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Zhang L.-M.,Beijing Institute of Pharmacology and Toxicology | Wang H.-L.,309 Hospital of PLA | Zhao N.,Beijing Institute of Pharmacology and Toxicology | Chen H.-X.,Beijing Institute of Pharmacology and Toxicology | And 2 more authors.
Neuroscience Letters | Year: 2014

Our previous studies have demonstrated that the total flavonoids (XBXT-2) isolated from the extract of Xiaobuxin-Tang (XBXT), a traditional Chinese herbal decoction, exerted antidepressant-like effects. Recently, accumulating studies have suggested that l-arginine-NO is implicated in the regulation of depression. Therefore, the aim of current study attempts to explore the involvement of l-arginine-NO pathway in the antidepressant-like effect of XBXT-2 in the mouse forced swim test (FST). Our results showed that the antidepressant-like action of XBXT-2 (100. mg/kg, i.g.) was reversed by pretreatment with l-arginine (a nitric oxide precursor, 750. mg/kg, i.p.). While co-administration of aminoguanidine (a specific inducible NOS inhibitor, 40, 80. mg/kg, i.p.) and sub-effective dose of XBXT-2 (50. mg/kg, i.g.) did not significantly alter the immobility in FST. In contrast, combined administration of 7-nitroindazole (a specific neuronal NOS inhibitor, 50. mg/kg, i.p.) potentiated the antidepressant-like effect of non-effective doses of XBXT-2 (50. mg/kg, i.g.). Meanwhile, NO modulators were devoid of any locomotor effects on the animals. In conclusion, the antidepressant-like action of XBXT-2 may be involvement of NO signaling pathway. © 2014.

Zhang H.,Air Force General Hospital of PLA | Liu C.,Air Force General Hospital of PLA | Kong Y.,Air Force General Hospital of PLA | Huang H.,309 Hospital of PLA | Wang C.,Air Force General Hospital of PLA
Tumor Biology | Year: 2015

Transforming growth factor β (TGFβ) receptor signaling plays a paradoxical effect in the tumorigenesis of pancreatic ductal adenocarcinoma (PDAC), in which its tumor-inhibitory role at early stages turns into a tumor-promoting role at later stages. The underlying mechanism remains far from clear. Here we provide strong evidence that the activation of TGFβ receptor signaling in PDAC cells increased SMAD3 phosphorylation and nuclear translocation to inhibit cell growth. Meanwhile, it also activated SMAD7 to induce nuclear translocation and retention of β-catenin, which not only attenuated the inhibition of cell growth by nuclear SMAD3 but also activated vascular endothelial growth factor A (VEGF-A) to promote vascularization. Our data thus support a model involving crosstalk of the TGFβ and Wnt signaling pathways, for regulating the complicated effect of TGFβ signaling on the tumorigenesis of PDAC. © 2014, International Society of Oncology and BioMarkers (ISOBM).

Jiang K.,Zhejiang University | He B.,309 Hospital of PLA | Lai L.,Zhejiang University | Chen Q.,Zhejiang University | And 3 more authors.
International Journal of Molecular Medicine | Year: 2012

The high proliferative rate of tumor cells leads to metabolic needs distinct from those of their normal counterparts. An embryonic- and tumor-specific isoform of the enzyme pyruvate kinase M2 (PKM2) is overexpressed in cancer cells to increase the use of glycolytic intermediates for macromolecular biosynthesis and tumor growth. We report that Cyclosporin A (CsA) can regulate the expression and activity of PKM2 in breast cancer cell lines MCF-7, MDA-MB-435 and MDA-MB-231. PKM2 was found to be highly expressed in the three breast cancer cell lines compared to normal primary breast cells. Treatment with CsA inhibited the viability of breast cancer cells in a time- and dose-dependent manner. CsA significantly downregulated the expression of PKM2 in breast cancer cells and decreased adenosine triphosphate (ATP) synthesis, which induced cancer cells to undergo necrosis. Furthermore, the growth suppression effect of CsA was impaired in MCF-7 cells when they were transfected with the PKM2 overexpression plasmid, suggesting that CsA was an effective inhibitor of PKM2-dependent proliferation of breast cancer cells. These results may provide new insights into the mechanism of CsA in cancer therapy.

Deng H.,CAS Beijing National Laboratory for Molecular | Li T.,309 Hospital of PLA | Xie J.,CAS Beijing National Laboratory for Molecular | Huang N.,Chinese PLA General Hospital | And 2 more authors.
Dyes and Pigments | Year: 2013

The phototherapeutic window from 600 to 900 nm is necessary for photodynamic therapy (PDT) of solid tumors, but may not suitable for PDT of some microvascular diseases, like age-related macular degeneration (AMD), because of its deep penetration. Moreover, absorption of some neighboring photoreceptors should be avoided for PDT of AMD. Considering these, yellow-orange light may be a proper phototherapeutic window of AMD. Herein, two novel amino-alkyl-sulfonic acid-substituted hypocrellin B derivatives, 3 and 4 were designed and synthesized. They exhibited the maximal absorption at yellow-orange light, and possessed higher PDT activity than 2, proved by the in vitro or in vivo experiments. Besides, 4 showed much higher PDT activity than 3, ascribed to its higher cellular uptake suggested by its optimized amphiphilicity and liposome-mimic results. And the vascular leakage of 4 was close to 2. Consequently, 4 has great potential for PDT of AMD or other superficial diseases. © 2013 Published by Elsevier Ltd.

Xue H.B.,309 Hospital of PLA
Zhongguo gu shang = China journal of orthopaedics and traumatology | Year: 2011

To evaluate the surgical indications and clinical effectiveness of different operative procedures in the treatment of lower lumbar tuberculosis. From June 2001 to Oct 2008, 72 patients with lower lumbar tuberculosis were treated by different operative procedures. Including 38 males and 34 females, with an average age of 38.5 years old ranging from 16 to 70 years. The average duration of symptom was 6.8 months (ranging from 4 months to 2 years). A single vertebrae was involved in 10 patients,two contiguous vertebrae in 50 cases and three vertebrae in 12 cases. The average preoperative lordotic angle was 13.1 degree (ranging from -5.0 degrees to 34.0 degrees). Three different operative procedures included: (1) posterior debridement and posterolateral fusion and posterior instrumentation in 28 patients; (2) anterior radical debridement and anterior fusion and anterior instrumentation in 32 patients; (3) image-guided percutaneous drainage (PCD) of tuberculous abscesses in 12 patients. The selection of the procedure was made according to the degree of the lesions. The resolution of inflammatory process, bony fusion, correction of sagittal angles and JOA scores were used for evaluating the result of the surgery and the complications were analyzed. All patients were followed up from 1.5 to 8.0 years (means 3.6 years). PCD was an effective treatment in 11 out of the 12 patients, one required surgical debridement and fusion. Among them, 57 (95%, 57/60) patients were treated by open operation showed successful bony fusion. The complications maily included common iliac vein injury in 3 patients, dural tear in 2 patients, they were all cured by intro-or postoperative treatment. The average immediate post-operative lordotic angle was 27.3 degree (35.0 degrees to 16.0 degrees), the average lordotic angle was 25.6 degree (33.0 degrees to 15.0 degrees) at final follow-up. Preoperatively and at final follow-up, JOA scores were respectively (15.2 +/- 3.4), (25.6 +/- 2.4) (P<0.01). Different operative procedures should be selected to treat lower lumbar tuberculosis according to the degree of lesions. Aggressive surgical treatment was found helpful in the resolution of inflammatory process and correcting the loss of lordosis, preventing progression of kyphosis.

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