Search Results (76,272)

Background/Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most consumed drugs worldwide and the main cause of drug hypersensitivity reactions (HSRs). The most common NSAID-HSR class is cross-hypersensitivity (CR), with patients reacting to NSAIDs from different chemical groups without specific immunological recognition, with NSAID-induced acute urticaria/angioedema (NIUA) being the most frequent clinical phenotype. Although CR-HSRs are triggered by arachidonic acid (AA) alterations following cyclooxygenase (COX)-1 inhibition and cysteinyl-leukotrienes synthesis by 5-lypoxygenase (5-LO), current evidence supports the participation of additional mechanisms. As COX-1 and 5-LO head oxidative pathways, it is conceivable that enzymes participating in antioxidant control are involved in these mechanisms. In addition, as the CR-HSR susceptibility seems to be influenced by genetic factors, the possibility of genetic variants playing a role in such enzymes should not be excluded. Methods: In this observational case–control study, we analysed for the first time in NIUA the overall genetic variability in key antioxidant defence enzymes genes, including catalase (CAT), glutathione peroxidase (GPX)-1 and 3, and superoxide dismutase (SOD)-1. We selected a set of tagging single nucleotide polymorphisms (tSNPs) in these genes using data from Europeans in the 1000 Genomes Project. Two independent Spanish populations (discovery and replication) of NIUA patients and NSAID-tolerant individuals were included. Results: Twenty-six tSNPs were genotyped in the discovery population, with three that were significantly associated with NIUA: rs3448 (GPX-1), rs3792798 (GPX-3), and rs10432782 (SOD-1). They were then genotyped in the replication group, with rs3792798 being protective and rs10432782 being associated with an increased NIUA risk. Conclusions: Our results suggest that a role for antioxidant enzyme polymorphisms in NIUA is required. Nevertheless, further research is needed to replicate our findings in other populations and their meaning at the molecular level and to investigate the role of such variants in other CR-HSR-induced phenotypes. Full article

To comprehend the current state and future of newborn screening (NBS), it is essential to understand its history. Over the past six decades, this well-established and exemplary population-based screening program has been guided by screening principles dating back more than half a century. Advances in laboratory and point-of-care testing, diagnostic methods, and a surge of available treatments and even cures have made it challenging to balance screening criteria that have not kept pace with the current landscape. The availability to screen as well as the demand from parents and stakeholders to screen for more and increasingly complex conditions while limiting the retention of NBS specimens and genetic material has been both exciting and challenging. This paper shares the history of NBS in the United States, followed by the development and integration of genomic sequencing as a complement to current practice. It explores evidence supporting the concomitant use of biomarker- and DNA-sequencing-based approaches for NBS, how disorders are selected for inclusion, and available treatments, and offers recommendations regarding what to consider and how to proceed in this ever-changing NBS landscape. Full article

Recurrent vulvovaginal candidiasis (RVVC) affects 5–8% of women of reproductive age. Host genetic factors, particularly single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs), may influence RVVC susceptibility by impairing vaginal mucosal antifungal immunity. The aim of this study was to assess the effect of SNPs in genes encoding TLRs on RVVC susceptibility. Τhe distribution of TLR2 Arg753Gln and TLR4 Asp299Gly/Thr399Ile polymorphisms in Greek women, including RVVC (n = 63), first-episode VVC (n = 37), Gardnerella vaginalis vaginitis (GV, n = 36) patients, and healthy controls (n = 61), was investigated using TaqMan SNP genotyping. Genotype and allele frequencies were analyzed under allelic and dominant models, with odds ratios (ORs), 95% confidence intervals (CIs), and linkage disequilibrium assessed. TLR4 Asp299Gly and Thr399Ile heterozygotes were significantly more frequent in RVVC patients compared with controls and affected RVVC susceptibility (OR: 5.57, 95% CI: 1.17–26.56, p: 0.0172; OR: 4.92, 95% CI: 1.02–23.78, p: 0.0306, respectively). No associations were observed for TLR2 Arg753Gln or for any SNP with GV or first-episode VVC. TLR4 variants co-segregated, indicating a haplotype effect. TLR4 haplotypes, rather than TLR2 polymorphism, confer increased RVVC susceptibility, supporting a genetically distinct, mucosal immunity-driven pathogenesis. Larger, ethnically diverse studies with functional assays are warranted to validate these findings and guide personalized prevention and treatment strategies. Full article

Argali (Ovis ammon), the largest wild sheep in Asia, are of high conservation concern and remain taxonomically and genetically debated across parts of their range. We investigated population structure, relatedness, and inbreeding within Argali sampled in Kyrgyzstan using the Illumina Ovine High-Density SNP array, with an emphasis on dense within-population sampling rather than range-wide comparisons. After quality control, 72 individuals and 135,242 markers were retained for analysis. Principal component analysis revealed subtle genetic variation within the sampled population, but no clustering consistent with discrete subspecies. In particular, we found no genomic support for separating O. a. polii and O. a. karelini within Kyrgyzstan, suggesting that they represent a single genetic unit in this region. Estimates of identity by descent indicated a high average relatedness (0.35), consistent with harem-based breeding systems typical of wild sheep, while individual inbreeding coefficients averaged near zero, with some evidence of moderate inbreeding in a subset of animals. Together, these results characterize fine-scale genetic structure and kinship within Tian Shan Argali and provide a regional genomic baseline for conservation planning in Kyrgyzstan. Our findings highlight the importance of maintaining connectivity within and among managed populations while acknowledging that broader inference will require sampling across the core Pamir range and other parts of the species’ distribution. Full article

The issue of emergency facility location is a long-term strategic issue, and the complexity and diversity of the decision-making environment force decision-makers to focus on multiple objectives when making location decisions. We develop a multi-objective optimization system centered on cost-effectiveness, service balance, and fairness, targeting three core objectives: minimizing total costs, minimizing differences in service quality among demand points, and minimizing material shortage gaps between demand points. To address the issue of limited facility service capacity induced by material shortages, we establish a multi-objective optimization model for the reliable location of emergency facilities. By combining the model’s characteristics with the Non-Dominated Sorting Genetic Algorithm (NSGA-II) and an elite retention strategy, the Pareto frontier solution set of the multi-objective model is obtained, and the model’s feasibility is verified through various examples of different scales. Finally, sensitivity analysis was conducted on the reliability location model of emergency facilities under different disruption risks using the control variable method, and the topology structure of the reliability location allocation network for emergency facilities under different disruption situations is obtained. The research findings provide decision-makers with actionable references and technical support for selecting reliable locations for emergency facilities amid disruption risks. Full article

Obesity represents a heterogeneous metabolic disorder characterized by substantial interindividual variation in inflammatory status, insulin sensitivity, and cardiometabolic risk. Traditional anthropometric measures fail to capture this metabolic diversity, limiting risk stratification and personalized intervention strategies. This review critically examines nutritional and metabolic biomarkers that reflect the physiological dysregulation underlying obesity, including adipokines (leptin, adiponectin, resistin), inflammatory markers (C-reactive protein, interleukin-6, TNF-α), insulin resistance indices (HOMA-IR, fasting insulin, HbA1c), and lipid metabolism indicators (LDL cholesterol, triglycerides, HDL cholesterol, and liver enzymes such as ALT and GGT). Among these, elevated CRP, reduced adiponectin, and increased HOMA-IR have demonstrated the strongest clinical utility for early metabolic risk identification. We further evaluate emerging biomarkers—including circulating microRNAs, gut microbiota-derived metabolites (short-chain fatty acids, TMAO, lipopolysaccharides), and bile acid profiles—which offer additional mechanistic insight into diet–microbiome–host interactions. We systematically assess the mechanistic basis, clinical relevance, and nutritional modulation of each biomarker class, emphasizing how dietary composition—particularly fatty acid quality, fiber intake, and overall dietary patterns such as the Mediterranean diet—influences biomarker profiles and metabolic outcomes. Furthermore, we explore how biomarker-based phenotyping enables precision nutrition approaches by identifying individuals most likely to benefit from specific dietary interventions. Integration of multi-biomarker panels with clinical and genetic data holds promise for advancing from population-based dietary guidelines toward individualized nutrition strategies that optimize metabolic health and prevent obesity-related complications. Future research should prioritize validating biomarker-guided intervention frameworks, establishing standardized thresholds across diverse populations, and developing clinically implementable tools for personalized nutritional medicine. Full article

Goji, a plant unique to China, is recognized for its dual use as both a food and a medicine and is rich in various nutrients. However, long-term asexual propagation often leads to cultivar degeneration and viral accumulation, which severely impact its yield, quality, and disease resistance. Homozygous seeds can stably produce offspring with uniform traits. Haploid breeding technology, which involves doubling the chromosomes of haploid plants to obtain homozygous diploids, can significantly accelerate the breeding process. The DMP (Domain of Unknown Function 679 Membrane Protein) family is a plant-specific family of membrane proteins involved in various biological functions, including physiological processes, reproductive development, and senescence. Concurrently, loss-of-function of the DMP gene impedes the proper integration of the paternal genome following fertilization. Consequently, the embryo develops with exclusively maternal chromosomes, a mechanism that underlies the induction of haploids. In this study, we conducted a genome-wide identification of the DMP gene family in goji, analyzing the physicochemical properties, chromosomal locations, cis-acting elements, phylogenetic relationships, sequence characteristics, expression patterns, and subcellular localization of its members. The objective was to identify DMP genes capable of inducing haploid production in goji berry for future breeding applications. The results revealed a total of 11 DMP family members in the goji berry genome, distributed across seven chromosomes. The proteins encoded by these members contain 136 to 237 amino acids, with molecular weights ranging from 15,267.96 to 26,141.01 Da and isoelectric points (pI) ranging from 5.14 to 9.32. The LbDMPs were found to contain numerous cis-acting elements that play roles in plant responses to abiotic stresses and various phytohormones. Notably, LbDMP1 and LbDMP11, which contain the typical DUF679 domain, are predominantly expressed in pollen, suggesting their involvement in the reproductive process of goji berry. They were therefore identified as candidate genes for haploid induction. Subcellular localization analysis demonstrated that LbDMP1 is localized to the plasma membrane, while LbDMP11 is localized to membrane systems such as the endoplasmic reticulum. This research provides a fundamental basis for further exploration of the functional roles of the DMP gene family in goji berry and offers valuable genetic resources for haploid induction in its breeding programs. Full article

Background/Objectives. The Black Death pandemic, combined with the antisemitic climate of 14th-century Europe, led to widespread violence against Jewish communities, including numerous pogroms such as the one in 1348 in Tàrrega (Catalonia, Spain). In the Roquetes necropolis of Tàrrega, six communal graves containing at least sixty-nine individuals, with signs of violence, were dated to the mid-14th century. Based on the hypothesis that Iberian medieval Jewish communities preserve genetic similarities to other ancient and modern Jewish communities, our study aims to provide genomic information on medieval Iberian communities, which to date have been unknown. Methods. We analyzed DNA from sixteen individuals from the Roquetes necropolis using Twist ancient DNA enrichment capture. Several paleogenomic analyses based on nuclear DNA and uniparental markers were conducted to determine their genetic relatedness and population origin. Results. PCA and ADMIXTURE analyses revealed genetic affinities with ancient and modern Jewish populations. Uniparental markers, which exhibited high diversity, aligned with typical patterns within the Jewish community. The qpAdm modeling suggested that the genetic composition of the Roquetes population can be explained by a mixture of Canaan individuals (0.69) and the Iberian non-Jewish non-Islamic medieval population (0.31). No close genetic kinship was detected, but RHO analyses indicated a certain level of background endogamy. Conclusions. This is the first study to report genomic data for medieval Iberian Jews. Our findings reveal genomic affinities of the Roquetes individuals with ancient and modern Jewish populations and corroborate the previous attribution of the burials to victims of the 1348 Tàrrega pogrom. Full article

Objectives. The aim of our study was to track changes in ODQ scores in adolescents with depressive episodes taking sertraline, depending on CYP2C19 polymorphisms. Methods. This study included 88 adolescents (88% were female) aged 12–17 who were prescribed sertraline. Emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ) scale when the antidepressant was prescribed, after one, three, and 8 weeks, taking into account other medications used. Part 3 of the ODQ scale assessed the changes that occurred after the prescription of an antidepressant. All patients were genotyped for CYP2C19*2, *3, and *17. Based on genotypes, the phenotypes of the CYP2C19 isoenzyme were determined. Results. The ODQ score at the time of enrollment was higher (65[50;79] points) compared with after 8 weeks (38.5[32.5;56.5] points). Part 3 of the ODQ-26 questionnaire remained approximately the same for 8 weeks. Patients with higher ODQ-26 values at enrollment (73[56;83] vs. 59[44;71] points) were more likely to be prescribed antipsychotics. Differences in ODQ scores remained significant up to 3 weeks after enrollment (50.5[41.5;68] vs. 45.5[36;54] points). The comparison of ODQ scores and their dynamics did not show significant differences depending on CYP2C19*2 or *17 polymorphisms, or the type of CYP2C19 metabolism. Conclusions. There was no increase in emotional blunting according to the ODQ score among adolescents with depression who took sertraline for eight weeks. No significant correlations were found between the carrier status of CYP2C19 gene variants and the development of apathy induced by antidepressants. Full article

African swine fever (ASF) is a contagious viral disease that causes severe economic losses in the global swine industry. Since its introduction to Vietnam in 2019, ASFV has evolved rapidly, with genotype II strains dominating initially and recombinant I/II variants emerging by 2023. Live attenuated vaccines (LAVs) have been developed and commercialized in Vietnam, including ASFV-G-ΔI177L, ASFV-G-ΔI177L/ΔLVR, and ASFV-G-ΔMGF, which confer homologous immune protection. Despite this, LAVs face challenges related to genetic stability, impossible protection against emerging recombinant strains, potential reversion to virulence, viral shedding, and safety in pregnant sows. ASFV’s ongoing evolution underscores the need for continuous genomic surveillance, evaluation of cross-protective efficacy, and implementation of biosecurity and DIVA strategies focused more on evaluating vaccine efficacy than safety. This review summarizes the current molecular epidemiology of ASFV in Vietnam after vaccines were licensed for use, the development and performance of commercial LAVs, and the practical challenges of their application in endemic settings, and provides insights for informed vaccine deployment and integrated ASF control strategies in rapidly evolving viral landscapes. Full article

Background/Objectives: Forensic kinship analysis is a rapidly developing practice that uses genetic data to identify unknown persons of interest through their genetic relatives. It can be used to generate new leads in forensic investigations, especially those involving long-term missing persons and unidentified human remains. More recently, the advent of SNP profiling panels designed specifically for forensic use has led to the exploration of kinship analysis using medium-density SNP data. This study aimed to evaluate the extent to which genetic relationships could be inferred using such data, and to assess the performance of different kinship inference methods. Methods: Kinship analysis was performed with both real and simulated profiles using the panel of SNPs contained within the Verogen ForenSeq^® Kintelligence Kit, with a wide range of relationship types and seven types of kinship inference methods. Results: It was determined that kinship inferences were possible out to the fourth degree of kinship, and all inference methods analysed were equally effective when tested using simulated data. However, some variation between methods was observed when they were analysed using real sample data, suggesting that further study is needed using a larger sample size. Conclusions: The results of this study demonstrate that medium-density SNP data is sufficient for extended kinship inference out to the fourth degree, and that several kinship inference methods are suitable for use with the Verogen ForenSeq^® Kintelligence Kit. These findings will support its application in forensic investigations involving the inference of distant genetic relationships. Full article

The etiology of autism spectrum disorder (ASD) implicates genetic predispositions and environmental chemicals, such as polybrominated diphenyl ethers (PBDEs). We aimed to identify whether mitochondrial quality control (MQC) was involved in ASD-relevant behavioral changes induced by decabromodiphenyl ether (deca-BDE, BDE-209) and the alleviation by melatonin. Pregnant rats exposed to BDE-209 (50mg/kg i.g.) were administrated melatonin through drinking water (0.2 mg/mL) during gestation and lactation. Behavioral assessments integrated open-field test, three-chamber social test, and Morris water maze; mitochondrial detections took transmission electron microscopy, immunofluorescence, and homeostasis together; hippocampal molecular network was identified through transcriptomics profiles, combining dendritic morphology analysis after Golgi-Cox staining. Melatonin supplementation attenuated BDE-209-reduced social and cognitive ability, accompanied by improvements in hippocampal synaptic plasticity (dendritic spines, PSD95, SNAP25). Mitochondrial dysfunctions, shown as decreases in complex IV activity, ATP content, and mtDNA copies, plus redox imbalance (ROS/SOD2) and resultant mitochondrial membrane potential disruption and apoptosis, together with fusion/fission dynamic (MFN2/DRP1), biogenesis (SIRT1-PGC1α-TFAM), and mitophagy (SIRT3-FOXO3-PINK1) suppression, were reversed by melatonin partially through SIRT1 (Sirtuin-1)-dependent pathways, as these protections were abolished by inhibitor EX527. This study highlighted the SIRT1–SIRT3 axis in MQC and behavioral effects, providing novel intervention for PBDEs’ neurodevelopmental impairment. Full article

Background/Objectives: Chronic lymphocytic leukemia (CLL) is characterized by genetic and epigenetic alterations. This study aimed to assess the methylation status of E-Cadherin and MMP-9 gene promoters and to explore their relationships with disease pathogenesis and hematological parameters in CLL patients. Methods: A case–control study was conducted with 70 newly diagnosed CLL patients and 70 age- and sex-matched healthy controls. Promoter methylation of E-Cadherin and MMP-9 genes was evaluated using methylation-specific PCR (MSP) and methylation-sensitive restriction enzyme PCR (MSRE-PCR), respectively. Results: The median patient age was 62 years, and 68.5% were males. Binet stage A was the most common stage (57.3%). E-Cadherin promoter methylation was detected in 75.7% of CLL patients and 77.1% of controls (p = 0.91), showing no significant association with disease occurrence; however, it showed a significant correlation with higher lymphocyte counts (p = 0.01). In contrast, MMP-9 promoter methylation was significantly less frequent in CLL cases (70.0%) than in controls (100%, p = 0.001). Unmethylated MMP-9 correlated significantly with female gender (p = 0.02), lower hemoglobin (p = 0.031), reduced platelet counts (p = 0.001), and higher lymphocyte counts (p = 0.035). Conclusion: MMP-9 promoter hypomethylation may play a pathogenic role in CLL and is associated with female gender and cytopenia, whereas E-Cadherin methylation appears to be non-specific. MMP-9 methylation status could therefore serve as a potential biomarker for CLL biology and prognosis. Full article

Growth impairment is a clinical manifestation frequently observed in pediatric patients with cardiomyopathy associated with various inherited disorders, including RASopathies, lysosomal storage diseases, neuromuscular disorders, and metabolic conditions. In this narrative review, we explored the genetic and pathophysiological mechanisms underlying the development of both growth and myocardial impairment in Noonan syndrome (NS)—the most common RASopathy—Duchenne and Becker muscular dystrophies, Pompe disease, mucopolysaccharidoses, and mitochondrial diseases. For each condition, we described the cardiac and growth phenotypes, focusing on epidemiology, clinical implications, and disease-specific therapeutic strategies. In the era of precision medicine, innovative etiologic treatments targeting the underlying molecular mechanisms have emerged. Therefore, elucidating the molecular pathways responsible for growth impairment in pediatric inherited cardiomyopathies remains essential for optimizing multidisciplinary management and improving patient outcomes. Full article

Cancer remains a significant challenge to global public health. Preliminary studies indicate that the protein Golgi-associated, Gamma-adaptin Ear Containing, ARF Binding Protein 2 (GGA2) may influence various cancers. However, the potential role of GGA2 in oncogenesis remains unknown. We utilized data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) projects to analyze GGA2 expression levels. Genetic variations and protein expression of GGA2 in human tissues were assessed using the cBioPortal. Gene Set Enrichment Analysis (GSEA) provided deeper insights into GGA2’s oncogenic functions. Comprehensive analysis of TCGA datasets combined with ESTIMATE and TIMER tools demonstrated significant correlations between GGA2 expression levels and clinical outcomes, survival metrics, genomic instability markers (microsatellite instability (MSI)/tumor mutational burden (TMB)), and immune microenvironment composition. Functional validation in prostate cancer models employed qRT-PCR quantification, immunoblotting verification, and cellular behavior assessments through colony formation, Transwell migration, and wound closure assays. Our findings suggest GGA2 could serve as a prognostic biomarker in various cancers. Abnormal levels of GGA2 promoter methylation and genetic alterations may contribute to its dysregulated expression in some cancers. Distinctly, GGA2 expression correlates with MSI and TMB across different cancers and is linked to the expression of immune checkpoint genes. Functionally, GGA2 is instrumental in inhibiting oncogenic mechanisms by diminishing the proliferation, colony formation, invasion, and migratory capabilities of prostate cancer cells. Our study shows that the oncogenic role of GGA2 in various cancers and GGA2 could be served as a biomarker of PARD. Full article