Employing machine learning to assess the accuracy of near-infrared spectroscopy of spent dialysate fluid in monitoring the blood concentrations of uremic toxins

Hemodialysis (HD) removes nitrogenous waste products from patients’ blood through a semipermeable mem- brane along a concentration gradient. Near-infrared spectroscopy (NIRS) is an underexplored method of monitoring the concentrations of several molecules that reflect the efficacy of the HD process in dialysate samples. In this study, we aimed to evaluate NIRS as a technique for the non-invasive detection of uremic solutes by assessing the correlations between the spectrum of the spent dialysate and the serum levels of urea, creatinine, and uric acid. Blood and dialysate samples were taken from 35 patients on maintenance HD. The absorption spectrum of each dialysate sample was measured three times in the wavelength range of 700-1700 nm, resulting in a dataset with 315 spectra. The artificial neural network (ANN) learn- ing technique was used to assess the correlations between the recorded NIR-absorbance spectra of the spent dialysate and serum levels of selected uremic toxins. Very good correlations between the NIR-absorbance spectra of the spent dialysate fluid with serum urea (R=0.91) and uric acid (R=0.91) and an excellent correlation with serum creatinine (R=0.97) were obtained. These results support the application of NIRS as a non-invasive, safe, accurate, and repetitive technique for online monitoring of uremic toxins to assist clinicians in assessing HD efficiency and individualization of HD treatments

Synthesis, characterization, HSA/DNA interactions and antitumor activity of new [Ru(η6-p-cymene)Cl2(L)] complexes

Three new ruthenium(II) complexes were synthesized from different substituted isothiazole ligands 5-(methylamino)-3-pyrrolidine-1-ylisothiazole-4-carbonitrile (1), 5-(methylamino)-3- (4-methylpiperazine-1-yl)isothiazole-4-carbonitrile (2) and 5-(methylamino)-3-morpholine-4- ylisothiazole-4-carbonitrile (3): [Ru(η6-p-cymene)Cl2(L1)]·H2O (4), [Ru(η6 -pcymene)Cl2(L2)] (5) and [Ru(η6-p-cymene)Cl2(L3)] (6). All complexes were characterized by IR, UV-Vis, NMR spectroscopy, and elemental analysis. The molecular structures of all ligands and complexes 4 and 6 were determined by an X-ray. The results of the interactions of CT-DNA (calf thymus deoxyribonucleic acid) and HSA (human serum albumin) with ruthenium (II) complexes reveal that complex 4 binds well to CT-DNA and HSA. Kinetic and thermodynamic parameters for the reaction between complex and HSA confirmed the associative mode of interaction. The results of Quantum mechanics (QM) modelling and docking experiments toward DNA dodecamer and HSA support the strongest binding of the complex 4 to DNA major groove, as well as its binding to IIa domain of HSA with the lowest ΔG energy, which agrees with the solution studies. The modified GOLD docking results are indicative for Ru(p-cymene)LCl··(HSA··GLU292) binding and GOLD/MOPAC(QM) docking/modelling of DNA/Ligand (Ru(II)-N(7)dG7) covalent binding. The cytotoxic activity of compounds was evaluated by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl2H-tetrazolium bromide) assay. Neither of the tested compounds shows activity against a healthy MRC-5 cell line while the MCF-7 cell line is the most sensitive to all. Compounds 3, 4 and 5 were about two times more active than cisplatin, while the antiproliferative activity of 6 was almost the same as with cisplatin. Flow cytometry analysis showed the apoptotic death of the cells with a cell cycle arrest in the subG1 phase

Ruthenium(II) Complexes of Isothiazole Ligands: Crystal Structure, HSA/DNA Interactions, Cytotoxic Activity and Molecular Docking Simulations

Two new neutral ruthenium(II) complexes [Ru(eta(6)-p-cymene)Cl-2(1)] (3) and [Ru(eta(6)-p-cymene)Cl-2(2)] (4) (1=5-(phenylamino)-3-pyrrolidin-1-ylisothiazole-4-carbonitrile;2=3-morpholin-4-yl-5-(phenylamino)isothiazole-4-carbonitrile) have been synthesized and characterized using elemental analysis, IR, UV-Vis and NMR spectroscopy. The crystal structure was confirmed for complex3and both ligands. Examination of the interactions of ligands and complexes with CT-DNA (Calf Thymus DNA), as well as with HSA (Human Serum Albumin) revealed that ligands and complexes could interact with CT-DNA through intercalation and could bind strongly with HSA. Docking experiments toward DNA dodecamer indicate excellent accordance with experimental Delta G values. The cytotoxic activity of ligands and complexes was evaluated by MTT assay against HCT116 and HeLa tumoral cells. The complexes3and4showed good activity and selectivity on HCT116 cells. Neither of the tested compounds shows cytotoxic activity against a healthy MRC-5 cell line. Flow cytometry analysis showed the apoptotic death of the HCT116 cells with a cell cycle arrest in the S-phase