Yazd University

Recent genomic research has identified several genetic factors contributing to B-cell acute lymphoblastic leukemia (B-ALL). However, the exact cause of the disease is still not fully understood. It is known that mutations in the TAL2 gene play important roles in the development of acute lymphoblastic leukemia. This study aimed to analyze the molecular and computational profile of the TAL2 mutations in a group of Iranian B-ALL patients for the first time.

In this study, 188 patients were enrolled, and the TAL2 gene was sequenced to identify gene variations. The study included structural/functional analysis, homology modeling, molecular docking, and molecular dynamics (MD) simulations to assess the potential impact of the missense mutations on the protein's structure. Three nucleotide variations in the exon, three variations in the 3'UTR, and one deletion variant in the 3'UTR were detected in patients. Through in-silico analysis, it was found that the p. Asp35Glu missense mutation is located in the bHLH domain of the TAL2 protein. Also, the structural and functional analyses predicted that this mutation is a pathogenic or likely pathogenic variant in B-ALL patients. Moreover, a multiple nucleotide deletion (g.659_668del) was found in the 3'UTR in most patients. This deletion occurs at the site of poly-A tail attachment and appears to have significant implications.

These findings offer new insights into the impact of genetic variants in the TAL2 gene on the development of B-ALL and their potential role as tumor biomarkers for the B-ALL. Further research is needed to explore the relationship between specific TAL2 mutations and the clinical presentation of B-ALL.

Diabetes, via chronic metabolic and inflammatory dysregulation, may impair immune function and contribute to cognitive decline, particularly in executive functions. In this study, we examined changes in the cytokines IL-10 and TNF, as well as their balance, alongside executive function, physical performance, and diabetes-related indices following a combined, dual-task, home-based exercise training program. A total of 85 inactive women aged 50-75 years with type 2 diabetes were randomly assigned to either an exercise training group or a control group. During the pre- and post-test phases, assessments were conducted in both groups to measure executive function, physical performance, levels of IL-10 and TNF, their ratio, and diabetes-related indices. The dual-tasked home-based exercise program improved physical performance and body composition (P < 0.05). Executive function significantly improved in the exercise group (Effect size (ES) = 0.44, P < 0.05), accompanied by reductions in IL-10 (ES = 1.11, P < 0.05) and TNF levels (ES = 0.76, P < 0.05). However, no significant changes were observed in the balance of these two cytokines or diabetes-related indices (P > 0.05), except for HDL levels (ES = 0.87, P < 0.05). Based on the results of the present study, engaging in multi-task home-based exercise training can enhance executive function and reduce inflammatory cytokines in women with type 2 diabetes. However, this training did not significantly affect the balance between IL-10 and TNF, which may be due to the moderate intensity of the exercises. Further long-term studies that take into account additional factors-such as nutrition, medication use, and cognitive status-are warranted to gain a clearer understanding of the cytokine-modulating effects of dual-task exercise training in individuals with type 2 diabetes.

Glutamate (Glu), the most abundant neurotransmitter in the central nervous system, plays a vital role in various physiol. processes.Abnormal Glu levels will lead to stroke, epilepsy, and Alzheimer′s disease.Consequently, detecting Glu is clin. important for effective diagnosis and treatment.Electrochem. techniques have been used for Glu detection due to their rapid response, portability, and cost-effectiveness, surpassing traditional methods like spectrophotometry, and chromatog.Enzymic electrochem. sensors have been utilized to measure Glu levels.They provide high sensitivity.However, they are expensive and unstable, leading to signal reduction and measurement inaccuracies.Recently, non-enzymic sensors, due to their cost-effectiveness, rapid response, ease of fabrication, low detection limits, and high sensitivity, have received more attention.This work introduces an electrochem. non-enzymic sensor to detect Glu using the nanocomposite of Ni metal-organic framework (Ni-MOF) and multiwall carbon nanotubes (MWCNTs) synthesized by a simple, one-step method.Electrochem. measurements indicated an amperometric curve with a limit of detection (LOD) value of 69.9 μM, and an excellent sensitivity value of 2.90 x 10² (μA mM^-1 cm^-2), comparable with some previous articles.This work presents the application of Ni-MOF-CNTs nanocomposite to detect Glu for the first time.Importantly, this sensor has emerged as a significant development, offering a non-enzymic approach to detection.It eliminates the complexities and costs associated with enzyme immobilization, which can lead to challenges in sensor design.Our findings indicate that this nanocomposite represents a promising electrochem. sensing material for the efficient detection of Glu, paving the way for more accessible sensing.