Search Results (934)

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

Epithelial ovarian cancer (EOC) represents the most lethal malignancy arising from the female reproductive tract, largely due to the clinical challenge of chemotherapy resistance. Recent studies indicate that ferroptosis—a distinct form of programmed cell death driven by iron accumulation and lipid peroxidation, could potentially exploit a vulnerability in chemoresistant cancer cells. Here, we identify MED12 as a critical regulator of ferroptosis sensitivity in EOC through modulation of the YAP–TEAD1 signaling pathway. Using CRISPR/Cas9-mediated knockout and rescue experiments in EOC cell lines, we demonstrate that MED12 deficiency significantly enhances sensitivity to ferroptosis inducers (RSL3 and Erastin), as evidenced by reduced IC50 values. Transcriptomic and chromatin accessibility analyses reveal that MED12 loss activates YAP signaling through TEAD1 upregulation, increasing chromatin accessibility at YAP–TEAD1 target loci and elevating the expression of downstream effectors CYR61 and CTGF. Pharmacological inhibition of YAP with verteporfin or siRNA-mediated TEAD1 knockdown reverses ferroptosis sensitivity in MED12-deficient cells, confirming pathway specificity. These findings establish MED12 as a modulator of the YAP–TEAD1–ferroptosis axis and suggest that targeting this pathway could overcome chemoresistance in MED12-deficient EOC. Our work provides a mechanistic foundation for exploiting ferroptosis induction as a therapeutic strategy in ovarian cancer. Full article

T-cell immunoglobulin and mucin domain 3 (TIM-3), a well-known immune checkpoint molecule, is increasingly recognized for its regulatory functions beyond T cell exhaustion, particularly in macrophages. Recent advances have revealed the important role of this molecule in various pathological and physiological conditions. The demand for a comprehensive study of TIM-3 is increasing, particularly as a result of ongoing clinical trials targeting TIM-3 in oncology. This review is devoted to the role of TIM-3 in macrophage biology, focusing on associations between TIM-3 expression and macrophage polarization states and functional activity, as well as its involvement in the pathogenesis of different diseases and reproductive immunology. The review examines known effects and molecular mechanisms by which TIM-3 regulates macrophage functional phenotype and the contribution of TIM-3-expressing macrophages to cancer, pregnancy, inflammation, infectious and autoimmune diseases, and fibrosis. Findings highlight the controversial role of TIM-3 in the regulatory function of macrophages and suggest that TIM-3 functions differently depending on the context. The review also touches on gaps and unexplored parts of the topic. A summary of current data allows us to conclude that TIM-3 is an important modulator of macrophage functions and can be considered a potential therapeutic target in various pathological conditions. Full article

Pseudouridine (Ψ), the most abundant RNA modification, plays essential roles in shaping RNA structure, stability, and translational output. Beyond cancer, Ψ is dynamically regulated across numerous physiological and pathological contexts—including immune activation, metabolic disorders, stress responses, and pregnancy-related conditions such as preeclampsia—where elevated Ψ levels reflect intensified RNA turnover and modification activity. These broad functional roles highlight pseudouridylation as a central regulator of cellular homeostasis. Emerging evidence demonstrates that Ψ dysregulation contributes directly to the development and progression of several women’s cancers, including breast, ovarian, endometrial, and cervical malignancies. Elevated Ψ levels in tissues, blood, and urine correlate with tumor burden, metastatic potential, and therapeutic responsiveness. Aberrant activity of Ψ synthases such as PUS1, PUS7, and the H/ACA ribonucleoprotein component dyskerin alters pseudouridylation patterns across multiple RNA substrates, including rRNA, tRNA, mRNA, lncRNAs, snoRNAs, and ncRNAs. These widespread modifications reshape ribosome function, modify transcript stability and translational efficiency, reprogram RNA–protein interactions, and activate oncogenic signaling programs. Advances in high-resolution, site-specific Ψ mapping technologies have further revealed mechanistic links between pseudouridylation and malignant transformation, highlighting how modification of distinct RNA classes contributes to altered cellular identity and tumor progression. Collectively, Ψ and its modifying enzymes represent promising biomarkers and therapeutic targets across women’s cancers, while also serving as sensitive indicators of diverse non-cancer physiological and disease states. Full article

Background/Objective: High-risk Human papillomavirus (hrHPV) is the leading cause of premalignant lesions and cervical cancer (CC), affecting disproportionally women living with HIV. Mozambique is among the countries with a heavy triple-burden of HIV, hrHPV infections and CC which accounts for more than 5300 new cases and 3800 deaths each year. In this study, we assessed the age-specific distribution and factors associated with hrHPV and cervical lesions among HIV-positive and -negative women from HPV-ISI (HPV Innovative Screening Initiative) study in Maputo, Mozambique. Methods: This cross-sectional study included 1248 non-pregnant women aged ≥18 years who attended CC screening at the DREAM Sant’Egídio Health Centre between July 2021 and April 2022. Screening involved visual inspection with acetic acid (VIA) and high-risk HPV DNA testing. Sociodemographic, lifestyle, and reproductive data were collected through a routine questionnaire. Logistic regression assessed associations between risk factors and hrHPV infection or cervical lesions. Age-specific hrHPV prevalence, partial HPV16/18 genotyping, and abnormal cytology rates were further analyzed by HIV status. Results: The mean age of participants was 43.0 ± 8.6 years. Overall hrHPV prevalence was 28.0%, being higher among HIV-positive women (46.8%) than HIV-negative women (23.8%). Non-16/18 hrHPV genotypes predominated across all age groups. VIA positivity was 11.1%, most frequently involving less than 75% of the cervical area and was more common among younger women (30–45 years) and those living with HIV. Increasing age was associated with lower odds of hrHPV infection (OR = 0.98, 95% CI: 0.97–1.00; p = 0.017), as was higher parity (≥3 deliveries vs. nulliparity: OR = 0.58, 95% CI: 0.36–0.94; p = 0.029). Contraceptive use (OR = 1.65, 95% CI: 1.15–2.38; p = 0.007) and a partially or non-visible squamocolumnar junction (SCJ) (OR = 2.88, 95% CI: 1.74–4.79; p < 0.001) were associated with higher odds of VIA positivity. Conclusions: hrHPV infection and cervical lesions were more frequent in younger and HIV-positive women, highlighting the need for strengthened targeted screening within HIV care services in Mozambique. Full article

Follicle-stimulating hormone receptor (FSHR) is expressed on the plasma membrane of granulosa cells in the ovarian follicles. FSHR is involved in the development and maturation of Graafian follicles, along with granulosa proliferation and estrogen synthesis. There are two well-characterized non-synonymous single-nucleotide gene polymorphisms in the exon 10 of the human FSHR gene, namely rs6165 (c.919G>A, Ala307Thr) and rs6166 (c.2039A>G, Ser680Asn). Recent research clarifies the association of rs6165/rs6166 with susceptibility to infertility-associated ovarian diseases, ranging from polycystic ovarian syndrome, premature ovarian insufficiency, endometriosis, to ovarian cancer, along with response/resistance to ovulation induction/ovarian stimulation with clomiphene citrate, letrozole, metformin, FSH preparations, and adjunctive growth hormone in infertility treatment. This narrative review aims to update the knowledge on the relationship among rs6165/rs6166, infertility etiology, and differential responses to oral ovulation induction agents, FSH preparations, and adjunctive growth hormone. The re6165/rs6166 genotype-guided choice of individualized ovulation stimulation preparations has great potential to reduce unexpected poor or high ovarian responses in ovulation induction and ovarian stimulation and improve clinical outcomes in reproductive medicine. Current evidence is insufficient, and further studies are warranted to ascertain its potential for clinical implementation. Full article

The Kazakh horse is an outstanding dual-purpose dairy and meat breed in China, characterized by early maturity, tolerance to coarse feed, and strong stress resistance. Previous studies have examined gene expression patterns in the testicular tissues of Kazakh horses at different age stages, but the molecular mechanisms regulating testicular sexual maturation remain unclear. To address this gap, this study conducted HE staining and in-depth transcriptome sequencing analysis of Kazakh horse testicular tissue before and after sexual maturity. HE staining showed that the G3 group had well-formed seminiferous tubule lumens, dense interstitial cells, and visible early spermatocytes and spermatozoa, indicating structural maturation. (G1 group: pre-sexual maturity; G3 group: post-sexual maturity), with four biological replicates per group (n = 4). Differentially expressed genes (DEGs) were called using the criteria of |log₂(fold change)| ≥ 1.5 and adjusted p-value ≤ 0.05. A total of 3054 differentially expressed genes (DEGs), including CABS1, RPL10, PGAM2, TMSB4X, and CYP17A1, were identified in the G1 and G3 groups. Among these, 402 genes showed upregulation and 2652 genes showed downregulation. GO annotation and KEGG enrichment analysis of DEGs revealed their predominant enrichment in the following categories: signaling pathways such as Focal adhesion, Pathways in cancer, and the PI3K-Akt signaling pathway. RT-qPCR validation confirmed the accuracy of the transcriptomic sequencing data. This study further elucidates the differentially expressed genes and associated signaling pathways in Kazakh stallion testes tissue before and after sexual maturity, providing a theoretical foundation and data reference for enhancing reproductive efficiency in equids and promoting biological processes such as testes development and spermatogenesis. Full article

Uterine leiomyomas or fibroids, are non-cancerous smooth muscle proliferations of the uterus, occurring mostly in women of reproductive age. Their pathogenesis involves complex growth factor interactions that regulate cellular proliferation, extracellular matrix (ECM) remodeling, and angiogenesis in myometrium. Women affected by fibroids often have a range of consequences such as infertility, endometriosis, and dysmenorrhea. Several growth factors such as vascular endothelial growth factor (VEGF), transforming growth factor (TGF-β), and platelet-derived growth factors (PDGF) have long been described as key regulators of angiogenic and fibrotic activities in fibroid tissue. Moreover, we summarized updated information between 2015 and 2025 following strictly inclusion/exclusion criteria and key research areas, including growth factors and its isoform-interaction, their roles within key signaling pathways, and the contribution of ECM deposition in uterine fibroids development and growth. Implementing growth factors in the clinical research field can develop new biomarkers and treatment options, focusing on effective and advanced management of uterine fibroids. Full article

Background/Objectives: The hypothalamic-pituitary-testis axis is known to be dysregulated in patients with hematological malignancies. However, data on the association between the type of hematological malignancies and semen quality are discordant. In the era of personalized medicine, identifying disease-specific patterns of reproductive impairment is crucial to optimize fertility preservation strategies. While patients with leukemia often show a clear deterioration in semen quality, studies on Hodgkin and non-Hodgkin lymphomas have shown that spermatogenesis is not always compromised. Indeed, some patients may present normospermia before treatment. This study aimed to assess semen parameters in males affected by hematological malignancies compared with a non-cancer population and to explore implications for individualized fertility preservation counseling. Methods: We performed a retrospective monocentric study including all patients affected by hematological malignancies who underwent fertility preservation at the Maternal and Child Department, Gynecology and Obstetrics, Oncofertility Unit, Federico II of Naples, from January 2017 through December 2024. In total, 247 patients with hematological malignancies and 63 non-cancer males undergoing in vitro fertilization for female tubal factor, selected as a control group, were included in the analysis. Sperm parameters (semen volume, sperm concentration, motility, and morphology) were first compared between the hematological malignancy group and the control group, and then among hematological malignancies classified as Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), and leukemia (L). Results: Overall, according to World Health Organization (WHO, 2021) criteria, semen parameters of patients with hematological malignancies were at the 25th percentile, except for motility, which was below the 5th percentile. Significant differences were observed in sperm concentration/mL, total sperm number, and percentage of total sperm motility between the hematological malignancy group and the control group (p = 0.0004; p = 0.0003; p < 0.0001). Based on disease classification, 158 patients had Hodgkin lymphoma, 54 had non-Hodgkin lymphoma, and 35 had leukemia. Significant differences in concentration/mL and total sperm number were found between the Hodgkin lymphoma group and the control group (p = 0.003; p = 0.001). The percentage of total sperm motility was significantly decreased in all subtypes of hematological malignancies compared with controls, especially in the leukemia group (HL p = 0.001; NHL p = 0.004; L p < 0.001). Conclusions: These findings highlight significant impairment of semen quality, particularly motility, reinforcing the role of personalized medicine in tailoring fertility preservation strategies according to malignancy subtype and baseline reproductive risk. Full article

Background: Testicular dysgenesis syndrome (TDS) is a complex disorder of the male reproductive system related to disfunction of the fetal testis. The clinical features of TDS may be evident at birth or infancy (cryptorchidism, hypospadias and/or reduced anogenital distance) or occur later in adulthood (testis cancer, infertility). Genetic background seems to be important for genetic predisposition, with new genes being associated with components of the syndrome in last years. Interestingly, the incidence of clinical manifestations of TDS has been increasing in many countries in recent decades, suggesting that genetic predisposition alone cannot explain this trend. Consequently, the hypothesis of multifactorial etiopathogenesis is becoming increasingly accepted nowadays, with environmental factors probably acting during early developmental stages in genetically predisposed individuals. Methods: In this narrative review, we aim to critically evaluate genetic and non-genetic factors involved in the pathogenesis of TDs. Results: Important associations with intrauterine growth disorders and maternal diseases (overweight/obesity and diabetes) as well as lifestyle factors (e.g., smoking and alcohol abuse) were found. In such context, endocrine disruptors probably play a major role. These substances are widely used in industry and can exert estrogenic and antiandrogenic effects, potentially interfering with the development of the fetal gonad. Conclusions: Considering their possible impact on male sexual health, more attention should be focused on maternal modifiable factors to confirm with prospective studies the mixed results of available evidence. Full article

Background/Objectives: Testicular dysfunction is a side effect of radiotherapy due to off-target damage. Germ cells are highly vulnerable. Although Sertoli and Leydig cells are more resistant, they are still affected, impairing spermatogenesis and steroidogenesis. With rising youth cancer rates, strategies to preserve fertility are crucial. Losartan (LOS) has potential to mitigate this damage. This work aimed to determine acute and late effects of radiotherapy in testicular metabolism and if LOS mitigates those effects. Methods: Male Wistar rats (n = 47, 12 weeks old) received 2.5 Gy of ionizing radiation to the scrotum (1.05 Gy/min). LOS-treated rats received 34 mg/kg twice daily before, during and after irradiation. Animals were euthanized at 2 and 60 days post-exposure, to represent acute and late effects, respectively. Reproductive organs were weighed, serum hormones assessed (ELISA), testicular mRNA expression quantified (qPCR) and oxidative stress markers, such as lipid peroxidation, protein carbonylation, and protein nitration measured (slot-blot). Metabolomic profiles were obtained via ¹H-NMR. Results: Acute irradiation reduced seminal vesicle weight, increased FSH, and decreased sperm concentration. Late effects included reduced testicular and epididymal weight, impaired sperm quality, increased protein carbonylation, and altered metabolic profiles. LOS mitigated acute weight loss but not sperm decline. Long-term, LOS improved sperm quality, reduced oxidative stress, and promoted adaptive metabolic responses. Conclusions: Irradiation-based cancer therapy causes structural and functional testicular damage and changes the testicular metabolome of rats, while LOS has the potential to be used as a radioprotector to mitigate the adverse acute and late effects of radiation on male fertility. Full article

Acetaminophen (paracetamol) is one of the most widely used analgesic and antipyretic drugs worldwide, yet its potential impact on hormonal balance and the risk of hormone-dependent cancers remains unclear. This study aimed to integrate epidemiological and bioinformatic evidence to assess the association between acetaminophen use and the risk of sex hormone–related cancers. A systematic review of preclinical and human studies was complemented by in silico analyses of acetaminophen’s molecular targets and their involvement in cancer-related pathways. Epidemiological data indicate that, although experimental studies suggest possible hormonal and reproductive effects, most population-based studies do not support an increased cancer risk, and some even suggest a potential protective effect. Bioinformatic analyses identified genes and pathways associated with ovarian and prostate cancers that may be modulated by acetaminophen, as well as possible links with breast cancer through drug metabolism–related genes. These findings reveal a shared molecular network that may underlie the observed epidemiological patterns. This integrative analysis underscores the need for further basic and clinical research to elucidate acetaminophen’s role in hormone-related carcinogenesis and to inform its safe therapeutic use. Full article

Ureaplasma species are associated with various reproductive health issues, while human papillomavirus (HPV) is associated with cervical, vaginal and vulvar cancers. Data on the association between Ureaplasma species and HPV are limited in South Africa. This study investigated the prevalence of Ureaplasma urealyticum (U. urealyticum), Ureaplasma parvum (U. parvum), and HPV coinfection and their associated factors, among adolescent girls and young women (AGYW) in the Eastern Cape Province, South Africa. A total of 214 participants were retrospectively recruited, and secondary data on HPV, U. urealyticum, U. parvum, demographics, and sexual behavior were used. HPV was detected using the Roche Linear Array HPV Genotyping Test, while U. urealyticum and U. parvum were detected using Allplex™ sexually transmitted infection (STI) essential Assay. Statistical analyses were performed using GraphPad Prism Version 8.0.1.244. The prevalence of U. urealyticum was 43.9% (94/214) and increased significantly with age (p = 0.036, R² = 0.8497); while U. parvum prevalence was 68.7% (147/214) and was not influenced by age. Having four to six lifetime sexual partners (PR: 1.77, 95% CI: 1.04–3.00, p = 0.043) was associated with increased risk of U. urealyticum. A proportion of 36.3% (77/212) had HPV-U. urealyticum coinfection and its risk was increased among those with 3–6 lifetime sexual partners (PR: 1.59, 95% CI: 1.10–2.53, p = 0.017), 2–4 new partners past three months (PR: 2.14, 95% CI: 1.19–2.42, p = 0.021); vaginal sexual intercourse frequency past 1-month (2–3 vaginal intercourse: PR: 1.54, 95% CI: 1.06–2.53, p = 0.037; 4–10 vaginal intercourse: PR: 1.91, 95% CI: 1.83–1.91, p = 0.005) and alcohol consumption (PR: 1.85, 95% CI: 1.20–3.28, p = 0.004). U. urealyticum positives had a significantly higher risk of HPV types targeted by Cervarix^® HPV vaccine than negatives (PR: 2.56, 95% CI: 1.23–5.37, p = 0.013), Gardasil^®4 (PR: 2.16, 95% CI: 1.25–3.75, p = 0.006) and Gardasil^®9 (PR: 1.70, 95% CI: 1.25–2.32, p = 0.001). AGYW of Eastern Cape Province, South Africa had high prevalence of U. urealyticum-HPV and U. parvum-HPV coinfections. Ureaplasma species coinfection was associated with HPV prevalence and distribution of genotypes. The U. urealyticum prevalence and its coinfection with HPV were associated with sexual behavior. Data from this study could contribute to the design of sexual health and STI interventions and could serve as a baseline for future epidemiological studies, which include ongoing surveillance of HPV genotype prevalence to evaluate the impact and effectiveness of HPV vaccination programs in the population. Full article

The ovary, as the primary organ responsible for reproduction and new life, plays a central role in female development, maturation, and health. Neoplasms arising from the ovary and its associated tissues exhibit substantial heterogeneity in their histopathological and molecular profiles, many of which remain poorly understood. This review aims to summarize recent advances in the understanding of genetic alterations underlying ovarian neoplasms and to explore therapeutic strategies informed by molecular biomarkers and tumor microenvironmental factors. A comprehensive literature search was performed, focusing on genomic alterations, biomarker-guided therapies, and tumor microenvironmental modulation in ovarian cancers. Emphasis was placed on studies addressing lipid mediator pathways and their roles in immune regulation and therapeutic response. Based on diagnostic classifications, recurrent alterations in TP53, MYC, PIK3CA, and KRAS are consistently observed across epithelial and germ cell ovarian tumors, whereas non-epithelial subtypes such as sex cord–stromal tumors (SCSTs) and small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), are predominantly associated with ARID1A and SMARCA4 mutations, respectively. These findings highlight distinct pathogenic mechanisms linked to specific genetic alterations and reveal potential therapeutic vulnerabilities. Moreover, lipid metabolism has been closely implicated in immune surveillance through STING signaling cascades within innate immune cells, suggesting that lipid mediators and their associated genes may represent promising therapeutic targets in ovarian cancers (OCs). Targeting lipid mediators could be particularly effective in relapsed OCs, as modulating innate immune cells within the tumor microenvironment (TME) may enhance immune surveillance and improve antitumor responses. Integrating genetic and microenvironmental insights offers a promising direction for developing more effective and personalized therapeutic strategies in OC. Full article

Cadmium (Cd), a toxic and mobile heavy metal, poses significant risks to agricultural systems due to industrial pollution. Tea plants (Camellia sinensis L.) efficiently absorb and accumulate Cd from soil, leading to contamination in leaves. Chronic consumption of Cd-laden tea can cause severe health issues, including neurological, reproductive, and immunological disorders, as well as increased cancer risk. Despite growing concerns, the molecular mechanisms of Cd stress response in tea plants remain poorly understood. Current research highlights key physiological adaptations, including activation of antioxidant defenses and modulation of secondary metabolite pathways, which influence tea quality. Cd disrupts photosynthesis, induces oxidative stress, and alters the biosynthesis of flavor-related compounds. Several critical genes involved in Cd transport (e.g., CsNRAMP5, CsHMA3, CsZIP1), sequestration (CsPCS1), and stress regulation (CsMYB73, CsWRKY53, CsbHLH001) have been identified, offering insights into molecular responses. This review systematically examines Cd dynamics in the soil-tea plant system, its effects on growth, photosynthesis, and quality, and the physiological and biochemical mechanisms underlying Cd tolerance. By consolidating recent findings on Cd-responsive genes and regulatory pathways, this study provides a theoretical foundation for breeding Cd-resistant tea varieties and ensuring production safety. Furthermore, it identifies future research directions, emphasizing the need for deeper mechanistic insights and practical mitigation strategies. These advancements will contribute to safer tea consumption and sustainable cultivation practices in Cd-contaminated regions. Full article