Search

Based on the detailed exploration of urban park soundscapes through graph theory, this study presents a nuanced examination of the acoustic environments of two urban parks located in Wrocław, Poland, and Ankara, Turkey. The research captures the diversity of sound events within these parks, emphasizing the co-occurrence and interconnectivity of natural and anthropogenic sounds. By mapping these sounds into a network, the research provides a novel perspective on urban soundscapes, emphasizing the usefulness of some of indicators stemming from graph science in the realms of urban park acoustics. The findings suggest that a holistic approach to urban park design, considering the various measures of acoustic ecosystem organization, can contribute significantly to urban planning and environmental conservation. Through detailed analysis, the study reveals the potential of graph-theoretical approaches in understanding and improving the auditory experiences in urban green spaces, highlighting the synergy between different sound sources and their collective impact on the urban park ecosystem.

Theobroma cacao L., commonly known as cocoa, has been an integral part of human culture and diet for thousands of years. However, recent scientific research has highlighted its potential therapeutic properties, particularly in the treatment of cancer and inflammatory diseases. This comprehensive review analyzes the anti-inflammatory and anticancer effects of Theobroma cacao extracts combined with nanoparticles using in vitro and in vivo studies. Its diverse biological activity can be attributed to its rich phytochemical profile, including polyphenols, flavonoids, and alkaloids. In vitro studies have found that cocoa extracts, alone or in combination with nanoparticles, inhibit cancer cell proliferation, induce apoptosis and modulate key signaling pathways in various cancer cell lines. The extracts have also been found to reduce tumor growth and enhance the efficacy of conventional chemotherapeutic agents, potentially reducing their side effects, in vivo. Its anti-inflammatory properties are based on its ability to modulate inflammatory mediators, inhibit NF-κB signaling, and regulate macrophage polarization. These effects have been observed in both cellular and animal models of inflammation. This review opens up new possibilities for future research and therapeutic applications, highlighting the potential of Theobroma cacao as a valuable complementary approach in the treatment and prevention of cancer and inflammatory diseases.

Background: Endoscopic cysto-gastrostomy (ECG) has become the treatment of choice for pancreatic pseudocysts (PPCs). Endoscopic drainage of PPCs requires the creation of an anastomosis between the lumen of the PPCs and the lumen of the gastrointestinal tract. Various types of stents are used for this purpose. The aim of the study is to compare the indications, quantity, and results of using double pigtail plastic stents (DPPSs) and lumen-apposing fully covered metal stents (LAMSs) in ECG. Methods: A retrospective analysis was conducted of 39 patients (24 men, 15 women) treated for PPCs in the Department of Digestive Tract Surgery and the Department of Gastroenterology and Hepatology between October 2018 and February 2023. The mean age of patients was 51.13 (28–77). Data about etiology, cyst diameter, type, and complications of the stents were collected. Results: DPPSs were placed in smaller cysts (108 vs. 140 millimeters, p = 0.04) and were maintained for a longer duration compared to LAMSs (106 vs. 34 days, p = 0.001). Cyst recurrence was reported less frequently in patients with a LAMS (0 (0%) vs. 4 (19.05%), p = 0.05) and the therapeutic success was non-significantly higher in the LAMS group compared to the DPPS group (100% vs. 85.71%), p = 0.095. Conclusions: Both DPPSs and LAMSs are characterized by high therapeutic success and low complication rates in patients undergoing ECG for PPCs.

Anthocyanins, a class of flavonoid compounds responsible for the vibrant colors of many fruits and vegetables, have received considerable attention in recent years due to their potential health benefits. This review, focusing on evidence from both in vitro and in vivo studies, provides a comprehensive overview of the current state of knowledge regarding the health-promoting properties of anthocyanins. The chemical structure and diversity of anthocyanins, their bioavailability, and their mechanisms of action at the cellular and molecular level are examined. Research on the antioxidant, anti-inflammatory, anticancer, and neuroprotective effects of anthocyanins is critically reviewed. Special emphasis is placed on the role of anthocyanins in the prevention and treatment of chronic diseases such as cardiovascular diseases, diabetes, and neurodegenerative diseases. This review also discusses the challenges of translating in vitro findings to in vivo and highlights the importance of considering dose, bioavailability, and metabolism when assessing the therapeutic potential of anthocyanins. This review concludes with the identification of gaps in current research and suggestions for future directions for anthocyanin studies, including the need for more long-term clinical trials and investigations into potential synergistic effects with other phytochemicals. This comprehensive analysis highlights the promising role of anthocyanins in promoting human health and provides valuable insights for researchers, health professionals, and the nutraceutical industry. This study provides new insights, as it comprehensively investigates the dual anti-inflammatory and anticancer effects of anthocyanins in both in vitro and in vivo models. By uncovering the biological properties of anthocyanins from a variety of natural sources, this research not only expands our knowledge of the action of these compounds at the cellular level, but also enhances their clinical relevance through in vivo validation. Furthermore, the innovative use of anthocyanins may lead to important advances in their therapeutic application in the future.

The abietane diterpenoid 7α-acetoxy-6β-hydroxyroyleanone (Roy) isolated from Plectranthus grandidentatus demonstrates cytotoxicity across numerous cancer cell lines. To potentiate anticancer attributes, a series of semi-synthetic Roy derivatives were generated and examined computationally. ADMET predictions were used to evaluate drug-likeness and toxicity risks. The antineoplastic potential was quantified by PASS. The DFT models were used to assess their reactivity and stability. Molecular docking determined cancer-related protein binding. MS simulations examined ligand–protein stability. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Favorable ADME attributes and acceptable toxicity profiles were determined for all compounds. Strong anticancer potential was shown across derivatives (Pa 0.819–0.879). Strategic modifications altered HOMO–LUMO gaps (3.39–3.79 eV) and global reactivity indices. Favorable binding was revealed against cyclin-dependent kinases, BCL-2, caspases, receptor tyrosine kinases, and p53. The ligand exhibited a stable binding pose in MD simulations. Network analysis revealed involvement in cancer-related pathways. In silico evaluations predicted Roy and derivatives as effective molecules with anticancer properties. Experimental progress is warranted to realize their chemotherapeutic potential.

BackgroundCancer continues to be the leading cause of mortality in high-income countries, necessitating the development of more precise and effective treatment modalities. Immunotherapy, specifically adoptive cell transfer of T cell receptor (TCR)-engineered T cells (TCR-T therapy), has shown promise in engaging the immune system for cancer treatment. One of the biggest challenges in the development of TCR-T therapies is the proper prediction of the pairing between TCRs and peptide-human leukocyte antigen (pHLAs). Modern computational immunology, using artificial intelligence (AI)-based platforms, provides the means to optimize the speed and accuracy of TCR screening and discovery. ObjectiveThis study proposes an observational clinical trial protocol to collect patient samples and generate a database of pHLA:TCR sequences to aid the development of an AI-based platform for efficient selection of specific TCRs. MethodsThe multicenter observational study, involving 8 participating hospitals, aims to enroll patients diagnosed with stage II, III, or IV colorectal cancer adenocarcinoma. ResultsPatient recruitment has recently been completed, with 100 participants enrolled. Primary tumor tissue and peripheral blood samples have been obtained, and peripheral blood mononuclear cells have been isolated and cryopreserved. Nucleic acid extraction (DNA and RNA) has been performed in 86 cases. Additionally, 57 samples underwent whole exome sequencing to determine the presence of somatic mutations and RNA sequencing for gene expression profiling. ConclusionsThe results of this study may have a significant impact on the treatment of patients with colorectal cancer. The comprehensive database of pHLA:TCR sequences generated through this observational clinical trial will facilitate the development of the AI-based platform for TCR selection. The results obtained thus far demonstrate successful patient recruitment and sample collection, laying the foundation for further analysis and the development of an innovative tool to expedite and enhance TCR selection for precision cancer treatments. Trial RegistrationClinicalTrials.gov NCT04994093; https://clinicaltrials.gov/ct2/show/NCT04994093 International Registered Report Identifier (IRRID)DERR1-10.2196/45872

Wounds and chronic wounds can be caused by bacterial infections and lead to discomfort in patients. To solve this problem, scientists are working to create modern wound dressings with antibacterial additives, mainly because traditional materials cannot meet the general requirements for complex wounds and cannot promote wound healing. This demand is met by material engineering, through which we can create electrospun wound dressings. Electrospun wound dressings, as well as those based on hydrogels with incorporated antibacterial compounds, can meet these requirements. This manuscript reviews recent materials used as wound dressings, discussing their formation, application, and functionalization. The focus is on presenting dressings based on electrospun materials and hydrogels. In contrast, recent advancements in wound care have highlighted the potential of thermoresponsive hydrogels as dynamic and antibacterial wound dressings. These hydrogels contain adaptable polymers that offer targeted drug delivery and show promise in managing various wound types while addressing bacterial infections. In this way, the article is intended to serve as a compendium of knowledge for researchers, medical practitioners, and biomaterials engineers, providing up-to-date information on the state of the art, possibilities of innovative solutions, and potential challenges in the area of materials used in dressings.

The paper discusses the state of stress in a slowly-closing valve during accelerated start-up of a steam turbine. The valve is one of the first components affected by high temperature gradients and is a key element on which the power, efficiency and safety of the steam system depend. The authors calibrated the valve model based on experimental data and then performed extended Thermal-FSI analyses relative to experiment. The issue is important as determining the possibility of accelerating the start-up of a steam turbine while not exceeding the strength limit in the design of the steam valve. The shorter the startup time, the more environmental and economic benefits. The most important results of the work include the possibility to reduce the start-up time of a steam machine without excessive strain on the valve structural components and not to exceed the stress limits. The important news for the industry is that there is no need to change the valves construction in terms of accelerated start-up of the steam engine. The results of the work confirm the belief that fast start-up of a steam turbine is possible without large capital expenditures for design changes in the components of the steam system.

Leonurus sibiricus L. has great ethnobotanical and ethnomedicinal significance. This study aimed to assess the antioxidant and anti-inflammatory properties of Leonurus sibiricus L. transgenic roots extracts transformed by Rhizobium rhizogenes, with and without the AtPAP1 transcriptional factor. The study determined the total phenolic and flavonoid contents, as well as in vitro antioxidant assays, including hydrogen peroxide and nitric oxide scavenging activity. In addition, in silico computational studies and molecular docking were conducted to evaluate the antioxidant and anti-inflammatory potential of the identified compounds. The ligands were docked to NADPH oxidase, cyclooxygenase 2,5-lipoxygenase, inducible nitric synthase and xanthine oxidase: enzymes involved in the inflammatory process. The total phenolic and flavonoid contents ranged from 85.3 ± 0.35 to 57.4 ± 0.15 mg/g GAE/g and 25.6 ± 0.42 to 18.2 ± 0.44 mg/g QUE/g in hairy root extracts with and without AtPAP1, respectively. H2O2 scavenging activity (IC50) was found to be 29.3 µg/mL (with AtPAP1) and 37.5 µg/mL (without AtPAP1 transcriptional factor), and NO scavenging activity (IC50) was 48.0 µg/mL (with AtPAP1) and 68.8 µg/mL (without AtPAP1 transcriptional factor). Leonurus sibiricus L. transformed root extracts, both with and without AtPAP1, are a source of phytochemicals belonging to different classes of molecules, such as flavonoids (catechin and rutin), phenolic compounds (caffeic acid, coumaric acid, chlorogenic acid, ferulic acid) and phenylpropanoid (verbascoside). Among the radicals formed after H removal from the different -OH positions, the lowest bond dissociation enthalpy was observed for rutin (4′-OH). Rutin was found to bind with cyclooxygenase 2, inducible nitric synthases and xanthine oxidase, whereas chlorogenic acid demonstrated optimal binding with 5-lipoxygenase. Therefore, it appears that the Leonurus sibiricus L. transformed root extract, both with and without the AtPAP1 transcriptional factor, may serve as a potential source of active components with antioxidant and anti-inflammatory potential; however, the extract containing AtPAP1 demonstrates superior activities. These properties could be beneficial for human health.

BackgroundEnteral nutrition (EN) with foods for special medical purposes (FSMP) is recommended for most patients on home enteral nutrition (HEN). Although there are disease-specific guidelines for energy, protein, and micronutrient provision, only a few studies are showing real-life experience in the long-term use of FSMP.MethodsIn a multicenter study, the influence of the FSMP composition and administration technique (bolus vs. continuous) on protein and energy provision in HEN was analyzed. Provision of vitamins and minerals was compared to recommended daily allowance (RDA) and upper tolerable limit (UL).ResultsApproximately, 772 patients on HEN, mostly (88.6%) with oncological and neurological diseases, were enrolled. The patients on standard FSMP received less protein and energy than those on hypercaloric and protein enriched despite receiving higher volumes of EN (p < 0.05). No differences were observed in jejunal feeding with oligomeric vs. polymeric FSMP in terms of energy, protein, and volume. Continuous gastric feeding provided more protein, energy, and volume vs. bolus feeding (p < 0.05). Significant number of patients received less than 100% RDA of vitamin D (50.5%), vitamin B3 (49%), vitamin K (21.8%), vitamin B5 (64.3%), vitamin B9 (60%). Majority of the patients received less than 100% RDA of sodium (80.2%), potassium (99%), chloride (98%), calcium (67%), magnesium (87%), fluoride (99%), and iodine (43%). Approximately, 43.63% of cancer and 49.9% of neurological patients received less than 1 g/kg/day of protein and 51.7% of cancer and 55.5% of neurological patients received less than 25 kcal/kg/day.ConclusionAwareness of the available compositions of FSMP and advantageous profiles of specific diets may lead to the implementation of recommendations for EN. HEN professionals need to analyze all the patient’s needs and requirements to provide more tailored matching of nutritional support.

Nanoparticles (NPs), due to their size, have a key position in nanotechnology as a spectrum of solutions in medicine. NPs improve the ability of active substances to penetrate various routes: transdermal, but also digestive (active endocytosis), respiratory and injection. Chitosan, an N-deacetylated derivative of chitin, is a natural biodegradable cationic polymer with antioxidant, anti-inflammatory and antimicrobial properties. Cross-linked chitosan is an excellent matrix for the production of nanoparticles containing active substances, e.g., the Ginkgo biloba extract (GBE). Chitosan nanoparticles with the Ginkgo biloba extract (GBE) were obtained by ion gelation using TPP as a cross-linking agent. The obtained product was characterized in terms of morphology and size based on SEM and Zeta Sizer analyses as well as an effective encapsulation of GBE in nanoparticles—FTIR-ATR and UV-Vis analyses. The kinetics of release of the active substance in water and physiological saline were checked. Biological studies were carried out on normal and cancer cell lines to check the cytotoxic effect of GBE, chitosan nanoparticles and a combination of the chitosan nanoparticles with GBE. The obtained nanoparticles contained and released GBE encapsulated in research media. Pure NPs, GBE and a combination of NPs and the extract showed cytotoxicity against tumor cells, with no cytotoxicity against the physiological cell line.

The results of ecological condition assessments of ecosystems are related to key decisions taken for the purpose of remedial measures or maintaining their current state. In the assessment process, experts come across extensive datasets, the quality, and completeness of which do not always allow for a reliable evaluation, especially if a single empirical approach is used. In this paper, results of machine learning algorithms are presented, with a focus on Self-Organizing Maps. In this context, measurements of component parameters for the assessment of the ecological state of lake ecosystems were subjected to the process of unsupervised machine learning with the aim to create an alternative assessment approach based on the capabilities of neural networks. Results are mapped and compared with expert evaluations, allowing to extend knowledge about sub-clusters present in the data. The primary target of this paper is the ecological assessment expert. At an early stage, information was obtained about the presence of ecological outliers that may be subject to separate monitoring or verification of environmental activities and objectives. In the back-mapping process, the presented technique of map construction and clustering with various versions of the division was referenced to a set of expert classification findings, revealing the underlying structure of the results when addressed with an unsupervised data comprehension. The approach introduced here does not intend to interfere with the format of an original assessment methodology. Rather it aims at obtaining useful additional information which may help in making better decisions.

Estimating the postmortem interval (PMI) has remained the subject of investigations in forensic medicine for many years. Every kind of death results in changes in metabolites in body tissues and fluids due to lack of oxygen, altered circulation, enzymatic reactions, cellular degradation, and cessation of anabolic production of metabolites. Metabolic changes may provide markers determining the time since death, which is challenging in current analytical and observation-based methods. The study includes metabolomics analysis of blood with the use of an animal model to determine the biochemical changes following death. LC-MS is used to fingerprint postmortem porcine blood. Metabolites, significantly changing in blood after death, are selected and identified using univariate statistics. Fifty-one significant metabolites are found to help estimate the time since death in the early postmortem stage. Hypoxanthine, lactic acid, histidine, and lysophosphatidic acids are found as the most promising markers in estimating an early postmortem stage. Selected lysophosphatidylcholines are also found as significantly increased in blood with postmortal time, but their practical utility as PMI indicators can be limited due to a relatively low increasing rate. The findings demonstrate the great potential of LC-MS-based metabolomics in determining the PMI due to sudden death and provide an experimental basis for applying this attitude in investigating various mechanisms of death. As we assume, our study is also one of the first in which the porcine animal model is used to establish PMI metabolomics biomarkers.

Plectranthus ornatus Codd, the genus Plectranthus of the Lamiaceae family, has been used as traditional medicine in Africa, India and Australia. Pharmacological studies show the use of this plant to treat digestive problems. In turn, leaves were used for their antibiotic properties in some regions of Brazil to treat skin infections. The present study examines the anti-inflammatory, antioxidant and cytotoxic effects of the halimane and labdane diterpenes (11R*,13E)-11-acetoxyhalima-5,13-dien-15-oic acid (HAL) and 1α,6β-diacetoxy-8α,13R*-epoxy-14-labden-11-one (PLEC) and the forskolin-like 1:1 mixture of 1,6-di-O-acetylforskolin and 1,6-di-O-acetyl-9-deoxyforskolin (MRC) isolated from P. ornatus on lung (A549) and leukemia (CCRF-CEM) cancer cell lines, and on normal human retinal pigment epithelial (ARPE-19) cell line in vitro. Additionally, molecular docking and computational approaches were used. ADMET properties were analysed through SwissADME and proTox-II—Prediction. The results indicate that all tested compounds significantly reduced the viability of the cancer cells and demonstrated no cytotoxic effects against the non-neoplastic cell line. The apoptosis indicators showed increased ROS levels for both the tested A549 and CCRF-CEM cancer cell lines after treatment. Furthermore, computational studies found HAL to exhibit moderate antioxidant activity. In addition, selected compounds changed mitochondrial membrane potential (MMP), and increased DNA damage and mitochondrial copy number for the CCRF-CEM cancer cell line; they also demonstrated anti-inflammatory effects on the ARPE-19 normal cell line upon lipopolysaccharide (LPS) treatment, which was associated with the modulation of IL-6, IL-8, TNF-α and GM-CSF genes expression. Docking studies gave indication about the lowest binding energy for 1,6-di-O-acetylforskolin docked into IL-6, TNF-α and GM-CSF, and 1,6-di-O-acetyl-9-deoxyforskolin docked into IL-8. The ADMET studies showed drug-likeness properties for the studied compounds. Thus, halimane and labdane diterpenes isolated from P. ornatus appear to offer biological potential; however, further research is necessary to understand their interactions and beneficial properties.

Automated and reproducible methodology for assessing the ecological condition of lakes is essential for effective monitoring and facilitating the decision-making process aimed at achieving the stated environmental goals. At the same time, multidimensional measurement datasets are often an obstacle to drawing insightful conclusions, thus becoming an incentive for overly simplified analyzes. In this article, a set of measurements and ecological status assessment results for a collection of 499 lakes in Poland was used. Expert assessment process was recreated using the supervised kernel Support Vector Machine algorithm on dataset with reduced dimensionality, thus a model that automates the ecological assessment process was obtained. The use of the explanatory skill of latent variables made it possible to present the assessed objects along with their position in individual classes. The visualization of the results in reduced dimensionality increased, without interfering with the size of the classes, the informative evaluation potential, which should be considered as an acompanying assessment parameter in the future. The primary target of this paper is the ecological expert coping with automatization of assessment process and obtaining latent information for sense-making visual comprehension during consultations regarding ecosystem-oriented ecological decision making.

Pseudoexfoliation syndrome (XFS) is stress- or inflammation-induced elastosis accompanied by excessive production of microfibrils and their deposition in the anterior segment of the eye. Approximately 60–70 million people are affected by XFS worldwide. It is a component of a systemic disorder, considered a major risk factor for accelerated cataract formation, cataract surgery complications and development of glaucoma, which untreated or inadequately treated may lead to blindness. Moreover, XFS has been associated with cardiovascular and cerebrovascular morbidity, dementia, sensorineural hearing loss and pelvic organ prolapse. The pathogenesis of XFS has not been fully elucidated yet. Aqueous humor (AH) is a transparent fluid filling the anterior and posterior chambers of the eye. Determination of AH metabolites that are characteristic for XFS may provide valuable information about the molecular background of this ocular disorder. The aim of this study was to compare the composition of AH in XFS and non-XFS patients undergoing cataract surgery. The AH samples from 34 patients (15 with XFS and 19 without) were analyzed using liquid chromatography coupled to a Quadrupole Time-of-Flight mass spectrometer (LC-QTOF-MS). The obtained metabolic fingerprints were analyzed using multivariate statistics. Eleven statistically significant metabolites were identified. Compared with the non-XFS group, the AH of patients with XFS contained significantly lower levels of amino acids and their derivatives, for example, arginine (−31%, VIP = 2.38) and homo-arginine (−19%, VIP = 1.38). Also, a decrease in the levels of two acylcarnitines, hydroxybutyrylcarnitine (−29%, VIP = 1.24) and decatrienoylcarnitine (−46%, VIP = 1.89), was observed. However, the level of indoleacetaldehyde in XFS patients was significantly higher (+96%, VIP = 2.64). Other significant metabolites were two well-recognized antioxidants, ascorbic acid (−33%, VIP = 2.11) and hydroxyanthranilic acid (−33%, VIP = 2.25), as well as S-adenosylmethionine, a compound with anti-inflammatory properties (−29%, VIP = 1.93). Metabolic pathway analysis demonstrated that the identified metabolites belonged to eight metabolic pathways, with cysteine and methionine metabolism as well as arginine and proline metabolism being the most frequently represented. XFS can be associated with enhanced oxidative stress and inflammation, as well as with the disturbances of cellular respiration and mitochondrial energy production. Implementation of non-targeted metabolomics provided a better insight into the still not fully understood pathogenesis of XFS.

Plants are a rich source of secondary metabolites that exhibit numerous desired properties. The compounds may influence the biology of melanocytes, pigment cells that produce melanin, by modulating numerous signaling pathways, including cAMP/PKA, MAPKs and PI3K/AKT. Its downstream target is microphthalmia-associated transcription factor, responsible for the expression of the tyrosinase enzyme, which plays a major role in melanogenesis. Therefore, this literature review aims to provide insights related to melanogenesis modulation mechanisms of plant extracts and isolated plant compounds in B16 cells. Database searches were conducted using online-based library search instruments from 2012 to 2022, such as NCBI-PubMed and Google Scholar. Upregulation or downregulation of signaling pathways by phytochemicals can influence skin hypo- and hyperpigmentation by changing the level of melanin production, which may pose a significant cosmetic issue. Therefore, plant extracts or isolated plant compounds may be used in the therapy of pigmentation disorders.

W dniu 3 grudnia 2020 roku zespół badawczy „Ochrona praw człowieka w polskim systemie prawnym”, działający w Instytucie Nauk Prawnych Uniwersytetu Szczecińskiego, zorganizował Ogólnopolską Konferencję Naukową „Dylematy polskiego prawa wyborczego”. Z uwagi na obostrzenia związane z pandemią koronawirusa wydarzenie odbyło się w formie webinarium (zdalnej wideokonferencji). Tego trudnego zadania podjęły się trzy osoby: dr hab. Jerzy Ciapała, prof. US, dr Agata Pyrzyńska i dr Radosław Zych. Współorganizatorami konferencji były: Krajowe Biuro Wyborcze, Województwo Zachodniopomorskie, Okręgowa Izba Radców Prawnych w Szczecinie oraz Stowarzyszenie Amicus Facultatis Iuris Stetinensis. Konferencja naukowa skierowana była w głównej mierze do teoretyków prawa konstytucyjnego oraz przedstawicieli organów administracji wyborczej. Spotkała się ona z dużym odzewem, ponieważ w obradach uczestniczyło ponad 100 osób (zarówno teoretyków, jak i praktyków prawa). Patronatu nad tym wydarzeniem udzielili: Państwowa Komisja Wyborcza, Marszałek Województwa Zachodniopomorskiego Olgierd Geblewicz, Prezydent Miasta Szczecin Piotr Krzystek, Polskie Towarzystwo Prawa Konstytucyjnego oraz dwa wysoko punktowane czasopisma naukowe: „Przegląd Prawa Konstytucyjnego” i „Studia Wyborcze”.

Background: Glycogen synthase kinase-3β (GSK3β) is a key regulator of cellular homeostasis. In neurons, GSK3β contributes to the control of neuronal transmission and plasticity, but its role in epilepsy remains to be defined. Methods: Biochemical and electrophysiological methods were used to assess the role of GSK3β in regulating neuronal transmission and epileptogenesis. GSK3β activity was increased genetically in GSK3β[S9A] mice. Its effects on neuronal transmission and epileptogenesis induced by kainic acid were assessed by field potential recordings in mice brain slices and video electroencephalography in vivo. The ion channel expression was measured in brain samples from mice and followed by analysis in samples from patients with temporal lobe epilepsy or focal cortical dysplasia in correlation to GSK3β phosphorylation. Findings: Higher GSK3β activity decreased the progression of kainic acid induced epileptogenesis. At the biochemical level, higher GSK3β activity increased the expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel 4 under basal conditions and in the epileptic mouse brain and decreased phosphorylation of the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA1 at Serine 831 under basal conditions. Moreover, we found a significant correlation between higher inhibitory GSK3β phosphorylation at Serine 9 and higher activating GluA1 phosphorylation at Serine 845 in brain samples from epileptic patients. Interpretation: Our data imply GSK3β activity in the protection of neuronal networks from hyper-activation in response to epileptogenic stimuli and indicate that the anti-epileptogenic function of GSK3β involves modulation of HCN4 level and the synaptic AMPA receptors pool. Keywords: Glycogen synthase kinases-3, GSK3, Epilepsy, AMPA receptors, GluA1 phosphorylation

Electrospun hybrid nanofibers, based on functional agents immobilized in polymeric matrix, possess a unique combination of collective properties. These are beneficial for a wide range of applications, which include theranostics, filtration, catalysis, and tissue engineering, among others. The combination of functional agents in a nanofiber matrix offer accessibility to multifunctional nanocompartments with significantly improved mechanical, electrical, and chemical properties, along with better biocompatibility and biodegradability. This review summarizes recent work performed for the fabrication, characterization, and optimization of different hybrid nanofibers containing varieties of functional agents, such as laser ablated inorganic nanoparticles (NPs), which include, for instance, gold nanoparticles (Au NPs) and titanium nitride nanoparticles (TiNPs), perovskites, drugs, growth factors, and smart, inorganic polymers. Biocompatible and biodegradable polymers such as chitosan, cellulose, and polycaprolactone are very promising macromolecules as a nanofiber matrix for immobilizing such functional agents. The assimilation of such polymeric matrices with functional agents that possess wide varieties of characteristics require a modified approach towards electrospinning techniques such as coelectrospinning and template spinning. Additional focus within this review is devoted to the state of the art for the implementations of these approaches as viable options for the achievement of multifunctional hybrid nanofibers. Finally, recent advances and challenges, in particular, mass fabrication and prospects of hybrid nanofibers for tissue engineering and biomedical applications have been summarized.

Abstract Brassica oleracea var. botrytis, a very popular crop grown for its edible inflorescence, is bred only as a mutated annual cultivar and does not naturally occur in environment. Since cauliflower is still described as the most troublesome of all the B. oleracea vegetables regarding transformation processes, it is fully justified to focus on the improvement of tools for its genetic modifications. Here, we present a successful protocol for genetic transformation of cauliflower employing the process of agroinfection. The primary analysis of in vitro response of five cultivars allowed us to have chosen Pionier as the most promising cultivar; in consequence the Pionier was transformed via Rhizobium-mediated techniques in order to evaluate both, R. radiobacter (EHA 105, LBA 4404) and R. rhizogenes (ATCC 18534, A4) species. However, the latter system turned out to be more effective and, the A4 strain, in particular (72% transformation efficiency, 55% confirmed by GUS assay). That shows a promising technical advance especially when compared to the results of previous literature reports (e.g. 8.7% reported efficiency using R. rhizogenes). The transgenic cauliflower was obtained from hairy roots via organogenic callus induction. The potential transformants were analysed at the genomic and proteomic levels and their transgenic character was fully confirmed.

In recent years, there has been a considerable increase in interest in the use of transgenic plants as sources of valuable secondary metabolites or recombinant proteins. This has been facilitated by the advent of genetic engineering technology with the possibility for direct modification of the expression of genes related to the biosynthesis of biologically active compounds. A wide range of research projects have yielded a number of efficient plant systems that produce specific secondary metabolites or recombinant proteins. Furthermore, the use of bioreactors allows production to be increased to industrial scales, which can quickly and cheaply deliver large amounts of material in a short time. The resulting plant production systems can function as small factories, and many of them that are targeted at a specific operation have been patented. This review paper summarizes the key research in the last ten years regarding the use of transgenic plants as small, green biofactories for the bioreactor-based production of secondary metabolites and recombinant proteins; it simultaneously examines the production of metabolites and recombinant proteins on an industrial scale and presents the current state of available patents in the field.

It is known that Senna obtusifolia has been used in medicine since ancient times due to the content of many valuable compounds with a pro-health effect. One of them is betulinic acid, which is a pentacyclic triterpene with antimalarial, antiviral, anti-inflammatory and anticancer properties. In this work, a continuation of our previous research, an attempt was made to increase the level of betulinic acid accumulation by the cultivation of transgenic hairy roots that overexpress the squalene synthase gene in a 10 L sprinkle bioreactor with methyl jasmonate elicitation. We present that the applied strategy allowed us to increase the content of betulinic acid in hairy root cultures to the level of 48 mg/g dry weight. The obtained plant extracts showed a stronger cytotoxic effect on the U87MG glioblastoma cell line than the roots grown without elicitors. Additionally, the induction of apoptosis, reduction of mitochondrial membrane potential, chromosomal DNA fragmentation and activation of caspase cascades are demonstrated. Moreover, the tested extract showed inhibition of topoisomerase I activity.

Plants are rich sources of a diverse range of chemicals, many of which have significant metabolic activity. One large group of secondary compounds are the phenolics, which act as inter alia potent reactive oxygen scavengers in cells, including fibroblasts. These common dermis residue cells play a crucial role in the production of extracellular matrix components, such as collagen, and maintaining the integrity of connective tissue. Chronic wounds or skin exposure to UV-irradiation disrupt fibroblast function by the generation of reactive oxygen species, which may damage cell components and modify various signaling pathways. The resulting imbalance may be reversed by the antioxidant activity of plant-derived phenolic compounds. This paper reviews the current state of knowledge on the impact of phenolics on fibroblast functionality under oxidative stress conditions. It examines a range of compounds in extracts from various species, as well as single specific plant-derived compounds. Phenolics are a good candidate for eliminating the causes of skin damage including wounds and aging and acting as skin care agents.

According to the present knowledge, this is the first report on establishing transformed root cultures of Leonotis nepetifolia after Rhizobium rhizogenes-mediated transformation. The preliminary phytochemical analysis showed differences in the content of phenols and flavonoids in transformed and nontransformed roots. The dominant compounds in the analyzed extracts were (+)-catechin (5464 and 6808 µg/g DW), p-coumaric acid (2549 and 4907 µg/g DW), m-coumaric acid (1508 and 2048 µg/g DW) and rosmarinic acid (1844 and 2643 µg/g DW) for nontransformed (LNNR) and transformed (LNTR4) roots, respectively. Initial biological studies carried out on LNNR, and LNTR4 extracts showed a cytotoxic effect on the A549 lung, HCC1937 breast and leukemia NALM-6 cell lines, antioxidants, as well as repair and protection against DNA damage induced by H2O2 in HUVEC cells. Due to the stronger effect of the LNTR4 root extract, which can be a relatively efficient and cheap source of bioactive secondary metabolites, further biological analyses are needed to discover in detail their potentially valuable biological properties.

Biorąc pod uwagę ograniczone zasoby wód Polski, obecne rozwiązania gospodarowania wodą powinny zmierzać w kierunku poprawy wykorzystania naturalnych zasobów wodnych w miejscu ich powstawania. Przykładem takich działań jest zastosowana na systemie melioracyjnym obiektu Samotwór (72 ha) metoda całorocznego regulowania odpływu. Ocenę skuteczności zastosowanego rozwiązania oparto na analizie rozkładu sum zapasów wody dla miesięcy okresu wegetacyjnego w charakterystycznych profilach glebowych o miąższości 1 m. W ramach badań polowych i laboratoryjnych określono zapasy aktualne oraz potencjalne możliwości retencjonowania wody w analizowanych glebach, do wartości polowej pojemności wodnej (PPW) oraz maksymalnego dopuszczalnego uwilgotnienia (MDU) – przyjęto 85% PePW. Badania wykazały, że potencjalna rezerwa retencyjna analizowanych profili glebowych w latach 1995–2012, liczona do PPW, kształtowała się średnio od 21 mm w kwietniu do 84 mm w sierpniu i odpowiednio od 115 mm w kwietniu do 177 mm w lipcu – liczona do MDU. Wieloletnie badania prowadzone na obiekcie Samotwór wykazały istnienie stosunkowo dużych i bezpiecznych dla upraw możliwości okresowego retencjonowania wody w profilach glebowych.

The major goal of this research was to establish a stable regeneration system for tomato cultivars in order to lay the foundations for the future genetic transformation of the tomato. The regeneration ability of two kinds of explants (cotyledons and hypocotyl segments) was compared for three Polish cultivars of the tomato (Solanum lycopersicum). Explants were cultured on 10 different regeneration media (basal mediums MS or B5, and with a combination of 6-benzylaminopurine (BAP) and indole-3-acetic acid (IAA). It was found that the ability to regenerate was substantially dependent on the cultivars, as well as on the kind of explant. The best explants for inducing shoot regeneration were cotyledons, followed by hypocotyls. It was noticed that the best formulation of the medium for this regeneration from the two types of explants used in this study, is MS with 2 mg/L BA and 0.1 mg/L IAA. Tomato shoots were transferred to a ½ MS medium and ½ MS complemented with 0.1 mg/L IAA for rooting and all of them responded positively to the rooting medium.

Koncepcja zielonych dachów i ich znaczenie dla krajobrazu miejskiego są zgodne z zasadami zrównoważonego rozwoju i gospodarowania wodami opadowymi. Aspekty te przyczyniają się do ciągłego poszukiwania rozwiązań w zakresie technologii tych systemów. W pracy dokonano oceny zdolności retencyjnych modelu zielonego dachu typu ekstensywnego opartego na profilach warstwy wegetacyjnej przygotowanej na bazie keramzytu oraz perlitu. Badania prowadzono od IV do IX w 2012 roku na obiekcie zlokalizowanym na terenie obserwatorium Agro- i Hydrometorologii Wrocław-Swojec. Ocenie poddano efektywność retencyjną dachów. Badania modelowe wykazały, że dachy zielone retencjonowały wodę w zakresie od 22,9 do 77,8 mm, a wskaźniki retencji mieściły się w zakresie od 67 do 98% opadów atmosferycznych. Wskaźniki odpływów były stosunkowo niewielkie i wynosiły od 0,5 do 18 mm.

Plectranthus spp. is widely known for its medicinal properties and bioactive metabolites. The cytotoxic and genotoxic properties of the four known abietane diterpenoids: 7α-Acetoxy-6β-hydroxyroyleanone (Roy), 6,7-dehydroroyleanone (Deroy), 7β,6β-dihydroxyroyleanone6 (Diroy), and Parvifloron D (Parv), isolated from P. madagascariensis (Roy, DeRoy, and Diroy) and P. ecklonii (Parv) were evaluated. The tested compounds showed cytotoxic effects against the human leukemia cell line CCRF-CEM and the lung adenocarcinoma cell line A549. All tested compounds induced apoptosis by altering the level of pro- and anti-apoptotic genes. The results show that from the tested diterpenoids, Roy and Parv demonstrated the strongest activity in both human cancer cell lines, changing the permeability mitochondrial membrane potential and reactive oxygen species (ROS) levels, and possibly inducing mtDNA or nDNA damage. In conclusion, the abietane diterpenoids tested may be used in the future as potential natural chemotherapeutic agents

In this publication, we present an energy and exergy analysis of the Szewalski binary vapor cycle based on a model of a supercritical steam power plant. We used energy analysis to conduct a preliminary optimization of the cycle. Exergy loss analysis was employed to perform a comparison of heat-transfer processes, which are essential for hierarchical cycles. The Szewalski binary vapor cycle consists of a steam cycle bottomed with an organic Rankine cycle installation. This coupling has a negative influence on the thermal efficiency of the cycle. However, the primary aim of this modification is to reduce the size of the power unit by decreasing the low-pressure steam turbine cylinder and the steam condenser. The reduction of the “cold end” of the turbine is desirable from economic and technical standpoints. We present the Szewalski binary vapor cycle in addition to a mathematical model of the chosen power plant’s thermodynamic cycle. We elaborate on the procedure of the Szewalski cycle design and its optimization in order to attain an optimal size reduction of the power unit and limit exergy loss.

Many biologically-active plant-derived compounds have therapeutic or chemopreventive effects. The use of plant in vitro cultures in conjunction with modern genetic engineering techniques allows greater amounts of valuable secondary metabolites to be obtained without interfering with the natural environment. This work presents the first findings concerning the acquisition of transgenic hairy roots of Senna obtusifolia overexpressing the gene encoding squalene synthase 1 from Panax ginseng (PgSS1) (SOPSS hairy loot lines) involved in terpenoid biosynthesis. Our results confirm that one of PgSS1-overexpressing hairy root line extracts (SOPSS2) possess a high cytotoxic effect against a human acute lymphoblastic leukemia (NALM6) cell line. Further analysis of the cell cycle, the expression of apoptosis-related genes (TP53, PUMA, NOXA, BAX) and the observed decrease in mitochondrial membrane potential also confirmed that the SOPSS2 hairy root extract displays the highest effects; similar results were also obtained for this extract combined with doxorubicin. The high cytotoxic activity, observed both alone or in combination with doxorubicin, may be due to the higher content of betulinic acid as determined by HPLC analysis. Our results suggest synergistic effects of tested extract (betulinic acid in greater amount) with doxorubicin which may be used in the future to develop new effective strategies of cancer chemosensitization.

The plant kingdom abounds in countless species with potential medical uses. Many of them contain valuable secondary metabolites belonging to different classes and demonstrating anticancer, anti-inflammatory, antioxidant, antimicrobial or antidiabetic properties. Many of these metabolites, e.g., paclitaxel, vinblastine, betulinic acid, chlorogenic acid or ferrulic acid, have potential applications in medicine. Additionally, these compounds have many therapeutic and health-promoting properties. The growing demand for these plant secondary metabolites forces the use of new green biotechnology tools to create new, more productive in vitro transgenic plant cultures. These procedures have yielded many promising results, and transgenic cultures have been found to be safe, efficient and cost-effective sources of valuable secondary metabolites for medicine and industry. This review focuses on the use of various in vitro plant culture systems for the production of secondary metabolites.

Natural compounds isolated from plants are excellent starting points in drug design and have been widely studied as anticancer agents; they hence find use in a considerable proportion of anticancer drugs. The genus Plectranthus (Lamiaceae) comprises a large and widespread group of species with various applications in traditional medicine. Therefore, the aim of the present study was to determine the effectiveness of treatment with four abietane diterpenoids isolated from P. madagascariensis and P. ecklonii, 6,7-dehydroroyleanone, 7β,6β-dihydroxyroyleanone, 7α-acetoxy-6β-hydroxyroyleanone and parvifloron D, in initiating apoptosis in a glioma cell line. The pure compounds were found to exhibit anticancer effects in primary H7PX glioma cells line by inducing apoptosis G2/M cell cycle arrest and double-strand breaks, indicated by increased levels of phosphorylated H2A.X and decreasing mitochondrial membrane potential; they also influenced the expression of pro- and anti-apoptotic genes (Bax, Bcl-2, TP53, or Cas-3). Our findings indicate that these compounds may offer potential as beneficial antitumor drugs but further in vivo studies are needed.

Aqueous humor (AH) is a transparent fluid which fills the anterior and posterior chambers of the eye. It supplies nutrients and removes metabolic waste from avascular tissues in the eye. Proper homeostasis of AH is required to maintain adequate intraocular pressure as well as optical and refractive properties of the eye. Application of metabolomics to study human AH may improve knowledge about the molecular mechanisms of eye diseases. Until now, global analysis of metabolites in AH has been mainly performed using NMR. Among the analytical platforms used in metabolomics, LC-MS allows for the highest metabolome coverage. The aim of this study was to develop a method for extraction and analysis of AH metabolites by LC-QTOF-MS. Different protocols for AH preparation were tested. The best results were obtained when one volume of AH was mixed with one volume of methanol : ethanol (1 : 1). In the final method, 2 µL of extracted sample was analyzed by LC-QTOF-MS. The method allowed for reproducible measurement of over 1000 metabolic features. Almost 250 metabolites were identified in AH and assigned to 47 metabolic pathways. This method is suitable to study the potential role of amino acids, lipids, oxidative stress, or microbial metabolites in development of ocular diseases.

As the current cancer treatment success rate is not sufficient, interest has grown in plants as possible sources of anti-cancer compounds. One such plant with a broad spectrum of activity is Lenourus sibiricus of the family Lamiaceae. This study investigates for the first time both the genotoxic and cytotoxic activities of TR (transformed) and AtPAP1 TR (with over-expression of transcriptional factor) root extracts of Lenourus sibiricus against various cancer cell lines (CCRF-CEM, K-562 and A549). Both tested extracts showed a cytotoxic effect on CCRF-CEM and K-562 cell lines, but strongest activity was observed for the AtPAP1 TR extract. No cytotoxic effect was observed against the A549 cell line in the tested concentration range, and it was found that both tested extracts may induce apoptosis by decreasing mitochondrial membrane potential and inducing nDNA damage lesion in the TP53 region and mtDNA in ND1 (mitochondrially encoded NADH: ubiquinone oxidoreductase core subunit 1) and ND5 (mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 5) regions in K-562 and CCRF-CEM. Our results confirmed that TR and AtPAP1 TR root extracts from L. sibiricus are cytotoxic and genotoxic against different model cell lines (CCRF-CEM and K-562). However, the observed genotoxicity of both extracts needs to be confirmed by additional studies. These preclinical observations support the use of L. sibiricus with other pharmacological purposes.

OBJECTIVE:Due to the capacity of the amniotic membrane (Am) to support re-epithelisation and inhibit scar formation, Am has a potential to become a considerable asset for reconstructive urology i.e., reconstruction of ureters and urethrae. The application of Am in reconstructive urology is limited due to a poor mechanical characteristic. Am reinforcement with electrospun nanofibers offers a new strategy to improve Am mechanical resistance, without affecting its unique bioactivity profile. This study evaluated biocomposite material composed of Am and nanofibers as a graft for urinary bladder augmentation in a rat model. MATERIAL AND METHODS:Sandwich-structured biocomposite material was constructed from frozen Am and covered on both sides with two-layered membranes prepared from electrospun poly-(L-lactide-co-E-caprolactone) (PLCL). Wistar rats underwent hemicystectomy and bladder augmentation with the biocomposite material. RESULTS:Immunohistohemical analysis (hematoxylin and eosin [H&E], anti-smoothelin and Masson's trichrome staining [TRI]) revealed effective regeneration of the urothelial and smooth muscle layers. Anti-smoothelin staining confirmed the presence of contractile smooth muscle within a new bladder wall. Sandwich-structured biocomposite graft material was designed to regenerate the urinary bladder wall, fulfilling the requirements for normal bladder tension, contraction, elasticity and compliance. Mechanical evaluation of regenerated bladder wall conducted based on Young's elastic modulus reflected changes in the histological remodeling of the augmented part of the bladder. The structure of the biocomposite material made it possible to deliver an intact Am to the area for regeneration. An unmodified Am surface supported regeneration of the urinary bladder wall and the PLCL membranes did not disturb the regeneration process. CONCLUSIONS:Am reinforcement with electrospun nanofibers offers a new strategy to improve Am mechanical resistance without affecting its unique bioactivity profile.

The purpose of this study was to compare: a new five-layered poly (L-lactide-co-caprolactone) (PLC) membrane and small intestinal submucosa (SIS) as a control in rat urinary bladder wall regeneration. The five-layered poly (L-lactide-co-caprolactone) membrane was prepared by an electrospinning process. Adipose tissue was harvested from five 8-week old male Wistar rats. Adipose derived stem cells (ADSCs) were seeded in a density of 3×10(6) cells/cm2 onto PLC membrane and SIS scaffolds, and cultured for 5-7 days in the stem cell culture medium. Twenty male Wistar rats were randomly divided into five equal groups. Augmentation cystoplasty was performed in a previously created dome defect. Groups: (I) PLC+ 3×10(6)ADSCs; (II) SIS+ 3×10(6)ADSCs; (III) PLC; (IV) SIS; (V) control. Cystography was performed after three months. The reconstructed urinary bladders were evaluated in H&E and Masson's trichrome staining. Regeneration of all components of the normal urinary bladder wall was observed in bladders augmented with cell-seeded SIS matrices. The urinary bladders augmented with SIS matrices without cells showed fibrosis and graft contraction. Bladder augmentation with the PLC membrane led to numerous undesirable events including: bladder wall perforation, fistula or diverticula formation, and incorporation of the reconstructed wall into the bladder lumen. The new five-layered poly (L-lactide-co-caprolactone) membrane possesses poorer potential for regenerating the urinary bladder wall compared with SIS scaffold.

The aim of this study was to compare two different acellular scaffolds: natural and synthetic, for urinary conduit construction and ureter segment reconstruction. Acellular aortic arch (AAM) and poly(L-lactide-co-caprolactone) (PLCL) were used in 24 rats for ureter reconstruction in both tested groups. Follow-up period was 4 weeks. Intravenous pyelography, histological and immunohistochemical analysis were performed. All animals survived surgical procedures. Patent uretero-conduit junction was observed only in one case using PLCL. In case of ureter segment reconstruction ureters were patent in one case using AAM and in four cases using PLCL scaffolds. Regeneration of urothelium layer and focal regeneration of smooth muscle layer was observed on both tested scaffolds. Obtained results indicates that synthetic acellular PLCL scaffolds showed better properties for ureter reconstruction than naturally derived acellular aortic arch.