Transforming Growth Factor-beta Levels Research Articles

Intestinal Microbiota and Derived Metabolites in Myocardial Fibrosis and Postoperative Atrial Fibrillation.

The high incidence of atrial fibrillation (AFib) following cardiac surgery (postoperative atrial fibrillation, POAF) relies on specific surgical features. However, in the setting of POAF, the role of the microbiome in the modulation of cardiac fibrosis is still not clear. This study aimed to analyze the effect of the microbiome and its main metabolic product (trimethylamine-N-oxide, TMAO) in the fibrosis of myocardial tissue, to investigate its role in POAF. Patients undergoing elective cardiac surgery with cardiopulmonary bypass, central atrio-caval cannulation and no history of AFib, were included. A fragment of the right atrium was analyzed for qualitative and mRNA-quantitative evaluation. A preoperative blood sample was analyzed with enzyme-linked immunosorbent assay (ELISA). A total of 100 patients have been included, with POAF occurring in 38%. Histologically, a higher degree of fibrosis, angiogenesis and inflammation has been observed in POAF. Quantitative evaluation showed increased mRNA expression of collagen-1, collagen-3, fibronectin, and transforming growth factor beta (TGFb) in the POAF group. ELISA analysis showed higher levels of TMAO, lipopolysaccharide and TGFb in POAF, with similar levels of sP-selectin and zonulin. TMAO ≥ 61.8 ng/mL (odds ratio, OR 2.88 [1.35-6.16], p = 0.006), preoperative hemoglobin < 13.1 g/dL (OR 2.37 [1.07-5.24], p = 0.033) and impaired right ventricular function (OR 2.38 [1.17-4.83], p = 0.017) were independent predictors of POAF. Also, TMAO was significantly associated with POAF by means of increased fibrosis. Gut microbiome product TMAO is crucial for myocardial fibrosis, which is a key factor for POAF. Patients in preoperative sinus rhythm who will develop POAF have increased genetic expression of pro-fibrotic genes and enhanced fibrosis in histological staining. Elevated TMAO level (≥61.8 ng/mL) is an independent risk factor for POAF.

Effects of honey administration on transforming growth factor beta-1 levels during orthodontic tooth movement in young and older rats

Effects of honey administration on transforming growth factor beta-1 levels during orthodontic tooth movement in young and older rats

Correlation between Transforming Growth Factor-Beta Levels and Skin Disorder Levels based on Modified Rodnan’s Skin Scores in Systemic Sclerosis Patients

Systemic sclerosis is a chronic connective tissue disease characterized by the excessive formation of fibrous tissue. The current determination of systemic sclerosis progression uses the modified Rodnan’s skin score (MRSS), which is checked manually by assessing skin stiffness based on subjective pinching. Transforming growth factor-beta (TGF-β) is a major cytokine in the formation of fibrous tissue as the potential marker of systemic sclerosis progression and the targeting therapy. This study aims to determine the correlation between TGF-β levels and modified Rodnan’s skin score in systemic sclerosis patients.This study was a cross-sectional design and carried out in September 2021 at RSUP Dr. Hasan Sadikin, Bandung. This research examined 33 samples of the biological material of systemic sclerosis patients obtained from a study entitled "Development of a Systemic Sclerosis Registry System Based on Electronic Medical Records" which were stored at -80 ºC. A TGF-β test was performed at the Clinical Laboratory of Hasan Sadikin General Hospital, Bandung.The results of this study showed that the mean TGF-β level was 19.6 + 4.7 ng/mL. We found a significant moderate correlation between TGF-β and modified Rodnan’s skin score with an R-value of 0.513 and a p-value of 0.002.In conclusion, there is a statistically significant moderate positive correlation between TGF-β levels and modified Rodnan’s skin scores in patients with systemic sclerosis. Although TGF-β is the main mediator of fibrous tissue formation, there are many other mediators.

The importance of biglycan, decorin and TGF-1 levels in the diagnosis of non-small cell lung cancer

BACKGROUND: Despite Non-small cell lung cancer (NSCLC) ranks among the most deadly cancers worldwide, and currently, apart from a low percentage, targetable molecules have not been identified in its etiopathogenesis. The relationship between the proteoglycans decorin and biglycan, which are present in the extracellular matrix of cells, and transforming growth factor Beta-1 (TGF-B1), has been shown in many cancers. We investigated the significance of these molecules in NSCLC. METHODS: Fasting serum levels of decorin, biglycan, and TGF-B1 were obtained from 48 newly diagnosed NSCLC patients and compared with those of 48 adult control subjects matched for age and demographics. Demographic data, baseline laboratory values, and ELISA results were compared between the groups. RESULTS: The median age was 65(39–83) similar in both groups. There was no relation between demographic and clinical parameters and the levels of decorin, biglycan, and TGF-B1 in the NSCLC group. However, in comparison to the control group, NSCLC patients had significantly higher levels of biglycan (42.55 ± 27.40 vs. 24.38 ± 12.05 ng/mL, p= 0.026) and TGF-B1 (15.55 ± 9.16 vs. 10.07 ± 7.8 pg/mL, p= 0.001), while decorin levels were significantly lower (6.64 ± 1.92 vs. 10.28 ± 3.13 ng/mL, p= 0.002). In the multivariate regression analysis; Decorin &lt; 8.13 ng/mL (OR, 10.96; 95% CI: 3.440–34.958), current smoking (OR, 3.81; 95% CI: 1.320–10.998), COPD (OR, 43.6; 95% CI: 2.082–913.081), and lower BMI (OR, 1.22; 95% CI: 1.070–1.405, p= 0.003) were identified as independent predictive markers for NSCLC diagnosis. CONCLUSION: The decreased serum decorin level is an independent marker for NSCLC. Further studies are needed to investigate the prognostic significance of decorin on survival and its potential as a target in treatment.

Molecular detection of Schistosoma haematobium in infected Bulinus truncatus snails associated with immune response.

Schistosomiasis is one of the most common waterborne parasite illnesses, it is a major public health issue in developing countries. The polymerase chain reaction (PCR) technique is used to find Schistosoma haematobium DNA in Bulinus truncatus, which could speed up the discovery of infections before cercariae are shed. DraI-PCR detected S. haematobium infection at different infection intervals with bands at 300 bp in shedding snails 40 days after exposure and even on the first day after B. turancuts snails exposure to miracidia. Transmission electron microscopy showed the structure of sporocyst from 1 to 40 days post-exposure and activated hemocytes in infected non-shedding snails as well as sporocyst degradation. Flow cytometry was used to measure the percentage of Bax and TGF-β1 positive stained cells that have been linked with infection progression. In conclusion, molecular tools and immune response play an important role in the strategy of controlling schistosomiasis through the early detection of larval stages in intermediate hosts toward certification of schistosomiasis elimination. RESEARCH HIGHLIGHTS: DraI-PCR allowed early detection of S. haematobium at 300 bp in B. truncatus snail. Transmission electron microscopy showed the structure of S. haematobium sporocyst in snail and activated hemocytes in non-shedding snail. Bax protein that induced apoptotic changes and Transforming Growth Factor Beta1 level have been linked with parasite development.

Serum transforming growth factor-beta levels and severity of retinoblastoma in children

Background Transforming growth factor-? (TGF-?) expression contributes to the growth of retinoblastoma. TGF-? is produced or released by infiltrating cells such as lymphocytes and monocytes/macrophages. TGF-? levels are a potential marker of disease severity.&#x0D; Objective To assess the difference in serum TGF-? levels before chemotherapy in patients with retinoblastoma grades III and IV. &#x0D; Methods This cross-sectional observational study was done at Dr. Wahidin Sudirohusodo Hospital, Makassar, Indonesia from January to November 2019. Subjects were pediatric patients with grade III and IV retinoblastoma who had not undergone chemotherapy. Patients who met the inclusion criteria provided blood specimens for TGF-? testing. We analyzed the difference in serum TGF-? level between grade III and grade IV patients.&#x0D; Results We obtained 38 subjects, consisting of 13 grade III and 25 grade IV retinoblastoma patients. Mean TGF-? levels were in 1,061 ng/L in grade III and 988 ng/L in grade IV patients. The Mann-Whitney U test revealed no significant difference between the levels of TGF-?, retinoblastoma grade III and IV (P=0.655). However, TGF-? levels in both groups were markedly above the normal value (100 ng/L).&#x0D; Conclusion TGF-? levels are markedly increased in grade III and IV retinoblastoma patients. There was no significant difference in TGF-? level between grade III and IV patients. Our findings suggest that TGF-? plays an important role in tumor cell development. Further research on differences in TGF-? levels between late stages (grades III and IV) and early stages (grades I and II) of retinoblastoma to elucidate the role of TGF-? as a marker of retinoblastoma severity.

Morphometric, Developmental, and Anti-Inflammatory Effects of Transamniotic Stem Cell Therapy (TRASCET) on the Fetal Heart and Lungs in a Model of Intrauterine Growth Restriction.

Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can attenuate placental inflammation and minimize intrauterine growth restriction (IUGR). We sought to determine whether MSC-based TRASCET could mitigate fetal cardiopulmonary effects of IUGR. Pregnant Sprague-Dawley dams were exposed to alternating 12-h hypoxia (10.5% O2) cycles in the last fourth of gestation. Their fetuses (n = 155) were divided into 4 groups. One group remained untreated (n = 42), while three groups received volume-matched intra-amniotic injections of either saline (sham; n = 34), or of syngeneic amniotic fluid-derived MSCs, either in their native state (TRASCET; n = 36) or "primed" by exposure to interferon-gamma and interleukin-1beta before administration in vivo (TRASCET-primed; n = 43). Normal fetuses served as additional controls (n = 30). Multiple morphometric and biochemical analyses were performed at term for select markers of cardiopulmonary development and inflammation previously shown to be affected by IUGR. Among survivors (75%; 117/155), fetal heart-to-body weight ratio was increased in both the sham and untreated groups (P < 0.001 for both) but normalized in the TRASCET and TRASCET-primed groups (P = 0.275, 0.069, respectively). Cardiac b-type natriuretic peptide levels were increased in all hypoxia groups compared with normal (P < 0.001), but significantly decreased from sham and untreated in both TRASCET groups (P < 0.0001-0.005). Heart tumor necrosis factor-alpha levels were significantly elevated in sham and TRASCET groups (P = 0.009, 0.002), but normalized in the untreated and TRASCET-primed groups (P = 0.256, 0.456). Lung transforming growth factor-beta levels were significantly increased in both sham and untreated groups (P < 0.001, 0.003), but normalized in both TRASCET groups (P = 0.567, 0.303). Similarly, lung endothelin-1 levels were elevated in sham and untreated groups (P < 0.001 for both), but normalized in both TRASCET groups (P = 0.367, 0.928). We conclude that TRASCET with MSCs decreases markers of fetal cardiac strain, insufficiency, and inflammation, as well as of pulmonary fibrosis and hypertension in the rodent model of IUGR.

Naringenin Impedes the Differentiation of Mouse Hematopoietic Stem Cells Derived from Bone Marrow into Mature Dendritic Cells, thereby Prolonging Allograft Survival.

The use of immature dendritic cells (imDCs) to induce donor-specific immunotolerance following in vivo stimulation is limited by their low rate of induction and their tendency to undergo maturation. We derived imDCs from bone marrow hematopoietic stem cells (HSCs-imDCs). We then tested the ability of naringenin (Nar) to impede the maturation of HSCs-imDCs for inducing transplantation immune tolerance. HSCs derived from bone marrow were collected and induced to differentiate into imDCs by treating with Nar (Nar-HSCs-imDCs). Flow cytometry was used to evaluate DC surface markers, apoptosis, and endocytic ability. The ability of DCs to influence the in vitro proliferation of T cells and of regulatory T cells (Tregs) was analyzed by mixed lymphocyte reaction assays. Enzyme-linked immunoassays were used to quantify cytokine levels in supernatants from co-cultured DCs and Tregs, as well as in the serum of experimental animals. The level of immunotolerance induced by Nar-HSCs-imDCs was evaluated by skin grafting in recipient Balb/c mice, while the Kaplan-Meier method was used to statistically evaluate graft survival. Compared with HSC-imDCs, Nar-HSCs-imDCs showed higher expression of cluster of differentiation 11c (CD11c), but lower expression levels of CD80, CD86, and major histocompatibility complex class II. Nar-HSCs-imDCs also showed stronger inhibition of T cells and higher Treg cell proliferation. Interleukin 2 (IL-2) and interferon gamma levels were downregulated in Nar-HSCs-imDCs, whereas IL-4, IL-10, and transforming growth factor beta levels were upregulated. The rate of apoptosis and endocytic capacity of Nar-HSCs-DCs increased significantly after treatment with lipopolysaccharide. HSCs-imDCs or Nar-HSCs-imDCs were injected into Balb/c mice via the tail vein 7 days before skin grafting. Significantly reduced donor-specific CD4+ T cells and induced proliferation of CD4+CD25+FoxP3+ Treg cells were observed in the spleen of mice from the Nar-HSCs-imDCs group, especially at a dose of 106 Nar-HSCs-imDCs. The latter group also showed significantly prolonged survival of skin grafts. Nar-HSCs-imDCs markedly improved the acceptance of organ allografts, offering a potentially new strategy for inducing immune tolerance in transplantation.

Combination of Cinnamaldehyde with Carvacrol or Thymol Improves the Mechanical Properties of Tibia in Post-Peak Laying Hens.

Roles of plant-derived cinnamaldehyde, carvacrol, and thymol in the gut and bone health of laying hens was evaluated in the present study. After acclimation for 2 weeks, a total 384 of 52-week-old laying hens were allocated into three groups for 6 weeks: (1) basal diet group (Ctrl), (2) combination of cinnamaldehyde with carvacrol group (CAR+CIN), and (3) blend of cinnamaldehyde with thymol (THY+CIN). The dietary essential oil level was 100 mg/kg. Each treatment group had eight replicate pens (16 birds/pen). The stiffness and ultimate load of the tibiae from both the CAR+CIN and THY+CIN groups were higher than that of the Ctrl group (p &lt; 0.05), along with comparable tibia ash, calcium, and phosphorus content among groups. At the same time, the manipulation of essential oils upregulated the transcription abundances of intestinal barrier proteins to varying degrees, whereas the experimental treatment failed to affect the composition in phyla of cecal microbiota. When compared to the Ctrl group, birds fed the CAR+CIN and THY+CIN diet displayed decreased bone resorption markers, reduced interleukin-1 concentrations, and increased transforming growth factor beta levels in serum. These findings suggest that cinnamaldehyde with carvacrol or thymol in feed of hens could enhance intestinal barrier and improve the mechanical properties of tibiae through structural modelling but not increase the mineral density, which might be involved in suppressing inflammation-mediated bone resorption.

Modulation of inflammatory M1-macrophages phenotype by valvular interstitial cells

BackgroundAortic valve stenosis involves inflammation, excess deposition of a collagen-rich extracellular matrix, and calcification. Recent studies have shown that M1 or inflammatory macrophages derived from infiltrating monocytes promote calcification of valvular interstitial cells, the most prevalent cell type of the aortic valve. We hypothesized that valvular interstitial cells could modulate inflammatory macrophages phenotype. MethodsWe first assessed macrophage phenotype in human aortic valve stenosis and control aortic valves from donors. Then, we examined profibrotic and inflammatory-related gene expression in valves and valvular interstitial cells. Finally, we investigated whether valvular interstitial cells can modify the phenotype of inflammatory macrophages. ResultsCirculating monocytes and plasma transforming growth factor beta-1 levels of patients with aortic valve stenosis were significantly higher compared with patients without aortic valve stenosis. Histologic analysis of thickened spongiosa of the aortic valve from patients with aortic valve stenosis showed a high macrophage infiltration but a low matrix metalloproteinase-9 expression compared with control aortic valves. On the other hand, valvular interstitial cell culture of aortic valve stenosis exhibited a profibrotic phenotype with a high expression of transforming growth factor beta-1 and transforming growth factor beta-1/transforming growth factor beta-3 ratio but a decreased expression of the peroxisome proliferator-activated receptor gamma nuclear receptor. Valvular interstitial cell–conditioned media of aortic valve stenosis led to a decrease in enzymatic activity of matrix metalloproteinase-9 and an increase in production of collagen in inflammatory macrophages compared with valvular interstitial cell–conditioned media from control aortic valve donors. ConclusionsThese findings indicate that profibrotic valvular interstitial cells promote the imbalance of extracellular matrix remodeling by reducing matrix metalloproteinase-9 production on inflammatory macrophages that lead to excessive collagen deposition observed in aortic valve stenosis. Further investigation is needed to clarify the role of transforming growth factor beta-1/proliferator-activated receptor gamma nuclear receptor/matrix metalloproteinase-9 in aortic valve stenosis.

Transforming Growth Factor-Beta Orchestrates Tumour and Bystander Cells in B-Cell Non-Hodgkin Lymphoma.

Simple SummaryTransforming growth factor-beta (TGFB) is a ubiquitously expressed cytokine involved in numerous functions in both normal and cancer cells. Here, we review, for the first time, the evidence of how B-cell lymphoma cells respond to TGFB and utilise TGFB to modulate surrounding cells in the microenvironment. We highlight recent data supporting the bi-directional signalling between B-cell lymphoma cells and their microenvironment. Targeting TGFB signalling in B-cell lymphoma may provide a future therapeutic strategy but further research is required to understand how lymphoma cells interact in different microenvironmental contexts.Transforming growth factor-beta (TGFB) is a critical regulator of normal haematopoiesis. Dysregulation of the TGFB pathway is associated with numerous haematological malignancies including myelofibrosis, acute myeloid leukaemia, and lymphoid disorders. TGFB has classically been seen as a negative regulator of proliferation in haematopoiesis whilst stimulating differentiation and apoptosis, as required to maintain homeostasis. Tumours frequently develop intrinsic resistant mechanisms to homeostatic TGFB signalling to antagonise its tumour-suppressive functions. Furthermore, elevated levels of TGFB enhance pathogenesis through modulation of the immune system and tumour microenvironment. Here, we review recent advances in the understanding of TGFB signalling in B-cell malignancies with a focus on the tumour microenvironment. Malignant B-cells harbour subtype-specific alterations in TGFB signalling elements including downregulation of surface receptors, modulation of SMAD signalling proteins, as well as genetic and epigenetic aberrations. Microenvironmental TGFB generates a protumoural niche reprogramming stromal, natural killer (NK), and T-cells. Increasingly, evidence points to complex bi-directional cross-talk between cells of the microenvironment and malignant B-cells. A greater understanding of intercellular communication and the context-specific nature of TGFB signalling may provide further insight into disease pathogenesis and future therapeutic strategies.

Microvessel quantification by fully convolutional neural networks associated with type 2 inflammation in chronic rhinosinusitis

BackgroundThe pathogenesis of chronic rhinosinusitis (CRS) is still unclear, and little is known about angiogenesis in this disease. We utilized a fully convolutional network (FCN), which has been extensively used in image processing to study angiogenesis in CRS. ObjectiveTo explore the tissue quantification of microvessels and their potential association with inflammation in CRS by using FCN to reflect the angiogenesis condition in CRS. MethodsFor endotyping of CRS, tissue homogenates of 79 patients with CRS who had undergone functional endoscopic sinus surgery and 17 control subjects were analyzed for interferon gamma, transforming growth factor beta, interleukin (IL)-1β, IL-5, IL-6, IL-8, IL-10, IL-17, tumor necrosis factor alpha, eosinophilic cationic protein, immunoglobulin E, and Staphylococcus aureus-immunoglobulin E(SE-IgE). A total of 552 hematoxylin and eosin-stained images of 27 CRS tissue samples were used to develop an FCN, going through training, validation, and evaluation processes. An optimized FCN was applied to quantify the microvessels of tissue samples of all subjects. Correlation analysis between microvessel quantification with phenotype, endotype, clinical characteristics, and cytokine expression of CRS was carried out. ResultsQuantification of microvessels in type 2 and non-type 2 CRS demonstrated considerable differences, with a higher expression in type 2 CRS. There was a strong negative correlation between the area ratio of microvessels with tissue tumor necrosis factor alpha and transforming growth factor beta levels and a mildly positive correlation with tissue IL-5 and eosinophilic cationic protein concentration. ConclusionFCN proved to facilitate the analysis of microvessels in airway tissue samples. This study elucidated the close association of angiogenesis with endotyping, suggesting that treatment aiming at antagonizing angiogenesis may assist to the therapy for the recrudescent and refractory CRS.

Therapeutic effects of asperosaponin VI in rabbit tendon disease

AbstarctIntroductionThis study explored the effects and molecular mechanisms of asperosaponin VI in tendon disease.MethodsForty-eight purebred adult male New Zealand white rabbits were randomly divided into the normal group (normal, n = 8); saline group (saline, n = 8) and prostaglandin E2 group (n = 32), which was further divided into four subgroups that were treated with asperosaponin VI doses of 0 mg/kg (model, n = 8), 10 mg/kg (10, n = 8), 20 mg/kg (20, n = 8) and 40 mg/kg (40, n = 8). The expression levels of matrix metallopeptidase 1 (MMP1), metallopeptidase inhibitor 1 (TIMP1), transforming growth factor beta 1 (TGFB1), serpin family E member 1 (SERPINE1), collagen Ⅰ (COL1), collagen Ⅲ (COL3) and tenomodulin (TNMD) in Achilles tendon tissue were determined through Western blot analysis. The histopathological changes in tendon tissue were observed by using Masson staining and haematoxylin–eosin staining.ResultsThe expression levels of MMP1, TIMP1 and COL3 were higher and those of TGFB1, SERPINE1, COL1 and TNMD were lower in the 0 mg/kg group than in the normal group (P < 0.05). Compared with those in the 0 mg/kg group, the levels of MMP1 were lower in the 20 and 40 mg/kg groups. Compared with those in the 0 mg/kg group, the levels of TIMP1 were lower and the levels of TGFB1, COL1 and TNMD were higher in the 10, 20 and 40 mg/kg groups. In addition, compared with those in other groups, the levels of SERPINE1 in the 40 mg/kg group were significantly higher and the levels of COL3 in the 10 and 20 mg/kg groups were significantly lower (P < 0.05). Fibrous tissue arrangements and structures in the 40 mg/kg group were similar to those in the control group.ConclusionThe effects of asperosaponin VI on injured tendons mainly involve eliminating inflammation, restoring balance to extracellular matrix collagen metabolism and inducing tendon cell proliferation. Asperosaponin VI is likely to be an ideal drug for the prevention and treatment of tendon disease.

Diagnostic Role of Transforming Growth Factor Beta Level in Necrotizing Enterocolitis in Extremely Low Birthweight Infants

Necrotizing enterocolitis (NEC) continues to be a leading cause of morbidity and mortality in premature infants.Premature infants may be at risk of NEC due to developmental deficiency of transforming growth factor Beta-1 level in the intestine, which is further accentuated during NEC. No significant differences in the incidence of NEC are noticed between male and female patients. TGF- β1 is an important marker for diagnosis and prognosis of necrotizing enterocolitis in extremely low birthweight infants and the aim of this work was to evaluate the diagnostic and prognostic value of transforming growth factor Beta-1 (TGF- β1) Level On necrotizing enterocolitis for greatly low birthweight babies. This might have been an instance - regulated study that incorporated 50 greatly low birthweight newely destined babies diagnosed Likewise necrotizing enterocolitis clinically and arranged as stated by altered Bell’s arranging criteria and 25 greatly low birthweight newely conceived babies without nec clinched alongside nicu of from june 2017 should june 2018. We established that the mean conception weight clinched alongside nec aggregation might have been 1. 61 ± 0. 35 (kg) Furthermore in control gathering might have been 1. 65 ± 0. 35 ( kg ) with male predominance. TGF- β1 level ≤ 864. 3 at onset about manifestations might altogether ( p = 0. 004 ) foresee nec Also TGF- β1 level ≥ 964. 7 after 7 times from claiming onset for manifestations could essentially ( p = 0. 011 ) anticipate seriousness of nec.

Circulating transforming growth factor-beta levels and myocardial remodeling in young adults with mitral valve prolapse patients

BackgroundLeft ventricular (LV) remodeling could be found in a range of connective tissue disorders with involvement of transforming growth factor (TGF)-β pathway. Only rare data are available on it in patients with mitral valve prolapse (MVP). ObjectivesThe aim of the study is to assess mechanisms of myocardial remodeling and diastolic dysfunction in asymptomatic young patients without mitral regurgitation. Methods78 asymptomatic young subjects with MVP were consecutively enrolled in our observational, single-center study. Concentrations of TGF-β1 and -β2 in serum were determined by enzyme-linked immunosorbent assay. Standard echocardiography extended with speckle-tracking echocardiography was performed in all patients. ResultsLevels of TGF-β1 (15.2 ± 12.3 ng/ml vs. 9.3 ± 7.7 ng/ml; р = 0.004) and -β2 (3.0 ± 1.9 ng/ml vs. 2.5 ± 1.2 ng/ml; р = 0.04) in serum were significantly higher in patients with MVP. LV myocardial mass index in patients with MVP did not differ from the controls but in MVP group there were more patients with concentric and eccentric hypertrophy. Significant deterioration of longitudinal early diastolic strain rate (SRe) was found in patients with MVP in the region of the interventricular septum (1.38 ± 0.22 s-1 vs. 1.54 ± 0.25 s-1; p = 0.00001) and anterior wall (1.44 ± 0.23 s-1 vs. 1.56 ± 0.22 s-1; p = 0.0007). In MVP group level of TGF-β2 correlated with LV mass index and SRe. Multivariate regression analysis between such factors as age and sex detected influence TGF-β2 concentration on SRe (OR 1.95; 95% CI 1.3–4.1; р = 0.01). ConclusionA circulating TGF-β is involved in the LV remodeling and deterioration of the diastolic function in MVP patients without significant mitral regurgitation, apparently due to the profibrotic nature of this cytokine.

Detecting tumor-infiltrating Forkhead box P3-positive T cells in the prognosis of lung adenocarcinoma: Possible role of clustering tumor interleukin-12 subunit alpha and transforming growth factor beta 1 expression.

While regulatory T cells (Tregs) are a poor prognostic factor for lung cancer, they may be detected as Forkhead box P3+ (FOXP3+) and cluster of differentiation (-CD) 4+ T cells by classifying FOXP3+CD4+ T cells into different subpopulations of CD4 cells. To classify clusters of tumor-infiltrating Tregs in lung adenocarcinoma based on the mRNA expression levels of interleukin-12 subunit alpha (IL12A) and transforming growth factor beta 1 (TGFB1) in tumor specimens. Seventy-nine patients with lung adenocarcinoma were evaluated in this study. Clinical data were obtained from the patients' medical records, while tumor tissue samples were preserved as formalin-fixed paraffin-embedded (FFPE) tissue specimens. Immunohistochemical staining for CD4, CD8 and FOXP3 was performed and stained cell counts were obtained under 5 high-power fields. cDNA was synthesized from total RNA extracted from FFPE tissue specimens and amplified with Taqman probes for FOXP3, IL12A, TGFB1, and the glyceraldehyde-3-phosphate dehydrogenase gene. Two clusters were identified: IL12AlowTGFB1low (Cluster 1: n = 44) and IL12AhighTGFB1high (Cluster 2: n = 39). Although no significant difference in the FOXP3+ cell/CD4+ cell ratio was observed between the 2 clusters (p = 0.921), the high FOXP3+/CD4+ cell ratio group showed a significantly poorer relapse-free survival rate than the low FOXP3+/CD4+ cell ratio group in Cluster 1 (p = 0.031). Although the results revealed no direct association between Tregs and prognosis according to each subtype, these results suggest that if a lung cancer specimen contains low levels of IL12A and TGFB1, the FOXP3+/CD4+ cell ratio is useful for predicting the prognosis of lung cancer.

Anti-invasive effect and pharmacological mechanism of genistein against colorectal cancer.

Colorectal cancer (CRC) refers to a deadly carcinoma following potent invasiveness and metastasis in advanced stage. Unfortunately, existing anti-CRC medicine is insufficient for chemotherapy in addition to adverse effects. Consequently, the candidate natural ingredient for treating CRC needs to be further developed. Our previous experiments report that genistein exerts beneficial effects to inhibit CRC cells via an antiproliferative mechanism. Based on the metastatic characteristics of staging CRC, anti-invasive and antimetastatic pharmacological activities using genistein remain uninvestigated. The scientific purpose of this study was to disclose the antimetastatic mechanism by using human and cell culture/nude mice samples, followed by biochemical tests and immunoassays. In human study, these CRC cases resulted in increased transforming growth factor beta-1 (TGF-β1) levels, long noncoding RNA (lncRNA) TTTY18 expressions, followed with up-regulated Ki-67, serum and glucocorticoid regulated kinase 1 (SGK1), AktSer473 expressions. In a study in vitro, genistein-dosed CRC cells showed suppressed cell viability, promoted cell apoptosis, reduced Ki-67 positive cells, reduced cellular migration, down-regulated expressions of TTTY18, SGK1, AktSer473 , p38 MAPKTyr323 . In a further study in vivo, genistein-dosed tumor-bearing nude mice exhibited visibly reduced body mass, lowered tumorous TGF-β1 and TTTY18 contents. In addition, intracellular numbers of SGK1, AktSer473 , p38 MAPKTyr323 positive cells were reduced dose-dependently. Collectively, these human and experimentative findings reveal that genistein pharmacologically exerts the potential antimetastatic CRC effects, possibly through a molecular mechanism of inhibiting TTTY18/Akt pathway in CRC cells.

Role of Urinary Transforming Growth Factor Beta-B1 and Monocyte Chemotactic Protein-1 as Prognostic Biomarkers in Posterior Urethral Valve.

Background:Posterior Urethral Valves (PUV) are the most common cause of congenital LUT obstruction in males. Biomarkers of glomerular or tubular injury may be of particular value in predicting the need for surgical intervention or in tracing progression of chronic kidney disease. Measurement of biomarker in urine is relatively easy.Aim:To evaluate the changes in values of urinary Transforming Growth Factor Beta 1(TGF-B1) and Monocyte Chemotactic Protein (MCP-1) before and after valve ablation and its prognostic value in Posterior urethral valve.Material and Method:This prospective study was conducted from September 2016 to August 2018. The study group included 20 consecutive male babies with the diagnosis of PUV treated and followed up versus equal numbers of age matched control without any renal or urinary tract disease. Pre-operative urine samples were collected in Operative room. Cystoscopy and valve ablation was done. Follow up was done clinically by urinary stream and radiologically with VCUG. Follow-up was planned at 1 month, 3 months and 6 months following cystoscopic valve ablation. All collected urine samples were centrifuged at 10,000 rpm for 20 minutes. Supernatant was collected and two divided aliquots were stored at -200c to be thawed on the day of assay. Optical density of each well was recorded at 450 nm and 540 nm A p-value of <0.05 was considered to be statistically significant.Result and Discussion:Out of 20 cases of PUV, 14 (70%) cases were 1st born males of their family. The median age at the time of valve ablation in PUV cases was 2.5 (1.20-3.87) years.. Most common symptoms are fever and UTI. The preoperative median serum creatinine level was 1.65 mg/dl(1.22-2.42) pre-ablation, and fall significantly after ablation. Median eGFR level (calculated) was 25.635 (16.38-35.40) and after 6 months was 71.490 (45.44-96.93). Preoperative median MCP1 in PUV cases was 147.2 (82.8-512.5) and significant difference was also found in 1st, 3rd and 6th months after surgery (p<0.001, p=0.004 and p=0.002).Preoperative median TGF-B1 level was 197.8 pg/ml (79.9-386.4). There was no statistically significant change in TGF-B1 level at preoperative to 1 month and preop to 3 months after surgery but at 6 months after surgery the median TGF-B1 level significantly decreased as compared with preoperative TGF-B1 level.Conclusion:TGF β1 and MCP1 can be considered as prognostic urinary biomarkers in patients of PUV and can be used to specify and counsel patient's attendant regarding possibility of ESRD and need for further intervention.

Biochemical and immunological investigation of fascioliasis in cattle in Egypt.

Background and Aim:Fasciola hepatica and Fasciola gigantica are two commonly reported liver flukes that cause fascioliasis in ruminants. Among the members of the genus Fasciola, F. hepatica was identified in the study area. Fascioliasis is a major disease that affects the production of livestock by causing liver damage. F. hepatica has developed advanced mechanisms to trick, elude, and alter the host immune response, similar to an extrinsic stressor. These mechanisms consequently affect the animals’ physiological and metabolic functions in vivo and postmortem changes, which have significant influences on animal welfare and meat quality development. Therefore, this study aimed to determine the current prevalence of cattle fascioliasis at abattoirs in El-Kharga city, New Valley Governorate, Egypt, and to investigate the changes in serum biochemical and immunological parameters and oxidative stress factors due to Fasciola spp. infection in terms of meat quality and immune response.Materials and Methods:A total of 226 cattle were inspected for the presence of Fasciola spp. The liver of each cattle was examined by making several incisions for detecting adult Fasciola spp. in El- Kharga. The blood samples were collected to analyze the changes in serum biochemical and immunological parameters and oxidative stress factors.Results:Of the 226 cattle, 38 (16.81%) were positive for F. hepatica at the postmortem examination. Cattle infected with F. hepatica had highly elevated serum alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase, γ-glutamyl transferase, urea, and creatinine levels. Immunological cytokine profiles showed significantly increased serum interleukin (IL)-4, IL-10, and transforming growth factor-beta levels and a significantly decreased interferon-γ level. Furthermore, oxidative stress profiles showed significantly increased serum malondialdehyde and nitric oxide levels and significantly decreased total antioxidant capacity and reduced glutathione level.Conclusion:This study demonstrated that F. hepatica infection alone is an oxidative stress factor that affects slaughtered animals, leading to biochemical and metabolic alterations in the early postmortem period.

New directions in metabolic syndrome diagnosis: assessment of vascular endothelial growth factor, pentraxin-3 and transforming growth factor beta levels

The article presents the results of Russian and international clinical studies on the levels of angiogenesis markers (vascular endothelial growth factor, pentraxin 3 and transforming growth factor beta) in patients with metabolic syndrome.