Search Results (1,108)

Triphenyl phosphate (TPhP) is a widely used organophosphate flame retardant and plasticizer, raising concerns over its health impacts. This study examined the effects of embryonic TPhP exposure on axial skeletal development and metabolism in medaka (Oryzias latipes), a vertebrate fish model relevant to human bone biology. Medaka embryos were exposed to 1 µM TPhP and assessed through early larval stages. TPhP impaired vertebral ossification, causing shortened centra and reduced cartilage in the caudal complex, alongside disrupted distribution of osteoblast-lineage cells. Key osteogenic genes were significantly downregulated at 14 days post fertilization, and transcriptomic analysis revealed altered mitochondrial pathways linked to skeletal disorders. Functionally, TPhP-exposed larvae showed reduced caudal fin regeneration and decreased metabolic rate and oxygen consumption, consistent with mitochondrial dysfunction. These findings indicate that TPhP disrupts bone development and metabolism by affecting osteoblast differentiation and mitochondrial regulation, highlighting the value of small fish models for studying environmental toxicants and bone metabolic disease risk. Full article

This review examines the regulatory role of m6A methylation modification in embryo implantation, focusing specifically on its impact on uterine receptivity and decidualization. It offers a comprehensive examination of the essential theoretical research on m6A methylation, clarifying its molecular mechanisms and roles in uterine receptivity and decidualization. Furthermore, this review examined the effects of m6A methylation on endometrial-related diseases and early embryonic development. It synthesizes early findings and recent advancements in m6A methylation studies. Through a comprehensive analysis of relevant studies, this review offers novel insights into the molecular mechanisms underlying embryo implantation and suggests potential strategies for assisted reproductive technologies and the treatment of related disorders, thereby serving as a comprehensive reference for future research in this domain. Full article

The epigenetic landscape plays a pivotal role in regulating the functions of both germ and somatic cells (Sertoli and Leydig cells) within the testis, which are essential for male fertility. While somatic cells support germ cell maturation and testosterone synthesis, the epigenetic regulation of germ cells is critical for proper spermatogenesis and function. Epigenetic modifications such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs (ncRNAs) are crucial for regulating gene expression that is essential for spermatogenesis and reproductive function. Although numerous studies have highlighted the significance of the epigenome and its implications for male reproductive health, a comprehensive overview of the existing literature and knowledge is lacking. This review aims to provide an in-depth analysis of the role of epigenetics in spermatogenesis and reproductive health, with a specific focus on DNA methylation, histone remodeling, and small noncoding RNAs (sncRNAs). Additionally, we examine the impact of lifestyle and environmental factors, such as diet, smoking, physical activity, and exposure to endocrine-disrupting chemicals, on the sperm epigenome. We emphasize how these factors influence fertility, embryonic development, and potential transgenerational inheritance. This review underscores how recent advances in the understanding of the epigenetic modulation of testicular function can inform the pathophysiology of male infertility, thereby paving the way for the development of targeted diagnostic and therapeutic strategies. Full article

Background: Often, neoadjuvant therapy, which relies on the induction of double-strand breaks (DSBs), is used prior to surgery to shrink tumors by inducing cancer cell apoptosis. However, recent studies have suggested that this treatment may also induce a fluctuating state between senescence and stemness in PA-1 embryonal carcinoma cells, potentially affecting therapeutic outcomes. Thus, the respective epigenetic pathways are up or downregulated over a time period of days. These fluctuations go hand in hand with changes in spatial DNA organization. Methods: By means of Single-Molecule Localization Microscopy in combination with mathematical evaluation tools for pointillist data sets, we investigated the organization of euchromatin and heterochromatin at the nanoscale on the third and fifth day after etoposide treatment. Results: Using fluorescently labeled antibodies against H3K9me3 (heterochromatin tri-methylation sites) and H3K4me3 (euchromatin tri-methylation sites), we found that the induction of DSBs led to the de-condensation of heterochromatin and compaction of euchromatin, with a peak effect on day 3 after the treatment. On day 3, we also observed the co-localization of euchromatin and heterochromatin, which have marks that usually occur in exclusive low-overlapping network-like compartments. The evaluation of the SMLM data using topological tools (persistent homology and persistent imaging) and principal component analysis, as well as the confocal microscopy analysis of H3K9me3- and H3K4me3-stained PA-1 cells, supported the findings that distinct shifts in euchromatin and heterochromatin organization took place in a subpopulation of these cells during the days after the treatment. Furthermore, by means of flow cytometry, it was shown that the rearrangements in chromatin organization coincided with the simultaneous upregulation of the stemness promotors OCT4A and SOX2 and senescence promotors p21Cip1 and p27. Conclusions: Our findings suggest potential applications to improve cancer therapy by inhibiting chromatin remodeling and preventing therapy-induced senescence. Full article

Skeletal muscle regeneration requires a reliable source of myogenic progenitor cells capable of forming new fibers and creating a self-renewing satellite cell pool. Human induced pluripotent stem cell (hiPSC)-derived teratomas have emerged as a novel in vivo platform for generating skeletal myogenic progenitors, although in vivo studies to date have provided only an early single-time-point snapshot. In this study, we isolated a specific population of CD82⁺ ERBB3⁺ NGFR⁺ cells from human iPSC-derived teratomas and verified their long-term in vivo regenerative capacity following transplantation into NSG-mdx^4Cv mice. Transplanted cells engrafted, expanded, and generated human Dystrophin⁺ muscle fibers that increased in size over time and persisted stably long-term. A dynamic population of PAX7⁺ human satellite cells was established, initially expanding post-transplantation and declining moderately between 4 and 8 months as fibers matured. MyHC isoform analysis revealed a time-based shift from embryonic to neonatal and slow fiber types, indicating a slow progressive maturation of the graft. We further show that these progenitors can be cryopreserved and maintain their engraftment potential. Together, these findings give insight into the evolution of teratoma-derived human myogenic stem cell grafts, and highlight the long-term regenerative potential of teratoma-derived human skeletal myogenic progenitors. Full article

Our previous research identified 12 small Cajal body-specific RNAs (scaRNAs) with reduced expression in the right ventricle in infant patients with tetralogy of Fallot. Likewise, we showed that there were significant changes in mRNA processing in the RV in these patients. ScaRNAs play a crucial role in the biochemical maturation of spliceosomal RNAs (pseudouridylation and 2′-O-methylation). We showed that variations in scaRNA1 levels resulted in changes in alternative splicing in human cells. To investigate further the role that scaRNAs play in mRNA processing, we examine here the impact of knocking down scaRNA1 in quail myoblast cells (Coturnix japonica, a well-established animal model for studying embryonic development). Following the knockdown of scaRNA1, transcriptome analysis revealed that the genes Tjp1, Map3k7, and Sppl2a were alternatively spliced. Growing evidence indicates that alternative splicing of mRNA plays an important role in regulating cell differentiation and tissue development. Our data presented here provide additional support for research to clarify the specific roles that individual scaRNAs play in regulating spliceosome function and mRNA splicing. Full article

Plant flowers are recognized as a rich source of bioactive phenolic compounds. In this study, for the first time, the recovery of antioxidant phenolic compounds from Cytisus striatus flowers (CF) was optimized using microwave-assisted extraction (MAE). The variables (% of ethanol, temperature, and time) were studied using a response surface methodology (RSM). Extraction efficiency was assessed by total phenol content, total flavonoid content, and the antioxidant capacity through DPPH, ABTS, FRAP, and CUPRAC assays. Additionally, cytotoxicity and anti-inflammatory properties were evaluated in different cell lines. The optimal extraction conditions (87.6% ethanol, 160.8 °C and 8.76 min) yielded extracts rich in phenolics (85.9 mg GAE/g CF) and flavonoids (120.3 mg RE/g CF), with strong antioxidant capacity. LC-MS/MS analysis identified 27 phenolic compounds, including chrysin, apigenin, and quercetin derivatives. Cytotoxicity tests showed that CF extract maintained high viability (>80%) in human embryonic kidney (HEK293T) and human lung adenocarcinoma (A549) cells up to 2000 µg/mL, indicating low cytotoxicity. The anti-inflammatory potential was evidenced by a decrease in IL-1β levels and an increase in IL-10 cytokine production in LPS-stimulated macrophages. These results highlight the great potential of CF as a promising bioresource to obtain value-added compounds for the development of functional foods, nutraceuticals, and cosmetic products. Full article

Epigenetic regulation, particularly DNA methylation, plays a crucial role in embryonic development by controlling gene expression patterns. The disruption of this regulation by environmental factors can have long-lasting consequences. Opioid drugs, such as morphine, are known to cross the placental barrier and affect the developing central nervous system, yet their precise epigenetic effects during early development remain unclear. This study aimed to elucidate the impact of chronic morphine exposure on the DNA methylation landscape and gene expression in mouse embryonic stem cells (mESCs). mESCs were chronically exposed to morphine (10 μM for 24 h). Genome-wide bisulfite sequencing was performed to identify DNA methylation changes, while RNA sequencing (RNA-Seq) assessed corresponding gene expression alterations. Global levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) were quantified using mass spectrometry. Morphine exposure induced global DNA hypomethylation and identified 16,808 differentially methylated genes (DMGs) related to development, cell signalling, metabolism, and transcriptional regulation. Integrative transcriptomic analysis with RNA-Seq data revealed 651 overlapping genes, including alterations in key epigenetic regulators involved on DNA methylation machinery. Specifically, Tet1 was upregulated with promoter hypomethylation, while Dnmt1 was downregulated, without changes in promoter methylation after morphine exposiure. Mass spectrometry results confirmed a global decrease in 5mC levels alongside increased 5hmC, indicating the involvement of both passive and active demethylation pathways. These findings demonstrate for the first time that morphine disrupts the epigenetic homeostasis of mESCs by promoting global and gene-specific DNA demethylation, which might be key to the phenotypic changes that occur in adulthood. This work provides novel mechanistic insights into how opioid exposure during early development may lead to persistent epigenetic alterations, with potential long-term implications for neurodevelopment and disease susceptibility. Full article

Grass carp is an economically important cultured species in China. Triploid embryo production is widely applied in aquaculture to achieve reproductive sterility, improve somatic growth, and reduce ecological risks associated with uncontrolled breeding. In this study, a simple cold shock method for inducing triploid grass carp was developed. The triploid induction rate of 71.73 ± 5.00% was achieved by applying a cold treatment at 4 °C for 12 min, starting 2 min after artificial fertilization. Flow cytometry and karyotype analysis revealed that triploid individuals exhibited a 1.5-fold increase in DNA content compared to diploid counterparts, with a chromosomal composition of 3n = 72 (33m + 36sm + 3st). Additionally, embryonic transcriptome analysis demonstrated that, in the cold shock-induced embryos, genes associated with abnormal mesoderm and dorsal–ventral axis formation, zygotic genome activation (ZGA), and anti-apoptosis were downregulated, whereas pro-apoptotic genes were upregulated, which may contribute to the higher abnormal mortality observed during embryonic development. Overall, this study demonstrates optimized conditions for inducing triploidy in grass carp via cold shock and provides insights into the transcriptomic changes that take place in cold shock-induced embryos, which could inform future grass carp genetic breeding programs. Full article

Zebrafish are model organisms for drug screening owing to their transparent bodies, rapid embryonic development, and genetic similarities with humans. However, using standard polystyrene culture plates can limit the oxygen supply, potentially affecting embryo survival and the reliability of assays conducted in zebrafish. In this study, we evaluated the application of a novel, highly oxygen-permeable culture plate (InnoCell^TM) in zebrafish development and drug screening assays. Under both normal and oxygen-restricted conditions, zebrafish embryos cultured on InnoCell^TM plates exhibited significantly improved developmental parameters, including heart rate and body length, compared with those cultured on conventional polystyrene plates. The InnoCell^TM plate enabled a significant reduction in medium volume without compromising zebrafish embryo viability, thereby demonstrating its advantages, particularly in high-throughput 384-well formats. Drug screening tests using antiangiogenic receptor tyrosine kinase inhibitors (TKIs) revealed enhanced sensitivity and more pronounced biological effects in InnoCell^TM plates, as evidenced by the quantification of intersegmental blood vessels and gene expression analysis of the vascular endothelial growth factor receptor (vegfr, also known as kdrl). These results indicate that the InnoCell^TM highly oxygen-permeable plate markedly improves zebrafish-based drug screening efficiency and assay reliability, highlighting its potential for widespread application in biomedical research. Full article

Bovine serum albumin (BSA), the most commonly used protein in preimplantation embryo culture media, performs a variety of physiological functions. However, its involvement in long-term effects remains largely unclear. To investigate its physiological importance in culture media, we examined the developmental and metabolic consequences of BSA deprivation during preimplantation stages in mice. Embryos cultured in BSA-free media during specific time windows exhibited impaired blastocyst formation, with continuous deprivation from the two-pronuclei (2PN) stage significantly reducing trophectoderm (TE) and inner cell mass (ICM) cell numbers (p < 0.05), indicating compromised viability. Short-term BSA deprivation similarly disrupted lineage allocation, underscoring the sensitivity of early embryos to nutrient availability during cell fate determination. Although birth rates remained unaffected, suggesting compensatory mechanisms, longitudinal analysis revealed sex-specific metabolic dysfunction. Male offspring developed progressive glucose intolerance by 16 weeks, exhibiting elevated fasting glucose levels (p < 0.05) and impaired glucose clearance, whereas females showed no significant alterations in glucose metabolism. This study demonstrates that protein restriction during the preimplantation period not only disrupts early embryonic development but also programs long-term metabolic dysfunction, underscoring the importance of optimizing culture conditions in assisted reproductive technologies to minimize future health risks. Full article

One of the goals of Agenda 2030 is to increase the share of renewable energy in the global energy mix. In this context, photovoltaic systems play a key role in the transition to clean energy. According to the International Energy Agency, in 2023, solar photovoltaic alone accounted for three-quarters of renewable capacity additions worldwide. Designing a performing photovoltaic system requires careful planning that takes into account various factors, both internal and external, in order to maximize energy production and optimize costs. In addition to the technical characteristics of the system (internal factors), the positions and the shapes of external buildings and surrounding obstacles (external factors) have a significant impact on the output of photovoltaic systems. However, given the complexity of these environmental factors, they cannot be treated accurately in manual design practice. For this reason, this paper proposes a Building Information Modeling-based workflow for the design of a photovoltaic system that can guide the professional step-by-step throughout the design process, starting from the embryonic phase to the definitive, and therefore more detailed, one. The developed methodology allows for an in-depth analysis of the shading, the photovoltaic potential of the building, the performance of the photovoltaic system, and the costs for its construction in order to evaluate the appropriateness of the investment. The main aim of the paper is to create a standardized procedure applicable on a large scale for photovoltaic integration within Building Information Modeling workflows. The methodology is tested on two case studies, characterized by different architectural features and geographical positions. Full article

Background: Prematurely born newborns with low birth weight constitute a group of patients who require special care from the first days of life. Prematurity and low birth weight affect about 13.4 million infants. Risk factors include placental disorders but also factors related to the mother, such as smoking, alcohol drinking, drug use, malnutrition, or certain diseases. It is imperative to educate women of reproductive age (15–49) about the basic factors influencing embryonic development, such as oral health, diet, medicine intake, and harmful habits. Even though most women are aware of the negative impact of harmful habits on the fetus, still too little attention is paid to oral health in pregnant women. Poor oral health may influence the well-being of the future mother, as well as of the child. Therefore, women of reproductive age and those who are pregnant must have adequate knowledge on this subject. The aim of this study was to assess the knowledge of Polish women of reproductive age (15–49) regarding oral health during pregnancy, including the impact of dental treatment, oral hygiene, and maternal oral conditions on pregnancy outcomes and the health of the newborn. Materials and Methods: This was a cross-sectional study of 508 women, in the reproductive age, whose age ranged from 18 to 49 years old. The surveys were conducted from April 2020 to November 2020. The questionnaire was originally developed based on the available literature and consisted of seven sections: basic information, general health and habits, pregnancy status and dental care, knowledge of treatment options during pregnancy, oral health status and its association with the risk of preterm birth, prematurity and the child’s oral health, and breastfeeding and oral development. Results: After excluding incomplete questionnaires, a total of 499 questionnaires were included in the analysis. Women participating in the study had a fairly good understanding of the impact of oral health on the fetus and the role of breastfeeding in the development of the stomatognathic system (from 50% to 70% correct answers). However, even though most respondents had completed higher education (344/68.94%), their knowledge of oral health, preterm birth, and low birth weight was very limited (including the impact of inflammation on the intrauterine development of the child or bacteria and transfer across the placenta). In these sections, the percentage of correct answers ranged from less than 20% to 50%. When analyzing knowledge by age, education, number of births, and place of residence, the highest levels of knowledge were observed among respondents with higher education, particularly those aged 27–32. Conclusions: Respondents had a fairly good understanding of the general impact of oral health during pregnancy and recognition of the importance of breastfeeding for infants. However, their knowledge about the impact of bacteria and inflammation in the mother’s oral cavity on prematurity and low birth weight was limited. Therefore, educating women of reproductive age and pregnant women on this topic is essential, as it may help reduce the adverse consequences of prematurity. Full article

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, comprises embryonal (ERMS) and alveolar (ARMS) subtypes with distinct histopathological features, clinical outcomes, and therapeutic responses. To better characterize their molecular distinctions, we performed untargeted plasma proteomics and metabolomics profiling in children with ERMS (n = 18), ARMS (n = 17), and matched healthy controls (n = 18). Differential expression, functional enrichment (GO, KEGG, RaMP-DB), co-expression network analysis (WGCNA/WMCNA), and multi-omics integration (DIABLO, MOFA) revealed distinct molecular signatures for each subtype. ARMS displayed elevated oncogenic and stemness-associated proteins (e.g., cyclin E1, FAP, myotrophin) and metabolites involved in lipid transport, fatty acid metabolism, and polyamine biosynthesis. In contrast, ERMS was enriched in immune-related and myogenic proteins (e.g., myosin-9, SAA2, S100A11) and metabolites linked to glutamate/glycine metabolism and redox homeostasis. Pathway analyses highlighted subtype-specific activation of PI3K-Akt and Hippo signaling in ARMS and immune and coagulation pathways in ERMS. Additionally, the proteomics and metabolomics datasets showed association with clinical parameters, including disease stage, lymph node involvement, and age, demonstrating clear molecular discrimination consistent with clinical observation. Co-expression networks and integrative analyses further reinforced these distinctions, uncovering coordinated protein–metabolite modules. Our findings reveal novel, subtype-specific molecular programs in RMS and propose candidate biomarkers and pathways that may guide precision diagnostics and therapeutic targeting in pediatric sarcomas. Full article

Seed vigor testing traditionally requires large sample sizes and extended durations. The biospeckle laser (BSL) technique offers a faster, image-based alternative for seed analysis though the standardization of set protocols. This study evaluated the efficiency of local and global BSL analyses in bean seeds (Phaseolus vulgaris L.). Two groups of seeds (872 in total) were classified into high- and low-vigor seeds using the emergence test over 800 samples. The BSL test was then applied to 72 seeds (36 per group), analyzing biological activity locally (vascular and embryonic areas) and globally (whole image). BSL analysis detected significant differences between the groups (p < 0.05). Among the methods, the local analysis of the embryonic axis was most effective (F = 44.252, p = 0.000), showing a clearer distinction than the global analysis (F = 19.484, p = 0.000). The vascular area analysis did not yield significant results. These findings highlight the efficiency of the local BSL analysis at the embryonic axis for vigor tests compared to the global analysis. However, it was observed that the selected point in the local analysis affects the reliability of the vigor test. It was a relevant step toward standardization demanding additional tests in other species and varieties. Full article