Search Results (1,219)

Propylparaben (PP) is a widely used preservative in cosmetics, pharmaceuticals, and food products, and its potential toxicity to non-target aquatic invertebrates remains a concern. This study used the freshwater snail Biomphalaria glabrata as a model organism to evaluate the toxic effects of PP through acute and chronic exposures at embryonic, newly hatched, and adult stages. Acute exposure experiments showed concentration-dependent mortality and developmental inhibition, with LC₅₀ values of 36.69 mg/L (embryos, 168 h), 33.48 mg/L (newly hatched snails, 96 h), and 57.05 mg/L (adults, 72 h). Chronic exposure of adult snails to 10–49 mg/L PP for 21 days significantly reduced growth and reproductive output, and no embryo masses were observed at concentrations ≥ 25 mg/L. Histological observations revealed progressive damage to the hepatopancreas and gonads. These results demonstrate that PP induces multiple toxic effects in B. glabrata, affecting survival, growth, reproduction, and tissue structure under both acute and chronic exposure conditions. The findings provide experimental evidence for evaluating the ecological risks of paraben contamination in freshwater ecosystems. Full article

Chronic kidney disease (CKD) represents a major global health burden, with growing evidence indicating that its origins extend back to early developmental stages. This narrative review integrates epidemiological, clinical, and mechanistic experimental evidence to position inflammation as a life-course driver of kidney vulnerability rather than a late-stage consequence. Inflammation has emerged as a central mechanistic link connecting adverse prenatal and postnatal exposures to lifelong kidney vulnerability. We highlight the translational potential by identifying pathways amenable to early-life interventions that could modify disease trajectory. During fetal development, maternal nutritional status, metabolic stress, and inflammatory exposures influence nephron endowment, immune maturation, and epigenetic regulation, thereby shaping long-term CKD risk. In childhood, early immune dysregulation and low-grade inflammation contribute to disease initiation, defining critical windows for preventive and renoprotective interventions that can be implemented in at-risk populations. In adulthood and aging, persistent activation of cytokine signaling, inflammasomes, oxidative stress pathways, autophagy–mitophagy imbalance, and cellular senescence drives progressive kidney injury, further amplified by gut microbiota dysbiosis and renin–angiotensin system interactions. Emerging life-course strategies include maternal nutrition optimization, early-life risk stratification, targeted anti-inflammatory and immunomodulatory therapies, and microbiota-directed interventions tailored to developmental stage and individual risk profile. By emphasizing inflammation as a developmentally programmed and preventable process, this review underscores opportunities for early-life and transgenerational CKD prevention, translating mechanistic insights into actionable strategies for preventive medicine and public health. Full article

Background/Objectives: Preterm birth interrupts nephrogenesis during a critical developmental window, resulting in reduced nephron endowment and lifelong renal vulnerability. Evidence indicates that individuals born preterm are at increased risk for hypertension, albuminuria, and chronic kidney disease (CKD) across the life course. This review synthesizes current evidence linking prematurity with adverse renal outcomes, explores key pathophysiological mechanisms, and discusses emerging biomarkers together with therapeutic strategies. Methods: This comprehensive review integrates evidence from clinical cohort studies, population-based registries, meta-analyses and experimental models. Factors such as neonatal acute kidney injury (AKI), nephrotoxic exposures and cardiometabolic interactions were integrated to provide a life-course perspective. Results: Preterm birth leads to reduced nephron endowment, compensatory glomerular hypertrophy, and hyperfiltration, which predispose to progressive nephron loss. Postnatal factors, including neonatal AKI, inflammation, nephrotoxic medications, and later cardiometabolic stress, act as cumulative “hits”, accelerating renal injury trajectories. Clinical studies demonstrate a higher prevalence of reduced estimated glomerular filtration rate, albuminuria, elevated blood pressure, and smaller kidney volumes from childhood into adulthood. Emerging biomarkers such as cystatin C, alongside imaging-based estimates of nephron endowment, may enhance early risk stratification. Conclusions: Preterm birth represents an independent, lifelong risk factor for CKD through combined developmental and postnatal mechanisms. Structured long-term surveillance and early preventive strategies are essential to preserve renal reserve in this population. Advances in biomarker-guided monitoring and targeted interventions may enable earlier identification of high-risk individuals and support precision approaches to nephroprotection after prematurity. Full article

Achievement of optimal nutritional status within the first 1000 days of life for a child with cystic fibrosis (CF) is of paramount importance, with an emphasis on favorable early life growth trajectories that best optimize pulmonary and extrapulmonary health. The ‘first 1000 days’ framework emphasizes that environmental, sociocultural and nutritional exposures during this period can have life-long consequences for physical, cognitive, social and emotional health and development. Optimal nutrition encompasses not just physical growth, but the provision of nutrients and optimal feeding throughout the preconception, pregnancy and first 1000-day period to ensure lifelong healthy development and aging. For children with CF (cwCF), the first 1000 days is marred by a myriad of complications, exposing a unique nutritional fragility within this critical developmental window. Conversely, as life expectancy increases for people with CF (pwCF), overnutrition is becoming increasingly prevalent and the widespread uptake of disease-modifying drugs challenges clinicians to take a nuanced and personalized approach to lifelong nutritional care. This review explores early disease manifestations of CF and their impact on early life growth and nutrition in the modern era of CF. This review also considers how we might theoretically view early life nutrition in CF from a lens which takes into consideration well-known frameworks such as ‘the first 1000 days’ and ‘developmental origins of health and disease’. Full article

Background/Objectives: The attention of world science has been focused on human umbilical cord blood cell (hUCB) products for the treatment of various human diseases. The prospects for using hUCB stem from the availability of the material, non-invasive collection procedure, low immunogenicity, multipotency and non-tumorigenicity. But information about the acute toxicity, reproductive and developmental toxicity of hUCB mononuclear cells (MNCs) remains insufficient. Thus, the aim of this study is to assess the reproductive and developmental toxicity of human umbilical cord blood mononuclear cells on Wistar rats. Methods: In the fertility and early embryonic development study, human umbilical cord mononuclear blood cells (hUCB-MNCs) were administered at dose levels of 4.28 × 10⁸ cells/kg and 8.57 × 10⁸ cells/kg to male and female rats during the pre-mating, mating and gestation period. In the embryo–fetal development study, the pregnant female rats also received hUC-MNCs at doses of 4.28 × 10⁸ cells/kg and 8.57 × 10⁸ cells/kg. Results: In gestational data, including fertility rate, pregnancy rate, corpora lutea and implantation sites counts, dead and absorption fetuses’ number, body weight and craniocaudal size of fetuses, anomalies in fetal development showed no statistically significant changes in 4.28 × 10⁸ cells/kg (low dose) and 8.57 × 10⁸ cells/kg (high dose) dose groups of hUCB-MNCs to negative control group. External, visceral and skeletal examination of the fetuses in all experimental groups also showed no changes. Embryo–fetal development study in low and high groups of hUCB-MNCs application also showed no changes in the negative control group. Conclusions: This reproductive and developmental toxicity study demonstrates that human umbilical cord blood mononuclear cells (hUCB-MNCs) administered intravenously at doses up to 8.57 × 10⁸ cells/kg do not cause adverse effects on fertility, embryo–fetal development, or postnatal offspring viability in Wistar rats. The absence of reproductive toxicity is mechanistically attributable to three intrinsic properties of hUCB-MNCs: their low immunogenicity, which prevents maternal immune activation; the protective function of the intact placental barrier; and their transient, paracrine-dominant mode of action, which limits exposure duration. Full article

Background: Di(2-ethylhexyl) phthalate (DEHP) is a high-production-volume plasticizer and ubiquitous environ-mental contaminant with established endocrine-disrupting potential. While zebrafish transcriptomic studies have typically used high concentrations and long exposure windows, less is known about genome-wide responses during late embryogenesis/early larval maturation under environmentally relevant exposures. Here we profiled whole-organism transcriptomic responses to a short DEHP exposure during a developmentally sensitive transition (96–120) hours post-fertilization, hpf) and interpreted responses using differential expression, enrichment analyses, and endocrine-focused protein–protein interaction (PPI) network modeling. Methods: Wild-type AB zebrafish lar-vae (96 hpf) were exposed to DEHP at [10⁻⁹ M] or solvent control for 24 h. Larvae were pooled per replicate (25 lar-vae/pool) and processed for poly(A)-selected RNA-seq. Reads were quality-controlled, aligned to the Danio rerio reference genome, and quantified at gene- level. Differential expression was performed using DESeq2. Functional enrichment used KEGG over-representation analysis (ORA) and gene set enrichment analysis (GSEA). Zebrafish genes were mapped to human orthologs for GO/KEGG and STRING-based endocrine subnetworks, which were visualized and interrogated using STRINGdb and visNetwork. Results: Low-dose, short-term exposure does not produce large gene-level effects but induces coordinated, pathway-level transcriptional remodeling. KEGG ORA showed significant enrichment of MAPK signaling and regulation of actin cytoskeleton with additional enrichment of axon guidance and neuroactive ligand–receptor interaction. GSEA detected coordinated downregulation of KEGG neurodegeneration collections with negative normalized enrichment scores reflecting shared gene sets re-lated to mitochondrial function, proteostasis, cytoskeletal organization, and stress-response pathways. Endo-crine-focused STRING subnetworks indicated consistent downregulation of CYP19A1 within estrogen metabo-lism/biosynthesis modules and downregulation of upstream androgen biosynthetic enzymes HSD3B2 and CYP17A1, alongside upregulation of HSD17B3 and proteostasis-associated factors including DNAJA1. Endocrine network to-pology highlighted regulatory and cofactor nodes affecting receptor-linked transcription, consistent with indirect endocrine modulation rather than large receptor-transcript changes. Conclusions: In summary, this study demon-strates that exposure to low-dose DEHP during a critical period of zebrafish embryonic development is associated with modest but coordinated transcriptomic changes across multiple biological pathways. Pathway enrichment and network-based analyses highlight estrogen- and androgen-associated processes, along with broader signaling, met-abolic, and structural pathways, as transcriptionally responsive during this window. Importantly, these findings reflect molecular-level associations rather than direct evidence of functional or physiological endocrine disruption. Instead, they identify candidate pathways and regulatory networks that may be sensitive to low-level environmen-tal exposure and warrant further investigation. Collectively, this work underscores the value of systems-level tran-scriptomic approaches for detecting subtle, pathway-wide responses to environmentally relevant exposures during development. Full article

Crohn’s disease (CD) is a chronic inflammatory disorder arising from the convergence of genetic susceptibility, immune dysregulation, environmental exposures, and perturbations of the gut microbiome. This review advances a developmental and compartment-aware framework for interpreting dysbiosis in CD, integrating spatial heterogeneity, transmural pathology, and mesenteric interactions. By synthesizing evidence on microbial composition, functional metabolism, and host-immune crosstalk, we describe a dysbiotic profile shaped by disease location, inflammatory activity, and therapeutic exposure, while also considering the emerging roles of non-bacterial members. We propose that microbiome alterations in CD reflect inflammation-driven ecosystem instability rather than a static taxonomic imbalance. Moving beyond descriptive compositional profiling toward a dynamic ecological model that incorporates disease trajectory and anatomical compartmentalization is essential to refine disease stratification and guide future microbiome-informed precision therapies. Full article

Introduction: Pediatric Functional Gastrointestinal Disorders (FGIDs), including infantile colic and constipation, may persist into later childhood and adulthood, sometimes manifesting as functional abdominal pain (FAP). Early exposure to probiotics during critical developmental windows may influence long-term susceptibility to disease. Background/Objectives: Building on our original randomized controlled trial, which demonstrated that Lactobacillus reuteri DSM 17938 reduced acute infantile FGID symptoms, a 10-year follow-up study was performed to evaluate whether this early intervention provided lasting protection against FAP in childhood. Methods: Two hundred participants from the original RCT cohort completed follow-up assessments at age ten. The primary outcome was the presence of FAP, analyzed according to the original randomization group (probiotic vs placebo). FAP was diagnosed at age 10 using the Rome IV criteria, based on a standardized clinical assessment by a pediatric gastroenterologist who was blinded to the original allocation. Results: FAP was diagnosed in 13/99 (13.1%) children in the probiotic group and 81/101 (80.2%) in the placebo group, corresponding to an absolute risk reduction of 67.1% (95% CI 56.8–77.3) and a relative risk of 0.16 (95% CI 0.10–0.27) (p < 0.001). Conclusions: Early supplementation with L. reuteri DSM 17938 was associated with a markedly lower prevalence of FAP at age 10. However, the long-term follow-up was observational and characterized by a 57.2% attrition rate. In addition, longitudinal data on potential confounders were unavailable; therefore, the findings should be interpreted as an association rather than proof of causality. Full article

Within the Developmental Origins of Health and Disease (DOHaD) framework, breast-feeding is a modifiable early postnatal exposure, but its long-term associations are difficult to separate from socioeconomic and family context. We conducted a structured literature search (PubMed/MEDLINE and Scopus; January 2015–December 2025) and prioritised large prospective/birth cohorts and genetic epidemiology studies reporting quantitative associations between breastfeeding in infancy (ever versus never, duration and, where available, exclusivity) and adult outcomes. Eighteen key primary studies were included in evidence tables across cardiometabolic, cancer, and neurocognitive domains. Overall, breastfeeding was associated with modestly lower all-cause and cardiovascular mortality, small reductions in cardiovascular disease and type 2 diabetes, and slightly more favour-able cardiometabolic profiles, including lower adiposity and higher HDL cholesterol. Where reported, effect sizes were generally small (e.g., hazard ratios typically close to 1.00), indicating limited clinical impact at the individual level but potential population relevance. Genetic analyses provide cautious support for a protective association with coronary outcomes, although lipid-mediated pathways appear to explain only a small proportion of the observed associations. Evidence for adult cancer outcomes remains mixed and largely inconclusive, while longer breastfeeding is associated with small ad-vantages in cognitive performance, educational attainment and selected psychological outcomes. Taken together, current evidence suggests that breastfeeding is associated with modestly more favourable adult cardiometabolic and neurobehavioural profiles, but its contribution to long-term health is small relative to the influence of later-life lifestyle and clinical risk factors and should therefore be interpreted cautiously. Full article

Since children spend a significant portion of their developmental years in educational settings, the environmental quality of these institutions—specifically, the extent to which they expose their occupants to green space and heat stress—is a critical determinant of well-being and academic performance. This study assesses the green environmental quality of 121 educational institutions (kindergartens, and elementary and secondary schools) in Debrecen, Hungary. The main objective of the research is to identify educational institutions that require immediate intervention to address their lack of green spaces, improve the green environment, and mitigate the urban heat island (UHI) effect. A further aim of the study is to understand how different urban planning practices over the past century have led to the current situation. Therefore, we utilized high-resolution geospatial data (specifically, WorldView-2 imagery) to classify schoolyard vegetation; Landsat data to derive Land Surface Temperature (LST); and the Hoover index to quantify institutions’ spatial concentration. We developed a composite indicator to categorize green environmental quality and heat stress exposure. Our results reveal deep spatial and institutional inequalities. 47.5% of students attend institutions with low environmental quality. While kindergartens typically offer green-rich environments, secondary schools with significant student populations—which are primarily concentrated in the dense historical downtown—are trapped in “grey” zones possessing poor environmental quality. Furthermore, we identify a “green paradox” in socialist housing estates: despite abundant surrounding greenery, schools here record high LST values due to the heat-trapping morphology of vertical concrete structures. The study also highlights institutional maladaptation, such as converting schoolyards into parking lots and using rubber pavements for safety reasons, which contributes to the deterioration of environmental quality. We conclude that current urban planning and school architecture must shift paradigms, treating schoolyards as integral components of the public green infrastructure network through climate-adaptive design. In addition, stakeholders should develop the green environment of educational institutions comprehensively, taking into account both on-site and surrounding green spaces. Full article

Laser radiation constitutes a promising technological advancement within the integrated weed management toolbox but is hindered by low energy use efficiency. This study investigated the efficiency of a pulsed blue diode laser for controlling small weed seedlings and seeds under controlled conditions. Dose–response experiments were conducted on three grasses (Poa annua, Echinochloa crus-galli, Digitaria sanguinalis) and three dicotyledonous species (Solanum nigrum, Chenopodium album, Senecio vulgaris). For seedlings, the effects of species, growth stage (cotyledon, 2-leaf), and leaf wetness (dry, wet) were tested. For seeds, burial depth (0 mm, 2 mm) and imbibition status (non-imbibed, imbibed) were examined. Biological efficiency was assessed through plant survival, aboveground dry biomass, leaf area, and seed viability. Laser application caused significant, dose-dependent reductions in biomass accumulation and plant survival, with up to 100% mortality. Seedlings were most sensitive at the cotyledon stage and when foliage was dry, requiring up to 68 and 52% lower energy doses compared to older or wet targets, respectively. Species-specific responses were observed, with dicotyledonous species generally requiring 80 to 99% lower energy doses than grasses. Laser exposure was also effective in reducing the viability of non-imbibed, surface-exposed seeds, requiring up to 64 and 99% lower energy doses than imbibed or buried seeds, respectively. These results confirm that laser efficiency is strongly influenced by species traits, developmental stage, surface moisture, and seed water status. Optimising and tailoring laser parameters to these factors enhances weed control efficacy while maximising energy efficiency, improving the performance and sustainability of laser-based weeding. Full article

Background: Idiopathic developmental intellectual disability (IDID) is a neurodevelopmental disorder that leads to poor health status. This study analyzes the burden of IDID attributed to lead (Pb) exposure in the United States of America (USA) from 1990 to 2023 and projects trends through 2050. Methods: Measurements on Disability-adjusted life years (DALYs) and Years lived with disability (YLDs) were downloaded from the Institute for Health Metrics and Evaluation (IHME). A joinpoint regression model was employed to assess the epidemiological change in this disease. The age–period–cohort (APC) model was used to examine the age, period, and birth cohort effects on DALYs. Decomposition analysis was applied to analyze the role of population, aging, and epidemiological factors in driving changes to DALYs. Bayesian age–period–cohort (BAPC) analysis was conducted to forecast sex-specific burden trends through 2050. Results: From 1990 to 2023, DALYs and age-standardized DALY rate (ASDR) showed an overall decreasing trend. Males bore a higher disease burden than females. In the USA, the average annual percentage change (AAPC) in ASDR was −1.41 (95% CI: −1.45 to −1.37), indicating an overall decline. BAPC analysis predicted that the ASDR will continue to decline for both females and males through 2050, with males showing a faster decline. Conclusions: Consistent efforts have led to significant progress in reducing lead exposure-related IDID in the USA. Prevention strategies focus on continuing to reduce lead exposure and minimize its impact on IDID. Full article

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that remain widely detectable in the environment and human tissues decades after their ban, raising concerns for brain health. Both dioxin-like (DL) and non-dioxin-like (NDL) congeners interfere with neuronal function through partially distinct pathways, including aryl hydrocarbon receptor activation, disruption of calcium and dopaminergic signaling, oxidative stress, and epigenetic remodeling. Experimental and epidemiological studies indicate that developmental PCB exposure is associated with impaired cognition, attention, motor function, and increased risk of neurodevelopmental disorders. Furthermore, chronic exposure in adulthood has been linked to neurodegenerative diseases. At the cellular level, NDL-PCBs sensitize ryanodine receptors, alter dendritic and axonal growth, promote mitochondrial dysfunction, generate reactive oxygen and nitrogen species, and compromise blood–brain barrier integrity, thereby fostering neuroinflammation, synaptic dysfunction, and neuronal loss. This review synthesizes current evidence on the molecular and cellular mechanismtable s underlying PCB-induced neurotoxicity across the lifespan, highlighting oxidative stress as a central factor, integrating calcium dysregulation, neurotransmitter imbalance, and apoptotic and epigenetic pathways. Finally, potential neuroprotective roles of antioxidant strategies are discussed, emphasizing their relevance for mitigating PCB-related neurodevelopmental and neurodegenerative risk. Full article

Antibiotic-induced dysbiosis has been increasingly implicated in a range of pediatric outcomes, yet the concept remains variably defined and often inconsistently applied. The purpose of this review is to provide an overview and critical evaluation of the available data regarding the effects of early-life exposure to β-lactam antibiotics on the developing microbiome. We conducted a narrative review of experimental and epidemiological studies examining β-lactam exposure during pregnancy, the perinatal period, and early childhood was conducted. β-lactams induce reproducible alterations in microbial composition, diversity, and metabolic function, including decreases in Bifidobacterium and Lactobacillus and a relative increase in Enterobacteriaceae and other facultative anaerobes, especially in early life. Reduced microbial diversity and changed short-chain fatty acid-producing taxa often accompany these compositional changes. However, associations with immune, metabolic, and neurodevelopmental outcomes are heterogeneous and frequently confounded by indication host-related factors. Evidence for causality in humans remains limited despite strong mechanistic support from animal models. Current data support cautious interpretation, even though β-lactam-associated microbiome perturbations may contribute to disease susceptibility during vulnerable developmental windows. While mechanistic and longitudinal evidence continues to develop, antibiotic stewardship focused on appropriate indication and duration is still crucial. Full article

A wealth of research in neuroscience and developmental psychology has documented the lasting detrimental effects of adverse early-life experiences on health and psychological well-being. To investigate these effects, researchers have developed self- and informant-report questionnaires, interview-based instruments, and experimental paradigms designed to assess exposure to early adversity, model its consequences under controlled laboratory conditions, and investigate the neurobiological mechanisms involved. In contrast, the role of positive early-life experiences in biobehavioral trajectories and adaptive functioning has received comparatively less empirical and theoretical attention. The existing work has largely conceptualized positive experiences in terms of their protective or buffering effects in the context of adversity, and/or their promotive role and independent contribution to physical and psychological well-being. Against this background, this narrative review comprehensively synthesizes (i) current definitions of positive early-life experiences, (ii) tools for their retrospective assessment, and (iii) experimental approaches aimed at manipulating and promoting such experiences in humans. Furthermore, this review advances time-sensitive and individual-centered attention for the study of positive early-life experiences, in which health- and well-being-promoting interventions are informed by an expanding understanding of normative human neuroplasticity as a heterosynchronous process and by dynamic, interdependent interactions operating across individual, family, and societal levels. Full article