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Accumulated evidence suggest that the adverse outcome of severe coronavirus disease 2019 (COVID-19) is closely related to prothrombotic microvascular pathology with a high risk of venous thromboembolism. Furthermore, the first observational studies indicated that adjunct therapy with low-molecular weight heparin (LMWH) was associated with lower mortality in this cohort of patients. However, the timing of starting LMWH and the dose remain controversial in COVID-19 patients. Considering the above, the aim of this study was to reveal the rationale for using LMWH in the therapy of symptomatic COVID-19 patients based on experimental and clinical studies on LMWH in inflammatory settings with special consideration given to randomized trials.

Introduction: The interleukin-12/23 (IL-12/23) signalling pathway plays an important role in the pathogenesis of psoriasis. In addition, even molecularly targeted therapy has been reported to lose adequate response to treatment. Aim: To determine the expression patterns of mRNAs and miRNAs related to IL-12/23 signalling pathways in the human keratinocyte culture exposed to liposaccharide A (LPS) and then adalimumab in comparison with untreated cells. Material and methods: Human, adult, low-Calcium, high-Temperature keratinocyte (HaCaT) cultures were exposed to 1 µg/ml LPS for 8 h, and then adalimumab was added to the cultures at a concentration of 8 µg/ml and incubated for 2, 8, and 24 h. We used mRNA and miRNA microarray, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay techniques. Results: STAT1, STAT3, STAT5, IL-6, IL-6R, SOCS3, and JAK3 genes differentiated HaCaT cultures with the drug from controls regardless of the time the cells were exposed to the drug. The addition of adalimumab to a culture previously exposed to LPS resulted in silencing of SOCS3 and IL-6 expression compared to the control, while for the other transcripts they were found to be overexpressed compared to the control culture. The assessment indicated the strongest connections between JAK3 and hsa-miR-373-5p (target score 96); SOCS3, STAT5, and hsa-miR-1827 (target score 96). Conclusions: Our study indicates that adalimumab has the strongest modulating effect on mRNA and miRNA expression of JAK/STAT and IL-6-dependent IL-12/23 pathways. [ABSTRACT FROM AUTHOR]

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The aim of this study was to characterise the expression of cell adhesion molecules (CAMs) and HLA antigens in biopsy specimens patients with two clinical suspected myocarditis. Study group consisted of 47 randomly selected patients (pts) classified in two groups based on left ventricular ejection fraction (LVEF): A - 29 pts, with LVEF £ 30% (24M, 5F, mean age 39±6) and B - 18 pts with LVEF >40% (15M, 3F, mean age 38±7). The expression of HLA class I (A,B,C) and II (DR) antigens and CAMs on frozen sections were examined using a Leica Bond Max autostainer (BOND Polymer Refine Red Detection; DS9390; Leica Biosystems) and monoclonal antihuman antibodies (HLA-DR, HLA-ABC, ICAM-1 and VCAM-1 from DAKO). The semiquantitative scoring system was defined as follows: 0-1, absent or slight focal staining of the endothelium; 2+, diffuse endothelial staining, 3+, diffuse endothelial and concomitant focal myocyte staining. The routine histopathological study was performed with hematoxylin & eosin and Masson trichrome stain. The data were analysed by a Mann-Whitney U test and Spearman R correlation coefficient test. A p value of <0.05 was statistically significant. The expression of HLA-DR antigens > 2+ was seen in the 17 (59%) pts in Gr. A and 12 (67%) in Gr. B. The expression of the HLA-A,B,C antigens was observed in the 11 (38%) and 12 (67%) pts, respectively. ICAM-1 and VCAM-1 immunoreactivity > 2+ was seen: ICAM-1, Gr. A - 12 (41%) and Gr. B - 9 (50%); VCAM-1, Gr. A - 6 (21%) and Gr. B - 9 (50%). There was no statistical differences between both groups and there was no relationship between LVEF and HLA-DR, HLAABC, ICAM-1 and VCAM-1 immunoreactivity. The lack relationship between positive staining for HLA antigens and CAMs in two groups of pts with clinically suspected myocarditis (with and without symptomatic congestive heart failure) indicates on independence of immunological reactions in myocardium. [ABSTRACT FROM AUTHOR]

Background: Growth differentiation factor-15 (GDF-15) is a hormone that regulates inflammatory responses, tissue repair, and cardiac remodeling, the three key processes underlying the development and progression of heart failure (HF). Furthermore, GDF-15 integrates information from cardiac and extracardiac disease pathways that are linked to multiorgan dysfunction in advanced stages of HF., Aim: This study aimed to determine which factors are associated with one-year mortality in patients with end-stage HF, with particular emphasis on GDF-15., Methods: We prospectively analyzed 315 consecutive hospitalized patients with end-stage HF who underwent heart transplantation evaluation between 2018 and 2022. The endpoint was all-cause mortality during one-year follow-up. We measured routine laboratory parameters and the serum GDF-15 concentration using a sandwich enzyme-linked immunosorbent assay (ELISA) (SunRedBio Technology Co, Ltd, Shanghai, China)., Results: The median age of the patients was 57 (50-62) years. During follow-up, 97 patients died. Higher serum concentrations of GDF-15 (hazard ratio [HR], 1.119; 95% CI, 1.095-1.144; P <0.001), high-sensitivity C-reactive protein (HR, 1.140; 95% CI, 1.037-1.253; P = 0.006), fibrinogen (HR, 1.003; 95% CI, 1.001-1.005; P = 0.003), bilirubin (HR, 1.055; 95% CI, 1.027-1.084; P <0.001), N-terminal pro-B-type natriuretic peptide (HR, 1.342; 95% CI, 1.206-1.493; P <0.001), and gamma-glutamyl transpeptidase (HR, 1.007; 95% CI, 1.002-1.012; P = 0.003) were independently associated with one-year mortality., Conclusions: Higher GDF-15, high-sensitivity C-reactive protein, fibrinogen, bilirubin, gamma-glutamyl transpeptidase, and N-terminal pro-B-type natriuretic peptide concentrations were independently associated with worse survival in patients with end-stage HF.

Introduction: The interleukin-12/23 (IL-12/23) signalling pathway plays an important role in the pathogenesis of psoriasis. In addition, even molecularly targeted therapy has been reported to lose adequate response to treatment., Aim: To determine the expression patterns of mRNAs and miRNAs related to IL-12/23 signalling pathways in the human keratinocyte culture exposed to liposaccharide A (LPS) and then adalimumab in comparison with untreated cells., Material and Methods: Human, adult, low-Calcium, high-Temperature keratinocyte (HaCaT) cultures were exposed to 1 µg/ml LPS for 8 h, and then adalimumab was added to the cultures at a concentration of 8 µg/ml and incubated for 2, 8, and 24 h. We used mRNA and miRNA microarray, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay techniques., Results: STAT1, STAT3, STAT5, IL-6, IL-6R, SOCS3, and JAK3 genes differentiated HaCaT cultures with the drug from controls regardless of the time the cells were exposed to the drug. The addition of adalimumab to a culture previously exposed to LPS resulted in silencing of SOCS3 and IL-6 expression compared to the control, while for the other transcripts they were found to be overexpressed compared to the control culture. The assessment indicated the strongest connections between JAK3 and hsa-miR-373-5p (target score 96); SOCS3, STAT5, and hsa-miR-1827 (target score 96)., Conclusions: Our study indicates that adalimumab has the strongest modulating effect on mRNA and miRNA expression of JAK/STAT and IL-6-dependent IL-12/23 pathways., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Termedia Sp. z o. o.)

Introduction: Cardiac allograft vasculopathy (CAV) is a major threat to long-term survival after heart transplantation (HT)., Aim: To determine factors associated with CAV detection in patients after HT., Material and Methods: We analyzed 299 consecutive patients after HT who underwent routine visits at our institution between 2016 and 2018. Human interleukin 33 (IL-33) and suppression of tumorigenicity 2 (ST2) were measured by sandwich enzyme-linked immunosorbent assay with a commercially available kit (Human ST-2 and IL-33 ELISA, SunRedBio Technology Co, Ltd, Shanghai, China)., Results: The patients' median age was 59.00 years, and 74.2% were men. The frequency of CAV was 47.5%. Multivariable logistic regression analysis showed that IL-33 (odds ratio (OR) = 1.044 (1.029-1.059), p < 0.001) and ST2 (OR = 1.061 (1.040-1.083), p < 0.001) serum concentrations, donor age (OR = 1.046 (1.009-1.085), p = 0.015), left ventricular diastolic dimension (LVDD) (OR = 1.081 (1.016-1.149), p = 0.013), and time from HT to blood collection (OR = 1.256 (1.151-1.371), p < 0.001) were independent risk factors for CAV. The area under the receiver operating characteristics curve (AUC) indicated good prognostic power of IL-33 and ST2 concentrations (AUC = 0.779 and AUC = 0.784, respectively) and excellent prognostic power of the IL-33/ST2 score (AUC = 0.863)., Conclusions: Lower IL-33 and higher ST2 serum concentrations, as well as older donor age, larger LVDD and longer time from HT to blood collection, are independently associated with CAV. IL-33 and ST2 have good discriminatory power and the IL-33/ST2 score has excellent strength for detecting CAV., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Termedia Sp. z o. o.)

Background: It is still uncertain whether de-novo expression of E-selectin in endothelial cells may be considered an additional marker of chronic inflammation in heart failure (HF)., Methods: We studied 393 consecutive patients (313 M, 80 F) with HF secondary to dilated cardiomyopathy in whom the right ventricular endomyocardial biopsy was performed. For immunohistochemistry, HLA class I and II, E-selectin (ELAM-1), CD3 + lymphocytes and CD68 + macrophages were studied. Patients were divided into two groups: Group A, with ELAM-1 (+), and Group B with ELAM-1 (-) in the biopsy sections., Results: Of all patients, 140 (35.6%) subjects were presented with ELAM-1 expression in endomyocardial biopsies. Patients in the Group A had a significantly lower LV ejection fraction compared to those from the Group B (31.3 ± 12.9 vs. 34.2 ± 12.7; 95% CI, 0.3-5.6, P = 0.029) and they showed a higher mean number of CD3 (+) lymphocytes in the biopsy sections, P = 0.006. In addition, ELAM-1 reasonably correlated with CD3 lymphocytes (r = 0.3, P < 0.001)., Conclusions: Our findings suggest that de-novo ELAM-1 expression in endothelial cells may be a useful marker of chronic inflammation in the biopsies of patients with HF secondary to dilated cardiomyopathy., (Copyright © 2022. Published by Elsevier GmbH.)