Search Results (4,322)

The advent of breast cancer molecular subtyping has transformed management, enabling treatment personalisation and de-escalation beyond traditional stage-based approaches. Established biomarkers, such as Ki-67 in luminal disease, HER2 amplification, and PD-L1 expression in triple-negative breast cancer, underpin seminal clinical trials yet remain imperfect predictors of response and long-term outcome. MicroRNAs have emerged as promising next-generation biomarkers and therapeutic tools. As master regulators of gene expression, both tumour-derived and circulating microRNAs can refine diagnosis and molecular subclassification, inform prognosis and therapeutic selection, act as treatment sensitisers, and potentially serve as direct therapeutic targets. Well-characterised miRNAs such as miR-221 have been implicated in endocrine resistance, while recent liquid-biopsy approaches have enabled the identification of circulating miR-145 and exosomal miR-155 as predictors of pathological complete response in HER2-positive disease. Their detectability in tissue, blood and other biofluids offers a minimally invasive means to dynamically monitor cancer behaviour and response, supporting more precise therapeutic decision-making. This review synthesises the current evidence for miRNA-based biomarkers across oestrogen-receptor positive, HER2-positive and triple-negative breast cancer and outlines their potential integration into biomarker-driven clinical trial designs and personalised treatment strategies. Full article

Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficient Disorder (CDD) is a rare X-linked developmental and epileptic encephalopathy characterized by early-onset refractory epilepsy, severe neurodevelopmental impairment, and lifelong disability. Although more than thirty anti-seizure medications are available, most CDD patients remain pharmaco-resistant. Gene-based therapies are emerging, but therapeutic development is hindered by marked clinical heterogeneity, small patient populations, and the lack of robust, translatable brain-based biomarkers for clinical trials. Genetically engineered Cdkl5 mouse models recapitulate many cognitive, behavioral, and molecular features of CDD, yet their utility is limited by the absence of overt seizures, precluding seizure-based outcome measures. Here, we establish high-definition brain network (HDBN) biomarkers using advanced diffusion MRI tractography combined with graph-theoretical analysis to quantify whole-brain network organization in Cdkl5 knockout mice. Diffusion MRI enables non-invasive mapping of axonal connectivity by leveraging anisotropic water diffusion, while high-angular-resolution acquisition overcomes key limitations of conventional diffusion tensor imaging in regions with complex fiber architecture. We demonstrate that Cdkl5 knockout mice exhibit reproducible and region-specific disruptions in brain network organization, prominently affecting the somatosensory and somatomotor cortex, hippocampus, hypothalamus, amygdala, and superior colliculus—regions implicated in cognition, learning and memory, homeostasis, anxiety, and visual–motor function. In contrast, networks within the entorhinal cortex remain largely preserved. These findings identify HDBN metrics as sensitive, non-invasive biomarkers that capture clinically relevant circuit-level abnormalities in CDD. Because diffusion MRI–based network analyses are directly translatable across species, HDBN biomarkers provide a unified framework for therapeutic evaluation in mouse models, large animals, and human clinical trials, enabling longitudinal monitoring of disease progression and treatment response. Full article

Retinal ganglion cell (RGC) degeneration underlies glaucomatous optic neuropathy and remains a leading cause of irreversible vision loss worldwide. Although elevated intraocular pressure (IOP) is the primary modifiable risk factor, RGC death reflects converging mechanisms including mechanical stress, vascular insufficiency, metabolic dysfunction, and neuroinflammation. We conducted a PRISMA-guided systematic review with PICOS-defined eligibility criteria, searching PubMed, Cochrane Library, ScienceDirect, Scopus, Google Scholar, and ProQuest for studies through January 2026 on RGC degeneration and neuroprotective or regenerative therapies in glaucoma. Included studies supported OCT-based structural assessment and imaging biomarkers as essential tools for early detection, risk stratification, and monitoring of progression and treatment response. Continued RGC loss despite IOP control in many patients highlights the need for mechanism-based interventions; neuroprotective strategies targeting excitotoxicity, oxidative stress, mitochondrial dysfunction, and neurotrophic insufficiency are emerging, while stem cell and gene-based regenerative therapies remain under active investigation. Integrating molecular insights with advanced imaging and biomarker-guided endpoints may enable earlier, more individualized intervention and help explain progression despite adequate pressure control. Full article

This study explores the influence of anion hydrogen-bond basicity, quantified by the Kamlet–Taft β parameter, on cellulose dissolution in imidazolium-based ionic liquids (ILs). A series of ILs sharing the common cation 1-benzyl-3-methylimidazolium were synthesized with varying anions, including chloride, acetate, formate, methoxyacetate, and methylphosphonate. The hydrogen-bond accepting ability (β) of each IL was experimentally determined and correlated with cellulose dissolution performance. Dissolution capability was evaluated by solubilizing 5 wt% cotton cellulose at 90 °C and monitoring under polarized light microscopy. Among the studied systems, 1-benzyl-3-methylimidazolium acetate (β = 1.01) demonstrated the highest dissolution efficiency, highlighting the critical role of strong hydrogen-bond basicity in disrupting the cellulose hydrogen-bonding network. To support the experimental observations, COSMO-RS simulations were conducted to probe the molecular-level interactions between anions and cellulose. Parameters such as anion size, theoretical density, viscosity, and surface charge density distribution were analyzed to elucidate their contributions to dissolution behavior. The regenerated cellulose was further characterized using scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. Full article

Background: Trichosporon japonicum is a rare but highly lethal pathogen causing fungemia in immunocompromised patients. With the expanding use of chimeric antigen receptor T (CAR-T) cell therapy, the spectrum of opportunistic fungal infections is changing, yet data on T. japonicum infections in this setting remain scarce. Case Presentation: A 69-year-old man with diffuse large B-cell lymphoma developed catheter-associated fungemia after CAR-T cell reinfusion. He initially presented with neck pain and white oral mucosal patches, followed by fever four days later. T. japonicum was isolated from both peripheral blood and central venous catheter tip cultures, identified by microscopic examination, mass spectrometry, and molecular sequencing. Antifungal prophylaxis was initiated before fever onset based on close monitoring of white blood cell count, procalcitonin, interleukin-6, and C-reactive protein; treatment was subsequently adjusted according to species identification and antifungal susceptibility results. Infection was controlled within two weeks after catheter removal and immune recovery. The patient remained well at six-month follow-up. Conclusion: This case adds to the limited literature on T. japonicum fungemia in patients receiving CAR-T therapy. Our experience, together with a review of the literature, underscores that successful management requires prompt catheter removal, immune restoration, and combination therapy with voriconazole and amphotericin B, as echinocandin monotherapy should be avoided. Awareness of this pathogen in immunocompromised patients is critical. Full article

Oil–water emulsions constitute essential components in a wide range of industries. Despite their extensive use in emulsion systems, synthetic emulsifiers are often associated with environmental concerns and high costs. In this study, lignin—a by-product of the pulping industry—was polymerized with acrylic acid and employed as an emulsifier in a xylene–water system to address this challenge. When testing two lignin–acrylic acid copolymers, the results confirmed that the one possessing a higher molecular weight (7.99 × 10⁵ g/mol) and charge density (4.7 mmol/g) (KL-AA-10) generated xylene–water emulsions with improved stability, and higher viscosity and viscoelastic moduli. These observations were consistent with the greater adsorption of this polymer, relative to the counterparts with a lower molecular weight and charge density at the xylene–water interface, as monitored using a Quartz Crystal Microbalance. The adsorption of KL-AA-10 resulted in the formation of smaller emulsion droplets (D50 = 0.6 µm) within the system, as evidenced by confocal microscopy analysis. This study underscores the potential of lignin as a renewable emulsifier for diverse applications. Full article

Background: Epimedium is a natural herb with immunomodulatory potential, but its vaccine adjuvant properties remain poorly understood. Objective: The aim of this study was to elucidate the adjuvant effects of Epimedium and the underlying molecular mechanisms. Methods: Network pharmacology was used to identify bioactive compounds and targets of Epimedium from the TCMSP database, and immunomodulation-related targets from GeneCards and OMIM. PPI networks, KEGG/GO enrichment, molecular docking, and molecular dynamics (MD) simulations were performed. In vivo, female BALB/c mice were immunized with the Staphylococcus aureus (S. aureus) vaccine subunit HI antigen, either alone or with low- or high-dose icariin (ICA). Serum antibody responses (IgG, IgG1, IgG2a, IgG2b) were measured by ELISA. Survival against lethal S. aureus USA300 challenge was monitored. Results: Network pharmacology predicted 488 targets and 13 pathways. Core targets included IL6, TP53, EGFR, CTNNB1, HIF1A, HSP90AA1, JUN, MTOR, SRC, and AKT1. KEGG/GO analysis indicated involvement of T cell receptor and NOD-like receptor signaling pathways in inflammatory responses. Molecular docking and MD simulations confirmed stable ligand-target binding. Experimental validation showed that ICA significantly enhanced HI-specific antibody responses and induced a Th2-biased humoral immune response (IgG1/IgG2a ratio > 1), which is particularly relevant for vaccines targeting extracellular pathogens such as S. aureus. ICA also improved survival after lethal bacterial challenge. Conclusions: This study identifies potential bioactive compounds, core targets, and key pathways of Epimedium as a vaccine adjuvant. Experimentally, ICA, as a representative component, enhanced HI-specific antibody responses and conferred protection against lethal S. aureus challenge. Together, these findings offer a computational–experimental basis that may guide further mechanistic investigation. Full article

Background: Gestation is a period of significant biological plasticity where the intrauterine environment influences fetal development via “fetal programming”. This study systematically reviews and meta-analyzes the association between genetic determinants—specifically the NR3C1, FKBP5, and CRHR1 genes, chosen for their pivotal role in the functional regulation and feedback sensitivity of the hypothalamic–pituitary–adrenal (HPA) axis—and stress reactivity during pregnancy. Methods: Following PRISMA guidelines, a systematic search was conducted across PubMed, Scopus, and Web of Science, yielding an initial total of 1430 records. After removing duplicates and screening 669 studies, a total of 34 primary observational studies were included in the systematic review and qualitative synthesis. For the quantitative synthesis, 27 articles provided sufficient data, resulting in k = 39 independent effect sizes analyzed via a mixed-effects model to account for tissue-specific and cohort-specific outcomes. Results: Systematic analysis reveals that maternal psychosocial stress significantly correlates with NR3C1 hypermethylation, acting as a biological mediator for neonatal cortisol dysregulation and hippocampal volume reduction. The FKBP5 rs1360780 polymorphism emerged as a key moderator of structural vulnerability, showing a “double-hit” effect when combined with epigenetic alterations. Furthermore, the study identifies sex-specific susceptibility, with divergent placental trajectories for male and female fetuses. Meta-analytic estimates confirmed the robustness of these associations (Rosenthal Fail-Safe N = 431,000), despite a general trend toward statistical significance (p = 0.079) in heterogeneous cohorts. Conclusions: The findings underscore a stable link between genetic determinants and prenatal stress reactivity. The interaction between molecular predisposition and environmental factors defines the health of the mother–infant dyad. These results advocate for a transition toward Precision Prenatal Medicine, integrating polygenic risk scores and epigenetic monitoring to implement early, targeted preventive interventions. Full article

Infectious bronchitis virus (IBV) is an avian coronavirus associated with respiratory, renal, and reproductive disease in chickens, with important economic consequences in intensive poultry production. This study aimed to estimate the seroprevalence of anti-IBV antibodies in vaccinated broiler flocks reared in south-western Romania and to characterize its distribution across counties and study years. Between 2018 and 2021, a total of 2466 blood samples were collected from Ross 308 broilers aged 35–45 days originating from five commercial farms (one per county) located in Caraș-Severin, Dolj, Gorj, Hunedoara, and Vâlcea. Samples were obtained from 137 production halls/series. Sera were tested using a commercial indirect ELISA kit and classified according to the manufacturer’s criteria based on the sample-to-positive (S/P) ratio and the corresponding antibody titer threshold. Overall, 2115/2466 sera were positive (85.77%) and 351/2466 were negative (14.23%). Anti-IBV antibodies were detected in all halls (137/137, 100%), although negative sera were recorded in 87/137 halls (63%). Seroprevalence by county ranged from 78.67% (Vâlcea) to 89.24% (Hunedoara). Significant differences in the proportions of positive and negative sera were identified between several county pairs by Fisher’s exact test. These findings indicate widespread serological evidence of anti-IBV antibodies in vaccinated broiler flocks from south-western Romania, which may reflect vaccine-induced immunity and/or field exposure. The results support the need for continued serological monitoring, alongside targeted molecular investigations to differentiate vaccine strains from circulating field variants. Full article

Bovine viral diarrhea virus (BVDV) is a major cattle pathogen associated with significant economic losses worldwide. In Brazil, the high genetic diversity of circulating strains represents an additional challenge for disease control. To update the molecular epidemiology of BVDV in southern Brazil, 16,198 bovine serum samples collected in 2020 through a national surveillance program were screened for pestivirus RNA by RT-qPCR. Forty-nine samples (0.36%) were positive and subjected to partial sequencing of the 5′UTR and N^pro regions. Phylogenetic analysis identified BVDV-1a (25/49; 51%), BVDV-1b (1/49; 2%), BVDV-1d (7/49; 14%), and BVDV-2b (16/49; 33%), with no detection of HoBiPeV. When compared descriptively with data from 2010 in the same region, BVDV-1a remained the most frequent subgenotype, while BVDV-2b also represented a substantial proportion of detections, contrasting with other regions worldwide. Although the two datasets are not directly comparable, and no statistically significant differences were observed, these findings provide an updated overview of circulating BVDV subgenotypes in Rio Grande do Sul. The absence of HoBiPeV contrasts with reports from other regions of Brazil and suggests a distinct regional pattern of pestivirus circulation. Overall, the results reinforce the importance of continuous genomic surveillance to monitor changes in viral diversity and support control strategies in cattle populations. Full article

[18F]fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) imaging has been explored for its potential use as an added modality for the assessment of gliomas. The aim of this review was to synthesize the existing literature investigating this topic. A comprehensive search of the PubMed/MEDLINE, Scopus, and Embase databases was performed to identify eligible original research investigating the role of [18F]FMISO PET imaging for the evaluation of gliomas. Thirty-tree studies were included in the present review. Overall, the findings reported suggest that [18F]FMISO PET may have relevant clinical implications in glioma assessment and management, including improved tumor characterization, differential diagnosis between different grades and other neoplasms, prognostic stratification, and potential guidance for personalized therapeutic strategies. The available evidence supports the idea that [18F]FMISO PET can act as a robust and biologically meaningful imaging modality in gliomas. Its strengths lie in tumor grading, prognostication, and treatment monitoring, particularly in glioblastoma. Future research should focus on standardized imaging protocols, integration with molecular classification frameworks, and validation of hypoxia-guided therapeutic strategies. Full article

Dickkopf-1 (DKK1) is a 266-amino-acid secreted glycoprotein originally identified as a high-affinity antagonist of the canonical Wnt/β-catenin signaling pathway and has emerged as a complex regulator in oncology. While historically considered as a tumor suppressor due to its ability to abrogate Wnt-driven proliferation, recent discoveries highlight a paradoxical pro-oncogenic role across various malignancies. The molecular mechanisms by which DKK1 promotes tumor progression, metastasis, and immune evasion are driven by its interaction with cell-surface receptors, specifically LRP5/6 and CKAP4. The DKK1-CKAP4 axis independently activates PI3K/AKT signaling, facilitating epithelial–mesenchymal transition (EMT), chemoresistance, and the formation of osteolytic bone lesions. Furthermore, DKK1 serves as a critical orchestrator of the tumor microenvironment (TME) by driving comprehensive immune reprogramming. It mediates the recruitment of myeloid-derived suppressor cells (MDSCs) and inactivates cytotoxic CD8⁺ T cells and natural killer (NK) cells, thereby fostering an immunosuppressive tumor microenvironment and resistance to checkpoint inhibitors. Interestingly, cancer-associated fibroblasts (CAFs) are a primary source of DKK1 in the stroma, where they facilitate immune evasion. Clinically, elevated circulating DKK1 levels correlate with advanced disease stages, increased metastatic potential, and poor overall survival in solid and hematological tumors. When used in combination with established biomarkers, serum DKK1 levels demonstrate significant utility for early detection and therapeutic monitoring. Given its intricate impact on malignancy, DKK1 has become a promising therapeutic target, with ongoing clinical trials investigating neutralizing antibodies such as DKN-01 to disrupt its oncogenic and immunosuppressive signaling. Understanding the context-dependent nature of DKK1 signaling remains essential for refining its application as both a biomarker and a component of emerging precision immunotherapy strategies. By prioritizing the literature from the last decade, this review characterizes DKK1 as a key mediator of tumor progression and immune reprogramming, while assessing its clinical potential as a biomarker and therapeutic target. Full article

Cholangiocarcinoma (CCA) is a highly aggressive malignancy that is difficult to diagnose early and carries a poor prognosis. Conventional serological diagnostics are limited by inadequate sensitivity and the risks of invasive procedures, resulting in most patients being diagnosed at an advanced stage. In recent years, liquid biopsy has emerged as a novel approach for non-invasive and dynamic molecular tumor monitoring by detecting biomarkers such as circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating tumor DNA (ctDNA) and clusterin (CLU). Furthermore, artificial intelligence (AI) has demonstrated strong potential in aiding diagnosis through medical image analysis, pathological pattern recognition, and multi-omics data integration, significantly improving the precision of early detection, risk stratification, and treatment response monitoring in CCA. This review systematically summarizes recent advances in liquid biopsy and AI for CCA diagnosis, discusses their clinical potential and current challenges, and offers perspectives on how their integration can propel the field toward earlier and more precise management of the disease. Full article

As global food security challenges intensify, edible crickets are recognized as sustainable protein alternatives; however, genomic resources for commercially important species remain limited, restricting evolutionary inference and the development of robust tools for farm management. We sequenced and assembled the complete mitochondrial genomes of Gryllus bimaculatus and provided the first report for Teleogryllus mitratus, both derived from commercial farms in Thailand, using high-throughput Illumina sequencing, achieving high coverage depths of 32,391× and 63,258×, respectively. The circular mitochondrial genomes were 15,955 bp and 16,046 bp and exhibited the typical insect mitochondrial gene complement of 37 genes, with a strong AT bias. Selective pressure analyses indicated pervasive purifying selection across all protein-coding genes (PCGs) (ω < 1), while episodic diversifying selection was detected in cox1, cox3, cytb, and nad5; additionally, atp8 displayed a comparatively elevated ω. Codon usage analyses revealed a strong preference for AT-ending codons, with leucine codons showing the highest bias. Phylogenetic analyses using concatenated protein-coding and ribosomal RNA genes recovered well-supported relationships within Gryllidae. These farm-derived mitogenomes provide practical foundations for molecular species authentication, population monitoring, and comparative analyses relevant to breeding and traceability. Furthermore, they provide candidate loci for future investigations into mitochondrial evolutionary dynamics and the potential development of molecular markers for commercial breeding management. Full article

Background/Objectives: Helicobacter pylori (HP) antibiotic eradication treatment in Germany is, at present, empirical according to the national guidelines. The aim of our prospective multicentre study was to implement routine susceptibility testing in daily clinical practice to facilitate resistance-oriented first-line antibiotic therapy and to collect local resistance data. Methods: From 1 January 2024 to 30 April 2025, in two German hospitals (in Bielefeld and Datteln), the patients who underwent gastroscopy and those who had biopsies for histopathology also underwent biopsies for the Helicobacter urease test (HUT). Positive HUT samples were sent for susceptibility testing: they were checked for phenotypic/cultural resistance to amoxicillin, clarithromycin, metronidazole, levofloxacin, rifampicin and tetracycline and genotypic/molecular resistance to clarithromycin and fluoroquinolones. Results: In total, in 1503 cases, both HUT and histology were performed, in which 256 (17.0%) histologies were HP-positive. We sent 311/1503 (20.7%) positive HUTs for susceptibility testing. In 120 (38.6%) of them, it was possible to culture HP, and for 118 cases, phenotypic resistance testing was performed. In 200/311 cases, PCR was also executed, with 111/200 cases being subjected to subsequent molecular resistance testing. Resistance patterns varied regionally, with metronidazole resistance observed in 3–33%, clarithromycin resistance in 16–20% and levofloxacin resistance in 13–16% cases. Conclusions: it is technically and logically feasible to perform HP antibiotic susceptibility testing via the same biopsy used for the HUT. The proposed procedures might be applied both in hospital and outpatient settings in endoscopic offices. Routine susceptibility testing is useful not only for the individual patient but also for monitoring the development of regional resistance patterns as a basis for better-targeted empiric therapy. Additionally, this approach might help to reduce the resistance dynamics at large in terms of antimicrobial stewardship. Full article