Behrooz Motlagh

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline, oxidative stress, and neuroinflammation. Betanin, a natural antioxidant, has shown neuroprotective potential, but its clinical use is limited by poor bioavailability. This study investigates the effects of betanin-loaded nanomicelles, designed to enhance brain delivery, in a scopolamine-induced rat model of AD. Nanomicelles were synthesized and characterized using TEM, DLS, and FT-IR. Rats received either pre- or post-treatment with betanin nanomicelles, free betanin, donepezil, or saline. Cognitive performance was assessed using the Morris Water Maze. Gene expression levels of AQP4, BDNF, SIRT6, and Seladin-1 were measured using real-time PCR, and antioxidant activity was evaluated by assessing glutathione (GSH) and glutathione reductase (GR) in hippocampal tissue. Betanin nanomicelles improved spatial memory, increased BDNF and SIRT6 expression, and reduced AQP4 levels, indicating potential neuroprotection. Seladin-1 expression was notably elevated in the pre-treatment group, suggesting support for neuronal survival. Antioxidant assays showed restoration of GSH and GR activity. These findings suggest that betanin nanomicelles may enhance cognitive function and modulate neuroprotective pathways more effectively than free betanin, supporting their potential as a novel therapeutic strategy for AD.

Background Continuing hyperglycemia causes and exacerbate oxidative stress. Betanin as the principal pigment of red beet root has antioxidant, anti-inflammatory, and anti-diabetic properties. The purpose of this study was to investigate the potency of betanin on antioxidant defense in STZ-induced diabetic rats’ livers. Methods STZ at a single dose of 60 mg/kg body weight was intraperitoneally injected and betanin (10, 20, and 40 mg/kg/day) was administered orally for 28 days. Malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC) levels, and the enzyme activity of superoxide dismutase (SOD), catalases and glutathione peroxidases (GPx) were evaluated in the liver. Furthermore, gene expression of Nrf2 and mentioned antioxidant enzymes were measured by Real-time PCR. Results Betanin (10 and 20 mg/kg) significantly reduced PC levels and increased antioxidant enzyme activity in diabetic rats compared to the control diabetic group (P < 0.01). In comparison to the diabetic control group, all studied genes expression in diabetic rats were increased significantly with betanin at doses of 10 and 20 mg/kg (P < 0.02). The increase in gene expression at 20 mg/kg of betanin was significantly stronger than others (P < 0.015) except for the catalase (P = 0.201), that was almost the same. Moreover, treatment of diabetic rats with 20 mg/kg of betanin could significantly increase TAC levels (P < 0.05) and decrease MDA levels (P < 0.001) compared to diabetic control group. Conclusions Betanin could increase the antioxidant capacity of liver tissue associated with the Nrf2-mediated pathway in a dose-dependent manner.

Background: Previous studies have shown the altered levels of long-chain polyunsaturated fatty acids (LCPUFAs) in pathological hypoxic conditions. Elevated soluble fms-like tyrosine kinase-1 (sFlt-1) expression in hypoxia plays an important role in the pathogenesis of placental as preeclampsia. Objectives: The eicosapentaenoic acid (EPA; 20:5, n-3) as LCPUFAs (omega-3) might attenuate sFlt-1 and hypoxia-inducible factor-1α (HIF-1α) expressions and secretions. Methods: JEG-3 cells were incubated with dimethyloxalylglycine (DMOG) and EPA. The SFlt-1 gene expression was determined using a real-time polymerase chain reaction. The protein secretion of sFlt-1 and HIF-1α were analyzed using Western blot. Results: The incubation of JEG-3 cells with DMOG significantly elevated messenger ribonucleic acid (mRNA) expression and protein secretion of sFlt-1 (P < 0.05); nevertheless, EPA decreased mRNA expression and protein secretion of sFlt-1 (P < 0.05). Moreover, EPA inhibited the effect of DMOG on sFlt-1 (P = 0.0361) gene expression and protein secretion and HIF-1α (P = 0.0241) protein secretion. Conclusions: The sFlt-1 expression decreased by n-3 fatty acids in trophoblast tumor cell line under induced hypoxia conditions. It seems that changes in sFlt-1 expression are mediated by the transcription factor HIF-1α.

Background: In the last few years, the effects of bioactive food components have received much attention because of their beneficial effects including decreasing inflammation, scavenging free radicals, and regulating cell signaling pathways. Betanin as a potent antioxidant has been previously reported to exhibit anti diabetic effects. The present study aimed to evaluate the effects of betanin on glycemic control, lipid profile, hepatic function tests, as well as the gene expression levels of 5′ adenosine monophosphate‑activated protein kinase (AMPK), sirtuin-1 (SIRT1), and nuclear factor kappa B (NF‑κB) in streptozocin (STZ) induced diabetic rats. Methods: Diabetes was induced in male Sprague–Dawley rats by intraperitoneal administration of STZ. Different doses of betanin (10, 20 and 40 mg/kg.b.w) was administered to diabetic rats for 28 days. Fasting blood glucose and serum insulin were measured. The histopathology of liver and pancreas tissue evaluated. Real-time PCR was performed to assess gene expression levels. Results: Treatment of diabetic rats with betanin (10 and 20 mg/kg.b.w) reduced FBG levels compared to the control diabetic rats (P < 0.001). Betanin at the dose of 20 mg/kg.b.w was most effective in increasing serum insulin levels (P < 0.001) improving glucose tolerance test (GTT) as well as improvement in lipid profile and liver enzymes levels. According to histopathologic assay, different damages induced by STZ to liver and pancreas tissues was largely eliminated by treatment with 10 and 20 mg/kg.b.w of betanin. Betanin also significantly upregulated the AMPK and SIRT1 and downregulated the NF-κB mRNA expression compared to the diabetic control rats (P < 0.05). Conclusion: Betanin could modulate AMPK/SIRT1/NF-κB signaling pathway and this may be one of its anti-diabetic molecular mechanisms.

Background: Depression and sexual problems are common in patients with coronary artery disease (CAD) and can influence their quality of life. Objectives: The aim of this study was to compare the efficacy of saffron and its main constituent, crocin, in improving mental and sexual health and ultimately quality of life in CAD patients. Methods: This double-blind, placebo-controlled, randomized clinical trial was carried out during 8 weeks in 3 groups, including 1 placebo and 2 intervention groups. The study sample included 58 CAD patients within the age range of 40 - 65 years, referred to Shahid Madani cardiovascular hospital, Tabriz, Iran, from April 2015 to November 2016. The intervention groups received saffron aqueous extract (SAE; 30 mg; n, 20) or crocin (30 mg; n, 19). All the groups completed the demographic questionnaire, Beck depression inventory-II (BDI-II), Hurlbert index of sexual desire (HISD), and MacNew health-related quality of life questionnaire. Results: The BDI-II score significantly decreased in the SAE (pre- and posttest scores, 26.10 ± 11.98 and 21.05 ± 9.93, respectively) and crocin (pre- and posttest scores, 27.89 ± 8.46 and 22.68 ± 8.01, respectively) groups (P < 0.001). After adjustments for age, sex, and diagnosis time, similar results were obtained. There was no significant difference between the crocin and SAE groups in terms of total BDI-II score at the end of the study (P = 0.999). SAE and crocin had no significant effects on HISD scores (P = 0.148 and 0.317, respectively). However, they could significantly improve the total quality of life and its subscales (P < 0.001). Conclusions: SAE and crocin could improve depression and health-related quality of life in patients with CAD, whereas they had no significant effects on sexual desire. Keywords: Saffron; Crocin; Depression; Quality of Life; Coronary Artery Disease

Background: The human chitinase chitotriosidase enzyme, which is encoded by the CHIT1 gene, is produced by macrophages, and may be important in immune responses to chitin-containing organisms, such as fungi. Plasma chitotriosidase activity is used to diagnose and monitor some forms of lysosomal storage disorders, such as Gaucher's and Niemann–Pick disease. However, homozygous duplication of a 24-bp region in exon 10 of the CHIT1 gene eliminates enzyme activity and may complicate disease monitoring. The high prevalence of this mutation highlights the need to determine its frequency in different populations and screen patients for this mutation to verify whether chitotriosidase activity is a reliable marker of lysosomal storage disease. This study investigated the allele frequency of the 24-bp duplication in the general Iranian population. Methods: To identify the 24-bp duplication in exon 10 of the CHIT1 gene (H allele), genotyping of DNA extracted from peripheral blood leukocytes of 577 healthy Iranians was performed using polymerase chain reaction (PCR) amplification and high resolution melting (HRM) PCR techniques. Results: In this study, heterozygous and homozygous duplications were detected in 183 (31.7%) and 35 (6.1%) subjects, respectively. In addition, the allelic frequency was 21.9% (95% confidence interval). Conclusion: Our study indicates that genotype analysis by HRM-PCR is a fast, reliable, and highly accurate screening approach for identifying the 24-bp duplication in CHIT1 exon 10. Due to the wide range of duplication frequencies among different ethnic groups, new biomarkers are necessary for assessing genetic characteristics of lysosomal storage disorders in different populations.

The aim of the present study was to investigate the in vitro effects of mercury (Hg+2), lead (Pb+2), silver (Ag+2), tin (Sn+2), bismuth (Bi+3) and indium (In+3) ions on sperm creatine kinase. creatine kinase was isolated from human sperm homogenates after chromatography on a DEAE cellulose column. At 60 mug ml-1 metal concentration, 70% of the creatine kinase activity was inhibited by Hg+2, while at the same concentration, Pb+2, Ag+2, Sn+2, Bi+3 and In+3 caused 68%, 66.5%, 65.7%, 64.7% and 62.7% inhibition, respectively. All six metal ions displayed a competitive type of inhibition mechanism for the isolated creatine kinase as analyzed by Lineweaver-Burk plot. Ki values of Hg+2, Pb+2, Ag+2, Sn+2, Bi+3 and In+3 were calculated and 8.34 mM, 5 mM, 4.54 mM, 3.45 mM, 3.12 mM and 2.63 mM values were obtained, respectively. All the studied metal ions, at levels of 60 mug ml-1, may reduce normal sperm metabolism by inhibition of sperm creatine kinase, which probably is an important cause of infertility in men. However, further investigations, as in vitro and in vivo, are needed to elucidate the exact mechanism of heavy metals on male reproductive functioning at the molecular level.