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The expression of human PLAUR gene, which encodes the urokinase plasminogen activator receptor (uPAR), is cell- and process-specific and elevated in inflammation, cancer and senescence. Its tight regulation is achieved by regulatory elements in the gene locus, such as the promoter and several enhancers. The promoter activity is not specific to a particular cell type and has been described earlier. The proximal enhancer is endothelial-specific and responsible for the PLAUR expression pattern in endothelial cells. In this study we described the enhancer activity and its cis-regulatory elements based on the published data. We showed a possible connection of the enhancer activity with known cellular phenotypes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The aim of the study was to develop polymer matrix tablets with modified release of dry Betula pendula leaf extract and to investigate basic parameters influencing the drug release pattern. To fully assess the statistical significance of the influence of the individual factors in the tablet formulation development as well as the combination of them, Tukey's tests and a complete 3 3 factor analysis of variance (ANOVA) were applied. The following three factors were studied at three levels (low, medium and high): influence of the hydrophobic/hydrophilic polymer ratio Ethylcellulose (EC)/Hydroxypropyl methylcellulose (HPMC) (40/60, 25/75 and 10/90), influence of HPMC molecular weight (500 kDa, 750 kDa and 1150 kDa), and influence of the compression force applied (1 t, 1.5 t and 2 t). The effect of these varied parameters on the drug release parameter t80 was evaluated statistically. Twenty-seven tablet models were formulated, including all possible combinations of the variables. The obtained drug release profiles demonstrated that a 25/75 (EC/HPMC) ratio was the most suitable for prolonging the release process. Increasing the molecular weight of HMPC from 500 kDa to 750-1150 kDa and applying higher compression force significantly influenced the studied t80 values and caused sustained drug release (t80 up to 7.97 h). The combination of the hydrophilic HPMC polymer with the hydrophobic EC can result in the formation of a promising drug-carrying matrix, offering effective control of the drug release process.

Mechanosignaling, initiated by extracellular forces and propagated through the intracellular cytoskeletal network, triggers signaling cascades employed in processes as embryogenesis, tissue maintenance and disease development. While signal transduction by transcription factors occurs downstream of cellular mechanosensing, little is known about the cell intrinsic mechanisms that can regulate mechanosignaling. Here we show that transcription factor PREP1 (PKNOX1) regulates the stiffness of the nucleus, the expression of LINC complex proteins and mechanotransduction of YAP-TAZ. PREP1 depletion upsets the nuclear membrane protein stoichiometry and renders nuclei soft. Intriguingly, these cells display fortified actomyosin network with bigger focal adhesion complexes resulting in greater traction forces at the substratum. Despite the high traction, YAP-TAZ translocation is impaired indicating disrupted mechanotransduction. Our data demonstrate mechanosignaling upstream of YAP-TAZ and suggest the existence of a transcriptional mechanism actively regulating nuclear membrane homeostasis and signal transduction through the active engagement/disengagement of the cell from the extracellular matrix., (© 2022. The Author(s).)

Tn5 transposase use in biotechnology has substantially advanced the sequencing applications of genome-wide analysis of cells. This is mainly due to the ability of Tn5 transposase to efficiently transpose DNA essentially randomly into any target DNA without the aid of other factors. This concise review is focused on the advances in Tn5 applications in multi-omics technologies, genome-wide profiling, and Tn5 hybrid molecule creation. The possibilities of other transposase uses are also discussed.

AIM: To introduce the indicators Clarc of energy distribution (CED) and Clarc of protein/amino acid transformation (CPT) and adapt the methodology for their calculation in aquaculture. MATERIAL AND METHODS: A 50-day experiment was carried out with juvenile carp fish (C. carpio L.) reared in net cages. The following characteristics were reported: fodder (nutritional) coefficient, digestible energy, and crude protein intake per unit of weight gain, percentage of the boneless fillet, the chemical composition of the fillet. The methodology for calculating the respective Clarcs was described. RESULTS: The following values of the newly introduced indicators were established: Clarc of energy distribution (CED) -- 0.0866 (8.66%); Clarc of protein transformation (CPT) -- 0.1052 (10.52%). [ABSTRACT FROM AUTHOR]

The article proposes a methodology for introducing objective criteria for accounting for the net utilization of energy and protein (amino acids) along the chain „forage consumed by sheep/goats - obtained sheep/goat milk.“ Adapted for dairy sheep/goats are the calculations of the introduced criteria Clarc of energy distribution and Clarc of protein (amino acid) transformation. The authors believe that the introduction of the methodology and the calculations based on it, will help to refine the scientific research in 3 aspects: selection, technological and ecological. [ABSTRACT FROM AUTHOR]

Smart self-organising systems attract considerable attention in the scientific community. In order to control and stabilise the liquid crystalline behaviour, and hence the self-organisation, the polymerisation process can be effectively used. Mesogenic units incorporated into the backbones as functional side chains of weakly cross-linked macromolecules can become orientationally ordered. Several new calamitic reactive mesogens possessing the vinyl terminal group with varying flexible chain lengths and with/without lateral substitution by the methyl (methoxy) groups have been designed and studied. Depending on the molecular structure, namely, the type and position of the lateral substituents, the resulting materials form the nematic, the orthogonal SmA and the tilted SmC phases in a reasonably broad temperature range, and the structure of the mesophases was confirmed by X-ray diffraction experiments. The main objective of this work is to contribute to better understanding of the molecular structure-mesomorphic property relationship for new functional reactive mesogens, aiming at further design of smart self-assembling macromolecular materials for novel sensor systems.

PURPOSE: Introducing a system for recording of the productive effect of energy and protein by their transformation into lamb/kids/small ruminant's meat. METHODS: The results were obtained in experiment with a 6 male Kalofer longhaired goat kids, slaughtered immediately at weaning at 90 days of age, without a period of intense fattening after weaning (so-called "milky kids"). The kids were rearing in traditional conditions in the real production system. RESULTS: Clarc of energy distribution - CPT (net energy fodder - gross energy meat) - 0.5871 (58.71%) and Clarc of protein transformation - CPT (protein digestible in the intestine fodder - crude protein meat) - 0.1958 (19.58%) have been calculated. CONCLUSIONS: The Clarc of energy distribution and Clarc of protein transformation are indexes for objective calculation of the energy and nutrient transformation between the preliminary and secondary parts of the eco-technical chain "fodder-edible parts of lambs/kids meat". [ABSTRACT FROM AUTHOR]

A methodology to account for transformation of metabolizable energy and crude protein in compound feed for laying hens to energy and protein in egg melange (albumen and egg yolk) has been developed. The introduction of Clarc of metabolizable energy transformation and Clarc of crude protein distribution could help to more exactly account of net utilization of nutrients in the eco-technical feed chain. "Clarc" is the ratio of the nutrients studied between primary (feed) and secondary level (animal products, edible by humans). For their establishing, original formulas have been used. They could be used in at least three important areas - ecological (bio-transformation); selectional (development of objective selection criteria and indices) and technological (as indicators to improve the feeding and housing technologies). In the scientific experiment the following values of energy and protein transformation in experiments with laying hens from Lohman Brown Klassik hybrid are observed: Clarc of metabolizable energy transformation (fodder-egg melange) - 0.2313 (23.13%); Clark of crude protein distribution (fodder-egg melange) - 0.2096 (20.96%). [ABSTRACT FROM AUTHOR]

Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF. In a rat model of myocardium infarction, we show that transplantation of SCF producing cell sheet induced activation of the epicardium and promoted the accumulation of c-kit positive cells in ischemic muscle. Morphometry showed the reduction of infarct size (16%) and a left ventricle expansion index (0.12) in the treatment group compared to controls (24-28%; 0.17-0.32). The ratio of viable myocardium was more than 1.5-fold higher, reaching 49% compared to the control (28%) or unmodified cell sheet group (30%). Finally, by day 30 after myocardium infarction, SCF-producing cell sheet transplantation increased left ventricle ejection fraction from 37% in the control sham-operated group to 53%. Our results suggest that, combining the genetic modification of MSCs and their assembly into a multilayered construct, we can provide prolonged pleiotropic effects to the damaged heart, induce endogenous regenerative processes, and improve cardiac function.

Background: Eggs are important foods in the daily diet of humans and have great biological activity and a high digestibility. Egg yolk is a good source of biologically active substances such as fatty acids, phospholipids, sterols and tocopherols. The eggs of seven chicken genotypes were analyzed for their chemical composition, and a detailed study of the lipids in egg yolk was conducted., Results: Energy composition of the egg yolk and egg albumen was 29.06-30.51 MJ kg -1 and 19.77-20.93 MJ kg -1 respectively. Regarding their chemical composition: water ranged from 471.7 to 515.4 g kg -1 and 878.3-885.9 g kg -1 ; fat content in dry matter ranged from 607 to 647 g kg -1 and 6.7-11.6 g kg -1 ; protein varied from 302 to 331.7 g kg -1 and 823.6-892.5 g kg -1 ; ash ranged from 33.7 to 37.7 g kg -1 and 63.8-74.0 g kg -1 ; and nitrogen-free extracts ranged from 12.7 to 36.5 g kg -1 and 35.0-96.2 g kg -1 . The sterols and phospholipids in the yolk lipids were 16-26 g kg -1 and 59-127 g kg -1 . The main fatty acids in the lipids were oleic (39.1-47.3%) and palmitic (26.0-35.5%) acids. Cholesterol in the yolk lipids ranged from 15.9 to 25.9 g kg -1 . Phosphatidylcholine (389-573 g kg -1 ), phosphatidylethanolamine (219-355 g kg -1 ) and phosphatidylinositol (112-284 g kg -1 ) were the main phospholipids. The content of saturated fatty acids in the phospholipids was significantly higher than that in triacylglycerols., Conclusion: Small variations in the chemical composition of eggs from seven different genotypes were observed. Significant differences in the fatty acid compositions of the main classes of phospholipids and the triacylglycerol fraction were established. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Molecular mechanisms governing cell fate decision events in bone marrow mesenchymal stromal cells (MSC) are still poorly understood. Herein, we investigated the homeobox gene Prep1 as a candidate regulatory molecule, by adopting Prep1 hypomorphic mice as a model to investigate the effects of Prep1 downregulation, using in vitro and in vivo assays, including the innovative single cell RNA sequencing technology. Taken together, our findings indicate that low levels of Prep1 are associated to enhanced adipogenesis and a concomitant reduced osteogenesis in the bone marrow, suggesting Prep1 as a potential regulator of the adipo-osteogenic differentiation of mesenchymal stromal cells. Furthermore, our data suggest that in vivo decreased Prep1 gene dosage favors a pro-adipogenic phenotype and induces a "browning" effect in all fat tissues.

Cell therapy remains a promising approach for the treatment of cardiovascular diseases. In this regard, the contemporary trend is the development of methods to overcome low cell viability and enhance their regenerative potential. In the present study, we evaluated the therapeutic potential of gene-modified adipose-derived stromal cells (ADSC) that overexpress hepatocyte growth factor (HGF) in a mice hind limb ischemia model. Angiogenic and neuroprotective effects were assessed following ADSC transplantation in suspension or in the form of cell sheet. We found superior blood flow restoration, tissue vascularization and innervation, and fibrosis reduction after transplantation of HGF-producing ADSC sheet compared to other groups. We suggest that the observed effects are determined by pleiotropic effects of HGF, along with the multifactorial paracrine action of ADSC which remain viable and functionally active within the engineered cell construct. Thus, we demonstrated the high therapeutic potential of the utilized approach for skeletal muscle recovery after ischemic damage associated with complex tissue degenerative effects.

The E2A-PBX1 gene fusion is a common translocation in B-cell acute lymphoblastic leukaemia. Patients harbouring the E2A-PBX1 fusion gene typically exhibit an intermediate prognosis. Furthermore, minimal residual disease has unsatisfactory prognostic value in E2A-PBX1 B-cell acute lymphoblastic leukaemia. However, the mechanism of E2A-PBX1 in the occurrence and progression of B-cell acute lymphoblastic leukaemia is not well understood. Here, we mainly review the roles of E2A and PBX1 in the differentiation and development of B lymphocytes, the mechanism of E2A-PBX1 gene fusion in B-cell acute lymphoblastic leukaemia, and the potential therapeutic approaches., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

TALE (three amino acids loop extension) homeodomain transcription factors are required in various steps of embryo development, in many adult physiological functions, and are involved in important pathologies. This review focuses on the PREP, MEIS, and PBX sub-families of TALE factors and aims at giving information on their biochemical properties, i.e., structure, interactors, and interaction surfaces. Members of the three sets of protein form dimers in which the common partner is PBX but they can also directly interact with other proteins forming higher-order complexes, in particular HOX. Finally, recent advances in determining the genome-wide DNA-binding sites of PREP1, MEIS1, and PBX1, and their partial correspondence with the binding sites of some HOX proteins, are reviewed. These studies have generated a few general rules that can be applied to all members of the three gene families. PREP and MEIS recognize slightly different consensus sequences: PREP prefers to bind to promoters and to have PBX as a DNA-binding partner; MEIS prefers HOX as partner, and both PREP and MEIS drive PBX to their own binding sites. This outlines the clear individuality of the PREP and MEIS proteins, the former mostly devoted to basic cellular functions, the latter more to developmental functions. Developmental Dynamics 243:59-75, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Betula pendula is widespread in Europe and Asia. It has been used in traditional medicine since ancient times. Birch leaf extracts are known to exhibit a number of pharmacological activities. Antioxidant activity has also been reported., Aim: The aim of this work was to investigate the antioxidant activity of a dry leaf extract from Betula pendula Roth., Materials and Methods: The total flavonoid content was determined. Some of the most commonly used methods were applied to evaluate the antioxidant capacity of the extract in vitro and in vivo. The ability of the extract to scavenge DPPH free radicals was evaluated by the method described by Brand-Williams with suitable modifications. ABTS decolorization assay was also applied. The in vivo assay was performed after acute and chronic administration of the extract into white albino rats, in a dose of 100 and 500 mg/kg bw. The antioxidant potential of the plasma was determined using FRAP reagent., Results: A total flavonoid content of 42.5 mg/g was found, expressed as quercetin. The antioxidant activity against ABTS was concentration and time dependent. For example the concentration of 200 μg/ml led to 70.95% - 99.46% scavenging activity. DPPH scavenging activity was found to be about 98% at a concentration of 80 μg/ml. The extract possesses antioxidant potential, comparable with that of Trolox, in acute application. In chronic application, poorer results are observed, probably due to biotransformation and elimination processes., Conclusion: Dried birch leaf extract has a relatively high antioxidant potential and could be used as a natural source of antioxidants.

The synthesis of middle-to-late-replicating DNA can be affected independently of the rest of the genome by down-regulating the tumor suppressor PREP1 (PKNOX1). Indeed, DNA combing shows that PREP1 down-regulation affects DNA replication rate, increases the number of simultaneously firing origins and the asymmetry of DNA replication, leading to DNA damage. Genome-wide analysis of replication timing by Repli-seq shows that, upon PREP1 down-regulation, 25% of the genome is replicated earlier in the S-phase. The targeted DNA sequences correspond to Lamin-Associated Domains (LADs), and include late-replicating (LRRs) and temporal transition regions (TTRs). Notably, the distribution of PREP1 DNA binding sites and of its target genes indicates that DNA replication defects are independent of the overall PREP1 transcriptional activity. Finally, PREP1 down-regulation causes a substantial decrease in Lamin B1 levels. This suggests that DNA is released from the nuclear lamina earlier than in the control cells and is available for replication, thus explaining timing defects and DNA damage.This is the first evidence that the replication timing of a specific fraction of the human genome is affected by PREP1 tumor suppressor. This previously unknown function might significantly contribute to the genomic instability observed in human tumors.