, proliferation, and migration when cultured in media supplemented with H 2 O 2 and hBMSC CM. Furthermore, the CM modulated the expressions of the studied inflammatory-related genes in HUVECs, promoting a more robust cellular response. Conclusion: This study has illuminated the protective role of hBMSC CM in mitigating the damaging effects of H 2 O 2 on endothelial cell function. Our data demonstrate that hBMSC CM enhances the viability, proliferation, and migration of HUVECs even under oxidative stress conditions. Additionally, the conditioned medium was found to modulate the gene expression of pivotal markers related to inflammation, suggesting a favorable influence on cellular response mechanisms., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Abdulmajeed Alqasoumi et al.)