Amiodarone (AM) is a highly efficient drug for arrhythmias treatment, but its extra-cardiac adverse effects offset its therapeutic efficacy. Nanoparticles (NPs)-based delivery system could provide a strategy to allow sustained delivery of AM to the myocardium and reduction of adverse effects. The primary purpose was to develop AM-loaded NPs and explore their ameliorative effects versus off-target toxicities.

Polymeric NPs were prepared using poly lactic-co-glycolic acid and their physicochemical properties were characterized. Animal studies were conducted using a rat model to compare exposure to AM versus that of the AM-loaded NPs. Biochemical evaluation of liver enzymes, lipid profile, and thyroid hormones was achieved. Besides, histopathological changes in liver and lung were studied.

Under optimal experimental conditions, the AM-loaded NPs had a size of 186.90nm and a negative zeta potential (-14.67mV). Biochemical evaluation of AM-treated animal group showed a significant increase in cholesterol, TG, LDL, T4, and TSH levels (ρ<0.05). Remarkably, the AM-treated group exhibited a significant increase of liver enzymes (ρ<0.05) coupled with an obvious change in liver architecture. see more The AM-loaded NPs displayed a reduction of liver damage and enzyme levels. Lung sections of the AM-treated group demonstrated thickening of interalveolar septa, mononuclear cellular infiltration with congested blood vessels, and heavy collagenous fibers deposition. Conversely, less cellular infiltration and septal thickening were observed in the animal lungs treated with the AM-loaded NPs-treated.

Our findings demonstrate the competence of the AM-loaded NPs to open several exciting avenues for evading the AM-induced off-target toxicities.

Our findings demonstrate the competence of the AM-loaded NPs to open several exciting avenues for evading the AM-induced off-target toxicities.

This study aimed to explore the therapeutic effects of amniotic fluid-derived extracellular vesicles including exosomes (AF-Exos) on the recovery of sperm production capacity in a rat model of azoospermia.

The non-obstructive azoospermia (NOA) was induced in rats using intratesticular administration of Busulfan. Azoospermia was confirmed by testis histology. AF-Exos samples containing 10 or 40μg exosomal proteins were injected into testicular tissue of NOA rats. After two months, the recovery of spermatogenesis was monitored via histopathological staining, spermiogram, and hormonal analysis. Immunohistochemistry staining for OCT-3/4 was used to identify of spermatogonial progenitors. The expression of DAZL and VASA, was also measured.

AF-Exos exhibited sphere-shaped morphology with the mean diameter and zeta potential of 50±7.521nm and -7.16mV. Immunoblots revealed that isolated nanoparticles were CD63, CD9, and CD81 positive. Histopathological evaluation revealed that spermatogenesis was improved significantly in NOA rats after AF-Exos injection. Data showed that the sperm parameters and spermatogenesis index were significantly improved after AF-Exos injection compared to azoospermic groups. OCT-3/4

cells were increased in NOA rats after AF-Exos injection, showing the restoration of spermatogenesis. In the present study, both doses of exosome (10 and 40μg) restored the testicular function of NOA rats. DAZL and VASA were increased significantly in animals who received 40μg exosomal protein compared to azoospermic rats. Except in a high dose of AF-Exos (40μg) for Testosterone and FSH, no statistically significant differences were found regarding hormones post-exosome injection.

Our study demonstrated that AF-Exos regenerated spermatogenesis and improved sperm quality in NOA rats.

Our study demonstrated that AF-Exos regenerated spermatogenesis and improved sperm quality in NOA rats.

Cyclophosphamide (CP) is a common therapeutic drug for cancer, but exposure to CP can cause acute hepatotoxicity. This study aimed to elucidate the protective effects of Ligustrazine (2, 3, 5, 6-tetramethylpyrazine, TMP) on hepatotoxicity induced by CP or its active metabolite 4-hydroperoxycyclophosphamide (4-HC).

We presented a comprehensive investigation about the hepatoprotection of TMP on CP-induced mice and 4-HC-treated HSC-LX2 cells. Liver function was detected via enzyme-linked immunosorbent assay (ELISA). Hepatic histopathology analysis was performed via hematoxylin and eosin (H&E) and Masson staining. Survival of hepatocytes was detected by TUNEL assay. Related proteins in the thioredoxin (Trx)-interacting protein (Txnip)/Trx/Nuclear factor-kappa B (NF-κB) pathway were measured by western blotting.

The results indicated that CP or 4-HC could increase the levels of alanine aminotransferase and aspartate aminotransferase, enhance inflammatory factors and oxidative indicators, and suppress theh pyroptosis, which was positively correlated with the inhibition of Txnip/Trx/NF-κB pathway.The COVID-19 pandemic surges on as vast research is produced to study the novel SARS-CoV-2 virus and the disease state it induces. Still, little is known about the impact of COVID-19-induced microscale damage in the lung on global lung dynamics. This review summarizes the key histological features of SARS-CoV-2 infected alveoli and links the findings to structural tissue changes and surfactant dysfunction affecting tissue mechanical behavior similar to changes seen in other lung injury. Along with typical findings of diffuse alveolar damage affecting the interstitium of the alveolar walls and blood-gas barrier in the alveolar airspace, COVID-19 can cause extensive microangiopathy in alveolar capillaries that further contribute to mechanical changes in the tissues and may differentiate it from previously studied infectious lung injury. Understanding microlevel damage impact on tissue mechanics allows for better understanding of macroscale respiratory dynamics. Knowledge gained from studies into the relationship between microscale and macroscale lung mechanics can allow for optimized treatments to improve patient outcomes in case of COVID-19 and future respiratory-spread pandemics.