Comparison of growth factor levels in injectable platelet-rich fibrin obtained from healthy individuals and patients with chronic periodontitis: a pilot study.

BACKGROUND: This study aimed to assess and compare the concentrations of growth factors, white blood cells (WBCs), and platelets in injectable platelet-rich fibrin (i-PRF) derived from people with healthy periodontal conditions and those with chronic periodontitis. METHODS: Venous blood samples were obtained from 30 patients diagnosed with chronic periodontitis (test group) and 30 participants with healthy periodontal conditions (control group). The i-PRF was then acquired from centrifuged blood. The growth factors (VEGF, IGF-1, TGF-ß1, PDGF-BB and EGF) released from the i-PRF samples were compared between groups with ELISA testing. The amounts of WBCs and platelets were also compared. RESULTS: No significant differences in the concentrations of growth factors were found between the groups (the mean values for the control and test groups were, respectively: IGF: 38.82, 42.46; PDGF: 414.25, 466.28; VEGF: 375.69, 412.18; TGF-ß1: 21.50, 26.21; EGF: 138.62, 154.82). The test group exhibited a significantly higher WBC count than the control group (8.80 vs. 6.60, respectively). However, the platelet count did not show a statistically significant difference between the groups (control group 242.0 vs. test group 262.50). No significant correlation was observed between WBC count and growth factor level in either group. CONCLUSIONS: The growth factor levels in i-PRFs did not exhibit significant difference between the two groups. This suggests that the levels of these growth factors may be unaffected by the periodontal disease.

Correlation between circulating fibrosis biomarkers with left atrial function and left atrial volume index in rheumatic mitral stenosis.

Mitral stenosis is the most common rheumatic heart disease (RHD) disorder worldwide, including in Indonesia. This pathological condition causes left atrial pressure, leading to left atrial fibrosis that affects the structure and function of the left atrial as well as the clinical condition. The aim of this study was to assess the correlation between circulating fibrosis biomarkers with net atrioventricular compliance (Cn) as a parameter of left atrial function, and left atrial volume index (LAVI) as a parameter left atrium structure of changes. A cross-sectional study was conducted at Panti Rahayu Hospital and Permata Bunda Hospital, Purwodadi, Central Java, with a total of 40 RHD patients with severe mitral stenosis. The ELISA was used to measure the levels of carboxy-terminal propeptide of type I procollagen (PICP), matrix metalloproteinase I (MMP-1), tissue inhibitor matrix metalloproteinase 1 (TIMP-1), and transforming growth factor-ß1 (TGF-ß1). The left atrial function was assessed by measuring Cn, and the LAVI parameters were measured to assess left atrium structure/size. The mean levels of circulating fibrosis biomarkers were as follows: PICP 153.96±89.12 ng/mL; MMP-1 1.44±2.12 ng/mL; MMP-1/TIMP-1 ratio 0.38±0.54 and TGF-ß1 2.66±1.96 pg/mL. From the echocardiographic evaluation, the mean Cn was 5.24±1.93 mL/mmHg and the mean LAVI was 152.55±79.36 mL/m2. There were significant correlation between MMP-1 and MMP-1/TIMP-1 ratio with Cn (r=0.345 and r=0.333, respectively; both had p<0.05). PICP and TGF-ß1 biomarkers did not significantly correlate with Cn (p>0.05). Meanwhile, none of the biomarkers had a significant correlation with LAVI (p>0.05). This study highlights that MMP-1 and MMP-1/TIMP-1 ratio are potentially to be used as markers to determine the Cn in RHD patients with severe mitral stenosis. However, further studies with a higher sample size are needed to confirm this finding.

Effects of 12 Weeks of Daily Melatonin Administration on Inflammatory Markers and Adipose Tissue Mass of Rats under Hypoestrogenism.

Background and Objectives: The hormonal state of hypoestrogenism is associated with the accumulation of white adipose tissue, which can induce an increase in pro-inflammatory markers, leading to progressive health complications. Melatonin can act on adipose tissue mass, promoting its reduction and influencing inflammation, reducing IL-6 and releasing IL-10, pro- and anti-inflammatory markers, respectively. However, the role of melatonin regarding such parameters under the context of hypoestrogenism remains unknown. The aim of this study was to determine the effect of 12 weeks of hypoestrogenism and melatonin on white adipose tissue mass and circulating levels of IL-6, IL-10, TGF-ß-1, and leukotriene C4 (LTC4). Materials and Methods: The animals (Wistar rats with sixteen weeks of age at the beginning of the experiment) under hypoestrogenism were submitted to the surgical technique of bilateral ovariectomy. The animals received melatonin (10 mg·kg-1) or vehicles by orogastric gavage every day for 12 weeks and administration occurred systematically 1 h after the beginning of the dark period. White adipose tissue (perigonadal, peritoneal, and subcutaneous) was collected for mass recording, while blood was collected for the serum determination of IL-6, IL-10, TGF-ß-1, and LTC4. Results: Hypoestrogenism increased the perigonadal and subcutaneous mass and IL-6 levels. Melatonin kept hypoestrogenic animals in physiological conditions similar to the control group and increased thymus tissue mass. Conclusions: Hypoestrogenism appears to have a negative impact on white adipose tissue mass and IL-6 and although melatonin commonly exerts a significant effect in preventing these changes, this study did not have a sufficiently negative impact caused by hypoestrogenism for melatonin to promote certain benefits.

Effect of ADSCs on Th17/Treg and T-bet/GATA-3 in model mice with primary immune thrombocytopenia.

We aimed to observe the effects of adipose-derived mesenchymal stem cells (ADSCs) on T helper 17 (Th17)/regulatory T cells (Treg) and T-box transcription factor (T-bet)/GATA-binding protein 3 (GATA-3) in model mice with primary immune thrombocytopenia (ITP). 32 BALB/C mice were selected. ADSCs were isolated from 2 mice and cultured. The other 30 mice were randomly divided into the normal control group, the ITP model control group, and the ITP experimental group. Platelet count (PLT), Th17/Treg cells, related serum cytokines [interleukin-6 (IL-6), IL-17A, IL-10, and transforming growth factor ß1 (TGF-ß1)], T-bet and GATA-3 mRNA levels in peripheral blood mononuclear cells (PBMCs) in the 3 groups were detected. PLT and Treg in the ITP experimental group were significantly lower than those in the normal control group (P<0.05), but significantly higher than those in the ITP model control group (P<0.05). Th17 and Th17/Treg in the ITP experimental group were significantly higher than those in the normal control group (P<0.05), but significantly lower than those in the ITP model control group (P<0.05). Serum IL-6 and IL-17A levels, and T-bet mRNA levels in the ITP experimental group were significantly higher than those in the normal control group (P<0.05), but significantly lower than those in the ITP model control group (P<0.05). Serum IL-10 and TGF-ß levels, and GATA-3 mRNA levels in the ITP experimental group were significantly lower than those in the normal control group (P<0.05), but significantly higher than those in the ITP model control group (P<0.05). ADSCs can effectively regulate Th17/Treg balance and improve T-bet/GATA-3 mRNA expression levels in ITP model mice.

Modulatory effect of interleukin-2 loaded chitosan nano sphere on regulatory T cell activity in streptozotocin-induced diabetic mice.

OBJECTIVE: The current study aimed to assess the modulating effect of IL-2 encapsulated chitosan-nanoparticles (CSNPs) on the function of Treg cells through induction of type 1 diabetes (T1D). Treg cell function was monitored by the forkhead box P3 (FoxP3) and transforming growth factor beta (TGFß) levels, correlating them with blood glucose and serum insulin levels. MATERIALS AND METHODS: In this case-control study, a low dose of IL-2 (free and chitosan-loaded) was injected into a diabetic mice group. The levels of FoxP3 and TGF-ß 1 were assessed using Enzyme-Linked Immunosorbent Assay. In addition, blood glucose and serum insulin levels were determined. RESULTS: The mean glucose level decreased significantly after free rIL-2 or rIL-2 / CSNPs treatment. Meanwhile, the mean serum insulin level was significantly increased after treatment with free rIL-2 or rIL-2/CSNPs. The mean levels of FoxP3 and TGFß 1 were significantly increased with either free rIL-2 or rIL-2/CSNPs compared to the T1D untreated group (P < 0.001). In the treated mice group receiving free CSNPs, there was a significant negative correlation between glucose and insulin levels. Moreover, FoxP3 & TGFß 1 levels had a significant positive correlation. In treated mice groups with free rIL-2 and IL-2 CSNPs, there was a significant positive correlation between FoxP3 and glucose levels. A significant negative correlation was found after conducting a correlation between insulin level and FoxP3 in the T1D/ rIL-2 / CSNPs group. CONCLUSIONS: Low-dose IL-2 selectively modulates FoxP3 + Tregs, and TGFß 1 increases their levels. These results demonstrated that IL-2-free and chitosan-loaded nanoparticles can be therapeutic agents in T1D.

CD109 identified in circulating proteomics mitigates postoperative recurrence in chronic rhinosinusitis with nasal polyps by suppressing TGF-ß1-induced epithelial-mesenchymal transition.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder with a high rate of recurrence. This study aimed to explore biomarkers for identifying patients with recurrent CRSwNP (rCRSwNP). METHODS: We recruited two independent cohorts. In the discovery cohort, rCRSwNP patients and non-recurrent CRSwNP (non-rCRSwNP) patients were recruited, and the serum proteomic profile was characterized. The top 5 upregulated and downregulated proteins were confirmed in the validation cohort by ELISA, WB, and qRT-PCR, and their predictive values for postoperative recurrence were assessed. In vitro, human nasal epithelial cells (HNEpCs) were employed to assess the ability of candidate proteins to induce epithelial-mesenchymal transition (EMT). RESULTS: Serum proteomics identified 53 different proteins, including 30 increased and 23 decreased, between the rCRSwNP and non-rCRSwNP groups. ELISA results revealed that serum levels of CD163 and TGF-ß1 were elevated, CD109 and PRDX2 were decreased in the rCRSwNP group compared to the non-rCRSwNP group, and serum CD163, TGF-ß1, and CD109 levels were proved to be associated with the risk of postoperative recurrence. In addition, qRT-PCR and WB revealed that tissue CD163, TGF-ß1, and CD109 expressions in rCRSwNP patients were enhanced compared to those non-rCRSwNP patients. Kaplan-Meier analysis showed that increased CD163 and TGF-ß1 expression and decreased CD109 expression are associated with the risk of recurrence in CRSwNP patients. Receiver operating characteristic curves showed that TGF-ß1 and CD109 had superior diagnostic performances for rCRSwNP. In vitro experiments showed that TGF-ß1 promoted EMT in HNEpCs, and overexpression of CD109 reversed this effect. Functional recovery experiments confirmed that CD109 could attenuate EMT in HNEpCs by inhibiting the TGF-ß1/Smad signaling pathway, attenuating EMT in epithelial cells. CONCLUSION: Our data suggested that TGF-ß1 and CD109 might serve as promising predictors of rCRSwNP. The TGF-ß1/Smad pathway was implicated in fostering EMT in epithelial cells, particularly those exhibiting low expression of CD109. Consequently, the absence of CD109 expression in epithelial cells could be a potential mechanism underlying rCRSwNP.

Correlation between changes in serum YKL-40, LXRs, PPM1A, and TGF-ß1 levels and airway remodeling and lung function in patients with bronchial asthma.

OBJECTIVE: This study investigates the correlation between serum levels of YKL-40, LXRs, PPM1A, and TGF-ß1 and airway remodeling and lung function in bronchial asthma patients. METHODS: The study involved 80 bronchial asthma patients and 92 healthy individuals. Serum cytokines, airway remodeling, and lung function markers were compared across mild, moderate, and severe asthma cases using high-resolution CT, t-tests, ANOVA, and Pearson correlation analysis. RESULTS: Asthmatic patients exhibited higher levels of serum YKL-40, LXRα, LXRß, TGF-ß1, airway wall thickness (T)/outer diameter (D), and WA% of total cross-sectional area compared to controls. Conversely, their serum PPM1A, Peak Expiratory Flow (PEF), and Forced Expiratory Volume in 1 s (FEV1) were lower. Serum YKL-40 and TGF-ß1 levels were positively correlated with T/D and WA%, and negatively correlated with PEF and FEV1. PPM1A levels were strongly associated with T/D, WA%, PEF, and FEV1. CONCLUSION: The severity of bronchial asthma is associated with increased serum levels of YKL-40, LXRα, LXRß, and TGF-ß1 and decreased PPM1A. The levels of YKL-40, PPM1A, and TGF-ß1 have a significant correlation with airway remodeling and lung function.

Transforming growth factor beta 1 is associated with subclinical carotid atherosclerosis in patients with systemic lupus erythematosus.

BACKGROUND: Transforming growth factor beta (TGF-ß1) is a multifunctional cytokine that has anti-inflammatory and immunosuppressive effects. TGF-ß1 has been linked to cardiovascular disease in the general population. The immunosuppressive effect of TGF-ß1 is believed to be dysregulated in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to study the relationship of serum levels of TGF-ß1 with subclinical carotid atherosclerosis in patients with SLE. METHODS: The study included 284 patients with SLE. Serum levels of TGF-ß1 and subclinical carotid atherosclerosis (by carotid ultrasonography) were evaluated. In addition, the complete lipid profile and insulin resistance were analyzed. Multivariable linear and logistic regression analysis was performed to establish the relationship of TGF-ß1 with carotid subclinical atherosclerosis adjusting for traditional cardiovascular risk factors that included lipid profile and insulin resistance. RESULTS: Circulating TGF-ß1 was positively and significantly associated with higher levels of LDL:HDL cholesterol ratio and atherogenic index. TGF-ß1 was also associated with significantly lower levels of HDL cholesterol and apolipoprotein A1. Remarkably, TGF-ß1 was associated with the presence of carotid plaque not only after adjustment for demographics (age, sex, body mass index, diabetes, hypertension, and aspirin use) but also after adjustment for relationships of TGF-ß1 with lipid profile molecules, insulin resistance, and SLEDAI disease score (odds ratio 1.14 [95% confidence interval 1.003-1.30], p = 0.045). CONCLUSION: TGF-ß1 serum levels are positively and independently associated with the presence of subclinical atherosclerosis disease in patients with SLE.

sVCAM-1, and TGFß1 in chronic phase, chronic myeloid leukemia patients treated with tyrosine kinase inhibitors.

The outcome for chronic phase (CP) chronic myelogenous leukemia (CML) patients has changed dramatically since the introduction of tyrosine kinase inhibitor (TKI) therapy. We examined the characteristics of CML patients during TKI therapy by determining the plasma concentrations of soluble vascular cell adhesion molecule 1 (sVCAM-1), and transforming growth factor (TGFß1) biomarkers. The plasma levels of sVCAM-1 and TGFß1 were measured by ELISA at baseline and after 3 months of TKI treatment. The levels of sVCAM-1, and TGFß1 were significantly elevated in patients with CML (P< 0.01). Dasatinib treatment was associated with a significant reduction in the levels of these biomarkers (P< 0.01). In conclusion, plasma levels of sVCAM-1 and TGFß1 could have a role in the pathogenesis of CML and may be used as predictors of hematological and molecular responses to TKIs. A favorable outcome for Dasatinib therapy was observed.

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.

BACKGROUND: Coronavirus disease-2019 (COVID-19) results in acute lung injury. This study examined the usefulness of serum transforming growth factor-beta 1 (TGF-ß1) 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-ß1 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-ß1 and CTGF levels were then compared among COVID-19 patients, based on clinical severity. RESULTS: Significantly higher mean serum TGF-ß1 and CTGF levels were observed on both days in Group 1 than in the control group. The mean serum TGF-ß1 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-ß1 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-ß1 and 626.2 pg/mL for CTGF emerged as predictors of COVID-19 with pulmonary involvement in receiver-operating characteristic curve analysis. CONCLUSIONS: TGF-ß1 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.

FOXP3 variants are independently associated with transforming growth factor Β1 plasma levels in female patients with inflammatory bowel disease.

OBJECTIVE: The aim of this study was to evaluate the association of -924 G>A (rs2232365) and -3279 C>A (rs3761548) FOXP3 variants with IBD susceptibility, clinical and endoscopic activity, and IL-10 and TGF-ß1 plasma levels. METHOD: The study included 110 IBD female patients, 60 with Ulcerative Colitis (UC) and 50 with Crohn's Disease (CD), and 154 female controls. FOXP3 variants were determined with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Plasma levels of IL-10 and TGF-ß1 were determined using immunofluorimetric assay. RESULTS: AA genotype of rs2232365 and rs3761548 was associated with CD (OR = 3.147, 95% CI 1.015-9.758, p = 0.047) and UC (OR = 3.221, 95% CI 1.050-9.876, p = 0.041) susceptibility, respectively. However, were not associated with TGF-ß1 and IL-10 levels, and endoscopic/clinical activity disease. GAGA haplotype was associated with IBD (OR = 4.003, 95% CI 1.100-14.56, p = 0.035) and UC susceptibility (OR = 6.107, 95% CI 1.609-23.18, p = 0.008). In addition, IBD patients with the GAGA haplotype had lower TGF-ß1 levels (p = 0.041). Moreover, G/C haplotype (dominant model) had a protective effect of 60% in CD susceptibility and lower Endoscopic Severity Index. CONCLUSIONS: These results suggest that FOXP3 variants could exert a role in the Treg, which could be one of the factors involved in the susceptibility and pathogenesis of IBD.

Modified Shenlingbaizhu Decoction represses the pluripotency of colorectal cancer stem cells by inhibiting TGF-ß mediated EMT program.

BACKGROUND: The Modified Shenlingbaizhu Decoction (MSD) utilizes various phytomedicines has been applied to treat colorectal cancer (CRC). Colorectal cancer stem cells (CSCs) have proven to be tightly associated with CRC progression and metastasis. The mechanism of MSD's inhibitory effect on CSCs has not been determined. PURPOSE: To figure out how MSD inhibits the pluripotency of CSCs and impedes the EMT program. METHODS: The ingredients of MSD extracts were characterized by high-performance liquid chromatography (HPLC). BALB/c-nu mice were transplanted into EGFP labeled SW480 CRC cells and the tumor weight and volume were recorded before and after various doses of MSD treatment. The concentration of TGF-ß1 was quantified with an Enzyme-linked immunosorbent assay. To delineate the logical relationship between EMT and CSCs regulated by MSD, TGF-ß/Smad inhibitor and activator were adopted in tumor-bearing mice and diverse CRC cell lines. Cancer stem cell markers were analyzed by flow cytometry. In vitro analysis of cell motility and viability were done using CCK-8, wound healing, and invasion assay. Immunohistochemistry (IHC) and western blotting (WB) were used for detecting protein expression. The collected results were statistically analyzed with GraphPad Prism 8.0. RESULTS: MSD treatment significantly reduced the size of colorectal cancer tumors and lowered the serum content of TGF-ß1 in mice. Importantly, MSD markedly reduced the expression of pluripotent factors and depressed CD133+ stem cells in the tumor tissues. The TGF-ß/Smad inhibitor neutralized the EMT signaling and lowered the pluripotency by dephosphorylation of SMAD2/3. Similarly, MSD attenuated the pluripotency by limiting TGF-ß/Smad signaling-induced EMT in vivo. MSD inhibited colorectal cancer cell proliferation, migration, and invasion. CONCLUSIONS: MSD inhibits the growth of colorectal cancer. It dampens the pluripotency of CSCs by repressing the TGF-ß-induced EMT program.

[Influence of Serum TGF-ß1 and EGFR Levels on the Therapeutic Effect of High-Dose AraC in Patients with Acute Myeloid Leukemia Based on the Decision Curve].

OBJECTIVE: To analyze the influence of serum levels of transforming growth factor-ß1 (TGF-ß1) and epidermal growth factor receptor (EGFR) on the therapeutic effect of high-dose cytarabine (HD-AraC) in patients with acute myeloid leukemia (AML). METHODS: 98 patients with AML treated in our hospital from January 2019 to June 2020 were selected as the research subjects, all patients were treated with HD-AraC for 1 course of treatment every week. The effect of 2 groups were evaluated during after one course of treatment and divided into effective group and ineffective group, statistical table of baseline data was designed, the baseline data of 2 groups were counted in detail, the baseline data and serum levels of TGF-ß1 and EGFR of 2 groups were compared, Logistic regression analysis was used to examine the relationship between the levels of serum TGF-ß1, EGFR and the therapeutic effect of HD-AraC in patients with AML, the value of serum TGF-ß1 and EGFR levels in predicting the therapeutic effect of HD-AraC in AML patients was analyzed based on ROC curve and decision curve. RESULTS: After 1 course of treatment, among the 98 patients, 26 cases had complete remission, 38 cases had partially remission and 34 cases no remission, the total effective rate was 65.31% (64/98); after comparing data of 2 groups, Logistic regression analysis showed that the overexpression of serum EGFR before treatment might be a risk factor for the ineffective treatment of HD-AraC in AML patients (OR>1, P<0.05), overexpression of serum TGF-ß1 before treatment might be a protective factor for the ineffective treatment of HD-AraC in AML patients (OR<1, P<0.05); the ROC curve results showed that the AUC of serum EGFR and TGF-ß1 before treatment in predicting the risk of ineffective HD-AraC treatment in AML patients were >0.70, which had certain predictive value. The decision curve results showed that in the threshold range of 0.15-044, the prediction model combined with serum EGFR and TGF-ß1 levels in predicting the net benefit rate of HD-AraC treatment in AML patients was better than that of serum EGFR or serum TGF-ß1 alone. CONCLUSION: The levels of serum TGF-ß1 and EGFR affect the therapeutic effect of HD-AraC in patients with AML and increase the risk of ineffective treatment, serum TGF-ß1 and EGFR can be used to predict the risk of ineffective HD-AraC treatment in AML patients, and the combined prediction of net benefit rate is higher.

Physical exercise is associated with a reduction in plasma levels of fractalkine, TGF-ß1, eotaxin-1 and IL-6 in younger adults with mobility disability.

Mobility disability (MD) refers to substantial limitations in life activities that arise because of movement impairments. Although MD is most prevalent in older individuals, it can also affect younger adults. Increasing evidence suggests that inflammation can drive the development of MD and may need to be targeted for MD prevention. Physical exercise has anti-inflammatory properties and has been associated with MD prevention. However, no studies to date have examined whether exercise interventions affect the peripheral inflammatory status in younger adults with MD. To this end, we used blood samples from young and middle-aged adults with MD (N = 38; median age = 34 years) who participated in a 12-week intervention that included aerobic and resistance exercise training. A pre-post assessment of inflammatory biomarkers was conducted in plasma from two timepoints, i.e., before the exercise trial and at follow-up (3-7 days after the last exercise session). We successfully measured 15 inflammatory biomarkers and found that exercise was associated with a significant reduction in levels of soluble fractalkine, transforming growth factor beta 1 (TGF-ß1), eotaxin-1 and interleukin (IL) 6 (corrected α = 0.004). We also found significant male-specific effects of exercise on (i) increasing IL-16 and (ii) decreasing vascular endothelial growth factor-A (VEGF-A). In line with our results, previous studies have also found that exercise can reduce levels of TGF-ß1, eotaxin-1 and IL-6. However, our finding that exercise reduces plasma levels of fractalkine in younger adults with MD, as well as the sex-dependent findings, have not been previously reported and warrant replication in larger cohorts. Given the suggested role of inflammation in promoting MD development, our study provides additional support for the use of physical exercise as a treatment modality for MD.

TGF-ß1 in plasma and cerebrospinal fluid can be used as a biological indicator of chronic pain in patients with osteoarthritis.

INTRODUCTION: Previous studies have demonstrated that cytokines, transforming growth factor (TGF-ß1), and brain-derived neurotrophic factor (BDNF) can impact the intensity of pain in rodents. However, the roles of cytokines, TGF-ß1 and BDNF in humans with chronic pain in osteoarthritis remains unclear, and no comparison between plasma and central cerebral spinal fluid (CSF) has been conducted. METHODS: Patients with osteoarthritis who were scheduled to receive spinal anesthesia were enrolled. The intensity of pain was evaluated with a visual analogue scale (VAS). In addition, patients with genitourinary system (GU) diseases and without obvious pain (VAS 0-1) were included as a comparison (control) group. The levels of TGF-ß1, BDNF, tumor necrosis factor-α (TNF-α), and interleukin (IL)-8 within the CSF and plasma were collected and evaluated before surgery. RESULTS: The plasma and CSF TGF-ß1 levels were significantly lower in the osteoarthritis patients with pain (VAS ≥ 3) than in the GU control patients. Downregulation of plasma BDNF was also found in osteoarthritis patients with pain. The Spearman correlation analysis showed that the VAS pain scores were significantly negatively correlated with the levels of TGF-ß1 in the CSF of patients with osteoarthritis. However, there was no significant correlations between the pain scores and the levels of BDNF, TNF-α, and IL-8 in either the CSF or plasma. CONCLUSIONS: TGF-ß1 but not BDNF, TNF-α, or IL-8 may be an important biological indicator in the CSF of osteoarthritis patients with chronic pain.

Preparation, biocompatibility, and wound healing effects of O-carboxymethyl chitosan nonwoven fabrics in partial-thickness burn model.

This study was aimed at preparing O-carboxymethyl chitosan (CM-CTS) fabrics, and examining the wound healing effects on partial-thickness burn. The functional polysaccharides were produced from chitosan needle-punched nonwovens reacted with chloroacetic acid. Then the biocompatibility and biological functions were evaluated through fibroblast L-929 and SD rats. CM-CTS fabrics were obtained with elongation at break more than 42%, tensile strength reaching 0.65 N/mm2, and water vapor transmission rate about 2600 g/m2∙24 h. Moreover, CM-CTS fabrics could effectively promote the mouse L-929 migration in vitro. CM-CTS fabrics yielded satisfactory results in angiogenesis, collagen deposition, interleukin-6 content, transforming growth factor level and healing rate, which were superior to the positive control and model groups after rats suffering with partial-thickness burn. In conclusion, CM-CTS fabrics possessed proper mechanical properties, air permeability, favorable biocompatibility, acceleration on fibroblasts migration and healing capacity for partial-thickness burn injury, and owned good potential as high-quality wound dressing.

Pilot study investigating diagnostic utility of serum MMP-1 and TGF-ß1 in asthma in 'real world' clinical practice in India.

AIMS: At a tissue level, matrix metalloproteinase-1 (MMP-1) and transforming growth factor-beta 1 (TGF-ß1) contribute to allergic airway inflammation, tissue remodelling and disease severity in asthma via different pathways. Their peripheral blood levels and role in diagnosis and therapeutic monitoring has not been adequately explored. We investigated the association between MMP-1 and TGF-ß in moderate and severe persistent asthma and evaluated their performance characteristics by constructing receiver operating characteristic curves. METHODS: Serum MMP-1 and TGF-ß1 were measured using ELISA in 75 adults; moderate persistent asthma (n=25), severe persistent asthma (n=25) and healthy community controls (n=25). Severity of asthma was determined as per Global Initiative for Asthma guidelines. Subjects were followed up for 3 months and treatment responsiveness was assessed by spirometry and symptom response. RESULTS: Serum MMP-1 and TGF-ß1 were significantly elevated in asthmatics compared with controls (p<0.0001 and p<0.01). While serum MMP-1 was elevated in severe asthma compared with moderate asthma (p<0.05), TGF-ß1 was lower in severe asthma compared with moderate asthma (p<0.05). The performance characteristics of serum MMP-1 and TGF-ß1 were promising in this cohort with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 82%, 100%, 100% and 99% and 62%, 100%, 100% and 97.8%, respectively; sensitivity of MMP-1 being superior. CONCLUSION: This pilot study showed that serum MMP-1 and TGF-ß1 levels are elevated in chronic asthma and may serve as a useful adjunct in differentiating moderate from severe asthma. A large multicentre study in well characterised cohort of asthmatics is warranted to investigate their role in diagnosis and therapeutic monitoring.

Expression dynamics of the immune mediators ARG1, TBET, CIITA, IL10 and TGFB1 in chronic myeloid leukaemia patients during the first year of imatinib therapy.

The use of tyrosine kinase inhibitors seems to restore the broadly compromised immune system described in chronic myeloid leukaemia (CML) patients at diagnosis leading to a re-activation of the effector-mediated immune surveillance. Here, we describe the expression dynamics of immune factors during the first year on imatinib therapy. Gene expression was evaluated in 132 peripheral blood samples from 79 CML patients, including 34 who were serially followed. An aliquot of the stored sample used to monitor BCR-ABL1 levels was retro-transcribed to cDNA and gene expression was quantified by real-time PCR. An elevated expression of ARG1 was observed at diagnosis, while TBET, CIITA, IL10 and TGFB1 were significantly decreased. Once on therapy, each gene displayed a particular behaviour. ARG1 normalized to control levels at 3 months only in optimal molecular responders and was identified as the major contributor to the difference among patients. TBET reached normal levels after 12 months in optimal responders and non-responders, regardless the Th1-response previously associated, and CIITA continued downregulated. IL10 and TGFB1 achieved normal levels early at 3 months in both groups, afterwards IL10 was sustained while TGFB1 was slightly increased after 1 year in responders. Our findings are in agreement with an immune re-activation after imatinib initiation; however, some immune mediators may require a longer exposition. The follow-up of novel and reliable biomarkers, such as ARG1, one of the principal mechanisms of myeloid-derived-suppressor cells to inhibit immune system, may be useful to deepen the characterization of early responder patients.

Influence of Serum TGF-β1 and EGFR Levels on the Therapeutic Effect of High-Dose AraC in Patients with Acute Myeloid Leukemia Based on the Decision Curve / 中国实验血液学杂志

OBJECTIVE@#To analyze the influence of serum levels of transforming growth factor-β1 (TGF-β1) and epidermal growth factor receptor (EGFR) on the therapeutic effect of high-dose cytarabine (HD-AraC) in patients with acute myeloid leukemia (AML).@*METHODS@#98 patients with AML treated in our hospital from January 2019 to June 2020 were selected as the research subjects, all patients were treated with HD-AraC for 1 course of treatment every week. The effect of 2 groups were evaluated during after one course of treatment and divided into effective group and ineffective group, statistical table of baseline data was designed, the baseline data of 2 groups were counted in detail, the baseline data and serum levels of TGF-β1 and EGFR of 2 groups were compared, Logistic regression analysis was used to examine the relationship between the levels of serum TGF-β1, EGFR and the therapeutic effect of HD-AraC in patients with AML, the value of serum TGF-β1 and EGFR levels in predicting the therapeutic effect of HD-AraC in AML patients was analyzed based on ROC curve and decision curve.@*RESULTS@#After 1 course of treatment, among the 98 patients, 26 cases had complete remission, 38 cases had partially remission and 34 cases no remission, the total effective rate was 65.31% (64/98); after comparing data of 2 groups, Logistic regression analysis showed that the overexpression of serum EGFR before treatment might be a risk factor for the ineffective treatment of HD-AraC in AML patients (OR>1, P<0.05), overexpression of serum TGF-β1 before treatment might be a protective factor for the ineffective treatment of HD-AraC in AML patients (OR<1, P<0.05); the ROC curve results showed that the AUC of serum EGFR and TGF-β1 before treatment in predicting the risk of ineffective HD-AraC treatment in AML patients were >0.70, which had certain predictive value. The decision curve results showed that in the threshold range of 0.15-044, the prediction model combined with serum EGFR and TGF-β1 levels in predicting the net benefit rate of HD-AraC treatment in AML patients was better than that of serum EGFR or serum TGF-β1 alone.@*CONCLUSION@#The levels of serum TGF-β1 and EGFR affect the therapeutic effect of HD-AraC in patients with AML and increase the risk of ineffective treatment, serum TGF-β1 and EGFR can be used to predict the risk of ineffective HD-AraC treatment in AML patients, and the combined prediction of net benefit rate is higher.

AT2R stimulation with C21 prevents arterial stiffening and endothelial dysfunction in the abdominal aorta from mice fed a high-fat diet.

The aim of the present study was to evaluate the effect of Compound 21 (C21), a selective AT2R agonist, on the prevention of endothelial dysfunction, extracellular matrix (ECM) remodeling and arterial stiffness associated with diet-induced obesity (DIO). Five-week-old male C57BL/6J mice were fed a standard (Chow) or high-fat diet (HF) for 6 weeks. Half of the animals of each group were simultaneously treated with C21 (1 mg/kg/day, in the drinking water), generating four groups: Chow C, Chow C21, HF C, and HF C21. Vascular function and mechanical properties were determined in the abdominal aorta. To evaluate ECM remodeling, collagen deposition and TGF-ß1 concentrations were determined in the abdominal aorta and the activity of metalloproteinases (MMP) 2 and 9 was analyzed in the plasma. Abdominal aortas from HF C mice showed endothelial dysfunction as well as enhanced contractile but reduced relaxant responses to Ang II. This effect was abrogated with C21 treatment by preserving NO availability. A left-shift in the tension-stretch relationship, paralleled by an augmented ß-index (marker of intrinsic arterial stiffness), and enhanced collagen deposition and MMP-2/-9 activities were also detected in HF mice. However, when treated with C21, HF mice exhibited lower TGF-ß1 levels in abdominal aortas together with reduced MMP activities and collagen deposition compared with HF C mice. In conclusion, these data demonstrate that AT2R stimulation by C21 in obesity preserves NO availability and prevents unhealthy vascular remodeling, thus protecting the abdominal aorta in HF mice against the development of endothelial dysfunction, ECM remodeling and arterial stiffness.