Search Results (16,183)

Acute lymphoblastic leukemia (ALL) remains the most frequent pediatric malignancy, accounting for approximately 34% of all pediatric cancers, with remarkable improvements in survival (approximately 85%) due to advances in chemotherapy, radiotherapy, and supportive care. However, as survival rates have increased, new challenges have emerged—particularly the growing prevalence of obesity and metabolic syndrome among survivors. This review compiles evidence from the past decade on the relationship between leukemia treatment, obesity, and metabolic risk. The findings indicate that cranial radiotherapy, corticosteroid use, and younger age at diagnosis are key risk factors for excessive weight gain and long-term metabolic disturbances. Genetic factors such as FTO, MC4R, and LEPR polymorphisms may further influence susceptibility to obesity. Nutritional analyses highlight poor diet quality, insufficient micronutrient intake, and high-fat, energy-dense dietary patterns in survivors. Beyond endocrine dysfunction, obesity and metabolic syndrome are associated with elevated cardiovascular morbidity and reduced quality of life. Personalized medicine approaches—integrating genomics, metabolomics, and lifestyle data—hold promise for targeted prevention and intervention strategies. Early detection, continuous metabolic monitoring, and health education remain essential components in the long-term management of childhood leukemia survivors. In this review, we analyzed the dietary patterns of children and long-term leukemia survivors explaining why higher rates of obesity and comorbidities appear during or after treatments, and discussed interventions to prevent these conditions. Full article

Background: The increasing attention on extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli strains isolated from poultry flocks stems from concerns about their virulence potential and zoonotic risk. Of particular significance is the identification of extraintestinal pathogenic E. coli (ExPEC) pathotypes in poultry, as these strains pose not only animal health concerns but also serious threats to food safety and public health. Mapping the genetic background of pathogenicity and antimicrobial resistance is essential for risk assessment and the development of effective control strategies. Methods: A total of 87 E. coli isolates were isolated from tracheal and cloacal swab samples collected from healthy chickens between 2022 and 2023. Whole-genome sequencing was performed using Illumina and MGI next-generation sequencing platforms. Bioinformatic analyses were conducted to identify virulence-associated genes and pathotype markers using multiple reference databases, including VirulenceFinder. The frequency of virulence genes was summarized both in tabular form and visualized through graphical representations. Results: A substantial proportion of the isolates harbored virulence genes linked to various ExPEC pathotypes, particularly uropathogenic E. coli (UPEC), avian pathogenic E. coli (APEC), and neonatal meningitis-causing E. coli (NMEC). The most frequently detected colonization factors included members of the fim, pap, ecp, and fae gene families. Among fitness-related genes, iron acquisition systems—ent, chu, iro, iuc, fep, and ybt—were especially prevalent. Classic UPEC-associated genes such as pap and fimH, along with the APEC-related iutA and vat, were found at high frequencies. Four isolates exhibited a virulence gene profile characteristic of the NMEC pathotype (ibeA, kpsD/M/T, fimH). In contrast, hallmark genes of enteric pathotypes were absent from all isolates. Conclusions: The predominance of extraintestinal virulence factors in the examined poultry-derived E. coli strains underscores their zoonotic potential. The complete absence of enteric pathotype markers indicates that the studied poultry populations primarily harbor ExPEC-like strains. These findings highlight the critical need for ongoing genomic surveillance and targeted preventive strategies within poultry production systems. Full article

Background/Objectives: North African catfish (Clarias gariepinus) and bighead catfish (Clarias macrocephalus) play crucial roles in Thai aquaculture. Although significant growth disparities exist among these species, the genetic factors underlying these differences are still unknown. This study aimed to identify GH1 gene polymorphisms, in North African and bighead catfish populations across Thailand and Laos. Methods: Sequencing, phylogenetic, and clustering analyses were performed to assess genetic diversity, selection patterns, and lineage differentiation of catfish partial GH1 fragment. Results: Six alleles of the studied fragment of GH1 gene were identified; they differed at 33 variable sites within intron 2, located between the conserved regions at the 3′ end of exon 2 and the 5′ end of exon 3. At the population-level, GH1 exhibited low heterozygosity (mean H_o = 0.043 ± 0.023; H_e = 0.059 ± 0.028). Bayesian clustering analyses identified two distinct genetic clusters, corresponding to North African and bighead catfish, apart from the bighead population in Laos, indicating their distinct genetic origins. Evidence of purifying selection was observed in both species. Phylogenetic analysis indicated the presence of lineage-specific alleles in the GH1 gene. Conclusions: These findings provide valuable insights into GH1 polymorphisms in commercially important catfish species and may help to develop future breeding programs aimed at enhancing aquaculture productivity. Full article

The species Panellus stipticus presents a unique situation whereby some geographic strains are bioluminescent while others are not. This study investigates the factors affecting the bioluminescence of P. stipticus, focusing on culture media optimization, oxygen dependency, and genetic variation between luminescent and non-luminescent strains. Experiments revealed that 10% breadcrumb agar (BCA) significantly enhanced bioluminescence and colony size while supplementation with activated charcoal reduced luminescence. Comparative analysis of carbohydrate-based media showed that BCA outperformed malt extract and molasses in promoting luminescence. Oxygen was confirmed as essential for bioluminescence, with light emission ceasing rapidly under anaerobic conditions and recovering within minutes upon re-exposure to air. Phylogenetic analysis using ITS sequences distinguished luminescent and non-luminescent strains, aligning with biogeographical patterns. Dot plot synteny analysis of draft genomes of a bioluminescent (Panst LUM) and a non-bioluminescent strain (KUC8834) revealed high genomic conservation. However, absence of key bioluminescence genes in non-luminescent strains explains their lack of light emission. Protein sequence comparisons of core enzymes—LUZ, HISP, and H3H—showed functional similarity with Mycenoid lineage species. These findings deepen our understanding of fungal bioluminescence and its genetic and environmental determinants. Full article

Glaucoma is a major ocular neurodegenerative disease and a leading cause of irreversible blindness worldwide, with prevalence projected to exceed 110 million by 2040. Although lowering intraocular pressure (IOP) remains the only proven treatment, glaucoma arises from a complex interplay of genetic, local, and systemic factors—including oxidative stress, vascular dysregulation, mitochondrial dysfunction, and neuroinflammation. Emerging evidence suggests that modifiable lifestyle factors may influence these pathogenic pathways. In this review, higher dietary nitrate from leafy greens is consistently associated with lower primary open-angle glaucoma risk, aligning with nitric-oxide-mediated endothelial support and more stable ocular perfusion pressure. Flavonoids (anthocyanins and flavanols), carotenoids (lutein/zeaxanthin), and B vitamins have strong biological rationale for glaucoma prevention but have limited support from long-term, large population-based studies. The effect of polyunsaturated fats on glaucoma remains inconsistent and warrants source-(plant vs. animal) and substitution-based analyses. Consistent protective effects of aerobic exercise and high-quality sleep may be associated with favorable metabolic profiles and ocular perfusion, potentially mitigating retinal ganglion cell loss. Conversely, smoking and alcohol use are frequently coupled with poorer diet quality (e.g., lower vegetable intake) and heightened oxidative stress, which may exacerbate glaucomatous neurodegeneration. However, much of the current literature is constrained by cross-sectional designs, reliance on self-reported food frequency questionnaires, and insufficient use of structural endpoints such as retinal nerve fiber layer imaging. This review focuses on the potential of lifestyle modification and future directions in prevention and treatment strategies for glaucoma, highlighting the need for large-scale, multi-ethnic, genotype-stratified longitudinal studies and randomized controlled trials to establish causality and define optimal intervention strategies. Full article

Hematopoietic stem cells (HSCs) are essential for lifelong blood production and immune homeostasis. However, aging induces functional declines in HSCs, leading to hematological disorders, immune dysfunction, and increased susceptibility to malignancies. This review explores the biological underpinnings of HSC aging, highlighting the intrinsic and extrinsic factors that drive this process. We discuss the molecular and cellular mechanisms contributing to HSC aging, including genetic instability, epigenetic alterations, metabolic shifts, and inflammation signaling. Additionally, we examine the role of the bone marrow microenvironment in modulating HSC aging, emphasizing the impact of niche interactions, stromal cell dysfunction, and extracellular matrix remodeling. To advance our understanding of HSC aging, pluripotent stem cell differentiation platforms provide a valuable tool for modeling aged HSC phenotypes and identifying potential therapeutic targets. We review current strategies for HSC rejuvenation, including metabolic reprogramming, epigenetic modifications, pharmacological interventions, and niche-targeted approaches, aiming to restore HSC function and improve regenerative potential. Finally, we present emerging perspectives on the clinical implications of HSC aging, discussing potential translational strategies for combating age-associated hematopoietic decline. By integrating insights from stem cell biology, aging research, and regenerative medicine, this review provides a comprehensive overview of HSC aging and its therapeutic potential. Addressing these challenges will be critical for developing interventions that promote hematopoietic health and improve outcomes in aging populations. Full article

Background/Objectives: Direct oral anticoagulants (DOACs) have transformed the prevention of thromboembolic events, but their efficacy and safety remain highly variable across individuals. DD217, a novel oral direct factor Xa inhibitor, has demonstrated potent anticoagulant activity in preclinical and clinical studies. No pharmacogenetic data are currently available for this compound. Based on in silico predictions of metabolic pathways and transporter involvement, and evidence from other DOACs, we hypothesized that variants in CYP2C and P-glycoprotein genes may contribute to variability in pharmacokinetics (PK) and clinical outcomes. Methods: Fifty-two patients undergoing total knee arthroplasty were enrolled, of whom 34 received the investigational drug (40 mg/day, n = 16; 60 mg/day, n = 18). DNA was extracted from peripheral blood cells, and genotyping of CYP2C9, CYP2C19, CYP2C8, CYP3A4, CYP3A5, and ABCB1 was performed by real-time PCR. Pharmacokinetics (PK) parameters (T_max, AUC_last, C_max) were assessed. In silico docking and pathway modeling predicted CYP2C and P-glycoprotein (ABCB1) involvement in drug disposition. Associations of genetic variants with PK parameters and adverse events (thrombosis, bleeding) were analyzed. Results: Carriers of reduced-function CYP2C9 alleles (intermediate [IM] or poor metabolizers [PM]) in the 60 mg group had a significantly shorter T_max compared with normal metabolizers (p = 0.005227), with trends toward higher AUC_last (p = 0.06926) and C_max (p = 0.1259). No significant associations were observed for CYP2C19, CYP3A4/5, or CYP2C8. In contrast, ABCB1 polymorphisms were associated with systemic exposure: carriers of the C allele at rs1045642 had higher AUC_last and C_max compared to TT (wild-type) homozygotes, while rs2032582 T allele carriers showed lower exposure (p < 0.05). At the haplotype level, the C–G–C–T combination of ABCB1 was more frequent in patients with thrombotic events at the 40 mg dose (p = 0.038). Overall, 5 thrombosis events and 1 bleedings were recorded on DD217, with no consistent associations to single SNPs. Conclusions: This first pharmacogenetic evaluation of DD217 shows that CYP2C9 variants are associated with differences in early-phase pharmacokinetics (T_max), while ABCB1 polymorphisms appear to modulate systemic exposure (AUC_last, C_max) and may influence thrombotic risk. These observations are consistent with in silico predictions of metabolic and transporter pathways. Despite limitations in sample size and event frequency, the study highlights the feasibility and importance of early pharmacogenetic evaluation during the drug development cycle of novel DOACs. Full article

Metabolic diseases such as obesity and related conditions have an inflammatory basis. Genetic and nutritional factors can influence the development of these diseases by altering the inflammatory state. This study aimed to analyse how the rs659366 (G/A) polymorphism in the UCP2 gene interacts with dietary capsaicin (CAP) consumption and affects inflammatory markers in Mexican adults. A cross-sectional, analytical study was conducted in 212 adult patients. The UCP2 rs659366 polymorphism was genotyped using an allelic discrimination assay. Dietary CAP intake was measured with a validated food frequency questionnaire. Multivariate linear regression analyses were performed for interaction analyses. The ancestral allele G accounted for 40.2% and the risk allele A accounted for 59.8% of samples. There was a significant interaction between CAP intake and the UCP2 rs659366 polymorphism for the inflammatory marker NLR (neutrophil-to-lymphocyte ratio) (p < 0.05). Among subjects with the G allele, higher CAP intake was associated with higher NLR scores (p < 0.001). Patients with the G allele of the UCP2 rs659366 polymorphism experienced increased inflammation with higher CAP intake. This finding highlights the need for future studies in personalised nutrition and could expand knowledge about the effects of CAP on obesity and inflammation. Full article

Colorectal cancer (CRC) is among the most prevalent malignancies worldwide, representing the second leading cause of cancer-related mortality and accounting for approximately 2 million new cases and nearly half a million deaths annually. Global age-standardized incidence rates are highest in Australia/New Zealand and other Western countries, and lowest in parts of sub-Saharan Africa and South Asia, reflecting variations in demographics, lifestyle exposures, and screening practices. Colon cancer constitutes the larger fraction of CRC cases, with rectal cancer contributing substantially, and early-onset CRC (<50 years) is increasing across both high-income and emerging regions. Established risk factors include age, hereditary syndromes, obesity, sedentary behavior, dietary patterns, metabolic disorders, and chronic inflammation, with notable distinctions between colon and rectal subsites. This narrative review provides a comprehensive overview of CRC epidemiology, molecular and genetic pathogenesis, staging, and modern therapeutic approaches, addressing colon and rectal cancers separately due to their distinct biology, clinical behavior, and treatment strategies. By integrating current knowledge on genetic drivers, systemic and local therapies, and patient stratification, the review aims to inform clinical practice, support clinical trial design, discuss ongoing challenges and future perspectives, and foster further research toward precision-guided management of CRC. Full article

Objectives: This study aimed to elucidate the determinants of interindividual variability in the pharmacokinetics of ibrutinib among healthy Chinese subjects, focusing on the influence of demographic characteristics, dietary conditions, and genetic polymorphisms on CYP enzymes and ABC transporters. Methods: Thirty-two participants were randomly assigned to either a fasting (n = 16) or fed (n = 16) group, each receiving a single 140 mg oral dose of ibrutinib. Plasma concentrations were quantified using a validated UPLC–MS/MS method. Genetic polymorphisms in CYP3A4, CYP3A5, CYP2D6, and ABCG2 were identified by Sanger sequencing. Pharmacokinetic parameters, including apparent clearance (CL/F), maximum plasma concentration (Cmax), area under the plasma concentration–time curve (AUC0-t), and time to maximum concentration (Tmax), were estimated by non-compartmental analysis and statistically evaluated for associations with demographic, dietary, and genetic variables. Results: Food intake significantly affected ibrutinib pharmacokinetics, with postprandial administration resulting in reduced CL/F and increased Cmax and AUC0-t (p < 0.01). Gender differences were also observed, as females exhibited higher CL/F, lower Cmax, and AUC0-t than males (p < 0.05). The CYP2D6 c.100C>T polymorphism significantly decreased CL/F and increased exposure in fasting and male subjects (p < 0.05), but this effect was absent under fed conditions. Conversely, the ABCG2 c.421C>A variant was associated with increased CL/F and decreased AUC0-t (p < 0.05), while other genotypes exerted negligible effects. Conclusions: Ibrutinib pharmacokinetics are significantly modulated by dietary status, gender, and genetic polymorphisms, particularly CYP2D6 c.100C>T and ABCG2 c.421C>A. These findings underscore the importance of integrating pharmacogenetic and physiological factors into individualized dosing strategies to optimize therapeutic efficacy and minimize adverse effects. Full article

Modern machining industries require high precision and efficiency in machine tools, where thermal deformations significantly impact accuracy. This study focuses on optimizing the structural parameters of a vertical turning center to minimize thermal displacements affecting machining precision. The optimization process is divided into parametric and topological methodologies. The parametric approach targets three primary objectives: minimizing mass (q₁), maximizing static stiffness (q₂), and reducing thermal displacement (q₃). Multi-criteria optimization techniques, including Pareto-based and scalarization methods, are applied to balance these conflicting factors. Finite Element Analysis (FEA) models assist in evaluating machine stiffness and displacement, with constraints imposed on structural mass and stiffness to maintain performance. Parametric optimization, using iterative computational algorithms such as Genetic Algorithm (GA) and Particle Swarm Optimization (PSO), refines rib and wall thicknesses of the lathe table to achieve displacement reductions. The optimization process successfully lowers displacement at critical measurement points while maintaining structural integrity. Hybrid PSO (hPSO) outperforms other algorithms in achieving optimal parameter sets with minimal computational effort. Topological optimization, based on the Solid Isotropic Microstructure with Penalization (SIMP) method, further enhances structural efficiency by refining material distribution. The iterative process identifies optimal energy flow paths while ensuring compliance with mechanical constraints. A hybrid approach integrating parametric adjustments with topological refinement leads to superior performance, achieving a 43% reduction in displacement at key measurement points compared to the initial design. The final optimized design reduces mass by 1 ton compared to the original model and 2.5 tons compared to the best rib–wall optimization results. The study’s findings establish a foundation for implementing active deformation compensation systems in machine tools, enhancing machining precision. The integration of parametric and topological optimization presents a robust framework for designing machine tool structures with improved thermal stability and structural efficiency. Full article

Flower pigmentation is a critical trait in plants, influencing ecological interactions and ornamental value. This study investigates the mechanisms underlying petal coloration in Prunus campanulata and its hybrids, Prunus ‘Okame’ and Prunus ‘Yoko’. Morphological analysis revealed consistent flower size across varieties, indicating that color variation is not linked to structural differences. Physiological and biochemical analyses identified stages III and IV as critical for pigmentation, characterized by the significant accumulation of flavonoids and anthocyanins. Metabolomic profiling highlighted flavonoids as the dominant metabolites, with key compounds including chalcones, flavones, and anthocyanins contributing to color formation. Weighted gene co-expression network analysis (WGCNA) further identified several hub genes, including RPL34, NUDT12, and CYP78A9, within modules strongly correlated with pigment accumulation, suggesting their potential non-canonical roles in the coloration process. Environmental factors such as temperature and pH were found to influence pigment stability. Overall, this study provides insights into the genetic and biochemical regulation of flower pigmentation in P. campanulata, emphasizing the central role of flavonoid and anthocyanin biosynthesis. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be a leading cause of morbidity and mortality in Mexico, with more than 20,000 new cases annually and a rising proportion of drug-resistant strains. This work addresses the molecular epidemiology of TB in the Mexican context, emphasizing its role in understanding transmission, genetic diversity, and resistance mechanisms. To achieve this, we reviewed molecular typing approaches including spoligotyping, Mycobacterial Interspersed Repetitive Unit–Variable Number Tandem Repeat (MIRU-VNTR) analysis, and whole-genome sequencing (WGS), which have been applied to characterize circulating lineages and identify drug-resistance-associated mutations. The results indicate that the Euro-American lineage (L4) predominates across the country, although significant regional variation exists, with Haarlem, LAM, T, and X sub lineages dominating in different states, and occasional detection of Asian (L2) and Indo-Oceanic (L1) lineages. Key resistance mutations were identified in katG, rpoB, pncA, and gyrA, contributing to the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, particularly in border and marginalized regions. These findings highlight how social factors, such as migration, urban overcrowding, and comorbidities including diabetes and HIV, influence transmission dynamics. We conclude that integrating molecular tools with epidemiological surveillance is crucial for strengthening public health strategies and guiding interventions tailored to Mexico’s heterogeneous TB burden. Full article

Arrhythmogenic cardiomyopathy (ACM) is a genetic cardiac disease characterized by a progressive loss of cardiomyocytes associated with fibrofatty myocardial replacement, resulting in a heightened risk of ventricular arrhythmias and sudden cardiac death. ACM is a common cause of sudden death in young individuals, and exercise has been proven to be a factor in disease progression. Current therapeutic strategies, including lifestyle modification, antiarrhythmic pharmacological therapy, catheter ablation, and the placement of implantable cardioverter-defibrillators, remain primarily palliative options rather than addressing the underlying molecular substrate. The pathogenesis of ACM includes complex molecular and cellular mechanisms, linking genetic mutations to structural and electrical anomalies of the ventricle. The lack of targeted therapies contributes to a challenging approach to the disease. It highlights the need for a better understanding of the mechanisms that lead to myocardial remodeling and arrhythmic predisposition. With the help of animal models (especially murine) and induced pluripotent stem cells, there have been advances in understanding the molecular pathogenesis of ACM. In this review, we summarized some of the pathogenic molecular pathways involved in the development of ACM and emerging therapies targeted towards disease modification, not just prevention. Full article

Follicular lymphoma management is rapidly evolving with advanced cellular therapies. This review examines the optimal sequencing of autologous stem cell transplantation (autoSCT), allogeneic stem cell transplantation (alloSCT), and CAR T-cell therapy. AutoSCT is a crucial intervention for chemosensitive relapsed FL, prolonging progression-free survival, though not typically curative. AlloSCT, offering a potential cure via a graft-versus-lymphoma effect, carries significant risks like graft-versus-host disease and non-relapse mortality, thus primarily serving as a salvage option for high-risk or treatment-refractory cases after other modalities, including autoSCT. CAR T-cell therapy, utilizing genetically modified T cells targeting CD19, has revolutionized relapsed/refractory FL. Products like axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have demonstrated high response rates and durable remissions even in heavily pretreated patients with high-risk features. This potent therapy is increasingly considered a bridge between autoSCT and alloSCT, expanding treatment options. Additionally, bispecific antibodies such as mosunetuzumab, epcoritamab and odrenextamab provide convenient off-the-shelf options, exhibiting strong efficacy and favorable safety. However, their impact on subsequent CAR-T outcomes, especially with CD19-targeting bispecifics, remains an area of ongoing investigation and uncertainty. The complex interplay of these therapies necessitates individualized decisions, emphasizing patient characteristics and disease-specific factors to optimize outcomes in FL. Further research into predictive biomarkers and refined treatment algorithms is crucial for future management. Full article