Serum Concentrations Of TGF-β Research Articles

Blood serum TGF-β1 content in children with new coronavirus infection

Impaired serum TGF-β1 production is one of the proposed mechanisms for coronavirus disease 2019 (COVID-19).Study objective: to study blood serum TGF-β1 content in children with new coronavirus infection.Materials and methods: a one-stage study was conducted in 119 patients with COVID-19 and compared with 118 healthy children of the same age and sex as a control group. The age range in both groups was 11.0 years. Preschoolers (0–6 years old) and schoolchildren (7–17 years old) in the group with COVID-19 were 21 (18%) and 98 (82%), respectively. Children with COVID-19 were divided into asymptomatic (n=23), mild (n=61), and moderate (n=35) subgroups. Serum samples for TGF-β1 concentration analysis were taken from all patients and tested by flow fluorimetry. The data were processed using the IBM SPSS Statistics Version 25.0 software package (International Business Machines Corporation, license No Z125-3301-14, USA).Results: median serum TGF-β1 levels of children 0–17 years old with COVID-19 regardless of the form of severity were significantly higher than in the control group. The serum concentration of TGF-β1 in children with COVID-19 of preschool age was increased comparing to schoolchildren. Children 0-6 years old with a moderate form of coronavirus infection had high serum TGF-β1 values when compared with school-age patients.Conclusion: elevated serum TGF-β1 levels were found in children both without clinical manifestations and with symptoms of coronavirus infection, reaching maximum values in the moderate form in children 0–6 years old.

Salivary Interleukin-13 and Transforming Growth Factor Beta as Potential Biomarkers of Cancer Cachexia.

serum and saliva specimens were obtained from 78 patients. Forty-six patients were non-cachectic, and 32 patients were cachectic (per SCRINIO group criteria), all with metastatic solid tumors. Commercial ELISA kits were used to determine the salivary and serum concentrations of interleukin 13 (IL-13) and transforming growth factor beta (TGF-β) in two patient groups and healthy controls. Laboratory values were obtained from the hospital information system, and weight and height were measured at the time of sampling. A statistically significant difference was observed between the groups in saliva IL-13 concentrations but no difference in serum concentrations. Statistically significant differences were also observed between the groups in saliva and serum concentrations of TGF-β. Logistic regression analysis has identified salivary IL-13 and TGF-β as independent factors for cancer cachexia. We demonstrated saliva as a valuable specimen for cachexia investigation and established IL-13 and TGF-β as potential cancer cachexia biomarkers. Further research is needed to evaluate these findings.

Impact of Photobiomodulation on IL1β and TGFβ-1 concentrations in patients with aphthous stomatitis.

Laser therapy has shown effectiveness in promoting wound healing by influencing various physiological factors such as blood flow, cytokines, histamine, nerve signals, lymphocyte function, tissue oxygenation, and cell growth. This study aims to evaluate the therapeutic efficacy of Photobiomodulation (PBM) treatment, by using diode laser, in modifying the levels of interleukin-1 beta (IL1β) and transforming growth factor beta-1 (TGFβ-1) in patients diagnosed with aphthous stomatitis. A before-after interventional design was conducted over 10 months with 20 subjects. Data on demographic details and serum concentrations of IL1β and TGFβ-1 were collected pre-treatment and on Days 3 and 7 post-treatments. The intervention involved a single session of four 30-second applications of a QuickLase dual-wavelength laser operating at 980nm. Results show significant reductions in IL1β and TGFβ-1 levels after 7 days of treatment, indicating a time-dependent effect of PBM therapy on these inflammatory markers. The findings suggest that PBM therapy holds promise as an intervention for reducing inflammation associated with aphthous stomatitis.

Agalactosyl IgG induces liver fibrogenesis via Fc gamma receptor 3a on human hepatic stellate cells.

The relevance of aberrant serum IgG N-glycosylation in liver fibrosis has been identified; however, its causal effect remains unclear. Because hepatic stellate cells (HSCs) contribute substantially to liver fibrosis, we investigated whether and through which mechanisms IgG N-glycosylation affects the fibrogenic properties of HSCs. Analysis of serum IgG1 N-glycome from 151 patients with chronic hepatitis B or liver cirrhosis revealed a positive correlation between Ishak fibrosis grading and IgG1 with agalactosyl N-glycoforms on the crystallizable fragment (Fc). Fc gamma receptor (FcγR) IIIa was observed in cultured human HSCs and HSCs in human liver tissues, and levels of FcγRIIIa in HSCs correlated with the severity of liver fibrosis. Additionally, agalactosyl IgG treatment caused HSCs to have a fibroblast-like morphology, enhanced migration and invasion capabilities, and enhanced expression of the FcγRIIIa downstream tyrosine-protein kinase SYK. Furthermore, agalactosyl IgG treatment increased fibrogenic factors in HSCs, including transforming growth factor (TGF)-β1, total collagen, platelet-derived growth factor subunit B and its receptors, pro-collagen I-α1, α-smooth muscle actin, and matrix metalloproteinase 9. These effects were more pronounced in HSCs that stably expressed FCGR3A and were reduced in FCGR3A knockout cells. Agalactosyl IgG and TGF-β1 each increased FCGR3A in HSCs. Furthermore, serum TGF-β1 concentrations in patients were positively correlated with agalactosyl IgG1 levels and liver fibrosis severity, indicating a positive feedback loop involving agalactosyl IgG, HSC-FcγRIIIa, and TGF-β1. In conclusion, agalactosyl IgG promotes fibrogenic characteristics in HSCs through FcγRIIIa. © 2024 The Pathological Society of Great Britain and Ireland.

Immunomodulatory properties of cholecalciferol in rats with experimentally induced inflammation

The study aimed to investigate anti-inflammatory and immunomodulatory effects of cholecalciferol (vitamin D3) in rats with complete Freund’s adjuvant-induced arthritis (AIA) and lipopolysaccharide (LPS)-induced inflammation. In the first experiment, rats were treated with cholecalciferol 14 days before or from the day of induction of arthritis. In the second set-up, animals received cholecalciferol for 14 days which was followed by LPS injection. TNF (tumour necrosis factor)-alpha, IL (interleukin)-1β, TGF (transforming growth factor)-β1 levels were measured by enzyme linked immunosorbent assay (ELISA). Cholecalciferol treatment reduced paw oedema and ankle joint diameter in AIA. Significantly lower IL-1β concentrations were found in cholecalciferol-treated arthritic rats. In LPS-challenged rats, cholecalciferol markedly lowered serum TNF-α, whereas an elevation in IL-1β concentrations was observed. Cholecalciferol slightly increased TGF-β1 serum concentration in arthritic rats and non-significantly reduced its level in LPS-challenged animals. Our findings showed that cholecalciferol exerts immunomodulatory properties which probably contribute to its anti-inflammatory effect.

The effect of vitamin D provision on biomarkers of inflammation in bronchial asthma in children

Introduction. Asthma is a widespread disease in childhood and has a persistent tendency to increase. Therefore, the search for factors influencing this process, as well as biomarkers reflecting the degree of asthma control, is an urgent problem. Objective. To study the relationship of vitamin D levels with the serum periostin and TGF-β1 concentration in children with asthma. Materials and methods. The cross-sectional (one-stage) study included 80 children aged 6 to 17 years (average age — 12 ± 3.2 g). The subjects were divided into 2 groups: children with asthma — group 1 (n = 40); group 2 — the control group (n = 40). In all children, the assessment of the concentration of 25(OH)D, periostin and TGF-β1 in the blood serum was studied. Results. Median (Me) 25(OH) in patients with asthma was statistically significantly lower than in children of the comparison group (16.7 ng/ml, versus 25.7 ng/ml, p = 0.017), and did not depend on the severity of the disease, corresponded to a deficiency condition in both mild (16.2 ng/ml) and with an average severity of asthma (16.8 ng/ml) (p = 0.041). Me of periostin in 1st group was within the normal range (730.2 ng/ml), but statistically significantly exceeded the indicator of 2nd group (539.7 ng/ml, p < 0.05) and did not depend on the age and duration of asthma. High rates of periostin were observed in children with moderate severity of asthma with a disease experience of 4–6 years (617.2 ng/ml). Me of TGF-β1 in both groups corresponded to normal values (309.0 and 369.6 pg/ml, respectively, p > 0.05) and did not depend on the age and duration of asthma. Conclusions. VD deficiency is registered in children with asthma 2 times more often than in healthy children in Ryazan region. The serum concentration of periostin increased in proportion to the severity of asthma. Vitamin D deficiency can be one of the risk factors for the development of asthma and lead to an imbalance in the periostin and TGF-β system.

The Depth of the Molecular Response in Patients with Chronic Myeloid Leukemia Correlates with Changes in Humoral Immunity.

Background and Objectives: The effective treatment of chronic myeloid leukemia leads to the restoration of proper immune system function. We aimed to investigate fluctuations in circulating cytokines, angiogenic factors and complement components in patients with CML during the first year of treatment with TKI and correlate them with the degree of achieved molecular response. Material and Methods: We recruited 31 patients with newly diagnosed CML. Peripheral blood and bone marrow samples were obtained, and concentrations of serum proteins were measured using an immunology multiplex assay. Results: The study cohort was divided into two groups of optimal or non-optimal in accordance with the European Leukemia Net (ELN) guidelines. We found significantly higher concentrations of C1q, C4 and C5a in serum after 3 months of TKI treatment in patients who achieved optimal responses in the 6 months after diagnosis. The most alterations were observed during 12 months of therapy. Patients in the optimal response group were characterized by higher serum concentrations of TGF-β, EGF, VEGF, Angiopoietin 1, IFN-γ and IL-8. Conclusions: The later plasma concentrations of complement components were significantly increased in patients with optimal responses. The changes after 12 months of treatment were particularly significant. Similar changes in bone marrow samples were observed.

Vitamin D Supplementation: Effect on Cytokine Profile in Multiple Sclerosis

Vitamin D is known for its role in modulating calcium and phosphate homeostasis and is implicated both in bone mineralization and immune system regulation. The immune-modulatory role of vitamin D and its impact on multiple sclerosis (MS) courses are still debated. The aim of this review was to check the effect of vitamin D supplementation on cytokine profile regulation in people with MS. A significant increase in serum concentrations of interleukin (IL)-10 and Transforming growth factor (TGF)-β1 after vitamin D supplementation was demonstrated in most studies, with some of them reporting a reduction in disability scores after vitamin D supplementation and an inverse correlation between IL-10 levels and disability. The effect of vitamin D on the serum levels of IL-17 and IL-6 was controversial; different results across studies could be explained by a variability in the treatment duration, route, and frequency of administration, as well as the dosage of vitamin D supplementation, responses to vitamin D treatment and the serum levels reached with supplementation, including the methods used for cytokine analysis and the different cell types investigated, the MS phenotype, the disease phase (active vs. non-active) and duration, and concomitant treatment with disease-modifying therapies. Nevertheless, the significant increase in the serum concentrations of IL-10 and TGF-β1, demonstrated in most studies, suggests an anti-inflammatory effect of vitamin D supplementation.

Assessing angiogenesis factors as prognostic biomarkers in breast cancer patients and their association with clinicopathological factors

Introduction Angiogenesis is fundamental for tumor growth and metastasis across many solid malignancies. Considerable interest has focused on the molecular regulation of tumor angiogenesis as a means to predict disease outcomes and guide therapeutic decisions. Methods In the present study, we investigated the prognostic value of transforming growth factor beta (TGF-β), epidermal growth factor (EGF), fibroblast growth factor (FGF), delta-like ligand 4 (DLL4), and vascular endothelial growth factor (VEGF) in the serum of 120 women diagnosed with breast cancer using ELISA as well as examined their associations with clinical parameters and the outcome of the disease. Results Our results demonstrated that the serum concentration of TGF-β and EGF were remarkably higher in patients with higher tumor size, end stages of the disease, and positive lymph node involvement compared to patients with lower tumor size, early stages of the disease, and negative lymph node involvement. In addition, we found a significant correlation between the serum concentration of VEGF and the level of EGF, FGF, and DLL4 in patients with breast cancer. Furthermore, both univariate and multivariate analyses showed that TGF-β and EGF can be used as end-stage predictors. Discussion/Conclusion Based on our findings, increasing the level of angiogenesis factors is significantly associated with higher tumor size and late stages of the disease in patients with breast cancer. Moreover, measuring the level of angiogenesis factors could lead to better prediction of disease outcomes and choosing the best treatments for patients.

Inhibition of TGFβ1 activation prevents radiation-induced lung fibrosis.

Radiotherapy is the main treatment modality for thoracic tumours, but it may induce pulmonary fibrosis. Currently, the pathogenesis of radiation-induced pulmonary fibrosis (RIPF) is unclear, and effective treatments are lacking. Transforming growth factor beta 1 (TGFβ1) plays a central role in RIPF. We found that activated TGFβ1 had better performance for radiation pneumonitis (RP) risk prediction by detecting activated and total TGFβ1 levels in patient serum. αv integrin plays key roles in TGFβ1 activation, but the role of αv integrin-mediated TGFβ1 activation in RIPF is unclear. Here, we investigated the role of αv integrin-mediated TGFβ1 activation in RIPF and the application of the integrin antagonist cilengitide to prevent RIPF. ItgavloxP/loxP ;Pdgfrb-Cre mice were generated by conditionally knocking out Itgav in myofibroblasts, and wild-type mice were treated with cilengitide or placebo. All mice received 16Gy of radiation or underwent a sham radiation procedure. Lung fibrosis was measured by a modified Ashcroft score and microcomputed tomography (CT). An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum TGFβ1 concentration, and total Smad2/3 and p-Smad2/3 levels were determined via Western blotting. Conditional Itgav knockout significantly attenuated RIPF (p<.01). Hounsfield units (HUs) in the lungs were reduced in the knockout mice compared with the control mice (p<.001). Conditional Itgav knockout decreased active TGFβ1 secretion and inhibited fibroblast p-Smad2/3 expression. Exogenous active TGFβ1, but not latent TGFβ1, reversed these reductions. Furthermore, cilengitide treatment elicited similar results and prevented RIPF. The present study revealed that conditional Itgav knockout and cilengitide treatment both significantly attenuated RIPF in mice by inhibiting αv integrin-mediated TGFβ1 activation. Activated TGFβ1 has a superior capacity in predicting radiation pneumonitis (RP) risk and plays a vital role in the development of radiation-induced pulmonary fibrosis (RIPF). Conditional knock out Itgav in myofibroblasts prevented mice from developing RIPF. Cilengitide alleviated the development of RIPF by inhibiting αv integrin-mediated TGFβ1 activation and may be used in targeted approaches for preventing RIPF.

NF-α, IL6, IL1-α, IL-10 and TGF-β1 Gene Expression in Iranian Acute Myeloid Leukemia Patients

Acute myeloid leukemia is a heterogeneous clonal disorder of blood-producing cells that are among the most common malignant disorders in adults. The purpose of this study was to examine the gene expression of TNF-α, IL6, IL1-α, IL-10, and TGF-β1 at diagnosis in acute myeloid leukemia. The current study included 50 patients with acute myeloid leukemia and 50 control subjects. ELISA was used to determine the serum concentrations of TNF-α, IL6, IL1-α, IL-10, and TGF-β1. After cDNA synthesis and RNA extraction, the expression of TNF-α, IL6, IL1-α, IL-10, and TGF-β1 genes was determined using real-time PCR (ΔΔCT computational). Statistical analysis was conducted with Statistical Package for the Social Sciences 19, and P&lt;0.05 was deemed statistically significant. The mean serum levels of TNF-α, IL6, IL1-α, IL-10, and TGF-β1 were lower in patients with acute myeloid leukemia than in the control group. In addition, cytokine mRNA expression in peripheral blood mononuclear cells was significantly lower in AML patients compared to the control group (p&lt;0.0001). Changes in TNF-α, IL6, IL1-α, IL-10, and TGF-β1 were associated with acute myeloid leukemia, according to the findings. The current study supports the use of cytokines as diagnostic biomarkers for acute myeloid leukemia.

TGFβ1, SMAD2, CTNNβ1, and Wnt3a gene mutational status and serum concentrations in individuals with non-small cell lung cancer.

The objective of the current investigation was to investigate the diagnostic utility of the serum concentrations and mutational status of TGFβ1, SMAD2, CTNNβ1, and Wnt3a. and the expression levels of human‑related genes in patients with non-small cell lung cancer (NSCLC). The serum concentrations were determined using the ELISA technique, and PCR for genotype variations of TGFβ1, SMAD2, CTNNβ1, and Wnt3a were examined using Sanger sequencing in tissue samples obtained from 93 patients with NSCLC and 84 healthy individuals for blood, and 20 Formalin Fixed Paraffin Embedded (FFPE) from normal samples dissected adjacent to the tumour. The findings of the current investigation indicate that individuals diagnosed with NSCLC exhibited significant elevation in the serum levels of CEA and CYFRA21-1, as well as TGFβ1, SMAD2, CTNNβ1, and Wnt3a. In total, 325 mutations in four trialled genes (243 mutations in TGFβ1, 24 mutations in SMAD2,47 mutation Wnt3a and 11 mutations in CTNNβ1) were identified in patients with NSCLC. Furthermore, all mutations were recorded in adenocarcinoma, not squamous and normal adjacent tumour cells. CYFRA21-1 and CEA are more significant between NSCLC and HC, gender, and NSCLC types (p<0.001). In detail, TGFβ1 exhibited the highest rate of mutations among other genes and three types of genomic mutations. Elevated levels and genetic polymorphisms of TGFβ1, SMAD2, CTNNβ1, and Wnt3a may play crucial functions in the pathogenesis and angiogenesis of non-small cell lung cancer (NSCLC). These biomarkers might play a role in future immunologic response and pharmacologically targeted NSCLC therapy.

Association of serum transforming growth factor β1 with left ventricular hypertrophy in children with primary hypertension

The current study was designed to assess the association of serum transforming growth factor β1 (TGF-β1) with left ventricular hypertrophy (LVH) in children with primary hypertension. The present single-center prospective trial examined 182 patients diagnosed with primary hypertension in Children’s Hospital, Capital Institute of Pediatrics, between January 2021 and September 2022. Clinical data were analyzed, and ambulatory blood pressure was assessed for 24 h. LVH, the commonest subclinical cardiac feature of hypertension, was assessed by echocardiography. According to left ventricular geometry, cases were assigned to the LVH (n = 44) and normal geometry (n = 138) groups. Serum TGF-β1 amounts were quantitated by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curves were established to analyze various variables for their predictive values in LVH. Among 182 children with primary hypertension, the concentrations of serum TGF-β1 were higher in stage 2 hypertension than in stage 1 (47.3 (38.8, 52.5) vs. 46.0 (38.6, 48.2) ng/L, Z = − 2.376; P = 0.018). Additionally, serum TGF-β1 content showed a positive correlation with BP levels (P < 0.05). TGF-β1 amounts were significantly elevated in the LVH group compared with the normal geometry group (51.7 (46.1, 54.9) vs. 46.1 (38.7, 48.1) ng/L, Z = − 4.324; P = 0.0000). Serum TGF-β1 content was positively associated with LVH (r = 0.321, P = 0.0000). Multivariable logistic regression analysis showed BMI (OR = 1.188, 95% CI 1.082–1.305; P = 0.0000) and elevated serum TGF-β1 content (OR = 1.063, 95% CI 1.016–1.113; P = 0.009) independently predicted LVH. A multivariable logistic regression model considering BMI and TGF-β1 content in LVH prediction was 0.771, with sensitivity and specificity of 72.7% and 70.3%, respectively.Conclusion: These data revealed an association of serum TGF-β1 with BP in children with primary hypertension. Serum TGF-β1 concentration was positively correlated with hypertensive cardiac damage. Serum TGF-β1 might constitute a valuable molecular marker for the prediction of LVH in children with primary hypertension. The combination of BMI and TGF-β1 has a certain diagnostic and predictive value for LVH in children with primary hypertension, which may provide a new reference index for early clinical identification of hypertensive cardiac damage.What is Known:• Experimental and clinical data indicated TGF-β1 is involved in BP elevation.• TGF-β1 is positively correlated with LVMI and hypertrophy in adults.What is New:• Our current study reveals an association of serum TGF-β1 with BP in children with primary hypertension.• Elevated serum TGF-β1 level is positively associated with LVH in children with primary hypertension.• The combination of BMI and TGF-β1 has a certain diagnostic and predictive value for LVH in children with primary hypertension.

Silk protein sericin: a promising therapy for Achilles tendinopathy-evidence from an experimental rat model.

This study investigated the efficacy of sericin in treating experimental Achilles tendinopathy (AT) in rats via the transforming growth factor-beta (TGF-β)/mothers against decapentaplegic (Smad) pathway compared with diclofenac sodium (DS). An AT model was induced in rats using collagenase enzyme type I and divided into 5 groups: C (control), AT (diseased control), ATS (AT treated with sericin), ATN (AT treated with DS), and ATSN (AT treated with sericin and DS). Sericin injection was given on the 3rd and 6th days by intratendinous injection (0.8 g/kg/mL), and DS was administered for 14 days by oral gavage (1.1 mg/kg/day). Serum concentrations of total oxidant-antioxidant status (TOS-TAS), TGF-β1, decorin, Smad2, and connective tissue growth factor (CTGF) were measured. Histopathologic and immunohistochemical (IHC) studies were conducted on Achilles tendon samples. The TOS, oxidative stress index (OSI), TGF-β1, Smad2, CTGF, and decorin serum concentrationswere significantly higher in AT than in C and significantly lower in ATS than in AT (P<0.05). Histopathological examination revealed that irregular fibers, degeneration, and round cell nuclei were significantly elevated in AT. Spindle-shaped fibers were similar to those in C, and degeneration was reduced in ATS. TGF-β1 and Smad2/3 expression was increased, and collagen type I alpha-1 (Col1A1) expression was decreased in AT vs. C (P=0.001). In the ATS, TGF-β1 and Smad2/3 expression decreased, and Col1A1 expression increased. The Bonar score significantly increased in the AT group (P =0.001) and significantly decreased in the ATS group (P =0.027). Sericin shows potential efficacy in reducing oxidative stress and modulating the TGF-β/Smad pathway in experimental AT models in rats. It may be a promising therapeutic agent for AT, warranting further clinical studies for validation. Key Points • This study revealed that sericin mitigates AT-induced damagethrough the TGF-β/Smad pathway in an AT rat model. • ELISA and IHC investigations corroborated the effectiveness ofsericin via the pivotal TGF-β/Smad pathway in tissue repair. • Evidence indicates that sericin enhances collagen synthesis,shapes tendon fiber structure, and diminishes histopathologicaldegeneration. • Sericin's antioxidant properties were reaffirmed in its AT treatmentapplication.

Issues of cytokine regulation in vibration disease and associated conditions

The article presents the data on the state of cytokine regulation and indicators of endothelial damage when exposed to industrial vibration (general or local) and in combination with arterial hypertension. Changes in the levels of pro-inflammatory and anti-inflammatory cytokines are described, and biomarkers of endothelial dysfunction in the combined course of vibration disease and arterial hypertension are investigated. The study of the cytokine profile and biomarkers of damage to the vascular endothelium in this pathology will allow making early diagnosis of vascular disorders and optimizing preventive measures for workers in vibration hazard industries. Purpose of the study. Improving the quality of early diagnosis and prevention of vibration dis ease in an isolated course and its combination with arterial hypertension based on a study of the cytokine profile and biomarkers of endothelial dysfunction in this pathology. Material and research methods. A comprehensive study included 84 patients with vibration disease from the exposure to local and general vibration of the first and second degree, 61 patients with a combined course of vibration disease from the exposure to local and general second degree vibration and arterial hypertension, and 30 participants in the control group not exposed to industrial vibration and healthy according to medical examination. The levels of pro-inflammatory (IL-1β, IL-8, TNF-α) and anti-inflammatory cytokines (IL-4) and the biomark ers of endothelial damage (EDN1, TGF-β1, VEGF-A, PDGF-BB, fibronectin, and von Willebrand factor) were determined by enzyme immunoassay. Results. The response of the immune system to the effects of industrial vibration is characterized by a cytokine imbalance — an increase in the level of pro-inflammatory cytokines (IL-1β, IL-8, TNFα) and a decrease in the level of anti-inflammatory cytokine (IL-4). With a combined course of vibration disease and arterial hypertension, the cytokine imbalance is characterized by an even more significant increase in serum concentration of IL-1β, IL-8, TNFα and a decrease in serum IL-4 concentration. Endothelial dysfunction in vibration disease from the exposure to both local and general vibration in combination with arterial hypertension is characterized by a significant increase in the serum concentration of EDN1, TGF-β1, VEGF-A, PDGF-BB, fibronectin, and von Willebrand factor. Conclusion. The study of the cytokine profile and biomarkers of damage to the vascular endothelium in this pathology will allow making early diagnosis of vascular disorders and optimizing preventive measures for workers in vibration hazard industries.

TGF Beta as a Prognostic Biomarker of COVID-19 Severity in Patients with NAFLD-A Prospective Case-Control Study.

Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease in Western countries, has been identified as a possible risk factor for COVID-19 severity. However, the immunological mechanisms by which NAFLD exacerbates COVID-19 remain unknown. Transforming growth factor-beta 1 (TGF-β1) has an important immunomodulatory and pro-fibrotic role, which has already been described in NAFLD. However, the role of TGF-β1 in COVID-19 remains unclear, and could also be the pathophysiology link between these two conditions. The aim of this case-control study was to analyze the expression of TGF-β1 in COVID-19 patients depending on the presence of NAFLD and COVID-19 severity. Serum TGF-β1 concentrations were measured in 60 hospitalized COVID-19 patients (30 with NAFLD). NAFLD was associated with higher serum TGF-β1 concentrations that increased with disease severity. Admission TGF-β1 concentrations showed good discriminative accuracy in predicting the development of critical disease and COVID-19 complications (need for advanced respiratory support, ICU admission, time to recovery, development of nosocomial infections and mortality). In conclusion, TGF-β1 could be an efficient biomarker for predicting COVID-19 severity and adverse outcomes in patients with NAFLD.

Transforming growth factor beta 1 (TGF-β1) in COVID-19 patients: relation to platelets and association with the disease outcome.

Transforming growth factor beta (TGF-β) is a ubiquitously distributed cytokine known to contribute to the pathogenesis of numerous pathological processes. The aim of this study was to measure serum concentrations of TGF-β1 in severely ill COVID-19 patients and to analyze its relationship with selected hematological and biochemical parameters and with the disease outcome. The study population included 53 COVID-19 patients with severe clinical expression of the disease and 15 control subjects. TGF-β1 was determined in serum samples and supernatants from PHA-stimulated whole blood cultures using ELISA assay. Biochemical and hematological parameters were analyzed using standard accepted methods. Our results showed that serum levels of TGF-β1 in COVID-19 patients and controls correlate with the platelet counts. Also, positive correlations of TGF-β1 with white blood cell and lymphocyte counts, platelet-to-lymphocyte (PLR) ratio, and fibrinogen level were shown, while negative correlations of this cytokine with platelet distribution width (PDW), D-dimer and activated partial thromboplastin time (a-PTT) values in COVID-19 patients were observed. The lower serum values of TGF-β1 were associated with the unfavorable outcome of COVID-19. In conclusion, TGF-β1 levels were strongly associated with platelet counts and unfavorable disease outcome of severely ill COVID-19 patients.

ПРОГНОСТИЧЕСКИЕ ПРЕДИКТОРЫ ТЯЖЕСТИ ТЕЧЕНИЯ КОРОНАВИРУСНОЙ ИНФЕКЦИИ У ДЕТЕЙ ДОШКОЛЬНОГО ВОЗРАСТА

As for adults, the prognostic predictive factors have been established, including some cytokines, associated with the diagnosis, pathogenesis, and severity of the coronavirus infection (COVID-19). However, predictors for the severity of the course of coronavirus infection in children are not well understood. In addition, there is no information on the cytokine profile in preschool children with COVID-19 as yet. The purpose of the research was to create a predictive model based on a comprehensive analysis of cytokine levels, which would then allow predicting the severity of the course of coronavirus infection in preschool children. Materials and methods used: 21 children (47.6% (10/21) boys and 52.4% (11/21) girls) aged 4.0 [3.0; 4.0] y/o with confirmed coronavirus infection (main group) vs. 25 children (44% (11/25) boys and 56% (14/25) girls) of health group I aged 3.0 [2.9; 3.7] y/o (the control group). Depending on the severity of COVID-19, patients of the main group were divided into subgroups: SG1 of 7 children with asymptomatic COVID-19; SG2 of 7 patients with a mild form; and SG3 of 7 cases of moderate form of the disease. In all children, the presence of SARS-CoV-2 in nasopharyngeal and oropharyngeal swabs was detected by PCR. The concentration of cytokines in blood serum was assessed by the flow fluorometry. Results: in children with COVID-19 at the time of admission to the hospital, the serum concentration of IL-1β, IL-2, IL-4, IL-6, IL-8, IP-10, MCP-1, IFN-γ, and TGF-β1 was statistically significantly higher than in the control group (p&lt;0.05). Thus, based on a comprehensive analysis of the levels of IL-1β, IL-2, IL-6, IL-8, IL-12p70, IP-10, and TGF-β1 at the time of admission to the hospital, the prognostic model was developed allowing predicting the severity of COVID-19 in preschool children (Se=1.0 [95% CI 0.99-1.00], Sp=0.98 [95% CI 0.96-0.99], ROC-AUC=1.0 [95% CI 0.99-1.00], p&lt;0.001; R2=0.93). Conclusion: the results of a comprehensive analysis allow us to consider the indicators of IL-1β, IL-2, IL-6, IL-8, IL-12p70, IP-10, and TGF-β1 as predictors for coronavirus infection severity in preschool children.

Long-term effects of ciclosporin and oclacitinib on mediators of tolerance, regulatory T-cells, IL-10 and TGF-β, in dogs with atopic dermatitis.

Atopic dogs often are managed with allergen-specific immunotherapy (AIT) and concurrent dosages of ciclosporin (CSA) or oclacitinib to alleviate their clinical signs. Both drugs might affect proper tolerance induction by inhibiting regulatory T-cell (Treg) induction. We evaluated Treg cell numbers and serum interleukin (IL)-10 and transforming growth factor-beta (TGF-β)1 levels in dogs diagnosed with atopic dermatitis (AD) and successfully treated with either CSA or oclacitinib for nine or more months. We included 15 dogs receiving oclacitinib, 14 dogs treated with CSA, 15 healthy dogs, 13 dogs with untreated moderate-to-severe AD and 15 atopic dogs controlled with AIT. Peripheral blood CD4+CD25+FOXP3+ T-cell percentages were determined using flow cytometry. Serum concentrations of IL-10 and TGF-β1 were measured by enzyme-linked immunosorbent assay. The percentage of Treg cells in the CSA group was significantly lower in comparison with the healthy group (p=0.0003), the nontreated AD group (p=0.0056) or the AIT group (p=0.0186). There was no significant difference in Treg cell percentages between the CSA and oclacitinib groups, nor between the oclacitinib and the healthy, nontreated AD or AIT-treated dogs. No significant differences were detected in IL-10 and TGF-β1 serum concentrations between the five groups. Lower Treg cell percentages in the CSA-treated dogs suggest an impact of this drug on this cell population; however, it does not necessarily mean that it diminishes tolerance. Functionality and cytokine production may be more important than the number of Treg cells. Further studies evaluating the treatment outcome of dogs receiving AIT and concurrent drugs are needed to show clinical relevance.

Circulating levels of IL-6 and TGF-β1 in patients with prostate cancer undergoing radiotherapy: associations with acute radiotoxicity and fatigue symptoms

BackgroundThe goal of research was to investigate the possible relations between serum concentrations of IL-6 and TGF-β1, individual and clinical characteristics, and adverse effects of radiotherapy in patients with prostate cancer: acute and late genitourinary and gastrointestinal toxicity, and fatigue.MethodsThirty-nine patients with localized or locally advanced prostate cancer who were treated with radiotherapy were enrolled in this study. The acute radiotoxicity grades and fatigue levels were assessed during the radiotherapy and 1 month after the radiotherapy. Estimation of the late radiotoxicity was performed every three months in the first year, every four months in the second year, and then every six months. Serum levels of IL-6 and TGF-β1 were determined before radiotherapy and after the 25th radiotherapy fraction by ELISA.ResultsThe significant positive association between diabetes mellitus and changes in acute genitourinary toxicity grades during the radiotherapy was observed in prostate cancer patients. In addition, patients who were smokers had significantly higher maximum fatigue levels in comparison with patients who were non-smokers. The circulating IL-6 levels were significantly higher after the 25th radiotherapy fraction in comparison with levels determined before radiotherapy. The significant positive correlations between pretreatment TGF-β1 levels and maximum genitourinary toxicity grades and between TGF-β1 levels after the 25th fraction and genitourinary toxicity grades after the 25th fraction, were found. The pretreatment IL-6 concentrations and TGF-β1 concentrations after the 25th fraction were positively correlated with maximum genitourinary toxicity grades. The IL-6 levels after the 25th fraction were positively associated with genitourinary toxicity grades after this fraction. The pretreatment IL-6 concentrations were significantly positively correlated with maximum fatigue scores. The significant positive correlation between IL-6 concentrations and fatigue scores after the 25th fraction was determined. The positive correlations between IL-6 and TGF-β1 concentrations measured after the 25th fraction and maximum fatigue scores were observed.ConclusionsOur results suggest that serum levels of IL-6 and TGF-β1 might influence the severity of acute genitourinary radiotoxicity and fatigue in patients with prostate cancer. Combining clinical parameters and circulating cytokine levels might be useful for the prediction of adverse reactions to radiotherapy.