Promising Avenue For Therapeutic Intervention Research Articles

An increase of lysosomes through EGF-triggered endocytosis attenuated zinc-mediated lysosomal membrane permeabilization and neuronal cell death.

In the context of acute brain injuries, where zinc neurotoxicity and oxidative stress are acknowledged contributors to neuronal damage, we investigated the pivotal role of lysosomes as a potential protective mechanism. Our research commenced with an exploration of epidermal growth factor (EGF) and its impact on lysosomal dynamics, particularly its neuroprotective potential against zinc-induced cytotoxicity. Using primary mouse cerebrocortical cultures, we observed the rapid induction of EGFR endocytosis triggered by EGF, resulting in a transient increase in lysosomal vesicles. Furthermore, EGF stimulated lysosomal biogenesis, evident through elevated expression of lysosomal-associated membrane protein 1 (LAMP-1) and the induction and activation of prominent lysosomal proteases, particularly cathepsin B (CTSB). This process of EGFR endocytosis was found to promote lysosomal augmentation, thus conferring protection against zinc-induced lysosomal membrane permeabilization (LMP) and subsequent neuronal death. Notably, the neuroprotective effects and lysosomal enhancement induced by EGF were almost completely reversed by the inhibition of clathrin-mediated and caveolin-mediated endocytosis pathways, along with the disruption of retrograde trafficking. Furthermore, tyrosine kinase inhibition of EGFR nullified EGFR endocytosis, resulting in the abrogation of EGF-induced lysosomal upregulation and neuroprotection. An intriguing aspect of our study is the successful replication of EGF's neuroprotective effects through the overexpression of LAMP-1, which significantly reduced zinc-induced LMP and cell death, demonstrated in both primary mouse cerebrocortical neuronal cultures and human embryonic kidney (HEK) cells. Our research extended beyond zinc-induced neurotoxicity, as we observed EGF's protective effects against other oxidative stressors linked to intracellular zinc release, including hydrogen peroxide (H2O2) and 1-methyl-4-phenylpyridinium ion (MPP+). Collectively, our findings unveil the intricate interplay between EGF-triggered EGFR endocytosis, lysosomal upregulation, an increase in the regulatory capacity for zinc homeostasis, and the subsequent alleviation of zinc-induced neurotoxicity. These results present promising avenues for therapeutic interventions to enhance neuroprotection by targeting lysosomal augmentation.

Unlocking the Epigenetic Symphony: Histone Acetylation Orchestration in Bone Remodeling and Diseases.

Histone acetylation orchestrates a complex symphony of gene expression that controls cellular fate and activities, including the intricate processes of bone remodeling. Despite its proven significance, a systematic illustration of this process has been lacking due to its complexity, impeding clinical application. In this review, we delve into the central regulators of histone acetylation, unveiling their multifaceted roles in modulating bone physiology. We explore both contradictory and overlapping roles among these regulators and assess their potential as therapeutic targets for various bone disorders. Furthermore, we highlight current applications and discuss looming questions for a more effective use of epigenetic therapy in bone diseases, aiming to address gaps in knowledge and clinical practice. By providing a panoramic view of histone acetylation's impact on bone health and disease, this review unveils promising avenues for therapeutic intervention and enhances our understanding of skeletal physiology, crucial for improving therapeutical outcomes and quality of patients' life.

MBNL deficiency in motor neurons disrupts neuromuscular junction maintenance and gait coordination.

Muscleblind-like proteins (MBNLs) are a family of RNA-binding proteins that play essential roles in the regulation of RNA metabolism. Beyond their canonical role in RNA regulation, MBNL proteins have emerged as key players in the pathogenesis of Myotonic Dystrophy type 1 (DM1). In DM1, sequestration of MBNL proteins by expansion of the CUG repeat RNA leads to functional depletion of MBNL, resulting in deregulated alternative splicing and aberrant RNA processing, which underlie the clinical features of the disease. While attention to MBNL proteins has focused on their functions in skeletal muscle, new evidence suggests that their importance extends to motor neurons (MNs), pivotal cellular components in the control of motor skills and movement. To address this question, we generated conditional double knockout mice in which Mbnl1 and Mbnl2 were specifically deleted in motor neurons (MN-dKO). Adult MN-dKO mice develop gait coordination deficits associated with structural and ultrastructural defects in the neuromuscular junction, indicating that MBNL activity in MNs is crucial for the maintenance of the neuromuscular junction. In addition, transcriptome analysis performed on the spinal cord of MN-dKO mice identified mis-splicing events in genes associated with synaptic transmission and neuromuscular junction homeostasis. In summary, our results highlight the complex roles and regulatory mechanisms of MBNL proteins in MNs for muscle function and locomotion. This work provides valuable insights into fundamental aspects of RNA biology and offers promising avenues for therapeutic intervention in DM1 as well as a range of diseases associated with RNA dysregulation.

Metabolic and Epigenetic Mechanisms in Hepatoblastoma: Insights into Tumor Biology and Therapeutic Targets

Background: Hepatoblastoma, the most common pediatric liver malignancy, is characterized by significant molecular heterogeneity and poor prognosis in advanced stages. Recent studies highlight the importance of metabolic reprogramming and epigenetic dysregulation in hepatoblastoma pathogenesis. This review aims to explore the metabolic alterations and epigenetic mechanisms involved in hepatoblastoma and how these processes contribute to tumor progression and survival. Methods: Relevant literature on metabolic reprogramming, including enhanced glycolysis, mitochondrial dysfunction, and shifts in lipid and amino acid metabolism, as well as epigenetic mechanisms like DNA methylation, histone modifications, and non-coding RNAs, was reviewed. The interplay between these pathways and their potential as therapeutic targets were examined. Results: Hepatoblastoma exhibits metabolic shifts that support tumor growth and survival, alongside epigenetic changes that regulate gene expression and promote tumor progression. These pathways are interconnected, with metabolic changes influencing the epigenetic landscape and vice versa. Conclusions: The dynamic interplay between metabolism and epigenetics in hepatoblastoma offers promising avenues for therapeutic intervention. Future research should focus on integrating metabolic and epigenetic therapies to improve patient outcomes, addressing current gaps in knowledge to develop more effective treatments.

Biological function of sialic acid and sialylation in human health and disease.

Sialic acids are predominantly found at the terminal ends of glycoproteins and glycolipids and play key roles in cellular communication and function. The process of sialylation, a form of post-translational modification, involves the covalent attachment of sialic acid to the terminal residues of oligosaccharides and glycoproteins. This modification not only provides a layer of electrostatic repulsion to cells but also serves as a receptor for various biological signaling pathways. Sialylation is involved in several pathophysiological processes. Given its multifaceted involvement in cellular functions, sialylation presents a promising avenue for therapeutic intervention. Current studies are exploring agents that target sialic acid residues on sialoglycans or the sialylation process. These efforts are particularly focused on the fields of cancer therapy, stroke treatment, antiviral strategies, and therapies for central nervous system disorders. In this review, we aimed to summarize the biological functions of sialic acid and the process of sialylation, explore their roles in various pathophysiological contexts, and discuss their potential applications in the development of novel therapeutics.

Repetitive Transcranial Magnetic Stimulation Modulates Brain Connectivity in Children with Self-limited Epilepsy with Centrotemporal Spikes.

Interictal epileptiform discharges (IEDs) alter brain connectivity in children with epilepsy; this connectivity change may be a mechanism by which epilepsy induces cognitive deficits. Here, we test whether repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, modulates connectivity and reduces IEDs in children with epilepsy. Nineteen children with self-limited epilepsy with centrotemporal spikes (SeLECTS) participated in a cross-over study comparing the impact of active vs. sham rTMS on IEDs and brain connectivity. SeLECTS is an epilepsy syndrome affecting the motor cortex, and prior studies show that motor cortices become pathologically hyper-connected to frontal and temporal language cortices. Using a crossover design, we compared the effect of single doses of active versus sham motor cortex rTMS. Connectivity, which was quantified by the weighted phase lag index (wPLI), was measured before and after rTMS using single pulses of TMS combined with EEG (spTMS-EEG). Analyses focused on six regions: bilateral motor cortices and bilateral inferior frontal and superior temporal regions. IEDs were counted in the five minutes before and after rTMS. Active, but not sham, rTMS significantly and globally decreased wPLI connectivity between multiple regions, with the greatest reductions seen in the superior temporal region connections in the stimulated hemisphere. Additionally, there was a trend suggesting that rTMS decreases IED frequency. These findings underscore the potential of low-frequency rTMS to target pathologic hyperconnectivity and reduce IEDs in children with SeLECTS and potentially other pediatric epilepsy syndromes, offering a promising avenue for therapeutic intervention.

GSK-3β and Non-Small Cell Lung Cancer: A Review of Its Role in Disease Mechanisms and Treatment Strategies

Introduction Recent molecular docking studies have identified potential inhibitors targeting GSK-3β, offering promising avenues for therapeutic intervention. These inhibitors could potentially disrupt the oncogenic signaling pathways mediated by GSK-3β, thereby halting or reversing tumor progression. This literature review seeks to deliver a thorough examination of the current knowledge regarding GSK-3β influence on NSCLC. Methods The author carried out an extensive literature review utilizing various electronic databases such as PubMed, Scopus, and Europe PMC. The search keywords included "GSK-3β," "glycogen synthase kinase-3 beta," "non-small cell lung cancer," "NSCLC," "prognosis," "apoptosis," "cell proliferation," "autophagy," "radiosensitivity," "tumor differentiation," and "molecular docking." The findings from the included studies were integrated into a narrative review, emphasizing GSK-3β role in NSCLC pathogenesis, its potential as a therapeutic target, and its utility as a prognostic biomarker. Results GSK-3β is a multifunctional serine/threonine kinase involved in various cellular processes, including proliferation, differentiation, motility, and survival. Its expression is associated with NSCLC differentiation, with GSK-3β-negative tumors showing better prognosis. Preclinical studies have identified potential GSK-3β inhibitors with favorable docking scores and ADME profiles for NSCLC treatment. However, targeting GSK-3β for NSCLC treatment faces several significant challenges. One major issue is the broad role of GSK-3β in various cellular processes, including metabolism and cell survival, which increases the risk of off-target effects and toxicity. Conclusions GSK-3β has emerged as a critical biomarker in NSCLC, exerting a significant impact on disease progression, treatment response, and prognosis.

Assessment of the Short-Term Efficacy of a Wet-Cupping Therapy Session in Alleviating Symptoms of Fibromyalgia Syndrome: A Single-Arm Clinical Trial

Fibromyalgia holds significant importance in both primary care and physical treatment settings due to its high prevalence and the challenges associated with its diagnosis and management. This study aims to assess the short-term efficacy of a wet-cupping therapy session in alleviating symptoms of Fibromyalgia Syndrome (FMS). This study employed a prospective, single-arm intervention design. Baseline and post-treatment evaluations encompassed a comprehensive battery of assessment tools: Socio-Demographic Questionary, Visual Analog Scale (VAS) for Pain, Fatigue Severity Scale (FSS), Beck Depression Scale (BDS), Fibromyalgia Impact Questionnaire (FIQ). A total of 20 eligible individuals were enrolled in the study. Significant alterations in pain perception, as measured by the VAS, were evident both prior to treatment and at the end of the first week of treatment (p < 0.001). Additionally, significant favorable effects of the treatment were observed on FSS and BDS levels during the initial week of therapy (p = 0.001, p = 0.01; respectively). Moreover, a marked improvement was identified in FIQ scores after treatment compared to baseline (p < 0.001). Across all evaluated clinical indicators, cupping therapy exhibited a significant positive influence on FMS. In conclusion, wet cupping therapy yields favorable outcomes in terms of pain perception, fatigue reduction, mood enhancement, and the overall impact of fibromyalgia syndrome. Thus, it offers a promising avenue for therapeutic intervention among individuals afflicted by this condition.

Multiple myeloma exosomal miRNAs suppress cGAS-STING antiviral immunity

DNA virus infection is a significant cause of morbidity and mortality in patients with multiple myeloma (MM). Monocyte dysfunction in MM patients plays a central role in infectious complications, but the precise molecular mechanism underlying the reduced resistance of monocytes to viruses in MM patients remains to be elucidated. Here, we found that MM cells were able to transfer microRNAs (miRNAs) to host monocytes/macrophages via MM cell-derived exosomes, resulting in the inhibition of innate antiviral immune responses. The screening of miRNAs enriched in exosomes derived from the bone marrow (BM) of MM patients revealed five miRNAs that negatively regulate the cGAS-STING antiviral immune response. Notably, silencing these miRNAs with antagomiRs in MM-bearing C57BL/KaLwRijHsd mice markedly reduced viral replication. These findings identify a novel mechanism whereby MM cells possess the capacity to inhibit the innate immune response of the host, thereby rendering patients susceptible to viral infection. Consequently, targeting the aberrant expression patterns of characteristic miRNAs in MM patients is a promising avenue for therapeutic intervention. Considering the miRNA score and relevant clinical factors, we formulated a practical and efficient model for the optimal assessment of susceptibility to DNA viral infection in patients with MM.

Excitotoxicity, Oxytosis/Ferroptosis, and Neurodegeneration: Emerging Insights into Mitochondrial Mechanisms.

Mitochondrial dysfunction plays a pivotal role in the development of age-related diseases, particularly neurodegenerative disorders. The etiology of mitochondrial dysfunction involves a multitude of factors that remain elusive. This review centers on elucidating the role(s) of excitotoxicity, oxytosis/ferroptosis and neurodegeneration within the context of mitochondrial bioenergetics, biogenesis, mitophagy and oxidative stress and explores their intricate interplay in the pathogenesis of neurodegenerative diseases. The effective coordination of mitochondrial turnover processes, notably mitophagy and biogenesis, is assumed to be critically important for cellular resilience and longevity. However, the age-associated decrease in mitophagy impedes the elimination of dysfunctional mitochondria, consequently impairing mitochondrial biogenesis. This deleterious cascade results in the accumulation of damaged mitochondria and deterioration of cellular functions. Both excitotoxicity and oxytosis/ferroptosis have been demonstrated to contribute significantly to the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's Disease (HD), Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS). Excitotoxicity, characterized by excessive glutamate signaling, initiates a cascade of events involving calcium dysregulation, energy depletion, and oxidative stress and is intricately linked to mitochondrial dysfunction. Furthermore, emerging concepts surrounding oxytosis/ferroptosis underscore the importance of iron-dependent lipid peroxidation and mitochondrial engagement in the pathogenesis of neurodegeneration. This review not only discusses the individual contributions of excitotoxicity and ferroptosis but also emphasizes their convergence with mitochondrial dysfunction, a key driver of neurodegenerative diseases. Understanding the intricate crosstalk between excitotoxicity, oxytosis/ferroptosis, and mitochondrial dysfunction holds potential to pave the way for mitochondrion-targeted therapeutic strategies. Such strategies, with a focus on bioenergetics, biogenesis, mitophagy, and oxidative stress, emerge as promising avenues for therapeutic intervention.

Calcium Deregulation in Neurodegeneration and Neuroinflammation in Parkinson's Disease: Role of Calcium-Storing Organelles and Sodium-Calcium Exchanger.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that lacks effective treatment strategies to halt or delay its progression. The homeostasis of Ca2+ ions is crucial for ensuring optimal cellular functions and survival, especially for neuronal cells. In the context of PD, the systems regulating cellular Ca2+ are compromised, leading to Ca2+-dependent synaptic dysfunction, impaired neuronal plasticity, and ultimately, neuronal loss. Recent research efforts directed toward understanding the pathology of PD have yielded significant insights, particularly highlighting the close relationship between Ca2+ dysregulation, neuroinflammation, and neurodegeneration. However, the precise mechanisms driving the selective loss of dopaminergic neurons in PD remain elusive. The disruption of Ca2+ homeostasis is a key factor, engaging various neurodegenerative and neuroinflammatory pathways and affecting intracellular organelles that store Ca2+. Specifically, impaired functioning of mitochondria, lysosomes, and the endoplasmic reticulum (ER) in Ca2+ metabolism is believed to contribute to the disease's pathophysiology. The Na+-Ca2+ exchanger (NCX) is considered an important key regulator of Ca2+ homeostasis in various cell types, including neurons, astrocytes, and microglia. Alterations in NCX activity are associated with neurodegenerative processes in different models of PD. In this review, we will explore the role of Ca2+ dysregulation and neuroinflammation as primary drivers of PD-related neurodegeneration, with an emphasis on the pivotal role of NCX in the pathology of PD. Consequently, NCXs and their interplay with intracellular organelles may emerge as potentially pivotal players in the mechanisms underlying PD neurodegeneration, providing a promising avenue for therapeutic intervention aimed at halting neurodegeneration.

Abstract Tu090: P21-activated kinase 1 safeguards cardiac function from impairment during fasting

Excessive calorie intake poses a heightened risk for cardiovascular disease, while caloric restriction and intermittent fasting have demonstrated benefits in enhancing cardiovascular health and improving cardiometabolic risk profiles. Despite this knowledge, the precise mechanisms underlying the cardioprotective effects of these dietary regimens remain inadequately understood. P21-activated kinase 1 (PAK1) is a serine/threonine protein kinase known to play a crucial role in promoting cardiomyocyte survival in response to various stressors. In this study, we aimed to elucidate the role of PAK1 in maintaining cardiac function during fasting, utilizing mice with modified PAK1 activity in the heart. Under normal feeding conditions, heart function exhibited no discernible differences among wild type (WT), transgenic (TG), and knockout (KO) mice, as evidenced by consistent fractional shortening (FS), ejection fraction (EF), E/A ratio, and isovolumic relaxation time (IVRT). After a one-day fast, systolic contractile function remained robust across all groups of mice. However, the E/A ratio decreased in KO mice, and IVRT was prolonged in KO mice, while shortened in TG mice, highlighting the crucial role of PAK1 in maintaining diastolic cardiac function. Upon a two-day fast, systolic function was compromised in both WT and KO mice, whereas TG mice exhibited preserved function, as evidenced by FS and EF measurements, emphasizing PAK1's equal significance in sustaining systolic cardiac function. Furthermore, fasting accelerated mitophagy, a process eliminating dysfunctional mitochondria through lysosomal degradation, as observed by mitochondria-associated LC3-II and a dual fluorescent mitophagy reporter. Additionally, we established PAK1 as a positive regulator of mitophagy, suggesting its potential protective role in the heart during fasting via mitophagy modulation. In summary, PAK1 emerges as a critical mediator of cardiac function during fasting, presenting promising avenues for therapeutic interventions aimed at improving cardiovascular health.

Research on the role of exosomes secreted by immortalized adipose-derived mesenchymal stem cells differentiated into pericytes in the repair of high glucose-induced retinal vascular endothelial cell damage

Diabetic retinopathy, a leading cause of vision impairment, is marked by microvascular complications in the retina, including pericyte loss, a key indicator of early-stage disease. This study explores the therapeutic potential of exosomes derived from immortalized adipose-mesenchymal stem cells differentiated into pericyte-like cells in restoring the function of mouse retinal microvascular endothelial cells damaged by high glucose conditions, thereby contributing to the understanding of early diabetic retinopathy intervention strategies. To induce immortalized adipose-mesenchymal stem cells differentiation into pericyte-like cells, the study employed pericyte growth supplement. And confirmed the success of cell differentiation through the detection of α-smooth muscle actin and neural/glial antigen 2 expression by Western blot and immunofluorescence. Exosomes were isolated from the culture supernatant of immortalized adipose-mesenchymal stem cells using ultracentrifugation and characterized through Western blot for exosomal markers (CD9, CD81, and TSG101), transmission electron microscopy, and nanoparticle tracking analysis. Their influence on mouse retinal microvascular endothelial cells under high glucose stress was assessed through various functional assays. Findings revealed that exosomes, especially those from pericyte-like immortalized adipose-mesenchymal stem cells, were efficiently internalized by retinal microvascular endothelial cells and effectively counteracted high glucose-induced apoptosis. These exosomes also mitigated the rise in reactive oxygen species levels and suppressed the migratory and angiogenic properties of retinal microvascular endothelial cells, as demonstrated by Transwell and tube formation assays, respectively. Furthermore, they preserved endothelial barrier function, reducing hyperglycemia-induced permeability. At the molecular level, qRT-PCR analysis showed that exosome treatment modulated the expression of critical genes involved in angiogenesis (VEGF-A, ANG2, MMP9), inflammation (IL-1β, TNF-α), gap junction communication (CX43), and cytoskeletal regulation (ROCK1), with the most prominent effects seen with exosomes from pericyte-like immortalized adipose-mesenchymal stem cells. High glucose increased the expression of pro-angiogenic and pro-inflammatory markers, which were effectively normalized post-exosome treatment. In conclusion, this research highlights the reparative capacity of exosomes secreted by pericyte-like differentiated immortalized adipose-mesenchymal stem cells in reversing the detrimental effects of high glucose on retinal microvascular endothelial cells. By reducing apoptosis, oxidative stress, inflammation, and abnormal angiogenic behavior, these exosomes present a promising avenue for therapeutic intervention in early diabetic retinopathy. Future studies can focus on elucidating the precise molecular mechanisms and exploring their translational potential in vivo.

Design of New Aromatic Tertiary Amine-based as Butyrylcholinesterase Inhibitors Relying on Molecular Docking, ADME-Tox and Molecular Dynamics.

Butyrylcholinesterase (BChE) plays a pivotal role in the progression of Alzheimer's disease. Empirical research demonstrated a fundamental alteration in the role of BChE concerning the reduction of cholinergic neurotransmission within the brains of individuals at advanced stages of Alzheimer's. This study focuses on developing potent inhibitors for Butyrylcholinesterase (BChE) in the context of Alzheimer's disease (AD) treatment. Building upon previous research, a series of 44 aromatic tertiary amine-based compounds was investigated. Starting with ADME-Tox studies, the pharmacokinetic and pharmacodynamic properties of the compounds were analyzed to select promising candidates for BChE inhibition, which is a crucial factor in AD pathology. Molecular docking analyses identified compound M18 as the most promising candidate, and further compounds (X9 and X10) were proposed based on M18's chemical structure. These compounds displayed superior properties in terms of binding energies and hydrogen bonds in comparison to M18. The Molecular Dynamics (MD) simulations, which are over a 500 ns timeframe, confirmed the conformational stability of compounds X9 and X10, compared to M18. Overall, the stated results suggest that the proposed compounds, including X9 and X10 specifically, have a significant potential as candidates for BChE inhibition. This presents a promising avenue for therapeutic intervention in Alzheimer's disease.

Nebulized milk exosomes loaded with siTGF-β1 ameliorate pulmonary fibrosis by inhibiting EMT pathway and enhancing collagen permeability

Pulmonary Fibrosis (PF) is a fatal disease in the interstitial lung associated with high mortality, morbidity, and poor prognosis. Transforming growth factor-β1 (TGF-β1) is a fibroblast-activating protein that promotes fibrous diseases. Herein, an inhalable system was first developed using milk exosomes (M-Exos) encapsulating siRNA against TGF-β1 (MsiTGF-β1), and their therapeutic potential for bleomycin (BLM)-induced PF was investigated. M-siTGF-β1 was introduced into the lungs of mice with PF through nebulization. The collagen penetration effect and lysosomal escape ability were verified in vitro. Inhaled MsiTGF-β1 notably alleviated inflammatory infiltration, attenuated extracellular matrix (ECM) deposition, and increased the survival rate of PF mice by 4.7-fold. M-siTGF-β1 protected lung tissue from BLM toxicity by efficiently delivering specific siRNA to the lungs, leading to TGF-β1 mRNA silencing and epithelial mesenchymal transition pathway inhibition. Therefore, M-siTGF-β1 offers a promising avenue for therapeutic intervention in fibrosis-related disorders.

Therapeutic Strategies for Ischemic Stroke: Modulating the Adult Neural Stem Cell Niche through the Wnt/β-catenin Pathway.

Stroke is a prominent contributor to mortality and impairment on a global scale. Ischemic stroke accounts for approximately 80% of stroke cases and is caused by occlusion of cerebral blood vessels. Enhancing neurogenesis through the modulation of the neural stem cell niche in the adult brain is a promising therapeutic strategy for individuals afflicted with ischemic stroke. Neurogenesis results in the generation of newborn neurons that serve as replacements for deceased neural cells within the ischemic core, thereby playing a significant role in the process of neural restoration subsequent to cerebral ischemia. Research has shown that activation of the Wnt/β-catenin pathway can augment neurogenesis following cerebral ischemia, suggesting that this pathway is a potentially beneficial therapeutic target for managing ischemic stroke. This review provides an extensive analysis of the current knowledge regarding the involvement of the Wnt/β-catenin pathway in promoting neurogenesis, thereby offering a promising avenue for therapeutic intervention in the context of ischemic stroke or other neurological impairments.

In Silico Drug Repurposing Against PSMB8 as a Potential Target for Acute Myeloid Leukemia Treatment.

PSMB8 emerges as a prominent gene associated with cancer survival, yet its potential therapeutic role in acute myeloid leukemia (AML) remains unexplored within the existing literature. The principal aim of this study is to systematically screen an expansive library of molecular entities, curated from various databases to identify the prospective inhibitory agents with an affinity for PSMB8. A comprehensive assortment of molecular compounds obtained from the ZINC15 database was subjected to molecular docking simulations with PSMB8 by usingtheAutoDock tool in PyRx (version 0.9.9) to elucidate binding affinities. Following the docking simulations, a select subset of molecules underwent further investigation through comprehensive ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis employing AdmetSar and SwissADME tools. Finally, RMSD, RMSF, Rg, and H bond analyses were conducted via GROMACS to determine the best conformationally dynamic molecule that represents the candidate agent for the study. Following rigorous evaluation, Adozelesin, Fiduxosin, and Rimegepant have been singled out based on considerations encompassing bioavailability scores, compliance with filter criteria, and acute oral toxicity levels. Additionally, ligand interaction analysis indicates that Adozelesin and Fiduxosin exhibit an augmented propensity for hydrogen bond formation, a factor recognized for its facilitative role in protein-ligand interactions. After final analyses, we report that Fiduxosin may offera treatment possibility by reversing the low survival rates caused by PSMB8 high activation in AML. This study represents a strategic attempt to repurpose readily available pharmaceutical agents, potentially obviating the need for de novo drug development, and thereby offering promising avenues for therapeutic intervention in specific diseases.

Glioblastoma stem cell long non-coding RNAs: therapeutic perspectives and opportunities.

Glioblastoma poses a formidable challenge among primary brain tumors: its tumorigenic stem cells, capable of self-renewal, proliferation, and differentiation, contribute substantially to tumor initiation and therapy resistance. These glioblastoma stem cells (GSCs), resembling conventional stem and progenitor cells, adopt pathways critical for tissue development and repair, promoting uninterrupted tumor expansion. Long non-coding RNAs (lncRNAs), a substantial component of the human transcriptome, have garnered considerable interest for their pivotal roles in normal physiological processes and cancer pathogenesis. They display cell- or tissue-specific expression patterns, and extensive investigations have highlighted their impact on regulating GSC properties and cellular differentiation, thus offering promising avenues for therapeutic interventions. Consequently, lncRNAs, with their ability to exert regulatory control over tumor initiation and progression, have emerged as promising targets for innovative glioblastoma therapies. This review explores notable examples of GSC-associated lncRNAs and elucidates their functional roles in driving glioblastoma progression. Additionally, we delved deeper into utilizing a 3D in vitro model for investigating GSC biology and elucidated four primary methodologies for targeting lncRNAs as potential therapeutics in managing glioblastoma.

POSSIBILITIES OF ART THERAPY IN WORKING WITH A CHILD WITH ATTENTION DEFICIT AND HYPERACTIVITY DISORDER

Art therapy offers promising avenues for therapeutic intervention in children diagnosed with Attention Deficit Hyperactivity Disorder (ADHD). This paper explores the potentials and benefits of utilizing art therapy techniques as part of a holistic treatment approach for children with ADHD. Through a review of existing literature and case studies, the effectiveness of art therapyin improving attention span, emotional regulation, and social skills is examined. Practical considerations for implementing art therapy in clinical and educational settings are discussed, including the role of the therapist, suitable techniques, and potential challenges. The paper concludes with recommendations for future research directions and underscores the importance of integrating art therapy into multidisciplinary ADHD treatment plans.

GARLIC: Nature's potent antifungal and antibacterial ally - cream formulation and evaluation

In the pursuit of effective and safe treatments for infectious diseases, herbal remedies have garnered significant attention due to their diverse phytochemical composition and potential therapeutic properties. This study aimed to explore the phytochemical profile and evaluate the antibacterial and antifungal properties of herbal garlic extracts. Traditional natural products continue to be sought after for their bioactive compounds, which offer promising avenues for therapeutic intervention in both human and veterinary medicine. Our investigation not only sheds light on the regional variation of stomach disease occurrence, highlighting the role of dietary factors, but also underscores the importance of herbal preparations in medicinal practice. By combining various plant classes, herbal formulations can exert localized effects upon application, penetrating the skin or mucous membranes to target underlying conditions. The effectiveness of these combined medications may lie in their synergistic mechanisms, offering a comprehensive therapeutic approach. This research contributes valuable insights into the potential of herbal remedies as adjuncts or alternatives to conventional treatments, paving the way for further exploration in infectious disease management and prevention strategies.