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20 pages, 3737 KB  
Article
Growth Performance, Digestive Capacity, and Transcriptomic Analysis of the Hybrid Offspring of Mastacembelus armatus × Mastacembelus favus
by Yiman Chen, Linan Zhang, Xianshan Lin, Hao Sheng, Weikai Chen, Mingxiang Cui, Chong Han and Hu Shu
Animals 2026, 16(1), 11; https://doi.org/10.3390/ani16010011 - 19 Dec 2025
Viewed by 68
Abstract
Hybrid breeding is a crucial approach in aquaculture for improving stock performance. This study systematically evaluated heterosis in hybrid offspring from a cross between the zig-zag eel (Mastacembelus armatus) and the tire track eel (Mastacembelus favus). The hybrids exhibited [...] Read more.
Hybrid breeding is a crucial approach in aquaculture for improving stock performance. This study systematically evaluated heterosis in hybrid offspring from a cross between the zig-zag eel (Mastacembelus armatus) and the tire track eel (Mastacembelus favus). The hybrids exhibited significantly superior growth performance and a higher survival rate than both parental populations. Physiological analyses revealed distinct advantages in digestive enzyme activity and intestinal tissue structure. Liver transcriptome sequencing revealed that most of the differentially expressed genes (DEGs) in the hybrids displayed non-additive expression patterns and were significantly enriched in pathways associated with growth hormone synthesis, insulin secretion and lipid metabolism. The upregulation of igf2 and the downregulation of socs1 were identified as key molecular drivers of enhanced growth. This multi-level analysis, spanning from phenotype to molecular mechanisms, sheds light on the heterogeneous basis of these hybrids and provides theoretical insights and practical guidance for breeding work with zig-zag eels and related species. Full article
(This article belongs to the Section Aquatic Animals)
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24 pages, 24946 KB  
Article
Hybrid Dihydropyrimidinones Targeting AKT Signaling: Antitumor Activity in Hormone-Dependent 2D and 3D Cancer Models
by Amanda Helena Tejada, Samuel José Santos, Gabriel Tofolli Lobo, Abu-Bakr Adetayo Ariwoola, Aryel José Alves Bezerra, Giulia Rodrigues Stringhetta, Izabela Natalia Faria Gomes, Luciane Sussuchi da Silva, Rui Manuel V. Reis, Daniel D’Almeida Preto, Dennis Russowsky and Renato José Silva-Oliveira
Pharmaceutics 2025, 17(11), 1470; https://doi.org/10.3390/pharmaceutics17111470 - 14 Nov 2025
Viewed by 607
Abstract
Background/Objectives: The development of effective oncologic therapies with fewer adverse effects is often limited by the intrinsic and acquired resistance of tumor cells. Hybrid molecules, rationally designed to combine different pharmacophores, represent a promising strategy by providing synergistic effects, dose reduction, and a [...] Read more.
Background/Objectives: The development of effective oncologic therapies with fewer adverse effects is often limited by the intrinsic and acquired resistance of tumor cells. Hybrid molecules, rationally designed to combine different pharmacophores, represent a promising strategy by providing synergistic effects, dose reduction, and a lower risk of resistance. In this study, the antitumor potential and mechanisms of action of 22 novel hybrid compounds derived from xanthene and pyran scaffolds (SJ022–SJ103) were investigated. The hybrids were initially evaluated through in vitro screening in four breast, three ovarian, and two prostate cancer cell lines, followed by the selection of T-47D, OVCAR-3, and LNCaP cells for detailed assays assessing cytotoxicity, apoptosis, cell cycle distribution, DNA damage, caspase-3/7 activity, morphology, and PI3K/AKT/mTOR pathway modulation. Methods: Cytotoxicity assays were performed in the selected cell lines, while mechanistic studies included apoptosis and cell cycle analysis by flow cytometry, γH2AX detection, Western blotting for PI3K/AKT/mTOR pathway proteins, and 3D spheroid assays. Combinatorial effects with hormone therapies (tamoxifen, fulvestrant, and letrozole) and the AKT inhibitor MK2206 were evaluated. AKT silencing by esiRNA and molecular docking was performed to confirm target engagement. Results: SJ028 demonstrated broad activity across all tested cell lines, whereas SJ064 and SJ078 exhibited higher selectivity. Treatments induced apoptosis, S/G2-M arrest, and DNA damage, accompanied by decreased phospho-AKT levels and stable PI3K and mTOR expression. In 3D models, the hybrids increased caspase-3/7 activity and necrotic core expansion. Co-administration with hormone therapies resulted in synergistic effects in breast and ovarian cancer cells, reducing IC50 values by more than 50% in both parental and resistant models, while combinations with MK2206 were antagonistic across all tumor subtypes. AKT silencing abrogated cytotoxicity, and docking confirmed SJ028 binding to AKT. Conclusions: Xanthene- and pyran-based hybrids—particularly SJ028, SJ064, and SJ078—showed strong antitumor activity through apoptosis induction, cell cycle arrest, and PI3K/AKT pathway modulation. Their preserved efficacy in resistant models and synergistic interactions with hormone therapies contrasted with the antagonism observed with AKT inhibition, highlighting their potential as promising candidates for the treatment of hormone-responsive and -resistant cancers. Full article
(This article belongs to the Special Issue Innovative Drug Delivery Strategies for Targeted Cancer Immunotherapy)
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20 pages, 1707 KB  
Article
Comparative Study on Growth Performance and Meat Production Traits of Reciprocal Crosses Between Guizhou Recessive White Chickens and Qiandongnan Xiaoxiang Chickens
by Yingping Tian, Xiaoya Wang, Yong Yue, Muhammad Arif, Yaozhou Jiang, Qinsong Liu, Yun Du, Xudong Zhao and Fuping Zhang
Animals 2025, 15(22), 3262; https://doi.org/10.3390/ani15223262 - 11 Nov 2025
Viewed by 664
Abstract
Indigenous chicken breeds often exhibit desirable meat quality but slower growth. This study evaluated growth, body size, slaughter traits, meat quality, and heterosis in reciprocal crosses between Guizhou recessive white (GW) and Qiandongnan Xiaoxiang (QX) chickens. A complete diallel cross produced four populations [...] Read more.
Indigenous chicken breeds often exhibit desirable meat quality but slower growth. This study evaluated growth, body size, slaughter traits, meat quality, and heterosis in reciprocal crosses between Guizhou recessive white (GW) and Qiandongnan Xiaoxiang (QX) chickens. A complete diallel cross produced four populations (WW: GW♂ × GW♀; QQ: QX♂ × QX♀; QW: QX♂ × GW♀; WQ: GW♂ × QX♀). To assess growth dynamics, body weight was recorded from hatch to 18 weeks and fitted with Logistic, Gompertz, and Von Bertalanffy models. At 18 weeks, 160 birds (40 per group, equal sex ratio) were assessed for body size, carcass yield, and meat quality. The results showed clear paternal effects. For instance, WQ (GW sire) outperformed QW (QX sire): WQ roosters had higher body weight at 18 weeks (1784.1 g vs. QW, p < 0.05) and greater heterosis (12.38%, 95%CI: 9.15–15.61 vs. 2.54%, 95%CI: −0.66–5.74). WQ hens also showed stronger heterosis despite similar body weight to QW hens (8.05%, 95%CI: 5.04–11.04 vs. 4.05%, 95%CI: 0.67–7.43). Growth curves were generally best described by the Von Bertalanffy model (R2 ≥ 0.998), except in QW roosters, where the Gompertz model fitted better. Hybrid progeny (WQ and QW) showed improved slaughter traits over QQ, with WQ roosters exhibiting higher heterosis rates (14.09–30.71%) than QW (1.08–21.93%). Meat tenderness was superior in QQ, while QW showed advantages over WQ in tenderness and water retention. Overall, crossbreeding enhanced growth and carcass traits, and using GW as the male parent (WQ) was most effective. These findings provide practical evidence for improving Qiandongnan Xiaoxiang chickens through crossbreeding. Moreover, the observed paternal effects on growth traits suggest the need for further investigation into underlying mechanisms such as genomic imprinting and growth-related hormonal pathways. Full article
(This article belongs to the Special Issue Advances in Genetic Analysis of Important Traits in Poultry)
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26 pages, 992 KB  
Review
Emotion and Feeling in Parent–Child Dyads: Neurocognitive and Psychophysiological Pathways of Development
by Antonios I. Christou and Flora Bacopoulou
Children 2025, 12(11), 1478; https://doi.org/10.3390/children12111478 - 2 Nov 2025
Viewed by 1779
Abstract
Although widely used across disciplines, the terms emotion and feeling remain conceptually ambiguous, particularly within developmental science. Emotion is defined as an evolutionarily conserved, biologically embedded system of action readiness and intersubjective communication, shaped by attentional, neural, and physiological reactivity to environmental salience. [...] Read more.
Although widely used across disciplines, the terms emotion and feeling remain conceptually ambiguous, particularly within developmental science. Emotion is defined as an evolutionarily conserved, biologically embedded system of action readiness and intersubjective communication, shaped by attentional, neural, and physiological reactivity to environmental salience. In contrast, feeling is conceptualized as the consciously experienced, representational outcome of emotional activation, emerging through cognitive appraisal and symbolic processing. Building upon this distinction, the review explores how emotion develops within parent–child dyads through coregulated neurocognitive and psychophysiological mechanisms. Drawing on empirical evidence from eye-tracking studies of visual attention to emotional faces, functional near-infrared spectroscopy (fNIRS) research on social-emotional activation in prefrontal brain regions, and cortisol-based assessments of hormonal synchrony, the paper highlights how emotional attunement and transmission are embedded in early caregiving interactions. The review also emphasizes the moderating role of environmental sensitivity—both in children and parents—in shaping these developmental pathways. By positioning emotion as a dynamic, intersubjective process and feeling as its emergent experiential correlate, this review offers a novel developmental framework for understanding affect and proposes directions for future research on resilience, dysregulation, and intervention. Full article
(This article belongs to the Special Issue Parental Mental Health and Child Development)
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12 pages, 806 KB  
Article
A Study on Parental Corticophobia in Pediatric Allergic Diseases
by Halil Alkaya, Uğur Altaş, Seda Çevik, Yakup Söğütlü and Mehmet Yaşar Özkars
Medicina 2025, 61(11), 1959; https://doi.org/10.3390/medicina61111959 - 31 Oct 2025
Viewed by 481
Abstract
Background and Objectives: Parental beliefs strongly influence treatment adherence in pediatric allergic diseases. Concerns about corticosteroid therapy—known as corticophobia—may disrupt disease control and compromise child well-being. This study aimed to evaluate parental knowledge, beliefs, and concerns regarding topical, inhaled, and intranasal corticosteroid [...] Read more.
Background and Objectives: Parental beliefs strongly influence treatment adherence in pediatric allergic diseases. Concerns about corticosteroid therapy—known as corticophobia—may disrupt disease control and compromise child well-being. This study aimed to evaluate parental knowledge, beliefs, and concerns regarding topical, inhaled, and intranasal corticosteroid use in children, and to identify sociodemographic factors associated with corticophobia. Materials and Methods: This prospective survey was conducted in a tertiary pediatric allergy and immunology clinic. A structured questionnaire was anonymously completed by 110 parents of children receiving corticosteroid therapy. The survey assessed demographics, family history of atopy, corticosteroid use, perceived disease severity, knowledge level, concerns, and sources of information. Descriptive statistics and chi-square tests were applied (p < 0.05 significant). Results: The most frequent concerns were growth retardation, hormonal imbalance, and long-term side effects. Corticophobia was significantly more prevalent among university-educated parents (p = 0.043) and those with a family history of atopy (p = 0.017). Despite generally high adherence to prescribed regimens, nearly 60% of parents sought additional information, highlighting the impact of knowledge gaps on health-related parenting practices. Conclusions: Corticophobia remains a common parental concern in pediatric allergy care, with implications for adherence, family decision-making, and child well-being. Addressing misinformation and providing family-centered, tailored educational strategies—particularly for highly educated parents and those with an atopic background—may reduce fears, strengthen trust, and promote sustainable healthy behaviors. Full article
(This article belongs to the Special Issue Research on Allergy, Asthma, and Clinical Immunology)
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27 pages, 2610 KB  
Article
Simulated Pharmacokinetic Compatibility of Tamoxifen and Estradiol: Insights from a PBPK Model in Hormone-Responsive Breast Cancer
by Beatriz Gomes and Nuno Vale
Targets 2025, 3(4), 33; https://doi.org/10.3390/targets3040033 - 30 Oct 2025
Viewed by 678
Abstract
Although traditionally contraindicated, the coadministration of tamoxifen and estradiol may hold clinical relevance in specific contexts, particularly in breast cancer survivors with premature menopause and a high risk of osteoporosis, thereby justifying the need to re-evaluate this therapeutic combination. This study presents an [...] Read more.
Although traditionally contraindicated, the coadministration of tamoxifen and estradiol may hold clinical relevance in specific contexts, particularly in breast cancer survivors with premature menopause and a high risk of osteoporosis, thereby justifying the need to re-evaluate this therapeutic combination. This study presents an innovative physiologically based pharmacokinetic (PBPK) modeling approach to evaluate the coadministration of tamoxifen and estradiol in women with breast cancer and a high risk of osteoporosis. Using GastroPlus® software, PBPK models were developed and validated for both drugs, based on physicochemical and kinetic data obtained from the literature and, where necessary, supplemented by estimates generated in ADMET Predictor®. The simulations considered different hormonal profiles (pre and postmenopausal) and therapeutic regimens, evaluating potential interactions mediated by the CYP3A4 enzyme. Analysis of the pharmacokinetic parameters (F, Cmax, Tmax and AUC) revealed strong agreement between the simulated and experimental values, with prediction errors of less than twofold. The drug interaction studies, carried out in dynamic and stationary modes, indicated that estradiol does not significantly alter the pharmacokinetics of tamoxifen, even at increasing doses or in enlarged virtual populations. These results represent the first in silico evidence that, under certain conditions, the concomitant use of estradiol does not compromise the pharmacokinetic efficacy of tamoxifen. Although the study is computational, it provides a solid scientific basis for re-evaluating this therapeutic combination and proposes a pioneering model for personalized strategies in complex oncological contexts. All simulations assumed average enzyme abundance/activity without CYP polymorphism parameterization; findings are restricted to parent-tamoxifen pharmacokinetics and do not infer metabolite (e.g., endoxifen) exposure or phenotype effects. Full article
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15 pages, 250 KB  
Article
The Mediating Role of Inner Strength in the Relationship Between Biological Factors and Depressive Symptoms
by Jia Jiao, Rewadee Jenraumjit, Shirley Worland, Saifon Bunyachatakul, Bijing He and Tinakon Wongpakaran
Nurs. Rep. 2025, 15(10), 348; https://doi.org/10.3390/nursrep15100348 - 25 Sep 2025
Viewed by 618
Abstract
Background: Depression is a significant public health concern, with working mothers at greater risk due to combined biological and psychosocial stressors. Recent evidence suggests that inner strength may play a mediating role in the link between biological risks and depression. Objectives: The primary [...] Read more.
Background: Depression is a significant public health concern, with working mothers at greater risk due to combined biological and psychosocial stressors. Recent evidence suggests that inner strength may play a mediating role in the link between biological risks and depression. Objectives: The primary objective was to determine whether inner strength mediates the relationship between biological risk factors (hormonal fluctuations, smoking, alcohol use, family psychiatric history, and physical diseases) and depressive symptoms among Chinese working mothers. A secondary objective was to assess the prevalence of depressive symptoms in this population, measured with the OI-Depression subscale (Outcome Inventory-21). Methods: A cross-sectional online survey was conducted with 330 Chinese working mothers aged 30–45 years, using validated instruments to measure depression, inner strength, and parental stress. Mediation analysis evaluated the indirect effect of inner strength, while covariate-adjusted regression analyses explored associated factors. Results: Biological risk factors showed a significant direct effect (β = 0.584, p < 0.001) and an indirect effect through inner strength (indirect effect = 0.623, 95% CI [0.294, 0.962]. The Sobel test indicated that the indirect effect of biological risk factors on depressive symptoms through inner strength was statistically significant (z = 3.67, p < 0.001). The prevalence of clinically significant depressive symptoms was 38.2%. Conclusions: Biological factors significantly contribute to depressive symptoms, but inner strength partially mediates this relationship, suggesting that interventions to enhance inner strength may help reduce depression risk in working mothers. Further research should investigate strategies to build inner resilience in this population. Full article
(This article belongs to the Section Mental Health Nursing)
34 pages, 1598 KB  
Review
Neuroendocrine Regulation and Neural Circuitry of Parenthood: Integrating Neuropeptides, Brain Receptors, and Maternal Behavior
by Philippe Leff-Gelman, Gabriela Pellón-Díaz, Ignacio Camacho-Arroyo, Nadia Palomera-Garfias and Mónica Flores-Ramos
Int. J. Mol. Sci. 2025, 26(18), 9007; https://doi.org/10.3390/ijms26189007 - 16 Sep 2025
Viewed by 1946
Abstract
Maternal behavior encompasses a range of biologically driven responses whose expression and duration vary across species. Maternal responses rely on robust adaptive changes in the female brain, enabling mothers to engage in caregiving, nourishing, and offspring protection. Morphological and functional changes in the [...] Read more.
Maternal behavior encompasses a range of biologically driven responses whose expression and duration vary across species. Maternal responses rely on robust adaptive changes in the female brain, enabling mothers to engage in caregiving, nourishing, and offspring protection. Morphological and functional changes in the maternal brain enhance sensitivity to offspring cues, eliciting maternal behaviors, rewarding responses, and social processing stimuli essential for parenting. Maternal behavior comprises a range of biological responses that extend beyond basic actions, reflecting a complex, evolutionarily shaped neurobiological adaptation. These behaviors can be broadly categorized into direct behaviors, which are explicitly aimed at the care of the offspring, and indirect behaviors that, overall, ensure the protection, nourishment, and survival of the newborn. The secretion of main neuropeptide hormones, such as oxytocin (OT), prolactin (PRL), and placental lactogens (PLs), during the peripartum period, is relevant for inducing and regulating maternal responses to offspring cues, including suckling behavior. Although PRL is primarily associated with reproductive and parental functions in vertebrates, it also modulates distinct neural functions during pregnancy that extend from lactogenesis to adult neurogenesis, neuroprotection, and neuroplasticity, all of which contribute to preparing the maternal brain for motherhood and parenting interactions. Parvocellular OT-containing neurons in the paraventricular nucleus (PVN) and in the anterior hypothalamic nucleus (AHN) project axon collaterals to the medial preoptic area, which, in turn, projects to the nucleus accumbens (NACC) and lateral habenula (lHb) via the retrorubral field (RRF) and the ventral tegmental area (VTA), which mediate the motivational aspects of maternal responses to offspring cues. The reshaping process of the brain and neural networks implicated in motherhood depends on several factors, such as up- and downregulation of neuronal gene expression of bioactive peptide hormones (i.e., OT, PRL, TIP-39, galanin, spexin, pituitary adenylate cyclase-activating polypeptide (PACAP), corticotropin-releasing hormone (CRH), peptide receptors, and transcription factors (i.e., c-fos and pSTAT)) in target neurons in hypothalamic nuclei, mesolimbic areas, the hippocampus, and the brainstem, which, overall, regulate the expression of maternal behavior to offspring cues, as shown in postpartum female rodents. In this review, we describe the modulatory neuropeptides, the neural networks underlying peptide transmission systems, and cell signaling involved in parenthood. We highlight the dysregulation of neuropeptide hormones and their receptors in the central nervous system in relation to psychiatric disorders. Full article
(This article belongs to the Section Molecular Neurobiology)
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16 pages, 276 KB  
Article
The Role of Preconception Parental Health on Embryo Quality—Preliminary Results of a Prospective Study Using Non-Invasive Preimplantation Genetic Testing for Aneuploidy
by Maja Tomic, Eda Bokal-Vrtacnik and Martin Stimpfel
Biomolecules 2025, 15(9), 1215; https://doi.org/10.3390/biom15091215 - 22 Aug 2025
Viewed by 1177
Abstract
In this study, we aimed to correlate embryonic ploidy status studied with non-invasive preimplantation genetic testing for aneuploidy with the basic patient characteristics of the infertile couple to gain insight into the effects of parental physical health on embryo ploidy. We recruited 131 [...] Read more.
In this study, we aimed to correlate embryonic ploidy status studied with non-invasive preimplantation genetic testing for aneuploidy with the basic patient characteristics of the infertile couple to gain insight into the effects of parental physical health on embryo ploidy. We recruited 131 couples, who were stratified into 4 groups based on female age. We gathered general patient characteristics of the couple and determined the female’s hormonal status. We included 316 embryos in our study. Embryos were either transferred in the uterus in a fresh cycle or vitrified for later use. We collected spent embryo culture medium on either day 5 or 6 and performed whole genome amplification before using Next Generation Sequencing. Pregnancy outcomes were noted and cross-referenced with patient characteristics and the embryo’s ploidy status in a retrospective manner. While we have indirectly observed a level of maternal contamination, we nevertheless found a significant correlation between embryo ploidy status and cell free deoxyribonucleic acid concentration in spent embryo culture, as well a correlation between female age and embryo ploidy status. We observed a significant correlation between male body mass index and cell free deoxyribonucleic acid concentration in spent embryo culture medium and between male body mass index and pregnancy outcome. We illustrated a connection between male body mass index and cell free deoxyribonucleic acid, independent of female markers. This is the first study to observe not only female but male parameters in correlation to cell free deoxyribonucleic acid. Full article
(This article belongs to the Special Issue Human Reproductive Biology: Uncertainties and Controversies)
26 pages, 857 KB  
Review
The Infant Oral Microbiome: Developmental Dynamics, Modulating Factors, and Implications for Oral and Systemic Health
by Paula Olate, Ailín Martínez, Eulàlia Sans-Serramitjana, Matías Cortés, Rommy Díaz, Genisley Hernández, Erwin A. Paz, Néstor Sepúlveda and John Quiñones
Int. J. Mol. Sci. 2025, 26(16), 7983; https://doi.org/10.3390/ijms26167983 - 19 Aug 2025
Cited by 2 | Viewed by 2465
Abstract
The infant oral microbiome is a complex and dynamic microbial community that undergoes various transformations during human development. From birth, these microorganisms are modulated by factors such as birth type, nutrition, oral hygiene, hormonal changes, and environmental and socioeconomic conditions. These elements interact [...] Read more.
The infant oral microbiome is a complex and dynamic microbial community that undergoes various transformations during human development. From birth, these microorganisms are modulated by factors such as birth type, nutrition, oral hygiene, hormonal changes, and environmental and socioeconomic conditions. These elements interact continuously, shaping the diversity and stability of the oral microbiome and consequently influencing the oral and general health of individuals. The main objective of this study was to review the literature on the evolution of the oral microbiome at different stages of growth, with special emphasis on the maintenance of dental homeostasis and prevention of pathologies such as caries and periodontitis. A bibliographic review of scientific databases was conducted, focusing on the last decade. In general, oral microbiome dysbiosis increases the risk of oral diseases and systemic conditions. Diet, parental practices, and horizontal transmission of bacteria from caregivers have been shown to modulate and influence the composition and functioning of the infant oral microbiome. Despite these advances, gaps remain in our understanding of the impact of the pediatric oral microbiome on long-term comprehensive health. Therefore, longitudinal research is needed to understand the development of the oral microbiome and its potential role in early prediction, prevention, and treatment of oral and systemic diseases. Full article
(This article belongs to the Topic Oral Health Management and Disease Treatment)
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26 pages, 745 KB  
Review
Parental Cigarette Smoke Exposure and Its Impact on Offspring Reproductive Health: A Systematic Review of Maternal, Paternal, and Dual-Smoking Effects
by Yasmin Azizbayli, Amanda Tatler, Victoria James, Adam Watkins and Lucy C. Fairclough
Int. J. Transl. Med. 2025, 5(3), 34; https://doi.org/10.3390/ijtm5030034 - 2 Aug 2025
Viewed by 6001
Abstract
Objectives: Parental exposure to tobacco smoke is a significant public health concern, with over 1.1 billion smokers worldwide. The aim of this systematic review was to evaluate the impact of maternal, paternal, and dual-parental cigarette smoke exposure on offspring reproductive health. Methods: Original [...] Read more.
Objectives: Parental exposure to tobacco smoke is a significant public health concern, with over 1.1 billion smokers worldwide. The aim of this systematic review was to evaluate the impact of maternal, paternal, and dual-parental cigarette smoke exposure on offspring reproductive health. Methods: Original human clinical and animal research studies were included; titles and abstracts were manually scanned for relevance to the effect of parental smoking on offspring reproductive outcomes (Date of search:18/03/2025). Results: This systematic review incorporates 30 studies identified from three databases (PubMed, Web of Science, and Scopus). The results indicate that male offspring exhibit reduced spermatogenic capacity, characterized by decreased testicular size, lower sperm count, and impaired hormonal biosynthesis, with reductions of 30–40% in sperm production. Dual-parental smoking exacerbates these effects, with sperm counts averaging 85 million per ml in human male offspring from dual-smoking households, compared to 111 million per ml in single-smoking households. Animal studies provide mechanistic insights, revealing reduced testis weight in nicotine-exposed male rats and increased oxidative stress in offspring. Conclusions: This review highlights the dose-dependent and sex-specific effects of smoking on the fertility of offspring and underscores the need for standardized protocols to enhance the consistency and comparability of future research in both human and animal studies. Full article
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18 pages, 305 KB  
Review
Causes of Childhood Cancer: A Review of Literature (2014–2021): Part 2—Pregnancy and Birth-Related Factors
by Rebecca T. Emeny, Angela M. Ricci, Linda Titus, Alexandra Morgan, Pamela J. Bagley, Heather B. Blunt, Mary E. Butow, Jennifer A. Alford-Teaster, Raymond R. Walston III and Judy R. Rees
Cancers 2025, 17(15), 2499; https://doi.org/10.3390/cancers17152499 - 29 Jul 2025
Cited by 2 | Viewed by 2720
Abstract
Purpose: To review parental pre-pregnancy and pregnancy exposures in relation to pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 17 March 2021. [...] Read more.
Purpose: To review parental pre-pregnancy and pregnancy exposures in relation to pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 17 March 2021. Results: Strong evidence links increased risk of childhood cancer with maternal diabetes, age, and alcohol and coffee consumption during pregnancy. Both paternal and maternal cigarette smoking before and during pregnancy are associated with childhood cancers. Diethylstilbestrol (DES) exposure in utero has long been known to be causally associated with increased risk of vaginal/cervical cancers in adolescent girls. More recent evidence implicates in utero DES exposure to testicular cancer in young men and possible intergenerational effects on ovarian cancer in the granddaughters of women exposed to DES during pregnancy. There is strong evidence that childhood cancer risk is also associated with both high and very low birth weight and with gestational age. Evidence is also strong for the protective effects of maternal vitamin consumption and a healthy diet during pregnancy. Unlike early studies, those reviewed here show no association between in utero exposure to medical ionizing radiation, which may be explained by reductions over time in radiation doses, avoidance of radiation during pregnancy, and/or by inadequate statistical power to detect small increases in risk, rather than a lack of causal association. Evidence is mixed or conflicting for an association between childhood cancer and maternal obesity, birth order, cesarean/instrumental delivery, and prenatal exposure to diagnostic medical radiation. Evidence is weak or absent for associations between childhood cancer and multiple gestations or assisted reproductive therapies, as well as prenatal exposure to hormones other than DES, and medications. Full article
10 pages, 345 KB  
Article
Natural History of Hyperphagia in Patients with Pseudohypoparathyroidism
by Jaclyn Tamaroff and Ashley H. Shoemaker
J. Clin. Med. 2025, 14(15), 5345; https://doi.org/10.3390/jcm14155345 - 29 Jul 2025
Cited by 1 | Viewed by 734
Abstract
Background/Objectives: Pseudohypoparathyroidism (PHP) is a group of genetic disorders characterized by end-organ resistance to multiple hormones, short stature, brachydactyly, subcutaneous ossifications, obesity, and developmental delays. The tissue specific imprinting of GNAS in the hypothalamus may lead to different eating behavior phenotypes in [...] Read more.
Background/Objectives: Pseudohypoparathyroidism (PHP) is a group of genetic disorders characterized by end-organ resistance to multiple hormones, short stature, brachydactyly, subcutaneous ossifications, obesity, and developmental delays. The tissue specific imprinting of GNAS in the hypothalamus may lead to different eating behavior phenotypes in maternally inherited (PHP1A, PHP1B) vs. paternally inherited (PPHP) variants. In this exploratory study, we aimed to evaluate differences in eating behaviors in a cohort of patients with PHP1A, PPHP and PHP1B. Methods: Assessments included caregiver-reported measures (hyperphagia questionnaire, children’s eating behavior questionnaire, child feeding questionnaire) and self-reported measures (three factor eating behavior questionnaire). Results: A total of 58 patients with PHP1A, 13 patients with PPHP and 10 patients with PHP1B contributed data, along with 124 obese pediatric controls. An increased risk of obesity was found in PHP1A vs. PPHP (adult body mass index (BMI) 39.8 ± 8.7 vs. 30.2 ± 7.4 kg/m2, p = 0.03). Parents reported significantly earlier onset of interest in food in children with PHP1A (2.0 ± 2.3 years) and PHP1B (1.1 ± 1.3 years) compared with controls (5.2 ± 3.2 years, p < 0.001). Measures of hyperphagia, satiety and other feeding behaviors were all similar to controls. The highest hyperphagia questionnaire scores were seen prior to adolescence. In a multi-year, longitudinal assessment of 11 pediatric patients with PHP1A, hyperphagia scores were stable and 25% showed an improvement in symptoms. Conclusion: Patients with PHP1A/1B may have hyperphagia symptoms from a young age but they do not worsen over time. Patients may overeat when allowed access to food, but do not usually have disruptive food seeking behaviors. Early diagnosis can give clinicians the opportunity to provide anticipatory diagnosis on the increased risk of obesity in PHP1A/1B and need for scheduled meals and controlled portions. Further studies with larger cohorts are needed to confirm these findings. Full article
(This article belongs to the Special Issue Research Progress in Pediatric Endocrinology)
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10 pages, 807 KB  
Case Report
A Case of Salt-Wasting Congenital Adrenal Hyperplasia Caused by a Rare Intronic Variant in the CYP21A2 Gene
by Zoia Antysheva, Anton Esibov, Ekaterina Avsievich, Ekaterina Petriaikina, Vladimir Yudin, Anton Keskinov, Sergey Yudin, Dmitry Svetlichnyy, Julia Krupinova, Aleksey Ivashechkin, Yulia Katsaran, Mary Woroncow, Veronika Skvortsova, Viktor Bogdanov and Pavel Volchkov
Int. J. Mol. Sci. 2025, 26(14), 6648; https://doi.org/10.3390/ijms26146648 - 11 Jul 2025
Viewed by 1892
Abstract
This case report describes a novel intronic mutation, CYP21A2:c.738+75C>T (rs1463196531), identified in a 4-year-old male with congenital adrenal insufficiency, and expands the known mutation spectrum associated with this condition. The patient, born full-term to unrelated parents, presented with adrenal failure within the [...] Read more.
This case report describes a novel intronic mutation, CYP21A2:c.738+75C>T (rs1463196531), identified in a 4-year-old male with congenital adrenal insufficiency, and expands the known mutation spectrum associated with this condition. The patient, born full-term to unrelated parents, presented with adrenal failure within the first month of life, characterized by acute adrenal crisis symptoms such as vomiting, dehydration, weight loss, hypotension, and electrolyte imbalances. Hormonal evaluations confirmed primary adrenocortical insufficiency, necessitating ongoing hydrocortisone and fludrocortisone therapy. Using family trio-based amplicon sequencing of the CYP21A2 gene, we identified compound heterozygosity consisting of a full gene deletion and a novel pathogenic intronic mutation. Additionally, analysis of WGS data was performed to rule out pathogenic variants in genes that might lead to a similar phenotype, thereby eliminating the possibility of other genes contributing to the proband’s disease. This case demonstrates the potential of using amplicon sequencing in molecular genetic diagnostic testing to detect rare intronic variants in the CYP21A2 gene in cases of early-onset adrenal failure. It also contributes to a better understanding of the genetic basis of congenital adrenal hyperplasia (CAH), which remains a significant autosomal recessive disorder affecting cortisol and aldosterone production, with an incidence of 1 in 10,000 to 1 in 15,000 globally. Full article
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Review
An Integrative Approach to Assessing the Impact of Mercury (Hg) on Avian Behaviour: From Molecule to Movement
by Dora Bjedov, Mirta Sudarić Bogojević, Jorge Bernal-Alviz, Goran Klobučar, Jean-Paul Bourdineaud, K. M. Aarif and Alma Mikuška
J. Xenobiot. 2025, 15(4), 117; https://doi.org/10.3390/jox15040117 - 9 Jul 2025
Viewed by 1711
Abstract
Mercury (Hg) pollution is a widespread ecological threat with sublethal effects on wildlife. Birds, due to their ecological diversity and sensitivity, serve as effective models for evaluating the behavioural impacts of Hg exposure. This review applies Tinbergen’s four questions: causation, ontogeny, function, and [...] Read more.
Mercury (Hg) pollution is a widespread ecological threat with sublethal effects on wildlife. Birds, due to their ecological diversity and sensitivity, serve as effective models for evaluating the behavioural impacts of Hg exposure. This review applies Tinbergen’s four questions: causation, ontogeny, function, and evolution, as an integrative framework. Mechanistically, Hg disrupts neuroendocrine pathways, gene expression, immune function, and hormone regulation, leading to behavioural changes such as reduced foraging, altered parental care, and impaired predator avoidance. Early-life exposure affects neural development, learning, and social behaviour into adulthood. Functionally, these changes reduce fitness by compromising reproduction and survival. Phylogenetic comparisons show interspecific variability, with piscivorous and insectivorous birds exhibiting high Hg burdens and sensitivity, linked to ecological roles and exposure. Behavioural responses often precede physiological or demographic effects, highlighting their value as early indicators. Both field and laboratory studies show that even low Hg concentrations can alter behaviour, though outcomes vary by species, life stage, and exposure route. Integrating behavioural endpoints into ecotoxicological risk assessments is essential to improve conservation strategies and understanding of sublethal pollutant effects on wildlife. Full article
(This article belongs to the Section Ecotoxicology)
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