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Chloride-capped silver nanoparticles (Cl-AgNPs) allow for high-intensity surface-enhanced Raman scattering (SERS) spectra of cationic molecules to be obtained (even at nanomolar concentration) and may also play a key role in understanding some fundamental principles behind SERS. In this study, we describe a fast (<10 min) and simple protocol for obtaining highly SERS-active colloidal silver nanoparticles (AgNPs) with a mean diameter of 36 nm by photoconversion from AgCl precursor microparticles in the absence of any organic reducing or capping agent. The resulting AgNPs are already SERS-activated by the Cl − ions chemisorbed onto the metal surface where the chloride concentration in the colloidal solution is 10 −2 M. Consequently, the enhanced SERS spectra of cationic dyes (e.g., crystal violet or 9-aminoacridine) demonstrate the advantages of Cl-AgNPs compared to the as-synthesized AgNPs obtained by standard Ag + reduction with hydroxylamine (hya-AgNPS) or citrate (cit-AgNPs). The results of SERS experiments on anionic and cationic test molecules comparing Cl-AgNPs, hya-AgNPs and cit-AgNPs colloids activated with different amounts of Cl − and/or cations such as Ag + , Mg 2+ or Ca 2+ can be explained within the understanding of the adatom model – the chemisorption of cationic analytes onto the metal surface is mediated by the Cl − ions, whereas ions like Ag + , Mg 2+ or Ca 2+ mediate the electronic coupling of anionic species to the silver metal surface. Moreover, the SERS effect is switched on only after the electronic coupling of the adsorbate to the silver surface at SERS-active sites. The experiments presented in this study highlight the SERS-activating role played by ions such as Cl − , Ag + , Mg 2+ or Ca 2+ , which is a process that seems to prevail over the Raman enhancement due to nanoparticle aggregation.

In our recent studies we highlighted the role of adsorbed ions (adions) in turning on the surface-enhanced Raman scattering (SERS) effect in a specific mode for anionic and cationic analytes. In this work, we emphasize the role of Ag+, Ca2+, Pb2+ and Al3+ adions in the specific adsorption of anionic analytes such as the citrate capping agent and three organic acids. Our results suggest an adion-specific adsorption mechanism: the adsorption of anionic analytes is facilitated by positively charged adions such as Ag+, Ca2+, Pb2+ or Al3+, which provide adsorption sites specific for the anionic analytes. The turn-on of the SERS effect is explained in the context of the chemical mechanism of SERS. The adions form SERS-active sites on the silver surface enabling a charge transfer between the adsorbate and the silver surface. High-intensity SERS spectra of uric acid, salicylic acid and fumaric acid could be recorded at a concentration of 50 µM only after activation of the colloidal silver nanoparticles by Ca2+, Pb2+ or Al3+ (50 µM). The chemisorption of the three anionic species to the silver surface occurs competitively and is enhanced with the anions of higher affinities to the silver surface as indicated by the SERS spectra of corresponding mixed solutions.

The high-throughput analysis of DNA methylation markers by label-free surface-enhanced Raman scattering (SERS) holds significant promise for advancing cancer detection. However, a deeper understanding of the factors governing DNA adsorption onto metal surfaces and the identification of reliable SERS bands indicative of DNA methylation levels are still needed. In this study, we evaluated the effects of several cations (Ca 2+ , Mg 2+ , Al 3+ , Be 2+ , Zn 2+ , Cu 2+ , Fe 2+ , and Na⁺) on the SERS signal of DNA and identified Ca 2+ as providing the highest enhancement. Thus, the addition of 5x10 -4 M Ca 2+ yielded optimal SERS signals for genomic DNA extracted from calf thymus and from six human cell lines, including both benign and malignant types with varying methylation levels. Notably, the SERS activation effect due to Ca 2+ could also be replicated by lowering the pH, suggesting that Ca 2+ increases the signal enhancement by generating surface Ag⁺ which favors the adsorption of DNA. A strong positive correlation (R = 0.94, p = 0.005) was observed between the intensity of the SERS band at 790 cm -1 and the level of 5-methylcytosine, establishing this band as a robust marker for DNA methylation. This finding was further validated by monitoring methylation levels in a 180 bp DNA sequence from the promoter region of the SEPT9 gene, an FDA-approved biomarker for colorectal cancer. Additionally, the use of SYBR Green fluorescence assays revealed that hypermethylated genomic DNA exhibits greater affinity for silver surfaces compared to lower methylated DNA. Collectively, these findings provide important theoretical insights and practical directions for the development of future nanoparticle-based cancer detection assays utilizing methylation markers.

Surface-enhanced Raman scattering (SERS) spectroscopy on serum and other biofluids for cancer diagnosis represents an emerging field, which has shown promising preliminary results in several types of malignancies. The purpose of this study was to demonstrate that SERS spectroscopy on serum can be employed for the differential diagnosis between five of the leading malignancies, ie, breast, colorectal, lung, ovarian and oral cancer. Serum samples were acquired from healthy volunteers (n=39) and from patients diagnosed with breast (n=42), colorectal (n=109), lung (n=33), oral (n=17), and ovarian cancer (n=13), comprising n=253 samples in total. SERS spectra were acquired using a 532 nm laser line as excitation source, while the SERS substrates were represented by Ag nanoparticles synthesized by reduction with hydroxylamine. The classification accuracy yielded by SERS was assessed by principal component analysis-linear discriminant analysis (PCA-LDA). The sensitivity and specificity in discriminating between cancer patients and controls was 98% and 91%, respectively. Cancer samples were correctly assigned to their corresponding cancer types with an accuracy of 88% for oral cancer, 86% for colorectal cancer, 80% for ovarian cancer, 76% for breast cancer and 59% for lung cancer. SERS on serum represents a promising strategy of diagnosing cancer which can discriminate between cancer patients and controls, as well as between cancer types such as breast, colorectal, lung ovarian and oral cancer.

EMT represents the dominant program within advanced stages of colon cancer, where cells acquire migratory characteristics in order to invade secondary tissues and form metastasis. Where the majority of the therapeutic strategies are concentrated on the reduction of the tumor mass through different apoptotic mechanisms, the present study advocates an important role for miR-205-5p in impairment of colon cancer cells migration and restoration of the epithelial phenotype. Upon identification of a homogenous downregulated profile for miR-205-5p in colon adenocarcinoma patients, functional studies demonstrated that experimental upregulation of this sequence is able to significantly raise the levels of E-cadherin through direct inhibition of ZEB1. Moreover, the elevation in CDH1 expression was translated into functional parameters where cells lost their invasion and migratory characteristics and formed homogenous clusters through adhesion interactions. Survival analysis of colon adenocarcinoma patients revealed that low levels of miR-205-5p are associated with an unfavorable prognostic compared to those with increased expression, demonstrating the possible clinical utility of miR-205-5p replacement. Exogenous administration of miRNA mimics was not associated with significant changes in cell viability or inflammatory pathways. Therefore, the proposed strategy is aiming towards inhibition of metastasis and limitation of the tumor borders in advanced stages patients in order to prolong the survival time and to increase the efficiency of the current therapeutic strategies.

Background/Objectives: Percutaneous dilatational tracheostomy (PDT) is a commonly performed procedure in critically ill patients. Various guidance techniques, including anatomical landmark-guided (ALG), ultrasound-guided (USG) and bronchoscopy-guided (BG), aim to enhance procedural safety and efficacy. This systematic review and meta-analysis aimed to compare the safety and efficacy across ALG, USG, and BG techniques in PDT, focusing on complications and procedure times. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. Studies identified through PubMed, CENTRAL, Scopus, and Web of Science databases up to July 2025 comparing ALG, USG, and BG PDT were included. Primary outcomes were minor and major bleeding, with transient hypoxia, transient hypotension, endotracheal tube cuff puncture, pneumothorax, and procedure time as secondary outcomes. Data were pooled using random-effects models, with risk ratios (RR) and 95% confidence intervals (CI) for complications and mean differences for procedure times. Heterogeneity was assessed using I2 statistics, with Bonferroni correction for multiple comparisons. Results: This meta-analysis included five RCTs (568 patients) comparing USG vs. ALG, six RCTs (404 patients) comparing USG vs. BG, and five RCTs (448 patients) comparing ALG vs. BG. USG significantly reduced minor bleeding compared to ALG (RR 2.30, 95% CI 1.38–3.84, p = 0.001) and BG (RR 0.42, 95% CI 0.20–0.91, p = 0.02), and major bleeding compared to ALG (RR 2.62, 95% CI 1.00–6.86, p = 0.04). ALG was associated with higher minor bleeding risk than BG (RR 1.81, 95% CI 1.05–3.12, p = 0.03). No significant differences were found for transient hypoxia, hypotension, endotracheal tube cuff puncture, or pneumothorax across comparisons, though trends suggested lower hypoxia risk with USG and higher pneumothorax risk with ALG. Procedure times were similar (ALG: 10.4 min, USG: 11.7 min, BG: 12.7 min; p = 0.493). Some rare complications, like paratracheal placement and mediastinitis, were too infrequent for analysis. Conclusions: USG PDT significantly reduces the risk of minor and major bleeding relative to ALG and minor bleeding compared to BG, without prolonging procedure time. USG and BG show comparable safety for most non-bleeding outcomes. No significant differences in procedure times. Future research should focus on larger RCTs to assess rare complications and explore hybrid USG-BG approaches to optimize PDT safety and efficacy.

Background: There is an ongoing research for breast cancer diagnostic tools that are cheaper, more accurate and more convenient than mammography. Methods: In this study, we employed surface-enhanced Raman scattering (SERS) for analysing urine from n = 53 breast cancer patients and n = 22 controls, with the aim of discriminating between the two groups using multivariate data analysis techniques such as principal component analysis—linear discriminant analysis (PCA-LDA). The SERS spectra were acquired using silver nanoparticles synthesized by reduction with hydroxylamine hydrochloride, which were additionally activated with Ca2+ 10−4 M. Results: The addition of Ca(NO3)2 10−4 M promoted the specific adsorption to the metal surface of the anionic purine metabolites such as uric acid, xanthine and hypoxanthine. Moreover, the SERS spectra of urine were acquired without any filtering or processing step for removing protein traces and other contaminants. Using PCA-LDA, the SERS spectra of urine from breast cancer patients were classified with a sensitivity of 81%, a specificity of 95% and an overall accuracy of 88%. Conclusion: The results of this preliminary study contribute to the translation of SERS in the clinical setting and highlight the potential of SERS as a novel screening strategy for breast cancer.

Receptor tyrosine kinases (RTKs) are key cell surface receptors involved in cell communication and signal transduction, with great importance in cell growth, differentiation, survival, and metabolism. Dysregulation of RTKs, such as EGFR, VEGFR, HER2 or ROR, could lead to various diseases, particularly cancers. ROR1 has emerged as a promising target in hematological malignancies. The development of ROR1 targeted therapies is continuously growing leading to remarkable novel therapeutical approaches using mAbs, antibody-drug conjugates, several small molecules or CAR T cells which have shown encouraging preclinical results. In the hematological field, mAbs, small molecules, BiTEs or CAR T cell therapies displayed promising outcomes with the clinical trials data encouraging the use of anti-ROR1 therapies. This paper aims to offer a comprehensive analysis of the current landscape of ROR1-targeted therapies in hematological malignancies marking the innovative approaches with promising preclinical and clinical. Offering a better understanding of structural and functional aspects of ROR1 could lead to new perspectives in targeting a wide spectrum of malignancies.

BackgroundAnti-PD-1 antibodies have revolutionized cancer immunotherapy due to their ability to induce long-lasting complete remissions in a proportion of patients. Current research efforts are attempting to identify biomarkers and suitable combination partners to predict or further improve the activity of immune checkpoint inhibitors. Antibody-cytokine fusions are a class of pharmaceuticals that showed the potential to boost the anticancer properties of other immunotherapies. Extradomain A-fibronectin (EDA-FN), which is expressed in most solid and hematological tumors but is virtually undetectable in healthy adult tissues, is an attractive target for the delivery of cytokine at the site of the disease.MethodsIn this work, we describe the generation and characterization of a novel interleukin-7-based fusion protein targeting EDA-FN termed F8(scDb)-IL7. The product consists of the F8 antibody specific to the alternatively spliced EDA of FN in the single-chain diabody (scDb) format fused to human IL-7.ResultsF8(scDb)-IL7 efficiently stimulates human peripheral blood mononuclear cells in vitro. Moreover, the product significantly increases the expression of T Cell Factor 1 (TCF-1) on CD8+T cells compared with an IL2-fusion protein. TCF-1 has emerged as a pivotal transcription factor that influences the durability and potency of immune responses against tumors. In preclinical cancer models, F8(scDb)-IL7 demonstrates potent single-agent activity and eradicates sarcoma lesions when combined with anti-PD-1.ConclusionsOur results provide the rationale to explore the combination of F8(scDb)-IL7 with anti-PD-1 antibodies for the treatment of patients with cancer.

Chimeric antigen receptor (CAR) T-cell technology has seen a rapid development over the last decade mostly due to the potential that these cells may have in treating malignant diseases. It is a generally accepted principle that very few therapeutic compounds deliver a clinical response without treatment-related toxicity, and studies have shown that CAR T-cells are not an exception to this rule. While large multinational drug companies are currently investigating the potential role of CAR T-cells in hematological oncology, the potential of such cellular therapies are being recognized worldwide as they are expected to expand in the patient to support the establishment of the immune memory, provide a continuous surveillance to prevent and/or treat a relapse, and keep the targeted malignant cell subpopulation in check. In this article, we present the possible advantages of using CAR T-cells in treating acute lymphoblastic leukemia, presenting the technology and the current knowledge in their preclinical and early clinical trial use. Thus, this article first presents the main present-day knowledge on the standard of care for acute lymphoblastic leukemia. Afterward, current knowledge is presented about the use of CAR T-cells in cancer immunotherapy, describing their design, the molecular constructs, and the preclinical data on murine models to properly explain the background for their clinical use. Last, but certainly not least, this article presents the use of CAR T-cells for the immunotherapy of B-cell acute lymphoblastic leukemia, describing both their potential clinical advantages and the possible side effects.