👤 Sedigheh Gholami

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

This study aims to identify new variants and haplotypes associated with monogenic obesity by analyzing known obesity genes in whole exome sequencing (WES) data. The monogenic obesity-associated genes were identified by using the National Institutes of Health (NIH) Genetic Testing Registry (GTR) monogenic obesity panels. WES was performed on ( Seventy-four genes were included in WES analyses. After Bonferroni correction, the T allele of rs2275155 on This study suggested that the T allele of two common variants rs2275155 and rs116167439, also rare variant rs201676524 are associated with an increased risk of monogenic obesity. The significant haplotype associations indicate these variants may be in linkage with causative rare variants and should be considered in future studies. The online version contains supplementary material available at 10.1007/s40200-024-01507-2. Show less

Recent studies suggest a link between dietary fat quality and obesity. Genetic risk scores (GRS) can predict obesity risk based on genetic factors. This study investigates how GRS and fatty acid quality affect visceral adiposity index (VAI) and body adiposity index (BAI) in overweight and obese women. In this study, 278 overweight and obese women (aged 18-58) participated. We have used a comprehensive food frequency questionnaire (FFQ) to evaluate dietary intake and the fatty acids quality indexes. We have employed standard methods to measure biochemical factors, anthropometrics, and physical activity levels. Finally, the GRS was created by combining three SNPs [CAV-1 (rs3807992), Cry-1 (rs2287161), and MC4R (rs17782313)]. The study found that there was no significant association between the quality of fat intake (as measured by CSI score and N6/N3 score) and VAI or BAI in both crude (B = 70.70, SE = 35.14, CI:1.81-139.55, P = 0.04) and adjusted models (B = 93.67, SE = 39.28, CI:16.68-17.68, P = 0.01). CSI provides information on cholesterol and saturated fats. However, there was a notable interaction between the GRS and the N6/N3 score on VAI, suggesting that obese women with high obesity-related SNPs who consumed foods with a higher ratio of N6/N3 fatty acids tended to have an increased VAI. This study shows; that eating more food sources containing a higher ratio of N6/N3 may be the reason for the increase in VAI in obese women who have high obesity-related SNPs and emphasizes the matter of personalized nutrition in obesity issues. 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

The GramAdapt Social Contact Dataset is a curated dataset of 34 language pairs with qualitative and quantifiable data on social interaction and aspects of societal multilingualism. The language pairs were sampled globally to represent the world's linguistic diversity. The dataset can be used to interrogate the social dimensions of language contact independently or in conjunction with appropriate linguistic data. The data were collected by distributing a questionnaire to experts who have experience with either one or both of the language communities of a pair. The data represent subjective expert assessments based on choices from predetermined answers which can be quantified. Authors 1, 2 and 3 manually checked the response to identify possible misjudgments or misunderstandings. This results in a dataset containing 13,493 data points. This dataset is a first of its kind in the field of linguistics, built upon wide findings from sociolinguistics, historical linguistics, psycholinguistics, and linguistic anthropology. Show less

Acute Respiratory Distress Syndrome is a lung disorder defined by the acute onset of hypoxemia, the commonest being abdominal sepsis.Many biomarkers have been studied for diagnostic prognostication and ARDS pharmacotherapy. The current study aim to assess the protective effects of UFH versus Enoxaparin in sepsis-induced ARDS and related metabolic sequelae. Sepsis was initiated through cecal ligation and puncture (CLP). Wistar rats were divided to: sham, CLP, CLP + unfractionated Heparin, and CLP + Enoxaparin and CLP + distilled water groups. Levels of serum Lipoxin A4 (LXA4), lipoprotein lipase (LPL), leukotriene E4 (LTE4), leukotriene B4 (LTB4), interleukin-8 (IL-8), were quantified. Furthermore, mRNA expression of receptors for advanced glycation end products (RAGE) and angiopoietin-2 (ANG-2) were assessed. Histopathological study was conducted to assess any lung injuries. Septic rats demonstrated higher levels of leukotriene E4, leukotriene B4, and interleukin-8, while treatment with unfractionated Heparin attenuated these levels but enoxaparin effectiveness on LTB-4 and IL-8 was not as significant as heparin while its was equally effective on LTE-4. Moreover, mRNA levels of RAGE and ANG-2 were enhanced in CLP rats. These elevations were mitigated by treatment with unfractionated Heparin and reduced by enoxaparin to a lesser extent. Treatment with unfractionated Heparin increased the lipoxin A4 and lipoprotein lipase levels but enoxaparin had no effect on the LPL level. Lung protective effect of unfractionated Heparin was further confirmed by histopathological observations of lung tissue samples. Our study demonstrates that UFH can modulate ARDS and metabolic dysfunction in hyperinflammatory conditions like sepsis. Show less

Obesity has become a common global problem. Some obese people can be metabolically healthy. Gene-environment interaction can be important in this context. This study aimed to assess the interaction between dietary fat quality indices and the Melanocortin 4 receptor (MC4R) gene in metabolically healthy and unhealthy overweight and obese women. This cross-sectional study was conducted on 279 women with overweight and obesity. The definition of metabolically healthy and unhealthy phenotypes was done according to Karelis criteria. Dietary assessment was done using a 147-item validated semi-quantitative food frequency questionnaire and dietary fat quality was assessed by cholesterol-saturated fat index (CSI) and the ratio of omega-6/omega-3 (N6/N3) essential fatty acids. MC4R was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. A generalized linear model was used to evaluate the interaction between dietary fat quality indices and the MC4R gene in both crude and adjusted models. Study subjects with higher ratio of N6/N3 had higher homeostatic model assessment for insulin resistance (HOMA IR) index (P = 0.03) and other variables showed no difference according to the tertile of CSI and N6/N3. Participants with the C allele of MC4R rs17782313 had lower height (P < 0.001) and higher HOMA index (P = 0.01). We found that the CC genotype of MC4R interacts with the N6/N3 ratio on the metabolically unhealthy phenotype in the crude model (β = 9.94, CI 2.49-17.39, P = 0.009) and even after adjustment for all confounders (β = 9.002, CI 1.15-16.85, P = 0.02, β =  - 12.12, CI 2.79-21.46, P = 0.01). The data of this study can justify one inconsistency observed in society, regarding dietary recommendations about metabolic health status. Those with CC genotype, are more likely to have an unhealthy phenotype with an increase in N6/N3 as one fat quality indices than those who do not have CC genotype. We found the interaction of dietary fat quality indices such as N6/N3 and the MC4R gene in metabolically unhealthy overweight and obese women. 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

Systemic sclerosis (SSc) is a connective tissue disease associated with vascular damage and multi organ fibrotic changes with unknown pathogenesis. Most SSc patients suffer from defective angiogenesis/vasculogenesis and cardiac conditions leading to high mortality rates. We aimed to investigate the cardiovascular phenotype of SSc by cardiogenic differentiation of SSc induced pluripotent stem cells (iPSC). In this experimental study, we generated iPSC from two diffuse SSc patients, followed by successful differentiation into endothelial cells (ECs) and cardiomyocytes (CMs). SSc-derived EC (SSc-EC) expressed KDR, a nearly EC marker, similar to healthy control-EC (C1-EC). After sorting and culturing KDR+ cells, the resulting EC expressed CD31, a late endothelial marker, but vascular endothelial (VE)-cadherin expression markedly dropped resulting in a functional defect as reflected in tube formation failure of SSc-EC. Interestingly, upregulation of SNAI1 (snail family transcriptional repressor 1) was observed in SSc-EC which might underlie VE-cadherin downregulation. Furthermore, SSc-derived CM (SSc-CM) successfully expressed cardiacspecific markers including ion channels, resulting in normal physiological behavior and responsiveness to cardioactive drugs. This study provides an insight into impaired angiogenesis observed in SSc patients by evaluating Show less