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Objective To investigate zinc finger of the cerebellum 4(ZIC4) expression in endometrial cancer tissue and its relationship with clinicopathological parameters. Methods Immunohistochemistry was used to detect ZIC4 expression in endometrial paraffin specimens. Results The positivity rate of ZIC4 expression in atypical hyperplasia and endometrial carcinoma was higher than that in normal endometrial tissue. ZIC4 expression was correlated with the clinical stage,differentiation,depth of uterine invasion,and lymph node metastasis of endometrial cancer. Survival analysis revealed that patients with endometrial cancer who had low ZIC4 expression levels had better prognosis. Conclusion The ZIC4 expression level in endometrial carcinoma is significantly increased;thus,ZIC4 expression level can be used to monitor the prognosis of patients with endometrial cancer.
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Objective To investigate the expression and significance of miR?135a?5p in endometrial carcinoma and to correlate expression levels with clinicopathological features. Methods Fifty five endometrial carcinoma samples and thirty normal endometrial tissue samples were surgically obtained,and the expression of miR?135a?5p was quantitated by real?time polymerase chain reaction. The relationship between the expression level of miR?135a?5p and clinicopathological data of individual patients was analyzed. Results The expression of miR?135a?5p was lower in the endo?metrial carcinoma group than in the normal endometrial group(P=0.021),and correlated significantly with the histologic grade of the endometrial neoplasm(P=0.008). Conclusion The expression of miR?135a?5p is lower in endometrial carcinoma than in normal endometrial tissue. In en?dometrial carcinoma,the miR?135a?5p expression status has a statistically significant relationship with the histological characteristics of the tumor.
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Objective To compare and analyze the formula composition based on their herbal nature for wind, cold, and dampness arthralgia. Methods The ancient formulas for wind, cold, and dampness arthralgia were searched and the database was established. The top 30 high-frequency herbs were analyzed with frequency, hypothesis testing and association rules. The nature, taste, and meridian distribution were used as the variable quantities for clustering analysis. Results Totally 338 formulas were collected, including 122 formulas for wind arthralgia, 110 formulas for cold arthralgia, and 106 formulas for dampness arthralgia. There are 21 same herbs among the top 30 high-frequency herbs;Tonic herbs were the highest frequently used, followed by the divergence of cold herbs in wind arthralgia, interior-warming herbs in cold arthralgia, and damp-resolving herbs in dampness arthralgia. The frequently used herbs in each kind of formula compared with other two kinds were:Cinnamomi Cortex, Aconiti Lateralis Radix Praeparata, Angelicae Sinensis Radix, Achyranthis Bidentatae Radix, Notopterygii Rhizome et Radix, Paeoniae Radix and Astrragali Radix in formulas for cold arthralgia, Poria and Atractylodis Macrocephalae Rhizoma in formulas for dampness arthralgia. Three kinds of formulas are given priority to slight warm, followed by warm and neutral. Classification is clear when most of the formulas were clustered into five classes according to their herbal nature in each kind of formula. Conclusion The three kinds of formulas cross each other but with own characteristics. A variety of data mining methods can be used to analyze scientific connotation of therapeutic principle for arthralgia.
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Chemotherapy is the preferred therapeutic approach for advanced ovarian cancer, but a successful long-term treatment is prevented by the development of drug resistance. Recent works have underlined the involvement of non-coding RNAs, microRNAs (miRNAs) in cancer development, with several conjectures regarding their possible involvement in the evolution of drug resistance. This study is to investigate the promoting effects and mechanism of miR-125b involved in the development of chemoresistance in ovarian cancer. The different expression of miR-125b in cisplatin-sensitive ovarian cancer cell line (OV2008) and its resistant variant (C13*) was identified by real-time PCR. An in vitro cytotoxicity assay and apoptosis assay using CCK-8 assay and flow cytometry, were carried out to detect the effect of miR-125b and Bak1 on cisplatin resistance of cells. Real-time PCR, Western blotting and luciferase reporter assay were used to detect whether Bak1 is a target of miR-125b. As compared with OV2008 cells, the expression levels of miR-125b in C13* cells were increased. It was found that the up-regulation of microRNA-125b caused a marked inhibition of cisplatin-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to cisplatin in OV2008 and C13* cells. Moreover, Bak1 was a direct target of miR-125b, and down-regulation of Bak1 suppressed cisplatin-induced apoptosis and led to an increased resistance to cisplatin. Our study indicates that miR-125b has a significantly promoting effect on chemoresistance of C13* cells and up-regulation of miR-125b expression contributes to cisplatin resistance through suppression of Bak1 expression. This finding has important implications in the development of targeted therapeutics for overcoming cisplatin resistance in ovarian cancer.
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Objective To explore the sensitivity and the molecular mechanism of cisplatinresistance ovarian cancer cell line C13 to proteasome inhibitors and the combination with cisplatin. Methods After different treatments, methyl thiazolyl tetrazolium (MTT) assay was applied to examine the cell viability, annexin-V/propidium iodide(PI) apoptosis detection kit was used to determine the apoptosis rate of different groups, western blot assay was introduced to evaluate the expression levels of Fas-associated death domain-like interleukin-1 beta converting enzyme inhibitory protein (cFLIPs), and the activity of caspase-8 was examined. Results MTT assay shown that the cell viability ratios of combination group at serial time points from 12, 24, 36, 48, 60, 72 hours were ( 56.0 ± 8.4 ) %, (44.7 ± 7.3 ) %, ( 33.7 ±11.2) %, (27.6 ± 8.0) %, (27. 6 ± 7.6) % and (28.1 ± 2.4) %, which were much lower than those of cisplatin group (P <0.05). After treated for 24 hours, apoptosis rates of cisplatin group, bortezomib group and combination group were ( 16.7 ± 1.7) %, (23.4 ± 2.1 ) % and (26.9 ± 1.6) %, respectively. The rate of combination group was much higher than that of non-treated group and that of cisplatin group or bortezomib group ( P < 0.05 ). Western blot assay showed the changes of expression levels of cFLIPs, which were downregulated seriously after cisplatin, bortezomib or combination treatment [ (43.2 ± 2.3 )% vs( 75.7 ± 3.0)%vs (67.9 ± 2.1 ) %, P < 0.05 ]. The caspase-8 activity of combination group was (5.6 ± 1.6) folds than that of non-treated group, which was higher than those of other two groups [ ( 2.3 ± 1.0) and (4.2 ± 0.9 ) folds,P < 0.05 ]. Conclusions The tumor cell lethal effect of cisplatin could be increase significantly by the combination application of proteasome inhibitors, bortezomib. And the cFLIPs/caspase-8 signaling pathway may be play an important role in the molecular mechanism of the combination treatment.
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BACKGROUND: Epidermal stem cells (ESCs) are of importance in the wound repair. Explaining the mechanism thatChinese herb speeds up the regeneration of injured skin from the angle of inducing stem cells deserves to be studied. OBJECTIVE: To observe the effect of Yuhong ointment on the proliferation and differentiation of ESCs during ratwound healing. DESIGN: A randomized controlled animal experiment. SETTING: Department of Pharmacology, Wangjing Hospital, China Academy of Chinese Medical Sciences. MATERIALS: This study was carried out in the Department of Pharmacology, Wangjing Hospital, China Academy ofChinese Medical Sciences between July and September 2006. Totally 114 healthy Wistar male adult rats, of cleangrade, weighing 180-210 g, were provided by the Laboratory Animal Center, Institute for Basic Theory of TraditionalChinese Medicine, China Academy of Chinese Medical Sciences were enrolled in this study. The processing ofanimals corresponded to the standard of Animal Ethics. Yuhong ointment was purchased from the PharmaceuticalCenter, Guanganmen Hospital, China Academy of Chinese Medical Sciences (Lot No. 20020110). Jingwanhong wasthe product of Tianjin Darentang Da'er Pharmcaceutical Co., Ltd (Lot No. Z12020440). METHODS: The 114 rats were completely randomly chosen and divided into 3 groups with 36 in each: Yuhongointment group, Jingwanhong group and model group, and the left 6 rats were involved as normal control group. Ratsin the normal control group were raised routinely, and no intervention was carried out. Immediately after beingmodeled, rats in the Yuhong ointment group were spread with Yuhong ointment, 0.1 g each wound, rats in theJingwanhong group were spread with Jingwanhong, 0.1 g each wound. Dressing change was daily carried out twice regularly until wound healing; The wounds of rats in the model group were untouched. MAIN OUTCOME MEASURES: On the 1st, 3rd, 5th, 7th, 14th and 21st days after modeling, wound healing time of rats in eachgroup was recorded, and integrinβ1 absorbance and transcription factor p63 positive cell amount were compared. RESULTS: Totally 114 rats were involved in the final analysis.① Wound healing time of rats in the Yuhong ointmentgroup and Jingwanhong group was significantly shorter than that in the model group, respectively (P ＜ 0.05). ② Integrinβ1 absorbance and transcription factor p63 positive cell amount of modeled rats in the Yuhong ointmentgroup, Jingwanhong group and model group were significantly higher than those in the normal control group, respectively (P ＜ 0.05); The above-mentioned two indexes in the Yuhong ointment group and Jingwanhong groupreached the peak on the 7th day, which was earlier than peak time in the model group, and peaked intensity of twoindexes was significantly higher than that in the model group, separately (P ＜ 0.05). CONCLUSION: Yuhong ointment can promote rat wound healing, which may be associated with Yuhong ointmentinducing the proliferation and differentiation of ESCS left in the wound edge.
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Objective To observe the effect of Yuhong ointment on secretion of Substance P of promoting wound healing and explore its mechanism. Methods The whole layer skin defection rat was used and randomly divided into 3 groups:Yuhong ointment group,Jingwanhong group,model group,with normal rats as control. The condition of skin wound surface and healing time were observed and recorded at 1,3,5,7,10,14,21,30 day after wound. The expression of Substance P were measured and compared by immunohistochemistry staining. Results Average wound healing rate had no significant difference between Yuhong ointment group and Jingwanhong group,which were higher than model group (P
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Objective To observe the effect of Yuhonggao on proliferation and differentiation of epidermal stem cells and investigate the mechanism of promoting wound healing. Methods The whole layer skin defection rat was used and randomly divided into 3 groups:Yuhonggao group,Jingwanhong group,model group,with normal rats as control. The condition of skin wound surface and healing time were observed and recorded,and then draw the wound skin. The p63 and?1 integrin expression,the marker of epidermal stem cells,were measured and compared by immunohistochemistry staining. Results Average wound healing time hadn’t significant difference between the Yuhonggao group (13.5? 0.9)d and Jingwanhong group (12.6?0.9)d,which were better than model group (P