Search

Agnieszka Turoń-Skrzypińska,1,* Grażyna Dutkiewicz,2,* Małgorzata Marchelek-Myśliwiec,2 Aleksandra Rył,1 Violetta Dziedziejko,3 Krzysztof Safranow,3 Kazimierz Ciechanowski,2 Iwona Rotter1 1Department of Medical Rehabilitation and Clinical Rehabilitation, Pomeranian Medical University, Szczecin 71-210, Poland; 2Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin 70-111, Poland; 3Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin 70-111, Poland*These authors contributed equally to this workCorrespondence: Agnieszka Turoń-Skrzypińska Email agi.skrzypinska@gmail.comIntroduction: Chronic kidney disease and renal replacement therapy are associated with reduced motor activity, which may result in the presence of mineral bone disorders and an increase in inflammation markers. The aim of the study was to assess the relationship between the performance of daily physical activity, expressed in the number of steps performed by patients undergoing hemodialysis and the concentration of selected biochemical parameters (SCL, IL-6).Patients and Methods: The study group (B) involved 33 patients aged 59.8 ± 9.8 years from the dialysis station at the Department of Nephrology, Transplantology and Internal Medicine PUM. In group B, interventions considering an increase in physical activity expressed in the number of steps were introduced. Group C consisted of 30 people aged 54.9 (9.37), with GFR over 60 mL/min/1.73m. Physical activity was measured with pedometers. Anthropometric and biochemical parameters were assessed at baseline, after the third and sixth month of the study. Descriptive statistics, intergroup comparisons using Mann–Whitney U test and Spearman correlation analysis were performed. The level of significance was set at p≤ 0.005.Results: A relationship between IL-6 concentration and the number of steps in group B after three months of intervention was demonstrated. In group C, the concentration of SCL and IL-6 decreased with the increase in the number of steps taken. Only in group C the waist circumference decreased with the increase of the number of steps performed.Conclusion: Patients receiving renal replacement therapy by hemodialysis showed significantly lower physical activity compared to people without kidney disease. Performing bigger number of steps can lower interleukin 6 levels in hemodialysis patients.Keywords: physical activity, hemodialysis, sclerostin, interleukin 6

Gestational diabetes mellitus ( GDM) is a metabolic disorder that occurs during pregnancy. HHEX and PROX1 are genetic loci associated with diabetes mellitus type 2. HHEX and PROX1 play significant roles in carbohydrate intolerance and diabetes because these transcription factors may be involved in the regulation of insulin secretion and in glucose and lipid metabolism. The aim of this study was to examine the association between HHEX (rs5015480) and PROX1 (rs340874) gene polymorphisms and GDM. This study included 204 pregnant women with GDM and 207 pregnant women with the normal glucose tolerance ( NGT). The diagnosis of GDM was based on a 75-g oral glucose tolerance test at 24-28 weeks' gestation. There was a statistically significant prevalence of the HHEX rs5015480 CC genotype and C allele among women with GDM (C vs T allele, p = 0.021, odds ratio OR = 1.40, 95% CI: 1.05-1.87). Statistically significant higher increase of body mass and BMI during pregnancy was found in women with the HHEX rs5015480 CC genotype. The results of our study suggest an association between the HHEX gene rs5015480 polymorphism and risk of GDM. The HHEX gene rs5015480 C allele may be a risk allele of GDM that is associated with increased BMI during pregnancy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Post-transplant diabetes mellitus (PTDM) is a common complica- tion after organ transplantation which leads to impaired graft function. Various factors may increase the risk of the development of PTDM. It has been reported that cytokines and genetic variations of inflammatory cytokines were associated with glucose homeostasis or diabetes. The pro-inflammatory cytokine IL-17, which is produced by T-helper 17 (Th17) cells, has been reported to be involved in the glucose metabolism and pathogenesis of diabetes via the induction of low-grade inflammation. The aim of this study was to examine the association between polymorphisms in the IL17A (rs2275913) and IL17F (rs11465553, rs2397084, rs763780) genes with post-transplant diabetes mellitus. PATIENTS AND METHODS: The study included 169 patients of Caucasian origin who received kidney transplants. For the purpose of the study, the patients were subdivided into two subgroups: patients with PTDM (n = 23) and patients without PTDM (n = 146). Standard immunosuppression consisted of tacrolimus, mycophenolate mofetil, and steroids. RESULTS: Post-transplant diabetes was diagnosed in 10.97% of the carriers of the IL17F rs763780 TT genotype and 42.86% of those with the TC genotype (TC vs TT: OR = 6.09, 95% CI 1.89-19.66, p = 0.0048). In multivariate analysis, older recipient age and the presence of the TC genotype were independent significant predictors of higher risk of post-transplant diabetes. CONCLUSIONS: The results of this study suggest an association between the IL17F rs763780 polymorphism and post-transplant diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Methotrexate (MTX) in low doses is used in the therapy of rheumatoid arthritis (RA).The aim of many studies is to identify factors predicting the outcome of treatment with methotrexate in rheumatoid arthritis. The action of MTX in RA is associated with the inhibition of inflammatory mediators synthesis. CXCL9 and CXCL10 chemokines play the important role in inflammatory response in RA patients. The aim of this study was to examine the association between CXCL9/10 gene polymorphisms and response to therapy of RA patients with MTX. PATIENTS AND METHODS: The study included 422 patients diagnosed with rheumatoid arthritis, treated with MTX in doses 20 mg weekly. Good responders were defined as patients who were receiving MTX and had a DAS28 of ≥ 2.5 at 6 months of therapy. Poor-re-sponders were defined as patients who were receiving MTX and had a DAS28 of > 2.5. RESULTS: There were not statistically significant associations between studied polymorphisms and the outcome of rheumatoid arthritis treatment with methotrexate. CONCLUSIONS: The results of this study suggest lack of associations between the polymorphisms in CXCL9 and CXCL10 genes and the response to MTX in RA patients. [ABSTRACT FROM AUTHOR]

Studies on mixed chimerism are currently focused primarily on obtaining less toxic conditioning protocols. With these issues in mind, we have undertaken the attempt to optimize the procedure of mixed chimerism induction in mice. In order to reduce toxicity, we used decreasing doses of total body irradiation (TBI) together with combination of blocking antibodies. We also tried to eliminate immunosuppression (cyclophosphamide - CP) treatment after bone marrow transplantation. B6.SJL-PtprcaPep3b mice were injected with 20-30 × 106 bone marrow cells from Balb C mice. Mice were treated with TBI (3 - 1.5 - 0 Gy) on "-1" day of the experiment and blocking antibodies against CD40L ("0", and "4" days) and additionally anti-CD8 ("-2" day) and/or anti-NK1.1 ("-3" day). Mice in certain groups also received CP (175 mg/kg) on "2" day. Presence of mixed chimerism was assessed in peripheral blood cells by flow cytometry on the 1st, 2nd, 3rd, 4th, 6th and 8th weeks of the experiment by detecting of CD45.1 (characteristic for B6.SJL-PtprcaPep3b strain) and CD45.2 (characteristic for Balb C strain) antigens expression. We also analyzed the percentage of peripheral blood CD8 T-cells (CD3e/CD8a) and NK cells (Ly-49D/NK1.1). We found that reduction of TBI dose and elimination of CP decrease the rate of mixed chimerism formation. The highest percentage of donor cells was obtained in the group of animals treated with 3 Gy of TBI, CP and combination of anti-CD40L, anti-CD8, and anti-NK1.1 antibodies. The 3 Gy TBI was necessary to induce stable mixed chimerism, but it could be obtained without the CP use. The percentage of CD3e/CD8a and Ly-49D/NK1.1 cells was significantly lower in the groups of mice treated by corresponding antibodies. Moreover, we observed the lowest number of peripheral blood Ly-49D/NK1.1 cells in the group of animals with highest mixed chimerism. Our experiments in mice model can help in better understanding of mixed chimerism phenomenon and in selecting the method of mixed chimerism induction with lowest possible toxicity. This also might improve the protocols of stable mixed chimerism induction in humans, and in the future, the effectiveness of vascularized organ transplantation. [ABSTRACT FROM AUTHOR]

Abstract: Many reports show that red blood cells of people exposed to lead have a decreased ATP concentration, decreased adenylate energy charge value and many metabolic and morphological abnormalities. Since the synthesis of nucleotides in erythrocytes occurs only through salvage pathways, we hypothesized that a decrease in nucleotide concentrations may be caused by lead-induced inhibition of erythrocyte phosphoribosyltransferases: adenine APRT (EC 2.4.2.7) and hypoxanthine-guanine HPRT (EC 2.4.2.8). These enzymes enable the reutilization of purine bases (adenine, guanine, hypoxanthine) converting them to mononucleotides (AMP, GMP, IMP), substrates for the synthesis of high-energy nucleotides. To confirm the hypothesis two experiments were performed: (i) in vitro, using a lysate of human erythrocytes incubated (5, 10, 30min) with lead ions (100μM, 10μM, 1μM, 500nM, 100nM lead acetate) and 100μM sodium acetate for the control, (ii) in vivo, using a lysate of rat erythrocytes taken from rats chronically exposed to lead (0.1% lead acetate in drinking water for 9 months, resulting in whole blood lead concentration 7μg/dL). The activities of APRT and HPRT were determined using HPLC method, which allowed concurrent determination of the activity of both enzymes in erythrocyte lysates. We have shown that, lead ions: (i) moderately inhibit both phosphoribosyltransferases in erythrocytes, this influence being detectable even at very low concentrations (ii) participate in hemolysis, the intensity of which negatively correlates with the activity of phosphoribosyltransferases. Our results indicate the necessity of further research on the role of lead-induced APRT and HPRT inhibition as one of the mechanisms of lead toxicity. [Copyright &y& Elsevier]

The objective of this study was to assess the effect of conjugated linoleic acid isomers (CLAs) on the expression and activity of phospholipases A(2) (PLA(2)) in human macrophages.Macrophages were incubated with 30 microM cis-9, trans-11 and trans-10, cis-12 CLAs for 48 h. After incubation, the total activity of phospholipases as well as the expression of mRNA for cytosolic (cPLA(2)) and secretory (sPLA(2)) phospholipases and activity of sPLA(2) were measured.Both CLA isomers reduced the total activity of PLA(2) (by 30.2%, P < 0.01 for cis-9, trans-11 CLA and by 30%, P < 0.001 for trans-10, cis-12 CLA). Trans-10, cis-12 CLA isomer downregulated the expression of mRNA of sPLA(2) and decreased the enzymatic activity of this enzyme (by 23%, P = 0.02) in macrophages.Conjugated linoleic acid isomers can significantly reduce the activity of PLA(2) in macrophages and downregulate sPLA(2) expression. The consequence of this effect may be reduction of releasing the arachidonic acid (AA) from the cellular membranes of macrophages. [ABSTRACT FROM AUTHOR]

Abstract Background The frequency of preterm labour has risen over the last few years. Hence, there is growing interest in the identification of markers that may facilitate prediction and prevention of premature birth complications. Here, we studied the association of the number of circulating stem cell populations with the incidence of complications typical of prematurity. Methods The study groups consisted of 90 preterm (23–36 weeks of gestational age) and 52 full-term (37–41 weeks) infants. Non-hematopoietic stem cells (non-HSCs; CD45-lin-CD184+), enriched in very small embryonic-like stem cells (VSELs), expressing pluripotent (Oct-4, Nanog), early neural (β-III-tubulin), and oligodendrocyte lineage (Olig-1) genes as well as hematopoietic stem cells (HSCs; CD45+lin-CD184+), and circulating stem/progenitor cells (CSPCs; CD133+CD34+; CD133-CD34+) in association with characteristics of prematurity and preterm morbidity were analyzed in cord blood (CB) and peripheral blood (PB) until the sixth week after delivery. Phenotype analysis was performed using flow cytometry methods. Clonogenic assays suitable for detection of human hematopoietic progenitor cells were also applied. The quantitative parameters were compared between groups by the Mann–Whitney test and between time points by the Friedman test. Fisher’s exact test was used for qualitative variables. Results We found that the number of CB non-HSCs/VSELs is inversely associated with the birth weight of preterm infants. More notably, a high number of CB HSCs is strongly associated with a lower risk of prematurity complications including intraventricular hemorrhage, respiratory distress syndrome, infections, and anemia. The number of HSCs remains stable for the first six weeks of postnatal life. Besides, the number of CSPCs in CB is significantly higher in preterm infants than in full-term neonates (p Conclusion We conclude that CB HSCs are markedly associated with the development of premature birth complications. Thus, HSCs ought to be considered as the potential target for further research as they may be relevant for predicting and controlling the morbidity of premature infants. Moreover, the observed levels of non-HSCs/VSELs circulating in CB are inversely associated with the birth weight of preterm infants, suggesting non-HSCs/VSELs might be involved in the maturation of fetal organism.

Solid organ transplantation is a life-saving treatment for patients with end-stage organ failure, but it poses unique challenges due to metabolic and immunological changes in recipients. One significant complication is post-transplant diabetes mellitus (PTDM), which affects a variety of solid organ recipients. Leptin, a hormone produced by adipose tissue, regulates appetite and affects glucose metabolism. High leptin levels are associated with the development of PTDM, especially in kidney transplant recipients. Adiponectin, another adipokine, increases insulin sensitivity and has anti-diabetic properties. Low adiponectin levels are associated with insulin resistance and increase the risk of PTDM. As the incidence of PTDM increases due to the increased life expectancy among transplant patients, understanding the role of adipokines such as leptin and adiponectin becomes crucial for early detection and treatment. Additional studies on other adipokines may also provide valuable information on the pathogenesis of PTDM., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)