Search Results (3,336)

Curcumin, the major polyphenolic constituent of Curcuma longa, has been widely investigated as a hepatoprotective adjunct due to its antioxidant and immunomodulatory properties. This review evaluates the relevance of curcumin for the prevention and management of liver dysfunction and hepatitis in pigs by synthesizing available porcine evidence and integrating mechanistic insights from translational liver injury models where pig-specific data remain limited. Across experimental hepatic injury contexts, curcumin administration is most consistently associated with reduced biochemical and structural indicators of hepatocellular damage, including decreased aminotransferase activity, attenuation of lipid peroxidation, and enhancement of endogenous antioxidant defenses. These effects are mechanistically linked to suppression of pro-inflammatory signaling pathways, particularly NF-κB-related transcriptional activity and inflammasome-associated responses, together with reduced expression of key cytokines such as TNF-α, IL-1β, and IL-6. Concurrent activation of Nrf2-centered cytoprotective pathways and induction of phase II antioxidant enzymes (including HO-1, GST, and NQO1) appear to constitute a conserved axis supporting hepatic oxidative stress resilience. In swine-relevant infectious settings, available data further support antiviral activity against selected porcine pathogens, including classical swine fever virus and porcine reproductive and respiratory syndrome virus, potentially mediated through interference with lipid-dependent stages of viral replication and modulation of Kupffer cell activation. Although combination strategies with established hepatoprotective approaches are conceptually attractive, current synergy evidence remains heterogeneous and largely extrapolated. Overall, curcumin represents a plausible adjunct candidate for supporting porcine liver health; however, translation into practice will depend on resolving formulation-dependent bioavailability constraints and strengthening the pig-specific evidence base. Full article

There is increasing evidence that exposure to environmental toxicants may impact fertility, especially during critical windows of reproductive axis development. Hypothalamic gonadotropin-releasing hormone (GnRH) neurons, essential for puberty onset and fertility, originate from the olfactory placode and migrate toward the hypothalamus during development, making them particularly vulnerable to environmental insults. Cadmium (Cd), a widespread heavy metal, is well known for its gonadotoxicity, but its impact on human hypothalamic neuron development remains unclear. Using human fetal GnRH neuroblasts (FNCB4) we investigated the effects of Cd exposure on their morpho-functional and developmental features. Cd induced oxidative stress and COX2 mRNA upregulation, indicative of inflammatory pathway activation, which was accompanied by reduced cell migration and downregulation of motility-related genes. These effects were associated with F-actin disassembly and altered expression of adhesion molecules. Electrophysiological analyses showed that Cd altered membrane potential, increased capacitance and permeability, and disrupted gap junctional communication, as also confirmed by connexin-43 delocalization. Moreover, Cd significantly reduced the expression of specific GnRH neuronal markers, suggesting impaired functional maturation. Overall, our findings provide the first evidence that Cd may interfere with mechanisms crucially involved in human GnRH neuron development, adding new mechanistic insights into the comprehension of how early-life exposure to Cd may contribute to fertility concerns. Full article

Methyl farnesoate (MF) is a sesquiterpenoid hormone that controls a variety of physiological processes in crustaceans, including morphogenesis, development, reproduction, and molting. MF action is mediated by a transcriptional signaling cascade consisting of Methoprene-tolerant (Met), Steroid receptor coactivator (Src), Krüppel homolog 1 (Kr-h1), and Ecdysone response gene 93 (E93) transcription factors (TFs), and transcriptional co-regulators CREB-binding protein (CBP) and C-terminal-binding protein (CtBP). Phylogenetic and sequence analyses revealed that these genes were highly conserved across pancrustacean species. Met and Src were characterized as basic helix-loop-helix, Period (Per)-Aryl Hydrocarbon Nuclear Translocator (ARNT)-Single-minded (Sim) protein (bHLH-PAS) TFs; Kr-h1 was characterized as a C₂H₂ zinc finger TF with seven zinc finger motifs; E93 was characterized as a helix-turn-helix, pipsqueak (HTH_Psq) TF. CBP was identified by several zinc finger-binding regions with Transcription Adaptor Zinc Finger 1 and 2, Really Interesting New Gene, Plant homeodomain, and Z-type zinc finger domains; the Kinase-inducible Domain Interacting-transcription factor docking site; the Bromodomain-acetylated lysine recognition and binding site; the histone acetyltransferase domain; and a C-terminal CREB-binding region containing a nuclear receptor co-activator-binding domain. CtBP had a dehydrogenase domain with arginine-glutamate-histidine catalytic triad. 81 Met contigs, 45 Src contigs, 136 Kr-h1 contigs, 66 E93 contigs, 60 CBP contigs, and 172 CtBP contigs were identified across pancrustacean taxa, including decapod crustaceans. Bioinformatic identification and annotation of these TFs and co-regulators in brachyuran Y-organ (YO) transcriptomes suggests that MF signaling influences YO ecdysteroidogenesis; functional tests in the YO are needed to establish causality. Full article

This study was conducted to investigate the effects of dietary polyunsaturated fatty acid (PUFA) levels and FME (flavor and multiple enzymes) on the reproductive performance, nutrient digestion, and metabolism, immunity, and antioxidant capacity of sows and piglets. Forty primiparous sows [Duroc × (Landrace × York)] were randomly assigned from day 107 of gestation to day 7 post-weaning to one of four dietary treatments, low PUFA (4.6% tallow, LP), high PUFA (4.6% fish oil, HP), and LP and HP, each supplemented with 600 mg/kg FME (LP + FME, HP + FME). Results showed that dietary HP + FME supplementation significantly alleviated sow backfat loss during lactation (p < 0.05). Dietary FME supplementation significantly increased milk lactose and solids-non-fat (p < 0.05) on day 15. Meanwhile, milk protein and true protein contents were significantly lower in the LP treatment than in the LP + FME and HP treatments. The apparent total-tract digestibility (ATTD) of ash and phosphorus was improved (p < 0.05) by both HP diets and FME supplementation. The ATTD of energy and dry matter was significantly higher in LP + FME treatment than in LP and HP + FME treatments (p < 0.05). HP diets increased serum malondialdehyde (MDA, p < 0.01), total superoxide dismutase (p < 0.05) in sows, and increased serum MDA and decreased hydrogen peroxide (H₂O₂) contents in piglets (p < 0.05). Dietary FME supplementation decreased serum H₂O₂ contents and increased serum catalase activity of sows and/or piglets (p < 0.05). The serum immune markers, lipid, and protein metabolites of sows and piglets were altered (p < 0.05 or p < 0.10) by HP diets and/or FME supplementation. In conclusion, dietary fish oil (4.6% of diet replacing tallow) and FME (600 mg/kg) supplementation improved lactating performance by improving nutrient digestibility, body reserve mobilization, antioxidant capacity, and health state of sows and piglets. Full article

Background: Preserving fertility in young women with cancer is crucial for comprehensive care. Based on GBD 2023 estimates, approximately 1000 women aged 15–39 are diagnosed with haematological malignancies annually in Italy. Guidelines recommend timely fertility preservation (FP) counselling for all at-risk patients, yet real-world access data remain limited. Methods: This multicentre, retrospective observational study analysed FP counselling for women aged 15–39 with haematological malignancies from 2015 to 2023. Counselling data were extracted from the Italian Assisted Reproductive Technology Registry (IARTR). This data collection system, known as PreFerIta, was developed within a project supported by the Italian Ministry of Health to collect data on Fertility Preservation (FP) treatments in oncology patients and/or those at risk of iatrogenic infertility, provided in seven specialised ART centres across Italy. The PreFerIta database includes data on both oocyte cryopreservation and ovarian tissue cryopreservation. Annual visits were related to the estimated regional incidence of new haematological malignancies (GBD 2023). Counselling-to-incidence ratios, absolute/relative gaps, and 95% confidence intervals (CIs) were calculated. Results: From 2015 to 2023, an estimated 4473 new haematological malignancies occurred in the catchment regions. Concurrently, 1200 FP counselling visits were recorded. While incidence modestly declined, counselling activity remained high. The counselling-to-incidence ratio increased from 17.33% in 2015 to 31.92% in 2018, stabilising between 26% and 31% thereafter (30.98% in 2023). The relative counselling gap decreased from 82.67% to 69.02%. These ratios represent lower-bound estimates of access to specialised oncofertility consultations. Conclusions: In this Italian network, approximately one in four to one in three incident haematological malignancies in young women were associated with specialised FP counselling. This reflects a substantial integration of oncofertility services into haematology care, highlighting opportunities to further strengthen referral pathways and achieve full guideline concordance. Full article

Fisetin is a naturally occurring flavonoid, a type of polyphenol found in fruits and vegetables such as strawberries, apples, persimmons, and onions. It has gained increasing attention for its antioxidant properties (enhancement of SOD1 and CAT activity and reduction of ROS), anti-inflammatory effects (suppression of NF-κB signaling), and senotherapeutic activity (senolytic and senomorphic effects). Although numerous studies have examined fisetin in the context of aging and chronic diseases, its role in women’s reproductive health has not been systematically explored. Mechanistically, fisetin regulates several pathophysiological processes, including ovarian aging, fibrosis, angiogenesis, and hormonal regulation, suggesting its potential relevance to female reproductive health and disease. Indeed, emerging evidence indicates that fisetin may support ovarian function and hormonal balance, modulate fibrosis and metabolism in benign gynecologic conditions, and suppress cell growth in gynecologic cancers. Early-phase clinical studies in non-gynecologic conditions suggest an acceptable safety profile, although evidence in reproductive health remains absent. This review summarizes current experimental and clinical evidence, identifies critical gaps in mechanistic understanding, and discusses future directions for advancing fisetin as a promising non-hormonal therapeutic option in reproductive health and diseases. Full article

Bump feeding is a nutritional management strategy in swine production that involves increasing feed allowance and/or dietary nutrient density during the final weeks of gestation, usually from day 90 to farrowing, to support rapid fetal growth and prepare sows for lactation. This strategy is widely applied to improve piglet birth weight, neonatal viability, and subsequent reproductive performance. This review synthesizes current evidence on the effects of increased maternal feed intake during late gestation on sow body condition and feeding-related behavioral responses, and farrowing outcomes. Available studies suggest that increasing feed allowance during late gestation can influence litter characteristics, piglet survival at birth, and sow energy reserves, as reflected by changes in backfat thickness (BFT) and body condition score (BCS). The nutritional composition of bump-feeding diets, including dietary energy and amino acid balance, is critically evaluated in relation to pregnancy maintenance, farrowing duration, and early lactation performance. In addition, the roles of parity and feeding behavior during late gestation are examined, with particular emphasis on their associations with sow activity patterns, restlessness around parturition, and farrowing efficiency. Despite these reported effects, findings across studies remain inconsistent, particularly regarding the balance between improved reproductive outcomes and the risk of excessive fat deposition in sows. This review highlights key knowledge gaps and underscores the need for optimized, parity-specific bump-feeding strategies that integrate nutritional management with feeding behavior to enhance farrowing performance, piglet survival, sow welfare, and economic sustainability in modern pig production. Full article

Psychological stress is increasingly investigated as a potentially modifiable factor in male infertility, in part through oxidative stress. This narrative review synthesizes mechanistic and translational evidence linking stress-related neuroendocrine activation and coping behaviors with redox imbalance in the male reproductive tract. Chronic activation of the hypothalamic–pituitary–adrenal axis and sympathetic outflow elevates glucocorticoids and catecholamines. In controlled animal stress paradigms, this is accompanied by suppression of the hypothalamic–pituitary–gonadal axis and by immune and metabolic changes that favor reactive oxygen species generation. The resulting oxidative stress may reduce Leydig cell steroidogenesis, impair testicular and epididymal function, and induce lipid peroxidation, mitochondrial dysfunction, and sperm DNA fragmentation. In such models, these lesions, together with apoptosis of germ and supporting cells, are associated with lower sperm concentration, reduced motility, compromised viability, and diminished fertilizing potential. Overall, preclinical animal studies using defined stress paradigms provide experimental evidence consistent with causal effects of stress on oxidative injury and reproductive impairment in preclinical settings. Human studies linking perceived stress, anxiety/depression, and disturbed sleep to adverse semen parameters and oxidative biomarkers are summarized. However, the human evidence is predominantly associative, and the available studies are cross sectional and remain vulnerable to residual confounding and reverse causality. Potential effect modifiers, including smoking, alcohol use, and circadian disruption, are also discussed as contributors to heterogeneity across clinical studies. Standardized assessment of stress biology and redox status, longitudinal designs aligned with spermatogenic timing, and well-powered intervention trials are needed to define dose–response relationships and support individualized prevention and care. Full article

The unicellular ciliate Paramecium caudatum undergoes a developmental transition from asexual binary fission to sexual reproduction during its mature stage. This transition is triggered by mating interactions between cells of complementary mating types, leading to aggregate formation, mating pairs, and the meiotic division of micronuclei. Although calcium-driven EF-hand kinases have been implicated as mating type proteins, the spatiotemporal dynamics of calcium signaling during conjugation have not been comprehensively characterized. In this study, we established a behavioral assay to isolate committed cells from aggregates immediately after mating onset, and developed an experimental system to monitor intracellular calcium fluctuations specifically expressed in these cells. By combining Ca²⁺/EGTA buffering and microinjection approaches, we manipulated extracellular and intracellular calcium levels and confirmed the continuous requirement of calcium ions for conjugation-specific functions. Two significant findings emerged. First, we identified, for the first time, a calcium atlas covering the entire cell, with ascending centers localized in the anterior, oral apparatus, and posterior regions. The calcium/Indo-1-AM fluorescence peaked at 6 h after mating initiation and declined gradually, but persisted until conjugation was completed at ~48 h. Second, we demonstrated that distinct intracellular calcium thresholds are required for each stage of mating, including maintenance of mating activity, commitment of micronuclei to meiosis, and two-stepwise formation of mating pairs. These thresholds function as regulatory checkpoints that coordinate subcellular localization and stage synchronization. Collectively, our findings highlight calcium ions as pivotal regulators of conjugation in Paramecium and propose a novel framework, the Paramecium calcium atlas, for understanding the cellular and molecular mechanisms underlying sexual reproduction in ciliates. Full article

Wee1-like protein kinase 2 (WEE2) is an oocyte-specific kinase that regulates meiotic arrest and fertilization. Its largely restricted expression in female germ cells and absence in somatic tissues make it a highly selective target for reproductive health interventions. Despite its central role in human fertility, no clinically approved WEE2 modulator is available. In this study, we employed an integrated in silico approach that combines structure-based virtual screening, molecular dynamics (MD) simulations, and MM-PBSA free-energy calculations to identify repurposed drug candidates with potential WEE2 inhibitory activity. Screening of ~3800 DrugBank compounds against the WEE2 catalytic domain yielded ten high-affinity hits, from which Midostaurin and Nilotinib emerged as the most mechanistically relevant based on kinase-targeting properties and pharmacological profiles. Docking analyses revealed strong binding affinities (−11.5 and −11.3 kcal/mol) and interaction fingerprints highly similar to the reference inhibitor MK1775, including key contacts with hinge-region residues Val220, Tyr291, and Cys292. All-atom MD simulations for 300 ns demonstrated that both compounds induce stable protein–ligand complexes with minimal conformational drift, decreased residual flexibility, preserved compactness, and stable intramolecular hydrogen-bond networks. Principal component and free-energy landscape analyses further indicate restricted conformational sampling of WEE2 upon ligand binding, supporting ligand-induced stabilization of the catalytic domain. MM-PBSA calculations confirmed favorable binding free energies for Midostaurin (−18.78 ± 2.23 kJ/mol) and Nilotinib (−17.47 ± 2.95 kJ/mol), exceeding that of MK1775. To increase the translational prioritization of candidate hits, we place our structure-based pipeline in the context of modern machine learning (ML) and deep learning (DL)-enabled virtual screening workflows. ML/DL rescoring and graph-based molecular property predictors can rapidly re-rank docking hits and estimate absorption, distribution, metabolism, excretion, and toxicity (ADMET) liabilities before in vitro evaluation. Full article

Short-term hypothermic storage at 4 °C represents a promising non-freezing alternative for transporting bovine embryos and synchronizing assisted reproductive procedures. However, chilling induces oxidative stress, mitochondrial dysfunction, and apoptosis, which markedly impair post-preservation embryonic viability. Glutathione (GSH), a key intracellular antioxidant, may mitigate these damaging effects, yet its protective mechanisms during bovine blastocyst hypothermic preservation remain unclear. Here, we investigated the impact of exogenous GSH supplementation on the survival, hatching ability, cellular integrity, mitochondrial function, and developmental potential of bovine blastocysts preserved at 4 °C for seven days. Optimization experiments revealed that 4 mM GSH provided the highest post-chilling survival and hatching rates. Using DCFH-DA, TUNEL, and γ-H2AX staining, we demonstrated that 4 °C preservation significantly increased intracellular reactive oxygen species (ROS), DNA fragmentation, and apoptosis. GSH supplementation markedly alleviated oxidative injury, reduced apoptotic cell ratio, and decreased DNA double-strand breaks. MitoTracker and JC-1 staining indicated severe chilling-induced mitochondrial suppression, including decreased mitochondrial activity and membrane potential (ΔΨm), which were largely restored by GSH. Gene expression analyses further revealed that chilling downregulated antioxidant genes (SOD2, GPX1, TFAM, NRF2), pluripotency markers (POU5F1, NANOG), and IFNT, while upregulating apoptotic genes (BAX, CASP3). GSH effectively reversed these alterations and normalized the BAX/BCL2 ratio. Moreover, SOX2/CDX2 immunostaining, total cell number, and ICM/TE ratio confirmed improved embryonic structural integrity and developmental competence. Collectively, our findings demonstrate that exogenous GSH protects bovine blastocysts from chilling injury by suppressing ROS accumulation, stabilizing mitochondrial function, reducing apoptosis, and restoring developmental potential. This study provides a mechanistic foundation for improving 4 °C embryo storage strategies in bovine reproductive biotechnology. Full article

Chlamydia trachomatis has a significant impact on public health, especially among adolescents and young women; it primarily affects urogenital epithelial cells, leading to cervicitis and urethritis, with >90% of cases showing no symptoms. Consequently, chlamydial infections are commonly misdiagnosed, and, if untreated, they may result in severe reproductive sequelae including infertility. A better understanding of C. trachomatis cell biology and bacterial–host cell interactions may be helpful to identify strategies able to counter its transmission among the population, as well as its dissemination in reproductive tissues, reducing the risk of developing severe reproductive sequelae. Therefore, the present review aims to summarize the evidence on the interplay between C. trachomatis and the host defence factors within the cervicovaginal environment. The sophisticated strategies employed by this clinically significant pathogen to counteract these mechanisms are also discussed. In the literature, the main defence factors include the microbiota dominated by Lactobacillus crispatus and several molecules like lactoferrin, able to protect the cervicovaginal microenvironment against C. trachomatis through several mechanisms (e.g., EB coaggregation and competitive exclusion, as well as anti-inflammatory activity). However, the major player in clearing chlamydial infections remains the interferon-gamma (IFN-γ) produced by natural killer and T cells, via the depletion of critical nutrients for C. trachomatis such as tryptophan, or via the ubiquitylation and destruction of chlamydial inclusions. Full article

Nanotechnology has emerged as a transformative tool in animal production, offering novel strategies to enhance productivity, health, and product quality. Among trace elements, selenium (Se) plays an essential role in antioxidant defence, immune regulation, and redox balance through its incorporation into selenoproteins. Selenium nanoparticles (SeNPs), synthesized via chemical, physical, or biological methods, have shown superior bioavailability, stability, and lower toxicity compared to traditional organic and inorganic selenium forms. This review explores the synthesis, physicochemical properties, and metabolic fate of SeNPs, emphasizing their advantages in poultry production systems. In poultry, SeNPs exhibit potent antioxidant and anti-stress effects by enhancing the activity of glutathione peroxidase, superoxide dismutase, and thioredoxin reductase, thereby mitigating lipid peroxidation and oxidative tissue damage. Their immunomodulatory effects are linked to improved lymphocyte proliferation, cytokine regulation, and increased immunoglobulin levels under normal and stress conditions. SeNP supplementation has been associated with enhanced growth performance, feed efficiency, carcass quality, and reproductive outcomes in broilers, layers, and quails. Furthermore, selenium nanoparticles have demonstrated therapeutic potential in preventing or alleviating chronic diseases such as cancer, diabetes, cardiovascular dysfunction, and neurodegenerative disorders. SeNPs also serve as biofortification agents, increasing selenium deposition in poultry meat and eggs, thus improving their nutritional value for human consumption. However, selenium’s narrow safety margin requires careful dose optimization to avoid potential toxicity. This review highlights the multifaceted benefits of selenium nanoparticles in poultry nutrition and health, while underscoring the need for further studies on grey SeNPs, long-term safety, and regulatory frameworks. Integrating SeNPs into poultry production represents a promising strategy to bridge animal health, food security, and public nutrition. Full article

Oocytes cultured in vitro are exposed to high oxygen tension and lack follicular antioxidants, leading to redox imbalance. Eicosapentaenoic acid (EPA), a marine long-chain n-3 polyunsaturated fatty acid, possesses strong antioxidant activity. Here, using pigs as a model, we examined the effects of EPA on oocyte in vitro maturation (IVM) and subsequent developmental competence. Cumulus–oocyte complexes were cultured with EPA, followed by assessment of nuclear and cytoplasmic maturation and embryonic development; transcriptomic and proteomic analyses were conducted to explore underlying mechanisms. Supplementation with 10 µM EPA significantly improved maturation and blastocyst rates by reducing spindle defects, facilitating a more uniform organization of cortical granules and mitochondria. EPA increased resolvin E1 accumulation and reduced cumulus-cell apoptosis through downregulation of TNF-α and BAX and upregulation of BCL2. In MII oocytes, EPA lowered apoptosis, DNA damage, and ROS levels while enhancing SOD2 and GPX4 expression. Mitochondrial quality and turnover were improved via upregulation of PPARGC1A, NDUFS2, PINK1, LC3, FIS1, MUL1, and OPA1, alongside strengthened ER–mitochondria contacts. These findings demonstrate that EPA alleviates oxidative stress, optimizes mitochondrial function, and enhances porcine oocyte maturation and developmental competence in a parthenogenetic model, highlighting its potential as a marine-derived functional additive for reproductive biotechnology. Future studies will be required to validate these effects under fertilization-based embryo production systems and to further refine dose–response relationships using expanded embryo-quality endpoints. Full article

Early weaning in intensive lamb production improves reproductive efficiency but predisposes lambs to diarrhea, oxidative stress, and intestinal barrier dysfunction, highlighting the need for non-antibiotic strategies to protect gut health. This study evaluated whether a sheep-derived mixed probiotic could alleviate early weaning–induced intestinal injury and clarified its potential molecular mechanisms. Early weaning reduced body weight, average daily gain and feed efficiency, increased diarrhea, decreased plasma and colonic catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) activities, increased malondialdehyde (MDA), elevated interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), reduced interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), increased plasma and mucosal immunoglobulin A, M, and G (IgA, IgM, IgG), and increased colonic lipopolysaccharide (LPS) with reduced diamine oxidase (DAO). Intestinally, EW induced villus atrophy, deeper crypts, lower villus height-to-crypt depth ratios, goblet cell loss, higher histopathological scores, and decreased colonic mucin 2, zonula occludens-1, claudin-1, and occludin. Probiotic supplementation partially reversed these alterations, restoring antioxidant enzyme activities, improving villus architecture and barrier protein expression, and rebalancing cytokine and immunoglobulin profiles. Transcriptomic and network analyses showed that early weaning activated Cytokine–cytokine receptor, NF-κB, TNF and Th17 pathways, whereas probiotics suppressed a weaning-responsive inflammatory gene module, downregulated key hub genes, and enhanced peroxisome proliferator-activated receptor (PPAR) signaling. These results show that supplementing early-weaned lambs with a mixed probiotic generated from sheep is an efficient nutritional strategy to reduce intestinal oxidative and inflammatory damage associated with weaning and to enhance their health and performance. Full article