Search Results (11,925)

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article

CD26 (dipeptidyl peptidase-4) is a marker of colorectal cancer stem cells with high metastatic potential and resistance to therapy. Although CD26 expression is known to be associated with tumor progression, its functional involvement in epithelial-mesenchymal transition (EMT) and metastasis remains to be fully elucidated. In this study, we aimed to investigate the effects of a monoclonal anti-CD26 antibody on EMT-related phenotypes and metastatic behavior in colorectal cancer cells. We evaluated changes in EMT markers by quantitative PCR and Western blotting, assessed cell motility and invasion using scratch wound-healing and Transwell assays, and examined metastatic potential in vivo using a splenic injection mouse model. Treatment with the anti-CD26 antibody significantly increased the expression of the epithelial marker E-cadherin and reduced levels of EMT-inducing transcription factors, including ZEB1, Twist1, and Snail1, at the mRNA and protein levels. Functional assays revealed that the antibody markedly inhibited cell migration and invasion in vitro without exerting cytotoxic effects. Furthermore, systemic administration of the anti-CD26 antibody significantly suppressed the formation of liver metastases in vivo. These findings suggest that CD26 may contribute to the regulation of EMT and metastatic behavior in colorectal cancer. Our data highlight the potential therapeutic utility of CD26-targeted antibody therapy for suppressing EMT-associated phenotypes and metastatic progression. Full article

Glioblastoma (GBM) is a highly aggressive brain tumor marked by invasive growth and therapy resistance. Tumor cells adapt to hostile conditions, such as hypoxia and nutrient deprivation, by activating survival mechanisms including autophagy and metabolic reprogramming. Among GBM-associated changes, hypersialylation, particularly, the aberrant expression of polysialic acid (PSA), has been linked to increased plasticity, motility, and immune evasion. PSA, a long α2,8-linked sialic acid polymer typically attached to the NCAM, is abundant in the embryonic brain and re-expressed in cancers, correlating with poor prognosis. Here, we investigated how PSA expression was regulated in GBM cells under nutrient-limiting conditions. Serum starvation induced a marked increase in PSA-NCAM, driven by upregulation of the polysialyltransferase ST8SiaIV and an autophagy-dependent recycling of sialic acids from degraded glycoproteins. Inhibition of autophagy or sialidases impaired PSA induction, and PSA regulation appeared dependent on p53 function. Immunohistochemical analysis of GBM tissues revealed co-localization of PSA and LC3, particularly around necrotic regions. In conclusion, we identified a novel mechanism by which GBM cells sustain PSA-NCAM expression via autophagy-mediated sialic acid recycling under nutrient stress. This pathway may enhance cell migration, immune escape, and stem-like properties, offering a potential therapeutic target in GBM. Full article

Multiple sclerosis (MS), a chronic disease of the central nervous system, is known to cause structural and vascular changes in the retina. Although optical coherence tomography (OCT) and fundus photography can detect retinal thinning and circulatory abnormalities, these findings are not specific to MS. This study explores the potential of Infrared Scanning-Laser-Ophthalmoscopy (IR-SLO) imaging to uncover vascular morphological features that may serve as MS-specific biomarkers. Using an age-matched, subject-wise stratified k-fold cross-validation approach, a deep learning model originally designed for color fundus images was adapted to segment optic disc, optic cup, and retinal vessels in IR-SLO images, achieving Dice coefficients of 91%, 94.5%, and 97%, respectively. This process included tailored pre- and post-processing steps to optimize segmentation accuracy. Subsequently, clinically relevant features were extracted. Statistical analyses followed by SHapley Additive exPlanations (SHAP) identified vessel fractal dimension, vessel density in zones B and C (circular regions extending 0.5–1 and 0.5–2 optic disc diameters from the optic disc margin, respectively), along with vessel intensity and width, as key differentiators between MS patients and healthy controls. These findings suggest that IR-SLO can non-invasively detect retinal vascular biomarkers that may serve as additional or alternative diagnostic markers for MS diagnosis, complementing current invasive procedures. Full article

Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC. In the non-metastatic setting, liquid biopsy is gaining traction in early detection through screening and in identifying minimal residual disease (MRD), potentially guiding adjuvant treatment and reducing overtreatment. In contrast, liquid biopsy is more established in metastatic CRC for monitoring treatment responses, clonal evolution, and mechanisms of resistance. The integration of ctDNA-guided treatment algorithms into clinical practice could optimize therapeutic strategies and minimize unnecessary interventions. Despite promising advances, challenges remain in assay standardization, early-stage sensitivity, and the integration of multi-omic data for comprehensive tumor profiling. Future efforts should focus on enhancing the sensitivity of liquid biopsy platforms, validating emerging biomarkers, and expanding multi-omic approaches to support more targeted and personalized treatment strategies across CRC stages. Full article

Cholangiocarcinoma (CCA) is highly prevalent in the Greater Mekong sub-region, especially northeastern Thailand, where infection with the liver fluke Opisthorchis viverrini is a major etiological factor. Limited therapeutic options and the absence of reliable early diagnosis tools impede effective disease control. Atractylodes lancea (Thunb.) DC.—long used in Thai and East Asian medicine, contains atractylodin (ATD), a potent bioactive compound with anticancer potential. Here, we developed ATD-loaded poly(lactic co-glycolic acid) nanoparticles (ATD PLGA NPs) and evaluated their antitumor efficacy against CCA. The formulated nanoparticles had a mean diameter of 229.8 nm, an encapsulation efficiency of 83%, and exhibited biphasic, sustained release, reaching a cumulative release of 92% within seven days. In vitro, ATD-PLGA NPs selectively reduced the viability of CL-6 and HuCCT-1 CCA cell lines, with selectivity indices (SI) of 3.53 and 2.61, respectively, outperforming free ATD and 5-fluorouracil (5-FU). They suppressed CL-6 cell migration and invasion by up to 90% within 12 h and induced apoptosis in 83% of cells through caspase-3/7 activation. Micronucleus assays showed lower mutagenic potential than the positive control. In vivo, ATD-PLGA NPs dose-dependently inhibited tumor growth and prolonged survival in CCA-xenografted nude mice; the high-dose regimen matched or exceeded the efficacy of 5-FU. Gene expression analysis revealed significant downregulation of pro-tumorigenic factors (VEGF, MMP-9, TGF-β, TNF-α, COX-2, PGE₂, and IL-6) and upregulation of the anti-inflammatory cytokine IL-10. Collectively, these results indicate that ATD-PLGA NPs are a promising nanotherapeutic platform for targeted CCA treatment, offering improved anticancer potency, selectivity, and safety compared to conventional therapies. Full article

Green synthesis of copper oxide (CuO) nanoparticles offers a sustainable alternative to conventional chemical methods that often involve toxic reagents and harsh conditions. This study investigates the use of Tithonia diversifolia, an invasive species in Sri Lanka, as a bioreductant for the eco-friendly fabrication of CuO nanoparticles. Using copper sulfate (CuSO₄·5H₂O) as a precursor, eight treatments were conducted by varying precursor concentration, temperature, and reaction time to determine optimal conditions. A visible color change in the reaction mixture initially indicated nanoparticle formation. Among all the conditions, treatment T4 (5 mM CuSO₄, 80 °C, 2 h) yielded the most favorable results in terms of stability, morphology, and crystallinity. UV-Vis spectroscopic analysis confirmed the synthesis, with absorbance peaks between 265 and 285 nm. FTIR analysis revealed organic functional groups and characteristic metal–oxygen vibrations in the fingerprint region (500–650 cm⁻¹), confirming formation. SEM imaging showed that particles were mainly spherical to polygonal, averaging 125–150 nm. However, dynamic light scattering showed larger diameters (~240 nm) due to surface capping agents. Zeta potential values ranged from −16.0 to −28.0 mV, indicating stability. XRD data revealed partial crystallinity with CuO-specific peaks. These findings support the potential of T. diversifolia in green nanoparticle synthesis, suggesting a low-cost, eco-conscious strategy for future applications. Full article

Background: RSV remains a leading cause of infant hospitalization worldwide, and the recently approved nirsevimab could represent an effective and safe prophylactic strategy to prevent severe infections in the general neonatal population. Objectives: We conducted a retrospective observational monocentric pilot study in a mixed preterm/term birth cohort to add real-world evidence of the efficacy and safety of nirsevimab in preventing severe RSV infection. Methods: We included a total of 2035 consecutive infants admitted to the Neonatal Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy, from November 2024 to April 2025. We evaluated 30-day safety profiles and season-wide RSV infection rates, and the outcomes were also compared to newborns’ birth rate in the two previous seasons (2022–2023 and 2023–2024). Results: After the introduction of nirsevimab, a lower RSV infection rate was reported compared to previous seasons, and no adverse effects were observed. Compared to previous seasons, the clinical outcomes were more favorable, as only one unvaccinated neonate with RSV infection required invasive ventilation. Conclusions: In this real-world analysis, we demonstrated a good short-term safety profile of nirsevimab, as well as a potentially high efficacy in the general neonatal population with lower RSV infection incidence. However, future studies are needed to better assess its long-term safety and season-wide efficacy. Full article

Amblyopia, commonly affecting children aged 0–6 years, results from disrupted visual processing during early development and often leads to reduced visual acuity in one eye. This study presents the development and preliminary usability assessment of a non-invasive ocular monitoring device designed to support oculomotor engagement and therapy adherence in amblyopia management. The system incorporates an interactive maze-navigation task controlled via gaze direction, implemented during monocular and binocular sessions. The device tracks lateral and anteroposterior eye movements and generates visual reports, including displacement metrics and elliptical movement graphs. Usability testing was conducted with a non-probabilistic adult sample (n = 15), including individuals with and without amblyopia. The System Usability Scale (SUS) yielded an average score of 75, indicating good usability. Preliminary tests with two adults diagnosed with amblyopia suggested increased eye displacement during monocular sessions, potentially reflecting enhanced engagement rather than direct therapeutic improvement. This feasibility study demonstrates the device’s potential as a supportive, gaze-controlled platform for visual engagement monitoring in amblyopia rehabilitation. Future clinical studies involving pediatric populations and integration of visual stimuli modulation are recommended to evaluate therapeutic efficacy and adaptability for early intervention. Full article

Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are aggressive malignancies characterized by a poor prognosis and resistance to conventional therapies. Mounting evidence suggests the pivotal role of epithelial–mesenchymal transition (EMT) in tumor progression, metastasis, and therapeutic resistance in these cancers. Protein induced by vitamin K absence II (PIVKA-II)—a valuable HCC detector—has ultimately emerged as a potentially relevant biomarker in PDAC, serving as both a serum biomarker and a prognostic indicator. This study investigates the putative link between PIVKA-II expression and the EMT process in HCC and PDAC. Using a Western blot analysis and electrochemiluminescence immunoassay (ECLIA), we quantified PIVKA-II serum levels alongside two canonical EMT markers—Vimentin and E-cadherin—in selected cohorts. Emerging data suggest a dual, context-dependent role for PIVKA-II. Beyond its diagnostic value in both malignancies, its co-expression with EMT markers points to a potential mechanistic involvement in tumor invasiveness and phenotypic plasticity. Notably, the selective detection of E-cadherin in HCC implies limited EMT activation and a preservation of the epithelial phenotype, whereas the higher expression of Vimentin in PDAC reflects a more substantial shift toward EMT. We provide a comprehensive analysis of key molecular markers, their involvement in EMT-driven pathophysiological mechanisms, and their potential as novel diagnostic tools. Full article

Macrophage-mediated inflammation is known to be involved in the epithelial–mesenchymal transition (EMT) of various types of cancer. This makes macrophage-derived inflammatory factors prime targets for the development of new treatments. This study uncovers the therapeutic potential and action mechanism of DAB-2-28, a small-molecule derived from para-aminobenzoic acid, in the treatment of breast cancer. The luminal MCF-7 and the triple-negative MDA-MB-231 cancer cell lines used in this study represent, respectively, breast cancers in which the differentiation states are related to the epithelial phenotype of the mammary gland and breast cancers expressing a highly aggressive mesenchymal phenotype. In MCF-7 cells, soluble factors from macrophage-conditioned media (CM-MØ) induce a characteristic morphology of mesenchymal cells with an upregulated expression of Snail1, a mesenchymal marker, as opposed to a decrease in the expression of E-cadherin, an epithelial marker. DAB-2-28 does not affect the differential expression of Snail1 and E-cadherin in response to CM-MØ, but negatively impacts other hallmarks of EMT by decreasing invasion and migration capacities, in addition to MMP9 expression and gelatinase activity, in both MCF-7 and MDA-MB-231 cells. Moreover, DAB-2-28 inhibits the phosphorylation of key pro-EMT transcriptional factors, such as NFκB, STAT3, SMAD2, CREB, and/or AKT proteins, in breast cancer cells exposed to different EMT inducers. Overall, our study provides evidence suggesting that inhibition of EMT initiation or maintenance is a key mechanism by which DAB-2-28 can exert anti-tumoral effects in breast cancer cells. Full article

Background: Parkinson’s disease (PD) often involves autonomic dysfunction, most notably impaired baroreflex sensitivity (BRS), which disrupts cardiovascular homeostasis and contributes to orthostatic hypotension (OH). Pharmacological and invasive treatments, including deep brain stimulation, have yielded inconsistent benefits and carry procedural risks, highlighting the need for safer, more accessible alternatives. In this systematic review, we evaluated non-invasive interventions—spanning somatosensory stimulation, exercise modalities, thermal therapies, and positional strategies—aimed at improving cardiovascular autonomic function in PD. Methods: We searched PubMed, Embase, MEDLINE (Ovid), Google Scholar, ScienceDirect, and Web of Science for studies published between January 2014 and December 2024. Eight original studies (n = 8) including 205 participants met the inclusion criteria for analyzing cardiac sympathovagal balance. Results: Five studies demonstrated significant post-intervention increases in BRS. Most reported favorable shifts in heart rate variability (HRV) and favorable changes in the low-frequency/high-frequency (LF/HF) ratio. Across modalities, systolic blood pressure (SBP) decreased by an average of 5%, and some interventions produced benefits that persisted up to 24 h. Conclusion: Although sample sizes were small and protocols heterogeneous, the collective findings support the potential of non-invasive neuromodulation to enhance BRS and overall cardiovascular regulation in PD. Future research should focus on standardized, higher-intensity or combined protocols with longer follow-up periods to establish durable, clinically meaningful improvements in autonomic function and quality of life for people living with PD. Full article

To determine the association between FGFR4 (rs351855 and rs7708357) gene variants, serum levels, and immunohistochemical markers (Ki-67 and p53) in pituitary adenoma (PA), a case-control study was conducted involving 300 subjects divided into two groups: the control group (n = 200) and a group of PA (n = 100). The genotyping of FGFR4 rs351855 and rs7708357 was carried out using the real-time polymerase chain reaction (RT-PCR) method. The serum FGFR4 levels were measured using the ELISA method. Immunohistochemical analysis (Ki-67 and p53) was conducted. Statistical analysis of the data was performed using IBM SPSS Statistics 30.0 software. There were no statistically significant differences after analyzing the genotypes and alleles of FGFR4 rs351855 and rs7708357 in patients with PA and control groups (all p > 0.05). After evaluating the distribution of genotypes and alleles of FGFR4 rs351855 and rs7708357 in micro/macro, invasiveness, activity, and recurrence of PA and the control groups, the analysis showed no statistically significant differences between the groups (p > 0.05). Similarly, no significant differences in FGFR4 levels were observed between PA patients and control group (median (IQR): 3642.41 (1755.08) pg/mL vs. 3126.24 (1334.15) pg/mL, p = 0.121). Immunohistochemistry for Ki-67 revealed a labeling index (LI) of <1% in 25.5% of patients with PA, an LI of 1% in 10.9%, and an LI of >1% in 63.6% of patients. Further analyses showed no statistically significant associations with tumor size, invasiveness, activity, or recurrence. Immunohistochemistry for p53 revealed that macroadenomas had a significantly higher p53 H-score compared to microadenomas (median (IQR): 30.33 (28.68) vs. 18.34 (17.65), p = 0.005). Additionally, a moderate, statistically significant positive correlation between the Ki-67 LI and the p53 expression was found (Spearman’s ρ = 0.443, p = 0.003, n = 43). FGFR4 variants and serum protein levels were not significantly associated with PA risk or tumor features. Conversely, immunohistochemical markers Ki-67 and p53 were more informative, with higher p53 expression in macroadenomas and a moderate positive correlation between Ki-67 and p53, highlighting their potential relevance in tumor growth assessment. Full article

Tuberculosis (TB) is an ancient and re-emerging granulomatous infectious disease that continues to challenge public health. Early diagnosis and prompt effective treatment are crucial for preventing disease progression and reducing both morbidity and mortality. These steps play a vital role in infection control and in lowering death rates at both individual and population levels. Although diagnostic methods have improved sufficiently in recent decades, TB can still present with ambiguous laboratory and imaging features. This ambiguity can lead to diagnostic pitfalls and potentially disastrous outcomes due to delayed diagnosis. In this article, we present a case of TB that was difficult to diagnose. The disease had invaded the mediastinum, right atrium, right coronary artery, and inferior vena cava (IVC), resulting in Budd–Chiari syndrome. This rare presentation created clinical, laboratory, and radiological confusion, resulting in a diagnostic dilemma that ultimately led to open cardiac surgery. The patient initially presented with progressive shortness of breath on exertion and fatigue, which suggested possible heart disease. This suspicion was reinforced by computed tomography (CT) imaging, which showed infiltrative mass lesions predominantly in the right side of the heart, invading the right coronary artery and IVC, with imaging features mimicking angiosarcoma. Although laboratory findings revealed an exudative effusion with lymphocyte predominance and elevated adenosine deaminase (ADA), the Gram stain was negative for bacteria, and an acid-fast bacilli (AFB) smear was also negative. These findings contributed to diagnostic uncertainty and delayed the confirmation of TB. Open surgery with excisional biopsy and histopathological analysis ultimately confirmed TB. We conclude that TB should not be ruled out solely based on negative Mycobacterium bacteria in pericardial effusion or AFB smear. TB can mimic aggressive tumors such as angiosarcoma or lymphoma with invasion of the surrounding tissues and blood vessels. Awareness of the clinical presentation, imaging findings, and potential diagnostic pitfalls of TB is essential, especially in endemic regions. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a significant comorbidity in individuals with type 1 diabetes (T1D), despite its historical association with type 2 diabetes. This review focuses on summarizing current findings regarding the role of insulin resistance in the development of MASLD in T1D, as well as examining the relationship between MASLD and diabetes-related complications. We will also briefly discuss the prevalence, diagnostic challenges, associated complications, and potential mechanisms underlying MASLD in T1D. Although insulin resistance is well established in MASLD among those with type 2 diabetes, its role in T1D requires further clarification. Emerging markers, such as the estimated glucose disposal rate, offer early insight into this relationship. MASLD in T1D is linked to both microvascular and macrovascular complications, including nephropathy, retinopathy, neuropathy, and cardiovascular disease. Variability in prevalence estimates reflects inconsistencies among imaging modalities, emphasizing the need for standardized, non-invasive diagnostic approaches. Recognizing and addressing MASLD and its links to insulin resistance and diabetes complications in T1D is vital for mitigating long-term complications and enhancing clinical outcomes. Full article