Baicalein attenuates bleomycin-induced lung fibroblast senescence and lung fibrosis through restoration of Sirt3 expression.

CONTEXT: Fibroblast senescence was reported to contribute to the pathological development of idiopathic pulmonary fibrosis (IPF), and baicalein is reported to attenuate IPF. OBJECTIVE: This study explores whether baicalein attenuates lung fibrosis by regulating lung fibroblast senescence. MATERIALS AND METHODS: Institute of Cancer Research (ICR) mice were randomly assigned to control, bleomycin (BLM), baicalein and BLM + baicalein groups. Lung fibrosis was established by a single intratracheal dose of BLM (3 mg/kg). The baicalein group received baicalein orally (100 mg/kg/day). Sirtuin 3 (Sirt3) siRNA (50 µg) was injected through the tail vein once a week for 2 weeks to explore its effect on the anti-pulmonary fibrosis of baicalein. RESULTS: BLM-treated mice exhibited obvious lung fibrosis and fibroblast senescence by showing increased levels of collagen deposition (27.29% vs. 4.14%), hydroxyproline (208.05 vs. 40.16 ng/mg), collagen I (25.18 vs. 9.15 µg/mg), p53, p21, p16, MCP-1, PAI-1, TNF-α, MMP-10 and MMP-12 in lung tissues, which were attenuated by baicalein. Baicalein also mitigated BLM-mediated activation of TGF-ß1/Smad signalling pathway. Baicalein restored the BLM-induced downregulation of Sirt3 expression in lung tissues and silencing of Sirt3 abolished the inhibitory role of baicalein against BLM-induced lung fibrosis, fibroblast senescence and activation of TGF-ß1/Smad signalling pathway. CONCLUSIONS: Baicalein preserved the BLM-induced downregulation of lung Sirt3 expression, and thus the suppression of TGF-ß1/Smad signalling pathway and lung fibrosis, which might provide an experimental basis for treatment of IPF.

Myeloid-derived suppressor cells promoted autologous B cell proliferation in rheumatoid arthritis / 北京大学学报(医学版)

Objective:To investigate the effect of myeloid-derived suppressor cells (MDSC) on pro liferation of B lymphocytes in rheumatoid arthritis (RA) patients.Methods:The peripheral blood specimens were collected from 15 healthy adults and 38 RA patients who were divided into high disease activity group,medium activity group and low activity group according to their 28-joint disease activity score (DAS28).And the frequencies of MDSC were determined by flow cytometry.Then,B cells and MDSC were isolated by flow cytometry,respectively.B cells were labeled with carboxyfluorescein diacetate suecinimidyl ester (CFSE) and then were co-cultured with MDSC in the presence of 3 mg/L anti-CD40 antibody and 10 mg/L CpG,for 3 days.Flow cytometry was performed to investigate the proliferation of B cells.Results:MDSC expanded markedly in high disease activity patients (7.13％ ±2.17％) compared with medium (5.35％ ±-1.36％) and low disease activity patients (4.72％ ± 1.08％) or healthy controls (4.79％ ± 1.02％) (P ＜ 0.05),and there were no statistical differences between healthy controls,medium and low disease activity RA (P ＞ 0.05).Moreover,the frequencies of MDSC were positively correlated with the DAS28 (P ＜ 0.05).After co-culture,MDSC significantly promoted B cell proliferation (P ＜0.01).Conclusion:Our studies showed that MDSC expanded obviously in high disease activity RA patients,and their frequencies were positively correlated with the disease activities.Furthermore,MDSC could promote autologous B cell proliferation remarkably in vitro.These findings suggest that MDSC might be involved in RA pathogenesis through regulating B cell functions.

Evaluation of the value of shear wave elastography in differential diagnosis of benign and malignant breast lesions by logistic regression / 中华医学超声杂志（电子版）

Objective To obtain the elasticity value of solid breast lesions with supersonic shear wave elastrography (SWE) and apply the binary Logistic regression in order to evaluate the value of SWE in differential diagnosis of benign and malignant breast lesions. Methods SWE quantitative elastography was preformed in 91 breast lesions of 91 patients in Zhenghai Longsai Hospital to obtain the maximum and mean elasticity value (Emax, Emean). And receiver operating characteristic (ROC) curves were used to assess the diagnostic performance. A Logistic regression for the gray scale ultrasound and the elastic modulus was conducted with multiple variables including Emax, Emean, border, echo, form, calcification. Results Pathological examination showed 73 benign lesions and 18 malignant lesions. Emax and Emean of malignant lesions were obviously higher than those of benign lesions [(99.73±41.15) kPa vs (38.59±14.28) kPa, (61.45±24.88) kPa vs (23.46±11.44) kPa, t=-15.05,-14.12, both P=0.000]. The area under the ROC curve of Emax and Emean were 0.932 and 0.915. Taking 63.70 kPa as the threshold of Emax, the sensitivity was 77.8%and the speciifcity was 97.3%. Then taking 44.22 kPa as the threshold of Emean, the sensitivity was 83.3%and the speciifcity was 94.5%. The results of Logistic regression analysis showed:the 3 most effective variables were Emax, border of the lesions and Emean. Conclusions The multivariate analysis model of binary Logistic regression can select the valuable indexes of differential diagnosis of benign and malignant breast lesions. SWE plays an important role in differentiating benign and malignant lesions and it is valuable in clinical practice.