Teriflunomide-related development of inverse psoriasis and worsening of pre-existing plaque psoriasis

Leflunomide can be used in management of psoriatic disease. Leflunomide's active metabolite, teriflunomide, is used in the treatment of multiple sclerosis and has unexpectedly been rarely reported to induce pustular psoriasis. In this report, we present a patient with multiple sclerosis who developed inverse psoriasis after starting teriflunomide

A necrotic stimulus is required to maximize matrix-mediated myogenesis in mice

Biomaterials that are similar to skeletal muscle extracellular matrix have been shown to augment regeneration in ischemic muscle. In this study, treatment with a collagen-based matrix stimulated molecular myogenesis in an mdx murine model of necrosis. Matrix-treated animals ran ≥ 40% further, demonstrating functional regeneration, and expressed increased levels of myogenic transcripts. By contrast, matrix treatment was unable to induce transcriptional or functional changes in an MLC/SOD1G93A atrophic mouse model. In vitro, satellite cells were cultured under standard conditions, on matrix, in the presence of myocyte debris (to simulate a necrotic-like environment) or with both matrix and necrotic stimuli. Exposure to both matrix and necrotic stimuli induced the greatest increases in mef2c, myf5, myoD and myogenin transcripts. Furthermore, conditioned medium collected from satellite cells cultured with both stimuli contained elevated levels of factors that modulate satellite cell activation and proliferation, such as FGF-2, HGF and SDF-1. Application of the conditioned medium to C2C12 myoblasts accelerated maturation, as demonstrated by increased mef2c, myf5 and myogenin transcripts and fusion indexes. In summary, the collagen matrix required a necrotic stimulus to enhance the maturation of satellite cells and their secretion of a myogenic cocktail. Considering that matrix treatment supports myogenesis only in in vivo models that exhibit necrosis, this study demonstrates that a necrotic environment is required to maximize matrix-mediated myogenesis

Design and Assembly Procedures for Large-Sized Biohybrid Scaffolds as Patches for Myocardial Infarct

[EN] Objective: To assemble a biohybrid cardiac patch consisting of a large (5x5 cm) elastomer scaffold whose pores are filled with a self-assembling peptide (SAP) gel entrapping adipose stem cells, to be used as a novel implant in a big animal model (sheep) of myocardial infarction. The study focuses on the way to determine optimal procedures for incorporating the SAP solution and the cells in the patch to ensure cell colonization and a homogeneous cell distribution in the construct before implantation. The problems associated with the scale-up of the different procedures raised by the large size of the construct are discussed. Materials and Methods: Experiments were performed to choose between different assembling alternatives: incorporation of the SAP gel before cell seeding or simultaneous SAP and cell loading of the scaffold; surface seeding of cells or cell injection into the scaffold pores; dissemination of the cells throughout the scaffold before incubation by gentle shaking or by centrifugation. Immunocytochemistry techniques and confocal and scanning electron microscopies were employed to assess and quantify cell colonization of the material and early cell distribution. Cell concentrations and the uniformity of cellular distribution throughout the scaffold were taken as the main criteria to decide between the different alternative procedures. Results: The combination of peptide preloading, cell injection, and shaking before incubation yielded the best results in terms of greater cell density and the most uniform distribution after 24 h of culture compared with the other methods. These techniques could be scaled-up to obtain large biohybrid cardiac patches with success. Conclusions: The results obtained after the different seeding methods allowed us to establish an effective protocol for the assembly of large biohybrid patches for their subsequent implantation in the heart of a big animal model of myocardial infarct in the context of a preclinical study.The authors acknowledge the financing from the European Commission through the ‘‘Regeneration of cardiac tissue assisted by bioactive implants’’ (RECATABI) FP7 NMP3-SL-2009-229239 project. MMP acknowledges support of Instituto de Salud Carlos III with assistance from the European Regional Development Fund through CIBER-BBN initiative.Martínez Ramos, C.; Rodríguez Pérez, E.; Perez Garnes, M.; Chachques, JC.; Moratal Pérez, D.; Vallés Lluch, A.; Monleón Pradas, M. (2014). Design and Assembly Procedures for Large-Sized Biohybrid Scaffolds as Patches for Myocardial Infarct. Tissue Engineering Part C Methods. 20(10):817-827. https://doi.org/10.1089/ten.TEC.2013.0489S817827201

Synergistic effect of bioactive lipid and condition medium on cardiac differentiation of human mesenchymal stem cells from different tissues

Human umbilical cord mesenchymal stem cells (hUCMSCs) and human adipose tissue mesenchymal stem cells (hATMSCs) have the potential to differentiate into cardiomyocytes, making them promising therapeutic candidates for treating damaged cardiac tissues. Currently, however, the differentiated cells induced from hUCMSCs or hATMSCs can hardly display functional characteristics similar to cardiomyocytes. In this study, we have investigated the effects of bioactive lipid sphingosine‐1‐phosphate (S1P) on cardiac differentiations of hUCMSCs and hATMSCs in condition medium composed of cardiac myocytes culture medium or 5‐azacytidine. Cardiac differentiations were identified through immunofluorescence staining, and the results were observed with fluorescence microscopy and confocal microscopy. Synergistic effects of S1P and condition medium on cell viability were evaluated by MTT assays. Functional characteristics similar to cardiomyocytes were evaluated through detecting calcium transient. The differentiated hUCMSCs or hATMSCs in each group into cardiomyocytes showed positive expressions of cardiac specific proteins, including α‐actin, connexin‐43 and myosin heavy chain‐6 (MYH‐6). MTT assays showed that suitable differentiation time was 14 days and that the optimal concentration of S1P was 0.5 μM. Moreover, incorporation of S1P and cardiac myocytes culture medium gave rise to calcium transients, an important marker for displaying in vivo electrophysiological properties. This feature was not observed in the S1P‐5‐azacytidine group, indicating the possible lack of cellular stimuli such as transforming growth factor‐beta, TGF‐β

Borax-loaded injectable alginate hydrogels promote muscle regeneration in vivo after an injury

[EN] Muscle tissue possess an innate regenerative potential that involves an extremely complicated and synchronized process on which resident muscle stem cells play a major role: activate after an injury, differentiate and fuse originating new myofibers for muscle repair. Considerable efforts have been made to design new approaches based on material systems to potentiate muscle repair by engineering muscle extracellular matrix and/or including soluble factors/cells in the media, trying to recapitulate the key biophysical and biochemical cues present in the muscle niche. This work proposes a different and simple approach to potentiate muscle regeneration exploiting the interplay between specific cell membrane receptors. The simultaneous stimulation of borate transporter, NaBC1 (encoded by SLC4A11gene), and fibronectin-binding integrins induced higher number and size of focal adhesions, major cell spreading and actin stress fibers, strengthening myoblast attachment and providing an enhanced response in terms of myotube fusion and maturation. The stimulated NaBC1 generated an adhesion-driven state through a mechanism that involves simultaneous NaBC1/?5?1/?v?3 co-localization. We engineered and characterized borax-loaded alginate hydrogels for an effective activation of NaBC1 in vivo. After inducing an acute injury with cardiotoxin in mice, active-NaBC1 accelerated the muscle regeneration process. Our results put forward a new biomaterial approach for muscle repair.PR acknowledges support from the Spanish Ministry of Science, Innovation and Universities (RTI2018096794) , and Fondo Europeo de Desarrollo Regional (FEDER) . CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors wish to thank also the intellectual and technical assistance from the ICTS "NANBIOSIS", more specifically by the Drug Formulation Unit (U10) of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) at the University of Basque Country (UPV/EHU) . The authors are grateful to A. Miralles for the credit of image of the mouse included in the graphical abstract.Ciriza, J.; Rodriguez-Romano, A.; Nogueroles, I.; Gallego Ferrer, G.; Martín Cabezuelo, R.; Pedraz, JL.; Rico Tortosa, PM. (2021). Borax-loaded injectable alginate hydrogels promote muscle regeneration in vivo after an injury. Materials Science and Engineering C: Materials for Biological Applications (Online). 123:1-14. https://doi.org/10.1016/j.msec.2021.112003S11412

Endothelial progenitor cells and integrins: adhesive needs

In the last decade there have been multiple studies concerning the contribution of endothelial progenitor cells (EPCs) to new vessel formation in different physiological and pathological settings. The process by which EPCs contribute to new vessel formation in adults is termed postnatal vasculogenesis and occurs via four inter-related steps. They must respond to chemoattractant signals and mobilize from the bone marrow to the peripheral blood; home in on sites of new vessel formation; invade and migrate at the same sites; and differentiate into mature endothelial cells (ECs) and/or regulate pre-existing ECs via paracrine or juxtacrine signals. During these four steps, EPCs interact with different physiological compartments, namely bone marrow, peripheral blood, blood vessels and homing tissues. The success of each step depends on the ability of EPCs to interact, adapt and respond to multiple molecular cues. The present review summarizes the interactions between integrins expressed by EPCs and their ligands: extracellular matrix components and cell surface proteins present at sites of postnatal vasculogenesis. The data summarized here indicate that integrins represent a major molecular determinant of EPC function, with different integrin subunits regulating different steps of EPC biology. Specifically, integrin α4β1 is a key regulator of EPC retention and/or mobilization from the bone marrow, while integrins α5β1, α6β1, αvβ3 and αvβ5 are major determinants of EPC homing, invasion, differentiation and paracrine factor production. β2 integrins are the major regulators of EPC transendothelial migration. The relevance of integrins in EPC biology is also demonstrated by many studies that use extracellular matrix-based scaffolds as a clinical tool to improve the vasculogenic functions of EPCs. We propose that targeted and tissue-specific manipulation of EPC integrin-mediated interactions may be crucial to further improve the usage of this cell population as a relevant clinical agent

Assessment of the limits of state control on the market

The main purpose of this work is to analyses government regulation of economy, to survey its policy of regulation and to give assessment. In the first part, on the grounds of scientific economical theories and ideologies of political economy, advantages and disadvantages of government intervention into economy are analyzed, as well as preconditions for such regulation. In the second part, the example of Lithuania is examined, analyzing those spheres where the regulation of market exists. In the third part, taking into consideration the contemporary economical situation, attempts to revive economy taken by the Lithuanian government are evaluated. While the economy in the whole world is facing recession, macroeconomic indicators in Lithuania are also low. As a result, this study analysis the reasons of this phenomenon and gives suggestions how to avoid it. As the problem is significant at the microeconomic level, the results of the study will help to reveal the reasons why this economic policy is ineffective. Furthermore, conclusions and suggestions at the end of this study will present methods of government regulation that could accelerate recovery from economical crisis recession. This work includes 8 charts and 24 pictures

Evangelization of Adults Within the Context of Pilgrimage and the Ways of Its Actualization in Lithuania

Šiuo darbu siekiama teoriškai ir empiriškai pagrįsti suaugusiųjų evangelizavimo reikalingumą piligriminių kelionių metu. Teorinėje dalyje pristatytos evangelizacijos ir piligrimystės sampratos bei sąsajos. Pagal Bažnyčios dokumentus bei kitą atitinkamą mokslinę literatūrą išskirta ir aptarta pagrindinė evangelizacijos reikšmė ir jos reikalingumas šiandieniniam žmogui. Taip pat aptarti bendrieji piligriminių kelionių ir turizmo aspektai, kurie atvedė į šio darbo pagrindinę problemą – nepakankamai išnaudotos galimybės evangelizuoti suaugusiuosius piligriminių kelionių metu. Empirinėje darbo dalyje pristatomas atliktas kiekybinis tyrimas, kuriame dalyvavo 54 respondentai, iš 5 skirtingų piligriminių kelionių. Apibendrinti anketinės apklausos duomenys iš dalies patvirtino išsikeltą darbo hipotezę, kad piligriminėms kelionėms gresia pavojus prarasti evangelizacijos aspektus. Baigiamojoje darbo dalyje pateikiamos išvados ir rekomendacijos piligrimams ir kelionių organizatoriams. Apibendrinus apklausos duomenis išryškėjo pagrindinė darbo išvada: sėkmingai evangelizacijai reikalingas dvasios vadovas ar kunigas, kuris kelionės metu sugebėtų sukurti laikinąją bendruomenę, kuri galėtų apsispręsti priimti Jėzų Kristų į savo gyvenimą – atsiversti. Iš apibendrintų atsakymų rezultatų matyti, kad suaugusieji yra praktikuojantys katalikai, bet maža jų dalis turi asmenį santykį su Jėzumi. Svarbiausi darbo rezultatai atskleidžia ir teoriškai pagrindžia suaugusiųjų poreikį būti evangelizuojamais piligriminių kelionių metu, bei parodo, kad pagrindiniai evangelizacijos stulpai kelionėse yra kunigai.This thesis is aiming for theoretical and empirical justification of the need of adults’ evangelization within the context of pilgrimages. The theoretical part of the thesis represents conceptions of pilgrimage an evangelization and links between these two. According to Church documents and other academic literature sources, the meaning of evangelization and the need of it for the modern-day human being is discussed in the thesis. Also, overall aspects of pilgrimages and touristic travels are discussed, which lead to the main problem of the thesis – insufficiently used potential to evangelize adults within the context of pilgrimage. In the empirical part of the thesis the analysis of quantitative research is represented, where 54 respondents of 5 different pilgrimages have participated. Generalized findings of this research partially prove hypothesis of the whole work - pilgrimages are in danger of losing the aspect of evangelization. The final part of the thesis represents findings and recommendations for pilgrims and travels’ organizers. Generalized findings of the research show the main conclusion the thesis: a spiritual leader or priest is necessary for successful evangelization, who would be able to create a temporal community during the journey that is ready to decide to accept Jesus Christ into one’s life – ready to convert. Summarized findings of the research data show that participated adults were practicing Catholics, however only a small part of them had personal relationship with Jesus. Main results of the thesis reveals and theoretically justifies adults’ need to be evangelized during pilgrimages, and shows that within the context of pilgrimage main pillars of evangelization are priests.Katalikų teologijos fakultetasVytauto Didžiojo universiteta