Excessive BMI is associated with higher C-peptide level at recognition but also with its greater loss in two years clinical observation in children with new onset type 1 diabetes

IntroductionThe prevalence of obesity in general pediatric population increases without sparing children with T1D. We intended to find factors associated with the possibility of preserving endogenous insulin secretion in individuals with long-standing T1D. At onset, higher BMI is associated with higher C-peptide level, which may indicate to be one of the favorable factors involved in preserving residual β-cell function. The study determines the influence of BMI on C-peptide secretion in children newly diagnosed with T1D in two years observation.MethodsWe assessed the possible relationship between selected pro- and anti-inflammatory cytokines, body mass at recognition and β-cell function status. 153 pediatric patients with newly diagnosed T1D were divided into quartiles according to BMI-SDS index. We separated a group consisted of patients with BMI-SDS >1. Participants were followed up for two years and examined for changes in body weight, HbA1c, and insulin requirement. C-peptide was assessed at baseline and after two years. We evaluated the patients’ levels of selected inflammatory cytokines at baseline.ResultsSubjects with higher BMI-SDS presented higher serum C-peptide levels and lower insulin requirements at diagnosis than children with lower body weight. The two-year follow-up showed that C-peptide levels of obese patients dropped more rapidly than in children with BMI-SDS within normal limits. The group with BMI-SDS >1 showed the greatest decrease in C-peptide level. Despite statistically insignificant differences in HbA1c at diagnosis between the study groups, in the fourth quartile and BMI-SDS >1 groups, HbA1c as well as insulin requirements increased after two years. The levels of cytokines varied the most between BMI-SDS <1 and BMI-SDS >1 groups and were significantly higher within BMI-SDS >1 group.DiscussionHigher BMI, associated with enhanced levels of inflammatory cytokines, relates to preservation of C-peptide at T1D recognition in children but is not beneficial in the long term. A decrease in C-peptide levels combined with an increase in insulin requirements and in HbA1c among patients with high BMI occur, which may indicate a negative effect of excessive body weight on the long term preservation of residual β-cell function. The process seems to be mediated by inflammatory cytokines

The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung

Mesenchymal stem cells (mesenchymal stromal cells; MSC)-based therapies remain a promising approach to treat degenerative and inflammatory diseases. Their beneficial effects were confirmed in numerous experimental models and clinical trials. However, safety issues concerning MSCs’ stability and their long-term effects limit their implementation in clinical practice, including treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease, and COVID-19. Here, we aimed to investigate the safety of intranasal application of human adipose tissue-derived MSCs in a preclinical experimental mice model and elucidate their effects on the lungs. We assessed short-term (two days) and long-term (nine days) effects of MSCs administration on lung morphology, immune responses, epithelial barrier function, and transcriptomic profiles. We observed an increased frequency of IFNγ- producing T cells and a decrease in occludin and claudin 3 as a long-term effect of MSCs administration. We also found changes in the lung transcriptomic profiles, reflecting redox imbalance and hypoxia signaling pathway. Additionally, we found dysregulation in genes clustered in pattern recognition receptors, macrophage activation, oxidative stress, and phagocytosis. Our results suggest that i.n. MSCs administration to noninflamed healthy lungs induces, in the late stages, low-grade inflammatory responses aiming at the clearance of MSCs graft

Regulatory B Cells Involvement in Autoimmune Phenomena Occurring in Pediatric Graves’ Disease Patients

Graves’s disease is the most common type of autoimmune hyperthyroidism. Numerous studies indicate different factors contributing to the onset of the disease. Despite years of research, the exact pathomechanism of Graves’ disease still remains unresolved, especially in the context of immune response. B cells can play a dual role in autoimmune reactions, on the one hand, as a source of autoantibody mainly targeted in the thyroid hormone receptor (TSHR) and, on the other, by suppressing the activity of proinflammatory cells (as regulatory B cells). To date, data on the contribution of Bregs in Graves’ pathomechanism, especially in children, are scarce. Here, we investigated the frequencies of Bregs before and during a methimazole therapy approach. We reported higher Foxp3+ and IL-10+ Breg levels with CD38- phenotype and reduced numbers of CD38 + Foxp3 + IL-10+ in pediatric Graves’ patients. In addition, selected Breg subsets were found to correlate with TSH and TRAb levels significantly. Noteworthy, certain subpopulations of Bregs were demonstrated as prognostic factors for methimazole therapy outcome. Our data demonstrate the crucial role of Bregs and their potential use as a biomarker in Graves’ disease management

Evaluating the Role of Circulating Dendritic Cells in Methimazole-Treated Pediatric Graves’ Disease Patients

Graves’ disease (GD) is hyperthyroidism associated with organ-specific autoimmune inflammation. GD occurs more frequently in adults than in children; however, pediatric patients are a therapeutic challenge due to cycles of remissions and relapses requiring constant monitoring at every stage of treatment administered. Dendritic cells (DCs) are considered to be a link between innate and adaptive immunity. DCs, as antigen-presenting cells (APCs), are involved in antigen presentation to T lymphocytes, thereby initiating a shift towards effector cells. In accordance, DCs also participate in the modulation of tolerance to specific antigens. To date, the data on DCs’ role in Graves’ pathological processes are scarce. Therefore, here, we evaluated the frequencies and role of circulating DCs in GD pediatric patients treated with methimazole. Flow cytometric analysis was implemented to evaluate three subsets of dendritic cells and their correlation with clinical GD-related parameters. We found significantly higher levels of DC subsets in patients at diagnosis. Furthermore, methimazole treatment seemed to effectively reduce subsets of DCs, which, in addition, were found to differentially correlate with thyroid function. Our study shed new light on DCs’ role in the pediatric GD pathomechanism. Further studies are required for the mechanistic assessment of DCs’ exact role in disease progression and influence on thyroid function

Lower proportion of CD19+IL-10+ and CD19+CD24+CD27+ but not CD1d+CD5+CD19+CD24+CD27+ IL-10+ B cells in children with autoimmune thyroid diseases

Introduction: As it is generally known, regulatory B cells (Bregs) control inflammation and autoimmunity. The significance of Bregs in the population of children with autoimmune thyroid diseases (AITD) still offers plenty of potential to explore. The aim of this study was to estimate the expression of Bregs (phenotype CD19+CD24+CD27+IL-10+, CD19+IL-10+, CD1d+CD5+CD19+IL-10+ and CD1d+CD5+CD19+CD24+CD27+) in a paediatric cohort with AITD and in health controls. Materials and methods: A total of 100 blood samples were obtained from 53 paediatric patients with Graves’ disease (GD) (N = 12 newly diagnosed, mean age 12.5 ± 3.5 and N = 17 during methimazole therapy, mean age 12.7 ± 4.4), Hashimoto’s thyroiditis (HT) (N = 10 newly diagnosed, mean age 13.3 ± 2.9 and N = 10 during L-thyroxine therapy, mean age 13.7 ± 3.4) and compared with healthy controls (C) (N = 15, mean age 13.1 ± 3.1). The expressions of the immune cell populations were analysed by four-color flow cytometry using a FASC Canto II cytometer (BD Biosciences). Results: There was a decreasing tendency in the number of lymphocytes B producing IL-10 (B10) cells among all B lymphocytes and more widely, also among all lymphocytes, in each study group, as compared to C. We reported a reduction in IL-10 production in Bregs with the expression of CD19+CD24+CD27+IL-10 and CD1d+CD5+CD19+IL-10+ in both untreated and treated AITD. Conclusions: Our data demonstrate that the reduction in the number of Bregs with CD19+CD24+CD27+IL-10+ and CD19+IL-10+ expression could be responsible for breaking immune tolerance and for AITD development in children

MMP-1, UCH-L1, and 20S Proteasome as Potential Biomarkers Supporting the Diagnosis of Brain Glioma

The diagnosis of brain gliomas is mainly based on imaging methods. The gold standard in this area is MRI. Recommendations for the prevention, diagnosis, and treatment of gliomas are periodically modified and updated. One of the diagnostic techniques used when a brain glioma is suspected is liquid biopsy. However, this technique requires further development to confirm its effectiveness. This paper presents a proposal of three potential biomarkers of brain gliomas—extracellular matrix metalloproteinase-1 (MMP-1), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and the 20S proteasome—which were quantified in blood plasma using SPRi biosensors. A statistical analysis of the results indicated no significant changes in the concentrations between the control group (K) and grades G1 and G2, and similarly between grades G3 and G4. However, the differences in the concentrations between the groups K/G1/G2 and G3/G4 were statistically significant. A positive average correlation was found between the concentrations of the proteins and the patient’s age. The individual tested proteins were also highly correlated with each other. Our work proposes a new diagnostic technique that may aid in the diagnosis of brain gliomas

Cathepsin B, D and S as Potential Biomarkers of Brain Glioma Malignancy

Brain gliomas constitute the vast majority of malignant tumors of the nervous system. There is still a lack of fast, reliable and non-invasive methods of diagnostics. Our work focuses on the quantification of cathepsin B, D and S in glioma. The research was conducted with the use of SPRi biosensors sensitive to individual cathepsins. Changes in the quantity of selected cathepsins (cathepsins B, D and S), depending on the advancement of glioma and the presence or absence of important features or comorbidities in the selected patient, were examined. The results were statistically analyzed and interpreted based on the available clinical description. Statistical significance was observed in the difference in the concentration of the studied cathepsins, mainly between the groups Control and G3/G4 and G1/G2 and G3/G4. The strength of the correlation between the concentrations of individual cathepsins and the age of the patient and the size of the tumor, as well as the correlation between individual proteins, was investigated. The influence of IDH 1/2 status on the concentration of determined cathepsins was investigated and ROC analysis was performed. As a result of our research, we have developed a method for the diagnosis of brain glioma that allows us to distinguish grades G1/G2 from G3/G4 and the control group from G3/G4. We found an average positive correlation between the concentrations of the proteins tested and the age of the patient and a high positive correlation between the cathepsins tested. Comparative analysis of the effect of the presence of IDH 1/2 mutations on the number of proteins tested allowed us to demonstrate that the cathepsins assayed can be independent markers

Situation of Pediatric Patients with Testicular Torsion in Times of COVID-19

Purpose. To assess whether the COVID-19 pandemic had an influence on presentation of testicular torsion and/or increase in the frequency of orchiectomy. Patients and Methods. This retrospective study included boys under 18 years of age with testicular torsion divided in two groups: pre-COVID operated in 2019 vs. COVID-19 group from 2020. We compared demographic data as well as local and general symptoms. We analyzed additional tests, intraoperative findings, length of operation and hospitalization, and followup. Results. We analyzed the data collected from 44 patients (24 boys from first group vs. 20 boys from second group). The median age was 13.4 years vs. 14.5 years in the latter. The median time of symptoms duration was 6.5 hours and 8.5 hours, respectively. The main manifestation was testicular pain without additional signs. The results of the laboratory tests did not reflect local advancement. In the 2019 group, Doppler ultrasound showed absent blood flow in the affected testicle in 62% vs. 80% in 2020. The mean time from admission to surgery was virtually identical: 75 minutes in 2019 vs. 76 minutes in 2020. The mean duration of scrotal revision was similar in both groups. There was only one significant difference: the degree of twisting. In 2019, the mean was 360° vs. 540° in 2020. Incidence of orchiectomy also did not significantly vary between the analyzed time periods, with 21% during the pandemic and 35% during the pre-COVID-19 period. Conclusion. We did not observe an increase in the number of testicular torsion cases during the COVID-19 pandemic. Most importantly, the rates of orchiectomy did not significantly differ between the patients with testicular torsion presenting during the COVID-19 outbreak

Laminin-5, Fibronectin, and Type IV Collagen as Potential Biomarkers of Brain Glioma Malignancy

The presented work is based on the quantification of LN-5, FN, and COL IV in blood plasma as potential biomarkers in patients diagnosed with glioma in grades G1 to G4. The obtained concentration results were compared with the protein content in the control group, which consisted of smokers of different ages. The obtained results were statistically analysed and interpreted based on the available clinical description. Quantitative determinations of LN-5, FN, and COL IV were performed with the use of SPRi biosensors specific to the tested proteins. Comparing groups K and G4, as well as G2 and G4, statistically significant relationships between changes in the concentration of individual proteins, were observed. The analysis showed significant correlations between FN and LN-5, between FN and COL IV, and between LN-5 and COL IV. There was a moderate positive correlation between individual proteins and the age of the patient. The ROC analysis distinguished patients with advanced disease from the control group. The results of the research show that LN-5, FN, and COL IV are effective biomarkers of brain glioma that may be helpful in non-invasive diagnosis and determining the grade of the disease