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Duan L.,Tianjin First Central Hospital | Hao X.,Hebei United University | Liu Z.,Hebei United University | Zhang Y.,Tianjin First Central Hospital | Zhang G.,Hebei United University
FEBS Letters | Year: 2014

Dysregulation of the REarranged during Transfection proto-oncogene (RET) pathway and microRNA (miRNAs) are crucial for the development of medullary thyroid carcinomas (MTC). Here we demonstrate that miR-129-5p is down-regulated in MTC tissues and cell lines and inhibits RET expression by directly binding its 3′ untranslated regions. Ectopic expression of miR-129-5p significantly decreases cell growth, induces apoptosis and suppresses migration ability in MTC cells through decreasing the phosphorylated AKT, thus functioning as a tumor suppressor. These findings give new clues for understanding MTC carcinogenesis and may help in developing a therapeutic approach for the treatment of RET-activated MTC. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Feng X.Q.,Tianjin First Central Hospital
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2010

To study the anti-glioma effect of recombinant adenovirus mediated combined gene therapy of bFGF-siRNA and HIV1-Vpr in vivo. Mouse glioma model was established by injecting 5 × 10(6) LN229 cells into BALB/c-nu nude mice. 30 nude mice were randomly divided into 5 groups: the negative control group, mock group, bFGF-siRNA group, Vpr group and combined therapy group, which at regular intervals were injected with PBS, rAd5-null, rAd5-bFGF-siRNA, rAd5-Vpr, rAd5-bFGF-siRNA plus rAd5-Vpr, respectively. The tumor volume was recorded every third day to draw a growth curve. After four weeks treatment, the mice were killed and specimens were taken. HE, immunohistochemical and TUNEL staining were performed to observe the cell morphology, detect the changes of relevant target proteins and cell apoptosis, respectively. Also the ultrastructural changes were observed by electron microscopy. The tumor growth inhibition rates were 36.9%, 37.2% and 58.6% in the bFGF-siRNA group, Vpr group and combined therapy group, respectively, and the combined therapy group showed the most significant effect (P < 0.05). Also the results of HE, immunohistochemical and TUNEL staining revealed that the combined therapy group had the best effects on proliferation inhibition and apoptosis induced in glioma cells (P < 0.05). The most significant ultrastructural changes were observed in the combined therapy group. The combined gene therapy of bFGF-siRNA with Vpr shows a prominent and synergistic anti-glioma effect compared with that of mono-gene therapy in nude mice.


Jing W.,Tianjin First Central Hospital | Jiang W.,Tianjin First Central Hospital
Cell Proliferation | Year: 2015

Objectives: Degenerated disc disease is one of the most common medical conditions in patients suffering from low back pain. Recent studies have shown that microRNAs can regulate cell function in many pathological conditions. The aim of this study was to investigate expression and role of miR-93 in disc degeneration. Materials and methods: Quantitative RT-PCR was employed to investigate level of miR-93 in degenerative nucleus pulposus (NP) tissues. Then, functional analysis of miR-93 in regulating collagen II expression was performed. Subsequently, western blotting and luciferase reporter assay were used to detect the target gene. Results: We showed that miR-93 was significantly down-regulated in degenerative NP tissues and its levels were associated with grade of disc degeneration. Overexpression of miR-93 stimulated type II collagen expression in NP cells. Moreover, MMP3 was identified as a putative target of miR-93. MiR-93 inhibited MMP3 expression by directly targeting its 3'UTR, and this was abolished by miR-93 binding site mutations. Additionally, restoration of MMP3 in miR-93-overexpressed NP cells reversed effects of type II collagen expression. Expression of MMP3 inversely correlated with miR-93 expression in degenerative NP tissues. Conclusions: Taken together, we demonstrated that miR-93 contributed to abnormal NP cell type II collagen expression by targeting MMP3, involved in intervertebral disc degeneration. © 2015 John Wiley & Sons Ltd.


Zhang W.X.,Tianjin First Central Hospital
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases | Year: 2012

To investigate the effect of prostaglandins E1 combined with Xuebijing injection on the expression of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) in rats with acute pulmonary interstitial fibrosis. A rat model of pulmonary interstitial fibrosis was established by intratracheal injection of bleomycin (1 ml/kg). One hundred and eight Wistar rats were randomly divided into six groups with 18 in each group, which were normal control group, model group, hormone (methylprednisolone) treatment group, Xuebijing treatment group, prostaglandin E1 treatment group and combination treatment group (prostaglandin E1 and Xuebijing injection). Except for those in the normal control group, the rats in each group were sacrificed on the 7th, 14th and 28th day after treatment. The TGF-β1 expression in lung tissue was measured by immunohistochemical staining. The TNF-α concentration in bronchoalveolar lavage fluid (BALF) of rat model was determined by enzyme-linked immunosorbent assay. The combination treatment group showed significantly more macrophages with TGF-β1 expression in lung tissue at each time point, as compared with the model group, Xuebijing treatment group, methylprednisolone treatment group and prostaglandin E1 treatment group (P < 0.05). On the 7th day, the TNF-α concentration in BALF in the combination treatment group was significantly lower than those in the model group, methylprednisolone treatment group and prostaglandin E1 treatment group (P < 0.05); on the 14th day, the TNF-α concentration in BALF in the combination treatment group was significantly lower than that in the model group (P < 0.05); on the 28th day, the levels of TNF-α in the prostaglandin E1 treatment group and combination treatment group were significantly lower than that in the model group (P < 0.05). Prostaglandin E1 combined with Xuebijing injection may significantly inhibit TGF-β1 expression in the lung tissue of rats with acute pulmonary interstitial fibrosis, which reduces alveolar inflammatory response.


Wang W.L.,Tianjin First Central Hospital
The American journal of emergency medicine | Year: 2015

Pulmonary toxicity has frequently been recognized as a potentially serious complication associated with sirolimus therapy. It consists of a wide spectrum of syndromes most characterized by the presence of lymphocytic alveolitis and lymphocytic interstitial pneumonitis. The most commonly presenting symptoms are fever and dyspnea. Chest computed tomography generally reveals bilateral, patchy, or diffuse alveolointerstitial infiltrates. The discontinuation or dose reduction of sirolimus usually leads in most cases to a good outcome with complete clinical and radiologic resolution. However, to establish a diagnosis is difficult because of the absence of specific diagnostic criteria, and in rare cases, it could be fatal or life threatening when the diagnosis was delayed. Here, we reported 2 severe cases of acute respiratory distress attributed to the therapy of sirolimus in solid organ transplant recipients. Although the diagnostic course was difficult, withdrawal of sirolimus and temporary administration of steroids eventually resulted in a rapid recovery in both 2 patients. In addition, possible mechanisms, clinical characteristics, approach to diagnosis, and treatment strategies of sirolimus-induced pulmonary toxicity were also discussed in this article.


Li Y.,Harvard University | Wang W.,Tianjin First Central Hospital | Wang W.,Harvard University | Winkelman J.W.,Harvard University | And 3 more authors.
Neurology | Year: 2013

Objective: To prospectively examine whether men with restless legs syndrome (RLS) had an increased risk of mortality. Method: This was a prospective cohort study of 18,425 US men free of diabetes, arthritis, and renal failure in the Health Professionals Follow-up Study (HPFS). In 2002, RLS was assessed using a set of standardized questions. Deaths were identified from state vital statistics records, the National Death Index, family reports, and the postal system. Results: During 8 years of follow-up (2002-2010), we documented 2,765 deaths. In an age-Adjusted model, RLS was associated with a 39% increased risk of mortality (hazard ratio [HR] 5 1.39; 95% confidence interval [CI] 1.19-1.62; p , 0.0001). The association between RLS and mortality was slightly attenuated after further adjustment for body mass index, lifestyle factors, chronic conditions, sleep duration, and other sleep-related disorders (adjusted HR5 1.30; 95%CI 1.11-1.52; p5 0.003). When we further excluded those with major chronic conditions (e.g., cancer, high blood pressure, cardiovascular disease, and other comorbidities), the adjusted HR was 1.92 (95% CI 1.03-3.56; p 5 0.04). The interactions between RLS and other risk factors (older age, overweight, short sleep duration, smoking, low physical activity, and unhealthy diet) in relation to total mortality riskwere not significant (p for interaction .0.2 for all). Conclusion: We observed that men with RLS had a higher overall mortality and this association was independent of known risk factors. The increased mortality in RLS was more frequently associated with respiratory disease, endocrine disease, nutritional/metabolic disease, and immunologic disorders. Future research exploring the pathophysiologic relationship between these disorders and RLS is warranted. © 2013 American Academy of Neurology.


Shen Z.-Y.,Tianjin First Central Hospital | Zhang J.,Tianjin First Central Hospital | Song H.-L.,Tianjin First Central Hospital | Zheng W.-P.,Tianjin First Central Hospital
World Journal of Gastroenterology | Year: 2013

AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury. METHODS: BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-α blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent assay. RESULTS: Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-α levels. Administration of anti-TNF-α IgG or anti-TNF-α receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption. CONCLUSION: Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury. © 2013 Baishideng. All rights reserved.


Chu Z.-Q.,Tianjin First Central Hospital | Ji Q.,Tianjin First Central Hospital
Transplantation Proceedings | Year: 2013

Introduction: To achieve a true state of allo-tolerance is one of the ultimate goals in transplantation. Many studies suggest that CD4 +CD25high T regulatory cells (Tregs) have a crucial role to down-regulate the immune response to allo-antigens. In this study, we investigated the possible influence of immunosuppressive therapy, including sirolimus (SRL) and calcineurin inhibitors (CNIs, tacrolimus, or cyclosporine), on the level of Tregs in renal allograft recipients. Materials and Methods: We assessed 88 renal transplant recipients with stable renal function for at least 2 years, dividing them into 2 groups: SRL-treated (n = 28) or CNIs-treated (n = 29 tacrolimus and n = 31 cyclosporine). Thirty-eight age-matched healthy subjects (HS) served as normal controls. We examined the expression of CD4, CD25, and forkhead box p3 (Foxp3) in peripheral blood mononuclear cells. Flow cytometry was performed with data analysis using Cell Quest software. The 5-year graft survivals were correlated with Tregs content. Results: CNIs significantly decreased the percentage of Tregs compared with the HS and SRL groups (P <.01). The percentage of Tregs in the SRL group was not significantly different from that among HS. The ratio of CD4+CD25 highTregs to CD4+ T cells was 0.88% (0.28-1.42%), 1.15% (0.57-1.48%), and 0.21% (0.11-0.29%) among the SRL, HS, and CNIs cohorts respectively (SRL vs CNIs, P =.000165; SRL vs HS, P =.258; CNIs vs HS, P =.00030). Foxp3 was expressed in >95% of CD4+CD25high T cells versus <20% among CD4+CD25low T cells and not at all in CD4+CD25- T cells. Five-year graft survivals showed no difference between the 2 cohorts (P >.05), and was not correlated with the level of CD4+CD25high T cells. Conclusions: Various immunosuppressive therapies may show different roles in tolerance induction. The present findings suggest that SRL facilitates the induction of CD4+CD25high T cells, whereas CNIs hamper their development. Graft success for 5 years did not correlate with the level of these putative regulatory cells. © 2013 Elsevier Inc.


Liu J.,Tianjin First Central Hospital
Transplantation Proceedings | Year: 2012

Objective. To evaluate the clinical value of serum cystatin C (ScysC) for the diagnosis of an acute rejection episode after renal transplantation. Methods. The 76 recruited renal transplant patients included 43 without and 33 with an acute rejection episode. We determined the values of serum creatinine (Scr), blood urea nitrogen (BUN), β2 microglobulin (β2-MG), uric acid (UA), and ScysC before surgery and at 1, 3, 5, 7, 14, 30, and 90 days thereafter. The glomerular filteration rate (GFR) was measured by 99mTc-DTPA to evaluate correlations. Results. No significant difference was observed between the groups before surgery (P > .05). In the rejection-free group ScysC was decreased by 48.1% at 1/day after surgery which was greater than the other cohorts. In the rejection group at day 3 the ScysC increased which was earlier than others. The highest coefficient correlation was observed between ScysC and GFR. The AUCROC of ScysC was greater than all of the others. Conclusion. ScysC was a more sensitive marker to detect changes in renal function than Scr, BUN, β2-MG or UA; therefore it can be used to predict an acute rejection episode after transplantation. © 2012 Elsevier Inc.


Han X.,Tianjin First Central Hospital
Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2013

To investigate the effect of demethylating agent 5-aza-2'-deoxycytidine (5-Aza-CdR) on the growth of human pancreatic cancer cell line MiaPaca2 and the expression and methylation of tumor suppressor gene RUNX3. Human pancreatic cancer cell line MiaPaca2 cells were treated with different concentrations of 5-Aza-CdR. Morphological changes of MiaPaca2 cells were observed by light microscopy. The activity of cell proliferation was analyzed by MTT assay. The changes of RUNX3 mRNA expression were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Changes of RUNX3 gene methylation was detected by methylation-specific polymerase chain reaction. MiaPaca2 cells were treated with 2.5, 5, 10 and 20 μmo1/L 5-Aza-CdR, respectively. The inhibition rates of MiaPaca2 cells treated for 24 h were (9.17 ± 2.15)%, (10.75 ± 2.04)%, (12.57 ± 1.64)% and (18.70 ± 1.51)%, respectively. The inhibition rates were (14.94 ± 1.68)%, (18.60 ± 1.57)%, (22.84 ± 1.58)% and (33.24 ± 1.53)%, respectively, after 48 h treatment; (21.46 ± 1.60)%, (28.62 ± 1.72)%, (35.14 ± 1.64)% and (45.06 ± 1.47)%, respectively, after 72 h treatment; and (26.35 ± 1.71)%, (34.48 ± 1.69)%, (40.05 ± 1.60)% and (49.99 ± 1.61)%, respectively, after 96 h treatment. The differences between inhibition rates of each experimental and control groups (0.00 ± 0.00)% were statistically significant (P < 0.05). At the same time, the inhibition rates of different concentration groups showed significant differences (P < 0.05). At 48 h, 72 h and 96 h, the inhibition rates of each pair concentration groups showed significant differences (P < 0.05). 5-Aza- CdR inhibited the growth of MiaPaca2 cells, and the higher the concentration, the stronger the inhibition after 24 h. 5-Aza-CdR also reversed the methylation status of RUNX3 gene, and restored the expression of RUNX3 mRNA with a dose-effect relationship. The methylation of RUNX3 gene is significantly related with the occurrence and development of pancreatic cancer, and abnormal methylation of RUNX3 gene may contribute to the loss of RUNX3 mRNA expression. 5-Aza-CdR may effectively cause reversion of RUNX3 methylation, and treatment with 5-Aza-CdR can reactivate the gene expression and inhibit the cell growth. This may provide a new way for diagnosis and treatment of pancreatic cancer.

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