Influence of adalimumab on interleukin 12/23 signalling pathways in human keratinocytes treated with lipopolysaccharide A.

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.

Treatment of an ossifying fibroma of the mandible with endodontic microsurgery and grafting with a biphasic calcium sulfate material: a case report.

A significant percentage of lesions of endodontic origin require surgical management due to the possible diagnosis of odontogenic cysts and tumors in the maxilla and mandible. Ossifying fibroma is a benign fibro-osseous lesion that typically presents as a painless, slow-growing, and expansile lesion that appears as a well-demarcated lesion with a variable degree of internal calcification on radiography. Treatment results in a large osseous defect, utilization of a graft to fill the void accelerates healing and prevents complications that may result from failure to fill by the host response. Case presentation: Following endodontic surgery placement of osseous graft material via Guided Tissue Regeneration to fill the defect aids to accelerate fill of the defect on a healthy 26-year-old female patient. A case discussing the one-step treatment of an ossifying fibroma of the anterior part of the mandible following endodontic microsurgery with associated retrograde fill of the apex, then site grating with biphasic calcium sulfate (Bond Apatite®) used in regeneration of the osseous defect related to the lesion and resulting surgery. Clinical discussion: Histologically, the ossifying fibroma is dominated by connective tissue containing cell rich areas with a few fragments of fibrosis. Moreover, in the connective tissue numerous small fragments of spongy and compact bone with areas of partial necrosis present and a significant number of inflammatory cells are observed. Surgical removal of the cyst with thorough curettage of the osseous walls and grafting of the defect provides predictable healing and the desired clinical results sought. Utilization of the biphasic calcium sulfate graft material allows the elimination of the need to overlay the area with a membrane before the flap due to its hard set and the prevention of soft tissue ingrowth into the graft material during the healing phase. Additionally, the hard set of the material allows tenting of the area to maintain the desired volume and ridge contour. Conversion of the graft material depending on the volume placed to host bone occurs over a 3-6 month period. Conclusion: The case report presented, as well as the authors experience mimics the literature on biphasic calcium sulfate in its use as an osseous graft material and is an effective method for the repair of osseous defects that result from the removal of tumors and cysts of the maxilla and mandible. Treatment of an ossifying fibroma is an ideal application of the use of this biphasic calcium sulfate material allowing tenting of the surgical site over the defect created after cyst removal without the need for resorbable collagen membranes. This simplifies its use and decreases material costs that may hamper patient acceptance of treatment without a decrease in expected clinical results.

The presence of E-selectin in the myocardium indicates a sustained inflammatory reaction in patients with dilated cardiomyopathy.

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.

The rationale for using low-molecular weight heparin in the therapy of symptomatic COVID-19 patients.

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.

Factors associated with cardiac allograft vasculopathy after heart transplantation.

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.

Decreased immunoreactivity of von Willebrand factor may reflect persistent nature of the endothelial dysfunction in non-ischemic heart failure.

INTRODUCTION: Endothelial dysfunction is a critical part of heart failure (HF) pathophysiology. It is not clear, however, whether it is present at the similar level in the early and late HF stages. MATERIAL AND METHODS: von Willebrand factor (vWF) and its mRNA levels in biopsies of non-ischemic patients with HF secondary to dilated cardiomyopathy were studied. Consecutive patients with HF were divided into two groups: group A with disease duration ≤ 12 months (n = 59) and group B with disease duration > 12 months (n = 68). The immunoreactivity of the vWF was compared with autopsy sections of 19 control cases. Tissue vWF gene expression was analyzed at the mRNA level by RT-PCR. RESULTS: In the group A, there was lower vWF immunoreactivity in the coronary microvessels compared to the group B [1.5 (1.0-2.0) vs. 2.0 (1.5-2.4), P = 0.001]. In the control group, only weak vWF expression was observed. Protein expression was not accompanied by vWF mRNA whose levels were significantly higher in the Group A as compared to the Group B [14671 (4932-51561) vs. 3643 (185.3-9030.8), P = 0.005]. Protein vWF expression was inversely associated with its mRNA levels (r = -0.34, P = 0.04). CONCLUSIONS: High myocardial protein expression of vWF in patients with long-lasting HF symptoms may highlight the persistent nature of endothelial dysfunction in such a cohort of patients.

Emergency Medical Teams Interventions due to Cardiovascular Diseases in 2018: Polish Regional Observational Study.

Background and objectives: The goal of this work was to assess the interventions for cardiovascular causes (ICD-10: I) and analyze the time between the request for intervention and the arrival of the Medical Emergency Team realized by the Voivodeship Rescue Service in Katowice in the period between 1 January 2018 to 31 December 2018. Materials and Methods: Analysis of the characteristics of the interventions was completed based on the information contained on the dispatch order cards and medical emergency services. Statistical analysis was done using the Chi-square test (p < 0.05). Results: Out of 211,548 cases, 26,672 were associated with cardiovascular diseases. It can be observed that the large majority of interventions took place in urban areas (89.98%; 23,998 cases), whereas only 11.02% took place in rural areas (2674 cases). The most common cause for medical interventions being made by the Medical Emergency Team was primary hypertension-11,649 cases. The average arrival time to urban areas was 9 min and 12 s ± 3 min and 54 s, whereas for rural areas it was 11 min and 57 s ± 4 min and 32 s (p < 0.05). Conclusions: It can be observed that the Medical Emergency System in Katowice operates accordingly with the intentions of the legislator. The obtained data also indicates that there is a high societal awareness of the residents about the purpose of the Medical Emergency Team.