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Patients receiving dialysis treatments suffer from a high rate of systemic comorbid conditions, including cardiovascular disease, mineral and bone disorders, chronic inflammation, amyloidosis, and recurring infections, leading to increased morbidity and mortality rates despite the progress made in the field of renal replacement therapies. The aforementioned conditions result from the continued dysregulation and overproduction of molecular biomarkers, which cannot be adequately monitored by traditional, intermittent laboratory tests. This review critically assesses the newly developed biosensor technologies for the detection of major dialysis biomarkers, including potassium, phosphorus, parathyroid hormone (PTH), β₂-microglobulin, creatinine, and cystatin C, with special emphasis on biosensors based on electrochemistry, optics, impedimetry, nanophotonics, and biological engineering techniques. These recent biosensors have been evaluated based on their analytical performance, the biofluids used in the studies, and their suitability for measuring relevant concentrations of these biomarkers. Special attention is given to biosensors capable of continuous operation or minimally invasive sampling, as well as to newly developed biofluid sampling techniques, including microneedle-, microtube-, and micropillar-based systems, for the long-term monitoring of the biomarkers in the serum of patients receiving dialysis treatments. The biosensing techniques for measuring infection biomarkers have also been discussed, given the high risk of bloodstream and access infections among patients receiving dialysis. The limitations of these biosensors include biofouling, calibration drift, and their integration into the dialysis treatment workflow. Finally, the future prospects of the recent biosensors offer the possibility of the proactive management of the high rate of comorbid conditions in this high-risk population of patients receiving dialysis treatments. Full article

The wide range of cellular target reactions (e.g., antitumor) of gonadotropin-releasing hormone (GnRH) variants provides the possibility to develop multifunctional GnRH conjugates. The aim of our work was to compare the cytotoxic/apoptotic activity of different GnRH-based, daunorubicin (Dau)-linked conjugates with or without butyrated Lys in position 4 (⁴Lys(Bu)) at a molecular level in a human colorectal carcinoma cell line. Cell viability was measured by impedimetry, cellular uptake and apoptosis were studied by flow cytometry, and the expression of apoptosis-related genes was analyzed by qRT-PCR. The modification with ⁴Lys(Bu) resulted in an increased cytotoxic and apoptotic effects and cellular uptake of the GnRH-I and GnRH-III conjugates. Depending on the GnRH isoform and the presence of ⁴Lys(Bu), the conjugates could regulate the expression of several apoptosis-related genes, especially tumor necrosis factor (TNF), tumor protein p53 (TP53) and the members of growth-factor signaling. The stronger cytotoxicity of GnRH-I and GnRH-III conjugates containing ⁴Lys(Bu) was associated with a stronger inhibitory effect on the expression of growth-factor signaling elements in comparison with their ⁴Ser counterparts, in which the upregulation of TP53 and caspases (e.g., CASP9) seemed to play a more important role. We were able to provide further evidence that targeting the GnRH receptor could serve as a successful therapeutic approach in colon cancer, and GnRH-III-[⁴Lys(Bu),⁸Lys(Dau=Aoa)] proved to be the best candidate for this purpose. Full article