Search Results (1,425)

Background/Objectives: Testicular germ cell tumours (GCT) have high cure rates, especially in early stages. MicroRNA-371a-3p (M371) has recently emerged as a highly sensitive biomarker for malignant GCTs, except teratoma. This study aimed to evaluate the diagnostic performance of M371-test in a real-life clinical setting, compared to conventional markers alpha-fetoprotein (AFP), lactate-dehydrogenase (LDH), and beta-human chorionic gonadotropin (β-HCG) in patients with suspected GCT. Methods: The study, approved by the Ethic-Committee of the Provincial Hospital of Bolzano (N.97-2021), included 91 M371-tests, performed from March 2021 to May 2025. A total of 75 patients had suspected GCT; 19 healthy males served as control. Serum levels of M371, AFP, LDH, and β-HCG were compared with final histopathological diagnosis. M371 was also assessed in controls to evaluate test performance. Secondary analyses investigated correlations between preoperative M371 levels and tumour size in non-metastatic patients, and between M371-levels and clinical stage in the entire GCT cohort. A cut-off of RQ > 5 (relative quantification) was used to calculate sensitivity, specificity, and predictive values. Results: M371 showed a sensitivity of 90.9% and specificity of 89.3%, outperforming in terms of sensitivity AFP (20.4%/96.4%), LDH (40.9%/96.4%), and β-HCG (43.1%/100%). Positive predictive value (PPV) and negative predictive value (NPV) were 93.0% and 86.2%, respectively. Sensitivity was 95% for non-seminomas and 87.5% for seminomas. In non-metastatic patients, M371 levels correlated with tumour size and were significantly higher in advanced stages (median RQ 1128.35 vs. 98.36; p = 0.015). Conclusions: M371 showed excellent diagnostic performance, even for small tumours, supporting its clinical use. Further studies are needed to define its role in treatment planning and follow-up. Full article

Background: Amino acid tracer positron emission tomography–magnetic resonance imaging (PET-MRI) was shown to be superior to MRI alone for evaluating central nervous system (CNS) tumours in adults. This study aimed to investigate the utility of amino acid PET-MRI in children with CNS tumours. Methods: We reviewed the amino acid PET-MRI findings of children with suspected or confirmed CNS neoplasms managed in a territory-wide referral centre in Hong Kong from 2022 to 2025. Maximal standardized uptake values (SUVmax) were captured, and tumour-to-background SUVmax ratios (TBRmax) were measured with reference to adjacent or contralateral normal brain structures. Comparisons were made among patients with clinical high-grade and low-grade/non-neoplastic lesions. Results: Thirty-seven patients were included, with 63 PET-MRIs performed. PET-MRI was performed as part of initial diagnostics in 41% of the cases, for response assessment in 48%, and evaluation of residual/relapsed disease in 11%. High-grade lesions had a significantly higher SUVmax and TBRmax compared to low-grade/non-malignant lesions (median SUVmax 3.7 vs. 1.6, p = 0.00006; median TBRmax 2.06 vs. 0.91, p = 0.00002). Optimal SUVmax and TBRmax cut-offs by ROC analysis were 2.38 and 1.62, respectively. Similar performance was reproduced by focusing on the subset of patients with suspected CNS germ cell tumours (CNS-GCT). The impact of amino acid PET availability is considerable, as clinical management was modified in 65% of patients. Conclusions: Our study demonstrates the performance and clinical utility of amino acid PET-MRI in the management of children with CNS pathologies. Amino acid PET-MRI contributes to the diagnosis, monitoring, and treatment guidance of these patients, providing crucial information for decision-making. Full article

Background/Objectives: Germ Cell Neoplasia In Situ (GCNIS) is considered the precursor lesion for the majority of testicular germ cell tumors (TGCTs). The aim of this study was to evaluate whether first-order radiomics features derived from volumetric diffusion tensor imaging (DTI) metrics—specifically apparent diffusion coefficient (ADC) and fractional anisotropy (FA) histogram parameters—can detect GCNIS. Methods: This study included 15 men with TGCTs and 10 controls. All participants underwent scrotal MRI, including DTI. Volumetric ADC and FA histogram metrics were calculated for the following tissues: group 1, TGCT; group 2: testicular parenchyma adjacent to tumor, histologically positive for GCNIS; and group 3, normal testis. Non-parametric statistics were used to assess differences in ADC and FA histogram parameters among the three groups. Pearson’s correlation analysis was followed by ordinal regression analysis to identify key predictive histogram parameters. Results: Widespread distributional differences (p < 0.05) were observed for many ADC and FA variables, with both TGCTs and GCNIS showing significant divergence from normal testes. Among the ADC statistics, the 10th percentile and skewness (p = 0.042), range (p = 0.023), interquartile range (p = 0.021), total energy (p = 0.033), entropy and kurtosis (p = 0.027) proved the most significant predictors for tissue classification. FA_energy (p = 0.039) was the most significant fingerprint of the carcinogenesis among the FA metrics. These parameters correctly characterized 88.8% of TGCTs, 87.5% of GCNIS tissues and 100% of normal testes. Conclusion: Radiomics features derived from volumetric ADC and FA histograms have promising potential to differentiate TGCTs, GCNIS, and normal testicular tissue, aiding early detection and characterization of pre-cancerous lesions. Full article

Abnormalities were observed in the testes of common carp Cyprinus carpio collected from Willow Beach, Arizona, USA, a site on the lower Colorado River, downstream of Lake Mead and Hoover Dam. Testicular tissue collected from this site in 2003 exhibited numerous large, pigmented macrophage aggregates (MAs) and a novel, previously undescribed hypertrophy and proliferation of putative Sertoli cells. In testes samples collected in 2007, numerous testicular MA, testicular oocytes, and proliferations of Sertoli cells were observed. Three carp collected in 2007 also had raised nodules within the testes, and, microscopically, seminoma, spermatogenic seminoma, and mixed stromal cell–germ cell neoplasms were diagnosed. Several risk factors for these adverse effects were identified. Carp collected at this site in 2003 ranged in age from 35 to 54 years and had the oldest mean age of the thirteen sites sampled within the Colorado River basin. This site also has an unusual thermal regime when compared to other sites studied in Lake Mead and upstream sites, in that temperatures varied little over the seasons (amplitude around 1.5 °C) and barely reached 15 °C. Additionally, carp from this site had the highest total polychlorinated biphenyl (PCB) body burden. Hence, advanced age, low water temperature, and exposure to PCBs and other environmental contaminants may contribute to the observed abnormalities, highlighting the complex environmental factors initiating pre-neoplastic and neoplastic changes in wild carp. Full article

The Nile tilapia (Oreochromis niloticus), a key aquaculture species, displays marked sexual growth dimorphism, with males growing faster than females. This process is governed by intricate interactions between antagonistic regulators, including transcription factors, growth factors, and steroid hormones, operating through sex-specific developmental pathways. While circular RNAs (circRNAs) are known to modulate gene expression by sponging microRNAs (miRNAs), their role in teleost sex differentiation remains poorly understood. To address this gap, we profiled circRNA expression in tilapia gonads by constructing six circRNA libraries from testes and ovaries of 180 days after hatching (dah) fish, followed by high-throughput sequencing. We identified 6564 gonadal circRNAs distributed across all 22 linkage groups, including 226 differentially expressed circRNAs (DECs; 108 testis-biased, 118 ovary-biased). Functional enrichment analysis linked their host genes to critical pathways such as cAMP signaling, cell adhesion molecules, and—notably—sexual differentiation processes (e.g., estrogen signaling, oocyte meiosis, and steroid hormone biosynthesis). Furthermore, we deciphered competing endogenous RNA (ceRNA) networks, uncovering circRNA–miRNA–mRNA interactions targeting germ cell determinants, sex-specific transcription factors, and steroidogenic enzymes. This study provides the first systematic exploration of circRNA involvement in tilapia sex differentiation and gonadal differentiation, offering novel insights into the post-transcriptional regulation of sexual dimorphism. Our findings advance the understanding of circRNA biology in fish and establish a framework for future studies on aquaculture species with similar reproductive strategies. Full article

Background: Radiation-induced lower motor neuron syndrome (LMNS) represents a rare but significant delayed complication of oncologic treatment. Methods: We present the case of a 56-year-old female who developed LMNS, myokymia, and osteoradionecrosis of the hip nearly two decades after receiving pelvic radiation therapy for cervical carcinoma. To the best of our knowledge, no previous reports have described this particular triad of neurological and tissue changes following radiation therapy. This clinical presentation is analyzed within the framework of a systematic review encompassing 58 documented cases, including our own. Results: The database searches yielded 530 records. In total, 32 studies were included in the qualitative synthesis, reporting 57 unique cases of post-radiation LMNS. With the addition of our present case, the final analysis comprised 58 cases. The majority of analyzed patients were male (77.2%), and the most frequent primary malignancies were germ cell tumors (57.9%). The mean age of the analyzed patients at symptom onset was 40.5 ± 13 years, with radiotherapy administered at a mean age of 30.3 ± 12.5 years. The latency period between radiation exposure and the emergence of neurological symptoms averaged 10.2 ± 8.7 years. The mean cumulative radiation dose was 49.0 ± 14.0 Gy. Myokymic discharges were identified in 6 patients (10.3% of cases). Comparative analysis revealed no significant clinical or radiological differences across malignancy subtypes in the manifestation of post-radiation LMNS. Conclusions: These findings highlight the need for long-term surveillance of irradiated patients. Full article

Medicinal plants remain central to traditional healthcare, yet their increasing integration into modern pharmacology necessitates robust toxicological evaluation. Origanum majorana L. (sweet marjoram), widely used in culinary and folk medicine, contains diverse secondary metabolites with both therapeutic and potential genotoxic activities. Despite its popularity, systematic in vivo and in vitro safety assessments remain limited. This study aimed to comprehensively evaluate the acute oral toxicity, cytotoxicity, and genotoxicity of O. majorana methanolic extract, providing baseline toxicological data to support its safe traditional use and potential pharmaceutical applications. The methanol extract of O. majorana leaves was tested in NIH-3T3 fibroblasts for cytotoxicity and genotoxicity. In vivo acute oral toxicity was assessed in rats according to OECD Guideline 420, with animals monitored over 14 days for clinical signs, hematological and biochemical alterations, and histopathological changes. The extract preserved fibroblast viability above 90% across all tested concentrations (10–200 µg/mL), indicating absence of cytotoxicity. However, comet and micronucleus assays revealed dose-dependent DNA damage, suggesting genotoxic potential at higher exposures. In vivo, no mortality or overt systemic toxicity was observed at doses up to 2000 mg/kg. Hematological analyses showed immunomodulatory shifts (increased neutrophils and monocytes, reduced eosinophils), while biochemical profiles indicated hepatoprotective and cardioprotective effects, with reduced ALT, AST, and LDH levels. Histopathological evaluation revealed only mild, focal changes consistent with adaptive rather than irreversible responses. O. majorana extract demonstrates a favorable acute safety profile with preserved hepatic and renal function, hematological modulation, and absence of in vitro cytotoxicity. Nevertheless, dose-dependent genotoxicity warrants caution for concentrated formulations. According to GHS classification, the extract aligns with Category 5 (acute oral toxicity, lowest hazard) and Category 2 (germ cell mutagenicity). These findings underscore the importance of dose management and further long-term genotoxicity studies before translational applications in nutraceutical or biomedical fields. Full article

Avian genome editing has historically lagged behind mammalian research. This disparity is primarily due to a unique reproductive biology that precludes standard techniques like pronuclear injection. A pivotal breakthrough, however, came from the development of efficient in vitro culture systems for primordial germ cells (PGCs). This has established the chicken as a tractable and powerful model for genetic engineering. Our review chronicles the technological evolution this has enabled, from early untargeted methods to the precision of modern CRISPR-based systems. We then analyze the broad applications of these tools, which are now used to engineer disease resistance, enhance agricultural traits, and develop novel platforms such as surrogate hosts and oviduct bioreactors. Collectively, these advances have established PGC-based genome editing as a robust and versatile platform. Looking forward, emerging precision editors and the expansion of these techniques to other avian species are poised to drive the next wave of innovation in poultry science and biotechnology. Full article

Low energy N⁺ ion beam implantation has been used to create the novel rice mutant “shuangli”, which produces partially fertile spikelets containing double grains. Abnormal ovule development is a major cause of partial fertility and grain diversity in rice mutants. To elucidate the developmental mechanism of ovule diversity in shuangli, ovules undergoing development were stained using eosin Y and H33342 and observed using confocal laser scanning microscopy. Different developmental abnormalities were observed in the ovary, embryo sac, and ovule. Abnormal development was observed in 35.18% of the ovary structures, primarily manifesting as “tumor” like cell clusters, “false ovaries”, stamen degeneration, and double ovaries. In the embryo sac, abnormal development occurred in about 17.35% of the megaspore cells, including the formation of three nuclei, two daughter cells of asynchronously divided dyads, multiple megaspore tetrads, and “narrow and elongated” cavities. At the female gametogenesis stage, the abnormal development rate was 27.53%, mainly involving the degeneration of the central polar nucleus, egg apparatus, antipodal cell mass, or female germ unit. In shuangli, abnormal development occurred in 28.06% of the ovule structures, including lateral tissue, nucellar tissue, double ovules and double embryo sacs. Of the observed lateral tissues, 8.27% did not differentiate into sexual reproductive tissue, which affected the fertilization of the embryo sac, leading to atrophy and degeneration. A new abnormal tissue similar to the inner integument was found on both sides of the nucellar tissue, and the two specialized nucellar tissues appeared to have “staggered” growth within a single ovary. Of the examined ovules, 10.79% exhibited different types of double ovules, including heart-shaped, “anatropous”, “conjoined” structures. However, the double ovules typically developed synchronously, explaining the production of different sizes of the two grains in shuangli. In addition, “double” embryo sacs from two “twinborn” nucelli were found in one ovule, and the frequency of “double” embryo sacs was 3.60%. Therefore, ovule development diversity may result in fertilization or gradual degeneration after fertilization, explaining the lower fertility of shuangli at the embryological level. Full article

Spermatogenesis in teleosts is essential for reproductive function; however, it varies considerably among species. The testis of the viviparous molly fish (Poecilia sphenops) was examined using both ultrastructural and immunohistochemical methods. The testis displays a restricted lobular type, where germ cells develop synchronously within Sertoli cell-forming cysts. Transmission electron microscopy (TEM) revealed all stages of spermatogenesis. Mature sperm are at the apex of the cysts and migrate toward the sperm ducts. Sperm duct epithelium is lined by cuboidal cells joined by tight junctions, with apical cilia and desmosomal complexes contributing to transport and structural integrity. The sperm ducts showed strong Periodic Acid–Schiff (PAS)-positive expression among negative stained spermatocysts. Centrally, a cavity serves as a storage area for spermatozoa that are organized into unencapsulated bundles known as spermatozeugmata. Sertoli cells exhibited extended cytoplasmic processes that supported developing germ cells, whereas Leydig cells occupied the interstitial tissue, contributing to hormonal regulation. Immunohistochemical labeling demonstrated strong vimentin expression in Sertoli cells and telocytes, indicating their mesenchymal origin and structural role. Calretinin expression was confined to Leydig cells and certain ductal epithelial cells, supporting its use as a marker for steroidogenic and secretory functions. These findings provide new insights into the testicular specialization of P. sphenops, highlighting key somatic–germ cell interactions, ductal adaptations, and marker expression patterns that underlie male reproductive success in viviparous fish. Full article

Fibrous sheath interacting proteins 1 and 2 (FSIP1 and FSIP2) are evolutionarily conserved testis-specific antigens, exclusively expressed in germ cells of adult human tissues, where they play essential roles in spermatogenesis and testicular development. Aberrant re-expression of FSIP1 and FSIP2, however, has been frequently reported in multiple malignancies, driving oncogenic processes including uncontrolled proliferation, invasion, migration, and metastasis, and correlating with unfavorable clinical outcomes. Their restricted expression in normal tissues, together with their consistent association with poor prognosis across cancer types, highlights their potential as diagnostic biomarkers, therapeutic targets, and prognostic indicators. This review summarizes the structural features and biological functions of the FSIP family, emphasizes recent advances in elucidating their regulatory roles in tumor-associated signaling pathways, and outlines the major challenges and future perspectives in this emerging field. Full article

X chromosome inactivation (XCI) is a fundamental epigenetic process that balances X-linked gene expression between females and males by silencing one X chromosome in female cells. Variability or skewing of XCI can influence the clinical presentation of X-linked disorders. Bain type X-linked intellectual disability syndrome (MRXSB), caused by mutations in the X-linked HNRNPH2 gene, is characterized by intellectual disability, developmental delay, and neurological abnormalities. In female patients, XCI heterogeneity complicates disease modeling and therapeutic development. Induced pluripotent stem cells (iPSCs) offer a unique platform to study patient-specific disease mechanisms, but the dynamics of XCI during iPSC reprogramming, maintenance, and differentiation are not fully understood. In this study, we generated 12 iPSC clones from fibroblasts of a female MRXSB patient heterozygous for the HNRNPH2 c.340C > T mutation. Four clones expressed the mutant HNRNPH2 allele and eight expressed the wild-type allele, indicating X chromosome reactivation (XCR) followed by random XCI during reprogramming. Importantly, these XCI patterns remained stable during long-term iPSC propagation and subsequent differentiation into the three germ layers and neural stem cells. Our findings provide new insights into XCI and XCR dynamics in the context of X-linked neurodevelopmental disorders and emphasize the importance of careful clone selection for accurate disease modeling using iPSC-based approaches. Full article

Male infertility is a global health concern, and many cases are idiopathic in nature. The development and differentiation of germ cells (Gcs) are supported by Sertoli cells (Scs). Differentiated Scs support the development of Gcs into sperm, and hence, male fertility. We previously reported on a developmental switch in Scs around 12 days of age onwards in rats. During the process of the differentiation of Scs, the differential expression of mitophagy-related genes and its role in male fertility are poorly understood. To address this gap, we evaluated the microarray dataset GSE48795 to identify 12 mitophagy-related hub genes, including B-Cell Leukemia/Lymphoma 2 (Bcl2) and FBJ murine osteosarcoma viral oncogene homolog (Fos). We identify Neuron-derived orphan receptor 1 (Nor1) as a potential mitophagy-related gene of interest due to its strong regulatory association with two hub genes, Bcl2 and Fos, which were differentially expressed during Sc maturation. To validate this finding, we generated a transgenic rat model with the Sc-specific knockdown of Nor1 during puberty. A functional analysis showed impaired spermatogenesis with reduced fertility in these transgenic rats. Our findings suggest that Nor1 may be an important mitophagy-related gene regulating the function of Scs and thereby regulating male fertility. Full article

Immature teratoma of the ovary is a rare condition primarily affecting young women and constitutes a significant proportion of ovarian cancer cases in adolescents and young adults. It is commonly diagnosed at stage I, though advanced-stage disease is not infrequent. Accurate diagnosis and a fertility-sparing approach are central to the management of this condition, as many affected women retain, or have yet to develop, a desire for childbearing. However, due to the rarity of this disease, management is often guided by retrospective data derived from subanalyses of studies on malignant ovarian germ cell tumors, which can complicate the treatment of these patients once diagnosed. The aim of this review is to summarize the current evidence on immature teratoma of the ovary, considering it as a distinct clinical and pathological entity. Full article

Background/Objectives: Inactivation of the dnd gene involved in the development of primordial germ cells (PGCs) leads to the loss of gametes and halts reproductive development. Studies on sterile fish allow for the identification of genes and processes associated with GC differentiation. Methods: Atlantic salmon with GC-ablated testes were produced by temporal silencing of dnd. Gene expression was analyzed in sterile and fertile testes using 44k microarray and qPCR. Results: In sterile testes, transcripts of several GC markers were detected at low levels, suggesting the presence of cells with a GC-related expression profile that failed to initiate spermatogenesis. Expression of 260 genes was undetectable in the gonads of sterile males and females, and 61.5% of these were also inactivated during first maturation of fertile testes. This group was enriched with genes highly expressed in the brain, including those involved in endocrine and paracrine regulation, synaptic transmission, and numerous genes critical for brain development; among them, 45 genes encoding homeobox proteins. Another group of 229 genes showed increased expression in developing testes and included genes involved in neurosecretion and brain development regulation. GC-ablated testes showed increased expression of reproductive regulators such as amh and sdy and numerous immune genes, suggesting a reprogramming of GC-depleted testes. Temporal silencing of dnd indicated common developmental processes in the brains and gonads of Atlantic salmon testis that become inactive in testes at first maturation. These processes may play roles in PGC homing, the creation of a specific environment required for spermatogenesis, or facilitating communication between the gonads. Full article