Cardioprotective effects of hesperidin on carbon monoxide poisoned in rats.

Carbon monoxide (CO) poisoning causes cardiotoxicity and so far, no definite antidote has been proposed to overcome CO-induced adverse outcomes. Hesperidin, a citrus flavonoid, has shown cardio-protective effects in cardiac ischemia/reperfusion models. This study investigated the protective effects of hesperidin against CO-induced cardiac injury. To induce CO poisoning, rats were exposed to CO at 3000 ppm for 60 min. On the exposure day and the four following days, hesperidin (at three different doses of 25, 50, and 100 mg/kg/day) was administered intraperitoneally. A group of animals received normal saline and served as the control group. The electrocardiogram (ECG) was recorded and evaluated with special focus on S-T segment changes (depression or elevation), T-wave alterations, AV block and ventricular and supraventricular arrhythmias. On day 6 (i.e., the day after the last injection day), the animals were sacrificed and the hearts were harvested and evaluated for necrosis using hematoxylin and eosin staining. In addition, Akt protein expression levels and BAX/BCL2 ratio were determined by western blotting. Our results showed that hesperidin decreased cardiac necrosis. In animals treated with hesperidin 100 mg/kg, Akt protein expression was increased, while the BAX/BCL2 ratio was significantly decreased. ECG changes were reversed in all groups 2 h following CO exposure, regardless of hesperidin administration. Overall, hesperidin decreased the deleterious cardiac effects of CO poisoning in rats.

Emerging Advances of Nanotechnology in Drug and Vaccine Delivery against Viral Associated Respiratory Infectious Diseases (VARID).

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines.

Novel delivery of sorafenib by natural killer cell-derived exosomes-enhanced apoptosis in triple-negative breast cancer.

Aim: We investigated the delivery of sorafenib (SFB) to breast cancer spheroids by natural killer cell-derived exosomes (NK-Exos). Methods: SFB-NK-Exos were constructed by electroporation. Their antitumor effects were evaluated by methyl thiazolyl tetrazolium, acridine orange/ethidium bromide, 4',6-diamidino-2-phenylindole, annexin/propidium iodide, scratch and migration assay, colony formation, RT-PCR, western blot and lipophagy tests. Result: The loading efficacy was 46.66%. SFB-NK-Exos-treated spheroids showed higher cytotoxic effects (33%) and apoptotic population (44.9%). Despite the reduction of SFB concentration in the SFB-NK-Exos formulation, similar cytotoxic effects to those of free SFB were observed. Increased intracellular trafficking, sustained release of the drug and selective inhibitory effects demonstrated efficient navigation. Conclusion: This is the first report for SFB loading into NK-Exos, which led to significant cytotoxic intensification against cancer cells.

What is this summary about? This study describes the delivery of an anticancer drug called sorafenib (SFB) to laboratory-grown spherical masses of cancer cells called spheroids. Saucer-like cellular structures called exosomes were used as drug-delivery tools. These exosomes were produced by a subgroup of immune cells called natural killer (NK) cells. NK cells are responsible for killing cancer cells. So, these exosomes share similar anticancer properties with NK cells. We wanted to test whether exosomes loaded with SFB would have better anticancer effects. What were the results? Using different methods, SFB was loaded within the exosomes and delivered to the spheroids. The obtained results showed that a combination of exosomes and SFB could improve the targeting efficacy, reducing the side effects to the normal cells and allowing continuous release of the drug. The spheroids were killed with higher efficacy following this treatment. What do the results of the study mean? The combination of NK cell-derived exosomes and SFB could lead to better cytotoxicity against cancer cells. Therefore, this strategy could have better anticancer effects compared with SFB treatment alone.