Chitosan and its nanoparticles (NPs) could be extracted from numerous fungal species and used as effectual carriers for bioactive compounds. The fungal chitosan (FC) was innovatively acquired from Fusarium oxysporum grown mycelia, characterized and used for NP synthesis and loading with bee venom (BV). The nano-FC (NFC) had 192.4 nm mean NP diameter, 38.22% loading capacity, and 92.42% entrapment efficiency. BV release from NFC was pH and time dependent; burst BV release was detected at the first 6 h, followed by gradual releases up to 30 h. The in vitro anticancer potentiality valuation, of NFC, BV, and NFC/BV nanoconjugates against HeLa cervix carcinoma, revealed that they all had potent dose-dependent anticancer activity; BV/NFC nanoconjugates were the most effective with IC50=200μg/mL. The fluorescent staining of treated HeLa cells with BV/NFC nanoconjugates, with DAPI and acridine orange/propidium iodide combination, indicated the appearance of early apoptosis, secondary apoptosis, and secondary necrosis markers and their increment with exposure prolongation. The production of NFC from F. oxysporum and their loading with BV are strongly counseled for production of potent natural antitumor agent with augmented activity against cervix carcinoma.

Triazole-based thiosemicarbazone derivatives (6a–u) were synthesized then characterized by spectroscopic techniques, such as 1HNMR and 13CNMR and HRMS (ESI). Newly synthesized derivatives were screened in vitro for inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All derivatives (except 6c and 6d, which were found to be completely inactive) demonstrated moderate to good inhibitory effects ranging from 0.10 ± 0.050 to 12.20 ± 0.30 µM (for AChE) and 0.20 ± 0.10 to 14.10 ± 0.40 µM (for BuChE). The analogue 6i (IC₅₀ = 0.10 ± 0.050 for AChE and IC₅₀ = 0.20 ± 0.050 µM for BuChE), which had di-substitutions (2-nitro, 3-hydroxy groups) at ring B and tri-substitutions (2-nitro, 4,5-dichloro groups) at ring C, and analogue 6b (IC₅₀ = 0.20 ± 0.10 µM for AChE and IC₅₀ = 0.30 ± 0.10 µM for BuChE), which had di-Cl at 4,5, -NO₂ groups at 2-position of phenyl ring B and hydroxy group at ortho-position of phenyl ring C, emerged as the most potent inhibitors of both targeted enzymes (AChE and BuChE) among the current series. A structure-activity relationship (SAR) was developed based on nature, position, number, electron donating/withdrawing effects of substitution/s on phenyl rings. Molecular docking studies were used to describe binding interactions of the most active inhibitors with active sites of AChE and BuChE.

Cyclosporine A’s (CsA) immunosuppressive effect makes it an ideal drug for organ transplantation. However, CsA’s uses are restricted due to its side effects. We investigated the effects of avocado seed (AvS) powder on CsA-induced nephrotoxicity and immunosuppression in rats. The injection of CsA (5 mg/kg, subcutaneously, for 10 days) increased serum levels of creatinine, uric acid, and urea, and the renal levels of the malondialdehyde. It decreased creatinine clearance and the renal activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and Na⁺/K⁺ ATPase. The administration of CsA also significantly downregulated the renal expression of interferon-gamma, tumor necrosis factor-alpha, interleukin 1 beta, monocyte chemotactic protein 1, intercellular adhesion molecule-1, and vascular cell adhesion molecule 1 genes, and increased renal DNA damage. Histopathological examination confirmed the biochemical and molecular alterations that accompanied CsA nephrotoxicity. All CsA-induced deleterious effects, except immunosuppression, were ameliorated by feeding rats on a basal diet supplemented with 5% AvS powder for 4 weeks. Importantly, AvS also maximized CsA’s immunosuppressive effect. These findings suggest a potential ameliorative effect of AvS on CsA-induced nephrotoxicity, and AvS enhances CsA’s immunosuppressive effect. Therefore, AvS might be used in combination with CsA in transplantation treatment to relieve the CsA-induced nephrotoxicity.

Previous studies reported disrupted hepatic function and structure following the administration of cyclosporine A (CsA) in humans and animals. Recently, we found that avocado seeds (AvS) ameliorated CsA-induced nephrotoxicity in rats. As a continuation, herein we checked whether AvS could also attenuate CsA-induced hepatotoxicity in rats. Subcutaneous injection of CsA (5 mg/kg) for 7 days triggered hepatotoxicity in rats, as indicated by liver dysfunction, redox imbalance, and histopathological changes. Oral administration of 5% AvS powder for 4 weeks ameliorated CsA-induced hepatotoxicity, as evidenced by (1) decreased levels of liver damage parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin), (2) resumed redox balance in the liver (reduced malondialdehyde (MDA) and increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), (3) downregulated hepatic expression of endoplasmic reticulum (ER) stress-related genes (X-box binding protein 1 (XBP1), binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP)), and apoptosis-related genes (Bax and Casp3), (4) upregulated expression of the anti-apoptotic gene Bcl2, (5) reduced DNA damage, and (6) improved liver histology. These results highlight the ability of AvS to ameliorate CsA-induced hepatotoxicity via the inhibition of oxidative stress and proapoptotic ER stress.

Liver fibrosis is a condition characterized by the excessive buildup of scar tissue in the liver. This scarring occurs as a result of chronic liver damage, often caused by conditions such as hepatitis, alcohol abuse, certain metabolic disorders, genetic abnormalities, autoimmunity, and noninfectious diseases such as fatty liver which leads to liver fibrosis. Nanoparticles have gained attention in recent years as potential therapeutic agents for liver fibrosis. They offer unique advantages due to their small size, large surface area, and ability to carry drugs or target specific cells or tissues. Studies have suggested that nanoemulsions may enhance drug delivery systems, enabling targeted drug delivery to specific sites in the liver and improving therapeutic outcomes. In this study, we explore the protective and therapeutic values with phytochemical profiling of the used agro-wastes decaffeinated palm date seeds (Phoenix dactylifera L., PSC) coffee and caffeinated Arabic coffee seeds (Coffea arabica L.; ACS). Both ACS and PSC extracts were converted into nanoemulsion (NE) forms using the oleic acid/Tween 80 system, which was recruited for the purpose of treating a rat model with liver fibrosis. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to record the sizes, morphologies, hydrodynamic diameters, and ζ-potentials of the prepared NE-ACSE and NE-PSCE. Accordingly, the NE-ACSE and NE-PSCE imaged via TEM and their ζ-potentials were recorded at 20.7, 23.3 nm and −41.4, −28.0 mV, respectively. The antioxidant properties were determined with a DPPH scavenging assay. The synthesized NE-PSCE and NE-ACSE were employed to treat a rat model with CCl₄-induced liver fibrosis, to estimate the role of each emulsion-based extract in the treatment of liver fibrosis through recording inflammatory parameters, liver functions, antioxidant enzymes, and histopathological analysis results. The nanoemulsion forms of both ACSE and PSCE provided significant increases in antioxidant enzymes, reducing inflammatory parameters, compared to other groups, where liver functions were decreased with values close to those of the control group. In conclusion, both nanoemulsions, ACSE and PSCE, provided a new avenue as therapeutic approaches for liver diseases, and further studies are encouraged to obtain maximum efficiency of treatment via the combination of both extracts.