Search Results (644)

Background/Objectives: Wilson’s disease (WD) is an autosomal recessive disorder characterized by pathological copper accumulation, primarily in the liver and brain. Severe hepatic involvement can be effectively treated with liver transplantation (LT). Geographic variation in ATP7B mutations suggests the presence of regional patterns that may impact disease presentation and management. This study aims to investigate the genetic basis of WD in patients from a major LT center in Iran. Methods: A retrospective analysis was conducted on clinical, biochemical, and pathological data from patients suspected of WD who underwent evaluation for LT between May 2020 and June 2025 at Shiraz University of Medical Sciences. Genetic testing was carried out on 20 patients at the Shiraz Transplant Research Center (STRC). Direct mutation analysis of ATP7B was performed for all patients, and the results correlated with clinical and demographic information. Results: In total, 20 WD patients who underwent liver transplantation (15 males, 5 females) carried 25 pathogenic or likely pathogenic ATP7B variants, 21 of which were previously unreported. Fifteen patients were homozygous, and five were compound-heterozygous; all heterozygous combinations occurred in the offspring of second-degree consanguineous unions. Recurrent changes included p.L549V, p.V872E, and p.P992S/L, while two nonsense variants (p.E1293X, p.R1319X) predicted truncated proteins. Variants were distributed across copper-binding, transmembrane, phosphorylation, and ATP-binding domains, and in silico AlphaMissense scores indicate damaging effects for most novel substitutions. Post-LT follow-up showed biochemical normalization in the majority of recipients, with five deaths recorded during the study period. Conclusions: This single-center Iranian study reveals a highly heterogeneous ATP7B mutational landscape with a large proportion of novel population-specific variants and underscores the benefit of comprehensive gene sequencing for timely WD diagnosis and family counseling, particularly in regions with prevalent consanguinity. Full article

The Ataxin-2-like (ATXN2L) protein is required to survive embryonic development, as documented in mice with the constitutive absence of the ATXN2L Lsm, LsmAD, and PAM2 domains due to knock-out (KO) of exons 5–8 with a frameshift. Its less abundant paralog, Ataxin-2 (ATXN2), has an extended N-terminus, where a polyglutamine domain is prone to expansions, mediating vulnerability to the polygenic adult motor neuron disease ALS (Amyotrophic Lateral Sclerosis) or causing the monogenic neurodegenerative processes of Spinocerebellar Ataxia Type 2 (SCA2), depending on larger mutation sizes. Here, we elucidated the physiological function of ATXN2L by deleting the LsmAD and PAM2 motifs via loxP-mediated KO of exons 10–17 with a frameshift. Crossing heterozygous floxed mice with constitutive Cre-deleter animals confirmed embryonic lethality among offspring. Crossing with CamK2a-CreERT2 mice and injecting tamoxifen for conditional deletion achieved chimeric ATXN2L absence in CamK2a-positive frontal cortex neurons and reduced spontaneous horizontal movement. Global proteome profiling of frontal cortex homogenate showed ATXN2L levels decreased to 75% and dysregulations enriched in the alternative splicing pathway. Nuclear proteins with Sm domains are critical to performing splicing; therefore, our data suggest that the Like-Sm (Lsm, LsmAD) domains in ATXN2L serve a role in splice regulation, despite their perinuclear location. Full article

Background. Whole-genome sequencing (WGS) enables comprehensive detection of genetic variants but faces limitations in benchmarking due to incomplete reference datasets. Trio-based analysis, leveraging Mendelian inheritance, provides an alternative strategy for validating sequencing results and estimating error rates, particularly in regulatory genomic regions. Methods. We extended the nf-core/sarek WGS pipeline by integrating a module that collects parental and offspring allele information, extracts regulatory genomic regions, and computes Mendelian-consistency scores. The algorithm processes variant calls from parents and children to identify expected versus anomalous inheritance patterns. The module was implemented in C++ and integrated into the Nextflow workflow, supporting automated analysis of trio datasets. Results. The method was validated on two real trio datasets, comparing DeepVariant and HaplotypeCaller as variant callers. For both trios, DeepVariant consistently achieved higher sensitivity and precision, with statistically significant differences confirmed using 95% confidence intervals. These results demonstrate that the proposed approach enables effective benchmarking of variant-calling performance in non-benchmark datasets. Conclusions. The developed method provides a practical and scalable framework for quantifying WGS outcomes from trio data. By incorporating Mendelian-inheritance validation into existing pipelines, researchers can estimate sequencing error rates, compare variant callers, and optimize workflows in regulatory genomic regions. Our findings confirm the superior performance of DeepVariant over HaplotypeCaller for the studied datasets. Full article

Hyperprolific genetic lines achieve large litters but are at increased risk of metabolic stress, impaired sow condition, and reduced piglet viability. This study aimed to evaluate whether a phase-specific feeding program from service to weaning improves sow metabolic status and body condition, and enhances offspring performance, compared with a standard program. Sixty gilts and 268 multiparous sows were randomly allocated to a control group (standard commercial diets; C) or a treatment group (phase-specific diet; T) covering early and late gestation, peripartum, and lactation. Compared to a commercial feeding strategy, four custom-made, phase-specific diets were fed as follows: for early gestation (greater amount of essential aa and fat content), late gestation (higher amount of CP and essential aa), peripartum (improved nutrient profile at lower fat and fiber content), and lactation (higher essential aa and calorie content). On gestation day 113, T gilts had greater backfat thickness (BFT) and lower blood β-hydroxybutyrate (BHBA) than C. T multiparous sows showed greater BFT and longissimus muscle depth (LMD) and lower BHBA on day 113, fewer stillborn piglets, lower incidences of neonatal diarrhea, and fewer negative lactation curves and postpartum hypophagia. On day 28 of lactation, T litters had heavier piglets, and LMD remained higher in T sows. The phase-specific feeding program improved the metabolic state, body condition, and reproductive outcomes in hyperprolific sows and enhanced offspring growth through weaning. Full article

Excessive maternal fructose intake contributes to the developmental programming of hypertension in offspring, partly via gut microbiota dysbiosis and oxidative stress. Fecal microbiota transplantation (FMT) may restore microbial balance and modulate short-chain fatty acid (SCFA) production. We investigated whether maternal FMT from healthy donors could prevent hypertension in offspring exposed to a high-fructose (HF) diet. Pregnant Sprague Dawley rats (n = 12) were fed normal chow (ND) or a 60% HF diet from mating to delivery. Cross-FMT was performed: HF dams received FMT from ND donors, and ND dams received FMT from HF donors. Male offspring (n = 8/group) were assigned to ND, HF, ND + HF-FMT, or HF + ND-FMT groups. Offspring of HF dams developed higher systolic blood pressure (+13 mmHg vs. ND, p < 0.05). Maternal FMT from ND donors reduced this elevation by ~8 mmHg (p < 0.05). Protective effects were accompanied by higher plasma butyrate, increased expression of SCFA receptors (GPR41, GPR43), reduced renal oxidative stress markers (8-OHdG), and distinct gut microbiota profiles. Maternal FMT generated four enterotypes in offspring, each associated with differential blood pressure outcomes. These findings suggest that maternal microbiota-targeted interventions, such as FMT, can mitigate hypertension of developmental origin by restoring gut microbial and metabolic homeostasis. Full article

DNA methylation holds promise for the early detection of tissue damage, making it crucial for identifying polycyclic aromatic hydrocarbon (PAH)-associated epigenetic biomarkers in childhood asthma. Sulforaphane (SFN), as a potential epigenetic modulator, can alleviate the adverse effects of environmental pollutants. This study quantified serum PAHs in 370 children via gas chromatography–mass spectrometry, assessed the methylation of target genes using bisulfite sequencing PCR (BSP), and performed mediation analysis to estimate the mediating effects of methylation levels between PAHs and childhood asthma. Murine models exposed to PAHs prenatally or postnatally, with offspring challenged with ovalbumin (OVA), were analyzed for lung DNA methylation. In vitro, HBE cells and HBSMCs treated with benzo(a)pyrene (BaP) and/or SFN were tested for inflammatory cytokines, methylation-related enzymes, and matrix metallopeptidase 9 (MMP9) modifications. The results showed total PAHs were associated with childhood asthma, with mediating effects of long interspersed nuclear element-1 (LINE-1) methylation. Prenatal PAH exposure enriched differentially methylated genes in the extracellular matrix (ECM)-receptor interaction pathway, while postnatal exposure enriched those in purine metabolism, and postnatal exposure also elevated Mmp9 expression via hypomethylation. BaP increased the expression of interferon gamma (IFN-γ), interleukin-4 (IL-4), interleukin-17A (IL-17A), transforming growth factor beta 1 (TGF-β), and ten-eleven translocation methylcytosine dioxygenases (TETs), and it upregulated MMP9 via enhancer hypomethylation and H3K27ac enrichment, while SFN reversed these effects by downregulating histone methyltransferase (HMT), leading to reduced H3K4me1 and subsequent H3K27ac depletion, thus suppressing MMP9 transcription. This study demonstrates that DNA methylation mediates PAH–childhood asthma associations, with distinct patterns in different exposure windows; MMP9 could serve as a crucial target for epigenetic modification during lung inflammation induced by PAH exposure, and SFN reverses PAH-induced epigenetic changes, aiding prevention strategies. Full article

Selenium (Se) is an essential trace element for animals and plays an important role in maintaining various physiological functions. In recent years, more and more studies have focused on the relationship between selenium and mammalian uterus health. This review comprehensively summarizes the current research progress in this field and introduces the physiological functions of selenium, including its antioxidant, anti-inflammatory, and immune regulatory functions. It also analyzed the role of selenium in uterine development, maintaining pregnancy, preventing and treating uterine diseases from multiple aspects. In addition, factors affecting animal selenium utilization and appropriate selenium supplementation strategies were also introduced. Understanding the relationship between selenium and animal uterine health is of great significance for improving animal reproductive performance, ensuring offspring health, and promoting sustainable development of the animal husbandry. Full article

Background/Objectives: Maternal vitamin supplementation (including folic acid, vitamin D, and multivitamin supplements) during pregnancy may lower the likelihood of neurodevelopmental disorders in offspring. This study examines the associations between maternal vitamin suppletion during pregnancy and morphological patterns in offsprings’ brain structure and traits of Autism Spectrum Disorder (ASD) and Attention-Deficit Hyperactivity Disorder (ADHD) in a large population-based study of child development. Methods: The study cohort included a total of 3937 children (aged 9–11) participating in the Generation R cohort in Rotterdam, the Netherlands. Maternal vitamin D and folateserum levels, multivitamin supplement use, and overall dietary quality (as assessed by the Food Frequency Questionnaire, FFQ) during pregnancy were used as predictors. T1 structural MRI scans were acquired and segmented using Freesurfer to assess brain morphometry. Cortical and subcortical brain volumes of children were separated into four independent components and used as mediators. ADHD and ASD traits, as measured by parent-completed questionnaires (Child Behavior CheckList and Social Responsiveness Scale, respectively) were used as outcome variables. Results: Results show that (1) maternal vitamin D, multivitamin supplementation, and better diet quality were associated with fewer ADHD or ASD traits in the offspring; (2) vitamin D and diet quality were associated with larger-volume childhood brain components; (3) larger-volume brain components were associated with fewer ADHD and ASD traits; (4) part of the association between dietary factors in pregnancy and offspring ADHD and ASD traits was mediated through the brain volumes of the children. Conclusions: Though all observed effect sizes were small, further population-based research should be performed to further delineate the effects of gestational multivitamin and vitamin D exposure and investigate whether this may be an avenue for preventive interventions. Full article

Background: Informal caregivers of individuals with mild cognitive impairment (MCI) experience high levels of psychological and physical stress, with limited access to supportive interventions and time constraints. Virtual Reality (VR) technologies may provide brief and accessible opportunities to support caregiver well-being, particularly during waiting periods in clinical settings. This pilot study aimed to explore the potential of a semi-immersive VR intervention to enhance psychological well-being in informal caregivers. Methods: This non-randomized pilot study investigated the effects of a semi-immersive VR-based physical training program (K-HERO^®) on psychological well-being and coping strategies in informal caregivers. Participants were recruited from January to May 2025 at the IRCCS Centro Neurolesi “Bonino-Pulejo” (Messina, Italy), and the intervention was delivered individually in a dedicated room within the rehabilitation facility, while caregivers accompanied their relatives to treatment sessions. Ten caregivers completed six sessions (30–40 min each). The study was conducted in accordance with TREND reporting guidelines. Pre- and post-intervention assessments included the State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS), COPE Inventory, Caregiver Burden Inventory (CBI), and International Physical Activity Questionnaire (IPAQ). Visual Analog Scales and instrumental data from the VR system were used to monitor physical performance and user experience. Non-parametric statistics were applied. Results: Significant reductions were observed in avoidance (p = 0.033) and social support-based (p = 0.023) coping strategies. Differences emerged based on caregiver-patient relationships: parental caregivers showed increased anxiety, while offspring caregivers showed improvements. The intervention was well tolerated, with high usability and no adverse events reported. Conclusions: A short, structured, VR-based intervention delivered during clinical waiting periods may effectively reduce maladaptive coping strategies and support emotional well-being in informal caregivers. These findings highlight the potential of brief digital interventions in real-world care contexts. Larger randomized studies are needed to validate these preliminary findings and personalize interventions to different caregiver profiles. Full article

This study aimed to evaluate the effects of dietary nano-selenium (Se-NP), nano-zinc (Zn-NP), and their combination, on the performance of Ossimi ewes and their offspring. Twenty-eight pregnant Ossimi ewes were randomly allotted to one of four equal experimental groups. The ewes were fed a basal diet with the addition of 0.3 mg selenium nanoparticles (Se-NP), 30 mg zinc (Zn-NP), or 0.3 mg Se-NP plus 30 mg Zn-NP (SZ-NP)/kg DM. The results showed that nutrient digestibility, nutritive values, milk yield, and fat corrected milk, as well as milk constituents yields, were improved (p < 0.05) for ewes fed Se-NP, Zn-NP, or SZ-NP vs. the control one. As well, lambs’ birth weight, final body weight, and average daily gain were increased (p < 0.05). Serum immunoglobulin G, total protein, albumin, globulin, and glucose values were higher (p < 0.05); however, serum cholesterol level tended to be decreased. Ewes and their respective lambs in the Se-NP, Zn-NP, or SZ-NP groups had lower (p < 0.05) urea concentrations and liver enzyme activity than the control. Thyroid hormones, total antioxidant capacity, and glutathione peroxidase activity were higher (p < 0.05) in the Se-NP-, Zn-NP-, or SZ-NP-fed groups. This improvement was accompanied by favored growth performance, immune function, and overall health in their suckling lambs, with selenium being more effective than zinc. In conclusion, the dietary inclusion of selenium, zinc nanoparticles, or their combination can be an effective strategy to enhance productivity and health in ewes and their offspring. Full article

Maternal nutrition during gestation and lactation influences offspring development and metabolic health. Lecithin, a crucial phospholipid commonly used in animal diets to improve lipid absorption and energy metabolism, is a viable approach to optimize this synergy and improve neonatal resilience. This study aimed to investigate the regulation mechanism of maternal lecithin supplementation during late gestation and lactation on the growth performance and hepatic glycolipid metabolism of offspring. Twenty-four multiparous sows were randomly allocated to receive either a control (CON) diet or a lecithin-supplemented diet (2 kg/t lecithin) on day 95 of gestation until weaning (day 21 postpartum). Blood samples were collected from sows during late gestation and on day 21 of lactation, as well as from umbilical cords and weaned piglets at 21 days. Results showed that suckling piglets from lecithin group had faster growth rate, especially during 1–7 d of suckling period. Lecithin supplement reduced the serum cholesterol of pregnant sows, while not affected it in serum of umbilical cord. In contrast, both the serum cholesterol and glucose level presented upward trend in lactating sows in the lecithin group. Accordingly, maternal lecithin supplement increased the serum glucose level, as well as the levels of hepatic lipid and glucose levels, accompanied by decreasing the hepatic levels of certain long-chain fatty acids of 21-day-old piglets compared with the CON group. Furthermore, maternal lecithin supplement activated hepatic glycolipid metabolism via regulating the mRNA level of hepatic gluconeogenesis and lipid synthesis in 21-day-old piglets. In short, this study demonstrated that maternal lecithin supplementation improved hepatic energy homeostasis in offspring by activating gluconeogenesis and optimizing lipid storage, thereby enhancing neonatal growth performance and metabolic resilience for weaning challenges. Full article

As an indigenous goat breed unique to southern China, Leizhou Black Goats (LZBGs) are highly valued for their rapid growth, high reproductive performance, and superior meat quality. However, their offspring frequently exhibit symptoms of muscle atrophy and malnutrition, suggesting potential genetic defects underlying these adverse phenotypes. As a unique extracellular matrix component, collagen Q (COLQ) is specifically enriched within the synaptic basal lamina at vertebrate neuromuscular junctions (NMJs), where it anchors acetylcholinesterase (AChE) to facilitate efficient acetylcholine hydrolysis, ensuring precise neuromuscular signaling. The current investigation sought to characterize the spectrum of genetic polymorphisms within the COLQ gene and assess their correlation with key production traits, including growth performance and meat quality parameters, in the LZBG population. Previously, through whole-genome sequencing and transcriptome sequencing analyses of an LZBG population, we identified four SNPs in the COLQ gene, namely, two missense mutations (SNP1: p.238A/S and SNP3: p.47G/S), one intronic variant (SNP2), and one synonymous mutation (SNP4: p.101P/P). Population genetic analysis revealed strong linkage disequilibrium between SNP1 and SNP2. Computational modeling of protein structures predicted that the identified missense mutations may lead to alterations in protein conformation. Association analyses demonstrated significant correlations of SNP1 and SNP3 with growth and meat quality traits (p < 0.05), where SNP3 reduced COLQ expression by 0.64-fold in homozygotes. Association analysis revealed that both SNP1 and SNP3 showed significant correlations with growth and meat quality traits in LZBGs (p < 0.05). Notably, SNP3 (p.47G/S) was found to regulate COLQ gene expression, reducing its levels by 0.64-fold in homozygous individuals, suggesting its potential as a genetic marker for selecting goats with superior growth performance and muscular development characteristics. The identified genetic variants establish a foundation for marker-assisted selection in LZBG breeding programs with particular relevance to growth performance enhancement, while also advancing the understanding of COLQ’s functional mechanisms in muscle development. Full article

Background: The potential impact of maternal SARS-CoV-2 infection during pregnancy on the neurodevelopment of offspring has raised considerable concern. Emerging studies have evaluated various developmental domains in exposed infants, yet findings remain inconsistent. Objective: To synthesize current evidence regarding neurodevelopmental outcomes in infants born to mothers with confirmed SARS-CoV-2 infection during pregnancy. Methods: We conducted a narrative review following PRISMA guidelines. A literature search was performed in PubMed, Cochrane, and ScienceDirect using keywords including “COVID-19”, “pregnancy”, “neurodevelopment”, and “SARS-CoV-2”. Nineteen studies were included. Data were extracted regarding study design, sample size, timing of exposure, age at assessment, developmental tools used, and key findings. Study quality was assessed using the Newcastle–Ottawa Scale. Results: Among 19 included studies, 12 reported at least some neurodevelopmental delays, particularly in motor and language domains. However, these delays were generally mild, domain-specific, and often not statistically significant. Seven studies, most of which were high-quality and low-risk, reported no significant differences between exposed and unexposed groups. Assessment tools and follow-up durations varied widely, limiting comparability. Conclusions: Current evidence does not support a consistent association between in utero SARS-CoV-2 exposure and an unfavorable neurodevelopmental outcome up to 24 months. However, heterogeneity in methods and short-term follow-up warrant further high-quality longitudinal research. Full article

Background: There is considerable evidence that breast feeding has a beneficial effect on the neurocognition of a child. However, most studies have confined their attention to the Intelligence Quotient (IQ), tending to ignore other aspects of neurodevelopment. Methodology: Here we present the relationship between breast feeding for at least 6 months with 373 neurocognitive outcomes measured from infancy through to late adolescence using data collected in the Avon Longitudinal Study of Parents and Children (ALSPAC). We first examined unadjusted regression associations with breast feeding at age 6 months. Where the unadjusted p-value was < 0.0001 (n = 152 outcomes), we adjusted for social and other factors. Results: This resulted in 42 outcomes with adjusted associations at p < 0.001. Specifically, these included associations with full-scale IQ at ages 8 and 15 years (adjusted mean differences [95% confidence interval (CI)] +4.11 [95% CI 2.83, 5.39] and +5.12 [95% CI 3.57, 6.67] IQ points, respectively, compared to not breastfeeding for 6 months). As well as the components of IQ, the other phenotypes that were strongly related to breast feeding for at least 6 months were measures of academic ability (reading, use of the English language and mathematics). In accordance with the literature, we show that children who are breast fed are more likely to be right-handed. The one association that has not been recorded before concerned aspects of pragmatic speech at 9 years where the children who had been breast fed were shown to perform more appropriately. Conclusions: We conclude that breast feeding for at least 6 months has beneficial effects on a number of neurocognitive outcomes that are likely to play a major part in the offspring’s future life course. We point out, however, the possibility that by using such stringent p-value criteria, other valid associations may have been ignored. Full article

Gestational complications, such as preeclampsia and gestational diabetes mellitus (GDM), pose significant risks to maternal and fetal health and increase long-term cardiovascular disease risk in offspring. This review aims to synthesize current knowledge on the roles of ferroptosis and neutrophil extracellular trap formation (NETosis)—two regulated cell death pathways—in these pregnancy-related conditions. We performed a comprehensive analysis of preclinical and clinical studies that investigate the involvement of dysregulated iron metabolism, oxidative stress, inflammation, and endothelial dysfunction mediated by ferroptosis and NETosis in gestational pathologies. Evidence indicates that disturbances in maternal iron homeostasis and enhanced formation of lipid peroxides and NETs contribute to placental dysfunction and systemic inflammation, exacerbating disease severity. Therapeutic strategies targeting these pathways are emerging but require further validation. Our review also identifies key gaps in mechanistic understanding, biomarker development, and translational research needs. We conclude that modulation of ferroptosis and NETosis offers promising avenues for improving diagnosis and treatment of pregnancy complications, though carefully designed clinical studies are essential to confirm their clinical utility and safety. Full article