Yang J.-H.,Xi'an Jiaotong University |
Li B.,the 451st Hospital of Peoples Liberation Army |
Wu Q.,Xi'an Jiaotong University |
Lv J.-G.,Xi'an Jiaotong University |
Nie H.-Y.,Xi'an Jiaotong University
Biochemical and Biophysical Research Communications | Year: 2016
Receptor activator of nuclear factor-κB ligand (RANKL) is a key factor in the differentiation and activation of osteoclasts. Echinocystic acid (EA), a pentacyclic triterpene isolated from the fruits of Gleditsia sinensis Lam, was reported to prevent reduction of bone mass and strength and improve the cancellous bone structure and biochemical properties in ovariectomy rats. However, the molecular mechanism of EA on the osteoclast formation has not been reported. The purpose of this study was to investigate the effects and mechanism of EA on RANKL-induced osteoclastogenesis. Our results showed that EA inhibited the formation of osteoclast, as well as the expression of osteoclastogenesis-related marker proteins in bone marrow macrophages (BMMs). At molecular levels, EA inhibited RANKL-induced NF-κB activation and ERK phosphorylation in BMMs. In conclusion, the present study demonstrated that EA can suppress osteoclastogenesis in vitro. Moreover, we clarified that these inhibitory effects of EA occur through suppression of NF-κB and ERK activation. Therefore, EA may be a potential agent in the treatment of osteoclast-related diseases such as osteoporosis. © 2016 Elsevier Inc.
Gao R.,The 451st Hospital of Peoples Liberation Army |
Sun Z.,Xianyang Normal University |
Niu M.,Northwest University, China |
Zhao H.,Northwest University, China |
And 2 more authors.
Shiyou Huagong/Petrochemical Technology | Year: 2015
The influence of asphaltene content in coal tar feedstock which consisted of deasphalted oil in medium and low temperature coal tar mixed with crude asphaltene on the compositions and structures of hydrotreated asphaltenes was studied in an autoclave. The results showed that, with increasing the asphaltene content in the feedstock, the average relative molecular mass and the contents of sulfur, nitrogen and oxygen in the hydrotreated asphaltenes increased, the H/C atomic ratio and condensation degree parameter of the aromatic ring system decreased, but the aromaticity factor of the hydrotreated asphaltene increased, which indicated that the condensation degree of the hydrotreated asphaltene increased and its coking reactivity was enhanced. When the asphaltene content reached 17%(w), both the total ring number and the aromatic ring number in the hydrotreated asphaltene were more than those in the coal tar feedstock, which showed that the condensation reactions were dominating when the asphaltene content in the feedstock was excessively high. © 2015, SINOPEC Beijing Research Institute of Chemical Industry. All right reserved.
PubMed | Xi'an Jiaotong University and The 451st Hospital of Peoples Liberation Army
Type: Journal Article | Journal: Biochemical and biophysical research communications | Year: 2015
Insulin resistance plays an important role in the development of hypertension, which is seriously detrimental to human health. Recently, Sirtuin-1 (SIRT1) has been found to participate in regulation of insulin resistance. Therefore, further studies focused on the SIRT1 regulators might provide a potential approach for combating insulin resistance and hypertension. Interestingly, in this study, we found that SIRT1 was the target gene of the miR-543 by the Dual-Luciferase Reporter Assay. Moreover, the miR-543 expression notably increased in the insulin-resistant HepG2 cells induced by TNF-. Further analysis showed that the overexpression of the miR-543 lowered the SIRT1 mRNA and protein levels, resulting in the insulin resistance in the HepG2 cells; the inhibition of miR-543, however, enhanced the mRNA and protein expression of the SIRT1, and alleviated the insulin resistance. Furthermore, the SIRT1 overexpression abrogated the effect of miR-543 on insulin resistance. In addition, the overexpression of the miR-543 by the lentivirus-mediated gene transfer markedly impaired the insulin signaling assessed by the Western blot analysis of the glycogen synthesis and the phosphorylation of Akt and GSK3. In summary, our study suggested that the downregulation of the miR-543 could alleviate the insulin resistance via the modulation of the SIRT1 expression, which might be a potential new strategy for treating insulin resistance and a promising therapeutic method for hypertension.
PubMed | Ninth Hospital of Xian and The 451st Hospital of Peoples Liberation Army
Type: Journal Article | Journal: International journal of molecular medicine | Year: 2014
Studies have shown that the oxidative modification of lowdensity lipoprotein (oxLDL) plays a major role in atherogenesis. Lectinlike oxidized lowdensity lipoprotein receptor1 (LOX1) mediated the transport of oxLDL into macrophages, which promoted foam cell formation. Targeting LOX1 may therefore be a promising approach to inhibit atherosclerosis. In the present study, we aimed to investigate the effect of berberine combined with atorvastatin on LOX1 and explore the underlying molecular mechanism involved. Expression of LOX1 in monocytederived macrophages (MDMs) exposed to berberine (0, 0.1, 1, 10 and 100 nM) and atorvastatin (100 nM) were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analysis. Results showed that the expression of LOX1 was decreased in a dosedependent manner. Additionally, knockdown of the endothelin1 (ET1) receptor significantly blocked the inhibitory effect of berberine on LOX1 expression. Body weight (BW), liver weight (LW) and kidney weight (KW) in the model rats were markedly increased at concentrations of berberine 1 mol/kg, while heart weight (HW) and spleen weight (SW) remained constant among all groups. Berberine combined with atorvastatin also decreased serum total cholesterol (TC), triglyceride (TG) and lowdensity lipoproteincholesterol (LDLC) levels in the rat model as well as inflammation and oxidative stress. Furthermore, plasma ET1 levels and LOX1 expression were decreased by berberine combined with atorvastatin treatment, and the inhibitory effect on LOX1 was impeded by an ET1 receptor antagonist. The results demonstrated that berberine combined with atorvastatin downregulates LOX1 expression through ET1 receptors in monocyte/macrophages in vitro and in vivo.
PubMed | Xi'an Jiaotong University and The 451st Hospital of Peoples Liberation Army
Type: | Journal: Biochemical and biophysical research communications | Year: 2016
Angiotensin II (AngII) is the most important component of angiotensin, which has been regarded as a major contributor to the incidence of hypertension and vascular endothelial dysfunction. The adipocytokine C1q/TNF-related protein 6 (CTRP6) was recently reported to have multiple protective effects on cardiac and cardiovascular function. However, the exact role of CTRP6 in the progression of AngII induced hypertension and vascular endothelial function remains unclear. Here, we showed that serum CTRP6 content was significantly downregulated in SHRs, accompanied by a marked increase in arterial systolic pressure and serum AngII, CRP and ET-1 content. Then, pcDNA3.1-mediated CTRP6 delivery or CTRP6 siRNA was injected into SHRs. CTRP6 overexpression caused a significant decrease in AngII expression and AngII-mediated hypertension and vascular endothelial inflammation. In contrast, CTRP6 knockdown had the opposite effect to CTRP6 overexpression. Moreover, we found that CTRP6 positively regulated the activation of the ERK1/2 signaling pathway and the expression of peroxisome proliferator-activated receptor (PPAR), a recently proven negative regulator of AngII, in the brain and vascular endothelium of SHRs. Finally, CTRP6 was overexpressed in endothelial cells, and caused a significant increase in PPAR activation and suppression in AngII-mediated vascular endothelial dysfunction and apoptosis. The effect of that could be rescued by the ERK inhibitor PD98059. In contrast, silencing CTRP6 suppressed PPAR activation and exacerbated AngII-mediated vascular endothelial dysfunction and apoptosis. In conclusion, CTRP6 improves PPAR activation and alleviates AngII-induced hypertension and vascular endothelial dysfunction.
PubMed | The 451st Hospital of Peoples Liberation Army, PLA Fourth Military Medical University and The 323rd Hospital of Peoples Liberation Army
Type: Journal Article | Journal: Cell death & disease | Year: 2016
Periodontitis impairs the osteogenic differentiation of human periodontal mesenchymal stem cells (hPDLSCs), but the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs (lncRNAs) have been demonstrated to have significant roles under both physiologic and pathological conditions. In this study, we performed comprehensive lncRNA profiling by lncRNA microarray analysis and identified a novel lncRNA, osteogenesis impairment-related lncRNA of PDLSCs from periodontitis patients (lncRNA-POIR), the expression of which was significantly decreased in PDLSCs from periodontitis patients (pPDLSCs) and was upregulated by osteogenic induction. To study the functions of lncRNA-POIR, we prepared cells with overexpression and knockdown of lncRNA-POIR and found that lncRNA-POIR positively regulated osteogenic differentiation of hPDLSCs and pPDLSCs both in vitro and in vivo. Using quantitative real-time PCRs (qPCRs) and luciferase reporter assays, we demonstrated that lncRNA-POIR may act as a competing endogenous RNA (ceRNA) for miR-182, leading to derepression of its target gene, FoxO1. In this process, lncRNA-POIR and miR-182 suppress each other and form a network to regulate FoxO1. FoxO1 increased bone formation of pPDLSCs by competing with TCF-4 for -catenin and inhibiting the canonical Wnt pathway. Finally, inflammation increases miR-182 expression through the nuclear factor-B pathway, and the miR-182 overexpression in the inflammatory microenvironment resulted in an imbalance in the lncRNA-POIR-miR-182 regulatory network. In conclusion, our results provide novel evidence that this lncRNA-miRNA (microRNA) regulatory network has a significant role in osteogenic differentiation of pPDLSCs and that it has potential as a therapeutic target in mesenchymal stem cells during inflammation.