The Serum ACE2, CTSL, AngII, and TNFα Levels after COVID-19 and mRNA Vaccines: The Molecular Basis.

BACKGROUND: The SARS-CoV-2 virus as well as the COVID-19 mRNA vaccines cause an increased production of proinflammatory cytokines. AIM: We investigated the relationship between ACE2, CTSL, AngII, TNFα and the serum levels of IL-6, IL-10, IL-33, IL-28A, CD40L, total IgM, IgG, IgA and absolute count of T- and B-lymphocytes in COVID-19 patients, vaccinees and healthy individuals. METHODS: We measured the serum levels ACE2, AngII, CTSL, TNFα and humoral biomarkers (CD40L, IL-28A, IL-10, IL-33) by the ELISA method. Immunophenotyping of lymphocyte subpopulations was performed by flow cytometry. Total serum immunoglobulins were analyzed by the turbidimetry method. RESULTS: The results established an increase in the total serum levels for ACE2, CTSL, AngII and TNFα by severely ill patients and vaccinated persons. The correlation analysis described a positive relationship between ACE2 and proinflammatory cytokines IL-33 (r = 0.539) and CD40L (r = 0.520), a positive relationship between AngII and CD40L (r = 0.504), as well as between AngII and IL-33 (r = 0.416), and a positive relationship between CTSL, total IgA (r = 0.437) and IL-28A (r = 0.592). Correlation analysis confirmed only two of the positive relationships between TNFα and IL-28A (r = 0.491) and CD40L (r = 0.458). CONCLUSIONS: In summary, the findings presented in this study unveil a complex web of interactions within the immune system in response to SARS-CoV-2 infection and vaccination.

Comparative analysis in diagnosis by real-time polymerase chain reaction versus direct microscopy, culture, and histology in fungal infections of the nails, scalp, and skin.

BACKGROUND: The diagnosis of superficial fungal infections is the subject of intensive research in many countries around the world. The diagnostic methods used are diverse, including both conventional and innovative techniques. METHODS: This study evaluates the sensitivity, specificity, and efficacy of the real-time polymerase chain reaction (PCR) methodology and compares them with those of the conventional methods - direct microscopic, cultural, and histological examinations of materials from hair, skin, and nails - in order to demonstrate the benefits and significance of real-time PCR for the diagnosis of dermatophytic infections. RESULTS: The values obtained for the sensitivity, specificity, and efficacy of direct microscopic, cultural, histological, and real-time PCR studies are as follows: 63.71, 88.89, and 72.96% (P < 0.001); 58.06, 100, and 73.47% (P < 0.001); 85.96, 100, and 90.70% (P < 0.001); 88.52, 100, and 92.63% (P < 0.001). CONCLUSION: The use of real-time PCR in the diagnosis of dermatophytic infections is a relatively new approach in mycology and is subject to testing and experience from its use. The results are promising, but the method has not yet established itself as a new gold standard in the diagnosis of superficial fungal infections caused by dermatophytes, though its application would be very useful in identifying isolates without conidiogenesis or absence of growth.

The lncRNAs/miR-30e/CHI3L1 Axis Is Dysregulated in Systemic Sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease with completely undefined etiology and treatment difficulties. The expression of both protein coding and non-coding RNAs is dysregulated during disease development. We aimed to examine a possible regulatory axis implemented in the control of chitinase-3 like protein 1 (CHI3L1) or YKL-40, an inflammation-associated glycoprotein, shown to be elevated in SSc. A panel of seven miRNAs and three lncRNAs potentially involved in the control of CHI3L1 were selected on the basis of in silico analysis. TagMan assay was used to evaluate the expression levels of miRNAs and RT-qPCR for lncRNAs in white blood cells (WBCs) and plasma from SSc patients and healthy controls. Among the eight screened miRNAs, miR-30e-5p (p = 0.04) and miR-30a-5p (p = 0.01) were significantly downregulated in WBCs and plasma of SSc patients, respectively. On the contrary, the expression of the metastasis associated lung adenocarcinoma transcript 1 (MALAT1) (p = 0.044) and the Nuclear enriched abundant transcript 1 (NEAT1) (p = 0.008) in WBCs was upregulated compared to the controls. Increased levels of MALAT1 and NEAT1 could be associated with the downregulation of miR-30e-5p and miR-30a-5p expression in WBCs and plasma. We present novel data on the involvement of a possible regulatory axis lncRNAs/miR-30e/CHI3L1 in SSc and hypothesize that MALAT1 and NEAT1 could act as miR-30e-5p and miR-30a-5p decoys. This may be a reason for the increased serum levels of CHI3L1 in SSc patients.

In search of dermatophytes - frequency and etiology of fungal infections in patients with and without diabetes mellitus.

INTRODUCTION: Onychomycosis is a frequent nail disorder, accounting for up to 50% of all nail problems. Treatment of onychomycosis is expensive and requires a long time of antifungal medications. Consequently, a proper and faster diagnosis is necessary. Especially for those patients with diabetes mellitus, where onychomycosis is among the most significant predictors of foot ulcer and possible severe complications.

Serum protein levels of YKL-40 and plasma miR-214 expression in patients with systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease with incompletely revealed etiology and pathophysiology. There are still no specific and reliable biomarkers. Here we examined YKL-40 as a biomarker of inflammation and fibrosis, and suggest a possible mechanism for its regulation. METHODS: Forty female patients with SSc (26 with diffuse cutaneous (dcSSc) and 14 with limited cutaneous SSc (lcSSc)) and 14 healthy female controls were enrolled in this cross-sectional study. Bioinformatic tools identified miR-214 binding site in the 3'-untranslated region (3'UTR) of YKL-40 mRNA. Serum levels of YKL-40 were examined by ELISA, while YKL-40 mRNA and miR-214 was measured by qPCR. RESULTS: The in silico analysis revealed several microRNAs (miRNAs) targeting YKL-40 mRNA, from which miR-214 was selected. YKL-40 serum levels were significantly higher in patients compared to controls (p = .0042). In contrary, miR-214 expression in plasma of SSc patients was significantly down-regulated compared to controls (p = .0058). Receiver operating characteristic (ROC) and area under the curve (AUC) analysis showed that both serum YKL-40 and plasma miR-214 levels had good capacity to distinguish patients with SSc, dcSSc and lcSSc from healthy subjects. CONCLUSION: YKL-40 and miR-214 have different expression profile in SSc. Increased serum levels of YKL-40 could be associated with down-regulation of miR-214 expression in plasma. Both, YKL-40 concentrations and miR-214 plasma fold change values might serve as possible biomarkers in SSc.

YKL-40 and neuron-specific enolase in neurodegeneration and neuroinflammation.

Neurodegenerative diseases comprise a large number of disorders with high impact on human health. Neurodegenerative processes are caused by various etiological factors and differ in their clinical presentation. Neuroinflammation is widely discussed as both a cause and a consequence in the manifestation of these disorders. The interplay between the two entities is considered as a major contributor to the ongoing disease progression. An attentive search and implementation of new and reliable markers specific for the processes of inflammation and degeneration is still needed. YKL-40 is a secreted glycoprotein produced by activated glial cells during neuroinflammation. Neuron-specific enolase (NSE), expressed mainly by neuronal cells, is a long-standing marker for neuronal damage. The aim of this review is to summarize, clarify, and evaluate the potential significance and relationship between YKL-40 and NSE as biomarkers in the monitoring and prognosis of a set of neurological diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. YKL-40 appears to be a more reliable biomarker in neurological diseases than NSE. The more prominent expression pattern of YKL-40 could be explained with the more obvious involvement of glial cells in pathological processes accompanying each neurodegenerative disease, whereas reduced NSE levels are likely related to low metabolic activity and increased death of neurons.

Serum YKL-40 and IL-6 levels correlate with ultrasound findings of articular and periarticular involvement in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vascular, immune and fibrotic abnormalities in the skin and in many internal organs. New biomarkers with predictive value associated with target organ involvement are needed. The up-regulation of IL-6 production is associated with the disease activity and in the development of cardiopulmonary manifestations in SSc patients. The protein YKL-40 is a promising and intensively investigated biomarker related to inflammatory and tumor diseases. The objective of the study was to investigate how serum levels of YKL-40 and IL-6 correlate with articular and periarticular involvement in patients with SSc assessed by high-frequency ultrasonography. 59 SSc patients (56 women, 3 men) and 23 age-matched healthy subjects (21 women and 2 men) were investigated for serum YKL-40 and IL-6 (by ELISA). All the patients and healthy controls underwent clinically and high-frequency ultrasound assessment of articular and periarticular structures. Joint involvement was scored according to the new US10SSc score. Clinical data about the SSc patients showed significantly higher mRSS in the dcSSc patients (p = 0.015). Clinical synovitis was diagnosed in 16.9% of all patients: 22.5% of the dcSSc group and 10.7% of the lcSSc group (p = 0.306). On the other hand, US synovitis was detected in a higher percentage: 44% of all SSc patients; 54.8% of the dcSSc group and 32% of the lcSSc patients (p = 0.116). Clinical tenosynovitis was established in 6.7% of all patients: 9.7% of the dcSSc group and 3.5% of the lcSSc group (p = 0.614). US tenosynovitis was detected at a higher rate: 27% of all patients; 32.25% of the dcSSc group and 21.4% of the lcSSc group (p = 0.393). Serum level of YKL-40 was significantly higher in SSc patients (115.62 ng/ml ± 89.51, median 86.76) compared to the healthy controls (46.28 ng/ml ± 18.91, median 44.02), p < 0.001. IL-6 level was also significantly higher in the patient group (27.60 ± 48.80 pg/ml; median 8.32) vs. the healthy controls (5.79 ± 2.46 pg/ml, median 5.52). In the patient subgroups, YKL-40 and IL-6 levels were significantly elevated in dcSSc compared to lcSSc patients: YKL-40 dcSSc (159.52 ng/ml ± 102.81; median 136.20 ng/ml) vs. lcSSc patients (89.31 ng/ml ± 50.36; median 68.03 ng/ml;), p < 0.001; IL-6 dcSSc patients (49.64 pg/ml ± 46.37; median 16.36 pg/ml) vs. lcSSc patients (13.22 pg/ml ± 8.95; median 8.65 pg/ml), p = 0.048. A statistically significant correlation of high magnitude (rs = 0.884, p < 0.001) was observed between YKL-40 and the ultrasound 10 Systemic sclerosis score (US10SSc) and between IL-6 and the US10SSc score (rs = 0.808, p < 0.001). Serum YKL-40 and IL-6 in combination with US may have a potential role in defining disease activity and stratification, predicting organ involvement, and in the prognosis of SSc.