OBJECTIVE To study the effects of sophoranone （SOP） on the biological behavior of nasopharyngeal carcinoma CNE-1 cells and mitogen-activated protein kinase （MAPK） signaling pathway. METHODS CNE-1 cells were divided into blank group and SOP low-， medium- and high-concentration groups （SOP-L group， SOP-M group， SOP-H group， 25， 50 and 100 μmol/L）. The number of invasive cells， the number of migratory cells， and the apoptosis rate of cells were detected. The expression levels of mitogen-activated protein kinase kinase （MEK）， extracellular signal-regulated kinase 1 （ERK1）， ERK2， and c-Jun N-terminal kinase （JNK） mRNA， as well as phosphorylation levels of ERK， JNK， and p38 mitogen-activated protein kinase （abbreviated as “p38”） proteins in cells were all detected. Additionally， cells were divided into blank group， SOP high-concentration group （SOP- H group， 100 μmol/L）， SOP high-concentration combined with p38 inhibitor group （SOP-H+SB group， 100 μmol/L SOP+10 μmol/L SB）， and SOP high-concentration combined with JNK inhibitor group （SOP-H+SP group， 100 μmol/L SOP+10 μmol/L SP）. The number of invasive cells， cell migration rate， and the protein phosphorylation levels of JNK and p38 in cells， as well as the protein expression levels of matrix metalloproteinase-9（MMP-9）， proliferating cell nuclear antigen Ki67， and cleaved-caspase-3 were measured. RESULTS Compared with the blank group， SOP for each concentration could significantly decrease the number of invasive cells， the number of migratory cells， and mRNA expressions of MEK， ERK1， ERK2 （except for the SOP-L group） and JNK， but increase the apoptosis rate of cells and phosphorylation levels of ERK， JNK， and p38 proteins （P＜0.05）. Compared with the SOP-H group， the protein phosphorylation levels of p38 and JNK， and the protein expression of cleaved-caspase-3 were decreased significantly in SOP-H+SB group and SOP-H+SP group， while the number of invasive cells， cell migration rate， and the protein expression levels of MMP-9 and Ki67 were all increased significantly （P＜0.05）. CONCLUSIONS SOP can inhibit the proliferation， migration and invasion of CNE-1 cells， and induce the apoptosis， the mechanisms of which may be associated with promoting the phosphorylation of proteins related to the MAPK signaling pathway.

Skin ulcers are the most prevalent consequence of diabetes mellitus, and people with diabetic ulcers have a substantially greater death risk than those who do not have ulcers. Herbal medications have gained wide concern in recent years due to their multi-component, multi-target, and multi-pathway synergistic therapeutic effects. Clinical trials have demonstrated the safety and efficacy of herbal treatments in diabetic refractory ulcers. To systematically evaluate the healing effect of herbs on diabetic wounds, a literature search was conducted, the mechanism of action of 15 herbal extracts in promoting diabetic wound healing were reviewed, and the classification based on traditional Chinese medicine theory was discussed, which could provide a reference for the precise treatment and exploitation of herbal medicines for diabetic ulcers.

Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors. Brain metastasis, such as breast cancer and lung cancer, also leads to high mortality. The available medicines are limited due to blood-brain barrier. Abnormal activation of phosphatidylinositol 3-kinases (PI3K) signaling pathway is prevalent in glioblastoma and metastatic tumors. Here, we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3K inhibitor with excellent anti-tumor activity against human glioblastoma. XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3K signaling pathway, induced cell cycle arrest in G1 phase as well. Additionally, XH30 inhibited the migration of glioma cells and blocked the activation of PI3K pathway by interleukin-17A (IL-17A), which increased the migration of U87MG. Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models. XH30 also repressed tumor growth in brain metastasis models of lung cancers. Moreover, XH30 reduced IL-17A and its receptor IL-17RA in vivo. These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.

Objective: To explore the effects and mechanisms of interfering with transient receptor potential melastatin subfamily member 7(TRPM7) on biological behaviors(proliferation, apoptosis, invasion) of laryngeal carcinoma cells. Methods: Human laryngeal carcinoma cells TU212 were culturedin vitro. TRPM7-shRNA plasmid vectors(TRPM7-shRNA1 group, TRPM7-shRNA2 group, TRPM7-shRNA3 group) and negative control shRNA-NC(shRNA-NC group) were constructed. TU212 cells were transfected by liposome transfection method. The cells transfected with empty vector were enrolled as Control group. The level of lactic dehydrogenase(LDH) in TU212 supernatant was detected by ELISA. The level of malondialdehyde(MDA) and activity of superoxide dismutase(SOD) in supernatant were detected by colorimetry. The effects of knocking-down TRPM7 on proliferation and invasion of TU212 cells were detected by CCK-8, clone formation assay and Transwell assay. The expressions of invasion and apoptosis-related proteins were detected by Western blot. Results: After transfection, expression levels of TRPM7 mRNA and protein were down-regulated in TRPM7-shRNA1 group, TRPM7-shRNA2 group and TRPM7-shRNA3 group compared with Control group(P<0.05), and the decrease was the most significant in TRPM7-shRNA1 group(P<0.05). In functional experiments, SOD level in TRPM7-shRNA1 group decreased compared with Control group(P<0.05), while MDA and LDH levels increased(P<0.05). The cells proliferation rate and clone formation rate were decreased(P<0.05), the number of invasion cells was reduced(P<0.05), the expressions of N-cadherin and Vimentin proteins were down-regulated(P<0.05), mitochondrial membrane potentials were reduced(P<0.05), Bax/Bcl-2 and cleaved caspase-3/caspase-3 increased(P<0.05). Conclusion Knocking-down TRPM7 can increase oxidative stress level in laryngeal carcinoma cells TU212, inhibit their proliferation and invasion, and induce their apoptosis by mitochondrial pathways.

Objective To establish a HPLC method for simultaneous determination of quercitrin, luteoloside, rutin and 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside in Yangxue Anshen syrup. Methods Waters symmetry C₁₈ column (250 mm×4.6 mm, 5 μm) was used with 0.1% acetic acid (A) and methanol (B) as the mobile phase. Gradient elution was performed at a flow rate of 1.0 ml/min, 0-15 min, 95%-90%A; 15-35 min, 90%-70%A; 35-55 min, 70%-60%A; 55-85 min, 60%-50%A; 85-95 min, 10%A. The detection wavelengths were 256 nm and 320 nm. Column temperature was 30 ℃ and the injection volume was 10 μl. Results Quercitrin, luteoloside, rutin and 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside showed good linear relationship within the range of 10-300, 5.0-150.0, 5.0-150.0, 20.0-600.0 µg/ml(r≥0.9989), respectively. The average recovery was (96.75±1.41)%, (99.61±1.01)%, (97.18±1.96)% and(99.12±0.97)% (n=6), respectively. Conclusion The established method is simple, accurate and stable, which can be used for the simultaneous determination of 4 components in Yangxue Anshen syrup.

Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear. In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β. Meanwhile, RBP-J deletion significantly hampered macrophage infiltration and activation in fibrotic kidney, although their proliferation appeared unaltered. By using macrophage clearance experiment, we found that kidney resident macrophages made negligible contribution, but bone marrow (BM)-derived macrophages played a major role in renal fibrogenesis. Further mechanistic analyses showed that Notch blockade reduced monocyte emigration from BM by down-regulating CCR2 expression. Finally, we found that myeloid-specific Notch activation aggravated renal fibrosis, which was mediated by CCR2 macrophages infiltration. In summary, our data have unveiled that myeloid-specific targeting of Notch could ameliorate renal fibrosis by regulating BM-derived macrophages recruitment and activation, providing a novel strategy for intervention of this disease.

Radiotherapy is the main way to treat the Nasopharyngeal Carcinoma. But there are a lot of serious complications, the most common one of then is radioactive xerostomia. It seriously affect the patients's quality of life, even make patients change or stop their radiotherapy. It is extremely important to prevent and treat xerostomia caused by radiotherapy.
Carcinoma ; Humans ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; complications ; radiotherapy ; Quality of Life ; Radiotherapy ; adverse effects ; Xerostomia ; etiology ; prevention & control

Objective To evaluate the relationships of the expression of orexin A in hypothalamus with hyperleptinemia, hyperinsulinism, and hyperlipidemia in alimentary obesity rats.Methods The alimentary obesity rat model was induced by high-fat diet in Wistar rats. The levels of leptin, insulin, C-peptide, total cholesterol (TC) and triglyeride (TG) were detected by luminescent immunoassay and biochemistry enzymic method. The gene expression of orexin A in rat hypothalamus was detected by real-time PCR. The correlation between orexin A and leptin was analyzed. Results After 8 weeks of high-fat diet feeding, the body weight, Lee's index, blood glucose, TG and TC significantly increased in obesity rat group (P＜0. 01). The levels of serum leptin, insulin and C-peptide were significantly higher in obesity rats than in controls [( 1.74±0. 36)μg/Lvs. (1.27±0.11) μg/L, (35±5) MIU/L vs. (23±4) MIU/L, (0.21±0.04) μg/L vs.(0. 14±0. 03) μg/L respectively, P＜0.01]. However, the level of orexin A mRNA was lower in obesity rats than in controls (6.8±2.3 vs. 14.5±3.6, t=-8.06, P＜0.01). The correlation coefficient (r) of orexin A mRNA with serum leptin, insulin, and C-peptide in alimentary obesity rat were -0. 726 (P＜0.01), -0. 506 (P＜0.01) and -0. 664 (P＜0.01), respectively. Conclusions High-fat diet can induce leptin-resistance and alimentary obesity in Wistar rat. The down-regulation of orexin A in rat hypothalamus would be correlated closely to the leptin and insulin resistance in alimentary obesity.