Repository of Research and Investigative Information Isfahan University of Medical Sciences
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Bridging the gap: The endocannabinoid system as a functional fulcrum for benzodiazepines in a novel frontier of anxiety pharmacotherapy
While benzodiazepines have been a mainstay of the pharmacotherapy of anxiety disorders, their short-term efficacy and risk of abuse have driven the exploration of alternative treatment approaches. The endocannabinoid (eCB) system has emerged as a key modulator of anxiety-related processes, with evidence suggesting dynamic interactions between the eCB system and the GABAergic system, the primary target of benzodiazepines. According to the existing literature, the activation of the cannabinoid receptors has been shown to exert anxiolytic effects, while their blockade or genetic deletion results in heightened anxiety-like responses. Moreover, studies have provided evidence of interactions between the eCB system and benzodiazepines in anxiety modulation. For instance, the attenuation of benzodiazepine-induced anxiolysis by cannabinoid receptor antagonism or genetic variations in the eCB system components in animal studies, have been associated with variations in benzodiazepine response and susceptibility to anxiety disorders. The combined use of cannabinoid-based medications, such as cannabinoid receptor agonists and benzodiazepine co-administration, has shown promise in augmenting anxiolytic effects and reducing benzodiazepine dosage requirements. This article aims to comprehensively review and discuss the current evidence on the involvement of the eCB system as a key modulator of benzodiazepine-related anxiolytic effects, and further, the possible mechanisms by which the region-specific eCB system-GABAergic connectivity modulates the neuro-endocrine/behavioral stress response, providing an inclusive understanding of the complex interplay between the eCB system and benzodiazepines in the context of anxiety regulation, to inform future research and clinical practice. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies
Deep Radiogenomics Sequencing for Breast Tumor Gene-Phenotype Decoding Using Dynamic Contrast Magnetic Resonance Imaging
PurposeWe aim to perform radiogenomic profiling of breast cancer tumors using dynamic contrast magnetic resonance imaging (MRI) for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) genes.MethodsThe dataset used in the current study consists of imaging data of 922 biopsy-confirmed invasive breast cancer patients with ER, PR, and HER2 gene mutation status. Breast MR images, including a T1-weighted pre-contrast sequence and three post-contrast sequences, were enrolled for analysis. All images were corrected using N4 bias correction algorithms. Based on all images and tumor masks, a bounding box of 128 x 128 x 68 was chosen to include all tumor regions. All networks were implemented in 3D fashion with input sizes of 128 x 128 x 68, and four images were input to each network for multi-channel analysis. Data were randomly split into train/validation (80) and test set (20) with stratification in class (patient-wise), and all metrics were reported in 20 of the untouched test dataset.ResultsFor ER prediction, SEResNet50 achieved an AUC mean of 0.695 (CI95: 0.610-0.775), a sensitivity of 0.564, and a specificity of 0.787. For PR prediction, ResNet34 achieved an AUC mean of 0.658 (95 CI: 0.573-0.741), a sensitivity of 0.593, and a specificity of 0.734. For HER2 prediction, SEResNext101 achieved an AUC mean of 0.698 (95 CI: 0.560-0.822), a sensitivity of 0.750, and a specificity of 0.625.ConclusionThe current study demonstrated the feasibility of imaging gene-phenotype decoding in breast tumors using MR images and deep learning algorithms with moderate performance
Thymoquinone mitigates diclofenac-induced hepatorenal toxicity in male Wistar rats by balancing the redox state and modulating Bax/Bcl-2/caspase-3 apoptotic pathways and NF-κB signaling
Background and purpose:Diclofenac (DF), a widely used non-steroidal anti-inflammatory drug, can induce hepatotoxicity and nephrotoxicity. This study investigated the protective effects of thymoquinone (TQ), a bioactive compound from Nigella sativa, against DF-induced organ damage in rats.Experimental approach:Forty-eight male rats were divided into six groups (8 each) and treated orally for seven days as follows: group 1 (control): normal saline; group 2: DF (50 mg/kg); group 3: DF (50 mg/kg) + silymarin (50 mg/kg); groups 4-6: DF (50 mg/kg) + TQ at 10, 20, or 40 mg/kg, respectively. Serum biochemical parameters, hepatorenal oxidative stress markers, pro-inflammatory cytokines, and apoptosis-related genes were assessed. Histopathological examinations of liver and kidney tissues were also performed.Findings/Results:DF administration induced significant liver and kidney damage, evidenced by elevated serum biochemical markers, increased oxidative stress, inflammation, apoptosis-related gene expression, and histopathological alterations. TQ treatment, particularly at the highest dose (40 mg/kg) effectively attenuated these changes. TQ improved liver and kidney function, reduced oxidative stress markers, suppressed inflammation, modulated apoptosis-related gene expression, and ameliorated histopathological damage.Conclusion and implication:TQ exerted significant protective effects against DF-induced hepatorenal toxicity in rats, potentially through its antioxidant, anti-inflammatory, and anti-apoptotic properties. These findings suggest that TQ may be a promising therapeutic agent for mitigating DF-induced organ damage. However, further research, including clinical trials, is needed to confirm its efficacy and safety in humans
Isfahan Artificial Intelligence Event 2023: Lesion Segmentation and Localization in Magnetic Resonance Images of Patients with Multiple Sclerosis
Background:Multiple sclerosis (MS) is one of the most common reasons of neurological disabilities in young adults. The disease occurs when the immune system attacks the central nervous system and destroys the myelin of nervous cells. This results in appearing several lesions in the magnetic resonance (MR) images of patients. Accurate determination of the amount and the place of lesions can help physicians to determine the severity and progress of the disease.Method:Due to the importance of this issue, this challenge has been dedicated to the segmentation and localization of lesions in MR images of patients with MS. The goal was to segment and localize the lesions in the flair MR images of patients as close as possible to the ground truth masks.Results:Several teams sent us their results for the segmentation and localization of lesions in MR images. Most of the teams preferred to use deep learning methods. The methods varied from a simple U-net structure to more complicated networks.Conclusion:The results show that deep learning methods can be useful for segmentation and localization of lesions in MR images. In this study, we briefly described the dataset and the methods of teams attending the competition
The effect of vitamin E supplementation on serum low-density lipoprotein oxidization: A systematic review and meta-analysis of clinical trials
Oxidation of low-density lipoprotein (LDL) accelerates atherosclerosis. Vitamin E is a powerful fat-soluble antioxidant; some studies have shown its beneficial effects in reducing oxidized LDL levels. Due to the inconsistent reports, we performed a systematic review and meta-analysis to evaluate the impact of vitamin E supplementation on oxidation of LDL levels. PubMed, Scopus, Web of Science, and Google Scholar were systematically searched to find clinical trials published in English. A total of 21 records with 29 intervention arms were included in this review. In the meta-analysis of 6 studies that reported changes in oxidized LDL levels, a significant decrease in LDL oxidation was observed (95 CI: -1.44 -2.5, -0.38; I-2 = 95.8%, P < 0.001; Tau-squared: 1.6171). Moreover, a meta-analysis of 7 studies that reported lag time as a measure of LDL oxidation showed that vitamin E supplementation significantly increased the lag time of LDL oxidation (95% CI: 20.45 12.46, 28.43; I-2 = 95.9%, P < 0.001; Tau-squared: 103.3545). Two studies used the thiobarbituric acid-reactive substances (TBARS) assay to evaluate the susceptibility to LDL oxidation. One of them showed a significant decrease in LDL susceptibility to oxidation after supplementation with tocopherol, while the other one did not show a significant effect. Vitamin E significantly reduced the susceptibility of LDL to oxidation and increased the lag time of LDL oxidation
Differential effects of β-hydroxybutyrate and α-ketoglutarate on HCT-116 colorectal cancer cell viability under normoxic and hypoxic low-glucose conditions: exploring the role of SRC, HIF1α, ACAT1, and SIRT2 genes
Recent therapeutic strategies have highlighted the potential of beta-hydroxybutyrate (BHB) and alpha-ketoglutarate (alpha-KG) as effective anticancer agents, particularly for colon cancer. These metabolites can modulate cellular metabolism and induce epigenetic changes, inhibiting tumor growth. Nonetheless, certain cancer cells may utilize ketone bodies, like BHB as nutrient sources under hypoxic conditions, potentially reducing treatment efficacy. Understanding these mechanisms is crucial for optimizing cancer therapies. This study evaluated the effects of BHB and alpha-KG on HCT-116 colorectal cancer cell viability under normoxic and low-glucose hypoxic conditions. HCT-116 cell lines were treated with different doses of BHB and alpha-KG in normoxic and low-glucose hypoxic conditions, and then cell viability was assessed by the MTT assay. Moreover, the mRNA expression levels of SRC, hypoxia-inducible factor 1 alpha (HIF-1 alpha), acetyl-CoA acetyltransferase 1 (ACAT1), and sirtuin 2 (SIRT2) genes were determined using quantitative reverse transcriptase-polymerase chain reaction (q RT-PCR). BHB significantly increased the proliferation of HCT-116 colon cancer cells under low-glucose hypoxic conditions, while alpha-KG maintained cell viability in normoxic conditions but not in hypoxia. BHB treatment reduced SIRT2 mRNA levels and increased ACAT1, SRC, and HIF-1 alpha expression. Conversely, alpha-KG decreased ACAT1, SRC, and HIF-1 alpha expression and increased SIRT2 levels in normoxia but could not reverse gene expression during hypoxia. Our study demonstrated that BHB and alpha-KG exhibited complex interactions with colon cancer cell viability under varying oxygen and glucose conditions. While BHB promoted cell proliferation in hypoxic environments, alpha-KG showed protective effects in normoxic conditions. This research contributed to the growing body of evidence supporting the role of metabolic modulators in cancer therapy and emphasized the importance of understanding tumor microenvironments to optimize treatment outcomes. However, the need for further research into the metabolic pathways is underscored to enhance therapeutic strategies for cancer treatment
Antimicrobial Peptides Against Arboviruses: Mechanisms, Challenges, and Future Directions
This review delves into the potential of antimicrobial peptides (AMPs) as promising candidates for combating arboviruses, focusing on their mechanisms of antiviral activity, challenges, and future directions. AMPs have shown promise in preventing arbovirus attachment to host cells, inducing interferon production, and targeting multiple viral stages, illustrating their multifaceted impact on arbovirus infections. Structural elucidation of AMP-viral complexes is explored to deepen the understanding of molecular determinants governing viral neutralization, paving the way for structure-guided design. Furthermore, this review highlights the potential of AMP-based combination therapies to create synergistic effects that enhance overall treatment outcomes while minimizing the likelihood of resistance development. Challenges such as susceptibility to proteases, toxicity, and scalable production are discussed alongside strategies to address these limitations. Additionally, the expanding applications of AMPs as vaccine adjuvants and antiviral delivery systems are emphasized, underscoring their versatility beyond direct antiviral functions
Mediterranean diet and prime diet quality score are associated with reduced risk of premature coronary artery disease in Iran: a multi-centric case-control study
The Mediterranean diet (Med-Diet) is widely recognized for its protective effect in cardiovascular diseases (CVDs), less is known about the associations between health and adherence to the Prime Diet Quality Score (PDQS). This study investigates the relationship between adherence to the Med-Diet and PDQS with the risk of premature coronary artery disease (PCAD) in an Iranian population. A total of 3287 participants were included in this multicenter case-control study across various ethnic groups in Iran, categorized into PCAD cases (n = 2106) and controls (n = 1181). PCAD cases were defined as individuals with at least one coronary artery exhibiting >= 75 stenosis or a left main coronary artery with >= 50 stenosis, while controls had normal coronary arteries. Dietary intake was assessed using a semi-quantitative food frequency questionnaire (FFQ), previously validated for accuracy in the Iranian population Adherence to the Med-Diet was assessed using a standardized scoring system, awarding one point for higher consumption of beneficial food groups (such as vegetables, whole grains, legumes, fish, nuts, and a high monounsaturated-to-saturated fat ratio) and one point for lower consumption of less favorable foods (such as red and processed meats). The total score ranged from 0 to 9, with higher scores indicating greater adherence to the Med-Diet. The PDQS, a dietary quality index, evaluated adherence across 14 healthy and 7 unhealthy food groups, with higher scores reflecting better diet quality. Logistic regression models were employed to examine the association between dietary scores and PCAD risk. Participants with higher adherence to both the Med-Diet and PDQS had significantly lower odds of PCAD (OR = 0.30, 95 CI: 0.22, 0.40; P for trend < 0.001 for PDQS), with a stronger association observed for the Med-Diet (OR = 0.08, 95 CI: 0.06, 0.10; P for trend < 0.001). Additionally, higher adherence to the Med-Diet (OR = 0.04, 95 CI 0.03, 0.05) and PDQS (OR = 0.21, 95 CI: 0.17, 0.26) was inversely associated with PCAD severity in the fully adjusted model. This study showed a protective association of the Med-Diet and PDQS with reduced risk of PCAD in the Iranian population
The Association Between Autism Spectrum Disorders and Dietary Intake of Carbohydrates in School-Aged Children in Iran: A Case-Control Study
BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder with both genetic and environmental risk factors. Imbalanced dietary Intake has recently been proposed as a possible environmental risk factor for ASD. The purpose of this study was to investigate the possible connection between ASD and intake of various carbohydrate types.Methods110 patients with autism from 5 to 15 years of age have been included as the case group and 110 neurotypical children who are part of a similar age category have been chosen as controls for this case-control study. To estimate the dietary intake of carbohydrates, a validated food frequency questionnaire (FFQ) was used.ResultsPositive connections were found between ASD and the intake of sugar (OR = 1.03, CI 95: 1.02-1.06, p = 0.001), and maltose (OR = 2.09, CI 95: 1.37-3.20, p = 0.001). A reverse correlation was found between ASD and dietary intake of carbohydrates (OR = 0.97, CI 95: 0.96-0.98, p = 0.001), fructose (OR = 0.85, CI 95: 0.77-0.94, p = 0.002), and lactose (OR = 0.89, CI 95: 0.83-0.96, p = 0.002).ConclusionThis study showed a direct link between autism and the intake of sugar and maltose and an inverse connection between autism and the dietary intake of total carbohydrate, fructose, and lactose. There is a need to carry out additional long-term studies
Investigating ethnic differences in risk factors and severity of developing premature coronary artery disease: Predicting the effect of risk factors through decision tree analysis in a multicenter case-control study; Results from Iran Premature Coronary Artery Disease (IPAD study)
Introduction: Premature coronary artery disease (PCAD) has an ascending trend especially in CAD across various Iranian ethnicities. Methods: This case-control study was done on 3015 Iranian patients undergoing coronary artery Arab, Fars, Kurd, Gilak, and Lur. This study was performed over three years in 14 capitals of provinces in Iran headed by Isfahan Cardiovascular Research Center, by including men <= 60 stenosis above 75 (more than 50 in the left main), they were categorized as Case group .The effects of conventional risk factors as well as psychosocial ones including age, gender, weight, diabetes, hypertension, etc. were determined in each ethnicity using decision tree statistical method. Also, via logistic regression method, the odds of incidence of CAD in each ethnicity were specified against the Fars ethnicity (the predominant ethnicity in Iran). Results: The most common risk factor among different ethnicities was age and male gender. Also, among the Iranian ethnicities, Kurd had the lowest chance while Gilak and Azari had the highest chance of developing PCAD as compared to the Fars ethnicity. Investigation of the behavioral and psychological dimensions indicated that stress was significantly higher among those without coronary artery involvement as compared to those with this involvement. The decision tree model could predict that among Gilakis, Fasting blood sugar (FBS) above 126 and in Lurs opium as well as diastolic blood pressure above 85, and in Kurds male gender would considerably increase the odds of developing CAD. Conclusion: The model obtained from the decision tree indicated that although variables of age, gender, cigarette, and opium are among the main risk factors for involvement of coronary arteries among young adult patients, in different ethnicities, the risk level of each of these risk factors in incidence of PCAD is different. This means among Kurds, age, among Gilakis diabetes, and among Lurs opium are more important