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Aging is a biological process determined through time-related cellular and functional impairments, leading to a decreased standard of living for the organism. Recently, there has been an unprecedented advance in the aging investigation, especially the detection that the rate of senescence is at least somewhat regulated via evolutionarily preserved genetic pathways and biological processes. Hematopoietic stem cells (HSCs) maintain blood generation over the whole lifetime of an organism. The senescence process influences many of the natural features of HSC, leading to a decline in their capabilities, independently of their microenvironment. New studies show that HSCs are sensitive to age-dependent stress and gradually lose their self-renewal and regeneration potential with senescence. MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally inhibit translation or stimulate target mRNA cleavage of target transcripts via the sequence-particular connection. MiRNAs control various biological pathways and processes, such as senescence. Several miRNAs are differentially expressed in senescence, producing concern about their use as moderators of the senescence process. MiRNAs play an important role in the control of HSCs and can also modulate processes associated with tissue senescence in specific cell types. In this review, we display the contribution of age-dependent alterations, including DNA damage, epigenetic landscape, metabolism, and extrinsic factors, which affect HSCs function during aging. In addition, we investigate the particular miRNAs regulating HSCs senescence and age-associated diseases. Video Abstract.
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Longevidad , MicroARNs , Longevidad/genética , MicroARNs/genética , Células Madre Hematopoyéticas , Senescencia CelularRESUMEN
Alzheimer's disease is a neurodegenerative disorder that impacts memory, thinking, and behavior, and currently, there is no effective cure available for its treatment. This study explored a one-pot strategy for synthesizing spiroindolinone-pyrazole derivatives through a sequential four-component condensation reaction. These derivatives were further investigated for their potential as anti-Alzheimer's disease agents. The developed synthetic procedure provides remarkable advantages, including a clean reaction profile, abundant starting materials, operational simplicity, and easy purification without traditional methods with good to excellent yields (84-96%). Next, the biological potencies of the newly synthesized spiroindolinone-pyrazole derivatives against AChE and BChE as Alzheimer's disease-related targets were determined. Also, the kinetic study and cytotoxicity of the most potent derivative were investigated. Furthermore, molecular docking and molecular dynamics evaluations were performed employing in silico tools to investigate the interaction, orientation, and conformation of the potent analog over the active site of the enzyme.
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Introduction and importance: This research was conducted to investigate the effectiveness of neurofeedback on the symptoms of hyperactivity and attention deficit in primary school students with attention deficit/hyperactivity disorder (ADHD) disorder. Case presentation: The present study utilized a randomized clinical trial with pre-test and post-test measurements and included a control group. The research population included all primary school students with ADHD in 2023; 50 of these children were selected as the experimental group based on the accessible sampling method, and 50 were also included in the control group. Neurofeedback treatment sessions for the experimental group were 30 sessions. Research data were collected in three stages: pre-test and post-test, using a questionnaire based on the Conners rating scale from parents. SPSS-25 analyzed the data. Clinical discussion: The results showed that neurofeedback is associated with significant effectiveness in the symptoms of attention deficit disorder and hyperactivity of students (P<0.05). Conclusion: Based on the findings of this research, it can be said that neurofeedback treatment is effective in reducing attention deficit and hyperactivity symptoms of students with ADHD disorder. It is suggested to widely use neurofeedback to reduce the symptoms of attention deficit and hyperactivity disorder.
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This study aimed to explore the neuro-cognitive paradigm in anxiety diseases by integrating neurobiological and cognitive perspectives. The ideal was to enhance our understanding of the complex interplay between neural and cognitive processes in anxiety and its counteraccusations for treatment. A comprehensive review of the literature was conducted, examining studies that delved into the neurobiological supplements and cognitive impulses in anxiety. The findings revealed the involvement of brain regions similar to the amygdala, prefrontal cortex, and hippocampus in anxiety diseases, along with dysregulation in neurotransmitter systems. Cognitive impulses, including attentional bias towards trouble, interpretation bias, and memory impulses, were constantly observed in individuals with anxiety. The results stressed the bidirectional relationship between neurobiology and cognition, demonstrating that neurobiological factors impact cognitive processes, and cognitive factors modulate neural exertion. Integrated interventions targeting both neurobiological and cognitive factors showed a pledge in treating anxiety diseases. The study linked gaps in the literature and emphasized the significance of considering artistic factors and developing individualized treatment approaches. Overall, this study contributes to a comprehensive understanding of anxiety diseases and informs unborn exploration and clinical practice.
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Emerging as a promising drug target for Alzheimer's disease (AD) therapy, glycogen synthase kinase 3ß (GSK-3ß) has garnered attention. This study sought to rigorously scrutinize a compendium of natural compounds retrieved from the ZINC database through pharmacodynamic experiments, employing a 1â¯H-indazole-3-carboxamide (INDZ) scaffold, to identify compounds capable of inhibiting the GSK-3ß protein. Utilizing a multi-step approach, the study involved pharmacophore analysis, followed by molecular docking to select five promising ligands for further investigation. Subsequently, ESMACS simulations were employed to assess the stability of the ligand-protein interactions. Evaluation of the binding modes and free energy of the ligands revealed that five compounds (2a-6a) exhibited crucial interactions with the active site residues. Furthermore, various methodologies, including hydrogen bond and clustering analyses, were utilized to ascertain their inhibitory potential and elucidate the factors contributing to ligand binding in the protein's active site. The findings from MMPBSA/GBSA analysis indicated that these five selected small molecules closely approached the IC50 value of the reference ligand (OH8), yielding energy values of -34.85, -32.58, -31.71, and -30.39â¯kcal/mol, respectively. Additionally, an assessment of the interactions using hydrogen bond and dynamic analyses delineated the effective binding of the ligands with the binding pockets in the protein. Through computational analysis, we obtained valuable insights into the molecular mechanisms of GSK-3ß, aiding in the development of more potent inhibitors.
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Enfermedad de Alzheimer , Glucógeno Sintasa Quinasa 3 beta , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Glucógeno Sintasa Quinasa 3 beta/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/química , Humanos , Ligandos , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Estructura MolecularRESUMEN
Background: Group cognitive-behavioral therapy has demonstrated its effectiveness in treating various psychological disorders. Nevertheless, there is insufficient evidence supporting its application in enhancing both the quality of life and depression among Parkinson's patients. Consequently, this study was undertaken to examine the efficacy of group cognitive-behavioral therapy in ameliorating depression symptoms and enhancing the quality of life in individuals afflicted with Parkinson's disease. Materials and methods: A randomized clinical trial with pre-test and post-test measurements, including a control group, was conducted. The sample consisted of individuals referred to Roozbeh Hospital in Tehran with Parkinson's disease in 2023. Ninety participants were selected using convenience sampling and randomly assigned to either an experimental or a control group, with 45 participants in each. The experimental group received a three-month cognitive-behavioral therapy intervention consisting of 12 sessions of 90 min. Pre-test and post-test measures included the Beck Depression Questionnaire and the World Health Organization Quality of Life Questionnaire. Data analysis was performed using multivariate analysis of covariance (MANCOVA) in SPSS-25. Results: The results revealed a significant difference between the experimental and control groups in terms of depression and quality of life. The cognitive-behavioral therapy intervention significantly reduced depression and significantly improved the quality of life in individuals with Parkinson's disease (P≤0.01). Conclusion: Group cognitive-behavioral therapy can be an effective approach for reducing depression and improving the quality of life in individuals with Parkinson's disease. Therefore, therapists and healthcare providers can utilize cognitive-behavioral therapy to enhance the well-being of individuals with Parkinson's disease.
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Introduction and importance: Autism spectrum disorder significantly impacts the life and psychosocial health of the family, resulting in high levels of anxiety, stress, isolation, and indecisiveness among parents. This study aimed to determine the effectiveness of cognitive therapy based on mindfulness in increasing the tolerance of mothers of children with autism. Case presentation: The study used a semi-experimental pre-test-post-test design with a control group. The study population comprised mothers referred to autism centers in Tehran. Eighty mothers were randomly divided into two groups, with 40 in each group. The Connor and Davidson Resilience Scale was used to measure the level of tolerance in both groups in the pre-test and post-test stages. The experimental group underwent cognitive therapy group therapy based on mindfulness, comprising eight sessions of 120 min. On the other hand, the control group did not receive any intervention. Clinical discussion: The results of the study showed that the tolerance scores of the experimental group significantly increased after the intervention, in both the post-test and follow-up stages. Conclusion: Therefore, the results of this research emphasize the importance of using this intervention in increasing the tolerance of mothers of children with autism spectrum disorder and creating new horizons in the clinical interventions of these people.
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Human polyomavirus type 1, or BK virus (BKV), is a ubiquitous pathogen belonging to the polyomaviridae family mostly known for causing BKV-associated nephropathy (BKVN) and allograft rejection in kidney transplant recipients (KTRs) following the immunosuppression regimens recommended in these patients. Reduction of the immunosuppression level and anti-viral agents are the usual approaches for BKV clearance, which have not met a desired outcome yet. There are also debating matters such as the effect of this pathogen on emerging various comorbidities and the related malignancies in the human population. In this study, a reverse vaccinology approach was implemented to design a mRNA vaccine against BKV by identifying the most antigenic proteins of this pathogen. Potential immunogenic T and B lymphocyte epitopes were predicted through various immunoinformatic tools. The final epitopes were selected according to antigenicity, toxicity, allergenicity, and cytokine inducibility scores. According to the obtained results, the designed vaccine was antigenic, neutral at the physiological pH, non-toxic, and non-allergenic with a world population coverage of 93.77%. Since the mRNA codon optimization ensures the efficient expression of the vaccine in a host cell, evaluation of different parameters showed our designed mRNA vaccine has a stable structure. Moreover, it had strong interactions with toll-like receptor 4 (TLR4) according to the molecular dynamic simulation studies. The in silico immune simulation analyses revealed an overall increase in the immune responses following repeated exposure to the designed vaccine. Based on our findings, the vaccine candidate is ready to be tested as a promising novel mRNA therapeutic vaccine against BKV.
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Virus BK , Trasplante de Riñón , Infecciones por Polyomavirus , Humanos , Virus BK/genética , Trasplante de Riñón/efectos adversos , Vacunología/métodos , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/etiología , Epítopos de Linfocito B/genética , ARN Mensajero/genética , Epítopos de Linfocito T/genética , Simulación del Acoplamiento Molecular , Biología Computacional , Vacunas de ARNmRESUMEN
The present study aimed to study the impact of neurofeedback on the academic performance of nursing students with academic failure. Methods: This study was an experimental one with a pretest-posttest design with a control group. The statistical population of this research was the nursing students of the Faculty of Nursing, Tehran University of Medical Sciences University of Medical Sciences. The sample of this study consisted of 60 individuals chosen by a simple random sampling method and two experiment groups (N=30) and a control group (N=30) were replaced by accident. Neurofeedback was an advanced Raven test and a researcher-made questionnaire for data collection. Thereafter, the experimental group was treated with neurofeedback for 7-10 weeks and 20 50-min therapeutic sessions as the experimental condition. In the first 130 s, the baseline was determined for the individual, and during the session, the baseline was practiced. Each session consisted of six exercises, each lasting 7 min. Results: The results of the covariance analysis showed that students who had an educational drop and were trained in neurofeedback sessions showed a significant increase in the next half (P<0.05) compared to the control group. Conclusion: The results of this study showed that neurofeedback is an effective method for managing the academic performance of nursing students with academic failure.
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The idea of applying ultrasound (US) as a green activation method in chemical transformations, especially in catalytic alcohol oxidations, technically and ecologically appeals to chemists. In the present work, as an attempt to fulfill the idea of designing an eco-friendly system to oxidize alcoholic substrates into corresponding aldehydes, we developed multifunctional tungstate-decorated CQD base catalyst, A-CQDs/W, and examined its sonooxidation performance in presence of H2O2 as a green oxidant in aqua media. By comparing the catalyst performance in oxidize benzyl alcohol as a testing model to benzaldehyde (BeOH) prior and after US irradiation-trace vs 93%- the key role of ultrasonic irradiation in achieving high yield is completely appreciated. Exceptional thermal and compression condition that is created as a result of acoustic waves is in charge of unparalleled yield results in this type of activation method. The immense degree of reagent interaction in this method, ensures the maximum yield in notably low time, which in turn leads to decrease in the number of unreacted reagents and by-products. Meanwhile, the need for using toxic organic solvents and hazardous oxidants, auxiliaries and phase transfer catalyst (PTC) is completely obviated.
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Alcoholes , Aldehídos , Catálisis , Peróxido de Hidrógeno , Oxidantes , Compuestos de TungstenoRESUMEN
Nanoparticles (NPs) are of the most interesting novel vehicles for effective drug delivery to humans. Freeze drying is known as an engaging process to improve the long lasting stability of NPs formulations. This study aims to elucidate the importance of various parameters involving in freeze-drying of the most common pharmaceutical/nutraceutical NPs including nanosuspensions, nanocrystals (NCs), cocrystals/nanococrystals, nanoemulsions (NEs), nanocapsules (NCPs) and nanospheres (NSPs). Regarding this, the therapeutic goals of NPs and specifications of drug must be considered. According to our survey, the most influential factors for achieving optimum results include type and concentration of cryoprotectant/lyoprotectant, stabilizer structure and concentration, the NPs concentration in solution, freezing, annealing, and drying rate, the interaction between protectants and stabilizer, solvent type and antisolvent to solvent ratio. The study shows that for each class of NPs, specific variables are of highest significance and should be optimized. For instance, about NCs, freezing rate and antisolvent/solvent ratio should be particularly considered and for emulsified NPs, the best results have been obtained by 5-20% of saccharides as cryoprotectants. These findings suggest that to obtain a product with the lowest aggregation and particle size (PS), optimization of the effective factors in formulation and lyophilization process are essential.
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Nanopartículas , Preparaciones Farmacéuticas , Química Farmacéutica , Suplementos Dietéticos , Liofilización , Humanos , Tamaño de la PartículaRESUMEN
Doublecortin-like kinase 1 (DCLK1) is a protein kinase that is known as a specific cancer stem cell (CSC) marker in colorectal cancer (CRC). Deregulation of DCLK1 expression has been reported in various cancers. We measured the protein expression of DCLK1 in 38 CRC and normal colon samples by immunohistochemistry (IHC). HCT-116 and SW-48 cells were transfected with DCLK1 siRNA and analyzed for expression of DCLK1 and miR-200c. The effects of DCLK1 knockdown on cell migration, invasion, sphere-forming, and apoptosis were explored. It was found that DCLK1 protein expression levels were significantly higher in CRC tissue than in normal colon specimens. Silencing of DCLK1 significantly inhibited cell migration, invasion, and sphere-forming potential; it also induced apoptosis as well as increased expression of miR-200c. Furthermore, silencing of miR-200c significantly up-regulated DCLK1 expression. Overall, our data demonstrated that DCLK1 plays an important role in cancer progression and is involved in the regulation of miR-200c expression.