The endothelial-to-mesenchymal transition (EndMT) in endothelial cells contributes to the development of cardiac fibrosis,ultimately leading to cardiac remodeling.In this study,the effects and molecular mechanisms of celastrol (CEL) on transforming growth factor-β1 (TGF-β1)-induced EndMT in human umbilical vein endothelial (HUVEC-12) cells were investigated.The presented data demonstrated.that CEL significantly blocked the morphology change of HUVEC-12 cells induced by TGF-β1 without cell cytotoxicity.In accordance with these findings,CEL blocked TGF-β1-induced EndMT as evidenced by the inhibition of the mesenchymal markers,including collagen Ⅰ,Ⅲ,α-SMA,fibronectin mRNA expression,and the increase in the mRNA expression of endothelial cell marker CD31.These changes were also confirmed by double immunofluorescence staining of CD31 and vimentin.The in vitro scratch assay showed that CEL inhibited the migration capacity of the transitioned endothelial cells induced by TGF-β1.Further experiments showed that the beneficial effect of CEL on blocking the EndMT in HUVEC-12 cells was associated with the suppression of the TGF-β1/Smads signalling pathway,which was also confirmed by the inhibition of its downstream transcription factor snail1,twistl,twist2,ZEB1 and ZEB2.These results indicate that CEL blocks TGF-β1-induced EndMT through TGF-β1/Smads signalling pathway and suggest that it may be a feasible therapy for cardiac fibrosis diseases.

China ; Humans ; Occupational Health Services ; manpower

Objective To evaluate the clinical effect of embolization of cerebral dural atreriovenous fistulas (cDAVF) of the eavemous sinus through the superior ophthalmic vein approach. Methods Twnety-seven patients with eDAVF of the cavernous sinus were embolized through the superior ophthalmic vein approach. Cerebral angiography and follow-up examination of the patients were performed to evaluate the effect ofernbolization. Results The fistulae showed complete angiographic disappearance in 15 patients, and 12 patients had blood velocity flow reduction at the fistula orifice. Ocular proptosis and chemosis deteriorated transiently in 11 patients after the procedure. The patients were followed-op for 3 to 48 months, and clinical cure was achieved in 17 patients, and 10 showed significant symptom relief. Conclusion cDAVF of the cavernous sinus can be effectively embolized through the superior ophthalmic vein approach.

Hyperglycemia is an important initiator of cardiovascular disease, contributing to the development of cardiomyocyte death and diabetic complications. The purpose of the present study was to investigate whether high glucose state could induce apoptosis of rat cardiomyocyte cell line H9c2 through microRNA-mediated Bcl-2 signaling pathway. The expression of miR-34a and Bcl-2 mRNA was detected by using real-time PCR. Western blotting was used to examine the changes in apoptosis-associated protein Bcl-2. Apoptosis of H9c2 cells was tested by using flow cytometry. The results showed that the expression of miR-34a was significantly elevated and that of Bcl-2 was strongly reduced, and apoptosis of cardiomyocytes was apparently increased in the high-glucose-treated H9c2 cells as compared with normal-glucose-treated controls. In addition, we identified Bcl-2 gene was the target of miR-34a. miR-34a mimics reduced the expression of Bcl-2 and increased glucose-induced apoptosis, but miR-34a inhibitor acted as the opposite mediator. Our data demonstrate that miR-34a contributes to high glucose-induced decreases in Bcl-2 expression and subsequent cardiomyocyte apoptosis.
Animals ; Apoptosis ; Cell Line ; Glucose ; metabolism ; MicroRNAs ; genetics ; metabolism ; Myocytes, Cardiac ; metabolism ; Rats

Objective: To explore the mechanism of herbal cake-partitioned moxibustion in Crohn disease (CD) treatment by observing the effect of herbal cake-partitioned moxibustion on protein expressions of colonic M2 macrophage marker CD206, AMP-activated protein kinase (AMPK) and tuberous sclerosis complex (TSC) 2. Methods: Twenty-six specific pathogen free male rats were randomly divided into a normal group, a model group and a herbal cake-partitioned moxibustion group. The CD model was prepared by enema with the mixture of 5％ (W/V) 2,4,6- trinitrobenzene sulfonic acid (TNBS) and 50％ ethanol at 2:1 (volume ratio). After the model was successfully prepared, rats in the herbal cake-partitioned moxibustion group received herbal cake-partitioned moxibustion at Qihai (CV 6) and bilateral Tianshu (ST 25). Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of rat colon; immunohistochemical technique was used to detect the expression of colonic CD206 protein; Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) technologies were used to detect the protein and mRNA expressions of colonic AMPK and TSC2. Results: Compared with the normal group, rats in the model group showed damaged colonic mucosa, missing of the epithelial layer, thickened submucosa, vascular proliferation, massive infiltration of monocytes and lymphocytes, and cracked ulcers that reached the muscle layer. Rats in the herbal cake-partitioned moxibustion group showed reduced intestinal inflammation and healing intestinal epithelium ulcers. Compared with the normal group, rat colonic CD206 protein expression, and the protein and mRNA expressions of colonic AMPK and TSC2 were decreased in the model group (all P<0.01); compared with the model group, rat colonic CD206 protein expression was increased (P<0.01), as well as the protein and mRNA expressions of AMPK and TSC2 in the herbal cake-partitioned moxibustion (all P<0.05). Conclusion: Herbal cake-partitioned moxibustion can reduce intestinal inflammation in CD rats, increase colonic CD206 protein expression, and up-regulate the protein and mRNA expressions of colonic AMPK and TSC2.

OBJECTIVETo study the value of immunomarkers CXCL13, CD10, bcl-6 in pathologic diagnosis of angioimmunoblastic T-cell lymphoma (AITL).

METHODSOne hundred and fifteen cases of AITL, 30 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) and 30 cases of reactive lymph nodes with paracortical hyperplasia (RH) encountered during the period from January, 1990 to January, 2008 were retrieved from the archival files of the Department of Pathology, West China Hospital of Sichuan University, China. The morphologic features were reviewed and compared. Immunohistochemical study was performed by SP method for CXCL13, CD10, bcl-6, CD21, CD3epsilon, CD3, CD45RO, CD20 and Ki-67. TCR-gamma gene rearrangement study was also carried out.

RESULTSRegressed follicles were evident in 7.8% (9/115) of AITL cases, 6.7% (2/30) of PTCL, NOS cases and 83.3% (25/30) of RH cases, respectively. A marked increase of number of arborizing venules was shown in 98.3% (113/115) of AITL cases, 63.3% (19/30) of PTCL, NOS cases and 76.7% (23/30) of RH cases, respectively. In lymph nodes with paracortical hyperplasia, the expression of CXCL13, CD10 and bcl-6 were restricted to the germinal centers. In AITL, 96.5% (111/115) of cases showed CXCL13 expression, in contrast to 26.7% (8/30) of PTCL, NOS. Expression of CD10 and bcl-6 were found in the neoplastic cells in 50.4% (58/115) and 78.3% (90/115) of AITL, and 3.3% (1/30) and 3.3% (1/30) of PTCL, NOS, respectively. Irregular meshworks of CD21-positive follicular dendritic cells were found in all the AITL cases. Clonal TCR-gamma rearrangement was detected in 83% (83/100) of the AITL cases.

CONCLUSIONSAITL is a type of lymphoma originated from the follicular helper T cells. Detailed morphologic assessment and use of immunohistochemical markers are essential for accurate diagnosis.

Adult ; Aged ; Aged, 80 and over ; Chemokine CXCL13 ; metabolism ; Diagnosis, Differential ; Female ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Humans ; Immunoblastic Lymphadenopathy ; metabolism ; pathology ; Lymph Nodes ; metabolism ; pathology ; Lymphoma, T-Cell, Peripheral ; metabolism ; pathology ; Male ; Middle Aged ; Neprilysin ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Pseudolymphoma ; metabolism ; pathology

Objective::To observe the clinical efficacy of modified Buyang Huanwu Tang combined with Sanrentang in treating early diabetic nephropathy(DN)with deficiency of spleen and kidney, damp-heat and blood stasis syndrome and its effect on glucose and lipid metabolism, oxidative stress and inflammatory factors, in order to explore its mechanism. Method::A total of 72 early DN atients were randomly divided into control group and treatment group, with 36 cases in each group. The control group was orally treated with losartan potassium tablets(50 mg every time, once/day), while the treatment group was treated with modified Buyang Huanwu Tang combined with Sanrentang orally in addition to the therapy of the control group(1 dose/day). Both groups were treated for 3 months. The changes in clinical efficacy and safety indicators were observed for both groups. The 24 h urine albumin excretion rate(UAER), serum creatinine(SCr), serum cystatin C(Cys C), urea nitrogen (BUN), fasting blood glucose (FBG), 2 h postprandial blood glucose (2 hPG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione Peroxidase(GSH-Px), interleukin-2(IL-2), interleukin-4(IL-4), interleukin-8(IL-8), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α)of patients in two groups were observed before and after treatment. Result::The total clinical effective rate was 88.9%in therapy group, which was higher than 61.1%in control group(P<0.05). After treatment, levels of UAER, SCr, Cys C and BUN were lower in both groups(P<0.05), and the levels in treatment group were all lower than those in control group(P<0.05). Levels of FBG, 2 hPG and HbA1c were lower in both groups(P<0.05). There was no significant difference in FBG, 2 hPG and HbA1c levels between two groups after treatment. The levels of HDL-C were higher in both groups(P<0.05), and the levels in treatment group were higher than that in control group(P<0.05). The levels of TC, TG and LDL-C were lower in both groups(P<0.05), and the levels in treatment group were all lower than those in control group(P<0.05). The level of MDA was lower in both groups(P<0.05), and the level in the treatment group was lower than that in control group(P<0.05). The levels of SOD and GSH-Px were higher in both groups(P<0.05), and the levels in the treatment group were all higher than those in the control group(P<0.05). Serum levels of IL-2, IL-8 and TNF-α were lower in both groups(P<0.05), and the levels in the treatment group were lower than those in control group(P<0.05). Serum levels of IL-4 and IL-10 were higher in both groups(P<0.05), and the levels in the treatment group was higher than those in control group(P<0.05). Conclusion::Modified Buyang Huanwu Tang combined with Sanrentang is effective and safe in the treatment of early DN with spleen and kidney deficiency, damp-heat and blood stasis syndrome. They can further improve renal function and lipid metabolism, inhibit oxidative stress reaction and regulate the secretion balance of inflammatory factors in early DN patients.