Pharmaco-molecular assessment of the effects of anandamide and its antagonists on hippocampal tissue in Wistar albino rats.

OBJECTIVE: The members of the matrix metalloproteinase (MMP) family and cannabinoids (CBs) are reportedly associated with hippocampus-dependent memory functions. However, the effects of endogenously formed CBs on hippocampal long-term potentiation remain unknown. The present study aimed to investigate the changes in the gene and protein expression levels of matrix metallopeptidase 9 (MMP-9), phosphatase and tensin homolog (PTEN), and NOTCH receptor 1 (NOTCH1) in rat hippocampal tissues treated with anandamide (AEA), AM251, 6-iodopravadolin (AM630), and N-[4-{[(3,4-Dimethyl-5-isoxazolyl)amino]sulfonyl}phenyl] (ML193). MATERIALS AND METHODS: The subjects were divided into 10 groups (n = five per group). The pharmaceuticals were administered via intraperitoneal injection once a day for seven days, except for the control group. The resected hippocampal tissues were then evaluated using a quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot analysis. The data obtained were statistically analyzed, and p < 0.01 was considered statistically significant. RESULTS: Contrary to the literature, the changes in MMP-9 expression were not statistically significant, but the changes in PTEN and NOTCH1 were. The findings of this in vivo experimental study revealed that the agonists and antagonists acting on the CB system have significant molecular effects on hippocampal tissue. CONCLUSIONS: The changes in gene and protein expressions may be one of the reasons for the neurodegenerative processes observed in patients using these agonists and antagonists, whose effects on the CB system have not been fully explained yet. Our study can contribute to the literature as it is the first study investigating the MMP-9, PTEN and NOTCH1 gene and protein expression.

Assessment of boron-containing compounds and oleoylethanolamide supplementation on the recovery trend in patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: In this study, we investigate the effect of boron-containing compounds and oleoylethanolamide supplementation on the recovery trend in patients with COVID-19. TRIAL DESIGN: The current study is a single-center, randomized, double-blind, placebo-controlled clinical trial with parallel groups. PARTICIPANTS: The inclusion criteria include male and female patients≥18 years of age, with a confirmed diagnosis of SARS-CoV-2 infection via polymerase chain reaction (PCR) and/or antibody test and with written informed consent to participate in this trial. The exclusion criteria include regular use of any other supplement, severe and critical COVID-19 pneumonia, pregnancy and breastfeeding. This study is being conducted at Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran. INTERVENTION AND COMPARATOR: Patients are randomly assigned to four groups. The first group (A) will take one capsule containing 5 mg of boron compounds twice a day for two weeks. The second group (B) will take one capsule containing 200 mg oleoylethanolamide twice a day for two weeks. The third group (C) will take one capsule containing 5 mg boron compounds with 200 mg oleoylethanolamide twice a day for two weeks, and the fourth group (D) does not receive any additional treatment other than routine treatments. Boron-containing compounds and oleoylethanolamide capsules will be synthesized at Nutrition Research Center of Tabriz University of Medical Sciences. MAIN OUTCOMES: The primary end point of this study is to investigate the recovery rate of clinical symptoms, including fever, dry cough, and fatigue, as well as preclinical features, including complete blood count (CBC), the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) profiles within two weeks of randomization. RANDOMISATION: Patients are randomized into four equal groups in a parallel design (allocation ratio 1:1). A randomized block procedure is used to divide subjects into one of four treatment blocks (A, B, C, and D) by a computer-generated allocation schedule. BLINDING (MASKING): The participants and investigators (enrolling, assessing, and analyzing) are blinded to the intervention assignments until the end of the study and data analysis. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The calculated total sample size is 40 patients, with 10 patients in each group. TRIAL STATUS: The protocol is Version 1.0, May 17, 2020. Recruitment began May 19, 2020, and is anticipated to be completed by October 19, 2020. TRIAL REGISTRATION: This clinical trial has been registered by the title of "Assessment of boron-containing compounds and oleoylethanolamide supplementation on the recovery trend in Patients with COVID-19: A double-blind randomized placebo-controlled clinical trial" in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20090609002017N35 ", https://www.irct.ir/trial/48058 . The registration date is 17 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.