Sub-acute administration of metal-organic Framework-5 induces behavioral impairments and augments the levels of oxidative stress and inflammation in the brain of rats.

Metal-organic frameworks (MOFs) are known as potential pharmaceutical carriers because of their structure. Here, we evaluated the sub-acute administrations of MOF-5 on behavioral parameters, oxidative stress, and inflammation levels in rats. Thirty-two male Wistar rats received four injections of saline or MOF-5 at different doses which were 1, 10, and 50 mg/kg via caudal vein. Y-Maze and Morris-Water Maze (MWM) tests were used to explore working memory and spatial learning and memory, respectively. The antioxidant capacity and oxidative stress level of brain samples were assessed by ferric reducing antioxidant power (FRAP) and thiobarbituric acid-reacting substance (TBARS) assay, respectively. The expression levels of GFAP, IL-1ß, and TNF-α were also measured by quantitative real-time reverse-transcription PCR (qRT-PCR). Sub-acute administration of MOF-5 reduced the spatial learning and memory as well as working memory, dose-dependently. The levels of FRAP were significantly reduced in rats treated with MOF-5 at higher doses. The Malondialdehyde (MDA) levels increased at the dose of 50 mg/kg. Additionally, the expression levels of IL-1ß and TNF-α were significantly elevated in the rats' brains that were treated with MOF-5. Our findings indicate that sub-acute administration of MOF-5 induces cognitive impairment dose-dependently which might be partly mediated by increasing oxidative stress and inflammation.

AMP-activated protein kinase as a mediator of mitochondrial dysfunction of multiple sclerosis in animal models: A systematic review.

Multiple sclerosis (MS) is a chronic central nervous system (CNS) disorder characterized by demyelination, neuronal damage, and oligodendrocyte depletion. Reliable biomarkers are essential for early diagnosis and disease management. Emerging research highlights the role of mitochondrial dysfunction and oxidative stress in CNS disorders, including MS, in which mitochondria are central to the degenerative process. Adenosine monophosphate-activated protein kinase (AMPK) regulates the mitochondrial energy balance and initiates responses in neurodegenerative conditions. This systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, aimed to comprehensively assess the literature on AMPK pathways, mitochondrial dysfunction, and in vivo studies using MS animal models. The search strategy involved the use of AMPK syntaxes, MS syntaxes, and animal model syntaxes. The PubMed, Scopus, Web of Science, and Google Scholar databases were systematically searched on August 26, 2023 without publication year restrictions. The review identified and analyzed relevant papers to provide a comprehensive overview of the current state of related research. Eight studies utilizing various interventions and methodological approaches were included. Risk of bias assessment revealed some areas of low risk but lacked explicit reporting in others. These studies collectively revealed a complex relationship between AMPK, mitochondrial dysfunction, and MS pathogenesis, with both cuprizone and experimental autoimmune encephalomyelitis models demonstrating associations between AMPK and mitochondrial disorders, including oxidative stress and impaired expression of mitochondrial genes. These studies illuminate the multifaceted role of AMPK in MS animal models, involving energy metabolism, inflammatory processes, oxidative stress, and gene regulation leading to mitochondrial dysfunction. However, unanswered questions about its mechanisms and clinical applications underscore the need for further research to fully harness its potential in addressing MS-related mitochondrial dysfunction.

Efficacy of Nanocurcumin as an Add-On Treatment for Patients Hospitalized with COVID-19: A Double-Blind, Randomized Clinical Trial.

Background: Curcumin is a polyphenol derivative of the Curcuma longa rhizome, with potential antioxidant, anticancer, antidepressant, antiviral, and anti-inflammatory effects. This compound can be prepared as biodegradable polymer nanoparticles, called nanocurcumin, to improve its solubility, stability, half-life, and bioavailability. Aim: We explored nanocurcumin's effect on the clinical manifestations of patients hospitalized with mild-to-moderate COVID-19. Methods: This double-blind, randomized clinical trial involved 76 COVID-19 patients admitted to Ali-Asghar Hospital from December 2021 to March 2022. All patients received standard coronavirus treatment as per national guidelines. In addition, four times a day for two weeks, the curcumin group received 40 mg of nanocurcumin, while the control group received a placebo. Clinical manifestations were examined and recorded by the associate doctors working in the department. Statistical analysis was done using SPSS v. 21. Results: Thirty-nine people from the control group and 29 from the curcumin group completed the study. At baseline, the groups were comparable in age, gender, body mass index, hospitalization duration, and background diseases. The mean age of patients in the control and treatment groups was 53.9 ± 11.9 and 54.6 ± 13.4, respectively. Compared with the placebo, nanocurcumin minimized coughs (P=0.036), fatigue (P=0.0001), myalgia (P=0.027), oxygen demand (P=0.036), oxygen usage (P=0.05), and respiratory rate (P < 0.0001). By discharge, the curcumin group had a significantly greater increase in SPO2 than the control group (P=0.006). Conclusions: This preliminary study suggests that nanocurcumin has a potentiating anti-inflammatory effect when combined with standard COVID-19 treatment, helping the recovery from the acute inflammatory phase of the disease in hospitalized patients with mild-to-moderate disease severity. This trial is registered with Iranian Registry of Clinical Trials: IRCT20211126053183N1 (registered while recruiting on 13/12/2021).