Carbon Dots (CDs) application in biomedicine has been increasing, due to their properties of high photoluminescence, biosafety and low cost, which allows for possible applications in bioimaging and as a drug carrier. However, their synthesis strategies are quite flexible, as tuning reaction precursors and synthesis procedures can lead to an endless number of CDs with distinct properties and applications, which difficult their rational development.

In this work [1,2], we performed a systematic evaluation of the effect of three representative bottom-up strategies (hydrothermal, microwave-assisted, and thermal heating) on the properties of CDs prepared from the same precursors (glucose and urea). In this way, the CDs were thoroughly evaluated in terms of structure, morphology and photoluminescent properties. To screen their potential as drug carriers, the biosafety of these CDs was tested against the normal breast cell line MCF-10A, as drug carriers need to be compatible with healthy cells to minimize harmful side-effects.

The characterization results demonstrated a similar size range and composition for all CDs. While hydrothermal synthesis generates CDs with lower fluorescence and synthesis yields, and present an emission more dependent on surface states, they have the most promising viability profile of MCF-10A when compared with microwave-assisted and thermal-heating CDs, which present better fluorescence properties and better efficiency towards nitrogen-doping.

Our results suggest these CDs have potential to proceed further investigation in animal models as imaging candidates or biosensing tools as well as drug carriers for a future application in medicine.

The peptidoglycan (PG) cell wall is an essential component of bacterial cell structure, and crippling its synthesis is one of the most successful strategies in the continuing war against pathogenic bacteria. MurJ is a member of THE multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) flippase superfamily critically required for the synthesis of PG from lipid II. Teixobactin (TXB) is a recently discovered promising macrocyclic depsipeptide natural antibiotic. TXB is claimed to “kill pathogens without detectable resistance” and considered a possible “paving stone toward a new class of antibiotics”. In the context of the current antibiotic resistance crisis, the rapid development of a plethora of TXB analogues with improved pharmacokinetics/pharmacodynamics (PK/PD) is a critical challenge. This study focuses on the computational design of new TXB analogue prototypes – disruptors of PG cell wall biosynthesis by inhibition of MurJ. A combinatorial library was generated in silico using a set of three scaffolds based on TXB structure and a selected list of building blocks in order to avoid the molecular obesity issue and minimalize the potential toxicity concerns and health risks. TXB and the combinatorial library were virtually screened with adequate drug-likeness filters, and PK/PD models. The safest drug candidates were docked with PyRx v.0.9.7 against the crystal structure of MurJ. What was found was that 26 virtual analogues had better binding affinities than TXB against MurJ. Overall, the proposed computational drug design approach for novel antibiotics might be a useful asset for medicinal chemists and translational pharmacologists.

Metal-based therapy remains a highly utilized and effective option in the treatment of many types of cancer. However, due to the persistence of severe side effects and the increase of resistance events, new metal-based chemotherapeutics that could overcome these limitations are required. In this context, the investigation of the mode of action of these metal compounds and their interaction with nucleic acids or proteins is necessary and could benefit the design of new powerful antitumor drugs.

The most effective and extensively studied inorganic antitumor drug, which is able to interfere with DNA replication and transcription, is cisplatin ([cis-Pt(NH₃)₂Cl₂]). The first crystal structure of an adduct formed upon interaction of cisplatin with a B-DNA double helix (the dodecamer CGCGAATTCGCG) was solved by Dickerson in 1984. Cisplatin binds to the duplex via ligation to the N7 position of the major groove guanines that are characterized by a conformational mobility. Since the discovery of the antitumor activity of cisplatin, many new antitumor Pt-based compounds have been synthetized; detailed structural information on their interaction with DNA is still lacking.

With the aim to fill this gap, we studied the interaction of cisplatin, the iodinated derivative of cisplatin ([cis-Pt(NH₃)₂I₂]), carboplatin, oxaliplatin, and arsenoplatin-1 ([Pt(μ-NHC(CH₃)O)₂ClAs(OH)₂]), with the Dickerson sequence both in solution and at solid state. These studies could help to understand the different reactivity of the investigated compounds.

Head and neck cancers (HNCs) are a group of neoplasms located in the area of oral cavity, pharynx, larynx, paranasal sinuses, nasal cavity and salivary glands. HNCs are the sixth most common type of cancer in Europe population. As in other neoplastic diseases, chronic inflammation occurs in HNC, affecting not only the location of the tumor, but also distant healthy tissues. In patients with HNC, changes in the levels of pro- and anti-inflammatory cytokines are observed. The aim of the study was to assess the level of interleukin 3 (IL-3), IL-4, IL-13, monocyte chemoattractant protein 1 (MCP-1) and MCP-2 in patients with HNC depending on the tumor localization. The study group consisted of 40 HNC patients divided into two groups according to the localization of the tumor: 20 subjects with cancer located in the area of oral cavity (OC) and 20 subjects with cancer located in the area of pharynx and larynx (PL). Blood serum samples were used to perform analysis. P < 0.05 was considered as statistically significant. In the PL group, statistically significant higher concentrations of IL-13 and MCP-1 were observed. The level of IL-13 in the OC group was 3.99 ± 0.50 pg/mL, while in the PL group it was 5.79 ± 0.64 pg/mL. The MCP-1 concentration was 68.15 ± 7.06 pg/mL and 109.01 ± 10.76 pg/mL, respectively. There were no statistically significant differences in the levels of IL-3, IL-4 and MCP-2. This experiment indicates that IL-13 and MCP-1 may be potential biomarkers differentiating tumor localization in patients with HNC.

Neuroendocrine tumors (NENs) originate from neuroendocrine cells located in a wide variety of organ systems. Gastrointestinal-pancreatic tumors (GEP-NETs) constitute the largest group (approx. 70%). NENs are heterogeneous in terms of location, malignancy potential, prognosis, treatment methods and functionality, which often makes their diagnosis difficult. Accumulating evidence points to the role of inflammatory factors in the GEP-NETs microenvironment. The aim of the study was to determine the concentrations of interferon gamma (IFN-γ), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and interleukin 10 (IL-10) in patients with GEP-NETs. The study included 63 patients of the Prof. F. Łukaszczyk Oncology Center in Bydgoszcz with a diagnosis of neuroendocrine neoplasms of the gastrointestinal tract (GT, n = 42) and pancreas (PA, n = 21). The concentration of cytokines was measured by the enzyme immunoassay method using ready-made ELISA kits. A statistical analysis was performed and P<0,05 was considered as statistically significant. The results were presented as the mean value and the standard error. The levels of IFN- γ, IL-6 and MCP-1 were statistically higher in the PA group than in the patients with GT-NENs. The concentration of IL-10, which is a factor inhibiting cytokine synthesis, did not show a significant difference between the GT and PA groups. Increased levels of inflammation in pancreatic NENs compared to gastrointestinal NENs have been observed. It has been noted that the disturbed balance between pro-inflammatory and anti-inflammatory factors may play a role in the development of neuroendocrine tumors.

Breast cancer is the second most diagnosed type of cancer in the world, although it is more prevalent in women and can affect both women and men. This type of cancer is the fifth leading cause of death. Even though there are multiple treatment protocols, there is a need to develop more effective alternatives. The current study explores the effects on breast cancer cell lines, MCF-7 (metastatic cell line) and MDA-MB-231 (non-metastatic), of pharmaceuticals like β-blockers already prescribed to treat other diseases. Thus, cell lines were exposed, up to 72h, to non-selective β-blockers, propranolol (10-250 μM) and carvedilol (0.1-100 μM), to antimetabolites, methotrexate (0.01-20 μM) and 5-fluorouracil (0.1-50 μM) and cell viability was assessed. The obtained results demonstrated higher sensitivity of MCF-7 to the tested drugs. Based on the estimated medium lethal concentration, carvedilol was the most toxic drug followed by propranolol and cytostatic drugs. Data support the potential application of beta-blockers in the treatment of breast cancer.

In 2020, lung cancer was the second most common type of cancer in the world and the most lethal. Due to the high mortality rate and the low efficiency of available treatments, there is the need for more efficient approaches to fight this disease. In this regard, the use of already approved pharmaceuticals for other purposes can be valuable. Thus, the study aimed to assess the potential application of beta-blockers, alone or combined with cytostatic drugs. The effects of the β-blockers propranolol (10, 25, 50, 100, 125, 150, 200 and 250 µM) and carvedilol (0.1, 1, 5, 10, 20, 60, 75 and 100 µM) and cytostatic drugs cisplatin (1, 5, 20, 50, 100, 150, 200, and 250 µM) and etoposide (0.005, 0.1, 0.5, 1, 2.5, 5, 7.5 and 10 µM) were evaluated in cancer cell lines, A549 and H460, at different time points (24/48/72h), through cell viability. Overall, A549 demonstrated higher sensitivity to propranolol, cisplatin, and etoposide and H460 was more sensitive to carvedilol. The study of combined effects of beta-blockers and cytostatic drugs revealed the potential value of beta-blockers in the treatment of cancer.

We present another paper in a series of studies on the effectiveness of preservation solutions modified with bio-elements in protecting ischemic organs for transplantation. Bio-elements as components of organ perfusion and preservation solutions can potentially increase the efficiency of graft preservation. Macro- and micronutrients are involved in biochemical reactions and metabolic processes of the cell. Many of them exhibit antioxidant properties, protecting against oxidative damage. The aim of this study was to evaluate the effectiveness of manganese (Mn²⁺) and magnesium (Mg²⁺) as components of Biolasol solution. The study was conducted in a model of isolated porcine kidneys collected from Polish Large White pigs. Approval was obtained from II Local Ethics Committee Krakow; number 1046/2013. Kidneys were preserved through static cold storage (SCS) using Biolasol (control) and modified Biolasol (A: Mn²⁺/1 µg/l; B: Mg²⁺/1 µg/l and Mn²⁺/1 µg/l). Kidneys were flushed with solutions after 48 hours of storage. Potassium, urea, and creatinine concentrations were highest in the Biolasol + Mn²⁺ group after 48h storage ([K⁺]: up by 50% vs Biolasol and 119% vs Biolasol + Mn²⁺ + Mg²⁺; urea: up by 18% vs Biolasol and 300% vs Biolasol + Mn²⁺ + Mg²⁺; creatinine: up by 250% vs Biolasol and 240% vs Biolasol + Mn²⁺ + Mg²⁺; p<0.05). Protein concentration was lowest in the Biolasol + Mn²⁺ + Mg²⁺ group ( by 81% vs Biolasol and 67% vs Biolasol + Mn²⁺; p<0.05). The simultaneous introduction of Mn²⁺ + Mg²⁺ ions into the Biolasol composition improved renal function indices.

Liver damage is a common issue of synthetic cathinones abuse. Human stem cell-derived hepatocyte-like cells (HLCs) has been suggested to hepatotoxicity studies, by their ability to maintain hepatic-specific phenotype. Furthermore, all cathinone derivatives are chiral, and their biological effects can differ for each enantiomer. Thus, the aim of this work was to evaluate the cytotoxicity and metabolism of pentedrone and methylone enantiomers using HLCs models. Human neonatal mesenchymal stem cells were differentiated into HLCs by a three-step differentiation protocol and maintained under 2D and 3D culture conditions. Subsequently, pentedrone and methylone enantiomers were isolated by HPLC using a chiral stationary phase. Cell viability was evaluated through CellTiter-Glo assay and the formation of methylone and pentedrone metabolites was analysed by GS-MS. Racemates of pentedrone and methylone exhibited potential hepatotoxic in a concentration-dependent manner in both models. It was also observe a different cytotoxic profile for pentedrone enantiomers in HLCs 3D, being R-(-)-pentedrone the most cytotoxic. Concerning HLCs 2D metabolic assays, S-(-)-methylone was preferentially metabolized via N-demethylation, whereas the R-(+)-methylone by O-demethylation and N-hydroxylation. Although, in HLCs 3D, R-(+)-methylone was preferential metabolized by all metabolic pathways, except for O-demethylation. Regarding pentedrone enantiomers, metabolic pathways studied were more pronounced for R-(-)-pentedrone, namely N-demethylation and β-keto reduction in both models. Overall, this study revealed stereoselectivity on cytotoxicity and metabolism pathways for pentedrone and methylone.

This research work allowed the development of a scientific approach to a remedy widely used until today in ranches or rural posts as an alternative medicine: The "guanaco stone" or bezoar. Bezoars are compactions of various chemical substances, hairs, vegetable fibers and foreign bodies, which are formed mainly between the divisions of the stomach of guanacos (Lama guanicoe). The ethnomedicine of this Patagonian region uses powdered bezoars ingested with water or in infusions, as a medicine that improves digestive and renal functions, and especially alexipharmaceuticals. The objective of this trial was to find "in vitro" the pharmacological foundations of bezoars. Samples of bezoars, obtained from the local refrigerator, were used in the test. For this, its density, colors, hardness were determined. One of the bezoars was totally pulverized, the powder obtained was observed under an optical microscope with a magnification of 1000X. Subsequently, the chemical composition was sought by examining the presence of P, K and N, as well as the pH. The results made it possible to determine the pH is neutral and the presence of P, N, and K is medium. It is concluded in this first approach to the subject that according to these determinations, bezoars can act by two mechanisms: the presence of phosphates acts as chelators of ingested toxins, facilitating their elimination from the body, but also the minerals that together stimulate the secretion of acid gastric and digestive enzymes.