In keeping with recent developments in basic research; the importance of the Cathepsins as targets in cancer therapy have taken on increasing importance and given rise to a number of key areas of interest in the clinical setting. In keeping with driving basic research in this area in a translational direction; recent findings have given rise to a number of exciting developments in the areas of cancer diagnosis; prognosis and therapeutic development. As a fast-moving area of research; the focus of this review brings together the latest findings and highlights the translational significance of these developments.

Metabolic Syndrome: Development of the Issue, Main Diagnostic Criteria

Metabolomics is a promising technology for the application of translational medicine to cardiovascular risk. Here, we applied a liquid chromatography/tandem mass spectrometry approach to explore the associations between plasma concentrations of amino acids, methylarginines, acylcarnitines, and tryptophan catabolism metabolites and cardiometabolic risk factors in patients diagnosed with arterial hypertension (HTA) (n = 61), coronary artery disease (CAD) (n = 48), and non-cardiovascular disease (CVD) individuals (n = 27). In total, almost all significantly different acylcarnitines, amino acids, methylarginines, and intermediates of the kynurenic and indolic tryptophan conversion pathways presented increased (p < 0.05) in concentration levels during the progression of CVD, indicating an association of inflammation, mitochondrial imbalance, and oxidative stress with early stages of CVD. Additionally, the random forest algorithm was found to have the highest prediction power in multiclass and binary classification patients with CAD, HTA, and non-CVD individuals and globally between CVD and non-CVD individuals (accuracy equal to 0.80 and 0.91, respectively). Thus, the present study provided a complex approach for the risk stratification of patients with CAD, patients with HTA, and non-CVD individuals using targeted metabolomics profiling.

The recent developments in Cathepsin protease research have unveiled a number of key observations which are fundamental to further our understanding of normal cellular homeostasis and disease. By far, the most interesting and promising area of Cathepsin biology stems from how these proteins are linked to the fate of living cells through the phenomenon of Lysosomal Leakage and Lysosomal Membrane Permeabilisation. While extracellular Cathepsins are generally believed to be of central importance in tumour progression, through their ability to modulate the architecture of the Extracellular Matrix, intracellular Cathepsins have been established as being of extreme significance in mediating cell death through Apoptosis. With these two juxtaposed key research areas in mind, the focus of this review highlights recent advancements in how this fast-paced area of Cathepsin research has recently evolved in the context of their mechanistic regulation in cancer research. Abbreviations : ECM, Extracellular Matrix; MMP, Matrix Metalloproteases; LL, Lysosomal Leakage; LMP, Lysosomal Membrane Permeabilisation; LMA, Lysosomorphic Agents; BC, Breast Cancer; ASM, Acid Sphingomyelinase; TNF-α, Tumor Necrosis Factor-alpha; LAMP, Lysosomal Associated membrane Protein; PCD, Programmed Cell Death; PDAC, Pancreatic Ductal Adenocarcinoma; ROS, Reactive Oxygen Species; aa, amino acids.

Heart failure (HF) is the ending of practically all cardiovascular diseases and the reason for hospitalization of 49% of patients in a cardiological hospital. Available instrumental diagnostic methods and biomarkers not always allow verification of HF, particularly in patients with preserved left ventricular ejection fraction. Prediction of chronic HF in patients with risk factors faces great difficulties. Currently, natriuretic peptides (NUP) are widely used for the diagnosis, prognosis and management of patients with HF and are included in clinical guidelines for diagnosis and treatment of HF. Following multiple studies, the understanding of NUP significance has changed. This resulted in a need for new biomarkers to improve the insight into the process of HF and to personalize the treatment by better individual phenotyping. In addition, current technologies, such as transcriptomic, proteomic and metabolomic analyses, provide identification of new biomarkers and better understanding of features of the HF pathogenesis. The aim of this study was to discuss recent reports on NUP and novel, most promising biomarkers in respect of their possible use in clinical practice.