Background: Vancomycin (VCM)-induced hepatotoxicity is a significant clinical concern due to its association with oxidative stress, apoptosis, and inflammatory responses. This study investigated the formulation and potential preclinical application of rutin-loaded nanocapsules (RUT-NC) as a hepatoprotective agent against VCM-induced liver injury. Methods: Hepatotoxicity was induced in rats through VCM administration, followed by oral treatment with RUT-NC. Liver function, oxidative stress markers, apoptotic proteins, lipid metabolism regulators, and inflammatory cytokines were subsequently evaluated. Results: RUT-NC treatment significantly improved liver function parameters, attenuated oxidative stress, and modulated apoptotic pathways by downregulating the expression of p38 , p53 , caspase-8 , miR-122 , miR-7 , and beclin-1. Furthermore, RUT-NC restored lipid metabolism homeostasis by regulating the expression of PPAR-α, FASN, and SREBP-1. Notably, it exerted potent anti-inflammatory effects by suppressing NF-κB , TNF-α , IL-1β , IL-6 , IL-17 , and Gasdermin-D , thereby mitigating chronic liver inflammation. The pathological effects of VCM administration on hepatocytes were effectively counteracted by RUT-NC. Conclusion: RUT-NC demonstrates promising hepatoprotective properties by enhancing antioxidant defenses, inhibiting apoptosis, regulating lipid metabolism, and reducing inflammation. These findings highlight its potential as a therapeutic intervention for drug-induced liver injury (DILI) and warrant further investigation for clinical application.

Dyslipidemia is a major risk factor for the development of NAFLD, atherosclerosis and cardiovascular diseases. Rosuvastatin (ROS) is a lipid-lowering drug that protects against the development of NAFLD and atherosclerosis. However, the mechanism of this protection remains obscure. Therefore, the current study aims to explore the mechanism by which ROS-loaded glycerosomes (ROS-GLY) protect against NAFLD and atherosclerosis. Hence, for this purpose, hepatic lncRNA-H19/miR-130a/PPAR-γ and aortic PPAR-γ/LXRα/ABCA1 signaling pathways were assessed. In addition, these target pathways were predicted using molecular docking analysis. Thirty-five male Sprague Dawley rats were separated into control, dyslipidemic (poloxamer 407 (P 407)), P 407+ROS-GLY, P 407+NC, and P 407+ROS-GLY+NC groups. ROS-GLY improved lipid profile, hepatic MDA, SOD, catalase and total antioxidant capacity (TAC) in compared to P 407 group. In the dyslipidemic group, ROS-GLY downregulated hepatic lncRNA-H19 expression which leads to an upregulate of the miR-130a level and subsequent reduction of the PPAR-γ level. Consequently, the hepatic expression level of lipogenic genes such as, ACC-1, FASN and SCD-1 was significantly downregulated in the ROS-GLY group than the dyslipidemic one. Aortic PPAR-γ/LXRα/ABCA1 signaling pathway was significantly upregulated in the ROS-GLY group compared to the dyslipidemic group. Furthermore, ROS-GLY modulated IL-6 and IL-10 immunoprotein expression in hepatic and aortic tissues. Interestingly, ROS showed a substantial binding affinity with PPAR-γ, LXR-α, and FASN, according to a molecular docking study. The current study indicated that ROS-GLY protected against the progression of NAFLD and atherosclerosis in dyslipidemic rats via modulation of lipid profile, oxidative stress, pro-/anti-inflammatory cytokines, hepatic lncRNA-H19/miR-130a/PPAR-γ, and aortic PPAR-γ/LXRα/ABCA1 signaling pathways.

Obesity is abnormal massive accumulation of fat in the body, which is cosidered one of the most common health problem worldwide. It is causing a state of oxidative stress and inflammation, which affects almost all body tissues including the brain. Obesity also affects cognitive development, executive function abilities, brain volume, and can increase the risk of dementia and Alzheimer's disease. Therefore, we assessed the effect of swimming exercise versus the ketogenic diet on the brain damage of obese rats. Thirty two rats were divided into 4 groups (8 rats each) include: Control group: Rats received standared rat diet, Obesity group: Rats received high fat diet, ketogenic diet group (KD): Obese rats received ketogenic diet/daily for 2 months and swimming exercise: Obese rats subjected to swimming (1 h/day/2 months). The results indicated that KD and swimming exercise improved waist circumference, total cholesterol, triacylglycerol, and HDL in comparison with obese group. Regarding oxidative status in the brain, Both KD and swimming exercise significantly reduced the level of MDA, while increased the level of total antioxidant capacity (TAC) and SOD. Both treatments downregulated the mRNA expression levels of TLR4/NF-κB signaling, mir-138-5p and mir-489-3p in the brain tissue of obese rats. However, KD and swimming exercise upregulated the mRNA expression levels of antioxidant-related genes (Nrf-2 and SIRT1), fission-related genes (Mfn1 and Mfn2), fussion-related gene (DRP-1), mitophagy-related genes (PINK1 and Parkin), mitochondrial respiratory chain-related genes (NDUFS1, SDHC, COQ8A, COX6A2 and ATP5F1A). Moreover, both tretments showed improvement in the brain tissue histopathology of obese rats. In conclusion, KD and swimming exercise restore the normal brain function in obese rats. Interestingly, the data of this study proved that swimming exercise showed higher potent effect than KD against brain damage in obese rats.

| Vaccination is a significant process for stimulating the immune response against infection. Adjuvant of vaccine is an important factor in enhancing the immune response. It must be safe, inexpensive and easy to prepare. This study aimed to develop a new RVF virus vaccine with chitosan nanoparticles and aluminum phosphate nanoparticles as adjuvants and evaluate their impact on biochemical, cellular and humoral immune response in sheep, The prepared vaccines were sterile, safe, emulsion is stable and validity within acceptable limit 0.02 ED F50 /ml up till 15 th month with AlP-NPsV and AlHV except Ch-NPsV that was valid up to 16 th month. Lymphocyte count increased from the 1 st week post-vaccination till the peak at 5 th , 4 th and 3 th months in groups vaccinated with Ch-NPsV, AlP-NPsV and AlHV respectively. Conversely, neutrophil count decreased in vaccinated groups. No change was detected between groups in serum kidney function enzymes. Cytokine profile including IL-2 was markedly increased from 1 st day after inoculation and elevated moderately till arrived to the peak at the 5 th , 7 th and 10 th days post-vaccination in groups vaccinated with Ch-NPsV, AlP-NPsV and AlHV respectively. The results IFN -γ mRNA expression level was consistent with the results of cytokine profile including IL-2. Neutralizing antibody was increased from the 2 nd week post-vaccination and reached the peak at 5 th , 4 th and 3 th months in groups vaccinated with Ch-NPsV, AlP-NPsV and AlHV respectively. It could be concluded that Ch-NPsV and AlP-NPsV are safe, potent and induce a higher antibody response than traditional vaccine.