The cardioprotective effects of cerium oxide nanoparticles against the poisoning generated by aluminum phosphide pesticide: Controlling oxidative stress and mitochondrial damage.

BACKGROUND: Aluminum phosphide (AlP) is a well-known toxic compound used as an agricultural pesticide to prevent insect damage to stored crops. However, even if just a small amount was consumed, it caused lasting harm to the human body and, in acute concentrations, death. The current study employed cerium oxide nanoparticles (CeO2 NPs) to reduce oxidative stress and various harmful outcomes of AlP poisoning. METHODS: Following finding effective concentrations of CeO2 NPs via MTT assay, Human Cardiac Myocyte (HCM) cells were pre-treated with CeO2 NPs for 24 h. After that, they were exposed to 2.36 µM AlP. The activity of oxidative stress and mitochondrial biomarkers, including mitochondrial swelling, mitochondrial membrane potential, and cytochrome c release, were evaluated in HCM cells. Finally, the population of apoptotic and necrotic cells was assessed via flow cytometry. RESULTS: After 24 h, data revealed that all tested concentrations of CeO2 NPs were safe, and 25 and 50 µM of that were selected as effective concentrations. Oxidative stress markers (malondialdehyde, protein carbonyl, superoxide dismutase, and catalase) showed that CeO2 NPs could successfully decrease AlP poisoning due to their antioxidant characteristics. Mitochondrial markers were also recovered by pre-treatment of HCM cells with CeO2 NPs. Furthermore, pre-treating with CeO2 NPs could compensate for the reduction of live cells with AlP and cause a diminishing in the population of early and late apoptotic cells. CONCLUSION: As a result, it is evident that CeO2 NPs, through the recovery of oxidative stress and mitochondrial damages caused by AlP, reduce apoptosis and have therapeutic potentials on HCM cells.

A Systematic Review of the Chemo/Radioprotective Effects of Melatonin against Ototoxic Adverse Effects Induced by Chemotherapy and Radiotherapy.

BACKGROUND: Although chemotherapy and radiotherapy are effective in cancer treatment, different adverse effects induced by these therapeutic modalities (such as ototoxicity) restrict their clinical use. Co-treatment of melatonin may alleviate the chemotherapy/radiotherapy-induced ototoxicity. OBJECTIVE: In the present study, the otoprotective potentials of melatonin against the ototoxicity induced by chemotherapy and radiotherapy were reviewed. METHODS: According to the PRISMA guideline, a systematic search was carried out to identify all relevant studies on "the role of melatonin against ototoxic damage associated with chemotherapy and radiotherapy" in the different electronic databases up to September 2022. Sixty-seven articles were screened based on a predefined set of inclusion and exclusion criteria. Seven eligible studies were finally included in this review. RESULTS: The in vitro findings showed that cisplatin chemotherapy significantly decreased the auditory cell viability compared to the control group; in contrast, the melatonin co-administration increased the cell viability of cisplatin-treated cells. The results obtained from the distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) tests demonstrated a decreased amplitude of DPOAE and increased values of ABR I-IV interval and ABR threshold in mice/rats receiving radiotherapy and cisplatin; nevertheless, melatonin co-treatment indicated an opposite pattern on these evaluated parameters. It was also found that cisplatin and radiotherapy could significantly induce the histological and biochemical changes in the auditory cells/tissue. However, melatonin co-treatment resulted in alleviating the cisplatin/radiotherapy-induced biochemical and histological changes. CONCLUSION: According to the findings, it was shown that melatonin co-treatment alleviates the ototoxic damage induced by chemotherapy and radiotherapy. Mechanically, melatonin may exert its otoprotective effects via its anti-oxidant, anti-apoptotic, and anti-inflammatory activities and other mechanisms.

NLRP3 inflammasome pathway in atherosclerosis: Focusing on the therapeutic potential of non-coding RNAs.

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome pathway has a critical role in the pathogenesis of atherosclerosis. Activation of this pathway is implicated in the subendothelial inflammation and atherosclerosis progression. The NLRP3 inflammasome are cytoplasmic sensors with the distinct capacity to identify a wide range of inflammation-related signals, which enhance NLRP3 inflammasome assembly and allow it to trigger inflammation. This pathway is triggered by a variety of intrinsic signals which exist in atherosclerotic plaques, like cholesterol crystals and oxidized LDL. Further pharmacological findings indicated that NLRP3 inflammasome enhanced caspase-1-mediated secretion of pro-inflammatory mediators like interleukin (IL)- 1ß/18. Newly published cutting-edge studies suggested that non-coding RNAs (ncRNAs) including microRNAs (miRNAs, miRs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) are major modulators of NLRP3 inflammasome in atherosclerosis. Therefore, in this review, we aimed to discuss the NLRP3 inflammasome pathway, biogenesis of ncRNAs as well as the modulatory role of ncRNAs in regulating the various mediators of NLRP3 inflammasome pathway including TLR4, NF-kB, NLRP3, and caspase 1. We also discussed the importance of NLRP3 inflammasome pathway-related ncRNAs as a diagnostic biomarker in atherosclerosis and current therapeutics in the modulation of NLRP3 inflammasome in atherosclerosis. Finally, we speak about the limitations and future prospects of ncRNAs in regulating inflammatory atherosclerosis via the NLRP3 inflammasome pathway.

Malignant function of nuclear factor-kappaB axis in prostate cancer: Molecular interactions and regulation by non-coding RNAs.

Prostate carcinoma is a malignant situation that arises from genomic alterations in the prostate, leading to changes in tumorigenesis. The NF-κB pathway modulates various biological mechanisms, including inflammation and immune responses. Dysregulation of NF-κB promotes carcinogenesis, including increased proliferation, invasion, and therapy resistance. As an incurable disease globally, prostate cancer is a significant health concern, and research into genetic mutations and NF-κB function has the efficacy to facilitate the introduction of novel therapies. NF-κB upregulation is observed during prostate cancer progression, resulting in increased cell cycle progression and proliferation rates. Additionally, NF-κB endorses resistance to cell death and enhances the capacity for metastasis, particularly bone metastasis. Overexpression of NF-κB triggers chemoresistance and radio-resistance, and inhibition of NF-κB by anti-tumor compounds can reduce cancer progression. Interestingly, non-coding RNA transcripts can regulate NF-κB level and its nuclear transfer, offering a potential avenue for modulating prostate cancer progression.