Early diagnosis of ovarian cancer could lead to decreased mortality. We assessed the possible use of urine autofluorescence analysis in its diagnostics and screening.We analysed urine from 42 healthy volunteers, 35 patients with benign, and 36 patients with malignant ovarian tumors. Synchronous fluorescence spectra with a 70 nm wavelength difference were recorded for (1:1 - 1:1024) urine dilutions. Concentration matrices of synchronous spectra (CMSS) were used to classify samples into tested groups.CMSS analysis allowed us to distinguish patients with malignant tumors from healthy ones with a high sensitivity (91.67 %) and specificity (100 %), a positive predictive value (PPV) 100 % and a negative predictive value (NPV) 93.33 %. However, discrimination between benign and malignant ovarian tumors was weaker, with sensitivity 86.11 %, specificity 77.14 %, PPV 79.49 % and NPV 84.38 %. Fluorescence intensity and the position of peaks at 330 and 360 nm were found to be associated with the grade and stage, suggesting that different fluorescent metabolites may prevail at different stages of the disease.CMSS analysis of urine provides an alternative for ovarian cancer screening method development and could be used as a diagnostic test to detect the recurrence of the disease after therapy.

Stress responses can impact bladder cancer (BC) outcomes via immune–inflammatory pathway modulation. This study explores heart rate variability (HRV) associations with serum immune–inflammatory biomarkers, blood count inflammatory markers, and psychosocial self-report measures in patients versus healthy controls. The TREM-1 and TREM-2 expressions on peripheral blood monocytes were analysed via flow cytometry; serum inflammatory biomarkers by ELISA; HRV (5-min ECG) pre-tumour resection; blood counts by haematology analyser; and psychosocial factors by validated questionnaires. Patients exhibited altered immune–inflammatory profiles with increased TREM-1/TREM-2, sTREM-1, sTREM-1/sTREM-2 ratio, BDNF, MCP-1, and NLR, and reduced IFN-γ, IL-10, LMR, and PMR. HRV analysis indicated sympathetic dominance (SNS, Stress indices, ACmod) and reduced parasympathetic modulation (PNS index, SDNN, RMSSD, 2UV%, DCmod, SD1). Sympathetic HRV indices correlated positively with sTREM-1, sTREM-1/sTREM-2 ratio, fractalkine, and inflammatory markers (SII, NLR, PLR) and negatively with parasympathetic HRV indices—correlations absent in controls. Only in patients, reduced physical function and social support, and higher anxiety, depression, and fatigue, associated positively with sympathetic HRV indices and inflammatory markers. This study links immune–inflammatory markers, HRV parameters, and psychosocial factors in BC, suggesting that immune and autonomic variations may relate to unfavourable outcomes. Incorporating these assessments could help tailor more personalised treatment strategies for BC patients.

Bladder cancer (BC) is the most common type of carcinoma of the urological system. Recently, there has been an increasing interest in non-invasive diagnostic tumor markers due to the invasive attribute of cystoscopy, which is still considered the gold standard diagnostic method. However, markers published in the literature so far do not meet expectations for replacing cystoscopy due to their low specificity and excessively high false-positive results, which can be mainly caused by frequently occurring hematuria also in benign cases. No reliable non-invasive method has yet been identified that can distinguish patients with bladder cancer and non-malignant hematuria patients. Our work examined the possibilities of non-targeted biomarkers of urine to distinguish patients with malignant and non-malignant diseases of the bladder using 3D HPLC in combination with computer processing of multiple datasets. Urine samples from 47 patients, 23 patients with bladder cancer (BC) and 24 patients with non-malignant hematuria (NMHU), were enrolled in clinical trials. For the separation and subsequent analysis of a large number of urine components, 3D HPLC (high-performance liquid chromatography) with an absorption and fluorescence detector was used. The obtained dataset was further subjected to various uni- and multi-dimensional statistical analyses and mathematical modeling. We found 334 chromatographic peaks, of which 18 peaks were identified as significantly different for BC and NMHU patients. Using receiver operating characteristic (ROC) analysis, we assessed the informative ability of significant chromatographic peaks (90% sensitivity and 74% specificity). By logistic regression, we identified the optimal and simplified set of seven chromatographic peaks (5 absorptions plus 2 fluorescence) with strong classification power (100% sensitivity and 100% specificity) for distinguishing patients with bladder cancer and those with non-malignant hematuria. Partial least square discriminant analysis (PLS-DA) model and orthogonal projection to latent structure discriminant analysis (OPLS-DA) with 100% sensitivity and 96% specificity were used to distinguish BC and NMHU patients. Multivariate statistical analysis of urinary metabolomic profiles of patients revealed that BC patients can be discriminated from NMHU patients and the results can likely contribute to an early and non-invasive diagnosis of BC.

Dendrons are branched synthetic polymers suitable for preparation of nanosized drug delivery systems. Their interactions with biological systems are mainly predetermined by their chemical structure, terminal groups, surface charge, and the number of branched layers (generation). Any new compound intended to be used, alone or in combination, for medical purposes in humans must be compatible with blood. This study combined results from in vitro experiments on human blood and from laboratory experiments designed to assess the effect of amphiphilic phosphorous dendrons on blood components and model membranes, and to examine the presence and nature of interactions leading to a potential safety concern. The changes in hematological and coagulation parameters upon the addition of dendrons in the concentration range of 2–10 µM were monitored. We found that only the combination of higher concentration and higher generation of the dendron affected the selected clinically relevant parameters: it significantly decreased platelet count and plateletcrit, shortened thrombin time, and increased activated partial thromboplastin time. At the same time, occasional small-sized platelet clumps in blood films under the light microscope were observed. We further investigated aggregation propensity of the positively charged dendrons in model conditions using zwitterionic and negatively charged liposomes. The observed changes in size and zeta potential indicated the electrostatic nature of the interaction. Overall, we proved that the low-generation amphiphilic phosphorous dendrons were compatible with blood within the studied concentration range. However, interactions between high-generation dendrons at bulk concentrations above 10 µM and platelets and/or clotting factors cannot be excluded.

Drug delivery by dendron-based nanoparticles is widely studied due to their ability to encapsulate or bind different ligands. For medical purposes, it is necessary (even if not sufficient) for these nanostructures to be compatible with blood. We studied the interaction of amphiphilic dendrons with blood samples from healthy volunteers using standard laboratory methods and rheological measurements. We did not observe clinically relevant abnormalities, but we found a concentration-dependent increase in whole blood viscosity, higher in males, presumably due to the formation of aggregates. To characterize the nature of the interactions among blood components and dendrons, we performed experiments on the liposomes and exosomes as models of biological membranes. Based on results obtained using diverse biophysical methods, we conclude that the interactions were of electrostatic nature. Overall, we have confirmed a concentration-dependent effect of dendrons on membrane systems, while the effect of generation was ambiguous. At higher dendron concentrations, the structure of membranes became disturbed, and membranes were prone to forming bigger aggregates, as visualized by SEM. This might have implications for blood flow disturbances when used in vivo. We propose to introduce blood viscosity measurements in early stages of investigation as they can help to optimize drug-like properties of potential drug carriers.