Regulatory effect of icariin and oleanolic acid combined with dexamethasone on JAKs/STATs signaling pathway in hormone-resistant CEM-C1 cells / 医学研究生学报

Objective The mechanisms of epimedium and Ligustrum Lucidum with glucocorticoid (GC) acting on asthma are closely related to the regulation of the JAKs / STATs pathway associated with the Th1/Th2 balance in the lung tissue of the asthmatic rats. This study aimed to investigate the synergistic effect of icariin and oleanolic acid with dexamethasone on the protein expressions of JAKs/STATs in GC-sensitive CEM-C7 and GC-resistant CEM-C1 cells.Methods We divided CEM-C7 and CEM-C1 cells into groups A (complete culture medium control), B (dexamethasone at 10-6mol/L), C (icarrin at 100 mg/mL), D (oleanolic acid at 100 mg/mL), E (icarrin+oleanolic acid both at 50 mg/mL), and F (icariin+oleanolic acid+dexamethasone at 50 mg/mL, 50 mg/mL and 10-6 mol/L, respectively), and treated them with corresponding agents for 24 hours. Then, we determined the protein expressions of JAKs (JAK1 and JAK2) and STATs (STAT1, STAT3, STAT5, and STAT6) in the CEM-C7 and CEM-C1 cells of different groups by Western blot.Results The protein expressions of JAK1 and JAK2 in the CEM-C1 cells were 0.22±0.01 and 0.23±0.01 in group A, 0.24±0.01 and 0.24±0.01 in group B, 0.23±0.01 and 0.22±0.01 in group C, 0.24±0.01 and 0.23±0.01 in group D, 0.22±0.01 and 0.21±0.01 in group E, and 0.18±0.01 and 0.19±0.01 in group F, both significantly lower in groups E and F than in B (P<0.01), and in groups C, D and F than in E (P<0.01). The expressions of STAT1 and STAT3 proteins were 0.23±0.01 and 0.23±0.01 in group A, 0.23±0.01 and 0.22±0.01 in group B, 0.23±0.01 and 0.22±0.01 in group C, 0.23±0.01 and 0.23±0.01 in group D, 0.18±0.01 and 0.20±0.02 in group E, and 0.17±0.01 and 0.16±0.01 in group F, both remarkably lower in groups E and F than in B (P<0.01), and that of STAT3 even lower in F than in E (P<0.01). The expressions of STAT5 and STAT6 were 0.24±0.01 and 0.24±0.01 in group A, 0.23±0.01 and 0.23±0.02 in group B, 0.23±0.01 and 0.24±0.01 in group C, 0.23±0.01 and 0.24±0.01 in group D, 0.19±0.01 and 0.19±0.01 in group E, and 0.16±0.01 and 0.20±0.02 in group F, both markedly lower in groups E and F than in B (P<0.01), and even lower in F than in E (P<0.01). The protein expressions of JAK1 and JAK2 in the CEM-C7 cells were 0.24±0.01 and 0.22±0.02 in group A, 0.12±0.01 and 0.49±0.01 in group B, 0.23±0.01 and 0.27±0.01 in group C, 0.25±0.01 and 0.25±0.02 in group D, 0.27±0.01 and 0.23±0.01 in group E, and 0.20±0.01 and 0.32±0.01 in group F, the former increased while the latter decreased significantly in groups B, C, D, E and F as compared with group A (P<0.01), the former even lower and the latter even higher in groups C and F than in E (P<0.01). The expressions of STAT1 and STAT3 were 0.23±0.01 and 0.23±0.01 in group A, 0.10±0.01 and 0.11±0.02 in group B, 0.27±0.01 and 0.26±0.01 in group C, 0.27±0.01 and 0.27±0.01 in group D, 0.28±0.01 and 0.27±0.01 in group E, and 0.21±0.01 and 0.23±0.02 in group F, both remarkably higher in groups C, D, E and F than in B (P<0.01), though lower in F than in E (P<0.01). The expressions of STAT5 and STAT6 were 0.24±0.01 and 0.24±0.01 in group A, 0.10±0.01 and 0.11±0.02 in group B, 0.23±0.01 and 0.23±0.02 in group C, 0.23±0.01 and 0.23±0.01 in group D, 0.24±0.01 and 0.24±0.01 in group E, and 0.20±0.01 and 0.21±0.05 in group F, both significantly upregulated in groups C, D, E and F as compared with B (P<0.01), though lower in F than in E (P<0.05).Conclusion In case of hormone resistance, icariin and oleanolic acid combined with dexamethasone may regulate the JAKs/STATs signaling pathway and improve the sensitivity to hormone action.

Study on effect of combination of Epimedii Folium and Ligustri Lucidi Fructus on osteoporosis rats induced by retinoic acid / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the effect of combination of Epimedii Folium and Ligustri Lucidi Fructus on osteoporosis rats induced by retinoic acid.</p><p><b>METHOD</b>Sixty three-month-old male Wistar rats were randomly divided into the normal control group, the model group, the Epimedii Folium group, the Ligustri Lucidi Fructus group, the combination group of Epimedii Folium and Ligustri Lucidi Fructus and the raloxifene group. The osteoporosis model was established through oral administration with retinoic acid for two weeks. Meanwhile, all of treatment groups were administered with corresponding drugs for three weeks. The contents of serum calcium (Ca), phosphorus (P), alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (StrACP) were detected, and the pathomorphological changes of femurs were observed.</p><p><b>RESULT</b>The model control group showed much lower contents of serum Ca and P than the normal control group, but with significantly higher AKP and StrACP activity than the normal control group. The femoral head area showed reduced, narrow and sparse trabecular bones, with typical osteoporosis-like changes. Compared with the model control group, all of treated groups showed significant increase in Ca and P contents in serum, and down-regulate AKP and StrACP levels, while trabecular bones became more and wider, and densely interweaved as a reticular formation. Among them, the combination group showed the most significant effect.</p><p><b>CONCLUSION</b>Epimedii Folium and Ligustri Lucidi Fructus could effectively correct the abnormal bone metabolism and improve pathological conditions of bone tissues, so as to show the anti-osteoporosis effect. The combined application of the two drugs showed a better efficacy.</p>

Significance of expressions of bone morphogenetic protein 2 and 4 in prostatic carcinoma / 中华男科学杂志

<p><b>OBJECTIVE</b>To determine the expression of bone morphogenetic protein 2 and 4 (BMP-2 and BMP-4) in prostatic carcinoma (PCa) and investigate their relationship with clinical stage and Gleason score of tumor.</p><p><b>METHODS</b>Forty-eight PCa cases and 5 normal prostatic tissue were analysed for the expressions of BMP-2 and BMP-4 by Western bolt assay.</p><p><b>RESULTS</b>The optical densities of BMP-2 expressions in the tumor with Gleason score < or =5, 6-8, and > or = 9 were 7547.1 +/- 1964.12, 9657.4 +/- 2010.54, 12467.7 +/- 2496.75 and of BMP-4 expressions were 5174.4 +/- 1400.54, 5940.3 +/- 1587.42, 6332.1 +/- 1647.83, respectively. The optical densities of BMP-2 expressions in the tumor in T1 - T2 and T3 - T4 stages were 8003.37 +/- 1889.23, 12385.55 +/- 2506.72 and of BMP4 expressions were 5267.41 +/- 1 464.19, 6543.75 +/- 1668.46, respectively. There were significant differences between tissues with Gleason score < or =5 and > or =9 (P <0.01), and tissues in T1 - T2 and T3 - T4 stages, in expressions of BMP-2 protein. The expression of BMP-2 protein was significantly high in the PCa with bone metastasis compared with that without bone metastasis.</p><p><b>CONCLUSION</b>The expressions of BMP-2 and BMP-4 increase with the progression of clinical stage and Gleason score compared with normal prostatic tissue. The expression of BMP-2 protein is significantly upregulated in bone metastasis of PCa, which indicates a poor prognosis.</p>