Clinical assessment of TGFB1 and HP Relative Gene Expression in the Peripheral Blood of Prostate Cancer Patients.

OBJECTIVE: This study aimed to assess the relative gene expression level of transforming growth factor-ß1 (TGFB1) and haptoglobin (HP) in the peripheral blood of prostate cancer (PCa) patients and evaluate their diagnostic ability. METHODS: A total of 125 participants were enrolled in the present study. Among them, 75 PCa patients, 25 benign prostatic hyperplasia (BPH) patients, and 25 healthy volunteers served as the control group. The relative TGFB1 and HP gene expression level was quantified using real-time polymerase chain reaction. Further, free and total PSA levels were determined using electrochemiluminescence assays. RESULTS: TGFB1 was significantly over-expressed, whereas HP was significantly downregulated in the peripheral blood of PCa patients compared to BPH and control groups (p-value ranges from 0.034 to <0.001). Moreover, the high expression level of TGFB1 was associated with an increased risk of PCa development with OR=1.412 (95%CI: 1.081-1.869, p= 0.012). TGFB1 and HP relative expression levels had lower diagnostic performance to differentiate PCa from normal and BPH individuals compared to PSA, however, the combination of the tested parameters improved the diagnostic efficacy. CONCLUSIONS: TGFB1 and HP relative expression have moderate diagnostic efficacy in discriminating patients with PCa from BPH and healthy subjects. Furthermore, over-expression of TGFB1 may contribute to the pathogenesis of PCa.

Liraglutide ameliorates diabetic-induced testicular dysfunction in male rats: role of GLP-1/Kiss1/GnRH and TGF-ß/Smad signaling pathways.

Introduction: Glucagon-like peptide -1 (GLP-1) is released by intestinal cells to stimulate glucose-dependent insulin release from the pancreas. GLP-1 has been linked to ameliorating obesity and/or diabetic complications as well as controlling reproductive function. Liraglutide is a GLP-1 receptor agonist (GLP-1RA) with 97% homology with GLP-1. The main objective of this study was to investigate the ameliorative role of liraglutide in diabetic-induced reproductive dysfunction in male rats. Methods: Rats were randomly allocated into 3 groups; a control group, a diabetic group, and a liraglutide-treated diabetic group. Results: In the diabetic group, a significant increase in BMI, FBG, HbA1c, HOMA-IR, TC, TAG, LDL, IL6, TNFα, and MDA, as well as decreased serum insulin, HDL, GSH, total testosterone, LH, and FSH, were shown compared to the control group. Furthermore, A significant downregulation in relative hypothalamic gene expression of GLP-1R, PPAR-α, PGC-1α, kiss, kiss1R, leptin, leptin R, GnRH GLP-1R, testicular PGC-1α, PPARα, kiss1, kiss1R, STAR, CYP17A1, HSD17B3, CYP19A, CYP11A1, and Smad7, as well as upregulation in hypothalamic GnIH and testicular TGF- ß and Smad2 expression, were noticed compared to the control group. Liraglutide treatment significantly improved such functional and structural reproductive disturbance in diabetic rats. Conclusion: GLP-1RAs ameliorated the deleterious effects of diabetes on reproductive function by targeting GLP-1/leptin/kiss1/GnRH, steroidogenesis, and TGF- ß/Smad pathways.

Evidence that cervical cancer cells cultured as tumorspheres maintain high CD73 expression and increase their protumor characteristics through TGF-ß production.

Recently, a link between the biological activity of CD73 and tumorigenicity in solid tumors has been proposed. We previously reported that the generation of adenosine (Ado) by the activity of CD73 in cervical cancer (CC) cells induces transforming growth factor-beta 1 (TGF-ß1) production to maintain CD73 expression. In the present study, we analyzed the participation of TGF-ß1 in CD73 expression and the development of protumoral characteristics in CaSki CC cells cultured as tumorspheres (CaSki-T) and in monolayers (CaSki-M). Compared with those in CaSki-M cells, CD73 expression and Ado generation ability were significantly increased in CaSki-T cells. CaSki-T cells exhibited enrichment in the CSC-like phenotype due to increases in the expression levels of stem cell markers (CD49f, CK17, and P63; OCT4 and SOX2), greater sphere formation efficiency (SFE), and an increase in the percentage of side population (SP) cells. Interestingly, compared with CaSki-M cells, CaSki-T cells produced a greater amount of TGF-ß1 and presented a marked protumor phenotype characterized by a significant decrease in the expression of major histocompatibility complex class-I (MHC-I) molecules, an increase in the expression of multidrug resistance protein-I (MRP-I) and vimentin, and an increase in the protein expression levels of Snail-1 and Twist, which was strongly reversed with TGF-ß1 inhibition. These results suggest that the presence of TGF-ß1-CD73-Ado feedback loop can promote protumoral characteristics in the CC tumor microenvironment.

Comprehensive Analysis of LncRNA AC010789.1 Delays Androgenic Alopecia Progression by Targeting MicroRNA-21 and the Wnt/ß-Catenin Signaling Pathway in Hair Follicle Stem Cells.

Background: Androgen alopecia (AGA), the most common type of alopecia worldwide, has become an important medical and social issue. Accumulating evidence indicates that long noncoding RNAs (lncRNAs) play crucial roles in the progression of various human diseases, including AGA. However, the potential roles of lncRNAs in hair follicle stem cells (HFSCs) and their subsequent relevance for AGA have not been fully elucidated. The current study aimed to explore the function and molecular mechanism of the lncRNA AC010789.1 in AGA progression. Methods: We investigated the expression levels of AC010789.1 in AGA scalp tissues compared with that in normal tissues and explored the underlying mechanisms using bioinformatics. HFSCs were then isolated from hair follicles of patients with AGA, and an AC010789.1-overexpressing HFSC line was produced and verified. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to verify the molecular mechanisms involved. Results: AC010789.1 overexpression promoted the proliferation and differentiation of HFSCs. Mechanistically, we demonstrated that AC010789.1 overexpression promotes the biological function of HFSCs by downregulating miR-21-5p and TGF-ß1 expression but upregulating the Wnt/ß-catenin signaling pathway. Conclusion: These results reveal that overexpression of AC010789.1 suppresses AGA progression via downregulation of hsa-miR-21-5p and TGF-ß1 and promotion of the Wnt/ß-catenin signaling pathway, highlighting a potentially promising strategy for AGA treatment.

Transforming Growth Factor-Beta (TGF-ß) Signaling in Cancer-A Betrayal Within.

A ubiquitously expressed cytokine, transforming growth factor-beta (TGF-ß) plays a significant role in various ongoing cellular mechanisms. The gain or loss-of-function of TGF-ß and its downstream mediators could lead to a plethora of diseases includes tumorigenesis. Specifically, at the early onset of malignancy TGF-ß act as tumour suppressor and plays a key role in clearing malignant cells by reducing the cellular proliferation and differentiation thus triggers the process of apoptosis. Subsequently, TGF-ß at an advanced stage of malignancy promotes tumorigenesis by augmenting cellular transformation, epithelial-mesenchymal-transition invasion, and metastasis. Besides playing the dual roles, depending upon the stage of malignancy, TGF-ß also regulates cell fate through immune and stroma components. This oscillatory role of TGF-ß to fight against cancer or act as a traitor to collaborate and crosstalk with other tumorigenic signaling pathways and its betrayal within the cell depends upon the cellular context. Therefore, the current review highlights and understands the dual role of TGF-ß under different cellular conditions and its crosstalk with other signaling pathways in modulating cell fate.

Immune responses to injury and their links to eye disease.

The eye is regarded as an immune privileged site. Since the presence of a vasculature would impair vision, the vasculature of the eye is located outside of the central light path. As a result, many regions of the eye evolved mechanisms to deliver immune cells to sites of dysgenesis, injury, or in response to the many age-related pathologies. While the purpose of these immune responses is reparative or protective, cytokines released by immune cells compromise visual acuity by inducing inflammation and fibrosis. The response to traumatic or pathological injury is distinct in different regions of the eye. Age-related diseases impact both the anterior and posterior segment and lead to reduced quality of life and blindness. Here we focus attention on the role that inflammation and fibrosis play in the progression of age-related pathologies of the cornea and the lens as well as in glaucoma, the formation of epiretinal membranes, and in proliferative vitreoretinopathy.

Structural and chemical role of mesenchymal stem cells and resveratrol in regulation of apoptotic -induced genes in Bisphenol-A induced uterine damage in adult female albino rats.

The probable beneficial effects of mesenchymal stem cells (MSCs) and resveratrol were assessed in an experimental model of Bisphenol-A (BPA)-evident uterine damage in rats. Thirty-five albino rats were involved and equally divided into five groups: Group I: negative control rats received usual diet, Group II: positive control rats received BPA by oral gavage for 15 days, Group III: BPA-treated rats received single oral gavage of resveratrol daily for two weeks, Group IV: BPA-treated rats received a single intravenous dose of MSCs and Group V: BPA-treated rats received combined treatment of resveratrol and MSCs. Oxidative stress markers, apoptosis-related genes, and gonadal hormones were assessed. Histological and immunohistochemical examination of uterine tissue was conducted for TGF-ß 1. Caspases-3, 8, and 9 (Casp3, Casp8, Casp9) genes were assessed in uterine tissues by quantitative real-time PCR. Results revealed that BPA induced significant changes in the endometrial tissue, inflammatory cell infiltration, focal blood extravasation, increase in collagen fibers, decrease in PAS staining, and increase in TGF-ß 1 immunoreactivity. BPA also induced a significant increase in oxidative stress markers; malondialdehyde (MDA), SOD, CAT, and apoptosis-related genes. BPA induced a significant change in blood levels of gonadal hormones; a significant increase in FSH and a significant decrease in estradiol (E2) and progesterone (P). Treatment with either resveratrol, MSCs, or a combination of them resulted in significant enhancement of histological findings, restoration of gonadal hormones to near-normal levels, and a significant decrease in oxidative stress markers and apoptosis genes. Combined treatment with resveratrol and MSCs demonstrated more significant therapeutic effects as regard to the studied parameters in association with rat groups treated with either MSCs or resveratrol separately.

Huoxin Pill () Attenuates Cardiac Fibrosis by Suppressing TGF-ß1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats.

OBJECTIVE: To evaluate the effects of Huoxin Pill (, HXP) on cardiac fibrosis and heart failure (HF) in isoproterenol (ISO)-induced HF rats. METHODS: Thirty Wistar rats were randomly divided into 5 groups including control, HF, isosorbide mononitrate (ISMN), HXP low (HXP-L), and HXP high (HXP-H) groups (n=6 for each group) according to the complete randomization method. Rats were pretreated with ISMN (5 mg/kg daily), low concentration of HXP (10 mg/kg daily) or high concentration of HXP (30 mg/kg daily) or equal volume of saline by intragastric administration for 1 week, followed by intraperitoneal injection of ISO (10 mg/kg, 14 days), and continually intragastric administrated with above medicines or saline for additional 6 weeks. The effects of HXP treatment on the cardiac function, heart weight index (HWI), pathological changes, and collagen content were further assessed. Moreover, the role of HXP on activation of transforming growth factor- ß 1 (TGF-ß 1)/Smads pathway was further explored using immunohistochemistry (IHC) and Western-blot assay. RESULTS: HXP treatment significantly alleviated the decrease of ejection fraction (EF) and fractional shortening (FS), while decreased the elevation of left ventricular end-systolic volume (LVESV) in ISO-induced HF rats (P<0.05). Moreover, HXP treatment obviously attenuated the increase of HWI and serum level of creatine kinase MB (CK-MB, P<0.05), as well as pathological changes in ISO-induced HF rats. Further determination indicated that HXP treatment alleviated the elevation of collagen I and collagen III protein expression in cardiac tissues of ISO-induced HF rats. Furthermore, HXP treatment significantly down-regulated the increase of TGF-ß 1 and p-Smad2/3 protein expression in cardiac tissues of HF rats (P<0.05), while did not affect the expression of total Smad2/3. CONCLUSIONS: HXP attenuated heart failure and cardiac fibrosis in ISO-induced HF rats by suppression of TGF-ß 1/Smad2/3 pathway.

Mechanisms of ivermectin-induced wound healing.

BACKGROUND: Wounds cause structural and functional discontinuity of an organ. Wound healing, therefore, seeks to re-establish the normal morphology and functionality through intertwined stages of hemostasis, inflammation, proliferation, and tissue remodelling. Ivermectin, a macrolide, has been used as an endectoparasiticide in human and veterinary medicine practice for decades. Here, we show that ivermectin exhibits wounding healing activity by mechanisms independent of its well-known antiparasitic activity. This study aimed to evaluate the wound healing property of ivermectin cream using histochemistry and enzyme-linked immunosorbent assay techniques. RESULTS: Non-irritant dose of ivermectin cream (0.03-1%) decreased wound macroscopic indices such as exudation, edge edema, hyperemia, and granulation tissue deposition by day 9 compared to day 13 for the vehicle-treated group. This corresponded with a statistically significant wound contraction rate, hydroxyproline deposition, and a decreased time to heal rate. The levels of growth factors TGF-ß1 and VEGF were significantly elevated on day 7 but decreased on day 21. This corresponded with changes in cytokines (IL-1α, IL-4, IL-10, and TNF-α) and eicosanoids (LTB4, PGE2, and PGD2) levels on days 7 and 21.. Interestingly, low doses of ivermectin cream (0.03-0.1%) induced wound healing with minimal scarring compared to higher doses of the cream and the positive control, Silver Sulfadiazine. CONCLUSION: Ivermectin promotes wound healing partly through modulation of the inflammatory process and the levels of Transforming Growth Factor-Beta 1 and Vascular Endothelial Growth Factor. Low doses of ivermectin cream have the potential to be used in treating wounds with minimal scar tissue formation.

Effects of latanoprost on the expression of TGF-ß1 and Wnt / ß-catenin signaling pathway in the choroid of form-deprivation myopia rats.

In this study, we investigated the effect of latanoprost on the expression of TGF- ß1 and Wnt / ß - Catenin signal pathway in the choroid of form-deprivation myopia model rats. Forty rats were randomly divided into two groups: the control group and the FDM model group. Each group had 20 rats. The FDM model group was established by feeding latanoprost daily for 28 days. 15 rats in each group were used to measure the length of the ocular axis and the level of TGF-ß1 in choroidal tissue; the remaining 5 rats in each group were used for choroidal fibroblast culture. After modeling, the rats were killed, the length of the ocular axis was measured with a vernier caliper, and the level of TGF - ß1 protein and mRNA in the choroidal tissue of each group were measured with RT-PCR method. Results showed that compared with the control group, there was a significant difference in the axial length of the FDM model group (P< 0.05). There was a significant difference in the expression of TGF- ß1 protein and mRNA between the two groups (P<0.05). The cultured cells were identified as choroidal fibroblasts by immunocytochemistry. There was no significant difference (P>0.05) in the comparison of GSK3 ß protein in choroidal fibroblasts of rats in each group. TGF-ß 1 and APC protein in FDM group were significantly lower than those in the control group (P<0.05), while dcl3, p21-gsk3 ß and ß - Catenin proteins were significantly higher (P<0.05), and there was no significant difference (P>0.05) in the ratio of various indexes protein in FDM + ddk1 group and the comparison of TGF - ß1 and APC protein in FDM + ddk1 group and FDM group The expression of dcl3, p21-gsk3 ß and ß - Catenin decreased significantly (P<0.05). There was no significant difference in the expression of GSK3 ß mRNA in the choroidal fibroblasts of each group (P>0.05). The expression of TGF - ß 1 and APC mRNA in FDM group was significantly lower than that in the control group (P<0.05), while the expression of dcl3, p21-gsk3 ß and ß-catenin mRNA in FDM + ddk1 group was significantly higher than that in the control group (P<0.05) >In FDM + ddk1 group, TGF-ß 1 and APC mRNA were significantly lower than those in FDM group (P<0.05), while dcl3, p21-gsk3 ß and ß-Catenin mRNA were significantly higher (P<0.05).

Platyconic Acid A, Platycodi Radix-Derived Saponin, Suppresses TGF-1-induced Activation of Hepatic Stellate Cells via Blocking SMAD and Activating the PPAR Signaling Pathway.

Platycodi radix is a widely sold health food worldwide, which contains numerous phytochemicals that are beneficial to health. Previously, we reported that saponin from the roots of Platycodi radix-derived saponin inhibited toxicant-induced liver diseases. Nevertheless, the inhibitory effect of platyconic acid A (PA), the active component of Platycodi radix-derived saponin, on the anti-fibrotic activity involving the SMAD pathway remains unclear. We investigated the inhibitory effects of PA on TGF-1-induced activation of hepatic stellate cells (HSCs). PA inhibited TGF-1-enhanced cell proliferation, as well as expression of -SMA and collagen 1 in HSC-T6 cells. PA suppressed TGF-1-induced smad2/3 phosphorylation and smad binding elements 4 (SBE4) luciferase activity. Reversely, PA restored TGF-1-reduced expression of smad7 and peroxisome proliferator-activated receptor (PPAR)γ. PA also repressed TGF-1-induced phosphorylation of Akt and MAPKs. In summary, the results suggest that the inhibitory effect of PA on HSCs occurs through the blocking of SMAD-dependent and SMAD-independent pathways, leading to the suppression of -SMA and collagen 1 expression.

Hepatocellular Carcinoma: Etiology and Current and Future Drugs.

Hepatocellular carcinoma (HCC) is swiftly increasing in prevalence globally with a high mortality rate. The progression of HCC in patients is induced with advanced fibrosis, mainly cirrhosis, and hepatitis. The absence of proper preventive or curative treatment methods encouraged extensive research against HCC to develop new therapeutic strategies. The Food and Drug Administration-approved Nexavar (sorafenib) is used in the treatment of patients with unresectable HCC. In 2017, Stivarga (regorafenib) and Opdivo (nivolumab) got approved for patients with HCC after being treated with sorafenib, and in 2018, Lenvima (lenvatinib) got approved for patients with unresectable HCC. But, owing to the rapid drug resistance development and toxicities, these treatment options are not completely satisfactory. Therefore, there is an urgent need for new systemic combination therapies that target different signaling mechanisms, thereby decreasing the prospect of cancer cells developing resistance to treatment. In this review, HCC etiology and new therapeutic strategies that include currently approved drugs and other potential candidates of HCC such as Milciclib, palbociclib, galunisertib, ipafricept, and ramucirumab are evaluated.

Impact of treatment with a Protein Tyrosine Kinase Inhibitor (Genistein) on acute and chronic experimental Schistosoma mansoni infection.

Schistosomiasis mansoni is considered one of the most common fibrotic diseases resulting from inflammation and deposition of fibrous tissue around parasitic eggs trapped in the liver, causing morbidity and mortality. Chemotherapy against schistosomiasis is largely dependent on Praziquantel (PZQ). Yet, the huge administration of it in endemic areas and its incompetence towards the immature stages have raised serious alarms against the development of drug resistance. Few drugs are directed to reverse schistosomal liver fibrosis, particularly at the chronic and advanced stages of the disease. Recently, protein tyrosine kinase (PTK) inhibitors have been identified as potent anti-schistosomal and anti-fibrotic drugs against schistosomes, that may suppress and reverse Schistosoma mansoni (S. mansoni) induced liver fibrosis. The present study was designed to assess the anti-schistosomal and antifibrotic activity of Genistein, a PTK inhibitor, in comparison to PZQ, on both acute and chronic S. mansoni-infected mice using different parasitological, histopathological and immunohistochemical studies. Genistein showed a significant reduction (P < .05) in total worm burden, tissue egg load, mean hepatic granulomas diameter and numbers, percentage of collagen and expression of transforming growth factor-beta 1 (TGF-ß 1) in the examined hepatocytes with elevation in percentage of degenerated ova, in comparison to the control groups, in both acute and chronic stages of infection. The best results were obtained when Genistein was combined with PZQ. Therefore, it was concluded that Genistein showed a promising anti-schistosomal and anti-fibrotic properties which could make it one of the new potential targets in chemotherapy against schistosomiasis.

Indoleamine 2, 3-dioxygenase (IDO) increases during renal fibrogenesis and its inhibition potentiates TGF-ß 1-induced epithelial to mesenchymal transition.

BACKGROUND: Indoleamine 2, 3-dioxygenase (IDO) is an immunomodulatory molecule that has been implicated in several biological processes. Although IDO has been linked with some renal diseases, its role in renal fibrosis is still unclear. Because IDO may be modulated by TGF-ß1, a potent fibrogenic molecule, we hypothesized that IDO could be involved in renal fibrosis, especially acting in the TGF-ß1-induced tubular epithelial-mesenchymal transition (EMT). We analyzed the IDO expression and activity in a model of renal fibrogenesis, and the effect of the IDO inhibitor 1-methyl-tryptophan (MT) on TGF-ß1-induced EMT using tubular cell culture. METHODS: Male Wistar rats where submited to 7 days of UUO. Non-obstructed kidneys (CL) and kidneys from SHAM rats were used as controls. Masson's Tricrome and macrophages counting were used to chatacterize the tissue fibrosis. The EMT was analysed though immunohistochemistry and qRT-PCR. Immunohistochemestry in tissue has used to show IDO expression. MDCK cells were incubated with TGF- ß1 to analyse IDO expression. Additionally, effects of TGF- ß1 and the inhibition of IDO over the EMT process was acessed by immunoessays and scrath wound essay. RESULTS: IDO was markedly expressed in cortical and medular tubules of the UUO kidneys. Similarly to the immunolocalizaton of TGF- ß1, accompanied by loss of e-cadherin expression and an increase of mesenchymal markers. Results in vitro with MDCK cells, showed that IDO was increased after stimulus with TGF-ß1, and treatment with MT potentiated its expression. MDCK stimulated with TGF-ß1 had higher migratory activity (scratch-wound assay), which was exacerbated by MT treatment. CONCLUSIONS: IDO is constitutively expressed in tubular cells and increases during renal fibrogenesis. Although IDO is induced by TGF-ß1 in tubular cells, its chemical inhibitor acts as a profibrotic agent.

Tongxinluo Inhibits Renal Fibrosis in Diabetic Nephropathy: Involvement of the Suppression of Intercellular Transfer of TGF-[Formula: see text]1-Containing Exosomes from GECs to GMCs.

Glomerular mesangial cells (GMCs) activation is implicated in the pathogenesis of diabetic nephropathy (DN). Our previous study revealed that high glucose (HG)-treated glomerular endothelial cells (GECs) produce an increased number of TGF-[Formula: see text]1-containing exosomes to activate GMCs through the TGF-[Formula: see text]1/Smad3 signaling pathway. We also identified that Tongxinluo (TXL), a traditional Chinese medicine, has beneficial effects on the treatment of DN in DN patients and type 2 diabetic mice. However, it remained elusive whether TXL could ameliorate renal structure and function through suppression of intercellular transfer of TGF-[Formula: see text]1-containing exosomes from GECs to GMCs. In this study, we demonstrate that TXL can inhibit the secretion of TGF-[Formula: see text]1-containing exosomes from HG-treated GECs. Furthermore, exosomes produced by HG induced-GECs treated with TXL cannot trigger GMC activation, proliferation and extracellular matrix (ECM) overproduction both in vitro and in vivo. These results suggest that TXL can prevent the transfer of TGF-[Formula: see text]1 from GECs to GMCs via exosomes, which may be one of the mechanisms of TXL in the treatment of DN.

[Effect of Combined Intervention of Electroacupuncture and Astragaloside IV on Myocardial Hypertrophy and TGF-ß 1/Smad Signaling in Rats with Myocardial Fibrosis].

OBJECTIVE: To observe the effect of combined intervention of electroacupuncture (EA) and astragaloside IV(ASIV) on cardiac hypertrophy and transforming growth factor ß 1 (TGF-ß 1)/Smad signaling in isoproterenol (ISO) induced cardiac hypertrophy rats, so as to investigate its underlying mechanisms in improving myocardial fibrosis. METHODS: A total of 50 SD rats were randomly divided into 5 groups: normal control, model (ISO), Propranolol (PRO)，ASIV and EA＋ASIV groups (n＝10 in each group). The myocardial fibrosis model was established by intraperitoneal injection (i.p.) of ISO (10 mg·kg－1·d－1), once daily for 30 days. Rats of the control group were given normal saline (i.p.), those of the PRO group given with PRO (40 mg·kg－1·d－1, gavage), and those of the ASIV and EA＋ASIV groups were treated by gavage of ASIV (40 mg·kg－1·d－1), once daily for 30 days. EA (20 Hz, 6 V) was applied to bilateral "Neiguan" (PC 6) for 10 min, once every day for 30 d. The heart mass index (HMI, whole heart weight/body weight) and left ventricular (LV) mass index (LVMI, weight of the LV/body weight) were calculated to assess the state of cardiac hypertrophy. The enzyme linked immunosorbent assay (ELISA) was used to determine the levels of procollagen I carboxy-terminal propeptide (PICP，a marker of extracellular matrix remodeling) and carboxyterminal telopeptide of type I collagen (ICTP, a metabolite of type I collagen) in serum, and Western blot was used to test protein contents of TGF- ß 1, Smad 2 / 3, Smad 4, Smad 7 in the left ventricle tissue of the heart. RESULTS: After modeling, the HMI and LVMI, serum PICP and ICTP contents and the expression levels of myocardial TGF-ß 1, Smad 2/3 and Smad 4 proteins were significantly increased in the model (ISO) group (P<0.05), suggesting a deposition of collagen and cardiac hypertrophy, and were considerably decreased in PRO, ASIV and EA＋ASIV groups after the intervention (P<0.05). The expression level of myocardial Smad 7 protein was significantly lower in the model group than in the normal control group (P<0.05), and significantly up-regulated in PRO, ASIV and EA＋ASIV groups (P<0.05). Sirius Red staining of the left ventricular myocardium showed a dense deposition of collagen and a severer myocardial fibrosis in the model group, and a relatively lighter fibrosis in the PRO, ASIV and EA＋ASIV groups. The therapeutic effects of EA＋ASIV were comparable to those of PRO, and were significantly superior to those of ASIV in down-regulating HMI, serum ICTP, and myocardial Smad 2/3 and Smad 4 expression and up-regulating Smad 7 protein (P<0.05). There were no significant differences among the PRO, ASIV and EA＋ASIV groups in LVMI, PICP and TGF-ß 1 levels, and between the PRO and EA＋ ASIV groups in HMI, ICTP, Smad 2/3, Smad 4 and Smad 7 levels (P> 0.05). CONCLUSIONS: EA stimulation of PC 6 combined with ASIV can relieve cardiac hypertrophy and myocardial fibrosis in rats, which may be associated with its effects in regulating myocardial TGF-ß 1/Smad signaling pathway.

Association between transforming growth factor-ß1 expression and the clinical features of triple negative breast cancer.

The aim of the present study was to investigate the association between the expression levels of transforming growth factor-ß1 (TGF-ß1) and the clinical pathological characteristics and prognosis of triple negative breast cancer (TNBC) through study of TNBC patient tissue samples. The biological effects of TGF-ß1 on TNBC cells and the potential signal transduction pathway are additoinally investigated. Immunohistochemistry was utilized to investigate expression changes of the positive rate of TGF-ß1 in the TNBC, compared with the non-TNBC group, to explain the association between TGF-ß1 and clinical pathological characteristics and prognosis. MDA-MB-231 cells were treated with TGF-ß1 and subsequently the invasion and migration abilities, and the expression of proteins in certain signaling pathways were assessed before and after the treatment. Positive expression of TGF-ß1 was observed in 52.5% of TNBC tissue samples, which was higher than that observed in non-TNBC group (27.5%). High levels of TGF-ß1 expression were not significantly associated age, menopausal status, family history of cancer or tumor size; however, tumor histological grade and axillary lymph node metastasis were significantly associated (P<0.05). In addition, when the TGF-ß1 expression levels are higher, the 5-year disease-free survival rate is lower. TGF-ß1 expression promoted the invasion and migration of MDA-MB-231 cells, and the expression of Smad2 protein and P38 protein was increased, indicating that Smad2 protein and the P38 signaling pathway may serve an important role in TNBC.

Expression and significance of E-cadherin, N-cadherin, transforming growth factor-ß1 and Twist in prostate cancer.

OBJECTIVE: To study the expression of E-cadherin, N-cadherin, TGF-ß1 and Twist protein and investigate its significance in the occurrence and development of prostate cancer. METHODS: The expression of E-cadherin, N-cadherin, TGF-ß1 and Twist protein in 59 prostate cancer tissues and 21 adjacent tissues were detected by immunohistochemical SABC staining, and the correlation with clinicopathological features was analyzed. RESULTS: Positive rates of E-cadherin, N-cadherin, TGF-ß1 and Twist were 32.2%, 54.2%, 71.2% and 74.6%, respectively, in prostate cancer tissues and 85.7%, 9.52%, 19.0% and 9.52%, respectively, in cancer-adjacent tissues, with significant differences between the two groups (P<0.05). The reduced expression of E-cadherin was related to the differentiation of prostate cancer tissues and PSA level, but was not associated with clinical stage, lymph node metastasis, bony metastasis and age. The increased expression of N-cadherin, TGF-ß1 and Twist was related to the differentiation of prostate cancer tissues, clinical stage, lymph node metastasis, bony metastasis, but not to age. The difference in positive expression of N-cadherin and TGF-ß1 was significant between PSA≤20 µg/L group and PSA>20µg/L group, but the positive expression of Twist was not significant between groups. The expression of E-cadherin was highly negatively correlated with that of N-cadherin and also highly negatively correlated with that of Twist. The expression of TGF-ß1 was correlated with those of E-cadherin, N-cadherin and Twist. CONCLUSIONS: The reduced expression of E-cadherin, abnormal expression of N-cadherin, transformation form E-cadherin to N-cadherin and the increased expression of TGF-ß1 and Twist play an important role in the occurrence and development of prostate cancer.

The Role of the NLRP3 Inflammasome in Fibrosis.

Fibrosis leads to the deposition of collagens in organs and tissues. The resulting pathology induces a loss of function in the organ it is manifested in and this loss of function modulates the morbidity and mortality in that individual. Indeed, approximately 45% of all deaths in the Western world can be attributed to fibrosis and there are no FDA approved drugs for the treatment of fibrosis. The recent discovery of the inflammasome has led to a plethora of studies investigating this inflammatory signaling pathway in a wide variety of pathogen associated diseases. Many studies have focused on the NLRP3 inflammasome and this inflammasome is activated by a wide variety of cellular alarm signals. Once activated, caspase-1 is cleaved, inducing the secretion of IL-1ß and IL-18 that signal to aid in the clearance of invading organisms. However, as the knowledge of the inflammasome has expanded, it was found that it can directly control collagen synthesis, leading to the increased deposition of collagens in the tissues such as the lung, liver, heart, and skin. Mice lacking the inflammasome adaptor protein, ASC, failed to become fibrotic when exposed to bleomycin. Inhibition of caspase-1 activity in fibroblasts from patients with the fibrotic disease systemic sclerosis, decreased collagen synthesis and reduced α-smooth muscle actin expression in myofibroblasts. Taken together, these observations suggest that the inflammasome can drive the fibrotic response and paves the way for novel therapeutics to be identified.

Expression of protein vEGF and TGF-?1 in the process of cicatrization of incised wounds on rat skin / 重庆医科大学学报

Objective:To investigate whether the expression of protein VEGF and TGF-?1 can be used as an indextoestimate injuryage in the field of forensic medicine by approaching the temporal relation of VEGF and TGF-?1 expression with injury in the healing process of the incised wounds on rat skin.Methods:Experimental rat models were established by incisions made on the rat skin.the rat models were divided randomly into three groups:the experimental group,the normal group,and the postmortem injured group.The expression of VEGF and TGF-?1 were observed with Immunohistochemical techniques in their process of cicatrization.Results:In the experimental group,the expression of VEGF and TGF-?1 were higher than those in the normal control and postmortem injury group(P