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Neda Eslahi,1,2,* Mahmoud Reza Hadjighassem,1,3 Mohammad Taghi Joghataei,1,2 Tooba Mirzapour,4 Mehrdad Bakhtiyari,1,2 Malak Shakeri,5 Vahid Pirhajati,1,2 Peymaneh Shirinbayan,6,* Morteza Koruji1,21Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; 2Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; 3Department of Neurosciences, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran; 5Department of Animal Science, Agricultural Campus, University of Tehran, Tehran, Iran; 6Pediatric Neuro-Rehabilitation Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran*These authors contributed equally to this articleIntroduction: A 3D-nanofiber scaffold acts in a similar way to the extracellular matrix (ECM)/basement membrane that enhances the proliferation and self-renewal of stem cells. The goal of the present study was to investigate the effects of a poly L-lactic acid (PLLA) nanofiber scaffold on frozen-thawed neonate mouse spermatogonial stem cells (SSCs) and testis tissues.Methods: The isolated spermatogonial cells were divided into six culture groups: (1) fresh spermatogonial cells, (2) fresh spermatogonial cells seeded onto PLLA, (3) frozen-thawed spermatogonial cells, (4) frozen-thawed spermatogonial cells seeded onto PLLA, (5) spermatogonial cells obtained from frozen-thawed testis tissue, and (6) spermatogonial cells obtained from frozen-thawed testis tissue seeded onto PLLA. Spermatogonial cells and testis fragments were cryopreserved and cultured for 3 weeks. Cluster assay was performed during the culture. The presence of spermatogonial cells in the culture was determined by a reverse transcriptase polymerase chain reaction for spermatogonial markers (Oct4, GFRα-1, PLZF, Mvh(VASA), Itgα6, and Itgβ1), as well as the ultrastructural study of cell clusters and SSCs transplantation to a recipient azoospermic mouse. The significance of the data was analyzed using the repeated measures and analysis of variance.Results: The findings indicated that the spermatogonial cells seeded on PLLA significantly increased in vitro spermatogonial cell cluster formations in comparison with the control groups (culture of SSCs not seeded on PLLA) (P≤0.001). The viability rate for the frozen cells after thawing was 63.00% ± 3.56%. This number decreased significantly (40.00% ± 0.82%) in spermatogonial cells obtained from the frozen-thawed testis tissue. Both groups, however, showed in vitro cluster formation. Although the expression of spermatogonial markers was maintained after 3 weeks of culture, there was a significant downregulation for some spermatogonial genes in the experimental groups compared with those of the control groups. Furthermore, transplantation assay and transmission electron microscopy studies suggested the presence of SSCs among the cultured cells.Conclusion: Although PLLA can increase the in vitro cluster formation of neonate fresh and frozen-thawed spermatogonial cells, it may also cause them to differentiate during cultivation. The study therefore has implications for SSCs proliferation and germ cell differentiation in vitro.Keywords: PLLA nanofibers, tissue cryopreservation, testis

Testis-specific gene antigen10 (Tsga10), as a cytoskeletal protein in the sperm tail, impacts the sperm motility. This study investigates the correlation between sperm profile alterations and Tsga10 gene expression in adult mice exposed to formaldehyde ( FA) and then treated with antioxidant effect of manganese (Mn2+). In this regard, we examined 35 NMRI adult male mice (6-8 weeks age) in 4 groups of control, sham, FA-exposed and FA+Mn2+. The mice in FA+Mn2+ group were exposed to FA (10 mg kg−1 twice a day) for 2 weeks and treated with daily Mn2+ administration (5 mg kg−1) in the second week prior to sacrificing the mice for testis dissection. The right testis was dissected in each group and subjected to RNA extraction and cDNA syntheses for gene expression analysis by real-time PCR. The findings revealed that FA decreased sperm parameters and Tsga10 expression (52.6 ± 24.37%). However, the injected powerful manganese antioxidant improved sperm profile through overexpression of Tsga10 (121.6 ± 27.13%) under FA-induced stressful condition which proves the correlation between sperm profile and Tsga10 expression ( P ≤ 0.05). This study also shows that Tsga10 expression protects sperm dysfunction in FA+Mn2+ group and resulting in better preservation of spermatozoa and improvement of male fertility. [ABSTRACT FROM AUTHOR]

Cadmium is a toxic heavy metal element, which probably cause infertility by impairment in spermatogenesis. The present work aimed (i) to study the toxic effect of cadmium on spermatogenesis in rat, as well as (ii) the protective effect of Crocus sativus L. on cadmium-intoxicated rats. Cadmium chloride was administered intraperitoneally during 16 days at intervals of 48 h between subsequent treatments. Crocus sativus L. was pre-treated in both of control and cadmium-injected rats. Animals were sacrificed on day 17 after the first treatment. The left cauda epididymis was removed and immediately immersed into Hank's balanced salt solution for the evaluation of sperm count and viability, and left testis was fixed in 10% formalin for histological evaluation. Following contamination with cadmium, a decrease was observed in the number and viability of cauda epididymis sperm, which were increased by Crocus sativus L. pre-treatment ( P < 0.05). In addition, cadmium decreased both cell proliferation and Johnsen Scores in the seminiferous tubules, which were reversed by Crocus sativus pre-treatment ( P < 0.05). Furthermore, cadmium-induced decrease in the amount of free serum testosterone as well as an increase in lipid peroxidation activity in the testicular tissue was reversed by Crocus sativus L. ( P < 0.05). These findings may support the concept that Crocus sativus L. can improve the cadmium toxicity on spermatogenesis. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common invasive cancer in women worldwide, necessitating innovative therapeutic strategies to enhance treatment efficacy and safety. This study focuses on the development and optimization of novel paclitaxel (PTX)-loaded nanostructured lipid carriers (NLCs) that incorporate components of MF59, an oil-in-water emulsion adjuvant approved for use in influenza vaccines and known for its safety in humans. The formulation of these NLCs is designed to overcome significant challenges in PTX delivery, particularly its poor solubility and the side effects associated with traditional formulations containing Cremophor EL. We prepared two sets of NLC formulations using different liquid-to-solid lipid ratios through hot melt ultrasonication. Characterization of the selected formulations, NLC Pre and NLC Lec , was conducted using dynamic light scattering (DLS), scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR) spectroscopy, and ultraviolet-visible (UV-Vis) spectroscopy. The mean diameters were 120.6 ± 36.4 nm and 112 ± 41.7 nm, with encapsulation efficiencies (EE) of 85% and 82%, and drug loading (DL) of 4.25% and 4.1%, respectively for NLC Pre and NLC Lec . In vitro cytotoxicity assays demonstrated that these MF59-based NLCs effectively target MCF-7 (Michigan Cancer Foundation) breast cancer cells while minimizing toxicity to normal HDF (human dermal fibroblasts) cells, thus enhancing the therapeutic index of PTX and offering promising clinical implications for breast cancer treatment., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This report presents an open-source dataset investigating neurodevelopmental profiles in children. The dataset consists of EEG, ERP, and cognitive assessments from 100 Iranian non-clinical participants (age range 6-11 years, Mean = 8.52 ± 1.5 SD). Notably, this is a smaller group drawn from a larger longitudinal ongoing study. The research aligns with the Research Domain Criteria (RDoC) framework, aiming to enhance diagnostic precision and intervention efficacy for specific learning disabilities (SLD) using EEG/ERP measures and machine learning. Cognitive assessments included non-verbal intelligence (Raven Test), attention (IVA-2), and working memory tasks. EEG recordings captured resting-state (eyes closed/open) and brain activity during working memory tasks with numerical and non-numerical stimuli (ERPs). Additionally, demographic information such as age, gender, education, handedness, parental history of learning difficulties, and child symptom inventory-4 (CSI-4) were collected. This dataset provides a valuable resource for exploring the neurophysiological correlates of cognitive functions in typically developing children, which can advance our understanding of the neural foundations of cognitive development in children., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: This study endeavors to draw a comparative analysis between a traditional herbal ointment, specifically Swalin, and silver sulfadiazine ointment in the context of repairing deep second-degree burns., Methods: A randomized clinical trial was conducted at the Iran University of Medical Sciences. In this investigation, a cohort comprising eighty-two patients was stratified into two groups, namely Swalin (n = 41) and Silver sulfadiazine (SSD) (n = 41). Over 28 days, ointment applications were administered twice daily. The quantification of ointment compounds was conducted employing Gas Chromatography-Mass Spectrometry (GC-MS). The study encompassed a comprehensive assessment involving clinical examination, quantitative and qualitative histopathological evaluations, pain level determination, and scrutiny of wound closure. Statistical analyses, encompassing chi-square and Mann-Whitney U tests, were performed using SPSS software., Results: Our investigation revealed that the predominant compounds in the ointment were linoleic acid (41.37 %) and elaidic acid (37.45 %). On the 28th day, the Swalin group demonstrated a significantly higher rate of wound closure (81.52 ± 7.76) compared to the SSD group (69.91 ± 2.48) (p < 0.001). Furthermore, a statistically significant distinction was observed between the two groups concerning the degree of epithelialization (P = 0.048). Fibroblast density exhibited a notable discrepancy between the groups (P = 0.02). In terms of angiogenesis and collagen deposition, the Swalin group displayed a significant contrast with the SSD group (P = 0.008 and P = 0.007, respectively), while no statistical distinction was discerned in the number of immune cells (P > 0.05). Histological examination of SSD illustrated a pronounced infiltration of inflammatory cells in the dermis, predominantly lymphocytes. Conversely, the Swalin group exhibited well-formed dermal layers, minimal infiltration, and a profusion of vessels., Conclusion: In conclusion, the findings of this study highlight the potential therapeutic benefits of Swalin ointment, attributed to its rich composition of fatty acids, particularly linoleic acid, and the presence of vitamins C and E., Competing Interests: Declaration of Competing Interest The authors declare no any financial or non-financial conflict of interests., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer that is notably associated with a high risk of lymph node metastasis, a major cause of cancer mortality. Current therapeutic options remain limited to surgery supplemented by radio- or chemotherapy; however, these interventions often result in high-grade toxicities. Distant metastasis significantly contributed to the poor prognosis and decreased survival rates. However, the underlying molecular mechanisms remain poorly understood. Disease-related "omics" data provide a comprehensive overview of gene relationships, helping to decode the complex molecular mechanisms involved. Interactions between biological molecules are complex and highly dynamic across various cellular conditions, making traditional co-expression methods inadequate for understanding these intricate relationships. In the present study, a novel three-way interaction approach was employed to uncover dynamic co-expression relationships underlying the metastatic nature of HNSCC. Subsequently, the biologically relevant triples from statistically significant ones were defined through gene set enrichment analysis and reconstruction of the gene regulatory network. Finally, the validity of biologically relevant triplets was assessed at the protein level. The results highlighted the "PI3K/AKT/mTOR (PAM) signaling pathway" as a disrupted pathway involved in the metastatic nature of HNSCC. Notably, Gins2, identified as a switch gene, along with the gene pair {Akt2, Anxa2}, formed a statistically significant and biologically relevant triplet. It suggests that Gins2 could serve as a potential upstream modulator in the PAM signaling pathway, playing a crucial role in the distant metastasis of HNSCC. In addition, survival analysis of significant switch genes indicated that two genes, C19orf33 and Usp13, may be especially important for prognostic purposes in HNSCC., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: This study investigated the effects of a single dose injection of mesenchymal stem cells (MSCs) under ultrasound guidance for knee osteoarthritis (KOA)., Design: The study included 30 subjects in the intervention group, who received the MSC injection and 27 in the control group who received triamcinolone. Various outcome measures, including pain levels, range of motion (ROM), and MRI parameters, were evaluated before the intervention and at different time points after treatment., Result: The results showed that the MSC group experienced more effective improvements in outcome measures compared to the control group. Pain improvement was significantly different in the MSC group at 2 weeks, 4 weeks, and 24 weeks after the treatment. ROM in extension improved significantly in the MSC group after 4 weeks. Physical function improved significantly in both groups at different time points. Furthermore, the MSC group showed some positive changes in MRI parameters, but it can't be said definitively that they led to an increase in cartilage thickness., Conclusion: In conclusion, the study suggests that a single dose injection of MSCs is safe and holds promise for long-term treatment of KOA. No significant negative effects were reported in either group as a result of the study., Competing Interests: a. Competing Interests: Authors declare no conflict of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Imbalance in inhibitory and excitatory neurotransmitters have been reported in tinnitus. Acamprosate modulates the excitatory and inhibitory neurotransmission in the nucleus accumbens (NAc). This study aims to assess the effect of Acamprosate on tinnitus, anxiety, depression, and molecular changes in nucleus accumbens (NAc), in Sodium-Salisylate (S-salicylate) model of tinnitus., Methods: Forty-four adult male wistar rats were used in this study. The study included Control, Saline, and S-salicylate groups during the first week, which then subdivided into five groups as Control, Saline, S-salicylate, Acamprosate, and S-salicylate+Acamprosate. Gap-in Noise (GIN) and pre-pulse inhibition (PPI) were used to assessment of tinnitus at baseline, day7 and day14. Anxiety and depression were evaluated on day 14, by elevated plus maze (EPM), open field (OF), and tail suspension (TST) tests. The protein expression of GABAAR-δ, NR1 and NR2B in NAc were also measured using western blot technique., Results: After seven days GIN reduced in S-salicylate compare to Control and Saline groups (P < 0.5), while PPI unchanged. After 14 days, GIN reduced in S-salicylate and S-salicylate+Acamprosate groups compare to Control; Saline; and Acamprosate groups (P < 0.5). Additionally, GIN was higher in S-salicylate+Acamprosate compare to S-salicylate group (P < 0.5). PPI was not changed after 14 days. Open arm time in EPM test was decreased in S-salicylate and S-salicylate+Acamprosate groups compare to Control; Saline; and Acamprosate groups (P < 0.5). Central Zone time in OF test was reduced in S-salicylate group compare to Control, Saline, Acamprosate, and S-salicylate+Acamprosate groups (P < 0.5). Immobility Time in TST was increased in S-salicylate group compare to Control, Saline, Acamprosate, and S-salicylate+Acamprosate groups (P < 0.5). GABAAR-δ was decreased in S-salicylate groups compare to Control, Saline, Acamprosate; and S-salicylate+Acamprosate groups (P < 0.5). NR1 and NR2B in NAc were increased in S-salicylate group compare to Control, Saline, Acamprosate, and S-salicylate+Acamprosate groups (P < 0.5)., Conclusion: S-salicylate can induce tinnitus-like behaviors in rat. Furthermore, S-salicylate induced depression/anxiety like behaviors, and changed the expression of GABAR and NMDAR subunits in NAc. Acamprosate partially reversed these changes. In conclusion, NAc may be involved in the pathophysiologic mechanisms of tinnitus., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

The relationship between the vitamin D receptor (VDR) gene and many pathogenic pathways in relapsing-remitting multiple sclerosis (RRMS) remains unclear. Given the significance of the topic, we conducted this study to explore the correlation between vitamin D receptor gene polymorphisms and clinical and inflammatory factors in patients suffering from relapsing-remitting multiple sclerosis. The current research is a case/control study conducted based on the Helsinki Ethical Principles. RRMS disease was confirmed based on history, clinical symptoms, radiological signs and neurologist diagnosis. The research population consisted of healthy people and patients with RRMS who were referred to Hazrat Rasool Akram Hospital between 2021 and 2023. For each person participating in the study (RRMS patient and healthy), five milliliters of peripheral blood containing the anticoagulant EDTA was collected. Polymerase chain reaction was performed using two specific and appropriate oligonucleotide primers. The restriction fragment length polymorphism technique was used, one of the standard methods for identifying polymorphisms. Statistical analysis was performed using SPSS software version 23. The odds ratio and 95% confidence limits were calculated. The SNP Analyzer software was used to analyze the allele frequency of each polymorphism in healthy and RRMS individuals and compare the values. Prism version 5 software was used to draw diagrams. In the present study, a statistically significant difference was observed between the percentage of FokI genotypes in RRMS patients and healthy individuals. FokI polymorphism showed a significantly increased risk with an odds ratio of 7.28 in patients with the FF genotype compared to healthy individuals. ApaI, TaqI, and BsmI were not significantly different between the two groups. Based on the findings of the present study, FokI polymorphism showed a significant risk increase in RRMS patients with FF genotype compared to healthy individuals.

Cocaine and amphetamine-regulated transcript (CART) mRNA and peptide are vastly expressed in both cortical and subcortical brain areas and are involved in critical cognitive functions. CART peptide (CARTp), described in reward-related brain structures, regulates drug-induced learning and memory, and its role appears specific to psychostimulants. However, many other drugs of abuse, such as alcohol, opiates, nicotine, and caffeine, have been shown to alter the expression levels of CART mRNA and peptides in brain structures directly or indirectly associated with learning and memory processes. However, the number of studies demonstrating the contribution of CARTp in learning and memory is still minimal. Notably, the exact cellular and molecular mechanisms underlying CARTp effects are still unknown. The discoveries that CARTp effects are mediated through a putative G-protein coupled receptor and activation of cellular signaling cascades via NMDA receptor-coupled ERK have enhanced our knowledge about the action of this neuropeptide and allowed us to comprehend better CARTp exact cellular/molecular mechanisms that could mediate drug-induced changes in learning and memory functions. Unfortunately, these efforts have been impeded by the lack of suitable and specific CARTp receptor antagonists. In this review, following a short introduction about CARTp, we report on current knowledge about CART's roles in learning and memory processes and its recently described role in memory-related neurological disorders. We will also discuss the importance of further investigating how CARTp interacts with its receptor(s) and other neurotransmitter systems to influence learning and memory functions. This topic is sure to intrigue and motivate further exploration in the field of neuroscience., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare they have NO financial interests or personal relationships, so there are NO potential competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Adipocyte levels including leptin and FABS-4 levels, adiponectin, obesity, and vitamin D can be related to the occurrence and exacerbation of MS disease., Objective: This research aimed at determining the relationship between VDR gene changes and clinical and inflammatory factors in patients with relapsing-remitting multiple sclerosis (RRMS)., Method: This case/control study was conducted based on the ethical principles of Helsinki. RRMS disease was confirmed based on history, clinical signs, radiological signs, and neurologist's diagnosis. The research population consisted of healthy people and patients with RRMS referring to Hazrat Rasool Akram Hospital between 2021 and 2023 who met the criteria for entering the research., Results: FokI polymorphism is associated with a substantial increase in risk, with an odds ratio of 7.28, for those with the FF genotype who have RRMS compared to healthy individuals (OR=7.28: 95% CI; 1.86, 28.41). The presence of FokI polymorphism significantly raises the likelihood of developing RRMS in persons with the FF genotype compared to healthy individuals, with an odds ratio of 28.7. RRMS patients with genotypes did not exhibit a significant increase in risk compared to controls for FokI, ApaI, TaqI, and BsmI polymorphisms., Conclusion: None of the studied polymorphisms revealed a significant risk in obese patients with different genotypes compared to the obese people. Further research, including more cases, is needed to avoid results that could be inflated by small samples or low frequencies of minor alleles.

Purpose: This research sought to ascertain the Minimal Clinically Important Difference (MCID) and Robust Clinically Important Difference (RCID) of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) and Chalder Fatigue Questionnaire-11 (CFQ-11) as two important concepts for the clinical interpretation of the results in chronic post-stroke population., Methods: A total of 128 subjects with chronic post-stroke completed the MFSI-SF and CFQ-11 before and after six weeks of intervention. The MCIDs were derived using both anchor- and distribution-based methods; however, only anchor-based methods were used to estimate RCIDs., Results: Anchor-based MCIDs for MFSI-SF and CFQ-11 were in the range of -5 to -6.28 and -2 to -4.56, respectively. Distribution-based MCIDs in MFSI-SF and CFQ-11 were calculated in the range of -4.17 to -24.05 and -1.72 to -7.68, respectively. RCID ranges of -10 to -15 were obtained for the MFSI-SF and -6 to -7.33 for the CFQ-11., Conclusion: These findings may have implications for clinical experts in the clinical interpretation of fatigue changes observed in MFSI-SF and CFQ-11 in individuals with chronic stroke.

Altered sensory processing especially in the auditory system is considered a typical observation in children with autism spectrum disorder (ASD). Auditory temporal processing is known to be impaired in ASD children. Although research suggests that auditory temporal processing abnormalities could be responsible for the core aspects of ASD, few studies have examined early time processing and their results have been conflicting. The present event-related potential (ERP) study investigated the early neural responses to duration and inter-stimulus interval (ISI) deviants in nonspeech contexts in children with ASD and a control group of typically developing (TD) children matched in terms of age and IQ. A passive auditory oddball paradigm was employed to elicit the mismatch negativity (MMN) for change detection considering both the duration and ISI-based stimulus. The MMN results showed that the ASD group had a relatively diminished amplitude and significant delayed latency in response to duration deviants. The findings are finally discussed in terms of hyper-hyposensitivity of auditory processing and the fact that the observed patterns may potentially act as risk factors for ASD development within the research domain criteria (RDoC) framework.

Purpose: The minimal and robust clinically important difference (MCID and/or RCID) are essential in assessing the clinical significance of multidimensional fatigue inventory-20 and checklist of individual strength-fatigue subscale questionnaires changes scores. This is the first study to determine the MCID and RCID of these questionnaires in chronic stroke survivors., Materials and Methods: A total of 125 participants in an observational cohort study completed MFI-20 and CIS-fs before and after receiving multidisciplinary rehabilitation (cognitive behavioral therapy, graded exercise and adaptive pacing therapy). Anchor-based MCIDs and RCIDs were calculated using the mean change, the mean difference and the receiver operating characteristics methods. To evaluate the accordance between of distribution-based MCIDs (1 SD, ½ SD, SEM, 1.96 SEM and MDC values) with anchored values, the accuracy, sensitivity, specificity and Youden's index were calculated., Results: The anchored MCIDs were between -5 to -7.33 for MFI-20 and -4.87 to -5.40 for CIS-fs. The anchored RCIDs ranged from -5 to -13.88 and -6 to -9.88 for MFI-20 and CIS-fs, respectively. The values of ½ SD and SEM for CIS-fs were consistent with anchored RCIDs., Conclusions: The estimated MCIDs and RCIDs of MFI-20 and CIS-fs can help researchers and clinicians interpret their chronic stroke patient data.

The absence of a definitive cure for amyotrophic lateral sclerosis (ALS) emphasizes the crucial need to explore new and improved treatment approaches for this fatal, progressive, and disabling neurodegenerative disorder. As at the end of 2023, five treatments - riluzole, edaravone, dextromethorphan hydrobromide + quinidine sulfate (DHQ), tofersen, and sodium phenylbutyrate-tauroursodeoxycholic acid (PB-TUDCA) - were FDA approved for the treatment of patients with ALS. Among them PB-TUDCA has been shown to impact DNA processing impairments, mitochondria dysfunction, endoplasmic reticulum stress, oxidative stress, and pathologic folded protein agglomeration defects, which have been associated with ALS pathophysiology. The Phase 2 CENTAUR trial demonstrated significant impact of PB-TUDCA on the ALS Functional Rating Scale-Revised (ALSFRS-R) risk of death, hospitalization, and the need for tracheostomy or permanent assisted ventilation in patients with ALS based on post hoc analyses. More recently, contrasting with the CENTAUR trial results, results from the Phase 3 PHOENIX trial (NCT05021536) showed no change in ALSFRS-R total score at 48 weeks. Consequently, the sponsor company initiated the process with the US FDA and Health Canada to voluntarily withdraw the marketing authorizations for PB-TUDCA. In the present article, we review ALS pathophysiology, with a focus on PB-TUDCA's proposed mechanisms of action and recent clinical trial results and discuss the implications of conflicting trial data for ALS and other neurological disorders., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

V-domain Imuunoglobulin suppressor of T-cell activation (VISTA) seems a promising immune checkpoint target in cancer treatment; however, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Herein, 29 fresh PDAC tissue samples were used to evaluate the mRNA expression level of VISTA by real-time polymerase chain reaction (PCR). Besides, 40 formalin-fixed paraffin-embedded PDAC tissues were collected to evaluate VISTA protein expression by immunohistochemistry. Real-time PCR indicated that high expression of VISTA was significantly correlated with advanced stages of the cancer, based on the tumor/node/metastasis (TNM) stagingand tumor cell differentiation.  Immunohistochemistry results also showed significant correlation of the elevated cytoplasmic expression of VISTA with advanced TNM stages, older age of the patients and was a worsening indicator, regarding the disease-specific survival. In conclusion, we found that the expression levels of VISTA can be a potential prognostic biomarker in PDAC patients and its elevated levels are correlated with poor prognostic outcomes.

The primary goal of this study was to evaluate the treatment effects of semantic feature analysis (SFA) and phonological components analysis (PCA) on word retrieval processing in persons with aphasia (PWAs). After identifying the locus of the breakdown in lexical retrieval processing, 15 monolingual native Persian speakers with aphasia were divided into two groups. After three naming trials, participants with dominant semantic deficits received SFA, and participants with primary phonological deficits were provided with PCA three times a week for eight weeks. Both approaches improved participants' naming and performance on language tests, including spontaneous speech, repetition, comprehension, and semantic processing. However, the correct naming of treated and untreated items was higher in mild-to-moderate participants, with mostly circumlocution and semantic paraphasias in the SFA group. The same holds for mild-to-moderate participants with mostly phonemic paraphasia who received PCA therapy. Moreover, the results showed that participants' baseline naming performance and semantic abilities could be associated with the treatment outcomes. Although limited by a lack of a control group, this study provided evidence supporting the possible benefits of focusing on the locus of the breakdown for treating anomia through SFA and PCA approaches, specifically in participants with mild to moderate aphasia. However, for those with severe aphasia, the treatment choice may not be as straightforward because several variables are likely to contribute to this population's word-finding difficulties. Replication with larger, well-stratified samples, use of a within-subjects alternating treatment design and consideration of treatments' long-term effects are required to better ascertain the effects of focusing on the locus of breakdown for treatment of anomia.

Introduction: Schizophrenia (SCZ) is a psychiatric disorder caused by environmental, social, and genetic factors. This phenomenon is a severe neuropsychiatric disorder with a 1% worldwide prevalence. As SCZ is an exclusively human disorder, animal models cannot mimic SCZ pathophysiology. Thus, it is crucial to develop a novel human-based specific model of SCZ to elucidate mechanisms of the occurrence of the disease. In this regard, the aim of this study was reprogramming somatic cells to human-induced pluripotent stem cells (hiPSCs), with possible potency to transformed to specific neural stem cells., Methods: In the present study, we directly reprogrammed the isolated human ear dermal fibroblasts (HDFs) from schizophrenic patients into hiPSCs using some episomal agents in Matrigel-coated plates. The existence of pluripotency markers was confirmed by the immunocytochemistry (ICC) test and alkaline phosphatase protocol. We performed karyotype analysis to ensure the maintenance of the normal chromosomes., Results: Analysis of colonies exhibited intense alkaline phosphatase engagement and Oct4, SSEA4, Nanog, and Tra-1-60. HiPSCs showed normal karyotypes and were potent to differentiate into ectoderm, endoderm, and mesoderm., Conclusion: This study showed human dermal mesenchymal fibroblasts taken from schizophrenic patients can be reprogrammed to hiPSCs, with potential to transformation to three germ layers with sufficient expression of relate molecular markers. This is the first steps to produce SCZ specific neural stem cells, which can be used in the assessment of cellular changes in schizophrenia and possible effects of antipsychotic agents. ., (Copyright© 2024 Iranian Neuroscience Society.)

Background: Various studies have shown that individuals with autism spectrum disorder (ASD) experience significant cognitive impairments during childhood. Individuals often experience various language disorders that can manifest in different ways. There are also studies indicating that these impairments persist into adulthood for individuals with ASD. This study aimed to evaluate and identify cognitive impairments among Persian-speaking adults with ASD., Methods: This research is of a quantitative nature and has been conducted using an experimental method in which two subtests from the Persian Version of the Montreal Protocol for the Evaluation of Communication (P.M.E.C.), including the Metaphor Interpretation and Speech Act Interpretation subtests, were utilized. Thirteen Persian-speaking men with ASD participated in this research, with ages ranging from 25 to 44 years (mean age 32.84, standard deviation 4.17), whose educational levels varied from primary school to 20 years of formal education. The control group consisted of 26 healthy Persian-speaking men who were matched in terms of age and educational level with the ASD group. The Kolmogorov-Smirnov test and a paired t-test were used to compare the two groups., Results: The results indicated that the ASD group performed significantly poorer in both the Metaphor Interpretation subtest ( P < 0.001) and the Speech Act Interpretation subtest ( P = 0.033) compared to the healthy control group, suggesting cognitive impairments in their abilities., Conclusion: The findings of this research can be valuable for assessment and intervention purposes in rehabilitation centers, as well as in academic and research settings., Competing Interests: The authors declare that they have no competing interests., (© 2024 Iran University of Medical Sciences.)

The infection hypothesis is a new causative explanation for Alzheimer's disease (AD). In recent decades, various species of bacterial pathogens have been distinguished in the autopsy of Alzheimer's patients; however, the mechanism of bacterial contribution to AD pathology is still unknown. To explore the hypothesis, Cutibacterium acnes (C. acnes) was selected, and effects of its intracerebroventricular (ICV) inoculation in rats was evaluated. The results revealed that C. acnes causes memory impairment, which might be a consequence of upregulated Amyloid β (Aβ) deposits in the hippocampus; Aβ aggregates are co-localized with C. acnes colonies. The key point of our hypothesis is that the activation of the innate immune system by C. acnes through the TLR2/NF-κB/NLRP3 signaling pathway, eventually leads to increased neuroinflammation, which might be resulted from microgliosis and astrogliosis. Neuroinflammation increases oxidative stress and cell apoptosis. Overall, the obtained results of this study support our hypothesis that brain exposure to C. acnes prompted neuroinflammation with similar AD-like pathology., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)

Background: The unique neurovascular structure of the retina has provided an opportunity to observe brain pathology in many neurological disorders. However, such studies on neurodegeneration with brain iron accumulation (NBIA) disorders are lacking., Objectives: To investigate NBIA's neurological and ophthalmological manifestations., Methods: This cross-sectional study was conducted on genetically confirmed NBIA patients and an age-gender-matched control group. The thickness of retinal layers, central choroidal thickness (CCT), and capillary plexus densities were measured by spectral domain-optical coherence tomography (SD-OCT) and OCT angiography, respectively. The patients also underwent funduscopy, electroretinography (ERG), visual evoked potential (VEP), and neurological examination (Pantothenate-Kinase Associated Neurodegeneration-Disease Rating Scale [PKAN-DRS]). The generalized estimating equation model was used to consider inter-eye correlations., Results: Seventy-four patients' and 80 controls' eyes were analyzed. Patients had significantly decreased visual acuity, reduced inner or outer sectors of almost all evaluated layers, increased CCT, and decreased vessel densities, with abnormal VEP and ERG in 32.4% and 45.9%, respectively. There were correlations between visual acuity and temporal peripapillary nerve fiber layer (positive) and between PKAN-DRS score and disease duration (negative), and scotopic b-wave amplitudes (positive). When considering only the PKAN eyes, ONL was among the significantly decreased retinal layers, with no differences in retinal vessel densities. Evidence of pachychoroid was only seen in patients with Kufor Rakeb syndrome., Conclusion: Observing pathologic structural and functional neurovascular changes in NBIA patients may provide an opportunity to elucidate the underlying mechanisms and differential retinal biomarkers in NBIA subtypes in further investigations. © 2023 International Parkinson and Movement Disorder Society., (© 2023 International Parkinson and Movement Disorder Society.)

Introduction: Pancreatic cancer is a truculent disease with limited treatment options and a grim prognosis. Immunotherapy has shown promise in treating various types of cancer, but its effectiveness in pancreatic cancer has been lacking. As a result, it is crucial to identify markers associated with immunological pathways in order to improve the treatment outcomes for this deadly cancer. The purpose of this study was to investigate the diagnostic and prognostic significance of three markers, CD8, CD68, and VISTA, in pancreatic ductal adenocarcinoma (PDAC), the most common subtype of pancreatic cancer., Methods: We analyzed gene expression data from Gene Expression Omnibus (GEO) database using bioinformatics tools. We also utilized the STRING online tool and Funrich software to study the protein-protein interactions and transcription factors associated with CD8, CD68, and VISTA. In addition, tissue microarray (TMA) and immunohistochemistry (IHC) staining were performed on 228 samples of PDAC tissue and 10 samples of normal pancreatic tissue to assess the expression levels of the markers. We then correlated these expression levels with the clinicopathological characteristics of the patients and evaluated their survival rates., Results: The analysis of the GEO data revealed slightly elevated levels of VISTA in PDAC samples compared to normal tissues. However, there was a significant increase in CD68 expression and a notable reduction in CD8A expression in pancreatic cancer. Further investigation identified potential protein-protein interactions and transcription factors associated with these markers. The IHC staining of PDAC tissue samples showed an increased expression of VISTA, CD68, and CD8A in pancreatic cancer tissues. Moreover, we found correlations between the expression levels of these markers and certain clinicopathological features of the patients. Additionally, the survival analysis revealed that high expression of CD8 was associated with better disease-specific survival and progression-free survival in PDAC patients., Conclusion: These findings highlight the potential of CD8, CD68, and VISTA as diagnostic and prognostic indicators in PDAC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rezagholizadeh, Tajik, Talebi, Taha, Shariat Zadeh, Farhangnia, Hosseini, Nazari, Mollazadeh Ghomi, Kamrani Mousavi, Haeri Moghaddam, Khorramdelazad, Joghataei and Safari.)

GBM, or glioblastoma multiforme, is a brain tumor that poses a great threat to both children and adults, being the primary cause of death related to brain tumors. GBM is often associated with epilepsy, which can be debilitating. Seizures and the development of epilepsy are the primary symptoms that have a severe impact on the quality of life for GBM patients. It is increasingly apparent that the nervous system plays an essential role in the tumor microenvironment for all cancer types, including GBM. In recent years, there has been a growing understanding of how neurotransmitters control the progression of gliomas. Evidence suggests that neurotransmitters and neuromodulators found in the tumor microenvironment play crucial roles in the excitability, proliferation, quiescence, and differentiation of neurons, glial cells, and neural stem cells. The involvement of neurotransmitters appears to play a significant role in various stages of GBM. In this review, the focus is on presenting updated knowledge and emerging ideas regarding the interplay between neurotransmitters and neuromodulators, such as glutamate, GABA, norepinephrine, dopamine, serotonin, adenosine, and their relationship with GBM and the seizures induced by this condition. The review aims to explore the current understanding and provide new insights into the complex interactions between these neurotransmitters and neuromodulators in the context of GBM-related seizures., (© 2023 International Society for Developmental Neuroscience.)

Objective: To evaluate the alterations of language and memory functions using dynamic causal modeling, in order to identify the epileptogenic hemisphere in temporal lobe epilepsy (TLE)., Methods: Twenty-two patients with left TLE and 13 patients with right TLE underwent functional magnetic resonance imaging (fMRI) during four memory and four language mapping tasks. Dynamic causal modeling (DCM) was employed on fMRI data to examine effective directional connectivity in memory and language networks and the alterations in people with TLE compared to healthy individuals., Results: DCM analysis suggested that TLE can influence the memory network more widely compared to the language network. For memory mapping, it demonstrated overall hyperconnectivity from the left hemisphere to the other cranial regions in the picture encoding, and from the right hemisphere to the other cranial regions in the word encoding tasks. On the contrary, overall hypoconnectivity was seen from the brain hemisphere contralateral to the seizure onset in the retrieval tasks. DCM analysis further manifested hypoconnectivity between the brain's hemispheres in the language network in patients with TLE compared to controls. The CANTAB® neuropsychological test revealed a negative correlation for the left TLE and a positive correlation for the right TLE cohorts for the connections extracted by DCM that were significantly different between the left and right TLE cohorts., Interpretation: In this study, dynamic causal modeling evidenced the reorganization of language and memory networks in TLE that can be used for a better understanding of the effects of TLE on the brain's cognitive functions., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Post-stroke fatigue is a disturbing condition with various physical and psychological facets, which needs to be assessed by meaningful and psychometrically valid and reliable tools. The Chalder Fatigue Questionnaire (CFQ) and Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) have been designed to assess diverse dimensions of fatigue., Objectives: The present study aimed to investigate the psychometric properties of the CFQ and MFSI-SF in people with chronic stroke., Methods: Both measures were translated according to forward-backward standard protocol. This cross-sectional study was conducted with 130 first-time stroke survivors. The multidimensional fatigue inventory, checklist individual strength, fatigue assessment scale, fatigue subscale of profiles of mood state, fatigue severity scale, visual analogue scale-fatigue, beck anxiety inventory, center for epidemiologic studies of depression scale, and 36-item short-form health survey were administered in addition to the CFQ and MFSI-SF. Reliability, precision, known-groups validity, and convergent validity were examined for the CFQ and MFSI-SF., Results: The results showed an acceptable (Cronbach's alpha = 0.81-0.97) internal consistency and test-retest reliability (intra-class correlation = 0.75-0.97). The CFQ and MFSI-SF revealed good ability ( P  < 0.001) to differentiate chronic stroke survivors with different disability levels. Significant high correlation ( P  = -0.61-0.87) was found between CFQ and MFSI-SF and other fatigue scales., Conclusions: The results of this study showed that the CFQ and MFSI-SF have high reliability and validity for chronic stroke survivors.

The pattern of brain neuroplasticity after naming therapies in patients with aphasia can be evaluated using task-based fMRI. This article aims to review studies investigating brain reorganization after semantic and phonological-based anomia therapy that used picture-naming fMRI tasks. We searched for those articles that compared the activation of brain areas before and after aphasia therapies in the PubMed and the EMBASE databases from 1993 up to April 2020. All studies (single-cases or group designs) on anomia treatment in individuals with acquired aphasia were reviewed. Data were synthesized descriptively through tables to allow the facilitated comparison of the studies. A total of 14 studies were selected and reviewed. The results of the reviewed studies demonstrated that the naming improvement is associated with changes in the activation of cortical and subcortical brain areas. This review highlights the need for a more systematic investigation of the association between decreased and increased activation of brain areas related to anomia therapy. Also, more detailed information about factors influencing brain reorganization is required to elucidate the neural mechanisms of anomia therapy. Overall, regarding the theoretical and clinical aspects, the number of studies that used intensive protocol is growing, and based on the positive potential of these treatments, they could be suitable for the rehabilitation of people with aphasia.

Aquaporin 4 (AQP4) is a protein highly expressed in the central nervous system (CNS) and peripheral nervous system (PNS) as well as various other organs, whose different sites of action indicate its importance in various functions. AQP4 has a variety of essential roles beyond water homeostasis. In this article, we have for the first time summarized different roles of AQP4 in motor and sensory functions, besides cognitive and psychological performances, and most importantly, possible physiological mechanisms by which AQP4 can exert its effects. Furthermore, we demonstrated that AQP4 participates in pathology of different neurological disorders, various effects depending on the disease type. Since neurological diseases involve a spectrum of dysfunctions and due to the difficulty of obtaining a treatment that can simultaneously affect these deficits, it is therefore suggested that future studies consider the role of this protein in different functional impairments related to neurological disorders simultaneously or separately by targeting AQP4 expression and/or polarity modulation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Spinal cord edema is a quick-onset phenomenon with long-term effects. This complication is associated with inflammatory responses, as well as poor motor function. No effective treatment has been developed against spinal edema, which urges the need to provide novel therapies. Astaxanthin (AST) is a fat-soluble carotenoid with anti-inflammatory effects and a promising candidate for treating neurological disorders. This study aimed to investigate the underlying mechanism of AST on the inhibition of spinal cord edema, astrocyte activation, and reduction of inflammatory responsesin a rat compression spinal cord injury (SCI) model. Male rats underwent laminectomy at thoracic 8-9, and the SCI model was induced using an aneurysm clip. After SCI, rats received dimethyl sulfoxide or AST via intrathecal injection. The effects of AST were examined on the motor function, spinal cord edema, integrity of blood-spinal cord barrier (BSCB), and expression of high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), glial fibrillary acidic protein (GFAP), and aquaporin-4 (AQP4), and matrix metallopeptidase- 9 (MMP-9) post-SCI. We showed that AST potentially improved the recovery of motor function and inhibited the spinal cord edema via maintaining the integrity of BSCB, reducing the expression of HMGB1, TLR4, and NF-κB, MMP-9 as well as downregulation of astrocyte activation (GFAP) and AQP4 expression. AST improves motor function and reduces edema and inflammatory responses in the spinal tissue. These effects are mediated by suppression of the HMGB1/TLR4/NF-κB signaling pathway, suppressing post-SCI astrocyte activation, and decreasing AQP4 and MMP-9 expression., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

There is accumulating evidence that the circulatory levels of autotaxin (ATX) and lysophosphatidic acid (LPA) are increased in patients with severe liver disease. However, the potential role of the ATX-LPA axis in hepatic encephalopathy (HE) remains unclear. Our study aimed to investigate the role of the ATX-LPA signaling pathway in mice with thioacetamide (TAA) induced acute HE. To show the role of the ATX-LPA axis in the context of HE, we first measured the involvement of ATX-LPA in the pathogenesis of TAA-induced acute HE. Then, we compared the potential effects of ATX inhibitor (HA130) on astrocyte responses at in vitro and gut-liver-brain axis at in vivo levels. The inflammatory chemokine (C-C motif) ligand 3 was significantly increased in the hyperammonemic condition and could be prevented by ATX inhibition in astrocytes at in vitro level. Further statistical tests revealed that plasma and tissue pro-inflammatory cytokines were inhibited by HA130 in mice. Furthermore, the stage of HE was significantly improved by HA130. The most surprising result was that HA130 alleviated immune infiltrating cells in the liver and intestine and decreased mucus-secreting cells in the intestine. Further analysis showed that the levels of liver enzymes in serum were significantly decreased in response to ATX inhibition. Surprisingly, our data indicated that HA130 could recover permeabilization of the blood-brain barrier, neuroinflammation, and recognition memory. Besides that, we found that the changes of Interleukin-1 (IL-1) and aquaporin-4 (AQP4) in HE might have a connection with the glymphatic system based on bioinformatics analyses. Taken together, our data showed that the ATX-LPA axis contributes to the pathogenesis of HE and that inhibition of ATX improves HE., (© 2023. The Author(s).)

Sufficient activation of the left fusiform gyrus is important in reading ability acquisition due to its role in reading and naming, working memory (WM), and balance tasks. Recently, a newly-designed training program, Verbal Working Memory-Balance (VWM-B), has been evaluated on children with dyslexia, and its positive effects were shown on reading ability, WM capacity, and postural control. In the present study, we aimed to estimate the functional connectivity alterations of the left fusiform gyrus following training by the VWM-B. Before and after 15 sessions of training, the fMRI and other tools data were collected on a sample of children with dyslexia, who were allocated into two control and experiment groups. Data analyses showed the increased functional connectivity of the left fusiform gyrus between the left anterior temporal fusiform cortex, left and right Crus II regions of the cerebellum, and the left middle frontal gyrus. Moreover, VWM-B training significantly improved the reading and naming ability, WM capacity, and postural control of participants in the experiment group in comparison to the control. The current study findings emphasize the critical role of the left fusiform gyrus in reading ability. Moreover, it provides evidence to support the existence of cerebellar deficits in dyslexia., (© 2023 John Wiley & Sons Ltd.)

The cancer microenvironment plays a crucial role in promoting metastasis and malignancy even in normal cells. In the present study, the effect of acidic and conditioned media of cancer cells (MDA-MB-231), separately and in combination, was studied for the first time on the cell death mechanisms and DNA methylation of normal fibroblasts (NIH/3T3). Cell survival of conditioned media was rescued by the addition of acidic media to conditioned media, as shown by the results. Cell metabolic activity is deviated in a direction other than the Krebs cycle by acidic media The mitochondrial metabolic activity of all groups was enhanced over time, except for acidic media. Unlike the highest amount of ROS in conditioned media, its level decreased to the level of acidic media in the combination group. Furthermore, cells were deviated towards autophagy, rather than apoptosis, by the addition of acidic media to the conditioned media, unlike the conditioned media. Global DNA methylation analysis revealed significantly higher DNA hypomethylation in acidic media than in normal and combination media. Not only were cells treated with conditioned media rescued by acidic media, but also DNA hypomethylation and apoptosis in the combination group were decreased through epigenetic modifications. The acidic and conditioned media produced by cancer cells can remotely activate malignant signaling pathways, much like zombies, which can cause metabolic and epigenetic changes in normal cells., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rabiee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Diabetic wounds are chronic wounds that are currently affecting many patient's quality of life. These wounds are challenging because of the impaired healing cycle and harsh environment. In this study in situ gelling hydrogels based on oxidized carboxymethyl cellulose (OCMC) and gelatin (Gel) were used to hasten the healing rate due to their ease of application. The suggested system in this work is synthesized from entirely natural renewable biomaterials to not only achieve the best biocompatibility and biodegradability but also to develop a sustainable product. The rheological studies showed that the hydrogel is turned into a gel after about 30 s of the mixing process. Moreover, the hydrogel can absorb about ten times its weight, keeping the wound hydrated. In vitro biological investigations indicated optimal biocompatibility, antibacterial, and antioxidant activity for faster tissue regeneration. This product was tested in vivo on normal rats and diabetic mice models to treat full-thickness incisional wounds. Results showed that the OCMC-Gel hydrogel is able to hasten the healing rate in both non-diabetic and diabetic wounds. Pathological examinations of the regenerated skin tissue revealed that the OCMC-Gel treated groups developed much more than the control group., Competing Interests: Declaration of competing interest We declare that this manuscript is original, has not been published elsewhere partially or fully, and is not currently being considered for publication. We know of no conflicts of interest associated with this publication, and there has been no significant financial support for this work that could have influenced its outcomes., (Copyright © 2023. Published by Elsevier B.V.)

Background: Neurostimulation is one of the new therapeutic approaches in patients with drug-resistant epilepsy, and despite its high efficiency, its mechanism of action is still unclear. On the one hand, electrical stimulation in the human brain is immoral; on the other hand, the creation of the epilepsy model in laboratory animals affects the entire brain network. As a result, one of the ways to achieve the neurostimulation mechanism is to use epileptiform activity models In vitro. In vitro models, by accessing the local network from the whole brain, we can understand the mechanisms of action of neurostimulation., Methods: A literature search using scientific databases including PubMed, Google Scholar, and Scopus, using "Neurostimulation" and "epileptiform activity" combined with "high-frequency stimulation", " low-frequency stimulation ", and "brain slices" as keywords were conducted, related concepts to the topic gathered and are used in this paper., Results: Electrical stimulation causes neuronal depolarization and the release of GABAA, which inhibits neuronal firing. Also, electrical stimulation inhibits the nervous tissue downstream of the stimulation site by preventing the passage of nervous activity from the upstream to the downstream of the axon., Conclusion: Neurostimulation techniques consisting of LFS and HFS have a potential role in treating epileptiform activity, with some studies having positive results. Further investigations with larger sample sizes and standardized outcome measures can be conducted to validate the results of previous studies., Competing Interests: The authors declare that they have no competing interests., (© 2023 Iran University of Medical Sciences.)

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with high mortality and morbidity rate affecting both upper and lower motor neurons (MN). Muscle force reduction, behavioral change, pseudobulbar affect, and cognitive impairments are the most common clinical manifestations of ALS. The main physiopathology of ALS is still unclear, though several studies have identified that oxidative stress, proteinopathies, glutamate-related excitotoxicity, microglial activation, and neuroinflammation may be involved in the pathogenesis of ALS. From 1995 until October 2022, only Riluzole, Dextromethorphan Hydrobromide (DH) with Quinidine sulfate (Q), Edaravone, and Sodium phenylbutyrate with Taurursodiol (PB/TUDCO) have achieved FDA approval for ALS treatment. Despite the use of these four approved agents, the survival rate and quality of life of ALS patients are still low. Thus, finding novel treatments for ALS patients is an urgent requirement. Masitinib, a tyrosine kinase inhibitor, emphasizes the neuro-inflammatory activity of ALS by targeting macrophages, mast cells, and microglia cells. Masitinib downregulates the proinflammatory cytokines, indirectly reduces inflammation, and induces neuroprotection. Also, it was effective in phase 2/3 and 3 clinical trials (CTs) by increasing overall survival and delaying motor, bulbar, and respiratory function deterioration. This review describes the pathophysiology of ALS, focusing on Masitinib's mechanism of action and explaining why Masitinib could be a promising actor in the treatment of ALS patients. In addition, Masitinib CTs and other competitor drugs in phase 3 CTs have been discussed., Competing Interests: Conflict of interest statement Authors declare no financial and non-financial conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

A patient with epilepsy was shown to have neurobiological, psychological, cognitive, and social issues as a result of recurring seizures, which is regarded as a chronic brain disease. However, despite numerous drug treatments, approximately, 30%-40% of all patients are resistant to antiepileptic drugs. Therefore, newer therapeutic modalities are introduced into clinical practice which involve neurostimulation and direct stimulation of the brain. Hence, we review published literature on vagus nerve stimulation, trigeminal nerve stimulation, applying responsive stimulation systems, and deep brain stimulation (DBS) in animals and epileptic patient with an emphasis on drug-resistant epilepsy., Competing Interests: Conflict of interest The authors declared no conflict of interest., (Copyright© 2023 Iranian Neuroscience Society.)

Background: Interneural gap junctional coupling represents neural development that decreases during the postnatal period. The decrease of gap junction function coincides with the main period of chemical synapse creation and increment of synaptic activity during postnatal weeks 1 to 3., Methods: Here, we have assessed the role of chemical synapses on connexin (Cx) expression in neurons and glial cells of hippocampal and cortical neurons. We characterized the impact of NMDA receptors blockade on the expression of Cx36 and Cx43 proteins by western blot analysis in postnatal day (PND)14 and PND28. MK801 was injected subcutaneously from the first day of birth until 14 or 28 days, depending on the experimental groups. Saline was injected in the same volumes in the control group., Results: Early postnatal blockade of the NMDA subtype of glutamate receptors by the non-competitive antagonist dizocilpine maleate (MK801) arrested the developmental reduction in gap junctions during the initial postnatal weeks. Expression of Cx43 declined in PND28 compared to PND14 in visual cortex (VC) neurons. Also, we found that the expression of Cx36 and Cx43 augmented in the rats' VC in PND28 following the blockade of NMDA receptors. Expression of Cx36 declined in PND28 compared to PND14 in hippocampal neurons. Also, we found that the expression of Cx36 augmented in the rats' hippocampal neurons in PND14 and PND28 following a blockade of NMDA receptors., Conclusion: These results suggest that the postnatal enhancement in glutamatergic synaptic activity is associated with the loss of gap junctional connections and downregulation of Cx36 and Cx43 between developing neurons and glial cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)