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Background: Glioma, a primary intracranial tumor, is marked by high rates of mortality and disability, making it a significant health concern. Understanding the molecular mechanisms underlying glioma initiation and progression and identifying potential therapeutic targets for gene therapy are crucial for improving patient outcomes. Golgi phosphoprotein 3 (GOLPH3), predominantly localized at the trans-Golgi network, has been implicated in the pathogenesis of various cancers. However, its precise role in glioma progression remains under active investigation. Methods: To elucidate the function of GOLPH3, U87 glioma cells were transfected with GOLPH3-specific small interfering RNA (siRNA) to suppress its expression. An in vivo glioma model was generated by implanting GOLPH3-knockdown U87 cells into nude mice. Apoptosis was assessed using flow cytometry, immunofluorescence staining, TUNEL assays, and Western blotting. The activation of the JNK signaling pathway was evaluated by analyzing the phosphorylation levels of JNK and c-Jun through Western blotting. Results: Downregulation of GOLPH3 in U87 glioma cells significantly enhanced apoptosis, as evidenced by increased levels of cleaved caspase-3 and higher apoptosis rates. Furthermore, GOLPH3 knockdown led to the activation of the JNK signaling pathway, as indicated by elevated phosphorylation of JNK and c-Jun. In vivo , suppression of GOLPH3 expression inhibited tumor growth and increased apoptosis within the tumor microenvironment. Conclusion: These findings suggest that GOLPH3 might play a pivotal role in regulating apoptosis in malignant glioma cells via the JNK signaling pathway. Thus, GOLPH3 may represent a promising therapeutic target for glioma treatment. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS), a chronic inflammatory and degenerative autoimmune disease characterized by the activation of various inflammatory cells, leads to demyelination and neuronal injury. Neutrophils, often underestimated in MS, are gaining increased attention for their significant functions in MS patients and the experimental autoimmune encephalomyelitis (EAE) animal model. Neutrophils play multiple roles in mediating the pathogenesis of autoimmune diseases, and numerous studies suggest that neutrophils might have a crucial role through neutrophil extracellular trap (NET) formation. Studies on NETs in MS are still in their infancy. In this review, we discuss the clinical perspective on the linkage between neutrophils and MS or EAE, as well as the role of NETs in the pathogenesis of MS/EAE. Further, we analyze the potential mechanisms by which NETs contribute to MS, the protective effects of NETs in MS, and their value as targets for disease intervention. NET formation and/or clearance as a therapeutic approach for MS still requires research in greater depth. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is one of the most prevalent gynecologic malignancies and exhibites the highest fatality rate among all gynecologic malignancies. The absence of an early diagnostic biomarker and therapeutic target contributes to an overall 5-year survival rate ranging from 30 to 50%. Plectin (PLEC), a 500 kDa scaffolding protein, has gained prominence in recent years due to its pivotal role in various cellular biological functions such as cell morphology, migration and adhesion, while the accurate role of PLEC in OC remains elusive. Results: In this study, our findings demonstrate that PLEC exerts a positive influence on the progression of OC, encompassing cellular proliferation, migration, invasion, and adhesion both in vitro and in vivo. Conclusions: The results providing new insights for the diagnosis and treatment in OC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, with approximately 800,000 deaths worldwide each year. Owing to the atypical early symptoms and characteristics of HCC, over 80% of HCC patients cannot receive curative treatment. The treatment of HCC is facing a bottleneck, and new treatment methods are urgently needed. Since the pathogenesis of HCC is not yet clear, identifying the molecular mechanisms and therapeutic targets related to it is crucial. Centromeres are considered special deoxyribonucleic acid (DNA) sequences with highly repetitive sequences that are physically connected to the spindle during cell division, ensuring equal division of genetic material between daughter cells. The numerous proteins that aggregate on this sequence during cell division are called centromere proteins (CENPs). Currently, numerous studies have shown that CENPs are abnormally expressed in tumor cells and are associated with patient prognosis. The abnormal expression of CENPs is a key cause of chromosomal instability. Furthermore, chromosomal instability is a common characteristic of the majority of tumors. Chromosomal instability can lead to uncontrolled and sustained division and proliferation of malignant tumors. Therapeutic plans targeting CENPs play important roles in the treatment of HCC. For example, small ribonucleic acid (RNA) can silence CENP expression and prevent the occurrence and development of liver cancer. In recent years, studies of HCC-targeting CENPs have gradually increased but are still relatively novel, requiring further systematic elaboration. In this review, we provide a detailed introduction to the characteristics of CENPs and discuss their roles in HCC. In addition, we discuss their application prospects in future clinical practice. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are non-coding RNAs that exist naturally in various eukaryotic organisms. The majority of circRNAs are produced through the splicing of exons, although there are a limited number that are generated through the circularization of introns. Studies have shown that circRNAs play an irreplaceable role in the pathogenesis, disease progression, diagnosis, and targeted therapy of motor system tumors (osteosarcoma), metabolic diseases (osteoporosis), and degenerative diseases (osteonecrosis of the femoral head, osteoarthritis, intervertebral disc degeneration). This review summarizes the advancements in circRNA detection techniques and the research progress of circRNAs in orthopedic diseases. [ABSTRACT FROM AUTHOR]

N6-methylation is a modification in which a methyl group is added to the adenine base of a nucleotide. This modification is crucial for controlling important functions that are vital for gene expression, including mRNA splicing, stability, and translation. Due to its intricate participation in both normal cellular processes and the course of disease, as well as its critical role in determining cell fate, N6-methyladenosine (m6A) alteration has recently attracted a lot of interest. The formation and progression of many diseases, especially cancer, can be attributed to dysregulated m6A alteration, which can cause disturbances in a variety of cellular functions, such as immunological responses, cell proliferation, and differentiation. In this study, we examine how m6A dysregulation affects hepatocellular carcinoma (HCC), with a particular emphasis on how it contributes to immunological evasion and carcinogenesis. We also investigate its potential as a novel therapeutic target, providing new perspectives on potential therapeutic approaches meant to enhance clinical results for patients with HCC. [ABSTRACT FROM AUTHOR]

The mitochondrial serine β-lactamase-like protein LACTB has emerged as a critical regulator in cancer biology, distinguished by its unique structural and functional attributes. Defined by its conserved penicillin-binding proteins and β-lactamases (PBP-βLs) domain and SXXK catalytic motif, LACTB demonstrates properties distinct from its prokaryotic homologs, including the ability to polymerize into filaments. These structural characteristics enable LACTB to modulate mitochondrial organization and enzymatic activity, influencing lipid metabolism and indirectly affecting cellular proliferation. Importantly, the expression and functional roles of LACTB exhibit cancer-type-specific variation, underscoring its dual function as both a tumor suppressor and an oncogene. Decreased LACTB expression is associated with poor clinical outcomes in cancers such as breast cancer, lung cancer, and colorectal cancer, while specific mutations and regulatory mechanisms have been linked to its oncogenic activity in osteosarcoma and pancreatic adenocarcinoma. Mechanistically, LACTB regulates key processes in cancer progression, including mitochondrial dynamics, epithelial–mesenchymal transition (EMT), and cell death pathways. This duality highlights LACTB as a promising therapeutic target and underscores its relevance in advancing precision oncology strategies. This review provides a comprehensive analysis of expression level, structure–function relationships, and the diverse roles of LACTB in oncogenesis, underscoring its promise as a focal point for precision cancer therapies. [ABSTRACT FROM AUTHOR]

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate a broad array of biological processes, including inflammation, lipid metabolism, cell proliferation, and apoptosis. Among the diverse family of NRs, peroxisome proliferator-activated receptors (PPARs), estrogen receptor (ER), liver X receptor (LXR), farnesoid X receptor (FXR), retinoid X receptor (RXR), and aryl hydrocarbon receptor (AhR) have garnered significant attention for their roles in neurodegenerative diseases, particularly Alzheimer's disease (AD). NRs influence the pathophysiology of AD through mechanisms such as modulation of amyloid-beta (Aβ) deposition, regulation of inflammatory pathways, and improvement of neuronal function. However, the dual role of NRs in AD progression, where some receptors may exacerbate the disease while others offer therapeutic potential, presents a critical challenge for their application in AD treatment. This review explores the functional diversity of NRs, highlighting their involvement in AD-related processes and discussing the therapeutic prospects of NR-targeting strategies. Furthermore, the key challenges, including the necessity for the precise identification of beneficial NRs, detailed structural analysis through molecular dynamics simulations, and further investigation of NR mechanisms in AD, such as tau pathology and autophagy, are also discussed. Collectively, continued research is essential to clarify the role of NRs in AD, ultimately facilitating their potential use in the diagnosis, prevention, and treatment of AD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a major neurodegenerative dementia, with its complex pathophysiology challenging current treatments. Recent advancements have shifted the focus from the traditionally dominant amyloid hypothesis toward a multifactorial understanding of the disease. Emerging evidence suggests that while amyloid-beta (A β) accumulation is central to AD, it may not be the primary driver but rather part of a broader pathogenic process. Novel hypotheses have been proposed, including the role of tau protein abnormalities, mitochondrial dysfunction, and chronic neuroinflammation. Additionally, the gut–brain axis and epigenetic modifications have gained attention as potential contributors to AD progression. The limitations of existing therapies underscore the need for innovative strategies. This study explores the integration of machine learning (ML) in drug discovery to accelerate the identification of novel targets and drug candidates. ML offers the ability to navigate AD's complexity, enabling rapid analysis of extensive datasets and optimizing clinical trial design. The synergy between these themes presents a promising future for more effective AD treatments. [ABSTRACT FROM AUTHOR]

Gene‒gene interactions play pivotal roles in disease pathogenesis and are fundamental in the development of targeted therapeutics, particularly through the elucidation of oncogenic gene drivers in cancer. The systematic analysis of pathways and gene interactions is critical in the drug discovery process for various cancer subtypes. SPAG5, known for its role in spindle formation during cell division, has been identified as an oncogene in several cancers, although its specific impact on AML remains underexplored. This study leverages a high-throughput swarm-based deep neural network (SDNN) and transcriptomic data—an approach that enhances predictive accuracy and robustness through collective intelligence—to augment, model, and enhance the understanding of the TP53 pathway in AML cohorts. Our integrative systems biology approach identified SPAG5 as a uniquely downregulated driver in adult AML, underscoring its potential as a novel therapeutic target. The interaction of SPAG5 with key hub genes such as MDM2 and CDK1 not only reinforces its role in tumour suppression through negative regulation but also highlights its potential in moderating the phenotypic and genomic alterations associated with AML progression. This study of the role and interaction dynamics of SPAG5 sets the stage for future research aimed at developing targeted and personalized treatment approaches for AML, utilizing the capabilities of genetic interventions. [ABSTRACT FROM AUTHOR]