👤 Mahsa Samadi

Nicotine withdrawal during adolescence induces severe neurobehavioral disturbances and neurochemical alterations, including anxiety, depression, affective dysregulation, oxidative stress, and neuroinflammation. Current therapeutic options for managing nicotine dependence remain suboptimal. This study investigated the neuroprotective potential of naringenin (NG) in alleviating behavioral and biochemical sequelae of nicotine withdrawal in adolescent rats. Male adolescent Wistar rats were allocated into eight groups and subjected to nicotine exposure (1 mg/kg) and NG treatment (50 or 100 mg/kg) across nicotine exposure and withdrawal phases. Behavioral assays (OFT, EPM, FST) were employed to evaluate anxiety- and depression-like behaviors. Neurochemical assessments of dopamine, serotonin, their metabolites (DOPAC, 5-HIAA), MAO-A activity, oxidative stress markers (MDA, Nit), antioxidant enzymes (SOD, CAT, TT), and neuroinflammatory/neurodegenerative biomarkers (GFAP, IL-10, BDNF, NSE) were conducted in prefrontal cortex (PFC) homogenates. Nicotine withdrawal significantly induced anxiety- and depression-like behaviors, disrupted monoaminergic balance, elevated MAO-A activity, and triggered oxidative and neuroinflammatory responses in the PFC. NG administration, particularly at 100 mg/kg across both phases, significantly ameliorated behavioral impairments, restored neurotransmitter homeostasis, inhibited MAO-A, suppressed lipid peroxidation and nitrosative stress, enhanced antioxidant defenses, reduced GFAP and NSE expression, and restored IL-10 and BDNF levels. NG exerts anxiolytic, antidepressant, antioxidant, and anti-inflammatory effects, likely via modulation of monoaminergic pathways and suppression of neuroinflammation and oxidative stress. These findings underscore the potential of NG as a promising candidate for mitigating neuropathological effects associated with nicotine withdrawal-induced neuropathology, particularly during adolescence. Show less

The growth in obesity and rates of abdominal obesity in developing countries is due to the dietary transition, meaning a shift from traditional, fiber-rich diets to Westernized diets high in processed foods, sugars, and unhealthy fats. Environmental changes, such as improving the quality of dietary fat consumed, may be useful in preventing or mitigating the obesity or unhealthy obesity phenotype in individuals with a genetic predisposition, although this has not yet been confirmed. Therefore, in this study, we investigated how dietary fat quality indices with metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUO) based on the Karelis criterion interact with genetic susceptibility in Iranian female adults. In the current cross-sectional study, 279 women with overweight or obesity participated. Dietary intake was assessed using a 147-item food frequency questionnaire and dietary fat quality was assessed using the cholesterol-saturated fat index (CSI) and the ratio of omega-6/omega-3 (N6/N3) essential fatty acids. Three single nucleotide polymorphisms-MC4R (rs17782313), CAV-1 (rs3807992), and Cry-1(rs2287161) were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and were combined to produce the genetic risk score (GRS). Body composition was evaluated using a multi-frequency bioelectrical impedance analyzer. Participants were divided into MHO or MUO phenotypes after the metabolic risk assessment based on the Karelis criteria. We found significant interactions between GRS and N6/N3 in the adjusted model controlling for confounding factors (age, body mass index, energy, and physical activity) (β = 2.26, 95% CI: 0.008 to 4.52, P = 0.049). In addition, we discovered marginally significant interactions between GRS and N6/N3 in crude (β = 1.92, 95% CI: -0.06 to 3.91, P = 0.058) and adjusted (age and energy) (β = 2.00, 95% CI: -0.05 to 4.05, P = 0.057) models on the MUH obesity phenotype. However, no significant interactions between GRS and CSI were shown in both crude and adjusted models. This study highlights the importance of personalized nutrition and recommends further study of widely varying fat intake based on the findings on gene-N6/N3 PUFA interactions. Show less

For more than eight decades, cardiovascular disease (CVD) has remained the leading cause of death in the world. CVD risk factors are multifaceted, with genetics and lifestyle both playing a role. The aim of this study was to investigate the association between a genetic profile risk score for obesity GRS and cardio-metabolic risk factors in overweight and obese women. The current cross-sectional study was conducted on 391 overweight and obese women. The genetic risk score was created by combining three single nucleotide polymorphisms [MC4R (rs17782313), CAV-1 (rs3807992), and Cry-1 (rs2287161)]. Anthropometric measurements, blood pressure, and some blood parameters were measured by standard protocols. A significant association between the GRS and some of cardiometabolic risk factors variables such as body mass index (β = 0. 49, 95%CI = 0.22 to 0.76, p < 0.001), waist circumference (β = 0. 86, 95%CI = 0.18 to 1.54, p = 0.01), body fat mass (β = 0. 82, 95%CI = 0.25 to 1.39, p = 0.005), %body fat (β = 0. 44, 95%CI = 0.06 to 0.82, p = 0.02), and hs-CRP (β = 0.46, 95% CI = 0.14 to 0.78, p = 0.005) was observed in crude model. After adjustment for confounding factors (age, BMI, and physical activity), a significant positive association was observed between BMI (p = 0.004), WC (p = 0.02), body fat mass (p = 0.01), %BF (p = 0.01), hs-CRP (p = 0.009), and GRS. In addition, we discovered a significant negative association between the GRS and BMC (= -0.02, 95%CI = -0.05 to -0.001, p = 0.04). But other variables did not show any significant association with GRS among obese and overweight women. We found a significant positive association between GRS, including MC4R (rs17782313), CAV-1 (rs3807992), and Cry-1 (rs2287161) and cardiometabolic risk factors among overweight and obese Iranian women. Show less

Preeclampsia (PE) is one of the most serious disorders of human pregnancy with a high rate of mortality for the fetus and mother. Several etiological factors are involved in the onset of this disease. Upregulation of IL-27 has been reported in placental tissue recovered from preeclamptic women, but the role of IL-27 has not yet been investigated in PE. The aim of the study was to investigate the association of IL-27 rs153109 and rs17855750 gene polymorphisms with PE; also, protein levels and susceptibility and severity of PE in Iranian women were evaluated. This case-control study was performed on 199 PE patients and 228 healthy women as the control group. IL-27 rs153109 and rs17855750 SNPs were genotyped using a PCR-RFLP method. Moreover, the levels of IL-27 were determined in 40 PE and 45 healthy women using ELISA method. Statistical analysis indicated that there were no differences in genotype, allele and genotype combination frequencies in the SNPs between cases and controls. The plasma level of IL-27 was elevated in the mild form of the disease compared with controls (p-value: 0.006). The effect of IL-27 in preeclampsia is not due to the studied cytokine polymorphisms, but the level of IL-27 might be associated with the severity of preeclampsia in Iranian women. Show less

Metabolic syndrome (MetS) is characterized by a clustering of cardiovascular risk factors that include: abdominal obesity, dyslipidemia, hypertension and glucose intolerance. Angiopoietin-like protein 4 (ANGPTL4) is a circulating peptide that is an inhibitor of lipoprotein lipase, a key enzyme in lipid metabolism. The objective of this study was to investigate the association of ANGPTL4 gene variants (E40K) with fasting serum triglyceride levels and with cardiovascular risk factors, that included the presence of MetS in 817 subjects recruited from the Mashhad stroke and heart Atherosclerosis Disorders (MASHAD) cohort Study. ANGPTL4 genotypes were determined using a TaqMan genotyping based real time PCR method. The association of the genetic variant with the risk of metabolic syndrome and its relationship with lipid profile were determined. The frequency of GG, GA and AA genotypes were 96.9, 2.7 and 0.4% in individuals with MetS, and 78.8, 20.8, 0.4%, in those without MetS. The GA genotype of the rs116843064 polymorphism was associated with a lower risk for MetS (e.g., OR in Codominant genetic model: 0.14, 95% CI: (0.06-0.33), p < 0.0001). Subject with an A allele had a higher risk for MetS (OR: 6.72, 95% CI: (3.05-14.82), p < 0.0001). There was a significant difference in fasted lipid profiles across the genotypes for ANGPTL4. Carriers of the AG genotype had higher levels of serum HDL-cholesterol (HDL-C) and lower TG, compared to the GG homozygotes genotype. The G allele at the rs116843064 polymorphic locus of the ANGPTL4 gene was associated with a lower prevalence of MetS. Show less

The objective of this study was to evaluate the biological activities of the major phytosterols present in argan oil (AO) and in cactus seed oil (CSO) in BV2 microglial cells. Accordingly, we first determined the sterol composition of AO and CSO, showing the presence of Schottenol and Spinasterol as major sterols in AO. While in CSO, in addition to these two sterols, we found mainly another sterol, the Sitosterol. The chemical synthesis of Schottenol and Spinasterol was performed. Our results showed that these two phytosterols, as well as sterol extracts from AO or CSO, are not toxic to microglial BV2 cells. However, treatments by these phytosterols impact the mitochondrial membrane potential. Furthermore, both Schottenol and Spinasterol can modulate the gene expression of two nuclear receptors, liver X receptor (LXR)-α and LXRβ, their target genes ABCA1 and ABCG1. Nonetheless, only Schottenol exhibited a differential activation vis-à-vis the nuclear receptor LXRβ. Thus Schottenol and Spinasterol can be considered as new LXR agonists, which may play protective roles by the modulation of cholesterol metabolism. Show less

The biochemical and biological properties of 4β-hydroxycholesterol and of its isomer, 4α-hydroxycholesterol, are not well known. So, we determined the ability of 4α- and 4β-hydroxycholesterol to react with LXRα and LXRβ, and we characterized the activities of these oxysterols on oligodendrocytes which are myelin synthesizing cells. The effects of 4α- and 4β-hydroxycholesterol were studied on 158N murine oligodendrocytes to assess their activities on cell growth and viability, oxidative and inflammatory status. To this end different parameters were used: cell counting with trypan blue; identification of dead cells and cell cycle analysis with propidium iodide; evaluation of mitochondrial depolarization, lysosomal membrane integrity, actin depolimerization, nuclear morphology, and superoxide anion production after staining with JC-1, acridine orange, rhodamine-phalloidin, Hoechst 33342, and dihydroethidium, respectively; evaluation of ultrastructural changes by transmission electron microscopy, and cytokine quantification with a cytometric bead array. Only 4β-hydroxycholesterol is a LXRα and β agonist. No cytotoxic effects were found with 4α-hydroxycholesterol except a slight inhibition of cell growth at elevated concentrations. At high concentrations, 4β-hydroxycholesterol was not only able to inhibit cell growth, but also to induce cell death associated with a loss of mitochondrial transmembrane potential, dysfunctions of lysosomal membrane integrity, and superoxide anion overproduction. These side effects were lower than those observed with 7-ketocholesterol and 25-hydroxycholesterol used as positive controls. On oligodendrocyte murine primary cultures, only lysosomal membrane integrity was slightly affected under treatment with 4α- and 4β-hydroxycholesterol. So, 4α- and 4β-hydroxycholesterol have different biological activities. Their ability to induce cytotoxic effects on oligodendrocytes can be considered as weak comparatively to 7-ketocholesterol and 25-hydroxycholesterol. Show less