Search Results (17,743)

Thyrotroph pituitary neuroendocrine tumors (PitNETs) are rare functional pituitary tumors characterized by autonomous secretion of thyroid-stimulating hormone (TSH), leading to central hyperthyroidism. Under the 2022 World Health Organization classification, these tumors are defined as PIT1-lineage PitNETs, reflecting lineage-specific differentiation and improving pathological accuracy. Clinically, thyrotroph PitNETs often present as macroadenomas with invasive growth, making complete surgical resection challenging and necessitating multimodal treatment strategies. From a molecular oncology perspective, thyrotroph PitNETs lack recurrent driver mutations and instead exhibit heterogeneous alterations involving dysregulated cell-cycle control, impaired thyroid hormone-mediated negative feedback, and aberrant growth factor signaling. Immunohistochemically, tumor cells express PIT1 and TSH and show strong membranous expression of somatostatin receptor subtype 2, providing a biological rationale for somatostatin receptor ligand -based therapy. Somatostatin receptor ligands play a central role in the management of thyrotroph PitNETs as preoperative, adjuvant, or primary treatment and achieve effective hormonal control and tumor stabilization or shrinkage in many patients. Accurate differentiation between thyrotroph PitNETs and resistance to thyroid hormone β is essential, as these entities share biochemical features but require fundamentally different management. Advances in lineage-based tumor classification, receptor profiling, and molecular pathology have refined diagnostic strategies and enabled a more personalized, tumor-oriented therapeutic approach. This review highlights current insights into the tumor biology and treatment of thyrotroph PitNETs and discusses future perspectives for receptor-targeted and molecularly informed therapies. Full article

Bighead carp (Hypophthalmichthys nobilis) is a key aquaculture species, with the head and its orbital fat being a commercially valuable product. To elucidate the molecular basis of growth variation, we performed comparative transcriptome analysis of orbital fat from extreme growth phenotypes at juvenile (6 months) and market-size (18 months) stages. In juveniles, slow growth was linked to upregulation of stress-responsive genes (sgk1, fkbp5, lipg), while fast growth correlated with higher expression of stress-buffering (crhbp) and nutrient-signaling (rbp2, mgea5) genes. At 18 months, divergent growth aligned with opposing lipid metabolic states: a pro-anabolic profile (dgat2, fads2) supported fast growth, whereas a catabolic profile (cpt1b, ppargc1a) was associated with slow growth. These results demonstrate stage-specific transcriptional reprogramming in orbital fat underlying growth variation. This study provides a molecular framework for orbital fat-mediated growth regulation and highlights potential candidate genes for molecular breeding in bighead carp. Full article

Background/Objectives: Hepatic encephalopathy (HE) is characterized by hyperammonemia, neuroinflammation, oxidative stress, and blood–brain barrier (BBB) dysfunction, with brain endothelial cells being highly vulnerable to ammonia-induced damage. Adiponectin is a cytoprotective adipokine that may enhance endothelial resilience; however, its specific role under hyperammonemic conditions remains unclear. This study aims to investigate the protective effects of adiponectin on brain endothelial function and BBB integrity. Methods: In vivo, male C57BL/6J mice underwent bile duct ligation (BDL) surgery and received daily intraperitoneal adiponectin injections (10 μg/kg/day) for 6 days, starting 5 days post-surgery. On day 11, brain tissues and serum were collected for molecular and cytokine analyses. In vitro, mouse brain endothelial cells (bEnd.3) were pretreated with adiponectin before exposure to ammonia. Assays for tight junction preservation, mitochondrial membrane potential, reactive oxygen species (ROS) generation, and total RNA sequencing were performed. Results: In BDL mice, adiponectin increased the expression of the tight junction protein claudin-5 and synaptic marker PSD95 across the cortex, hippocampus, and striatum, while reducing pro-oxidant (Cyp2e1, Cyp4a1) and apoptotic (Caspase-9) markers. In vitro, adiponectin pretreatment maintained tight junction proteins, suppressed inflammatory markers, restored mitochondrial membrane potential, and decreased ROS generation in ammonia-exposed bEnd.3 cells. Transcriptomic profiling revealed that adiponectin modulates stress-related gene expression under hyperammonemic conditions. Conclusions: Adiponectin enhances cellular stress resistance and maintains BBB structural integrity under ammonia-induced toxicity. These findings suggest that adiponectin serves as a promising therapeutic target for mitigating neurovascular unit dysfunction in hepatic encephalopathy. Full article

The sustainability of egg production in the poultry industry is frequently challenged by the progressive decline in ovarian function as laying chickens age. A primary driver of this reproductive transition is the functional deterioration of small white follicles (SWFs), which constitute the vital pre-hierarchical follicular reserve necessary for sustained egg production. However, the molecular mechanisms underlying age-associated SWF atresia remain poorly understood. In this study, we investigated the protective efficacy of apigenin (AP), a natural bioactive flavonoid, in mitigating follicular senescence by targeting calcium ion (Ca²⁺)-mediated endoplasmic reticulum stress (ERS) in D-galactose (D-gal)-induced SWFs and in naturally aged chickens. Our results revealed that AP treatment effectively rebalanced the D-gal-induced disruption of cell proliferation and survival. Molecular analysis of SWFs revealed that AP treatment promoted the coordinated restoration of transcriptional profiles of key Ca²⁺-handling genes, effectively counteracting the age-related disruption of ionic regulation. In addition, AP suppressed the aberrant upregulation of IP₃R and modulated the expression of other key Ca²⁺-regulatory genes, including CACNA1C, CACNA1D, CAMKII, MCU, and ATP2B1. This restoration of intracellular Ca²⁺ homeostasis was associated with attenuation of the ERS response, as evidenced by the decreased levels of GRP78 and CHOP, and the suppression of Caspase-3-mediated apoptotic signaling. The biological relevance of these findings was further validated in vivo using naturally aged chickens. Dietary supplementation with AP significantly enhanced pre-hierarchical follicle recruitment in aged laying chickens, and improved egg production and eggshell quality in aged laying chickens. Collectively, these findings indicate that AP can modulate ERS signaling in laying chickens by maintaining intracellular Ca²⁺ homeostasis, thereby enhancing laying performance. These results highlight AP as a promising nutritional intervention to enhance reproductive performance and extend productive longevity in poultry. Full article

Systemic infection with Acanthamoeba spp. can induce inflammatory responses within the visual axis, yet the underlying molecular mechanisms in the optic nerve remain poorly understood. The aim of the study was to determine the gene expression of Nlrp3 (encoding NOD-, LRP- and pyrin domain-containing protein 3, NLRP3), Ptgs2 (encoding cyclooxygenase-2, COX-2), Rela (encoding nuclear factor kappa B, NF-κB), and several cytokines in the optic nerve of mice during disseminated infection with Acanthamoeba sp. (T16 genotype) under various immunological conditions. In immunocompetent mice, Ptgs2 and Ifng expressions were upregulated at the beginning of infection. In the late stages, we found increased levels of Il10 and Nlrp3. In immunosuppressed mice, higher expressions of Nlrp3, Ptgs2, Rela, Il1b, Il10, Il17a, Il21, and Ifng were found in the infected mice compared to the control group. These results indicate that immunosuppression promotes prolonged inflammation by altering innate and adaptive immune responses, contributing to sustained neuroinflammatory processes affecting the optic nerve. This study provides mechanistic insight into host–pathogen interactions in the optic nerve during systemic Acanthamoeba infection. Due to the analysis being based on mRNA expression levels, direct inference regarding protein levels and the actual activity of the investigated immunological pathways is limited. Full article

Hull-less barley (HB) has gained attention for its various health supplements and use in beer brewing across China. The role of HB is somewhat limited, accounting for only 2% of the total production for human food; while approximately 6% is used in malt production, HB contains multiple key ingredients and functional components beneficial for health. These include dietary fiber (DF), protein, starch, and barley malt. These components are instrumental in promoting health benefits, including cardiovascular protection, glycemic regulation, lowering blood cholesterol levels, reducing the risk of colorectal cancer, improving cellular signaling, producing short-chain fatty acids (SCFAs), and promoting the growth of beneficial gut microflora. The structural characteristics of HB, such as size and shape, which are important in influencing these traits, are briefly discussed. Additionally, genetics insights into these traits are vital for understanding the molecular mechanisms and gene expression in response to environmental factors. By leveraging genetic studies, we explore the biosynthesis pathways and quantitative trait loci (QTL) regions that influence these health-promoting traits. Given its versatility, HB has the potential to improve cardiovascular health, supporting nutritional food goals, and enhance malting quality. This review highlights HB’s nutritional profile and genetic potential, showing its promise in supporting both health goals and the malting industry. Full article

Cybersecurity risk is commonly expressed as impact × probability, yet probability is rarely defensible because incidents are underreported, data are heterogeneous, and adversary behavior changes quickly. We present a preliminary, data-driven framework to estimate cyber likelihood without relying on naive event frequencies. The approach fuses incident narratives, threat intelligence, vulnerabilities, and control mappings into an organization-specific cyber-exposure profile represented as a typed knowledge graph and a normalized metric vector. Four measurable variables—Exposure, Traceability, Motivation, and System Update—are computed from standardized sensors spanning attack surface, observability, asset value, and patch velocity, then combined into a refreshable likelihood score for monitoring and control prioritization and to support transparent, repeatable risk governance. Unsupervised NLP (TF–IDF, latent semantic representations, and spherical clustering) supports construct discovery and profile population. Full article

Fruit quality in melon (Cucumis melo L.) is determined by complex traits such as texture and aroma, which are shaped by both genetic factors and environmental conditions. In this study, we applied an integrated physiology–metabolomics–transcriptomics approach to examine the genetic and seasonal regulation of these traits in the near-isogenic line SC10-2, carrying a defined introgression on linkage group X (LG X), in comparison with its recurrent parent ‘Piel de Sapo’ (PS). Fruit firmness, juiciness, respiration, ethylene production, and volatile organic compounds (VOCs) were evaluated over postharvest ripening across two growing seasons. SC10-2 consistently exhibited firmer flesh, reduced juiciness, and distinct VOC profiles relative to PS, although the magnitude of these differences varied between seasons. Transcriptomic analysis identified 2954 differentially expressed genes genome-wide, including 909 genes located within the LG X introgression, among which candidate genes such as CmTrpD, CmHK4-like, and CmNAC18 showed expression patterns associated with texture- and aroma-related traits. Seasonal comparisons indicated that VOC composition was particularly sensitive to environmental variation, underscoring the contribution of genotype × season interactions to fruit quality expression. Together, these results refine the phenotypic and molecular characterization of the LG X introgression in SC10-2 and provide testable candidate genes and hypotheses for understanding the genetic basis of melon texture and aroma under the studied conditions. Full article

Mitochondrial dysfunction is an early driver of Alzheimer’s disease (AD), and the decline in sex hormones, including 17β-estradiol (E2), at menopause has been linked to AD risk in women. While E2 exerts potent neuroprotective and mitochondrial-regulatory effects, its clinical utility in estrogen replacement therapy (ERT) may be limited by thrombotic and oncologic risks. Estetrol (E4), a fetal estrogen with a selective safety profile, may represent a promising alternative. This study evaluated the impact of E4 on mitochondrial bioenergetics and neuronal morphology in human SH-SY5Y neuroblastoma cells, including models of AD-related amyloidopathy (amyloid precursor protein overexpression) and tauopathy (P301Ltau mutation overexpression). E4 significantly enhanced ATP levels, mitochondrial membrane potential, and oxidative respiration in all cell models, notably outperforming E2 in P301L cells. E4 also promoted significant neurite outgrowth, alleviating deficits observed in AD models. In addition, we demonstrated that the bioenergetic effects of E4 were mediated by the estrogen receptors ERα, ERβ, and GPER1. Furthermore, E4 modulated the expression of key mitochondrial genes, specifically upregulating the phosphate carrier SLC25A23 while downregulating the complex I subunit NDUFA1. In conclusion, E4 improves mitochondrial health and supports neuronal integrity via a multi-receptor mechanism, highlighting its potential as a safe neuroprotective therapy for AD. Full article

Background: Etoricoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is widely prescribed for the management of inflammatory conditions. Despite its extensive clinical use, evidence regarding its hepatic safety profile remains limited and incompletely characterized. Aims: This study aimed to systematically evaluate the hepatic effects of etoricoxib in a murine model by integrating histopathological assessment with analysis of mRNA expression of key enzymes involved in arachidonic acid metabolism Methods: Male BALB/c mice (n = 7 per group) received either low or high doses of etoricoxib (10.5 or 21 mg/kg/day) or celecoxib (35 or 70 mg/kg/day) for 28 consecutive days. Liver tissues were examined histologically using hematoxylin and eosin staining, while molecular alterations were assessed by quantitative PCR targeting representative cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) isoforms involved in arachidonic acid metabolism. Results: High-dose etoricoxib exposure was associated with pronounced hepatic histopathological alterations, including hepatocellular necrosis, inflammatory cell infiltration, and sinusoidal congestion. In contrast, low-dose treatment resulted in only mild vascular and cellular changes. At the molecular level, etoricoxib administration was associated with marked downregulation of several arachidonic acid–metabolizing genes (including Cyp4a12 and Alox12), whereas Cox2 expression was significantly upregulated (p < 0.05), indicating a shift toward a pro-inflammatory transcriptional profile. Conclusions: Etoricoxib exposure is associated with dose-dependent hepatic injury in mice, accompanied by coordinated transcriptional alterations in arachidonic acid–metabolizing pathways. Notably, molecular changes were detectable even at low doses in the absence of overt histological damage, suggesting potential early indicators of hepatic stress. These findings underscore the importance of cautious dose optimization and further translational studies to clarify the long-term hepatic safety of etoricoxib in clinical settings. Full article

Virgin olive oil (VOO) quality is strongly influenced by olive cultivar and fruit maturity stage, yet their combined effects remain insufficiently characterized in many traditional olive-growing regions. This study evaluated the physicochemical parameters, phenolic compounds content, antioxidant activity, fatty acid profile, volatile compounds, and sensory attributes of VOOs obtained from five autochthonous cultivars of Extremadura (Spain)—‘Corniche’, ‘Manzanilla Cacereña’, ‘Morisca’, ‘Pico Limón’, and ‘Verdial de Badajoz’—harvested at three ripening stages (Green, Verging-on-ripe, and Ripe). Early harvest oils exhibited significantly higher total phenolic content (up to 478 mg/kg expressed by caffeic acid equivalent, CAE), oxidative stability (up to 188 h), intense green-fruity notes dominated by (E)-2-hexenal and (Z)-3-hexenal, and stronger bitterness and pungency. As ripening progressed, phenolic compounds and LOX-derived C6 volatiles markedly decreased, while oil yield, linoleic acid, saturated aldehydes, and oxidation markers increased in most cultivars. Cultivar-specific responses were evident: ‘Corniche’ and ‘Manzanilla Cacereña’ maintained higher oleic acid and stability, whereas ‘Morisca’ and ‘Pico Limón’ were more prone to phenolic compound loss and sensory deterioration at full ripeness. Multivariate analysis confirmed strong genotype × maturity interactions shaping oil quality. Optimal harvest timing must therefore be tailored to each cultivar to maximize phenolic content, oxidative stability, and sensory excellence while balancing industrial yield. Full article

Contagious bovine pleuropneumonia (CBPP) is a significant respiratory disease in cattle caused by Mycoplasma mycoides subsp. mycoides (Mmm). A better understanding of the pathogenesis of CBPP and the immune response of the host to infection will assist in the development of novel interventions to prevent disease progression. In this study, bovine lung explants (BLEs) were exposed to Mmm to investigate the upregulation and release of early inflammatory cytokines, mediators and receptors following tissue infection. Immunomodulatory molecules indicative of cell activation were investigated by immunoblotting on the BLEs and the tissue culture supernatants, and quantitative real-time PCR (RTq-PCR) was performed on the BLEs to determine the fold change in the expression of the respective mRNA. Immunoblotting indicated the production of inflammatory cytokines, mediators and receptors in Mmm-infected BLEs; however, this contrasted strongly with the mRNA expression profile, which did not show any significant fold increase. Infection of the BLEs with Mmm stimulated the production of some pro-inflammatory cytokines and mediators, including IL-1β, COX-2, 5-LOX and iNOS. Toll-like receptor proteins TLR2 and TLR4 were detected solely in the tissue culture supernatant of Mmm-infected BLEs. These receptors are considered to be involved in the recognition of Mmm by BLE tissue cells, thus triggering intracellular pathways that produce specific inflammatory cytokines and mediators, initiating the inflammatory response. Full article

Background: The reproductive cycle of Octopus mimus is regulated by environmental and hormonal factors, with photoperiod playing a key role in spawning induction and reproductive maturation. Understanding its underlying molecular mechanisms is essential for developing strategies to enhance controlled reproduction in aquaculture. Methods: We analyzed the expression of genes involved in the photoperiod-activated spawning induction cascade in the optic lobe and its downstream effects on the oviducal gland by performing transcriptomic analyses on females exposed to continuous light (24:0), which inhibits reproductive development, and a natural photoperiod, which induces spawning. The mRNA sequencing (RNA-Seq), quality control, gene annotation, and differential expression analyses were conducted using edgeR. Results: Spawning was completely inhibited under constant light, while 80% of control females spawned. Expression profiling revealed 89 downregulated and 34 upregulated genes in the optic lobe, and 178 downregulated and 237 upregulated genes in the oviducal gland (FDR < 0.05, |log2FC| ≥ 2), including key orthologs such as FMRFamide and myomodulin. Conclusions: These results show that the optic lobe integrates photoperiodic cues that modulate reproductive activation via a neuroendocrine cascade and coordinates spawning regulation through the oviducal gland, providing insights for improving reproductive control in aquaculture systems. Full article

Background: HER2-low breast cancer is a biologically heterogeneous subgroup in which hormone receptor (HR) expression critically shapes prognosis and treatment, but the underlying regulatory mechanisms remain unclear. MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and may contribute to HR heterogeneity. This study aimed to identify deregulated miRNAs and associated gene networks distinguishing HER2-low/HR-positive from HER2-low/HR-negative tumors, elucidating the molecular mechanisms underlying this divergence. Methods: Differential expression analyses of miRNAs and genes were performed using Wilcoxon tests and DESeq2 (|log2FC| > 1; FDR-adjusted p-value < 0.05). Survival analyses were conducted using Cox proportional hazards models to evaluate the individual miRNAs and miRNA signature. Functional enrichment analyses, including GO, KEGG and Reactome pathways, were performed. Correlation analysis and the miRNA target predicted were integrated to identify regulatory interactions. Results: Comparisons between HER2-low/HR-positive and HER2-low/HR-negative tumors identified 165 significantly deregulated miRNAs and 170 strongly deregulated genes. Intersection analysis highlighted miR-9-5p, miR-532-5p and miR-576-5p as specifically associated with HR-negative status. Survival analyses showed non-significant trends for the overall survival and progression-free interval. Functional enrichment analysis revealed hormone-related pathways in HR-positive tumors and immune, inflammatory and proliferative pathways in HR-negative tumors. Integrative correlation and target prediction analyses identified two miRNA–mRNA regulatory axes, miR-576-5p/TGFBI and miR-9-5p/POU2F2. Conclusions: Our study demonstrated that HER2-low breast cancer exhibits distinct miRNA and gene expression profiles, which highlight different transcriptomic profiles according to HR status for the first time. Specific miRNA–gene networks may drive transcriptional heterogeneity, serving as potential biomarkers for stratification and as therapeutic targets. These findings provide insight into the molecular basis of HER2-low tumor diversity and support future development of HR-directed therapeutic strategies. Full article

Background and Objectives: Prostate cancer exhibits substantial biological heterogeneity. Although several biomarkers reflecting aggressive tumor behavior have been identified, molecular indicators related to biological adaptation to androgen deprivation remain limited. This study aimed to comparatively evaluate ISM-1 and B7-H3 expression in localized prostate cancer (LPC) and the pre-CRPC group (pre-treatment diagnostic biopsy tissue from patients who subsequently developed CRPC), and to investigate their clinicopathological associations in the pre-CRPC group. Materials and Methods: This retrospective study included 30 surgically treated LPC cases and 32 pre-CRPC cases with available prostate tissue samples obtained prior to the development of castration resistance. ISM-1 and B7-H3 expression levels were evaluated immunohistochemically using the H-score method (intensity 0–3 × proportion score 0–3 [0%, 1–19%, 20–50%, >50%]). Expression patterns were compared between LPC and pre-CRPC groups. Within the pre-CRPC group, associations with clinicopathological parameters were evaluated using H-scores as continuous variables, and time to castration resistance was analyzed using Cox regression. Results: ISM-1 expression was generally low in LPC cases, with a median H-score of 0, whereas pre-CRPC biopsy tissues demonstrated a marked increase in ISM-1 expression. B7-H3 expression was higher and more homogeneous in the pre-CRPC group compared with LPC. In the pre-CRPC group, ISM-1 and B7-H3 H-scores showed a strong positive correlation. No statistically significant associations were identified between ISM-1 or B7-H3 expression levels and most conventional clinicopathological parameters; however, both markers differed significantly across Grade Groups. Neither marker showed a statistically significant association with time to castration resistance, although ISM-1 demonstrated a non-significant trend toward a longer time to resistance. Conclusions: ISM-1 and B7-H3 exhibit distinct expression patterns across different stages of prostate cancer but show associated expression profiles in the pre-CRPC group. While B7-H3 appears to reflect aggressive tumor biology, the independent expression pattern of ISM-1 and its non-significant trend toward a longer time to resistance suggest a potential role in the clinical trajectory toward castration resistance. Combined assessment of ISM-1 and B7-H3 may contribute to a better understanding of tumor biology in patients who subsequently develop CRPC. These findings are descriptive and hypothesis-generating. Full article