Mesoporous silica particles (MSPs) are promising micronized carriers for pulmonary drug delivery, combining excellent aerodynamic properties with the ability to dissolve into nanoparticles in lung fluid, enabling intracellular drug transport. In this study, we evaluated the interactions between three MSPs with distinct dissolution profiles in lung fluid and human macrophage models (primary M1, M2, and dTHP-1 cells). Following 4-hour exposure, all MSPs maintained high mitochondrial activity above the IC50 threshold, regardless of concentration, up to 1 mg/mL. MSPs did not induce TNF-α release, indicating a minimal immunological response. However, in simulated lung fluid, MSPs dissolved into nanoparticles exhibited greater toxicity than their microparticle counterparts. Toxicity correlated with dissolution rate: faster-dissolving particles were more toxic at short exposure times, while all MSPs reached similar toxicity levels after 24 h, independent of medium composition. Albumin, the predominant lung fluid protein, was found to mitigate particle toxicity, enhancing biocompatibility. Drug release studies revealed that faster-dissolving particles produced a rapid but unstable supersaturated drug solution, whereas slower-dissolving particles offered a more sustained release profile, supporting its potential for prolonged pulmonary therapy. The lowest observed adverse effect level (LOAEL) in vitro was determined to be 0.06 mg/mL for all the MSPs. This concentration maintained mitochondrial activity, oxidative stress and cell membrane integrity above 70%. These findings highlight the translational potential of MSPs as dual-scale carriers for targeted pulmonary delivery, combining effective drug release with favorable safety profiles.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-46033-8.

Early detection of cancer via biomarkers is vital for improving patient survival rates. In the case of skin cancers, low-molecular-weight biomarkers can penetrate the skin barrier, enabling non-invasive sampling at an early stage. This study focuses on detecting tryptophan (Trp) and kynurenine (Kyn) on the surface of reconstructed 3D melanoma and melanocyte models. This is examined in connection with IDO-1 and IL-6 expression in response to IFN-γ or UVB stimulation, both crucial factors of the melanoma tumor microenvironment (TME). Using a polystyrene scaffold, full-thickness human skin equivalents containing fibroblasts, keratinocytes, and melanocytes or melanoma cells were developed. The samples were stimulated with IFN-γ or UVB, and Trp and Kyn secretion was measured using HPLC-PDA and HPLC-MS. The expression of IDO-1 and IL-6 was measured using RT-qPCR. Increased Trp catabolism to Kyn was observed in IFN-γ-stimulated melanoma and melanocyte models, along with higher IDO-1 expression. UVB exposure led to significant changes in Kyn levels but only in the melanoma model. This study demonstrates the potential of skin surface Trp and Kyn monitoring to capture TME metabolic changes. It also lays the groundwork for future in vivo studies, aiding in understanding and monitoring skin cancer progression.

Background and aim: Melanoma is a fatal form of skin cancer that carries a grave prognosis if the cancer cells spread and form metastases. The Kynurenine (Kyn) pathway is activated by the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1) and has been shown to have a role in tumour progression. We have previously shown that interferon-γ (IFN-γ) acts as an inducer of tryptophan (Trp) degradation to Kyn in keratinocytes of the basal layer in a 3D epidermis model. Before extending our reconstructed human epidermis model to not only contain keratinocytes but also fibroblasts and melanocytes/melanoma cells, we have in this study set out to investigate possible differences between primary adult melanocytes and six melanoma cell lines regarding the expression of the immune checkpoint inhibitors IDO-1 and programmed death ligand 1 (PD-L1) together with Kyn production.

Methods: The melanocytes and melanoma cells were stimulated with 1–20 ng/ml of IFN-γ and the levels of Trp to Kyn degradation were monitored with high-performance liquid chromatography (HPLC). To analyze the viability of the cell types after IFN-γ treatment, an MTT assay was performed. mRNA quantity of IDO-1, PD-L1 and IFN-γ receptor (IFN-GR1) was analyzed with qPCR.

Results: After 24 h, only the metastatic cell line WM-266-4 was affected by all concentrations of IFN-γ, whereas at 48 h, the higher IFN-γ concentrations gave a more pronounced effect on the viability in all cell types. Trp was detected at various levels in the culture medium from all cell types before and after IFN-γ treatment. The degradation to Kyn was detected in primary melanocytes, Mel Juso, and Mel Ho cell lines after 24 h of treatment and low levels of IFN-γ. However, the higher concentration of IFN-γ, 20 ng/ml, induced Kyn to various degrees in all cell types after 24 h. The change in mRNA quantity of IDO-1 and PD-L1 was similar in all cell types.

Conclusion: To conclude, no significant difference in upregulation of the immune checkpoint inhibitors PD-L1 and IDO-1 was seen between primary tumour and metastatic melanoma. IFN-γ stimulation of melanocytes and different stages of melanoma cell lines resulted in an increased Kyn/Trp ratio in the more aggressive melanoma cells when a high concentration was used (20 ng/ml) but when a lower concentration of IFN-γ (5 ng/ml) was used an increased Kyn/Trp ratio were detected in media from primary melanocytes and early-stage melanoma.

Spherical, multicellular aggregates of tumor cells, or three-dimensional (3D) tumor models, can be grown from established cell lines or dissociated cells from tissues in a serum-free medium containing appropriate growth factors. Air–liquid interfaces (ALIs) represent a 3D approach that mimics and supports the differentiation of respiratory tract and skin 3D models in vitro. Many 3D tumor cell models are cultured in conjunction with supporting cell types, such as fibroblasts, endothelial cells, or immune cells. To further mimic the in vivo situation, several extracellular matrix models are utilized to support tumor cell growth. Scaffolds used for 3D tumor cell culture growth include both natural and synthetic hydrogels. Three-dimensional cell culture experiments in vitro provide more accurate data on cell-to-cell interactions, tumor characteristics, drug discovery, metabolic profiling, stem cell research, and diseases. Moreover, 3D models are important for obtaining reliable precision data on therapeutic candidates in human clinical trials before predicting drug cytotoxicity. This review focuses on the recent literature on three different tissue types of 3D tumor models, i.e., tumors from a colorectal site, prostate, and skin. We will discuss the establishment of 3D tumor cell cultures in vitro and the requirement for additional growth support.

BACKGROUND AND OBJECTIVES: L was investigated both in normal and malignant skin cells.

METHODS: Antioxidant activity of the extracts was analyzed by using the Trolox Equivalent Antioxidant Capacity (TEAC) assay. High-Performance Thin-Layer Chromatography (HPTLC) was performed to demonstrate the phytochemical profile, and the total flavonoid content was analyzed with an aluminum chloride colorimetric method. The anti-inflammatory effect was investigated by cell treatments using the plant extracts. Thereafter, the possible suppression of induced IL-6 response was measured from the cultured skin cancer cell lines A2058 and A431, and normal primary keratinocytes with Enzyme-Linked Immunosorbent Assay (ELISA).

RESULTS: also had the highest flavonoid content and showed the highest antioxidant activity of the three extracts tested.

CONCLUSION: possess properties such as antioxidant and anti-inflammatory activities in both normal and malignant keratinocytes, and thus could be a promising agent controlling the pro-inflammatory IL-6 production.

Background After completing university education, biomedical laboratory scientists work in clinical laboratories, in biomedical research laboratories, in biotech, and in pharmaceutical companies. Laboratory diagnostics have undergone rapid development over the recent years, with the pace showing no signs of abatement. This rapid development challenges the competence of the staff and will most certainly influence the education of future staff. This study aimed to examine what was considered the necessary competencies needed to pursue a career as a biomedical laboratory scientist. Methods A modified Delphi technique was used, with the panel of experts expressing their views in a series of three questionnaire. Consensus was defined as the point which 75 % or more of the panel participants agreed that a particular competency was necessary. Results The study highlights the perceived importance of mostly generic competencies that relate to quality, quality assurance, and accuracy, as well as different aspects of safety, respect, trustworthiness (towards patients/clients and colleagues), and communication skills. The results also stress the significance of self-awareness and professionality. Conclusions We identified important competencies for biomedical laboratory scientists. Together with complementary information from other sources, i.e., guidelines, laws, and scientific publications, the competencies identified can be used as learning outcomes in a competency-based education to provide students with all the competencies needed to work as professional biomedical laboratory scientists.

Monitoring of low-molecular weight cancer biomarkers, such as tryptophan (Trp) and its derivative kynurenine (Kyn), might be advantageous to non-invasive skin cancer detection. Thus, we assessed several approaches of topical sampling of Trp and Kyn, in relation to phenylalanine (Phe) and tyrosine (Tyr), on the volar forearm of six healthy volunteers. The sampling was performed with three hydrogels (made of agarose or/and chitosan), hydrated starch films, cotton swabs, and tape stripping. The biomarkers were successfully sampled by all approaches, but the amount of collected Kyn was low, 20 ± 10 pmol/cm2. Kyn quantification was below LOQ, and thus, it was detected only in 20% of topical samples. To mitigate variability problems of absolute amounts of sampled amino acids, Tyr/Trp, Phe/Trp, and Phe/Tyr ratios were assessed, proving reduced inter-individual variation from 79 to 45% and intra-individual variation from 42 to 21%. Strong positive correlation was found between Phe and Trp, pointing to the Phe/Trp ratio (being in the 1.0–2.0 range, at 95% confidence) being least dependent on sampling materials, approaches, and sweating. This study leads to conclusion that due to the difficulty in quantifying less abundant Kyn, and thus the Trp/Kyn ratio, the Phe/Trp ratio might be a possible, alternative biomarker for detecting skin cancers.

High-performance autotolerant bioelectrodes should be ideally suited to design implantable bioelectronic devices. Because of its high redox potential and ability to reduce oxygen directly to water, human ceruloplasmin, HCp, the only blue multicopper oxidase present in human plasma, appears to be the ultimate biocatalyst for oxygen biosensors and also biocathodes in biological power sources. In comparison to fungal and plant blue multicopper oxidases, e.g. Myrothecium verrucaria bilirubin oxidase and Rhus vernicifera laccase, respectively, the inflammatory response to HCp in human blood is significantly reduced. Partial purification of HCp allowed to preserve the native conformation of the enzyme and its biocatalytic activity. Therefore, electrochemical studies were carried out with the partially purified enzyme immobilised on nanostructured graphite electrodes at physiological pH and temperature. Amperometric investigations revealed low reductive current densities, i.e. about 1.65 µA cm−2 in oxygenated electrolyte and in the absence of any mediator, demonstrating nevertheless direct electron transfer based O2 bioelectroreduction by HCp for the first time. The reductive current density obtained in the mediated system was about 12 µA cm−2. Even though the inflammatory response of HCp is diminished in human blood, inadequate bioelectrocatalytic performance hinders its use as a cathodic bioelement in a biofuel cell.

The generation of reactive oxygen species presents a destructive challenge for the skin organ and there is a clear need to advance skin care formulations aiming at alleviating oxidative stress. The aim of this work was to characterize the activity of the antioxidative enzyme catalase in keratinocytes and in the skin barrier (i.e., the stratum corneum). Further, the goal was to compare the activity levels with the corresponding catalase activity found in defatted algae biomass, which may serve as a source of antioxidative enzymes, as well as other beneficial algae-derived molecules, to be employed in skin care products. For this, an oxygen electrode-based method was employed to determine the catalase activity and the apparent kinetic parameters for purified catalase, as well as catalase naturally present in HaCaT keratinocytes, excised stratum corneum samples collected from pig ears with various amounts of melanin, and defatted algae biomass from the diatom Phaeodactylum tricornutum. Taken together, this work illustrates the versatility of the oxygen electrode-based method for characterizing catalase function in samples with a high degree of complexity and enables the assessment of sample treatment protocols and comparisons between different biological systems related to the skin organ or algae-derived materials as a potential source of skin care ingredients for combating oxidative stress.