University of Information Technology and Management in Rzeszow

Przybyła G.W., Szychowski K.A., Gmiński J.

Paracetamol (acetaminophen) is the most commonly used over-the-counter (OTC) drug in the world. Despite its popularity and use for many years, the safety of its application and its mechanism of action are still unclear. Currently, it is believed that paracetamol is a multidirectional drug and at least several metabolic pathways are involved in its analgesic and antipyretic action. The mechanism of paracetamol action consists in inhibition of cyclooxygenases (COX-1, COX-2, and COX-3) and involvement in the endocannabinoid system and serotonergic pathways. Additionally, paracetamol influences transient receptor potential (TRP) channels and voltage-gated Kv7 potassium channels and inhibits T-type Cav3.2 calcium channels. It also exerts an impact on L-arginine in the nitric oxide (NO) synthesis pathway. However, not all of these effects have been clearly confirmed. Therefore, the aim of our paper was to summarize the current state of knowledge of the mechanism of paracetamol action with special attention to its safety concerns.

Zagórska-Dziok M., Sobczak M.

Hydrogels are playing an increasingly important role in medicine and pharmacy. Due to their favorable physicochemical properties, biocompatibility, and designed interaction with living surroundings, they seem to be one of the most promising groups of biomaterials. Hydrogel formulations from natural, semi, or synthetic polymeric materials have gained great attention in recent years for treating various dermatology maladies and for cosmetology procedures. The purpose of this review is to present a brief review on the basic concept of hydrogels, synthesis methods, relevant mechanisms, and applications in dermatology or cosmetology. This review discusses transdermal therapies and the recent advances that have occurred in the field.

Copeland H., Knezevic I., Baran D.A., Rao V., Pham M., Gustafsson F., Pinney S., Lima B., Masetti M., Ciarka A., Rajagopalan N., Torres A., Hsich E., Patel J.K., Goldraich L.A., et. al.

The proposed donor heart selection guidelines provide evidence-based and expert-consensus recommendations for the selection of donor hearts following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review. The proposed donor heart selection guidelines provide evidence-based and expert-consensus recommendations for the selection of donor hearts following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review. In 1995, Dr J. Copeland noted that “only optimal donors should be accepted for heart transplantation,” implying that extended-criteria donor organs may not be viable.1Copeland JG. Only optimal donors should be accepted for heart transplantation: protagonist.J Heart Lung Transplant. 1995; 14: 1038-1042PubMed Google Scholar Despite this awareness raised from over 25 years ago, this topic has remained much debated. While older donors are more routinely used in Europe, younger donors with short ischemic times are more commonly used in the United States. Mortality rates differ worldwide, and some of these differences are due to donor selection and/or recipient urgency. Seeking a balance between maximizing the number of transplants (by taking greater risk) and minimizing the risk to meet societal needs, while controlling cost, is difficult and frequently related to a lack of reliable data regarding both donors and recipients. The issue is further complicated by the fact that the peri-operative surgical risk is a combination of risk factors that include donor, recipient, and ischemic time. Lastly, meaningful comparisons of transplant outcomes across countries require proper risk-adjustment. The proposed guidelines provide evidence-based as well as expert-consensus recommendations for the selection of donors following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review. Controversial subjects are dealt with one by one and current state-of-the-art information is provided to help define risk. The strength of each recommendation and the corresponding level of available evidence were classified following the International Society for Heart and Lung Transplantation protocol for developing guideline documents.2International Society for Heart Lung Transplantation. Protocol and policies for developing standards statements, guidelines, and consensus documents and for conducting consensus conferences. 2017; https://ishlt.org/ishlt/media/documents/STANDARDS_AND_GUIDELINES_DEVELOPMENT_PROTOCOL_FINAL.pdfGoogle Scholar Task forces were established with an international panel of experts. The task forces reviewed donor characteristics (Task force 1), international donor practices (Task force 2), donor and recipient matched characteristics (Task force 3), extended donor characteristics (Task force 4), and donor risk scores (Task force 5). Factors considered in the clinical stability of the cardiac donor are hemodynamics, hormonal resuscitation,3Dhar R Cotton C Coleman J et al.Comparison of high- and low-dose corticosteroid regimens for organ donor management.J Crit Care. 2013; 28 (111.e111-117)Crossref PubMed Scopus (39) Google Scholar, 4Dupuis S Amiel JA Desgroseilliers M et al.Corticosteroids in the management of brain-dead potential organ donors: a systematic review.Br J Anaesth. 2014; 113: 346-359Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 5Pinsard M Ragot S Mertes PM et al.Interest of low-dose hydrocortisone therapy during brain-dead organ donor resuscitation: the CORTICOME study.Crit Care. 2014; 18: R158Crossref PubMed Scopus (40) Google Scholar, 6Buchanan IA Mehta VA. Thyroid hormone resuscitation after brain death in potential organ donors: a primer for neurocritical care providers and narrative review of the literature.Clin Neurol Neurosurg. 2018; 165: 96-102Crossref PubMed Scopus (9) Google Scholar, 7Cooper LB Milano CA Williams M et al.Thyroid hormone use during cardiac transplant organ procurement.Clin Transplant. 2016; 30: 1578-1583Crossref PubMed Scopus (17) Google Scholar, 8Holndonner-Kirst E Nagy A Czobor NR et al.The impact of l-thyroxine treatment of donors and recipients on postoperative outcomes after heart transplantation.J Cardiothorac Vasc Anesth. 2019; 33: 1629-1635Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 9Mi Z Novitzky D Collins JF Cooper DK. The optimal hormonal replacement modality selection for multiple organ procurement from brain-dead organ donors.Clin Epidemiol. 2015; 7: 17-27PubMed Google Scholar, 10Novitzky D Mi Z Sun Q Collins JF Cooper DK Thyroid hormone therapy in the management of 63,593 brain-dead organ donors: a retrospective analysis.Transplantation. 2014; 98: 1119-1127Crossref PubMed Google Scholar, 11Roels L Spaight C Smits J Cohen B. Critical care staffs' attitudes, confidence levels and educational needs correlate with countries' donation rates: data from the donor action database.Transpl Int. 2010; 23: 842-850Crossref PubMed Scopus (0) Google Scholar and the restoration of intravascular volume and electrolyte imbalance,12Al-Khafaji A Elder M Lebovitz DJ et al.Protocolized fluid therapy in brain-dead donors: the multicenter randomized MOnIToR trial.Intensive Care Med. 2015; 41: 418-426Crossref PubMed Scopus (44) Google Scholar, 13Barklin A. Systemic inflammation in the brain-dead organ donor.Acta Anaesthesiol Scand. 2009; 53: 425-435Crossref PubMed Scopus (129) Google Scholar, 14Kuecuek O Mantouvalou L Klemz R et al.Significant reduction of proinflammatory cytokines by treatment of the brain-dead donor.Transplant Proc. 2005; 37: 387-388Crossref PubMed Scopus (64) Google Scholar, 15McKeown DW Ball J. Treating the donor.Curr Opin Organ Transplant. 2014; 19: 85-91Crossref PubMed Scopus (14) Google Scholar, 16Abdelnour T Rieke S. Relationship of hormonal resuscitation therapy and central venous pressure on increasing organs for transplant.J Heart Lung Transplant. 2009; 28: 480-485Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar, 17Dimopoulou I Tsagarakis S Anthi A et al.High prevalence of decreased cortisol reserve in brain-dead potential organ donors.Crit Care Med. 2003; 31: 1113-1117Crossref PubMed Scopus (76) Google Scholar, 18Plurad DS Bricker S Neville A Bongard F Putnam B. Arginine vasopressin significantly increases the rate of successful organ procurement in potential donors.Am J Surg. 2012; 204 (discussion 860-851): 856-860Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar, 19Hadjizacharia P Salim A Brown C et al.Does the use of pulmonary artery catheters increase the number of organs available for transplantation?.Clin Transplant. 2010; 24: 62-66Crossref PubMed Scopus (0) Google Scholar, 20Novitzky D Mi Z Videla LA Collins JF Cooper DK. Hormone resuscitation therapy for brain-dead donors - is insulin beneficial or detrimental?.Clin Transplant. 2016; 30: 754-759Crossref PubMed Scopus (0) Google Scholar, 21Stoica SC Satchithananda DK Charman S et al.Swan-Ganz catheter assessment of donor hearts: outcome of organs with borderline hemodynamics.J Heart Lung Transplant. 2002; 21: 615-622Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 22Saner FH Kavuk I Lang H Radtke A Paul A Broelsch CE. Organ protective management of the brain-dead donor.Eur J Med Res. 2004; 9: 485-490PubMed Google Scholar as well as donor metabolism. 1.Donors receiving low dose norepinephrine (e.g., ≤0.1 µg/kg/min) may be considered suitable for transplantation if (other) inotropes are not required. In general, the higher the dose of norepinephrine in the donor, the poorer the expected outcome after transplant. Level of Evidence: C. 1.If inotropes and/or vasopressors are required to maintain adequate circulatory function in the donor, placement of a Swan-Ganz catheter and goal-directed therapy should be considered to maximize the likelihood of donor heart utilization. Level of Evidence: C.2.Suggested hemodynamic targets for donor hearts include the following:•Mean arterial pressure >60 mm Hg•Cardiac index >2.4 liter/min/m2•Central venous pressure

Skóra B., Krajewska U., Nowak A., Dziedzic A., Barylyak A., Kus-Liśkiewicz M.

Drug-resistance of bacteria is an ongoing problem in hospital treatment. The main mechanism of bacterial virulency in human infections is based on their adhesion ability and biofilm formation. Many approaches have been invented to overcome this problem, i.e. treatment with antibacterial biomolecules, which have some limitations e.g. enzymatic degradation and short shelf stability. Silver nanoparticles (AgNPs) may be alternative to these strategies due to their unique and high antibacterial properties. Herein, we report on yeast Saccharomyces cerevisiae extracellular-based synthesis of AgNPs. Transmission electron microscopy (TEM) revealed the morphology and structure of the metallic nanoparticles, which showed a uniform distribution and good colloid stability, measured by hydrodynamic light scattering (DLS). The energy dispersive X-ray spectroscopy (EDS) of NPs confirms the presence of silver and showed that sulfur-rich compounds act as a capping agent being adsorbed on the surface of AgNPs. Antimicrobial tests showed that AgNPs inhibit the bacteria growth, while have no impact on fungi growth. Moreover, tested NPs was characterized by high inhibitory potential of bacteria biofilm formation but also eradication of established biofilms. The cytotoxic effect of the NPs on four mammalian normal and cancer cell lines was tested through the metabolic activity, cell viability and wound-healing assays. Last, but not least, ability to deep penetration of the silver colloid to the root canal was imaged by scanning electron microscopy (SEM) to show its potential as the material for root-end filling.

Mishchenko M., Shtrygol S., Kaminskyy D., Lesyk R.

Here, we describe the synthesis and anticonvulsant activity of thiazole-bearing hybrids based on 2-imino-4-thiazolidinone and 2,4-dioxothiazolidine-5-carboxylic acid cores. The structure of target compounds was based on the following: (i) A combination of two thiazole cores; (ii) similarity to ralitolin’s structure; (iii) the compliance with structural requirements for the new anticonvulsants. Target compounds were synthesized via known approaches based on Knoenavegel reaction, alkylation reaction, and one-pot three-component reaction. Anticonvulsant properties of compounds were evaluated in two different models—pentylenetetrazole-induced seizures and maximal electroshock seizure tests. Among the tested compounds 5Z-(3-nitrobenzylidene)-2-(thiazol-2-ylimino)-thiazolidin-4-one Ib, 2-[2,4-dioxo-5-(thiazol-2- ylcarbamoylmethyl)-thiazolidin-3-yl]-N-(2-trifluoromethylphenyl)acetamide IId and (2,4-dioxo-5- (thiazol-2-ylcarbamoylmethylene)-thiazolidin-3-yl)acetic acid ethyl ester IIj showed excellent anticonvulsant activity in both models. The directions of compounds modification based on SAR aspects were discussed. The results of the study provide a basis for further study of the anticonvulsant properties of selected thiazole-thiazolidinones.

Szychowski K.A., Skóra B., Pomianek T., Gmiński J.

The Inonotus obliquus ( I. obliquus ) mushroom was traditionally used to treat various gastrointestinal diseases. For many years, mounting evidence has indicated the potential of I. obliquus extracts for treatment of viral and parasitic infections. Furthermore, substances from I. obiquus have been shown to stimulate the immune system. The most promising finding was the demonstration that I. obliquus has hypoglycemic and insulin sensitivity potential. This review summarizes the therapeutic potential of I. obliquus extracts in counteracting the progression of cancers and diabetes mellitus as well as their antiviral and antiparasitic activities and antioxidant role. As shown by literature data, various authors have tried to determine the molecular mechanism of action of I. obliquus extracts. Two mechanisms of action of I. obliquus extracts are currently emerging. The first is associated with the broad-sense impact on antioxidant enzymes and the level of reactive oxygen species (ROS). The other is related to peroxisome proliferator-activated receptor gamma (PPARγ) effects. This receptor may be a key factor in the anti-inflammatory, antioxidant, and anti-cancer activity of I. obliquus extracts. It can be concluded that I. obliquus fits the definition of functional food and has a potentially positive effect on health beyond basic nutrition; however, studies that meet the evidence-based medicine (EBM) criteria are needed. • Extracts or polysaccharides from I. obliquus exhibit an anti-cancer potential in vitro . • Extracts or polysaccharides from I. obliquus exhibit anti-inflammation potential. • Extracts or polysaccharides from I. obliquus exhibit hypoglycemic and insulin sensitivity potential.

Wang L., Mao S., Wilamowski B.M., Nelms R.M.

In this paper, an ensemble learning approach is proposed for load forecasting in urban power systems. The proposed framework consists of two levels of learners that integrate clustering, Long Short-Term Memory (LSTM), and a Fully Connected Cascade (FCC) neural network. Historical load data is first partitioned by a clustering algorithm to train multiple LSTM models in the level-one learner, and then the FCC model in the second level is used to fuse the multiple level-one models. A modified Levenberg-Marquardt (LM) algorithm is used to train the FCC model for fast and stable convergence. The proposed framework is tested with two public datasets for short-term and mid-term forecasting at the system, zone and client levels. The evaluation using real-world datasets demonstrates the superior performance of the proposed model over several state-of-the-art schemes. For the ISO-NE Dataset for Years 2010 and 2011, an average reduction in mean absolute percentage error (MAPE) of 10.17% and 11.67% are achieved over the four baseline schemes, respectively.

Osieczko K., Zimon D., Płaczek E., Prokopiuk I.

As one of the possibilities of reducing exhaust emissions, the article takes into account infrastructure and electric vehicles used in road transport. Taking into account the goal to achieve a 30% share of vehicle electric, the number of charging stations available in the entire European Union is not sufficient. There has been a slight increase in sales of electric vans and trucks in the EU in recent years. This may be due to the lack of available infrastructure which would render it possible to power them, and also from the lack of available delivery vehicles in the market. What is interesting, the number of electric vehicles in a country is not necessarily in proportion to the number of available charging stations. It is the authors' intention as well to indicate the potential directions of the development of a low-emission cargo transport in the European Union. Upon the basis of the results, it is ascertained that there is a strong correlation between the value of a country's GDP and the number of electric vehicle charging stations. A moderate correlation is also observed in the case of a country's population, as well as in the case of the market share of registered electric delivery vehicles in a country.

Ziemlewska A., Zagórska-Dziok M., Nizioł-Łukaszewska Z.

Vaccinum myrtillus L., Ribes nigrum L., Rubus fruticosus L., Fragaria vesca L. leaves are considered an agro-waste of the berry industry. Although numerous studies indicate fruit is a rich source of bioactive compounds, the authors prove leaves can also be a valuable source of compounds used in the pharmaceutical and cosmetic industries. The study attempts to assess and compare the antioxidant and cytotoxic properties of berry leaves extracts. The total phenolic compounds, flavonoids, anthocyanins and procyanidins content were determined. Antioxidant potential was evaluated using the DPPH radical scavenging method. Cytotoxicity studies were conducted to evaluate the effect of the extracts on the metabolism and proliferation of keratinocytes and fibroblasts in vitro. The effect on the migration capacity of these cells was also assessed. The obtained results show that the examined extracts are a source of valuable bioactive agents. All tested extracts show significant ability to remove free radicals in higher concentrations. Cytotoxicity assessments have shown that leaf extracts of the analyzed plants differ in cytotoxicity, both for keratinocytes and fibroblasts. The results of the assessment of cell migration capacity correlate with cytotoxicity tests, because the concentration of extracts showing cytotoxic activity towards the tested cells also inhibited their migration.

Buzun K., Gornowicz A., Lesyk R., Bielawski K., Bielawska A.

Autophagy is a process of self-degradation that plays an important role in removing damaged proteins, organelles or cellular fragments from the cell. Under stressful conditions such as hypoxia, nutrient deficiency or chemotherapy, this process can also become the strategy for cell survival. Autophagy can be nonselective or selective in removing specific organelles, ribosomes, and protein aggregates, although the complete mechanisms that regulate aspects of selective autophagy are not fully understood. This review summarizes the most recent research into understanding the different types and mechanisms of autophagy. The relationship between apoptosis and autophagy on the level of molecular regulation of the expression of selected proteins such as p53, Bcl-2/Beclin 1, p62, Atg proteins, and caspases was discussed. Intensive studies have revealed a whole range of novel compounds with an anticancer activity that inhibit or activate regulatory pathways involved in autophagy. We focused on the presentation of compounds strongly affecting the autophagy process, with particular emphasis on those that are undergoing clinical and preclinical cancer research. Moreover, the target points, adverse effects and therapeutic schemes of autophagy inhibitors and activators are presented.