Search Results (2,038)

Background: Pregnancy after solid organ transplantation carries increased maternal and fetal risks, compounded by the teratogenicity, nephrotoxicity, and metabolic effects of available immunosuppressive agents. Belatacept, a calcineurin inhibitor-sparing T-cell costimulation blocker with favorable renal and metabolic profiles, has emerged as an alternative; however, evidence regarding its safety during pregnancy remains scarce. Methods: A scoping review was conducted per PRISMA-ScR recommendations. PubMed, Google Scholar, Web of Science, Scopus, and the Cochrane Library were searched (January 2015–March 2025), supplemented by citation searching, for studies reporting pregnancy outcomes in solid organ transplant recipients receiving belatacept. Methodological quality was assessed using Joanna Briggs Institute critical appraisal tools. Results: Three studies (one case series and two case reports) encompassing 21 pregnancies among 15 recipients were included, predominantly in kidney transplant recipients; several recipients contributed more than one pregnancy, so pregnancy-level outcomes are not statistically independent. Sixteen pregnancies resulted in live birth and five ended in miscarriage, at least four of which occurred in pregnancies with periconception mycophenolate exposure. No congenital malformations were reported among live-born infants, although the number of exposures is far too small to characterize teratogenic risk. Stable allograft function was reported in 14 of 19 pregnancies with available follow-up, with no rejection episodes during belatacept exposure. Maternal complications included preeclampsia (8 of 16 in the case series), gestational diabetes, cytomegalovirus reactivation, and acute kidney injury. Low birth weight (<2500 g) was reported in all live births, predominantly in the context of preterm delivery. Conclusions: The published cases have not identified congenital malformations to date, but the number of documented exposures is far too small to characterize teratogenic risk, and the overall certainty of evidence is very low. Because no comparative studies were available, maternal and neonatal outcomes cannot be assumed equivalent to those of conventional immunosuppression. Belatacept cannot be recommended for routine use during pregnancy; clinical decisions must remain individualized, and preconception counseling and prospective multicenter registries are urgently needed. Full article

Fetal bovine serum (FBS) is commonly added to cell culture media, but for cultivated meat production to become truly sustainable, ethical and affordable, an alternative to it is necessary. The purpose of this study was to demonstrate how myoblasts could be cultivated in reduced-serum media using animal-free scaffolds. Novel chitosan/carrageenan hydrogels were developed and conjugated with peptides obtained by digestion of C-phycocyanin from cyanobacteria Arthrospira platensis, their physico-chemical properties were assessed, and their ability to serve as scaffolds for myoblast cultivation in reduced-serum media was examined. These hydrogels were found to possess suitable physical characteristics to serve as scaffolds for cell culture, and it was demonstrated that their use made quail muscle clone 7 (QM7) cell cultivation possible in reduced-FBS media. These hydrogels, therefore, are a promising candidate for use as scaffolds in future cultivated meat production studies. Full article

Background/Objectives: Preeclampsia is a heterogeneous hypertensive disorder of pregnancy, and accessible hematologic indices may reflect maternal physiologic differences before the clinical syndrome becomes evident. This study evaluated whether the first-trimester hemoglobin-to-red cell distribution width (Hb/RDW) ratio was associated with later documented preeclampsia and assessed its discrimination, relation to disease severity, and association with maternal–neonatal outcomes in a tertiary-care cohort. Methods: This retrospective cohort study included 224 singleton pregnancies managed at a tertiary referral center between January 2024 and December 2025. Data extraction, anonymization, and analysis were performed after ethics approval (Approval No. 72; 2 March 2026). Participants were categorized as preeclampsia-negative (n = 131) or preeclampsia-positive (n = 93). Preeclampsia and severe features were defined according to American College of Obstetricians and Gynecologists criteria. The Hb/RDW ratio was calculated from routine first-trimester complete blood count parameters obtained before clinical diagnosis or final outcome classification. ROC analysis, multivariable logistic regression, multicollinearity assessment, events-per-variable evaluation, calibration testing, and exploratory incremental discrimination analyses were performed. Results: The first-trimester Hb/RDW ratio was higher in pregnancies later complicated by preeclampsia. Single-marker ROC analysis showed moderate discrimination (AUC = 0.687; bootstrap 95% CI: 0.618–0.755). At the 0.63 cut-off, sensitivity was 89.2%, specificity 47.3%, positive predictive value 54.6%, and negative predictive value 86.1%. In the primary multivariable model, Hb/RDW remained associated with later preeclampsia (adjusted OR per 0.1-unit increase = 1.45; 95% CI: 1.22–1.72; p < 0.001). However, Hb/RDW was not independently associated with severe preeclampsia among affected patients, fetal growth restriction, or composite maternal morbidity. VIF values ranged from 1.00 to 1.07. Secondary models for fetal growth restriction and composite maternal morbidity had borderline events-per-variable values and were interpreted as exploratory. Conclusions: First-trimester Hb/RDW was associated with later documented preeclampsia in this retrospective tertiary-care cohort, but its single-marker performance was modest and specificity was limited. The ratio should be interpreted as an inexpensive research marker of hematologic phenotype rather than a stand-alone screening, diagnostic, or management tool. Prospective multicenter validation with standardized first-trimester sampling and adjustment for hematinic and nutritional variables is required before clinical implementation. Full article

Rice bran oil (RBO) is a rich source of lipophilic bioactive compounds that may contribute to antioxidant, anti-inflammatory, and bone-health-promoting activities. This study investigated the effects of RBOs containing tocopherols, tocotrienols, and γ-oryzanol derived from Thai pigmented and non-pigmented rice cultivars on oxidative stress, inflammatory responses, and bone-remodeling-related activities. The content of tocopherols, tocotrienols, and γ-oryzanol was determined by high-performance liquid chromatography (HPLC). Reactive oxygen species (ROS) production was determined in human fetal osteoblast (hFOB 1.19) cells where nitric oxide (NO) and inducible nitric oxide synthase (iNOS) production were evaluated in RAW264.7 cells. Following compositional profiling and correlation analyses of antioxidant and anti-inflammatory activities, three representative RBOs were subsequently evaluated for their effects on bone-remodeling-related activities in hFOB 1.19 cells through alkaline phosphatase (ALP) activity and the production of osteocalcin (OC), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL). Additionally, calcification was investigated by Alizarin Red S staining. Pigmented RBOs, particularly Khao’ Hom Nil and RD69, contained higher levels of tocopherols, tocotrienols, and γ-oryzanol than non-pigmented RBOs. These oils significantly suppressed ROS, NO, and iNOS production, which correlated with tocopherol, tocotrienol, and γ-oryzanol content, while enhancing ALP activity, OC and OPG production, reducing RANKL levels and the RANKL/OPG ratio, and promoting matrix mineralization. Overall, pigmented RBOs represent promising natural sources of lipophilic bioactive compounds with potential antioxidant, anti-inflammatory, and bone-remodeling-related activities under in vitro conditions. Full article

Background/Objectives: Large-for-gestational-age (LGA) birth is associated with adverse perinatal outcomes and increased risk of metabolic disease later in life. Despite these risks, epigenetic studies of LGA remain limited, particularly those using umbilical cord blood DNA methylation (DNAm) as the tissue of interest. Methods: We conducted an epigenome-wide association study of cord blood DNAm in a nested case–control sample from the Gestational Regulators of Weight (GROW) cohort. The analysis included 28 term LGA infants and 63 term appropriate-for-gestational-age (AGA) controls. DNAm was measured using the Illumina HumanMethylation450 BeadChip. Epigenome-wide association analyses were performed with adjustment for residual principal components and estimated cord blood cell-type proportions. Results: No CpG sites reached statistical significance after false discovery rate correction. Twenty-four CpGs showed nominal associations with LGA status at p-value < 1.00 × 10⁻⁴, including five CpGs with absolute methylation differences greater than 0.05. Among annotated loci, the strongest interpretable signals included cg06750897 in PBX1 (Δβ = 0.110, p-value = 1.70 × 10⁻⁵) and two nearby CpGs in SMAD3, cg23731272 (Δβ = 0.111, p-value = 4.31 × 10⁻⁵) and cg02486855 (Δβ = 0.109, p-value = 9.45 × 10⁻⁵). These two SMAD3 CpGs showed concordant hypermethylation in LGA infants and formed a candidate regional methylation signal in exploratory targeted regional analysis. Conclusions: In this pilot study, LGA was associated with modest cord blood DNAm differences, although no CpG sites reached genome-wide significance. The strongest interpretable signals involved PBX1 and SMAD3, suggesting candidate loci for further evaluation in larger studies of fetal overgrowth. Full article

Prompted by a fetus with a homozygous PPP1R13L pathogenic variant and persistent open eyelids on sonography, suggesting fusion failure, this study marks the first prenatal human description linking PPP1R13L to eyelid closure, mirroring waved with open eyelids 2(woe2) and waved 3 (wa3) mouse models. Eyelid morphogenesis involves complex epidermal–dermal interactions. We reviewed the literature to understand embryonic/fetal development and identify molecular pathways crucial for proper eyelid morphology. Known signaling pathways in eyelid closure and reopening include NF-κB, p53, Wnt, TGF-β, BMP4, MAPK, SMAD, ECM–receptor interaction, and integrin signaling. Open-eye phenotypes are associated with pathogenic variants affecting the Wnt/β-catenin pathway, p63, and the TGFβ family. Notably, SMAD molecules are common to all these pathways. Eyelid closure seems regulated by SMAD protein activation in the supraorbital epithelium and underlying mesenchyme, promoting cell proliferation and adhesion. Physiological SMAD1 downregulation is crucial for eyelid reopening. Given SMAD signaling’s importance in development, its disruption likely impacts eyelid closure or reopening. Full article

Recurrent pregnancy loss (RPL) continues to be a significant challenge in reproductive medicine, particularly in women for whom standard examinations do not reveal a conclusive underlying reason. There is growing evidence that several instances may result from nuanced alterations in the endometrial milieu, particularly with decidualization and maternal–fetal immune tolerance. In recent years, vitamin D has gained recognition for its significance in early pregnancy, serving not only as a regulator of calcium metabolism but also as an active contributor to endometrial and immunological functions. The human endometrium exhibits the vitamin D receptor (VDR) and the enzyme CYP27B1, facilitating the local activation and signaling of vitamin D inside the uterine milieu. Experimental investigations have shown that vitamin D influences many processes critical for effective implantation and placentation, including stromal cell differentiation, cytokine equilibrium, trophoblast invasion, oxidative stress responses, and immune cell communication. Aberrant vitamin D signaling has been associated with heightened inflammatory activity, impaired decidual transformation, altered uterine natural killer cell functionality, and alteration of the Treg/Th17 equilibrium, all of which have been implicated in recurrent pregnancy loss. Concurrently, there is an increasing emphasis on the association between vitamin D and mitochondrial function as well as oxidative stress in decidual and endometrial cells. Interruption of these pathways may influence implantation and early embryonic development by impacting cellular metabolism and immunological control at the maternal–fetal interface. The clinical interest in vitamin D supplementation for women experiencing repeated reproductive failure is increasing; nevertheless, the existing results are conflicting, mostly due to the predominance of research focusing on circulating vitamin D levels rather than localized tissue-specific processes. Our review encapsulates new findings about the function of vitamin D in endometrial biology and reproductive immune regulation, emphasizing its involvement in decidualization, inflammatory signaling, oxidative stress, and maternal–fetal immunological tolerance in recurrent pregnancy loss. The potential ramifications for assisted reproduction and forthcoming tailored therapy techniques are also examined. Full article

Background/Objectives: Advanced maternal age (≥35 years) significantly increases the risk of fetal chromosomal abnormalities, particularly trisomies 21, 18, and 13. Non-invasive prenatal testing (NIPT) based on cell-free fetal DNA (cffDNA) in maternal plasma has substantially improved the accuracy and safety of prenatal screening. Methods: We previously developed and clinically validated a multiplex droplet digital PCR (ddPCR)-based NIPT assay for detecting fetal trisomies 21, 18, and 13 in Mongolia. The assay targeted specific loci on chromosomes 21, 18, and 13, using chromosome 1 as an internal reference. A Z-score threshold > 3 indicated high risk, and all positive results were confirmed by invasive karyotyping. Results: In this study, we collected 74 pregnant women of advanced maternal age and samples were successfully analyzed, with high technical performance (mean > 100,000 accepted droplets per reaction and clear signal separation). Ten high-risk pregnancy cases were identified (eight trisomy 21 and two trisomy 18), all of which showed complete concordance with confirmatory karyotyping. Complete concordance with available reference standard results were observed in this limited cohort. No trisomy 13 cases were detected. Conclusions: This ddPCR-based NIPT assay exhibited excellent diagnostic accuracy and reproducibility in a Mongolian cohort of advanced-maternal-age pregnancies. Its technical simplicity, relatively low cost, and minimal infrastructure requirements make it a promising tool for implementation in resource-limited settings. However, the small sample size limits generalizability, and larger multicenter studies are needed to confirm clinical utility across broader populations, including low-risk pregnancies. Full article

The designation of O RhD-negative blood as a “universal donor” misrepresents the complexity of red blood cell (RBC) compatibility. With 47 recognized blood group systems encompassing 366 antigens, non-ABO antigen exposure drives alloimmunization in 20–50% of chronically transfused patients. A narrative review of PubMed, Scopus, and EMBASE was conducted for studies published between 2016 and 2025, with selective inclusion of foundational pre-2016 works. Enzymatic approaches using Flavonifractor plautii CAZymes and Akkermansia muciniphila exoglycosidase cocktails enable near-complete ABO antigen removal, though group A conversion remains incomplete. CRISPR-Cas9 multiplex editing of immortalized erythroblasts has achieved simultaneous deletion of ABO, Rh, Kell, Duffy, and MNS antigens. Induced pluripotent stem cell platforms enable scalable manufacture; however, enucleation efficiency (40–70%), yield (4.6 × 10³ RBCs/iPSC), and fetal hemoglobin prevalence remain translational barriers. Convergence of enzymatic and gene-editing technologies on GMP-compatible iPSC platforms represents the most credible pathway to truly universal RBCs, although current evidence remains largely confined to immortalized cell lines and early-stage iPSC proof-of-concept studies rather than clinically validated products. Regulatory frameworks, scalability, and rigorous off-target profiling define the key challenges ahead. Full article

The human placenta is a temporary organ structured to optimize exchange between the maternal and fetal circulatory systems. Its fetal component consists of highly branched chorionic villi, which are anchored to the maternal uterine wall and project into the intervillous space. The outer surface of these villi is lined by a multinucleated, continuous layer called the syncytiotrophoblast, which is supported by an underlying layer of proliferative cytotrophoblast cells and the invasive extravillous trophoblast (EVT). This cellular bilayer forms a selective barrier that directly bathes in maternal blood, allowing for the efficient transfer of oxygen and nutrients while structurally preventing the direct mixing of maternal and fetal blood cells. Human placental studies have been stymied by ethical and accessibility constraints. Stem cell biology has now revolutionized the capacity to model human placental development, in particular with the derivation of human trophoblast stem cells (hTSCs) and organoids. Authentic, self-renewing human trophoblast stem cells (hTSCs) were first derived not from pluripotent stem cells but from primary tissue—first-trimester villous cytotrophoblasts and blastocysts. Derivation from human pluripotent stem cells (PSCs) followed only subsequently, along two principal routes: conversion of naive PSCs, which retain extraembryonic competence, and induction from primed PSCs, as well as by direct reprogramming of somatic cells to induced hTSCs. An important advance underlying these improvements is the mapping of a global reprogramming roadmap. Multi-omic and lineage-tracing experiments have mapped the stepwise transcriptional and epigenetic conversions of fibroblasts to hTSCs, including sequential chromatin reconfiguration, trophoblast gene network activation, and repression of somatic signatures. These results identify major regulatory bottlenecks and intermediate states, improving reprogramming fidelity. The derivation of stem-cell-based trophoblast organoids now enables complex modeling of placental architecture, function, and disease susceptibility in vitro. These organoids accurately recapitulate placental barrier functions and immunological features, allowing for examinations of maternal–fetal health, pregnancy disorders, and placental infection response to viruses like cytomegalovirus and SARS-CoV-2. Looking ahead, the integration of reprogramming and organoid technologies will propel patient-specific and tailor-made models for personalized diagnostics, drug screening, and mechanism studies. As we unravel the molecular ballet of trophoblast induction, such discoveries have the potential to bridge basic translational gaps in reproductive biology and maternal–fetal medicine. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is associated with placental structural and functional alterations that may impair trophoblast integrity and maternal–fetal exchange. Ezrin, radixin, and moesin (ERM) proteins are membrane–cytoskeleton linker proteins involved in microvillous organization, cell polarity, and signal transduction. This study aimed to investigate placental ERM protein expression in GDM and to explore ERM-associated molecular pathways through bioinformatic analysis. Methods: This prospective observational study included placental tissues obtained from 40 women with GDM and 40 healthy pregnant women. Immunohistochemical staining for ezrin, radixin, and moesin was performed on paraffin-embedded placental sections, and quantitative image analysis was conducted using QuPath software (version 0.7.0) to calculate H-scores. Correlation and receiver operating characteristic (ROC) analyses were performed to evaluate associations between ERM expression and clinical parameters. In addition, bioinformatic analyses were conducted using the publicly available GSE154414 placental transcriptomic dataset to investigate ERM-associated signaling pathways and interaction networks. Results: Ezrin immunoreactivity was significantly increased in the GDM group compared with controls (118.63 ± 20.56 vs. 107.95 ± 17.41, p = 0.026), whereas Radixin and Moesin expression levels did not differ significantly between groups (p > 0.05). Ezrin expression demonstrated significant positive correlations with maternal body mass index, birth weight, fasting glucose, and HbA1c levels. ROC analysis demonstrated modest discriminatory performance of the Ezrin H-score for distinguishing GDM from control pregnancies (AUC = 0.645, p = 0.018). Bioinformatic analyses identified enrichment of ERM-associated pathways involved in cytoskeletal remodeling, inflammatory signaling, and protein phosphorylation-related cellular processes. Conclusions: Placental Ezrin expression was significantly increased in women with GDM and was positively associated with maternal glycemic parameters. These findings suggest that altered Ezrin expression may reflect adaptive cytoskeletal remodeling in diabetic placentas. ERM-associated signaling pathways may contribute to placental responses to metabolic stress in GDM. Full article

Bisphenols, phthalates, and other plastic-associated compounds are endocrine-disrupting chemicals (EDCs), common environmental contaminants that can disrupt hormonal homeostasis. Human exposure to such chemicals occurs mainly through food packaging, consumer goods, medical devices, and the environment, starting right from early development stages up to adulthood. These chemicals might cause damage to male reproductive systems as a result of being anti-androgens and estrogenic chemicals. However, the proper development of the male reproductive system requires well-regulated hormonal signaling pathways; hence, exposure to such compounds during the developmental stages poses a great risk. Environmental exposure to plastics during fetal development may influence the development of the testes, reduce the function of the Leydig cells, disrupt steroidogenesis, and produce epigenetic modifications, as documented through studies. This has been shown to increase the risk of developing reproductive disorders and reduce the production of testosterone. Therefore, one of the pathophysiological links between endocrine disruptor exposure and ED might be testosterone deficiency. Apart from disrupting testosterone production, the plastic-sourced EDCs could influence various physiological processes associated with erectile performance, such as those related to vasculature, inflammation, metabolism, and endocrinology. In this review, a comprehensive overview of the scientific data on the effect of plastic-based EDCs on testosterone regulation and male reproductive health has been provided. The role of developmental programming, endocrine disruption, oxidative stress, epigenetics, and vascular dysfunction has been explored in detail. Moreover, the possible involvement of micro- and nanoplastics has also been reviewed. From the data that is currently available, there seems to be a physiologically plausible association between plastic-based contaminants, testosterone dysregulation, and adverse reproductive outcomes. Full article

Importance: Sickle cell retinopathy and maculopathy are frequent but underdiagnosed complications of sickle cell disease that can lead to vision loss. Unfortunately, there is currently no ophthalmological follow-up protocol to best diagnose and treat these complications. Objective: To identify the most important risk factors associated with the progression of sickle cell retinopathy and maculopathy, review the current screening techniques and effective treatments and propose a follow-up protocol tailored to the patient’s risk profile. Evidence Review: Relevant studies were selected using the PICO framework and a structured search strategy across multiple databases including PubMed, Scopus, Cochrane Library, Cible+, ScienceDirect and the American Academy of Ophthalmology network. The search spanned from 1980 to 2025. Original research articles addressing risk factors, screening, and treatment methods for sickle cell retinopathy and maculopathy were included. In total, 48 studies met the inclusion criteria. Data extraction and quality assessment were applied uniformly. Findings: The systematic review included 48 articles (10,543 participants), representing a mix of study types: randomized clinical trials, prospective and retrospective cohort studies, and cross-sectional studies. Major findings included: Risk Factors: Commonly identified risk factors for sickle cell retinopathy and maculopathy include genotype SS, increased age, male sex, and low fetal hemoglobin levels. Screening and Diagnosis: Wide-field fluorescein angiography and optical coherence tomography angiography were the most effective tools for early detection of peripheral ischemia and macular thinning, respectively. Treatment and Management: Laser photocoagulation remains the standard intervention for proliferative sickle cell retinopathy. Preventive strategies and regular ophthalmologic monitoring are emphasized across high-quality studies. Conclusions and Relevance: Risk stratification based on genotype, hemoglobin F levels, and imaging findings allows for tailored ophthalmologic management of patients with sickle cell disease. A structured follow-up protocol is proposed, aiming to improve early detection, prevent complications, and optimize resource allocation. Full article

Background/Objectives: Non-invasive prenatal testing for monogenic disorders (NIPT-MD) provides a safe alternative to invasive procedures. However, its clinical utility is often limited by challenges such as low fetal fractions (FF), technical artifacts, and the difficulty in resolving maternally inherited pathogenic variants from the overwhelming background of maternal cell-free DNA (cfDNA). This study aimed to develop and validate a robust NIPT-MD platform for monogenic disorders, applicable across major common Mendelian inheritance patterns, by enhancing the accuracy of fetal variant detection in cfDNA. Methods: We developed a novel NIPT-MD platform validated using both simulated samples and a retrospective clinical cohort. The workflow involves a single-strand capture library preparation incorporating unique molecular identifiers (UMIs) to mitigate amplification artifacts. FF was precisely quantified using a fixed panel of high-minor-allele-frequency single-nucleotide polymorphisms (SNPs). Fetal genotypes were then inferred by resolving parental haplotypes through a statistical model that integrates weighting of variant allele frequency (VAF) and haplotype-informative SNP counts. Results: The single-strand capture protocol incorporating UMIs significantly reduced amplification biases. Validation of the fetal DNA fraction estimation algorithm revealed strong concordance with a Y-chromosome-derived method and expected spike-in samples. Optimization of the FF estimation panel conferred greater experimental stability. The platform reliably detected both paternally and maternally inherited pathogenic variants. In a retrospective cohort of 35 clinical cases, the NIPT-MD platform achieved high concordance with genotypes determined by invasive testing. Conclusions: These findings present an accurate and robust NIPT-MD platform for monogenic disorders, with high concordance to invasive testing validated in a retrospective cohort of 35 clinical cases. This method holds promise for clinical application in managing families at high risk of monogenic diseases. Full article

Chromosome preparation from peripheral blood in felids is often difficult because lymphocytes respond inconsistently to standard mitogens like phytohemagglutinin (PHA), resulting in low and variable mitotic indices. Here, we present a standardized and reproducible protocol for lymphocyte culture and metaphase chromosome preparation in felids using concanavalin A (ConA) as a mitogenic stimulus. A total of 300 µL of peripheral blood consistently produced optimal chromosome preparations and was cultured in RPMI 1640 medium supplemented with fetal bovine serum, antibiotics, and Concanavalin A (40 µg/mL), then incubated at 37 °C for 70 h. Mitotic arrest was induced with colchicine, and cells were subjected to hypotonic treatment and fixation using methanol–acetic acid before slide preparation and Giemsa staining. This approach consistently yielded high-quality metaphase spreads across the eight felid species examined, with mean values ranging from 32 ± 5 to 55 ± 7 metaphases per slide, while maintaining chromosome morphology appropriate for cytogenetic investigation. Compared with fibroblast-based approaches, this methodology is less invasive and more feasible for clinical and conservation applications because it relies on peripheral blood collection rather than tissue biopsy, reducing the invasiveness of sampling procedures. This optimized lymphocyte culture workflow enhances mitotic yield and repeatability, serving as a significant resource for cytogenetic research, particularly in veterinary genetics, evolutionary biology, and the conservation of endangered felid species. Full article