Genetic Predisposition Research Articles

Integrated multi-omics analysis revealed the molecular networks and potential targets of cellular senescence in Alzheimer's disease.

Cellular senescence (CS) is a hallmark of Alzheimer's disease (AD). However, the mechanisms through which CS contributes to AD pathogenesis remain poorly understood. We found that CS level in AD was higher compared with the healthy control group. Transcriptome-based differential expression analysis identified 113 CS-related genes in blood and 410 in brain tissue as potential candidate genes involved in AD. To further explore the causal role of these genes, an integrative mendelian randomization analysis was conducted, combining AD genome-wide association study summary statistics with expression quantitative trait loci (eQTL) and DNA methylation quantitative trait loci (mQTL) data from blood samples, which identified five putative AD-causal genes (CENPW, EXOSC9, HSPB11, SLC44A2, and SLFN12) and 18 corresponding DNA methylation probes. Additionally, integrative analysis between eQTLs and mQTLs from blood uncovered two genes and 12 corresponding regulatory elements involved in AD. Furthermore, two genes (CDKN2B and ITGAV) were prioritized as putative causal genes in brain tissue and were validated through in vitro experiments. The multi-omics integration study revealed the potential role and underlying biological mechanisms of CS driven by genetic predisposition in AD. This study contributed to fundamental understanding of CS in AD pathogenesis and facilitated the identification of potential therapeutic targets for AD prevention and treatment.

Effects of the Interaction Between Oxidative Balance Score and Polygenic Risk Scores on Incidence of Metabolic Syndrome in Middle-Aged Korean Adults

Oxidative stress is implicated in insulin resistance, obesity, and metabolic syndromes (MetSs). However, the interplay between oxidative stress and genetic predisposition during the development of MetS remains unclear. In this study, we aimed to investigate the effects of the interaction between oxidative balance score (OBS) and polygenic risk score (PRS) on the incidence of MetS in middle-aged Korean adults. We analyzed data from 25,879 participants aged ≥40 years from the Health Examinees Cohort of the Korean Genome and Epidemiology Study. The OBS was calculated using 11 antioxidant and five pro-oxidant factors. A genome-wide association study and clumping analysis identified 16 independent single-nucleotide polymorphisms associated with MetS that were used to calculate individual PRSs. Multivariable Cox proportional hazard models adjusted for confounding variables were used to assess the impact of OBS and PRS on the incidence of MetS. During a mean follow-up period of 4.3 years, we recorded 3153 cases of MetS. In both men and women, the group with the lowest OBS and a high PRS had a 1.50-fold (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.07–2.11) and 1.89-fold (HR 1.89, 95% CI 1.40–2.56) higher incidence, respectively, of MetS compared to those with the highest OBS and a low PRS. Among women with a high PRS, the HRs decreased significantly across OBS quintiles 1 through 5 (p for trend = 0.009). These findings suggest that managing the oxidative balance may be particularly crucial for individuals with a high genetic risk for MetS.

Research progress on the first‐night effect in polysomnography studies

AbstractThe first‐night effect (FNE) is a prevalent occurrence in sleep monitoring that can impact the accuracy of monitoring results, encompassing both FNE and reverse first‐night effect. FNE is characterized by extended sleep onset latency, reduced total sleep time, diminished sleep efficiency, prolonged wake‐time after sleep onset, among other manifestations. The physiological and psychological mechanisms underlying FNE are primarily linked to acute stress induced by the environment and heightened levels of anxiety, involving the default mode network. FNE exhibits varying manifestations and impacts across individuals of different age groups and genetic predispositions. We also discuss the influence of placebo and sedative‐hypnotics on FNE. Understanding these factors is crucial for guiding clinicians and technologists in standardizing polysomnography (PSG) practices and improving the accuracy of sleep disorder diagnoses.

Assessment of Relationship between Dietary Factors, Socioeconomic Factor, Behavioral Factor, Physical Measurement and Risk of Migraine: A Univariable and Multivariable Mendelian Randomization Study.

Although numerous studies have identified associations between socioeconomic, behavioral, dietary, and physical factors and migraine, the causal nature of these relationships has yet to be adequately established. We utilized two-sample Mendelian randomization to elucidate the causal associations of 28 distinct traits for socioeconomic factor, behavioral factor, dietary factor and physical measurement with migraine. In the univariable Mendelian randomization analysis, the inverse-variance weighted method served as the primary analytic approach. Robustness checks included Cochran Q test, Egger intercept test, and leave-one-out analysis. A multivariable Mendelian randomization analysis framework was utilized to assess the direct causal impacts of these traits on migraine risk. The univariable Mendelian randomization analysis analysis revealed that genetic predispositions to higher coffee intake (OR=0.547; 95% CI=0.359-0.834; P=0.005), greater oily fish intake (OR=0.556; 95% CI=0.394-0.785; P=0.001), and higher educational attainment (OR=0.916; 95% CI=0.884-0.949; P<0.001) were associated with reduced migraine risk. In contrast, predispositions to higher poultry intake (OR=4.690; 95% CI=1.377-15.977; P=0.013) and longer mobile phone use (OR=1.526; 95% CI=1.080-2.157; P=0.017) correlated with increased risk. These associations remained consistent in the multivariable Mendelian randomization analysis after adjusting for stroke and particulate matter air pollution. Our study robustly supports the significant causal roles of specific socioeconomic, behavioral, and dietary factors with physical measurement in the development of migraine. Notably, coffee intake, oily fish intake, and educational attainment appear protective, whereas poultry intake and extensive mobile phone use elevate risk. These insights pave the way for developing targeted preventive strategies for migraine.

Immunotherapy for Type 1 Diabetes: Mechanistic Insights and Impact of Delivery Systems.

Type 1 Diabetes is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells, leading to hyperglycemia and various complications. Despite insulin replacement therapy, there is a need for therapies targeting the underlying autoimmune response. This review aims to explore the mechanistic insights into T1D pathogenesis and the impact of delivery systems on immunotherapy. Genetic predisposition and environmental factors contribute to T1D development, triggering an immune-mediated attack on β-cells. T cells, particularly CD4+ and CD8+ T cells, play a central role in β-cell destruction. Antigen- specific immunotherapy is a unique way to modify the immune system by targeting specific antigens (substances that trigger the immune system) for immunotherapy. It aims to restore immune tolerance by targeting autoantigens associated with T1D. Nanoparticle-based delivery systems offer precise antigen delivery, promoting immune tolerance induction. Various studies have demonstrated the efficacy of nanoparticle-mediated delivery of autoantigens and immunomodulatory agents in preclinical models, and several patents have been made in T1D. Combining antigen-specific immunotherapy with β-cell regeneration strategies presents a promising approach for T1D treatment. However, challenges remain in optimizing delivery systems for targeted immune modulation while ensuring safety and efficacy.

Risk factors associated with hypertensive nephropathy in patients of the Farmadial Clinic

The objective of this study was to determine the risk factors in patients with hypertensive nephropathy in our study population. This is a quantitative cross-sectional analytical study with an inductive method. The selection and collection of information was carried out through the search for studies and works related to the subject of the study. Interviews were conducted to patients arriving at the dialysis unit, with the objective of obtaining the necessary information with the amplitude of the radius of the patients this way to obtain the necessary data to determine that the factors present prevail in our studied population. According to the findings observed in our study, in terms of risk factors related to hypertensive nephropathy, it was found that the disease was manifested in a higher proportion in males, older than 65 years and black race, indicating the Relation of the results found with other studies cited in this study, where these risk factors are presented as triggers in the presence of this disease. It is believed that the race, gender, age, genetic predisposition and lifestyle of people are risk factors directly related to the onset or progression of hypertensive nephropathy, which allows us to have a guideline to generate preventive measures in people who present these risk factors.

A Rare Case Report on Jaundice, Alcoholic Liver Disease with a History of Herbal Medicine Induced Liver Injury

Background: Alcoholic liver disease (ALD) is a complex condition caused by excessive alcohol consumption, affecting fatty liver, alcoholic hepatitis, and cirrhosis. Risk factors include alcohol intake, genetic predisposition, and co-existing liver conditions. Alcoholic fatty liver disease (AFLD) accumulates excessive fat in the liver, leading to steatosis and fibrosis. ALD complications include portal hypertension, liver failure, and hepatocellular carcinoma. The use of herbal medicines, such as tamarind and neem extracts, is also concerning due to potential liver damage. Increased awareness and caution are needed from patients and healthcare providers. Case report: A 33-year-old male patient presented with symptoms including right hypochondrium pain, yellowish discoloration of the sclera, fever, decreased urine output, light yellow tongue, and generalized weakness. He was a chronic alcoholic, consuming various alcoholic beverages for 15 years. His dietary routine was mixed, but he preferred non-vegetarian foods. His family suggested he consume traditional herbal medicine to treat jaundice. After collecting his history, lab tests were conducted to confirm his diagnosis of alcoholic liver disease (ALD) with herbal medicine-induced liver (DILI). LFT tests were alarming, and he was diagnosed with alcoholic liver disease with jaundice and DILI due to herbal medicine. To improve his symptoms and prevent liver failure complications, he was prescribed a list of medications to improve his symptoms and to prevent complications of liver failure. Discussion: A holistic treatment approach is needed for patients with alcoholic liver disease and herbal medicine-induced liver injury, focusing on symptom relief, liver function enhancement, and complication prevention. This includes lifestyle changes, nutritional support, and managing potential issues. Regular monitoring is crucial for adjustments. Conclusion: This case report highlights the complex relationship between alcoholic liver disease and herbal medicine-induced liver injury, especially in jaundice cases. It emphasizes the need for thorough patient histories, increased awareness of hepatotoxic potential, and educating patients about alcohol and herbal supplement risks. It calls for multidisciplinary collaboration, enhanced regulation, and safety evaluations of herbal medicines to protect public health. It also underscores the importance of continuous monitoring and monitoring patients with liver injury histories. Keywords: ALD, Herbal medicine, DILI, Liver failure, Patient care

Exploring the Genetic Underpinnings of Bullying: A Contemporary Analysis of Scholarly Investigations

Since the early 21st century, bullying has been a central focus for scholars, with various forms, such as relational, physical, cyber, and social bullying, receiving extensive attention. However, the role of genetic and hereditary factors in bullying remains underexplored. This study systematically reviews 31 scholarly articles published between January 2000 and December 2021. Articles were selected based on predefined inclusion criteria, including methodological rigor, relevance to genetic influences on bullying, and clear population samples. Data sources included Google Scholar, ResearchGate, SAGE Journals, and ERIC, with keywords such as “bullying and genetics,” “bullying and hereditary,” and “family genetics involvement.” The findings reveal significant associations between genetic predispositions and bullying behaviors. For example, genetic factors were found to account for approximately 70–77% of bullying perpetration and victimization in multiple studies, highlighting a strong hereditary influence. Traits such as impulsivity and aggression, often linked to genetic predispositions, were also shown to interact with environmental factors such as family dynamics and peer relationships, amplifying bullying tendencies. These results underscore the critical role of genetic and hereditary transmission in shaping bullying behaviors across generations. The study emphasizes the need for a multidisciplinary approach that integrates genetic research with environmental interventions to address bullying effectively. Practical implications include the development of targeted anti-bullying programs that consider individual genetic susceptibility alongside fostering supportive family and school environments to reduce the intergenerational transmission of bullying behaviors.

Genetic Risk of Ankylosing Spondylitis and Second-Line Therapy Need in Crohn’s Disease: A Mendelian Randomization Study

Background: Crohn’s disease (CD) and Ankylosing Spondylitis (AS) are chronic conditions with overlapping inflammatory pathways. This research investigates the genetic association between AS and the requirement for more aggressive therapeutic interventions in CD, suggesting a likelihood of increased severity in CD progression among individuals diagnosed with AS. Methods: This study utilized two-sample Mendelian randomization (TSMR) to analyze GWAS datasets for AS and CD requiring second-line treatment. Instrumental variables were selected based on single-nucleotide polymorphisms of genome-wide significance. Analytical methods included inverse-variance weighted (IVW), MR Egger, and other MR approaches, alongside sensitivity analysis, to validate the findings. Results: Our results indicated a significant association between AS genetic predisposition and the increased need for second-line treatments in CD. The IVW method showed an Odds Ratio (OR) of 2.16, and MR Egger provided an OR of 2.71, both were statistically significant. This association persisted even after the exclusion of influential outlier SNP rs2517655, confirming the robustness of our findings. Conclusions: This study suggests that genetic factors contributing to AS may influence the progression of CD, potentially necessitating more intensive treatment strategies. These findings underscore the importance of early screening in patients with co-existing AS and CD for tailoring treatment approaches, thus advancing personalized medicine in the management of these complex conditions.

Functional Neurologic Disorder, La Lésion Dynamique: 2024 Wartenberg Lecture.

Functional neurologic disorder is common and a significant cause of disability and stress in neurologic patients. The nature of this disorder has been unclear. Originally called hysteria, the disorder interested Charcot who postulated that a functional lesion, la lésion dynamique, was responsible. Recent studies of functional neurologic disorders now allow us to understand what la lésion dynamique is and identifies these disorders without ambiguity as arising from the brain. Functional neurologic disorders are best understood as a multifactorial process with a biopsychosocial model. There can be a genetic predisposition. Commonly there is early life trauma that leads to a developmental abnormality of the amygdala, including loss of inhibition. This abnormality can be considered a predisposing factor. When stressed, the amygdala becomes hyperactive, driving the limbic system to cause widespread network dysfunction in the brain. This dysfunction can improve, correlating with clinical improvement. Network dysfunction is becoming recognized as an important pathologic process in neurology and psychiatry, as real as any other pathology. We should be able to make progress in helping patients with functional neurologic disorders with this understanding of la lésion dynamique.

Examining causal relationships between educational attainment and type 2 diabetes using genetic analysis: findings from the EPIC-InterAct study through Mendelian randomisation

IntroductionObservational studies have shown that more educated people are at lower risk of developing type 2 diabetes (T2D). However, robust study designs are needed to investigate the likelihood that such...

Metabolic, genetic and immunological features of relatives of type 1 diabetes patients with elevated insulin resistance.

Insulin resistance plays a pivotal role in the preclinical stages of type 1 diabetes (T1D). This study aims at exploring the genetic, metabolic, and immunological features associated with insulin resistance among individuals at risk of developing T1D. We retrospectively selected relatives of individuals with T1D from participants in the TrialNet Pathway to Prevention study. They were categorized into two groups: high-H (n = 27) and low-H (n = 30), based on the upper and lower quartiles of insulin resistance assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Genetic predisposition was determined using the T1D Genetic Risk Score 1 (GRS1). Additionally, glucose control was evaluated through an oral glucose tolerance test and levels of metabolic hormones and inflammatory cytokines were measured in the serum. Flow cytometry analysis was employed to assess frequency and phenotype of islet-specific CD8 T cells. While GRS1 were similar between the low-H and high-H groups, high-H individuals displayed a distinct metabolic profile, characterized by compensatory hyperinsulinemia, even while maintaining normoglycemia. Circulating cytokine levels were similar between the two groups. However, immune profiling revealed a central memory and activated profile of GAD65-specific CD8 T cells, along with an increased frequency of insulin-specific CD8 T cells in high-H individuals. The enrichment in insulin-specific CD8 T cells was independent of body mass. These findings highlight the intricate interplay between insulin resistance, genetic factors, and immune activation in the context of T1D susceptibility, indicating potential connections between insulin resistance and immune responses specific to islet cells.

Metallic nanoparticles for tumor microenvironment modulation

Cancer is a complex, multifaceted disease influenced by genetic predispositions, lifestyle factors such as nutrition, exercise, and toxin exposure, as well as environmental conditions. A key element in cancer initiation, progression, metastasis, and therapeutic response is the tumor microenvironment (TME). Within the TME, immune cells like T cells, B cells, and immunoglobulins have a profound and direct impact on the growth and spread of tumor cells. As a result, effective regulation of the TME has become crucial for successful cancer treatment. Metal nanoparticles (MNPs), ranging from 1 to 100 nanometers, have shown great potential as agents for modulating the TME, delivering drugs, and improving cancer diagnostics. This discussion explores both the internal and external components of the TME, focusing on how MNPs influence the microenvironment. We highlight their targeting mechanisms and interactions with immune responses and tumor-associated inflammation. Due to their unique properties, MNPs offer distinct advantages in cancer therapy, and their range of applications continues to expand. This review underscores the potential of MNPs as a promising material in the future of cancer treatment.

Peripartum cardiomyopathy: current state of the problem

Peripartum cardiomyopathy (PCMP) is cardiomyo-pathy with left ventricular systolic dysfunction that develops in late pregnancy or in the first months of postpartum period. Clinical manifestations can vary from mild or moderate to severe symptoms of heart failure with significant functional limitation and high mortality. PCMP has a rather heterogeneous and incompletely studied pathophysiology, which includes hormonal, vascular, metabolic, and immunological pathways, whose implementation becomes possible on the background of genetic predisposition. Treatment is based on heart failure therapy, taking into account the risks associated with pregnancy and lactation. Bromocriptine is being considered as a specific therapy; however, the level of evidence for such treatment is insufficient. The article covers basic information about the pathophysiology, diagnosis, prognosis, prevention and treatment of PCMP at the current stage. For writing this review, the literature search was conducted using the MEDLINE, Scopus, and Web of Science databases.

Genetic, Neurobiological, and Social Determinants of Adolescent Behavior: Risk Pathways and Protective Mechanisms

Adolescence is a critical period, marked by heightened risk-taking and experimentation, which are significantly influenced by the interactions between genetic predisposition and environmental contexts [...]

Polygenic Selection and Environmental Influence on Adult Body Height: Genetic and Living Standard Contributions Across Diverse Populations.

We analyzed whole-genome sequencing (WGS) data from 51 populations and combined WGS and array data from 89 populations. Multiple types of polygenic scores (PGS) were employed, derived from multi-ancestry, between-family genome-wide association study (GWAS; MIX-Height), European-ancestry, between-family GWAS (EUR-Height), and European-ancestry siblings GWAS (SIB-Height). Our findings demonstrate that both genetic and environmental factors significantly influence adult body height between populations. Models that included both genetic and environmental predictors best explained population differences in adult body height, with the MIX-Height PGS and environmental factors (Human Development Index [HDI] + per capita caloric intake) achieving an R2 of .83. Our findings shed light on Deaton's 'African paradox', which noted the relatively tall stature of African populations despite poor nutrition and childhood health. Contrary to Deaton's hypotheses, we demonstrate that both genetic differences and environmental factors significantly influence body height in countries with high infant mortality rates. This suggests that the observed tall stature in African populations can be attributed, in part, to a high genetic predisposition for body height. Furthermore, tests of divergent selection based on the QST (i.e., standardized measure of the genetic differentiation of a quantitative trait among populations) and FST (neutral marker loci) measures exceeded neutral expectations, reaching statistical significance (p < .01) with the MIX-Height PGS but not with the SIB-Height PGS. This result indicates potential selective pressures on body height-related genetic variants across populations.

Single-Nucleotide Polymorphisms in Thrombotic Thrombocytopenic Purpura: A Genetic Predisposition to Immune Thrombotic Thrombocytopenic Purpura

Single-Nucleotide Polymorphisms in Thrombotic Thrombocytopenic Purpura: A Genetic Predisposition to Immune Thrombotic Thrombocytopenic Purpura

Multiple thyroid disorders and risk of osteoporosis: a two-sample Mendelian randomization study.

Previous research has demonstrated that even minor changes in thyroid function are associated with an increased risk of osteoporosis (OP). However, the causal relationship between thyroid disorders and the development of OP remains unclear. To address this, we aim to investigate the connection between genetic predispositions to various thyroid disorders and OP using a two-sample Mendelian randomization (MR) approach. Instrumental variables (IVs) for multiple thyroid disorders were sourced from a large genome-wide association study (GWAS) meta-analysis dataset. Summary-level data for OP were obtained from the FinnGen consortium. Inverse variance weighting (IVW) methods served as the primary approach for MR analysis. Sensitivity analyses included MR-Egger regression, heterogeneity testing, multiple validity tests, and leaFve-one-out sensitivity tests. IVW analysis revealed a direct causal effect of hypothyroidism (OR = 1.105, 95% CI 1.023-1.194, P 0.011) and Hashimoto's thyroiditis (OR = 1.142, 95% CI 1.026-1.271, P 0.015) on OP. However, no direct causal association was found between hyperthyroidism (OR = 1.030, 95% CI 0.944-1.123, P 0.508) or thyroid cancer (OR = 0.971, 95% CI 0.898-1.051, P 0.469) and OP. Our MR analysis revealed a causal association between hypothyroidism, Hashimoto's thyroiditis, and OP. This highlights the significant impact of thyroid function on bone health. However, further longitudinal studies are needed to confirm these findings conclusively.

Atopic dermatitis in children of the first year of life: clinical and pathogenetic aspects, modern views on treatment from the perspective of a dermatologist

Atopic dermatitis is one of the most common skin diseases in children. Genetic disorders that determine the development of persistent dysfunction of cellular immunity play an important role in the development of clinical symptoms of atopic dermatitis. In the new concept of the occurrence of clinical manifestations of atopic dermatitis (AD), T-regulatory lymphocytes are assigned, in the form of CD4+CD25+ phenotype, which is controlled by the transcription factor FoxP3. The study of the mechanism of itching, which is more or less observed in all children with blood pressure, showed that in the case of the island-inflammatory course of Th2-dependent blood pressure, itching is histamine-conditioned. According to the concept of «Outside to Inside – outside – inside», the most significant mechanisms causing the appearance of blood pressure are a genetic predisposition that causes the formation of allergic reactions, changes in the permeability of the epidermal barrier, against the background of transepidermal moisture loss, the occurrence of xerosis phenomena and a decrease in the itching threshold. Significant abnormalities in the state of the skin microbiota were found in children with AD. The species composition of the intestinal microbiota in children with AD differs significantly from that in children with healthy skin. Intestinal microbiocenosis largely determines the direction of morphofunctional processes in the epidermis, by means of translocation of intestinal bacteria regulating the humoral response directly in the skin. Most often, allergic reactions are triggered when food proteins enter the body. Among other allergens, cow’s milk protein is the most significant in the development of allergic reactions in young children. In many cases, in 1-year-old children with AD, goat’s milk mixtures are a good alternative to cow’s milk-based milk mixtures. At the present stage, the most important in the complex of therapeutic measures in children with blood pressure from the first year of life are diet therapy and active external therapy, including the phased use of topical steroids, calcineurin inhibitors, emollients.

BUD23 promote the cell proliferation ability by affecting the PPAR signaling pathways: evidence from the online dataset and cell experiment

IntroductionProstate cancer is a major public health challenge for men worldwide, being the second most common cancer diagnosis and the fifth leading cause of cancer-related deaths among men. The etiology of prostate cancer is multifactorial, with age, genetic predispositions, and lifestyle factors playing critical roles. The role of the peroxisome proliferator-activated receptors (PPARs) in prostate cancer remains complex and not fully elucidated.MethodsTranscriptomic data from The Cancer Genome Atlas (TCGA) were utilized for this study. The data were analyzed using single-sample Gene Set Enrichment Analysis (ssGSEA), Gene Ontology (GO) enrichment analysis, KEGG pathway analysis, and Gene Set Enrichment Analysis (GSEA). A prognosis-prediction model was constructed using Cox regression and LASSO analysis. Functional experiments, including Western blotting, quantitative PCR (qPCR), Cell Counting Kit-8 (CCK-8) assays, and EdU incorporation assays, were performed to validate the role of BUD23 in prostate cancer.ResultsSignificant differences were observed in the immune microenvironment and HLA gene expression profiles between high and low PPAR expression groups in prostate cancer. The high PPAR group exhibited a less active immune microenvironment with higher fractions of immunosuppressive T regulatory cells (Tregs). A robust prognostic model identified key genes, including BUD23, associated with patient survival. Elevated BUD23 expression was correlated with more aggressive clinical features such as advanced pathological stages, nodal metastasis, and higher Gleason scores. Knockdown of BUD23 in PC-3 and LNCaP prostate cancer cell lines significantly inhibited cell proliferation. Western blotting and qPCR confirmed effective BUD23 knockdown, and CCK-8 and EdU assays demonstrated reduced cell proliferation. BUD23 knockdown resulted in significant reductions in PPAR-α, PPAR-β, and PPAR-γ protein levels, suggesting a regulatory axis between BUD23 and PPARs in prostate cancer.ConclusionThe study highlights the distinct roles of PPARα, PPARβ/δ, and PPARγ in prostate cancer progression and their potential as therapeutic targets. Elevated BUD23 expression is associated with aggressive prostate cancer features and patient survival, making it a potential prognostic biomarker. The knockdown of BUD23 not only inhibited cell proliferation but also reduced the expression of PPAR-related proteins, indicating a potential regulatory axis between BUD23 and PPARs. These findings suggest that targeting BUD23 could modulate PPAR signaling and inhibit tumor growth in prostate cancer.