High-throughput screening (HTS) is one of the newest techniques used in drug design and may be applied in biological and chemical sciences. This method, due to utilization of robots, detectors and software that regulate the whole process, enables a series of analyses of chemical compounds to be conducted in a short time and the affinity of biological structures which is often related to toxicity to be defined. Since 2008 we have implemented the automation of this technique and as a consequence, the possibility to examine 100,000 compounds per day. The HTS method is more frequently utilized in conjunction with analytical techniques such as NMR or coupled methods e.g., LC-MS/MS. Series of studies enable the establishment of the rate of affinity for targets or the level of toxicity. Moreover, researches are conducted concerning conjugation of nanoparticles with drugs and the determination of the toxicity of such structures. For these purposes there are frequently used cell lines. Due to the miniaturization of all systems, it is possible to examine the compound’s toxicity having only 1–3 mg of this compound. Determination of cytotoxicity in this way leads to a significant decrease in the expenditure and to a reduction in the length of the study.

Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer’s disease (AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties. Recently, scientists have put their efforts in establishing metformin’s role in the treatment of neurodegenerative diseases, such as AD, amnestic mild cognitive impairment and Parkinson’s disease. Results of several clinical studies confirm that long term use of metformin in diabetic patients contributes to better cognitive function, compared to participants using other anti-diabetic drugs. The exact mechanism of metformin’s advantageous activity in AD is not fully understood, but scientists claim that activation of AMPK-dependent pathways in human neural stem cells might be responsible for the neuroprotective activity of metformin. Metformin was also found to markedly decease Beta-secretase 1 (BACE1) protein expression and activity in cell culture models and in vivo, thereby reducing BACE1 cleavage products and the production of Aβ (β-amyloid). Furthermore, there is also some evidence that metformin decreases the activity of acetylcholinesterase (AChE), which is responsible for the degradation of acetylcholine (Ach), a neurotransmitter involved in the process of learning and memory. In regard to the beneficial effects of metformin, its anti-inflammatory and anti-oxidative properties cannot be omitted. Numerous in vitro and in vivo studies have confirmed that metformin ameliorates oxidative damage.

Metformin, a synthetic biguanide, is currently one of the most frequently recommended medications for type 2 diabetes treatment around the world. This review presents the latest discoveries in the pharmacokinetics of metformin, especially the role of transporters (e.g. Organic Cation Transporters OCTs, Multidrug and Toxin Extrusion transporters MATE) in oral absorption, distribution, elimination and biochemical effects of metformin in humans. We also review the associations between genetic variations of metformin transporters, their pharmacokinetics and drug efficacy or drug responses. In the second part of this paper, we highlight the current knowledge on novel metformin actions including favourable effects on lipid profile (e.g. decreasing plasma triglycerides (TG) and low density lipoprotein (LDL) cholesterol levels) and the cardiovascular system (e.g. decline in systolic and diastolic blood pressure, and vasoprotective effects). Furthermore, we provide an up-to-date overview of multidirectional activities of metformin, including the effects on coagulation and fibrinolysis, polycystic ovary syndrome, as well as the anti-ageing and antiinflammatory properties. Over the past two decades, metformin's antineoplastic properties have been drawing increasing attention of scientists; herein, we outline the state-of-the-art discoveries concerning metformin use in the field of oncology. Finally, we review the newly synthesized derivatives and pro-drugs of metformin and other biguanides.

Copper is one of the most interesting elements for various biomedical applications. Copper compounds show vast array of biological actions, including anti-inflammatory, anti-proliferative, biocidal and other. It also offers a selection of radioisotopes, suitable for nuclear imaging and radiotherapy. Quick progress in nanotechnology opened new possibilities for design of copper based drugs and medical materials. To date, copper has not found many uses in medicine, but number of ongoing research, as well as preclinical and clinical studies, will most likely lead to many novel applications of copper in the near future.

PurposeA diet rich in berries is believed to play a distinct role in the prevention of metabolic diseases associated with obesity. So far, there have been no published clinical observations evaluating the influence of Aronia melanocarpa on hemostasis. The aim of our study was to investigate the effects of A. melanocarpa extract (AM) supplementation on platelet aggregation, clot formation, and lysis in patients with metabolic syndrome (MS).MethodsMiddle-aged non-medicated subjects with MS (n = 38) and 14 healthy volunteers were included in this study. Patients with MS were treated with 100 mg of AM three times daily for 2 months.ResultsWe observed a significant reduction in the concentration of TC, LDL-C, and TG after AM supplementation. Beneficial changes in coagulation parameters were also observed. After 1 month of AM administration, we noticed significant inhibition of platelet aggregation. However, this effect became less pronounced after 2 months of supplementation. In the case of coagulation induced by endogenic thrombin, a significant decrease in the overall potential for coagulation was induced after 1 or 2 months of supplementation. Moreover, after 1 month of AM extract supplementation, we observed a beneficial reduction in the overall potential for clot formation and fibrinolysis.ConclusionsWe observed the normalization of hemostasis parameters in MS patients after both 1 and 2 months of AM administration. After 1 month of AM supplementation, we found favorable changes in regards to the overall potential for plasma clotting, clot formation, and lysis, as well as in the lipid profiles of subjects.