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Resocialization mitigates depressive behaviors induced by social isolation stress in mice: Attenuation of hippocampal neuroinflammation and nitrite level
No full textBackground and aim: Social isolation stress (SIS) is a stressor known to trigger depressive behaviors. Psychiatric disorders are associated with neurobiological changes, such as neuroinflammation and an increase in nitric oxide (NO) signaling. Despite the well-established detrimental effects of SIS and the involvement of neuroinflammation and NO in depression, potential management strategies, especially resocialization, remain insufficiently explored. Our aim was to elucidate the effects of resocialization on depressive behaviors in socially isolated mice, with a focus on the possible involvement of neuroinflammation and nitrite in the hippocampus (HIP). Methods: We utilized 24 Naval Medical Research Institute male mice, maintained under both social and isolation conditions (SC and IC). After the isolation period, the mice were divided into two groups of eight, including the SIS group and a resocialized group. The SC group was kept without exposure to isolation stress. We conducted the open-field test, forced swimming test, and splash test to evaluate depressive behaviors. Additionally, nitrite levels, as well as the gene expression of interleukin (IL)-1β, tumor necrosis factor (TNF), and toll-like receptor 4 (TLR4) in the HIP, were measured. Results: The study found that resocialization significantly reduces depressive behaviors in SIS mice. The results suggest that the antidepressive effects of resocialization may be partially due to the modulation of the neuroinflammatory response and nitrite levels in the HIP. This is supported by the observed decrease in hippocampal gene expression of IL-1β, TLR4, and TNF, along with a reduction in nitrite levels following resocialization. Conclusion: These insights could pave the way for new management strategies for depression, emphasizing the potential benefits of social interactions
Gut—brain barrier dysfunction bridge autistic‐like behavior in mouse model of maternal separation stress: A behavioral, histopathological, and molecular study
No full textAutism spectrum disorder (ASD) is a fast-growing neurodevelopmental disorder throughout the world. Experiencing early life stresses (ELS) like maternal separation (MS) is associated with autistic-like behaviors. It has been proposed that disturbance in the gut–brain axis-mediated psychiatric disorders following MS. The role of disruption in the integrity of gut–brain barrier in ASD remains unclear. Addressing this knowledge gap, in this study we aimed to investigate role of the gut–brain barrier integrity in mediating autistic-like behaviors in mouse models of MS stress. To do this, mice neonates are separated daily from their mothers from postnatal day (PND) 2 to PND 14 for 3 hours. During PND58–60, behavioral tests related to autistic-like behaviors including three-chamber sociability, shuttle box, and resident-intruder tests were performed. Then, prefrontal cortex (PFC), hippocampus, and colon samples were dissected out for histopathological and molecular evaluations. Results showed that MS is associated with impaired sociability and social preference indexes, aggressive behaviors, and impaired passive avoidance memory. The gene expression of CLDN1 decreased in the colon, and the gene expression of CLDN5, CLDN12, and MMP9 increased in the PFC of the MS mice. MS is associated with decrease in the diameter of CA1 and CA3 areas of the hippocampus. In addition, MS led to histopathological changes in the colon. We concluded that, probably, disturbance in the gut–brain barrier integrities mediated the autistic-like behavior in MS stress in mice
Designing a Self-Assembled Peptide Nano-vaccine Against Staphylococcus aureus: An In Silico Approach
No full textStaphylococcus aureus (S. aureus) is a bacterium capable of inducing a range of human infections, varying from mild skin infections to more serious diseases like pneumonia and bloodstream infections. Different studies have focused on designing epitope vaccines against S. aureus. Nevertheless, the primary drawback of epitope vaccines is their reduced ability to stimulate an immune response. Recently, self-assembled peptide nanoparticle (SAPN) vaccines have emerged as one of the latest innovations in vaccine design. This arises from their ability to have multiple functions, act as self-adjuvants, exhibit biocompatibility, and closely resemble the size of the pathogen. Therefore, this investigation aimed to design a new SAPN vaccine to combat S. aureus infection effectively through computational approaches. Antigenic proteins ClfA, IsdB, and Hla were selected to design the SAPN vaccine. Cytotoxic T lymphocyte (CTL) epitopes from ClfA and IsdB, helper T lymphocytes (HTL) from Hla, and linear B-cell epitopes from ClfA and IsdB were chosen. Subsequently, the chosen epitopes and the oligomeric domains of the pentamer and trimmer were employed as a self-assembled framework fused with suitable linkers. Physicochemical properties, solubility, antigenicity, and allergenic potential of the designed vaccine were examined. The obtained results indicate the SAPN vaccine was antigenic, stable, and non-allergenic. Afterward, the 3D structure of the construct was initially forecasted and subsequently refined and validated to reach the best 3D model. Finally, molecular docking and molecular dynamics (MD) simulation were conducted between the SAPN vaccine and toll-like receptor 4 (TLR4). The results of molecular dynamic simulation studies demonstrated the stable interactions between the construct and TLR4. In conclusion, we devised an in silico SAPN vaccine, which is anticipated to induce robust cellular and humoral immune responses against S. aureus, making it a noteworthy prospect for subsequent in vitro and in vivo studies related to immunology
Factors affecting the choice of neurosurgery: Medical student’s perspective
No full textIntroduction: Choosing a promising specialty for medical students is not an easy decision, particularly in a field like neurosurgery known for its high levels of stress. However, in recent years, there has been a decrease in interest, especially among female students, in choosing surgical specialties. Therefore, the present study aimed to identify influential factors in the selection of neurosurgery as a specialty from the perspective of medical students. Methods: This descriptive-analytical study was conducted in 2023 at the Shahr-e Kord University of Medical Sciences. we estimated a sample size of 425 individuals from the study population. We collected the data using a questionnaire, which was administered through an online questionnaire system. Results: Male and female perceptions of neurosurgery was similar across many of the surveyed factors, except for: “Male dominated”,“ Tolerant of criticism”, “Duration of residency” and “Must be an athlete”. The factor analysis reduced the 28-variable dimensionality to six latent factors that accounted for 60.72% of the variance found. The factor analysis recognized that, although male and female medical students do have some similar Survey Variable, the influence or weighing of those preferences is different for male and female students. The first latent factor for females consisted of: “Diverse patient population,” and “Procedural based.” The first latent factor for males consisted of: “Male dominated,” and “Prestige.” Conclusion: The factor analysis indicated that male and female students weight differently when selecting a specialty; this difference may account for the large differences in proportion between males and females in Neurosurgery residency
In silico design of a novel multi-epitope vaccine against HCV infection through immunoinformatics approaches
No full textInfection with the hepatitis C virus (HCV) is one of the causes of liver cancer, which is the world's sixth most prevalent and third most lethal cancer. The current treatments do not prevent reinfection; because they are expensive, their usage is limited to developed nations. Therefore, a prophylactic vaccine is essential to control this virus. Hence, in this study, an immunoinformatics method was applied to design a multi-epitope vaccine against HCV. The best B- and T-cell epitopes from conserved regions of the E2 protein of seven HCV genotypes were joined with the appropriate linkers to design a multi-epitope vaccine. In addition, cholera enterotoxin subunit B (CtxB) was included as an adjuvant in the vaccine construct. This study is the first to present this epitopes-adjuvant combination. The vaccine had acceptable physicochemical characteristics. The vaccine's 3D structure was predicted and validated. The vaccine's binding stability with Toll-like receptor 2 (TLR2) and TLR4 was confirmed using molecular docking and molecular dynamics (MD) simulation. The immune simulation revealed the vaccine's efficacy by increasing the population of B and T cells in response to vaccination. In silico expression in Escherichia coli (E. coli) was also successful
Asthma and chronic obstructive pulmonary disease (COPD) in people with multiple sclerosis: A systematic review and meta-analysis
No full textBackground: Studies have found that multiple sclerosis (MS) has an impact on the initiation or the course of asthma and chronic obstructive pulmonary disease (COPD). This review amied to investigate the prevalence and odds of asthma and COPD among people with MS (pwMS). Method: PubMed, Embase, Scopus, and Web of Science were systemically searched from inception to May 2023. R version 4.3.2 and random-effect model were used to calculate the pooled prevalence and odds ratio (OR), with their 95 % confidence interval (CI), in pwMS. Results: A total of 40 studies consisting of 287,702 pwMS were included. 37 studies indicated that the pooled prevalences of asthma and COPD among pwMS were 5.97 % (95 % CI: 4.62 %-7.69 %, I2=99 %) and 3.03 % (95 % CI: 1.82 %-5.00 %, I2=99 %), respectively. 24 studies on 236,469 pwMS and 85,328,673 healthy controls revealed that the overall odds of asthma and COPD in MS were 1.14 (95 % CI: 0.76–1.71, p-value=0.53, I2=97 %) and 1.28 (95 % CI: 1.11–1.47, p-value<0.01, I2=70 %), respectively. Conclusion: MS can increased the risk of developing COPD, while asthma does not exhibit a significant relationship with MS. Our study highlights the importance of identifying pwMS who face greater risks of respiratory issues to monitor efficiently and initiate suitable preventative actions
Design and psychometric evaluation of the collaborative coping with infertility questionnaire in candidate of assisted reproductive techniques
No full textEvaluating couples’ coping with infertility and its impact on their mental health is valuable in designing supportive programs. Since infertility is a shared problem in married life, coping with it requires collaborative coping strategies. Therefore, the aim of the present study was to design and psychometrically evaluate the collaborative coping with infertility questionnaire (CCIQ) in candidates of assisted reproductive techniques (ART). The exploratory factor analysis of a 27-item questionnaire designed based on the Likert scale in the Persian language was evaluated through the principal component analysis method in a cross-sectional study conducted on 200 couples who volunteered for ART. The cut-off point of factor loadings was considered 0.4. Furthermore, the criterion validity of the questionnaire was evaluated using a 12-item revised Fertility Adjustment Scale (R-FAS) and its relationship with the score of the CCIQ. Moreover, the internal consistency of the questionnaire was evaluated using Cronbach’s alpha correlation coefficient. In the exploratory factor analysis, 20 items with a factor loading above 0.4 were extracted under three factors. The three extracted factors with a value above one explained 43.78% of the variance of CCIQ. The factor loading of the accepted items ranged between 0.402 and 0.691. External reliability was confirmed with Cronbach’s alpha coefficient of 0.98. The relationship between CCIQ and R-FAS score was significant (p < 0.0001). The results of the study showed that the 20-item CCIQ enjoyed acceptable validity and reliability in the three dimensions of ‘dynamic interaction,’ ‘reorganizing married life goals,’ and ‘perception about infertility,’ which can be used to evaluate collaborative coping with infertility questionnaire in ART candidates
Valproate modulates the activity of multidrug resistance efflux pumps, as a chemoresistance factor in gastric cancer cells
No full textBackground: Drug resistance is one of the most critical problems in gastric cancer therapy. This study was performed to investigate the valproic acid effects on the proliferation of sensitive and resistant cell lines of human gastric cancer, and to explore the mechanism of the agent on multi drug resistance and apoptosis genes. Methods: The cytotoxicity effect of valproic acid on the EPG85.257 and EPG85.257RDB cells was assessed by the MTT assay, and the IC50 concentration was evaluated. Apoptosis, genotoxicity, and drug resistance pump activity were evaluated using comet assay, Real-time PCR, and flow cytometry, respectively. Cell proliferation was assayed using a scratch test. Results: Dose-dependent toxicity was recorded after treatment of cells with valproic acid. Valproic acid represented a significant growth inhibition on EPG85.257 cells with IC50 values of 5.84 µM and 4.78 µM after 48 h and 72 h treatment, respectively. In contrast, the drug-resistant counterpart represented 8.7 µM and 7.02 µM IC50 values after the same treatment time. Valproic acid induced PTEN, Bcl2, P53, Bax, P21, and caspase3 expression in EPG85.257 cells, whereas p21, p53, PTEN, and ABCB1 were overexpressed in EPG5.257RDB. Valproic acid hindered cell migration in both cell lines (P < 0.01). Valproate genotoxicity was significantly higher in the parent cells than in their resistant EPG85.257RDB counterparts. Valproate led to a 62% reduction in the daunorubicin efflux of the MDR1 pump activity. Conclusions: Valproate can affect drug resistance in gastric cancer via a unique mechanism independent of MDR1 expression
Climatic conditions and concentrations of BTEX compounds in atmospheric media
No full textClimatic and meteorological conditions are among the factors affecting the ambient concentrations of BTEX compounds. This systematic review and meta-analysis aimed to interrogate the seasonal effect of climatic conditions on the concentrations of BTEX compounds. Three electronic bibliographic databases including Scopus, PubMed, and Web of Science were systematically searched up to November 14, 2023. The search algorithm followed PRISMA guidance and consisted of three groupings of keywords and their possible combinations. For various climatic conditions, the overall mean and 95% confidence interval (CI) of effect size related to BTEX concentrations were calculated using a random-effect model. In total, 104 articles were included for evaluation in this review. BTEX ambient concentration was higher in winter (ranging from 36 out of 79 relevant studies for xylene to 52 out of 97 relevant studies for benzene) followed by summer and autumn. For humidity conditions, the highest exposure values for BTEX were detected for rainy weather (ranging from 3 out of 5 relevant studies for toluene and xylene to 4 out of 5 relevant studies for benzene and ethyl benzene) compared to dry conditions. The pooled concentration (μg/m3) of benzene, toluene, ethyl benzene, and xylene were computed as 2.61, 7.12, 2.21, and 3.61 in spring, 2.13, 7.53, 1.61, and 2.75 in summer, 3.04, 9.59, 3.14, and 5.50 in autumn, and 3.56, 8.71, 2.35, and 3.91 in winter, respectively. Moreover, the pooled concentrations (μg/m3) of BTEX were measured as 2.98, 7.22, 1.90, and 3.03 in dry weather and 3.15, 6.30, 2.14, and 3.86 in rainy or wet weather, respectively. In most seasons, the ambient concentrations of BTEX were higher in countries with low and middle incomes and in Middle Eastern countries and East/Southeast Asia compared to those in other regions (P < 0.001). The increasing concentrations of BTEX in winter and autumn followed by the summer season and during rainy/wet weather appear to be reasonably consistent despite variations in study methods, quality, or geography. Therefore, it is recommended that more serious control measures are considered for decreasing exposure to BTEX in these climatic conditions
Prioritization of Kidney Cell Types Highlights Myofibroblast Cells in Regulating Human Blood Pressure
No full textIntroduction: Blood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP. Methods: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years. Results: Our analyses prioritized myofibroblasts and endothelial cells, among the total of 33 annotated cell type, as specifically involved in BP regulation (P < 0.05/33, i.e., 0.001515). Enrichment of heritability for systolic BP (SBP) was observed in myofibroblast cells in mature human kidney cortex, and enrichment of heritability for diastolic BP (DBP) was observed in descending vasa recta and peritubular capillary endothelial cells as well as stromal myofibroblast cells. The new finding of myofibroblast, the significant cell type for both BP traits, was consistent in 8 replication efforts using 7 sets of independent data, including in human fetal kidney, in East-Asian (EAS) ancestry, using mouse single-cell RNA sequencing (scRNA-seq) data, and when using another prioritization method. Conclusion: Our findings provide a solid basis for follow-up studies to further identify genes and mechanisms in myofibroblast cells that underlie the regulation of BP