Abstract: Neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are characterized by the pathological aggregation of proteins such as amyloid-β, tau, and alpha-synuclein. These hallmark proteins play central roles in disease progression and represent promising targets for therapeutic intervention. Advances in precision medicine, driven by genomic technologies such as CRISPR-Cas systems, RNA-based therapies, and high-throughput sequencing, have enabled the development of tailored strategies to modulate these pathological pathways. This review examines the integration of genomic approaches in targeting amyloid-β, tau, and alpha-synuclein, emphasizing their potential to mitigate disease progression and improve patient outcomes. We highlight current progress in preclinical and clinical studies, discuss challenges associated with translating these therapies into clinical practice, and explore future directions for achieving therapeutic precision in neurodegenerative disorders. By examining the interplay of genetic, molecular, and therapeutic innovations, this review underscores the transformative potential of genomic medicine in addressing the unmet needs of neurodegenerative disease treatment.

Introduction: Osteonecrosis of the Femoral Head (ONFH) is one of the common refractory diseases. However, the role of cuproptosis in ONFH pathogenesis remains unexplored. This study aimed to investigate the potential relationship between cuproptosis and ONFH. Methods: ONFH-related datasets were obtained from the Gene Expression Omnibus (GEO) database, and cuproptosis-related genes in the GSE123568 dataset were identified through differential expression analysis. To further discover potential cuproptosis-related biomarkers, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and Support Vector Machine (SVM) analysis were conducted. The Receiver Operating Characteristic (ROC) curve analysis was used to explore the diagnostic value of cuproptosis-related biomarkers. The summary Statisticsbased Mendelian Randomization (SMR) algorithm was used to investigate the causal relationship between the related genes and ONFH. The immune infiltration analysis was conducted to assess the effect of immune cells on ONFH. Subsequently, the GSE74089 and GSE89587 datasets were used to validate gene expression levels and predict the lncRNA-miRNA-mRNA network. Finally, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was employed to validate the expression of these genes. Results: The study showed that the upregulation of PDHB, a cuproptosis-related biomarker, may contribute to the development of ONFH. Additionally, immune cells were found to play a crucial role in ONFH, and PDHB showed a significant association with various immune cells. Furthermore, the study identified the existence of the MIR22HG/let-7c-5p/PDHB regulatory pathway, which may play a critical role in ONFH through cuproptosis. Discussion: This study discovered a cuproptosis-related regulating pathway, MIR22HG/let-7c- 5p/PDHB. This can provide new insights into the treatment of ONFH. However, further experimental validation is needed. result: This study showed that upregulation of the cuproptosis-related biomarker, PDHB, could lead to ONFH. At the same time, the study found that immune cells play an important role in ONFH, and PDHB is significantly associated with a variety of immune cells. The study also found the existence of MIR22HG/let-7c-5p/PDHB regulatory pathway, which may play an important role in ONFH through cuproptosis Conclusion: PDHB, identified as a cuproptosis-related biomarker, can induce ONFH through cuproptosis. PDHB also contributes to the pathogenesis and progression of ONFH by influencing immune cell function. This is most likely mediated through the regulatory interaction between MIR22HG, let-7c-5p, and PDHB.

Background: Yin Yang 2 (YY2) plays a pivotal role in various tumorigenic processes; however, its specific involvement in esophageal carcinoma (ESCA) remains elusive. This study aims to investigate the expression and potential functional significance of YY2 in ESCA. Methods: The expression and functions of YY2 in ESCA were analyzed using a broad range of bioinformatics databases and tools, including TCGA, TIMER, TISIDB, QUANTISEQ, cBioPortal, DNMIVD, LinkedOmics, DAVID, GSEA, GEPIA2, LASSO, miRWalk, miRDB, and TargetScan. Furthermore, RT-qPCR, immunohistochemical staining, western blot, CCK8 assay, and wound healing assay were employed to validate the involvement of YY2 in ESCA pathogenesis. Results: Bioinformatics analyses revealed that the YY2 gene is upregulated in ESCA tissues, with its high expression significantly associated with poor prognosis and elevated levels of M2 macrophages, NK cells, Tregs, CTLA4, TIGIT, and Siglec-15. Validating the ESCA samples demonstrated that knockdown of YY2 effectively inhibited cell proliferation and migration in ESCA cells. The biological functions of YY2 and its co-expressed genes were primarily associated with transcriptional regulation, DNA methylation, glycometabolism, and ubiquitination. Moreover, the regulatory network of YY2 in the glycolysis pathway was found to involve multiple genes and miRNAs. Finally, a prognostic model based on YY2 and its associated glycolysis genes revealed a strong inverse correlation between higher risk scores and lower survival rates in esophageal adenocarcinoma (EAC). Conclusion: YY2 may serve as a promising prognostic biomarker and an innovative therapeutic target for patients with ESCA, regulating cell proliferation, migration, immune microenvironment, and glycolysis.

The study by Sun et al. , which sequenced exomes from 983,578 individuals, provides a comprehensive resource on protein-coding genetic variation. This commentary examines the key findings, including rare biallelic variants and loss-of-function intolerant genes, while emphasizing their implications for gene splicing, human knockouts, and disease-associated genes. Additionally, we discuss how these insights propel advancements in precision medicine and suggest future research directions, particularly in the study of non-coding DNA and regulatory RNAs at population scales.

Copy Number Variations (CNVs) involving 16p11.2 or 22q11.2 are often linked to neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, cognitive impairment, epilepsy, and schizophrenia. The pathogenetic mechanisms underlying these neurological phenotypes remain incompletely understood, partly due to the multitude of genes involved and the complex gene-gene interactions at these loci. Nonetheless, recent advances in experimental technology and bioinformatics have greatly enhanced our understanding of the neurobiology of 16p11.2- and 22q11.2-related disorders. Herein, we aim to provide an updated mini-review on neurological aspects of these disease-associated CNVs, with emphasis on clinical and mechanistic insights as well as potential therapeutic implications.

Introduction: Recent investigations have underscored the importance of long non-coding RNAs (lncRNAs), which exhibit more specific expression in tissues and cells than mRNA and are involved in gene regulation during development, pathology, and other processes through various mechanisms. Despite the predominant focus on the role of lncRNA Dio3os in cancer research, there has been relatively limited exploration of its potential involvement in glycolipid metabolism. Therefore, this study aims to consolidate existing knowledge on the function of Dio3os in glycolipid metabolism and calls for a broader investigation into its physiological roles. Methods: This review synthesizes available literature to detail the gene characteristics of lncRNA Dio3os and its expression patterns. It also compiles recent insights and mechanisms pertaining to Dio3os's involvement in glycolipid metabolism, particularly its participation in the ceRNA regulatory network. Results: Recent studies demonstrate that lncRNA Dio3os regulates glycolysis in cancer cells and impacts obesity, potentially serving as an indicator for diabetic peripheral neuropathy. Furthermore, its diminished expression has been noted in atherosclerotic plaques. Conclusion: lncRNA Dio3os exerts a significant regulatory influence on glycolipid metabolism, with variations in its expression levels potentially affecting disease presentations. Further investigations are warranted to elucidate the precise relationship between lncRNA Dio3os and its associated pathologies.

Rare genetic disorders collectively affect millions of individuals worldwide, presenting a significant clinical and research challenge due to the diversity and complexity of the underlying mutations. Current treatment options are often limited, focusing on symptom management rather than addressing the root genetic causes. This review article aims to provide a perspective on the evolving field of gene therapy for rare genetic disorders, emphasizing recent advancements, current challenges, and future directions. A comprehensive review of recent advancements in gene therapy for rare genetic disorders was conducted, focusing on therapeutic strategies, delivery systems, and clinical outcomes. Key examples, such as the use of viral vectors and gene-editing technologies (e.g., CRISPR), were highlighted. The challenges, including immune responses and ethical concerns, were also examined. Gene therapy has achieved significant milestones, with the successful development of therapies like Zolgensma for spinal muscular atrophy and Luxturna for retinal dystrophy. However, several hurdles, including efficient gene delivery, immune reactions, and longterm safety, remain unresolved. Gene therapy holds transformative potential for the treatment of rare genetic disorders. While recent successes mark a new era in genetic medicine, ongoing research is required to refine delivery mechanisms, overcome immune-related barriers, and ensure ethical and safe therapeutic interventions.

Background: Retinal Vein Occlusion (RVO) is a common and main cause of blindness. Causal, possible risk variables must be identified to develop preventative strategies for RVO.. Thus, we decided to evaluate whether smoking, alcohol, obesity, sedentary behaviour, hypertension, and hyperglycemia are associated with increased risk of RVO. Methods: The data sources of Mendelian Randomization (MR) study included FinnGen consortium and the original GWAS article. A total of 130,604 cases with RVO from FinnGen consortium and 12,136 cases with RVO from the original GWAS article. The exposures of this MR study included smoking, alcoholic consumption, obesity, sedentariness, hypertension, and hyperglycemia. The outcome of this MR study was RVO. Results: Genetic predispositions to alcohol consumption (OR (odds ratio), 1.124; 95%CI, 1.007- 1.254; P=0.037) and hyperglycemia (OR, 1.108; 95%CI, 1.023-1.200; P=0.012) were associated with increased risks of RVO in FinnGen. There were no significant associations of genetically predicted consumption of smoking (OR, 1.037; 95%CI, 0.341-3.155; P=0.949), obesity (OR, 1.045; 95%CI, 0.975-1.119; P=0.213), sedentariness (OR, 1.022; 95%CI, 0.753-1.38-; P=0.888), or hypertension (OR, 0.944; 95%CI, 0.848-1.051; P=0.290) with RVO. Conclusion: This MR analysis provides genetic evidence that increased alcohol consumption and hyperglycemia may be causal risk factors for RVO. In addition, no genetic evidence in this MR analysis supported that there were causal associations between smoking, sedentariness, obesity and hypertension with RVO.