Serum Concentrations Of TGF-β Research Articles

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.

Biomarkers of infectious pneumonia in naturally infected calves.

To investigate the clinical value of selected biomarkers for evaluation of systemic inflammatory response and pulmonary inflammation and damage pattern in calves with different pneumonia forms. 16 calves with fibrinous pneumonia (FP group; infected with Mannheimia haemolytica or Pasteurella multocida), 12 calves with caseonecrotic pneumonia (CNP group; infected with Mycoplasma bovis), and 10 healthy calves (C group) based on results of bronchoalveolar lavage fluid (BALF) examination. Blood and BALF samples were collected. Annexin-A2 (Anx-A2), endothelin-1 (ET-1), calgranulin B (S100A9), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), interleukin-17A (IL-17A), haptoglobin (Hp), lipopolysaccharide-binding protein (LBP), and albumin (Alb) concentrations and lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) activities were measured and compared across groups. Serum concentrations of Anx-A2, S100A9, TGF-β1, TNF-α, IL-17A, Hp, and LBP and activities of LDH and ALP were higher and Alb concentrations were lower for the pneumonia groups versus C group. BALF concentration ratios of S100A9:Alb, LBP:Alb, LDH:Alb, and ALP:Alb were higher for the pneumonia groups versus C group (P < .05). BALF concentration ratios of Anx-A2:Alb, TGF-β1:Alb, and IL-17A:Alb were higher for the FP group versus other groups (P < .05). Results indicated that serum Anx-A2, S100A9, TGF-β1, TNF-α, IL-17A, Hp, LBP, and Alb concentrations were useful in determining the systemic inflammatory response and that BALF concentration ratios of S100A9:Alb, TGF-β1:Alb, LBP:Alb, and ALP:Alb were useful biomarkers in determining pulmonary inflammation and damage. Measurements of BALF concentration ratios of Anx-A2:Alb, TGF-β1:Alb, and IL-17A:Alb could be beneficial to defining fibrinous characterization of pulmonary inflammation.

Fabrication, characterization and application of novel nanoemulsion polyvinyl alcohol/chitosan hybrid incorporated with citral for healing of infected full-thickness wound

Chitosan (Csn) and polyvinyl alcohol (PVA) have mechanical strength properties and can be encapsulated with citral (Cil) into nanoemulsions (NEs) and applied for the treatment of infected wounds. This study investigates the effects PVA/Csn/Cil-NEs for the treatment of infected wounds in a mouse model. The NEs were prepared by the help of Cil, PVA and 10% and 20% Csn. In vitro release and antibacterial properties and also cytotoxicity analysis were done. The therapeutic formulations were prepared and administrated in circular wounds infected with Acinetobacter baumannii and Streptococcus pyogenes. Wound contraction, histopathological parameters total bacterial count, the serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), transforming growth factor-β or (TGF-β), interleukin-10 (IL-10), reactive oxygen species (ROS), and malondialdehyde (MDA), and activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were evaluated. The NEs were safe and addition of Csn decreased rapid release of Cil. The mice treated with the NEs containing higher concentrations of Csn exhibited lower bacterial count, the serum concentrations of TNF-α, IL-1β, ROS, MDA, edema, and immune cells and higher the serum concentrations of TGF-β and IL-10, activities SOD and GPx, and collagen deposition. In conclusion, the PVA/Csn/Cil-NEs expedited infected wounds in a mice model.

Serum concentration and mRNA expression of Transforming Growth Factor-Beta 1 (TGF-β1) in stunted and non- stunted toddlers

West Nusa Tenggara Province has the fifth-highest prevalence of stunting cases in Indonesia. So far, limited research is available to understand the likelihood of stunting in this region. Transforming Growth Factor-Beta 1 (TGF-β1), an immunoregulatory cytokine, may affect the stunting progression. Knowledge of messenger mRNA expression in the TGF-β1 gene in stunted toddlers could help to determine therapeutic targets to catch up on their growth. This study compared the expression of TGF- β1 mRNA and TGF-β1 concentrations in the stunted and the non-stunted toddlers. The nutritional status of all participants was also gathered and linked to the stunting issue. A cross-sectional study was conducted on 48 toddlers aged 12-36 months. The stunting case was defined as a Z-Score of less than-2 of length/height for age according to WHO. The serum TGF-β1 and TGF-β1 gene mRNA were measured using ELISA and RT-PCR, respectively. The nutritional status data were collected through interviewer-administered structured questionnaire to the toddlers' parents and 48-h food recalls. Descriptive analyses were applied to determine the distribution of participants' macronutrient and micronutrient levels. Results show that there were significant differences in expressions of the TGF- β1 gene mRNA of the stunted and the non-stunted toddlers. The expression of the TGF- β1 mRNA gene in the non-stunted toddlers was also higher with 13.7±0.859 fold change than those of the stunted toddlers with 9.01±1.76 fold change with a p-value <0.001. The serum TGF-β1 concentrations in the stunted toddler (6.20±3.60pg/ml) were significantly lower than the ones in the non-stunted toddlers (14.3±1.05pg/ml) with p-value <0.001. However, there was no clear relationship between the likelihood of stunting and the nutritional status from the obtained data. Overall findings demonstrate the significantly lower both the TGF-β1 gene mRNA expression and serum TGF-β1 for the stunted toddlers than the non-stunted toddlers, impacting bone formation and resorption. The outcomes of this study encourage the development of interventional therapy for stunted toddlers by increasing the serum TGF-β1 concentrations.

Effects of chlorpyrifos on transient receptor potential channels

The well-known toxicity of chlorpyrifos (CPF) occurs via inhibition of cholinesterase (ChE), but in recent years the detrimental effects of low-dose CPF exposure have been attributed to an unknown non-cholinergic mechanism of action. We previously showed that CPF can alter gene expression of transient receptor potential canonical (TRPC) channels in vitro. In this study, we analyzed the gene expression of TRPCs at various time points after CPF treatment in vivo. The results showed that TRPC1 mRNA expression in mouse brain was significantly reduced 2−8 h after CPF treatment, but the TRPC4 mRNA expression was not significantly changed. To investigate the possible involvement of Transforming Growth Factor-beta1 (TGF-β1) in contributing to TRPCs gene alteration by CPF, we used TGF-beta receptor inhibitor (LY2109761) as a pretreatment prior to CPF treatment. The serum TGF-β1 concentration was significantly increased 24 h after CPF treatment. After pretreatment with LY2109761, both TRPC1 and TRPC5 mRNAs were significantly downregulated 1 and 2 h after CPF treatment, but were significantly upregulated 3 and 24 h after CPF treatment. TRPC4 mRNA was also significantly downregulated at 1 h. These results suggest that interference with ion channels, a non-cholinergic mechanism of CPF, may contribute to the cellular neurotoxicity of CPF.

Role of transforming growth factor-beta 1 and connective tissue growth factor levels in coronavirus disease-2019-related lung Injury: a prospective, observational, cohort study.

ABSTRACTBackground: Coronavirus disease-2019 (COVID-19) results in acute lung injury. This study examined the usefulness of serum transforming growth factor-beta 1 (TGF-β1) and connective tissue growth factor (CTGF) levels in predicting disease severity in COVID-19 patients with pulmonary involvement.Methods: Fifty patients with confirmed COVID-19 and pulmonary involvement between September 2020, and February 2021 (Group 1) and 45 healthy controls (Group 2) were classified into three subgroups based on clinical severity: moderate, severe, and critical pneumonia. Serum TGF-β1 and CTGF concentrations were measured on days 1 and 7 of admission in Group 1 using an enzyme-linked immunosorbent assay. These concentrations were also measured in control cases. The mean serum TGF-β1 and CTGF levels were then compared among COVID-19 patients, based on clinical severity.Results: Significantly higher mean serum TGF-β1 and CTGF levels were observed on both days in Group 1 than in the control group. The mean serum TGF-β1 and CTGF levels on day 7 were also significantly higher than those on day 1 in Group 1. The critical patient group had the highest serum TGF-β1 and CTGF levels on both days, and the difference between this group and the moderate and severe pneumonia groups was significant. Cutoff values of 5.36 ng/mL for TGF-β1 and 626.2 pg/mL for CTGF emerged as predictors of COVID-19 with pulmonary involvement in receiver-operating characteristic curve analysis. Conclusions: TGF-β1 and CTGF are potential markers that can distinguish COVID-19 patients with pulmonary involvement and indicate disease severity. These findings may be useful for initiating treatment for early-stage COVID-19.

Positive Association of Matrix Proteins Alteration with TAZ and The Progression of High-Grade Bladder Cancer.

ObjectiveBladder cancer is the 9th cause of human urologic malignancy and the 13th of death worldwide. Increased collagen cross-linking, NIDOGEN1 expression and consequently stiffness of extracellular matrix (ECM) may be responsible for the mechanotransduction and regulation of transcriptional co-activator with PDZ-binding motif (TAZ) and transforming growth factor β1 (TGF-β1) signaling pathways, resulting in progression of tumorigenesis. The present study aimed to assess whether type 1 collagen expression is associated with TAZ nuclear localization.Materials and MethodsIn this case-control study, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analysis were performed to evaluate the activation of the TAZ pathway in patients with bladder cancer (n=40) and healthy individuals (n=20). The ELISA method was also conducted to measure the serum concentrations of TGF-β1. Masson’s trichrome staining was carried out to histologically evaluate the density of type 1 collagen. Results Our findings that the expression levels of COL1A1, COL1A2, NIDOGEN1, TAZ, and TGF-β1 genes were overexpressed in patients with bladder cancer, and their expression levels were positively associated with the grade of bladder cancer. The immunohistochemical analysis demonstrated that the nuclear localization of TAZ was markedly correlated with high-grade bladder cancer. We also found that TAZ nuclear localization was substantially higher in cancerous tissues as compared with normal bladder tissues. Masson's trichrome staining showed that the tissue density of type I collagen was considerably increased in patients with bladder cancer as compared with healthy subjects. ConclusionAccording to our findings, it seems the alterations in the expression of type I collagen and NIDOGEN1, as well as TAZ nuclear localization influence the progression of bladder cancer. The significance of TGF-β1 and TAZ expression in tumorigenesis and progression to high-grade bladder cancer was also highlighted. However, a possible relationship between TGF-β1 expression and the Hippo pathway needs further investigations.

Dietary spray-dried plasma supplementation in late-gestation and lactation enhanced productive performance and immune responses of lactating sows and their litters.

The study was conducted to evaluate the effects of spray-dried plasma (SDP) supplementation during late gestation and lactation on productive performance and immune responses of sows and their litters. Twelve sows (227.78 ± 2.16 kg average body weight; 2.0 average parity) were randomly allotted to two dietary treatments: a basal diet (CON) and the basal diet supplemented with 1% SDP. Sows were fed experimental diets from d 30 before farrowing to weaning of their piglets. Blood samples were collected from sows on d 1, 3, and 7 of lactation and from two randomly selected nursing pigs per litter on d 3 and 7 after birth, and d 1, 3, and 7 after weaning. Productive performance and immune responses of sows and their piglets were measured. There was a trend of less body weight loss in sows supplemented with SDP (p < 0.10) during the lactation period and a trend of greater (p < 0.10) average daily gain in SDP piglets compared to those in the CON group. Sows in the SDP group tended to have lower (p < 0.10) serum concentrations of tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and cortisol on d 3 and lower serum concentration of TNF-α on d 7 compared with sows in CON group. In comparison with CON piglets, piglets from SDP sows tended to have lower (p < 0.10) serum concentrations of TNF-α, TGF-β1, and cortisol on d 7 after birth, lower (p < 0.10) serum TNF-α and C-reactive protein on d 3 and 7 after weaning, and greater (p < 0.10) average daily gain after weaning. Moreover, weaned pigs from sows fed SDP had significantly lower (p < 0.05) serum concentrations of cortisol and TGF-β1 on d 3 and 7 postweaning, respectively, than CON piglets. In conclusion, SDP supplementation in sow diets from late gestation to weaning improved the productive performance of sows and their offspring; the beneficial effects of SDP may be mediated in part through modulation of immune responses of both sows and piglets.

Role of Toll-Like Receptor 2 in Regulation of T-Helper Immune Response in Chronic Obstructive Pulmonary Disease.

Objective According to modern views, the differences in the clinical course of chronic obstructive pulmonary disease (COPD) are associated with certain types of T-helper (Th) immune response. Recent data have shown that toll-like receptor 2 (TLR2) is involved in the development of Th immune response. However, TLR2-mediated regulation of Th subpopulation balance in COPD needs to be elucidated. The aim of our work is to determine the mechanisms of TLR2-mediated regulation of Th immune response in COPD of varying severity. Methods The study included 323 smokers/ex-smokers with stable COPD (GOLD I, GOLD II, and GOLD III) and 97 healthy nonsmokers (control group). Serum levels of Th1 (TNF-α and IFN-γ), Th2 (IL-4), Th17 (IL-6 and IL-17A), Treg (IL-10) cytokines, and the percentage of peripheral blood Th cells expressing TLR2 (CD4+CD282+) were assessed by flow cytometry. Serum concentrations of IL-21 (Th17) and TGF-β1 (Treg) were measured using the ELISA method. The predominant Th cytokine profile in serum was determined by calculating the ratios between levels of Th1 and Th17 cytokines. Spearman's correlation test was performed. Results Patients with COPD GOLD II and III with Th1 and Th17 cytokine profiles exhibited an increase in the percentage of CD4+CD282+ cells compared to the control group. In COPD GOLD I–III, positive correlations between CD4+CD282+ cell frequency and Th17 cytokine levels (IL-6, IL-17A, and IL-21) were found. In COPD GOLD I, IL-10 concentration was negatively correlated with the percentages of studied cells; in COPD GOLD II, a positive correlation between these parameters was noted. Conclusions Enhanced TLR2 expression on CD4+ cells shifts cytokine profile toward Th17 phenotype that plays a crucial role in COPD progression. The level of TLR2 expression on peripheral blood CD4+ cells may be considered as a biomarker for diagnosing and predicting the progression of COPD.

Decreased levels of immune-regulatory cytokines in patients with immune thrombocytopenia and long-lasting overexpression of these cytokines in the splenectomized patients.

Immune thrombocytopenia (ITP) is an autoimmune-mediated disease characterized by decreased platelet counts. Cytokines play important roles in modulating the immune response and are involved in the pathogenesis of many autoimmune diseases. This study aimed at exploring the serum levels of a core set of cytokines that exert immune-regulatory functions in newly diagnosed ITP patients (both before and after treatment) and splenectomized ITP patients. Using the Bio-Plex suspension array system and ELISA, the serum levels of IL-10, IL-21, IL-27, IL-33, IL-35, IL-37, and TGF-β1 were detected. The data showed that the serum levels of the immune regulatory cytokines IL-10, IL-35, and TGF-β1 were significantly lower in newly diagnosed ITP patients. Decreased cytokine levels could be improved in patients with a complete response or a response after steroid-based treatment(s). The serum concentrations of TGF-β1 were positively correlated with the platelet counts both before and after treatment. All the detected immune-regulatory cytokines, except IL-37, showed significantly higher levels in splenectomized ITP patients than pretreatment ITP patients and healthy controls. In conclusion, these data suggest that lower levels of immune-regulatory cytokines are involved in the pathogenesis of ITP and that there is a long-lasting overexpression of immune-regulatory cytokines in ITP patients with splenectomy.

MO1019ASSOCIATION OF VEGF ANF TGF1 GENES POLYMORPHISMS WITH SERUM CONCENTRATION OF GENE PRODUCTS IN CHILDREN WITH LUPUS NEPHRITIS

Abstract Background and Aims Previously it was shown that significantly elevated serum concentration of vascular-endothelial growth factor (VEGF) and transforming growth factor β (TGF-β1) is observed in Lupus Nephritis (LN) patients, especially in those with disease exacerbation. In this study we investigated the association of selected single nucleotide polymorphisms (SNP) in TGF-β1 and VEGF genes with serum concentration of the gene product in children with LN. Method We enrolled 22 children with LN (m:f 2/20) aged 10 to 17 years. Blood samples were taken twice in every child – in remission and during exacerbation of the disease. Serum concentration of VEGF and TGF-β1 was measured using R&amp;D Systems Quantikine ELISA “Human TGF-β1” and “VEGF” kits. DNA was analyzed by polymerase chain reaction for identification of selected SNPs – VEGF rs699947 (A/C), rs2010963 (G/C), TGF-β1 rs1800469 (G/A). Results We didn’t find any association of serum concentration of TGF-β1 with rs1800469 polymorphism in individuals with LN in exacerbation and in remission either (p&amp;gt;0,05). Concentration of VEGF was associated with genotypes of VEGF gene. It was significantly higher in LN patients harboring AA genotype for rs699947 comparing with those with CC+CA group of genotypes (ie carrying at least one minor allele A). This association was observed in exacerbation period (p&amp;lt;0,001), but not in remission (p&amp;gt;0,05). We compared major genotype GG and group of genotypes GC+CC (ie patients with at least one minor allele C) of VEGF gene (rs2010963). It was found that statistically significant elevation of gene product was found in individuals with group of genotypes GC+CC in exacerbation period (p=0,036). In remission concentration of the gene product didn't differ in patients with GG and GC+CC genotypes (p=0,97). VEGF gene genotypes rs699947 and rs2010963 are in high linkage disequilibrium (LD). Having analyzed combined genotypes we found that association with the gene product was the same as in rs699947 alone analysis. This may suggest functional importance of this SNP. Rs2010963 more likely to show association with the gene product due to linkage with rs699947. Conclusion There is an association between VEGF gene genotypes (rs699947 and rs2010963) and gene product serum concentration in LN pediatric patients in exacerbation period. Among two investigated loci of VEGF gene rs699947 might be considered more relevant risk marker of VEGF disfunction. No statistically significant association was found in our study for TGF-β1 gene genotypes (rs1800469) and its' product serum concentration.

Tumor expression of cGAS, not STING, negatively impacts on the efficacy of PD-1/L1 inhibitors in non-small cell lung cancer with PD-L1 TPS ≥50.

e21048 Background: The cGAS/STING pathway is an innate immune pathway that promotes cytokine production in response to cytoplasmic DNA, and its activation is important for the induction of anti-tumor immunity. However, predictivity of cGAS/STING tumor expression on the efficacy of PD-1/L1 inhibitors and subsequent immune responses (e.g., changes in serum cytokines) remain to be elucidated. Non-small cell lung cancer with PD-L1 tumor proportion score (TPS) of 50% or higher respond well to immune checkpoint inhibitor (ICI) monotherapy, but there is still a poor response group among them, and the extraction of such patients is an urgent issue. Methods: This is a post hoc analysis of prospective biomarker study, which enrolled 106 patients with advanced non-small cell lung cancer (NSCLC) who were treated with ICI monotherapy between December 2015 and September 2018. We investigated in 68 patients with preserved evaluable tissue samples taken before start of ICI treatment. cGAS, STING, and PD-L1 expression in tumors were stained by immunohistochemistry. cGAS and STING were evaluated by H-score. Using peripheral blood which was collected by the observational study, 41 serum proteins at the time of PD-1/L1 inhibitors initiation and in 4 – 6 weeks later were quantified. Results: The median cGAS and STING H-SCORE were 220 (5 – 300) and 190 (0 – 300), respectively. There were no differences in cGAS or STING H-SCORE between PD-L1 high (TPS ≥50) and low (TPS &lt; 50) groups ( p= 0.990 and 0.283). Cases were divided into two groups according to median of the H-SCORE, respectively, and compared. Unexpectedly, cGAS high (H-SCORE ≥220) patients showed significantly shorter progression free survival of ICI when PD-L1 TPS ≥50 (median progression free survival (PFS); 143 days vs. not reached, p = 0.028) and progression free rate at 18 months was 7 and 53%, while no association was observed when PD-L1 TPS &lt; 50 (median PFS; 47 vs. 61 days, p= 0.798). STING tumor expression was not associated with PFS regardless of PD-L1 TPS. In cytokine analysis, cGAS high was associated with significantly higher serum concentrations of TGF-β1 and β2 before ICI initiation (47.5 vs. 22.3hg/l, p= 0.023; 2118 vs. 882rg/ml, p= 0.037), and H-SCORE of cGAS, not STING, were significantly correlated with TGF-β1 and β2 basal levels (r = 0.447, p= 0.009; r = 0.373, p= 0.033). Analysis about fold change from baseline to 4 – 6 weeks later of 41 cytokines revealed that leptin significantly increased in cGAS high tumor while no difference was seen in all of cytokines between STING high and low tumor. Conclusions: Tumor expression (H-Score) of cGAS, not STING, is a candidate for predictor of poor response to ICI monotherapy in NSCLC with PD-L1 high (TPS ≥50). cGAS tumor expression may be associated with TGF-β producing, immune-suppressive tumor microenvironment in NSCLC. Clinical trial information: UMIN000024414.

Evaluating the Serum Transforming Growth Factor-Beta 1 Level in Chronic Kidney Disease Caused by Glomerulonephritis

Background: The transforming growth factor-beta 1 (TGF-β1) has been demonstrated as one of the main factors in the progression of fibrosis and sclerosis glomerular damages. Glomerulonephritis is one common cause of chronic kidney disease (CKD) with the promotion of inflammatory renal damage containing fibrosis and sclerosis glomerular. Objectives: This study aimed to evaluate the TGF-β1 level in CKD patients and compare it with the healthy control group. Methods: This cross-sectional case-control study was carried out on 212 subjects admitted to the Nghe An Friendship General Hospital in Vietnam from March 2018 to February 2020. The case group included 152 patients diagnosed with CKD caused by glomerulonephritis, and the control group included 60 healthy individuals. The TGF-β1 was determined in serum by ELISA method. Results: The serum TGF-β1 concentration of the healthy control group and CKD group was 13.45 ± 7.17 and 32.35 ± 11.74, respectively. The CKD group had a significantly higher TGF-β1 level than the control group (P &lt; 0.05). The CKD group with the eGRP ≥ 60 mL/min/1.73 m2 group had a higher TGF-β1 level than the eGRP &lt; 60 mL/min/1.73 m2 group, and the TGF-β1 level increased from stage 1 to stage 5 (P &lt; 0.001). The TGF-β1 had a medium correlation to urea, creatinine, and hs-CRP. Conclusions: The concentration of TGF-β1 in the CKD group was higher than the control group so that it increased early from the first stage of the disease.

Associations between the concentrations of CD68, TGF-β1, renal injury index and prognosis in glomerular diseases.

The present study aimed to investigate the association between the concentrations of CD68, TGF-β1, renal injury index and prognosis in glomerular diseases. Altogether 218 patients with glomerular diseases admitted to Weifang People's Hospital from January, 2014 to March, 2017 were used as the study group. A total of 100 healthy individuals who visited Weifang People's Hospital for a physical examination during the same time period were used as the control group. The levels of CD68 in peripheral blood obtained from the 2 groups of subjects were detected by flow cytometry, and the expression of TGF-β1 in serum was detected by enzyme-linked immunosorbent assay (ELISA). The concentrations of CD68 and TGF-β1 between the 2 groups were compared. The correlation between the concentrations of CD68, TGF-β1 and renal injury indexes in the study group was analyzed, as well as prognostic significance. The diagnostic value of CD68 and TGF-β1 in patients with glomerular disease was analyzed using a ROC curve, and the recovery of the patients was observed. The serum concentrations of CD68 and TGF-β1 in the study group were higher than those in the control group (P<0.05). The concentrations of CD68 and TGF-β1 in the study group positively correlated with the renal injury indexes, such as blood urea nitrogen (BUN), serum creatinine (SCR), uric acid (UA) and the 24-h urinary protein quantity (P<0.05). ROC curve analysis revealed that the area under the curve of CD68 and TGF-β1 as regards the diagnostic value in patients with glomerular disease was 0.808 and 0.738, respectively, while the area under the combined detection curve was 0.866. Multivariate unconditional logistic regression analysis revealed that the clinical classification and the concentrations of CD68 and TGF-β1 were independent prognostic factors in the study group. On the whole, the findings of the present study demonstrate that clinical classification, and the CD68 and TGF-β1 concentrations are independent prognostic factors for patients with glomerular disease. CD68 and TGF-β1 have certain value in the diagnosis of glomerular diseases, and may thus be used as predictors of the diagnosis and recovery of glomerular disease.

Transforming growth factor beta variation with physical activity in knee osteoarthritis

Purpose: Transforming growth factor beta (TGF-β) is a multifunctional cytokine with three different mammalian isoforms. All three isoforms of TGF-β are secreted as inactive latent complexes. Bound to latency-associated peptide, TGF-β is unable to bind to membrane receptors. Therefore, even though TGF-β is constitutively expressed throughout the body, only the free ligand is biologically active and able to modulate the metabolic activity of cartilage. An existing theory likens the latent TGF-β complex to a molecular sensor that monitors the extracellular matrix and responds to perturbations by releasing free TGF-β. In the cartilage, TGF-β1 plays an essential role in regulating cartilage matrix metabolism. The goal of this study was to assess the effects of physical activity on free and total TGF-β isoforms in plasma from individuals with knee osteoarthritis (OA). Methods: To assess the impact of physical activity on biomarker variation, participants (n=20; 65% female; 80% white; mean age 70 years; mean BMI 31.72 kg/m2) were recruited on the basis of symptomatic OA in at least one knee. Knee OA severity was assessed from a postero-anterior semi-flexed radiograph with a SynaFlexer positioning device and quantified by Kellgren Lawrence (K-L) score for each knee. Blood was obtained at 4 different time points (Figure 1). The interval from T0 to T1A was devoted to physical activity including activities of daily living and non-brisk walking for 1 hour, with no more than 10 minutes rest at any one time. All procedures were approved by the Institutional Review Board. Using commercially available ELISA assays, we quantified free and total TGF-β1 (BioLegend) in plasma samples (n=80) and available matched serum (n=79) samples. Total TGF-β2 and TGF-β3 (MSD U-PLEX ELISA) were also quantified in plasma (n=80). The data for TGF-β3 should be interpreted with caution, as 47.5% of samples had concentrations below the LLOD so were imputed as 1/2 LLOD for analyses. To assess variations in TGF-β over this time period, biomarker concentrations for the four time points were normalized to the mean across all four time points for each individual. Significance was assessed by non-parametric Friedman test and Dunn’s post-hoc test. Spearman correlation was used to evaluate associations between non-normalized: free and total plasma TGF-β1; serum and plasma free and total TGF-β1; all total TGF-β isoforms; and free and total TGF-β1 (T1A and change from T0 to T1A) with sum K-L grade. Results: Median plasma concentrations (range pg/ml) were as follows: free TGF-β1: 8.53 (0-40.71); total TGF-β1: 27343.00 (6760.00-81815.00); total TGF-β2: 24.99 (0-170.30); and total TGF-β3: 1.03 (0-3.10). Free plasma TGF-β1 represented 0.032% of total plasma TGF-β1. Free and total TGF-β1, and total TGF-β2, increased significantly after one hour of activity (Figure 2; time point T0 to T1A). The mean fold-change increase with activity was 1.7 for free TGF-β1, 1.4 for total TGF-β1, and 1.5 for total TGF-β2. After food consumption (T1B), TGF-β3 concentrations decreased an average of 62% from T1A, but no significant changes occurred in the other TGF-β isoforms at this time point. In plasma, total TGF-β1 strongly correlated with free TGF-β1 (rs=0.36, p=0.008), total TGF-β2 (rs=0.69, p<0.0001), and total TGF-β3 (rs=0.36, p=0.001). Total TGF-β2 also correlated with Total TGF-β3 (rs=0.29, p=0.01). Serum TGF-β1 concentrations were consistently higher than plasma concentrations (a mean 17.5-fold for free TGF-β1 and a mean 1.6-fold for total TGF-β1). Plasma and matched sera did not correlate for free TGF-β1 (rs=0.09, p=0.43) or total TGF-β1 (rs=0.19, p=0.09). Neither free nor total TGF-β1 were associated with sum K-L grade. Conclusions: This study demonstrates that plasma concentrations of both free and total TGF-β1, and total TGF-β2, all significantly increased with physical activity, suggesting release from a mechanically sensitive reservoir. These results are consistent with known release of TGF-β1 from extracellular matrix of myofibroblasts upon mechanical contraction in vitro. We observed an effective 1.7-fold increase of circulating free (active) TGF-β1 during an hour of activity (from a mean 8.45 to a mean 13.08 pg/ml). Based upon previous published studies, these concentrations may represent a physiologically relevant modulation. These results suggest the need for standardization of activity prior to biofluid sampling intended for TGF-β analyses to assess its impact on musculoskeletal health and disease.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Evaluation of Circulatory Concentration of Cytokines Platelet-Derived Growth Factor-BB, Transforming Growth Factor Beta-1, and IL-10 in Canine Generalized Demodicosis

The purpose of this study was to investigate the changes in circulating concentrations of PDGF-BB, TGF-β1 and interleukin-10 (IL-10) in dogs with generalized demodicosis. Twelve dogs with generalized demodicosis were diagnosed based on clinical findings and microscopic examination of the cutaneous scrapings. Six healthy dogs were included in the study as a control. Commercial specific ELISA assays were used to measure circulating concentrations of plasma PDGF-BB, and serum TGF-β1 and IL-10. Marked and significant increase in plasma PDGF-BB and serum TGF-β1 concentrations was evidenced in diseased dogs, while increase in serum IL-10 concentration was non-significant. The levels of all three markers dropped down to near normal/healthy status after the treatment of diseased dogs. These results indicate that the increased concentrations of circulating PDGF-BB, TGF-β1, and IL-10 play a pivotal role in the pathogenesis of the canine demodicosis.

Analysis of gut microbiome, nutrition and immune status in autism spectrum disorder: a case-control study in Ecuador

ABSTRACT Most studies on autism spectrum disorder (ASD) risk factors have been conducted in developed countries where ethnicity and environment are different than in developing countries. We compared nutritional status, immune response and microbiota composition in mestizo children with ASD with matched controls in Ecuador. Twenty-five cases and 35 controls were matched by age, sex and school location. The prevalence of under- and overweight was higher in children with ASD. Nutritional differences were accompanied by abnormal food habits and more frequent gastrointestinal symptoms in children with ASD. Also, greater serum concentrations of TGF-β1 were observed in children with ASD. Finally, there was greater alpha diversity and abundance of Bacteroides (2 OTUs), Akkermansia, Coprococcus and different species of Ruminococcus in ASD children.

TGF-β1 and VCAM-1 Serum Concentrations as Diagnostic Biomarkers of Diabetic Kidney Disease Progression

Abstract Background and aims: Transforming growth factor-beta 1 (TGF-β1) and vascular adhesion molecule 1 (VCAM-1) have been proposed as promising biomarkers for multiple diseases. TGF-β1 and VCAM-1 are reported to be associated with diabetic kidney disease (DKD) and end stage renal disease in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM). Material and methods: The aim of this study was to investigate the expression of circulating TGF-β1 and VCAM-1 and to assess their potential as a blood-based biomarker for DKD in T1DM and T2DM patients. Results:. The study included 124 participants: 66 patients with T1DM, 58 with T2DM and 20 healthy controls. The diabetic patients were classified according to the estimated glomerular filtration rate (eGFR). First group - eGFR ≥90ml/min/1.73 m2 (n=39), second group eGFR 89-60 ml/min/1.73m2 (n=45), and third group eGFR 59-45 ml/min/1.73m2 (n=40). Enzyme-linked immunosorbent assay for the quantitative detection of was used to evaluate blood TGF-β1 and VCAM-1 expression. It was found that there were higher TGF-β1 and VCAM-1 in all diabetic patients compared with healthy controls (P&lt;0.05). TGF- β1 and VCAM-1 were higher in group with eGFR ≥90ml/min/1.73 m2 and gradually increased in the groups with eGFR89-60 ml/min/1.73m2 and eGFR 59-45 ml/min/1.73m2. TGF- β1 and VCAM-1 were less in T1DM, than T2DM in all study groups. Regression analysis revealed reverse associations between TGF- β1, VCAM-1 and eGFR (P&lt;0.05). TGF- β1 and VCAM-1 correlated positively with albuminuria and negatively with renal function. Conclusion: In discriminating overall patients from healthy subjects, ROC analysis revealed areas under the curve (AUCs) of 1,0 for TGF- β1 for T1DM and T2DM, VCAM-1 0,866 for T1DM, 0,923 for T2DM (P&lt;0.001). The results suggested that blood-based TGF- β1 and VCAM-1 may serve as potential biomarkers for early detection of DKD.

The Prospective Association Between Plasma Concentrations of Cellular Growth Factors and Risk of Heart Failure Mortality in Japanese Population.

BackgroundLimited evidence is available on the association of insulin-like growth factors (IGFs) and risk of heart failure in population-based samples. We investigated whether serum IGFs concentrations can predict mortality from heart failure.MethodsWe conducted a nested case-control study of 39,242 subjects aged 40–79 years who participated in the JACC study, a large Japanese prospective cohort study; participants provided serum samples and were followed up for 9 years. In heart failure cases and age-, sex-, community-, and year of blood withdrawal-matched controls, we measured serum concentrations of IGF-I, IGF-II, and IGF binding protein 3 (IGFBP3) and transforming growth factor (TGF-β1).ResultsDuring the follow-up, there were 88 heart failure deaths (44 men and 44 women). Each increment of 1 standard deviation [SD] of IGF-II (120.0 ng/mL in women and 143.7 ng/mL in men) was associated with a 47% reduced risk of mortality from heart failure; multivariable odds ratio was 0.53 (95% confidence interval [CI], 0.30–0.94, P-trend = 0.03). The multivariable odds ratio in the highest quartile of IGFBP3 serum concentrations (≥3.29 µg/mL in women and ≥3.31 µg/mL in men) compared with the lowest (<2.11 µg/mL in women and <2.56 µg/mL in men) was 0.24 (95% CI, 0.05–1.11; P-trend = 0.12). No association was found between serum concentrations of IGF-I or TGF-β1 and risk of heart failure.ConclusionsHigher serum concentrations of IGF-II were associated with lower mortality from heart failure, which might suggest a possible role of IGF-II in the occurrence or prognosis of heart failure.