Recent advances in the three-dimensional (3D) cancer models give rise to a plethora of new possibilities in the development of anti-cancer drug therapies and bring us closer to personalized medicine. Three-dimensional models are undoubtedly more authentic than traditional two-dimensional (2D) cell cultures. Nowadays, they are becoming preferentially used in most cancer research fields due to their more accurate biomimetic characteristics. On the contrary, they still lack the cellular and matrix complexity of the native tumor microenvironment (TME). This review focuses on the description of existing 3D models, the incorporation of TME and fluidics into these models, and their perspective in the future research. It is clear that such an improvement would need not only biological but also technical progress. Therefore, the modern approach to anti-cancer drug discovery should involve various fields.
This study aimed to determine the prevalence of endoparasites in dog feces from public places, investigate the occurrence of endoparasites in soil, and identify potential risk factors associated with the dog endoparasites infection spread in East Slovak Lowland - the region near the EU border with Ukraine. In a one-year study, a total of 803 dog fecal samples and 148 soil samples from public places were examined for the presence of endoparasite developmental stages. In general, 43.59 % of dog excrements were positive. Six different species of intestinal parasites were detected: Toxocara canis (22.65 %), Trichuris vulpis (14.07 %), family Ancylostomatidae (10.09 %), Capillaria aerophilla (5.60 %), Ascaris spp. (1.49 %). Altogether, 52.03 % of soil samples were positive for at least one endoparasites species. The occurrence of parasitic eggs in the soil was as follows: Ascaris spp. (37.16 %), Toxocara spp. (29.05 %), Trichuris spp. (29.05 %) %), family Ancylostomatidae (2.03 %) and Toxascaris leonina (2.03 %). The occurrence of endoparasites between the towns and villages varied significantly. The distribution of endoparasites in dogs and soil was affected by the population density, the minority people living in the studied territory, the number of people living in poor hygienic conditions with limited access to drinking water and the usage of sewerage. Persisting endoparasitic contamination of the environment in East Slovak Lowland forms a reservoir with zoonotic potential representing public and environmental health problems.
The paper presents a comprehensive design of metrological equipment for torque sensor verification and calibration, detailing the process from conception to construction and highlighting the specifics of the structural design to meet metrological requirements. The measuring device’s functionality and the individual structural components are described, as is the methodology for creating a complete product. The paper addresses the crucial issue of measurement uncertainty and the required accuracy, achieved through the construction of a special measuring arm made of carbon material. FEM analyses of the carbon arm are presented and compared with the required metrological accuracies. In addition, we discuss the different properties of various carbon structures in Pre-preg materials used in the construction of the measuring arm and present the results of measurements on such carbon materials. This paper provides a comprehensive insight into the design and construction of metrological equipment for torque sensors, with a focus on its compliance with metrological requirements. The proposed device aims to establish the foundations for primary metrology of torque in Slovakia and has potential applications in a wide range of industries.
We redescribe the holotype and only known specimen of the early eureptile Coelostegus prothales from the Upper Carboniferous of the Czech Republic using photogrammetric scanning and a virtual 3D rendition of its skull. New information is available on several skull and lower jaw bones, including the postorbital, supratemporal, tabular, postparietal, angular, and prearticular. The new data also permit the correct identification of previously undetected or mis-identified elements (e.g., supratemporal; quadratojugal; angular). We provide an amended diagnosis of Coelostegus and a new reconstruction of the skull in dorsal and lateral views. To evaluate the affinities of Coelostegus , we code this taxon in two recently published taxon-character matrices. Parsimony and Bayesian analyses do not permit firm conclusions on the phylogenetic position of Coelostegus or, indeed, the status and extrinsic relationships of protorothyridid amniotes. Coelostegus emerges either as the sister taxon to the recently redefined Diapsida (Araeoscelidia; Varanopidae; Parareptilia; Neodiapsida), as one of the most basal protorothyridids, or as a derived stem-group amniote in various parsimony-based analyses, or as the basalmost protorothyridid in one Bayesian analysis, with protorothyridids forming a paraphyletic array relative to Diapsida. We review the cranial similarities and differences between Coelostegus and other protorothyridid genera and discuss the implications that various phylogenetic results have for our understanding of early amniote relationships.
Recent work has paid close attention to the first principle of Granger causality, according to which cause precedes effect. In this context, the question may arise whether the detected direction of causality also reverses after the time reversal of unidirectionally coupled data. Recently, it has been shown that for unidirectionally causally connected autoregressive (AR) processes X → Y , after time reversal of data, the opposite causal direction Y → X is indeed detected, although typically as part of the bidirectional X ↔ Y link. As we argue here, the answer is different when the measured data are not from AR processes but from linked deterministic systems. When the goal is the usual forward data analysis, cross-mapping-like approaches correctly detect X → Y , while Granger causality-like approaches, which should not be used for deterministic time series, detect causal independence X ⫫ Y . The results of backward causal analysis depend on the predictability of the reversed data. Unlike AR processes, observables from deterministic dynamical systems, even complex nonlinear ones, can be predicted well forward, while backward predictions can be difficult (notably when the time reversal of a function leads to one-to-many relations). To address this problem, we propose an approach based on models that provide multiple candidate predictions for the target, combined with a loss function that consideres only the best candidate. The resulting good forward and backward predictability supports the view that unidirectionally causally linked deterministic dynamical systems X → Y can be expected to detect the same link both before and after time reversal.
Although β1-adrenoceptor (β1-AR) signal transduction, which maintains cardiac function, is downregulated in failing hearts, the mechanisms for such a defect in heart failure are not fully understood. Since cardiac hypertrophy is invariably associated with heart failure, it is possible that the loss of β1-AR mechanisms in failing heart occurs due to hypertrophic process. In this regard, we have reviewed the information from a rat model of adaptive cardiac hypertrophy and maladaptive hypertrophy at 4 and 24 weeks after inducing pressure overload as well as adaptive cardiac hypertrophy and heart failure at 4 and 24 weeks after inducing volume overload, respectively. Varying degrees of alterations in β1-AR density as well as isoproterenol-induced increases in cardiac function, intracellular Ca2+-concentration in cardiomyocytes and adenylyl cyclase activity in crude membranes have been reported under these hypertrophic conditions. Adaptive hypertrophy at 4 weeks of pressure or volume overload showed unaltered or augmented increases in the activities of different components of β1-AR signaling. On the other hand, maladaptive hypertrophy due to pressure overload and heart failure due to volume overload at 24 weeks revealed depressions in the activities of β1-AR signal transduction pathway. These observations provide evidence that β1-AR signal system is either unaltered or upregulated in adaptive cardiac hypertrophy and downregulated in maladaptive cardiac hypertrophy or heart failure. Furthermore, the information presented in this article supports the concept that downregulation of β1-AR mechanisms in heart failure or maladaptive cardiac hypertrophy is not due to hypertrophic process per se. It is suggested that a complex mechanism involving the autonomic imbalance may be of a critical importance in determining differential alterations in non-failing and failing hearts.
Interventional radiologists are chronically exposed to low-dose ionizing radiation (IR), which may represent a health risk. The aim of the present study was to evaluate genomic instability by analyzing chromosomal aberrations, micronuclei, and 53BP1 DNA repair foci in peripheral blood lymphocytes of radiologists. Based on the IAEA guidelines on biodosimetry using dicentrics, the average protracted whole-body dose in radiologists were estimated. Since preleukemic fusion genes (PFG) are the primary events leading to leukemia, we also studied their presence by RT-qPCR and FISH. No significant difference in 53BP1 foci and incidence of PFG (MLL-AF4, MLL-AF9, AML1-ETO, BCR-ABL p190) was found in cells of interventional radiologists in comparison to controls. However, our results showed an increased frequency of micronuclei and various types of chromosomal aberrations including dicentrics in interventional radiologists. The average protracted whole body estimated dose was defined at 452.63 mGy. We also found a significantly higher amplification of the MLL gene segment and increased RNA expression in cells of interventional radiologists in comparison to controls. In conclusion, our results showed that long-term low-dose IR induces genomic instability in interventional radiologists.
The study of the ectoparasite fauna of the insectivores—Sorex araneus, Sorex minutus, Neomys fodiens, and Neomys anomalus (subfamily Soricinae)—was carried out in three locations in Poland: Białowieża National Park, Kosewo Górne in the Masurian Lake District, and in vicinity of Warsaw. Three species of Ixodidae ticks, eleven species of fleas, and four species of mites from the order Mesostigmata were noted. The most numerous ectoparasites are ticks Ixodes ricinus (larvae), Dermacentor reticulatus (nymphs), and fleas Palaeopsylla soricis, Megabothris walkeri, and Hystrichopsylla orientalis. These species show the highest prevalence and show the highest dominance index. The parasitofauna of S. araneus is much richer in species than other shrew species. The structure and dominance of parasite assemblages differ between locations.
In this work, WC-Co cermet was successfully joined to AISI 304L stainless steel using flash spark plasma sintering (FSPS) technique under a constant load of 5 MPa with ultra-rapid holding times. The results revealed that increasing the holding time to 12s resulted in massive interfacial deformations accompanied with an important diffusion activity of Co, Ni and Fe across the interface. Toughness measurement of WC-Co cermet at the vicinity of the bonding interface was assessed using Vickers indentation fracture (VIF) method. The results revealed that the mechanical properties of the bonded joints deteriorated with increasing holding time, leading to increased brittleness. This outcome was observed despite the significant inter-diffusion that occurred between the WC-Co cermet and the constituents of the 304L steel
We investigated growth performance and ruminal fermentation associated with gastrointestinal nematode (GIN) Haemonchus contortus in lambs and in vitro ruminal fermentation of mallow, chamomile, fumitory, wormwood (Herbmix), and chicory using inoculum from GIN-infected lambs. Twelve lambs were equally divided into two groups: uninfected animals (CON) and animals infected (INF) with approximately 5000 third-stage larvae derived from the MHCo1 strain of GIN H. contortus. Two lambs per group were killed on days 48, 49, and 50 after infection and ruminal content was collected separately from each lamb. Batch cultures of ruminal fluid from CON and INF were incubated for 24 h in vitro with 0.25 g meadow hay, Herbmix, and chicory using an in vitro gas production technique. Daily weight gain was relatively lower in the INF than the CON group, but not significantly (72.6 vs. 130.1 g/day). The ruminal populations of protozoa, bacteria, total Archaea, Methanobacteriales, and Methanomicrobiales were significantly higher in the INF than in the CON group. The substrates affected the concentrations of n-butyrate, iso-butyrate, n-valerate, iso-valerate, ammonia-N, total gas, and methane (p < 0.001) in vitro. GIN infection affected fermentation and microbial population in the rumens of the lambs, and chicory was a promising substrate to modulate ruminal fermentation in vitro.
While the reverse water-gas shift (RWGS) reaction holds great promise as a method of converting CO2 to CO and subsequently into valuable fuels, achieving its commercial viability requires the development of highly efficient, selective, durable, and low-cost catalysts. Recently, thin-film nanocatalysts produced through plasma deposition (PECVD) have garnered significant attention in this domain. Among them, FeOx-based catalytic films deposited using Fe(CO)5 as a precursor, under reduced pressure (4–5 Pa) and a 13.56 MHz glow discharge, have demonstrated particular interest. Our study shows that by appropriately tuning the parameters of the plasma deposition process, it is feasible to generate nanocatalyst films exhibiting exceptional CO2 conversion (38% at 673 K) and CO selectivity (97%). Moreover, the study has revealed the formation of a carbon deposit containing carbon nanotubes (CNTs) during the RWGS reaction, significantly increasing the catalytic activity of the films. Through an analysis involving X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and electron microscopy techniques (SEM and HRTEM), we have determined that CNTs not only serve as carriers for highly catalytically active Fe nanoparticles but also create nanoscale heterojunctions (p-n) with Fe2O3 nanoparticles, thereby enhancing their catalytic effect. This paper attempts to elucidate the differences and changes in the surface structure of FeOx-based films dictating the catalytic activity, which stems from both the conditions of plasma deposition and the environmental impact during the catalytic process.
Objectives. Bisphenol A (BPA) is an indispensable industrial chemical. However, as a proven endocrine disruptor, it may be associated with several health disturbances, including the reproductive functions impairment and cancer. Due to the restriction of BPA usage, many bisphenol derivatives gradually substitute BPA. However, studies have reported adverse biological effects of BPA analogs, but the specific sites of their action remain largely unknown. Nuclear receptors (NRs) appear to play significant roles in various types of cancer. In addition, they are considered relevant targets of bisphenols. In the present study, we investigated the effects of BPA and its analogs bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF) on mRNA expression of selected NRs in the human ovarian epithelial cell line Caov3. The NRs examined included retinoic acid receptor α (RARA), retinoid X receptor α (RXRA), peroxisome proliferator activating receptor β/δ (PPARD), chicken ovalbumin upstream promoter-transcription factor 2 (COUPTFII), and nuclear receptor-related protein 1 (NURR1).
The purpose of this experiment was to determine the impact of feed supplementation with organic zinc and/or a medicinal plants mixture on the composition and enzymatic activity of intestinal microflora as well as on the duodenal and jejunal barrier integrity in lambs. A total of 28 lambs were randomly allocated into 4 dietary treatments (n = 7) and were fed an unsupplemented basal diet (BD), or the BD enriched with organic Zn (Zn, 70 mg/kg diet), an herbal mixture (Herbmix, 100 g/day) or a combination of both additives (Zn+Herbmix). The Herbmix contained 33% each of Fumaria officinalis, Malva sylvestris, Matricaria chamomilla and 1% Artemisia absinthium. No significant effect on the fecal microbiota composition was observed due to the 35-day or 70-day dietary treatment. The intake of Zn alone resulted in decreased bacterial enzyme activities, such as β-glucuronidase, N-acetyl-glucosaminidase, β-galactosidase and β-glucosidase. The transepithelial electrical resistance of the small intestinal mucosa was not influenced by the dietary treatment, whereas simultaneous feeding of Zn and Herbmix exhibited higher claudin-1 and occludin levels in the jejunal mucosa. These results indicate that dietary intake of organic zinc and/or medicinal plants in the mentioned dosage did not alter the diversity of intestinal bacteria in growing lambs but did significantly influence bacterial enzyme activity. Supplementing the zinc and herbs combination showed the potential to regulate intestinal permeability by increasing the level of tight junction proteins in the jejunal mucosa.
Therapeutic peptides are a growing class of innovative drugs with high efficiency and a low risk of adverse effects. These biomolecules fall within the molecular mass range between that of small molecules and proteins. However, their inherent instability and potential for degradation underscore the importance of reliable and effective analytical methods for pharmaceutical quality control, therapeutic drug monitoring, and compliance testing. Liquid chromatography–mass spectrometry (LC–MS) has long time been the “gold standard” conventional method for peptide analysis, but capillary electrophoresis (CE) is increasingly being recognized as a complementary and, in some cases, superior, highly efficient, green, and cost-effective alternative technique. CE can separate peptides composed of different amino acids owing to differences in their net charge and size, determining their migration behavior in an electric field. This review provides a comprehensive overview of therapeutic peptides that have been used in the clinical environment for the last 25 years. It describes the properties, classification, current trends in development, and clinical use of therapeutic peptides. From the analytical point of view, it discusses the challenges associated with the analysis of therapeutic peptides in pharmaceutical and biological matrices, as well as the evaluation of CE as a whole and the comparison with LC methods. The article also highlights the use of microchip electrophoresis, nonaqueous CE, and nonconventional hydrodynamically closed CE systems and their applications. Overall, the article emphasizes the importance of developing new CE-based analytical methods to ensure the high quality, safety, and efficacy of therapeutic peptides in clinical practice.
Identification of therapeutic targets for treating fibrotic diseases and cancer remains challenging. Our study aimed to investigate the effects of TGF-β1 and TGF-β3 on myofibroblast differentiation and extracellular matrix deposition in different types of fibroblasts, including normal/dermal, cancer-associated, and scar-derived fibroblasts. When comparing the phenotype and signaling pathways activation we observed extreme heterogeneity of studied markers across different fibroblast populations, even within those isolated from the same tissue. Specifically, the presence of myofibroblast and deposition of extracellular matrix were dependent on the origin of the fibroblasts and the type of treatment they received (TGF-β1 vs. TGF-β3). In parallel, we detected activation of canonical signaling (pSMAD2/3) across all studied fibroblasts, albeit to various extents. Treatment with TGF-β1 and TGF-β3 resulted in the activation of canonical and several non-canonical pathways, including AKT, ERK, and ROCK. Among studied cells, cancer-associated fibroblasts displayed the most heterogenic response to TGF-β1/3 treatments. In general, TGF-β1 demonstrated a more potent activation of signaling pathways compared to TGF-β3, whereas TGF-β3 exhibited rather an inhibitory effect in keloid- and hypertrophic scar-derived fibroblasts suggesting its clinical potential for scar treatment. In summary, our study has implications for comprehending the role of TGF-β signaling in fibroblast biology, fibrotic diseases, and cancer. Future research should focus on unraveling the mechanisms beyond differential fibroblast responses to TGF-β isomers considering inherent fibroblast heterogeneity.
The main aim of this work was to develop a suitable sorbent for the separation and determination of ²²⁶ Ra through ¹³³ Ba (radio tracer) in water samples using fly ash sorbent. After the modification with KMnO 4 the effects of pH, competing ions, the possibility of elution, and the effect of water volume were tested. As a suitable eluent 6 mol/L HCl was chosen, while the sorbent worked best at pH 6–8. The developed method is advantageous for minimizing the time required for separation, the volume of chemicals used, and the waste generated after separation.
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