Zastosowanie terapii komórkowych w leczeniu cukrzycy typu 1

Nowadays, an increase in new cases of type 1 diabetes has been observed. Therefore, the researchers and physicians have been working on new drugs that could stop development of type 1 diabetes or cure the existing disease. The results of cellular therapies based on stem cells, regulatory T-cells or pancreatic islets are promising. All procedures improve glycaemic control, and some of them eliminate the need for supply of exogenous insulin for a long term.Współcześnie obserwujemy wyraźny wzrost liczby zachorowań na cukrzycę typu 1. Z tego względu naukowcy oraz lekarze pracują and nowymi terapiami, które pozwoliłyby zatrzymać rozwój lub całkowicie wyleczyć z cukrzycy typu 1. Wyniki terapii komórkowych z zastosowaniem komórek macierzystych, limfocytów T regulatorowych oraz wysp trzustkowych są obiecujące. Wszystkie poprawiają kontrolę glikemii, a niektóre z nich pozwalają na uzyskanie nawet długoterminowej niezależności od egzogennej insuliny

Mild hypothermia provides Treg stability

Regulatory T cells (Tregs) play crucial role in maintenance of peripheral tolerance. Recent clinical trials confirmed safety and efficacy of Treg treatment of deleterious immune responses. However, Tregs lose their characteristic phenotype and suppressive potential during expansion ex vivo. Therefore, multiple research teams have been studding Treg biology in aim to improve their stability in vitro. In the current paper, we demonstrate that mild hypothermia of 33 °C induces robust proliferation of Tregs, preserves expression of FoxP3, CD25 and Helios, and prevents TSDR methylation during culture in vitro. Tregs expanded at 33 °C have stronger immunosuppressive potential and remarkably anti-inflammatory phenotype demonstrated by the whole transcriptome sequencing. These observations shed new light on impact of temperature on regulation of immune response. We show that just a simple change in temperature can preserve Treg stability, function and accelerate their proliferation, responding to unanswered question- how to preserve Treg stability in vitro

Mast cell derived carboxypeptidase A3 is decreased among patients with advanced coronary artery disease

Background: Coronary artery disease (CAD) affects milions of people and can result in myocardialinfarction (MI). Previously, mast cells (MC) have been extensively investigated in the context of hypersensitivity,however as regulators of the local inflammatory response they can potentially contribute toCAD and/or its progression. The aim of the study was to assess if serum concentration of MC proteases:carboxypeptidase A3, cathepsin G and chymase 1 is associated with the extension of CAD and MI.Methods: The 44 patients with angiographically confirmed CAD (23 subjects with non-ST-segmentelevation MI [NSTEMI] and 21 with stable CAD) were analyzed. Clinical data were obtained as wellserum concentrations of carboxypeptidase A3, cathepsin G and chymase 1 were also measured.Results: Patients with single vessel CAD had higher serum concentration of carboxypeptidase thanthose with more advanced CAD (3838.6 ± 1083.1 pg/mL vs. 2715.6 ± 442.5 pg/mL; p = 0.02). Therewere no significant differences in levels of any protease between patients with stable CAD and those withNSTEMI. Patients with hypertension had ≈2-fold lower serum levels of cathepsin G than normotensiveindividuals (4.6 ± 0.9 pg/mL vs. 9.4 ± 5.8 pg/mL; p = 0.001). Cathepsin G levels were also decreasedin sera of the current smokers as compared with non-smokers (3.1 ± 1.2 ng/mL vs. 5.8 ± 1.2 ng/mL,p = 0.02).Conclusions: Decreased serum level of carboxypeptidase is a hallmark of more advanced CAD. Lowerserum levels of carboxypeptidase A3 and catepsin G are associated with risk factors of blood vessel damagesuggesting a protective role of these enzymes in CAD

Treatment of Graft-versus-Host Disease with Naturally Occurring T Regulatory Cells

A significant body of evidence suggests that treatment with naturally occurring CD4(+)CD25(+) T regulatory cells (Tregs) is an appropriate therapy for graft-versus-host disease (GvHD). GvHD is a major complication of bone marrow transplantation in which the transplanted immune system recognizes recipient tissues as a non-self and destroys them. In many cases, this condition significantly deteriorates the quality of life of the affected patients. It is also one of the most important causes of death after bone marrow transplantation. Tregs constitute a population responsible for dominant tolerance to self-tissues in the immune system. These cells prevent autoimmune and allergic reactions and decrease the risk of rejection of allotransplants. For these reasons, Tregs are considered as a cellular drug in GvHD. The results of the first clinical trials with these cells are already available. In this review we present important experimental facts which led to the clinical use of Tregs. We then critically evaluate specific requirements for Treg therapy in GvHD and therapies with Tregs currently under clinical investigation, including our experience and future perspectives on this kind of cellular treatment

Cytokine Imprint in Preeclampsia

The hallmark of preeclampsia (PE) is a shift toward persistent inflammatory response, accompanied by endothelial dysfunction. The driving forces in PE are proinflammatory cytokine and growth factors, in parallel with reduced functionality of anti-inflammatory effectors, like regulatory T cells are observed. Unfortunately, no conclusive mechanism underlying preeclampsia has been identified. For this reason, research on preeclampsia is needed to provide a state of the art understanding of the pathophysiology, identification of new diagnostics tools and the development of targeted therapies. The 68 patients were divided into three groups: gestational hypertension (GH) group (n = 19) and PE group (n = 28) and a control group (n = 21). We have tested a set of 53 cytokines, chemokines and growth factors in preeclampsia and gestational hypertension, and then compared them with normal pregnancies. Using a diagnostic test assessment characteristic parameters (IL-22, MDC/CCL22, IL-2/IL-4 ratio) have been identified and cut-off values have been proposed to diagnose preeclampsia. All parameters had high negative or positive predictive values, above 80%. In conclusion, we have proposed a potential set of immune parameters to diagnose preeclampsia

Beyond FOXP3:a 20-year journey unravelling human regulatory T-cell heterogeneity

The initial idea of a distinct group of T-cells responsible for suppressing immune responses was first postulated half a century ago. However, it is only in the last three decades that we have identified what we now term regulatory T-cells (Tregs), and subsequently elucidated and crystallized our understanding of them. Human Tregs have emerged as essential to immune tolerance and the prevention of autoimmune diseases and are typically contemporaneously characterized by their CD3+CD4+CD25high CD127lowFOXP3+ phenotype. It is important to note that FOXP3+ Tregs exhibit substantial diversity in their origin, phenotypic characteristics, and function. Identifying reliable markers is crucial to the accurate identification, quantification, and assessment of Tregs in health and disease, as well as the enrichment and expansion of viable cells for adoptive cell therapy. In our comprehensive review, we address the contributions of various markers identified in the last two decades since the master transcriptional factor FOXP3 was identified in establishing and enriching purity, lineage stability, tissue homing and suppressive proficiency in CD4+ Tregs. Additionally, our review delves into recent breakthroughs in innovative Treg-based therapies, underscoring the significance of distinct markers in their therapeutic utilization. Understanding Treg subsets holds the key to effectively harnessing human Tregs for immunotherapeutic approaches

Perinatal and neonatal outcome in patients with preeclampsia

Objectives: Preeclampsia (PE) affects 2–5% of pregnant women. Hypertensive disorders of pregnancy are associated with adverse maternal and perinatal outcomes. Material and methods: This study included 88 women showing gestational hypertension (GH) or PE symptoms, and their newborns. Results: The rate of FGR was 43% for mothers with PE, compared to 8% with GH. The association was significant, p = < 0.001 but with moderate strength, Cramer’s V = 0.40. The risk of FGR increased nine times when PE occurred, as the odds ratio was 9.25 (CI: 2.46–34.83), p = 0.001. PE was associated with FGR risk if delivery time was less than 34 weeks compared to a delivery time of more than 34 weeks. This was 82% of FGR cases for < 34 weeks, compared with 35% of cases in > 34 group, (p = 0.001; Cramer’s V = 0.50). PE was also associated (p = 0.01, Cramer’s V = 0.27) with the type of delivery, as the caesarean section rate was 74%, compared to 50% in the GH group. This made it three times higher the likelihood of delivery by caesarean section, as the odds ratio was 3.10 (CI: 1.24–7.75), p=0,02. Delivery time was significantly (p < 0.001) shortened to 38 weeks (27–41), compared to 40 weeks (38–42) GH mothers. There was no distinction in median age for PE and GH mothers (p = 0.124). The overall clinical status of neonates was proportional despite the mother’s PE. The sum of Apgar points in the first, and then the second to third minute, did not differ significantly, p = 0.370 and 0.560, respectively. The number of peripheral blood platelets and leucocytes was not reduced (p = 0.821 and 0.534) in infants when the mother suffered from PE. Conclusions: The prediction of adverse maternal outcomes from hypertensive diseases of pregnancy is key to optimal management, including the timing of delivery and planning for the most appropriate place of care.

A new class of exact solutions of the Schrodinger equation

The aim of this paper is to find the exact solutions of the Schrodinger equation. As is known, the Schrodinger equation can be reduced to the continuum equation. In this paper, using the non-linear Legendre transform the equation of continuity is linearized. Particular solutions of such a linear equation are found in the paper and an inverse Legendre transform is considered for them with subsequent construction of solutions of the Schrodinger equation. Examples of the classical and quantum systems are considered.Comment: 26 pages, 34 figure