Search Results (3,230)

Dysregulation of the kynurenine pathway (KYNP) is increasingly recognized as a hallmark of cancer-associated metabolic reprogramming, contributing to immune evasion, oxidative stress, and tumor progression through the activity of enzymes such as indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan 2,3-dioxygenase (TDO2). This systematic review aimed to evaluate the current evidence on the ability of phytochemicals to modulate the KYNP and their potential implications for cancer prevention and therapy. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included English-language articles and book chapters published between 2016 and 2026 that were retrieved from the Scopus and PubMed databases. A keyword co-occurrence network was generated using VOSviewer (v1.6.20) based on the complete Scopus and PubMed exports of the included studies to identify major research themes. The available evidence indicates that phytochemicals restore anticancer immunity by targeting multiple components of the KYNP, including inhibition of IDO1-mediated kynurenine production and suppression of downstream aryl hydrocarbon receptor signalling, thereby enhancing cytotoxic T-cell responses, reducing immunosuppressive cell populations, and improving antitumor immune activity. Collectively, these findings support the KYNP as a promising immunometabolic target and highlight phytochemicals as potential complementary agents for cancer immunotherapy while emphasizing the need for further investigation of the biological and immunological roles of IDO2. Full article

Diabetes mellitus represents a growing global health challenge, establishing oral antidiabetic drugs as a therapeutic class of paramount importance. Consequently, to ensure drug safety, therapeutic efficacy, and accurate therapeutic drug monitoring, robust, selective and highly reproducible analytical methods are indispensable. This review provides a comprehensive overview of instrumental analytical techniques developed between 1985 and 2026 for quantifying oral antidiabetic agents. Based on a literature search across major databases—including PubMed, ScienceDirect and Springer—we systematically evaluated the application of UV-VIS spectrophotometry, liquid chromatography, and advanced electroanalytical methods. The reviewed literature encompasses methodologies ranging from routine quality control of bulk powders and pharmaceutical formulations to complex bioanalytical and pharmacokinetic applications. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) emerged as the gold standard for precise bioanalysis due to its superior selectivity and sensitivity in complex biological matrices. Conversely, UV-VIS spectrophotometry and electrochemical methods remain highly relevant for cost-effective routine quality control in industrial manufacturing. Methodologies are categorized by drug therapeutic class, including biguanides, sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, meglitinides, highlighting key validation parameters such as linearity, accuracy, and limits of detection. Finally, this review outlines future directions in the field of antidiabetic drug quantification. Full article

In recent years, aquaculture, a critical pillar of global food security, has faced challenges including germplasm resource degradation, frequent disease outbreaks, and insufficient environmental adaptability. To address these issues, omics technologies—centered on genomics, transcriptomics, and related fields—are driving the transformation of aquaculture toward precision and intelligence by establishing a three-dimensional “genotype–phenotype–environment” knowledge network. In this review, we outline foundational applications of omics in aquaculture and highlight the characteristics and current applications of distinct omics approaches. Furthermore, we summarize three core application domains of omics in aquaculture: (1) genetic breeding via genomic selection (GS), gene editing, and multi-omics molecular dissection of economic traits; (2) disease prevention through host–pathogen interaction studies and microbial engineering; and (3) environmental assessment through multi-omics characterization of biological and ecological responses. Additionally, we identify challenges in applying omics technologies to aquatic breeding and database development. Overall, this review aims to provide aquaculture practitioners with actionable insights by enhancing understanding of omics-driven innovations in sustainable aquaculture advancement. Full article

Fruit production represents a major agricultural sector worldwide; however, it is severely affected by pests that reduce fruit yield, quality, and marketability. The intensive use of chemical insecticides has generated environmental contamination, resistance in pest populations, and risks to human health, increasing the demand for sustainable alternatives. In this context, endophytic fungi (EF) have gained relevance as biological control agents due to their ability to colonize plant tissues and produce bioactive metabolites that affect agricultural pests. This systematic review aimed to evaluate the current scientific knowledge regarding EF as biological control agents against pests in fruit crops and to analyze the tripartite interactions among fungi, plants, and pests. The review was conducted following PRISMA guidelines using the databases Web of Science, Scopus, PubMed, and OpenAlex. Studies were selected according to predefined exclusion criteria focused on the simultaneous presence of endophytic fungi, fruit crops, and agricultural pests. A total of 24 fruit species, 51 endophytic fungi, and 33 agricultural pest species were identified. The most frequently reported fungal genera were Penicillium, Cladosporium, Fusarium, Aspergillus, Gnomoniopsis, and Trichoderma, while a broad diversity of pest species affected by these fungi was recorded. Interaction analyses revealed complex and highly interconnected tripartite relationships, in which some fungi exhibited strong host specificity whereas others displayed broader interaction ranges. The findings demonstrate that EF possess significant potential as sustainable biological control agents in fruit production systems. However, research in this field remains limited and fragmented, highlighting the need to develop standardized models, validate their efficacy under field conditions, and conduct studies focused on the commercial scalability of EF-based management strategies. Full article

Background: Population aging is driving a convergent rise in three disorders historically managed in isolation: cardiovascular disease, neurocognitive decline, and osteoporotic bone loss. Mechanistic data indicate that these systems are coupled through shared regulators of calcium trafficking, inflammation resolution, vascular integrity, and inflammaging. On this basis, a “Heart–Brain–Bone” axis has been proposed; it should be understood as an integrative conceptual framework that organizes evidence drawn from three separate studies, not as a validated physiological entity with agreed diagnostic criteria or demonstrated modifiability. Three lipid-soluble nutrients—long-chain omega-3 polyunsaturated fatty acids (EPA/DHA), vitamin D3 (cholecalciferol), and vitamin K2 (menaquinone-7 [MK-7])—act on overlapping nodes of this network. Methods: We performed a structured narrative review. PubMed/MEDLINE, Embase, the Cochrane Library, and Web of Science were searched from database inception to 25 June 2026 using predefined term blocks for each nutrient, each organ domain, and each candidate mechanism, and the search was updated on 7 August 2026. Records were screened against prespecified inclusion and exclusion criteria by two authors independently, with disagreements resolved by a third. The strength of evidence for each nutrient–organ relationship was graded with an explicitly defined four-level scheme ((−) to (+++)) applied separately to preclinical, observational, randomized and meta-analytic evidence. Results: Vitamin K2-dependent gamma-carboxylation of matrix Gla protein (MGP) and osteocalcin has been proposed to influence whether calcium is incorporated into the bone matrix or deposited in the arterial wall, offering a candidate mechanistic account of the “calcium paradox” associated with isolated vitamin D3 supplementation; EPA/DHA-derived specialized pro-resolving mediators may support resolution of endothelial and neuronal inflammation; and bone-, vascular- and brain-derived signals (osteocalcin, FGF23, the neurovascular unit) interconnect the three organs. These mechanisms are biologically plausible but remain insufficiently confirmed in humans. The clinical evidence is heterogeneous, formulation- and population-dependent, and comprises positive, neutral and null results: cardiovascular omega-3 trials are discordant (REDUCE-IT, which used icosapent ethyl [an EPA ethyl ester], positive; VITAL/STRENGTH/ASCEND null, predominantly in lower-risk or replete cohorts); cognitive trials are largely null or subgroup-dependent (MAPT, DO-HEALTH, VITAL); and MK-7 improves surrogate bone and calcification biomarkers and slowed coronary artery calcification in one recent randomized imaging trial (VitaK-CAC), whereas combined MK-7 plus vitamin D3 did not slow aortic valve or coronary calcification in AVADEC and MK-7 did not reduce bone loss in early menopausal women. Recognized safety signals include a dose-dependent increase in atrial fibrillation with high-dose omega-3, adverse skeletal effects of high-dose or bolus vitamin D, and clinically relevant interference of even low-dose MK-7 with vitamin K antagonist therapy. Conclusions: No adequately powered randomized trial has demonstrated that the combination of long-chain omega-3, vitamin D3 and MK-7 is superior to its individual components or to placebo for any clinical endpoint. The combined regimen is therefore mechanistically rational and hypothesis-generating rather than clinically established; benefit appears most plausible in individuals with elevated risk or demonstrable nutritional insufficiency, and least in replete, low-risk populations. Findings should be interpreted within a broader healthy-aging context that includes lifestyle and psychosocial factors. Adequately powered factorial randomized controlled trials stratified by baseline Omega-3 index, 25(OH)D and vitamin K status, with prespecified mechanistic biomarkers and hard endpoints, are required. Full article

Forensic genetics is moving from locus-based DNA profiling toward genome-wide inference enabled by high-density single-nucleotide polymorphism (SNP) data. While short tandem repeats remain central to routine human identification, SNP-based technologies and massively parallel sequencing have expanded the analysis of distant kinship through detection of identity-by-descent (IBD) segments and shared autosomal DNA. This narrative review synthesizes the biological basis of SNP-based distant kinship inference, the statistical and computational frameworks used to model genomic relatedness, and the operational transition from relatedness detection to forensic genetic genealogy (FGG). It distinguishes genetic genealogy database matching from formal forensic kinship testing, targeted SNP panels, SNP capture, low-coverage sequencing, Bayesian and machine-learning approaches, and independent forensic confirmation. Applications in criminal investigations, unidentified human remains, historical identifications, and broader relationship-inference contexts are discussed. The review also examines limitations related to recombination, stochastic inheritance, marker density, genotype quality, degraded or mixed forensic samples, population structure, endogamy, database composition, and genealogical record availability. Ethical and regulatory issues involving consent, privacy, database governance, law-enforcement access, data retention, and non-consenting relatives are considered. Overall, SNP-based forensic genomics can generate powerful investigative leads, but its outputs must be interpreted within method-specific analytical and evidentiary boundaries. Full article

Background/Objectives: The identification of novel therapeutic targets is imperative to overcome the limitations of current anti-toxoplasmosis treatments. This study aims to investigate the potential of repurposing Pentamidine as an inhibitor against the HMG-Box domain-containing protein (TGARI_247020) in Toxoplasma gondii, a protein hypothesized to be essential for the parasite’s genomic stability. Methods: The study utilized a multi-layered in silico approach. First, the biological essentiality of the target gene was validated by analyzing CRISPR-Cas9-based phenomics data from the ToxoDB database. Second, the structural properties of the HMG-Box domain (ID: A0A139YAG1) were characterized using AlphaFold models. Finally, molecular docking simulations were conducted via the SwissDock server to evaluate the binding affinity and interaction dynamics between Pentamidine and the target protein. Results: Genomic analysis revealed a phenotype score of −1.2, confirming the indispensable role of the TGARI_247020 gene for parasite viability. Structural analysis identified a well-defined binding pocket within the HMG-Box domain. Molecular docking results demonstrated a high binding affinity for Pentamidine, yielding an optimal AC Score of −44.93, supported by a FullFitness value of −1134.13 kcal/mol. The interaction was primarily stabilized by a network of hydrogen bonds and favorable steric fits within the catalytic groove of the protein. Toxoplasmosis is widely classified as a neglected parasitic disease, posing persistent public health challenges and veterinary economic concerns globally. Traditional de novo drug discovery is often hindered by high costs and prolonged timelines, making drug repositioning (repurposing) a highly attractive and cost-effective strategy to identify novel therapeutics from established clinical agents over the past decade. Computer-Aided Drug Design (CADD), particularly Structure-Based Drug Design (SBDD), has provided a robust molecular framework to prioritize candidate drugs against essential parasitic targets. In apicomplexan parasites, high-mobility group box (HMGB) proteins, such as TgHMGB1a, serve as critical nuclear architectural factors that bind to distorted DNA structures and modulate genomic transcription, disrupting these essential DNA–protein interactions, representing a promising, yet under-explored, therapeutic target. The hypothesis for evaluating Pentamidine—an aromatic dicationic diamidine traditionally used in African trypanosomiasis—lies in its established ability to interact with nucleic acids and block critical molecular targets in other protozoa, providing a logical biochemical rationale for testing its potential as a structural inhibitor of the T. gondii HMG-box protein. Conclusions: Our findings provide preliminary in silico evidence that Pentamidine targets the HMG-Box protein, suggesting its potential for drug repurposing. However, due to established clinical limitations of Pentamidine (such as nephrotoxicity and poor blood–brain barrier permeability), further experimental in vitro and in vivo validation is strictly required to evaluate its therapeutic efficacy. Full article

Background/Objectives: Feature engineering remains a major challenge in metabolomics-based prediction, particularly when rich biochemical knowledge is available but underutilized. Conventional metabolomics models rely primarily on measured variables and statistically driven feature selection, overlooking the molecular and pathway context encoded in curated metabolite knowledge bases. We propose SEFA (Semantic Embedding-based Feature Augmentation), a model-agnostic framework that integrates metabolite-level textual knowledge from the Human Metabolome Database (HMDB) into structured metabolomics modeling for lung-cancer prediction. Methods: SEFA encodes HMDB metabolite descriptions as 768-dimensional MedBERT vectors and projects measured metabolite concentrations into this semantic space via concentration-weighted aggregation, producing a 928-dimensional candidate feature matrix that concatenates 11 clinical variables, 149 metabolite concentrations, and 768 semantic projection features. Sparse L1-guided feature selection reduced this representation to 24 features (2.6% of candidates) within a leakage-free cross-validation pipeline. Six classifiers were evaluated on a lung-cancer plasma metabolomics cohort of 800 participants (586 cases, 214 controls) with a stratified 80:20 split, and a controlled ablation study compared the augmented representation with a 24-metabolite-only baseline. Pathway-enrichment analysis of the metabolite sets associated with the retained embedding dimensions was performed using MetaboAnalyst 5.0. Results: Logistic regression on the 24-feature SEFA representation achieved a test ROC-AUC of 0.969, a precision-recall AUC of 0.987, and an accuracy of 94.4%, competitive with less interpretable approaches. Under the same 24-feature budget, embedding augmentation improved test ROC-AUC by 0.008, precision-recall AUC by 0.004, and accuracy by 3.1 percentage points over the metabolite-only baseline. Five retained embedding dimensions mapped onto coherent metabolic themes—sphingolipids and acylcarnitines, carnitine and glutamine metabolism, one-carbon and nitrogen handling, purine catabolism, and oxidative stress markers—and their associated metabolite sets were enriched for arginine and proline metabolism and glycine, serine, and threonine metabolism, pathways with established roles in lung-cancer biology. Conclusions: SEFA demonstrates that semantic embeddings derived from biomedical language models can convert curated metabolite annotations into patient-level features that supply complementary predictive signal while preserving biological interpretability through pathway-level analysis. The present evidence is limited to a single region-specific cohort; external, cross-platform, and cross-disease evaluation is required before broader generalization or clinical application. Full article

Athletic environments—ranging from natural grass pitches and synthetic crumb–rubber turf to indoor mats and hardwood courts—are increasingly recognized as dynamic built-environment microbiomes rather than inert platforms. These surfaces are continuously exposed to human skin contact, perspiration and environmental debris, and may act as reservoirs for both beneficial commensals and opportunistic pathogens. The present study characterized and compared the taxonomic diversity of bacterial communities across four distinct sports surfaces and tested whether surface material or intensity of human use is the stronger determinant of community structure. Environmental swabs were collected from natural grass pitches, synthetic crumb–rubber turf, polyvinyl chloride (PVC) karate mats and hardwood squash courts, before and after sporting activity. Bacterial communities were profiled by 16S rRNA gene amplicon sequencing, with taxonomic assignment against the SILVA reference database. Alpha diversity was quantified using the Shannon and Simpson indices, and community structure (beta diversity) was visualized by Principal Coordinates Analysis (PCoA) on Bray–Curtis dissimilarities. Surface material was the strongest predictor of microbial composition. Natural grass exhibited high alpha diversity dominated by soil-dwelling Proteobacteria and Actinobacteria, whereas synthetic surfaces showed reduced diversity but a markedly higher prevalence of human skin-associated taxa (Staphylococcus, Corynebacterium and Streptococcus). High-contact PVC mats underwent a significant relative enrichment in these skin-associated genera following active training. PCoA revealed clear spatial segregation by material. A multivariate PERMANOVA confirmed surface material as the primary driver of microbial structure, explaining 52.2% of the total variance (p < 0.001), whereas the intensity of human use (pre- vs. post-activity) explained only 2.8% of the variance (p = 0.035), with a non-significant interaction term (p = 0.178). These findings demonstrate that sports surfaces are living biological landscapes whose microbial fingerprint is strongly associated with specific surface types. This provides a molecular baseline for targeted hygiene interventions and future antimicrobial-material design tailored to specific athletic disciplines. Full article

The aorta is a single arterial organ, yet the clinical response to its diseases is fragmented across specialties, institutions, and nations. Acute aortic syndromes remain lethal at every stage of the care continuum: a large share of patients with type A dissection die before reaching any hospital, roughly half die before reaching a specialist centre, a substantial proportion are misdiagnosed at first medical contact, and untreated mortality has historically been estimated at approximately one to two percent per hour. Reported 30-day mortality differs across surgical registry cohorts—for example, 7.6% in the Japan Cardiovascular Surgery Database and 16.9% in the cited GERAADA cohort—but such ecological comparisons are descriptive and cannot identify the contribution of organisational, biological, clinical, or ascertainment differences. This review synthesises registry, population, and health-services data from Europe, Japan, North America, and low- and middle-income settings to characterise where the pathway fails and what each system has already demonstrated. We argue that the next material advance in aortic care will come not from any single innovation in isolation but from the architecture that connects prevention, diagnosis, treatment, and follow-up and that system redesign and technological progress are complementary rather than competing; we propose a five-pillar framework (Prevention, Presentation, Pathway, Person, and Learning) mapped throughout to published exemplars and future research priorities. Full article

Background: Parkinson’s disease (PD) exhibits remarkable clinical heterogeneity, with substantial variability in motor progression, cognitive decline, and the development of non-motor manifestations. Although the propagation of pathological alpha-synuclein is considered a central mechanism of PD pathogenesis, it does not fully explain why specific neuronal populations demonstrate differential susceptibility to degeneration. Emerging evidence suggests that selective neuronal vulnerability is determined by the interaction of multiple biological domains, including calcium homeostasis, mitochondrial bioenergetic capacity, lysosomal function, axonal architecture, synaptic resilience, and neuroinflammatory responses. Methods: A structured critical narrative review was performed using PubMed/MEDLINE, Scopus, and Web of Science databases from inception to March 2025. Only full-text articles published in English and peer-reviewed journals were included. Evidence from human post-mortem studies, genetic analyses, biomarker investigations, experimental models, induced pluripotent stem cell studies, and longitudinal clinical cohorts were systematically synthesised to identify the principal mechanisms underlying selective neuronal vulnerability and their potential translational application. To capture evidence published after this electronic cut-off, a supplementary manual review of reference lists of key systematic reviews and landmark publications was conducted up to the date of manuscript submission; references with 2025 or 2026 publication dates entered through this supplementary process. The supplementary manual review was conducted as a targeted scan of reference lists of key systematic reviews and high-impact publications identified during the primary search and did not constitute an independent updated systematic search. Results: Five interconnected biological domains emerged as key determinants of neuronal susceptibility in PD: calcium-mediated metabolic stress associated with autonomous pacemaker activity, mitochondrial dysfunction and energetic failure, impaired lysosomal degradation and proteostasis (particularly involving the GBA1–glucocerebrosidase pathway), vulnerability related to extensive axonal and synaptic architecture, and neuroinflammatory mechanisms involving microglial and astrocytic activation. Among these domains, the lysosomal pathway currently provides the strongest translational link between molecular mechanisms and measurable clinical outcomes. Based on this integrated framework, we propose the Parkinson’s Vulnerability Index (PVI), a hypothesis-generating multidimensional model combining genetic, enzymatic, alpha-synuclein seeding, cognitive, olfactory, and neuroimaging biomarkers to facilitate biological stratification and improve the design of mechanism-targeted clinical trials. Conclusions: Selective neuronal vulnerability provides a complementary framework to alpha-synuclein propagation models for understanding the heterogeneity of PD. The proposed PVI is not intended as a diagnostic or prognostic clinical instrument but as a research tool requiring prospective validation. Future precision medicine approaches in PD may benefit from integrating vulnerability-related biomarkers with existing biological staging systems to identify patients most likely to benefit from targeted disease-modifying therapies. Full article

Background: Mitochondrial dysfunction is increasingly recognized as a central contributor to intrinsic skin aging, photoaging, cellular senescence, impaired extracellular-matrix homeostasis, dysregulated pigmentation, and delayed recovery after energy-based or minimally invasive procedures. Pyrroloquinoline quinone (PQQ) is a redox-active ortho-quinone that has attracted interest because it can participate in repeated redox cycling, protect mitochondrial function, and activate signaling associated with mitochondrial biogenesis. Objective: This narrative review evaluates the mechanistic basis, available dermatologic evidence, translational opportunities, and major uncertainties surrounding PQQ as a mitochondrial rejuvenation strategy in aesthetic dermatology. Methods: PubMed/MEDLINE and Europe PMC were searched from database inception through 10 August 2026 using PQQ-, mitochondrial-, skin-, delivery-, and safety-related terms; reference lists were also screened. Mechanistic, preclinical, skin-focused, human, and regulatory evidence was synthesized narratively. Results: Experimental studies support PQQ-mediated activation of mitochondrial biogenesis pathways and protection against oxidative injury in several cell and animal systems. Skin-specific evidence includes attenuation of oxidative stress, DNA damage, senescence markers, and matrix metalloproteinases in accelerated-aging mouse models; protection of UVA-exposed human dermal fibroblasts; suppression of UVB-induced caspase-1 release in keratinocytes; a small oral dry-skin study; and a multi-ingredient topical study containing an allyl PQQ derivative. These studies do not establish PQQ-specific clinical aesthetic efficacy. Conclusion: PQQ is a biologically plausible mitochondrial-support compound, but it should currently be regarded as an investigational ingredient rather than an established aesthetic treatment. Carefully designed formulation, toxicology, dose-finding, biomarker, and randomized clinical studies are required before claims regarding wrinkle reduction, pigment improvement, enhanced collagen production, or accelerated post-procedure recovery can be justified. Full article

Background/Objectives: Epoxide hydrolase 2 (EPHX2), which encodes soluble epoxide hydrolase (sEH), is involved in arachidonic acid metabolism and has been associated with inflammation, lipid metabolism, and tumor biology. However, its prognostic significance and biological associations in lung adenocarcinoma (LUAD) remain unclear. This study aimed to investigate the expression profile, prognostic value, and molecular pathways of EPHX2 in LUAD using bioinformatics analyses. Methods: EPHX2 expression was evaluated using TNMplot, GEPIA2, and GEO datasets, while protein expression was assessed using the Human Protein Atlas and CPTAC/UALCAN platforms. Prognostic analyses were performed using Kaplan–Meier Plotter, GEPIA2, and Human Protein Atlas datasets. Co-expression and gene set enrichment analyses were conducted using LinkedOmics, and functional enrichment analyses were performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome databases. Correlation and protein–protein interaction (PPI) analyses were evaluated using GEPIA2 and STRING. Results: EPHX2 expression was significantly reduced in LUAD tissues compared with normal lung tissues across datasets, and these findings were supported at the protein level. High EPHX2 expression was associated with better overall survival and retained independent prognostic significance in multivariate Cox analysis. Functional enrichment analyses demonstrated associations with lipid metabolism, arachidonic acid metabolism, cytochrome P450-related pathways, and oxidative processes. Correlation analyses suggested potential associations between EPHX2 and angiogenesis, extracellular matrix remodeling, and hypoxia-related pathways. Conclusions: Bioinformatics analyses suggest that EPHX2 may participate in metabolic and tumor progression-related regulatory networks and may serve as a prognostic biomarker in LUAD. Full article

Background: Pancreatoblastoma (PB) is an exceptionally rare malignant epithelial neoplasm of the pancreas that recapitulates the developing pancreatic anlage. It is defined histologically by acinar-predominant differentiation with characteristic squamoid nests, and it may also show ductal and endocrine differentiation within the same tumor, features that distinguish it from acinar cell carcinoma and solid pseudopapillary neoplasm but that are readily overlooked. It occurs predominantly in young children, although adult-onset disease is well documented. We provide a population-based characterization of PB across the full age spectrum and benchmark it against pancreatic ductal adenocarcinoma (PDAC). Methods: Cases diagnosed between 2000 and 2021 were identified in the Surveillance, Epidemiology, and End Results (SEER) 17-registry database using site and histology codes. Cancer-specific survival (CSS) was estimated and compared, and Cox proportional hazards regression was used to explore associations with cancer-specific mortality. Results: Thirty-nine cases of PB were identified, compared with 155,924 cases of PDAC. The median age at diagnosis was 17 years (range, under 1 to 78 years); 12.8% (n = 5) were younger than 1 year. Males accounted for 69.2% (n = 27) of cases. The cohort was divided at the conventional pediatric-to-adult threshold of 18 years into a pediatric subgroup (age < 18 years; n = 20) and an adult subgroup (age ≥ 18 years; n = 19). CSS at 1 and 5 years was 95.0% and 83.5% in the pediatric subgroup, versus 67.7% and 24.6% in the adult subgroup (log-rank p < 0.001). Five-year CSS was 44.8% in males and 75.0% in females. In an exploratory multivariable model, older age was associated with higher cancer-specific mortality both as a dichotomous variable (adjusted hazard ratio [HR] for age ≥ 18 years 10.7, 95% confidence interval [CI] 2.4–48.2; p = 0.002) and, in a parallel model, as a continuous variable (adjusted HR 1.4 per 10-year increment, 95% CI 1.1–1.8; p = 0.002), indicating an age–mortality gradient. Male sex showed an association in the same direction that did not reach statistical significance (adjusted HR 3.3, 95% CI 0.96–11.6; p = 0.06). Relative to PDAC, PB was more frequently diagnosed in males and was associated with markedly superior survival (1- and 5-year CSS 81.8% and 54.9%, versus 28.8% and 4.0%). Conclusions: Pancreatoblastoma is predominantly a malignancy of young males and carries a substantially more favorable prognosis than PDAC, but outcomes differ markedly across the age spectrum, with adult-onset disease showing considerably poorer survival. Translationally, these population-level estimates support age-stratified prognostic counseling, argue for the referral of adults to centers experienced in rare pancreatic tumors, and provide a rationale for prospective molecular profiling to determine whether adult and pediatric PBs are biologically distinct and whether Wnt/beta-catenin pathway activation is therapeutically actionable. Full article

Indoles are chemical compounds that naturally occur in Prokaryotes and Eukaryotes. For example, indole alkaloids mainly occur in plant families such as Nyssaceae, Rubiaceae, Apocynaceae, and Loganiaceae. The popularity of indoles has led to further research into their function and synthetic modification. Meanwhile, the Wnt (Wingless and Int-1) signaling pathway is responsible for cell regulatory processes, while its dysfunction often constitutes the molecular basis for the pathogenesis of neoplastic processes. Databases such as PubMed, Scopus, Google Scholar, and Science Direct were used to perform a literature search with keywords including “indoles” and those related to their biological activity, as well as “Wnt pathway” and “thyroid cancer (TC)”. We used ClinicalTrials.gov to search current clinical trials for selected indoles, such as melatonin, indole-3-propionic acid, and indole-3-carbinol. While indoles possess many therapeutic properties, we focused here on the following: antitumor, antiviral, anti-inflammatory, antidepressant, antimigraine, antiemetic, and antihypertensive activities. We analyzed the Wnt pathway and its disruptions in thyroid cancer. In this manuscript, seventy-six (76) indoles, which have natural and synthetic origins, are presented. In addition to all activities mentioned, we discuss the therapeutic goals of indole applications in anticancer research. The Wnt signaling pathway can be changed in tumor cells, and such disruptions can occur in thyroid cancers. Full article