1.The research on the change of chemosensitivity of geiftinib-resistant lung adenocarcinoma cell caused byEGFR-T790M mutation
Xuezhen LI ; Wen ZOU ; Jinan MA ; Xingnan ZHANG
China Oncology 2015;(2):129-134
Background and purpose:Chemotherapy is an alternative treatment option, which could still get a therapeutic effect, when the EGFR-TKI treatment of non-small cell lung cancer failed. Studies have shown that RR, TYMS, ERCC1 and TUBB3 have respectively relationship with chemosensitivity of gemcitabine, pemetrexed, platinum-based drugs and microtubule-based chemotherapy drugs.The expression levels of these molecular markers can predict the sensitivity of these chemotherapy drugs. The patients with RRMI, TS, ERCC1 and TUBB3 higher expression have reduced chemosensitivity, and lower expression have increased sensitivity. The purpose of this study was to explore the sensitivity of tumor cell lines with acquired resistance to geiftinib caused byEGFR-T790M mutation to cisplatin, gemcitabine, pemetrexed, vinorelbine, paclitaxel and docetaxel.Methods:MTT assay was used to detect the IC50 values of cisplatin, gemcitabine, vinorelbine, paclitaxel and docetaxel, pemetrexed to PC9 and PC9/GR cells, and to explore the chemosensitivity of lung adenocarcinoma cells to these chemotherapy drugs; Luminex method was used respectively to detect the expression levels of ERCC1 mRNA, TUBB3 mRNA, TS mRNA, and RRM1 mRNA in PC9 and PC9/GR cells. Western blot was used to detect the protein expression levels of ERCC1, TUBB3, TS and RRM1 in PC9 and PC9/GR cells.Results: The IC50 values of cisplatin, gemcitabine and pemetrexed to PC9/GR cells were signiifcantly higher than those to PC9 cells (P<0.05), while the IC50 values of vinorelbine, paclitaxe and docetaxel to PC9/GR cells were signiifcantly decreased (P<0.05). Luminex method showed the expressions of ERCC1 mRNA, TS mRNA and RRM1 mRNA in PC9/GR cells were signiifcantly increased than those in PC9 cells (P<0.05), while the expression of TUBB3 mRNA was signiifcantly decreased (P<0.05). Western blot method showed the expressions of TUBB3, TS and RRM1 protein in PC9/GR cells were signiifcantly increased than those in PC9 cells (P<0.05), while TUBB3 protein expression in PC9/GR cells was signiifcantly decreased (P<0.05). Western blot method analysis result showed that the expressions of TUBB3, TS and RRM1 protein in PC9/GR cells were significantly increased than those in PC9 cells (P<0.05), while TUBB3 protein expression in PC9/GR cells was signiifcantly decreased (P<0.05). Conclusion:The chemosensitivity of lung adenocarcinoma with EGFR-T790M mutation is changed. It has decreased sensitivity to cisplatin, gemcitabine, pemetrexed and increased sensitivity to vinorelbine, paclitaxel and docetaxel. The reason of the change of chemosensitivity of geiftinib-resistant lung adenocarcinoma cell maybe related to the changes of ERCC1 mRNA, RRM1 mRNA and TS mRNA and their protein expressions.
2.An examination of the OMIM database for associating mutation to a consensus reference sequence.
Zuofeng LI ; Beili YING ; Xingnan LIU ; Xiaoyan ZHANG ; Hong YU
Protein & Cell 2012;3(3):198-203
Gene mutation (e.g. substitution, insertion and deletion) and related phenotype information are important biomedical knowledge. Many biomedical databases (e.g. OMIM) incorporate such data. However, few studies have examined the quality of this data. In the current study, we examined the quality of protein single-point mutations in the OMIM and identified whether the corresponding reference sequences align with the mutation positions. Our results show that close to 20% of mutation data cannot be mapped to a single reference sequence. The failed mappings are caused by position conflict, site shifting (peptide, N-terminal methionine) and other types of data error. We propose a preliminary model to resolve such inconsistency in the OMIM database.
Amino Acid Sequence
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Consensus Sequence
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Databases, Genetic
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Molecular Sequence Data
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Point Mutation
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Sequence Alignment
3.The mechanism,safety and application of berberine in promoting bone regeneration
Yulin LI ; Haipeng YU ; Huajing TANG ; Zitong ZHANG ; Xingnan LIN
Chinese Journal of Tissue Engineering Research 2024;28(35):5702-5708
BACKGROUND:Berberine has the potential to induce osteogenic differentiation of various mesenchymal stem cells under normal conditions and special conditions such as high glucose,infection and inflammation.It is a natural small molecule drug that can induce bone formation in seed cells instead of growth factors,and has great application prospect in bone tissue engineering. OBJECTIVE:To review and summarize the research progress in the osteogenic mechanism and efficacy of berberine,especially its osteogenic potential under high glucose,infection and inflammation conditions,and its biological safety,so as to provide theoretical basis for its development and application in bone tissue engineering. METHODS:PubMed,WanFang,and CNKI were searched for relevant literature using the keywords of"berberine,bone defects,bone repair,bone regeneration,osteoinductive,osteoporosis,osteoblast,osteoclast,bone tissue engineering,bone,high glucose,diabetes,inflam*,infect*"in English and Chinese,respectively.A total of 105 literatures were selected for review. RESULTS AND CONCLUSION:Berberine can be used to treat multiple diseases including bone diseases,and it has the ability to promote bone regeneration.This article systematically reviews the mechanism of berberine on bone regeneration and in vivo and in vitro studies.Studies have shown that it can play a role in bone repair by promoting osteogenesis,inhibiting osteoclast formation and activity,and preventing osteoporosis.It shows excellent osteogenic differentiation potential mainly via Wnt/β-catenin,PI3K/AKT,EGFR/MEK/p38MAPK,cAMP/PKA/CREB,ERK and other signaling pathways.Berberine can also relieve the inhibition of osteogenic differentiation caused by high glucose,infection and inflammation,which provides more possibilities for the treatment of bone defects in patients with diabetes or infection and inflammation in the bone defect site.Berberine also has the advantages of low toxicity,low price,easy access(currently it can be synthesized),which is a relatively ideal bone induction potential drug.In recent years,the application of berberine in the treatment of bone defect tends to be localized,mainly through the combination with bone tissue engineering technology to improve bioavailability,and has shown good bone repair effect and excellent biological safety in animal experiments.In addition,preclinical experiments have shown splendid bone regeneration potential in the conditions of diabetes,local infection and inflammation.In the future,more studies are needed to fully reveal the osteogenic mechanism and biological safety of berberine,and seek the most suitable controlled release loading system to make artificial bone replacement materials with good mechanical strength,efficacy and biological safety.
4.Analysis and comparison of major plant databases in China and ASEAN countries
Shuo WANG ; Yuanchen ZHAO ; Zijun ZHANG ; Yan WANG ; Xingnan YUE ; Lu GAO ; Zhiyong LI
International Journal of Traditional Chinese Medicine 2023;45(1):17-23
At present, countries around the world are paying greater attention to the protection of medicinal plants and traditional medicinal knowledge resources, and are looking for various ways to protect medicinal plants. Many countries have established their own databases to save the medicinal plant information resources. This paper focuses on the introduction of medicinal plant databases in six countries including Malaysia, Philippines, and Singapore, and compares their basic information. It is difficult to achieve integration and sharing among these databases. It brings certain difficulties to the use of researchers in related fields. It is suggested that the construction of a multinational common medicinal plant database should be included in the "Belt and Road Initiative" to systematically organize massive information, enhance exchanges between countries on traditional medicinal plants, and achieve medicinal plant information sharing, and the establishment of a shared database will reduce optimization and maintenance to a certain extent or renewal work, laying the foundation for the protection, development and sustainable use of traditional medicinal plant resources.
5.Cost-effectiveness Analysis of Domestic and Imported Vancomycin in the Treatment of Intracranial Infection Induced by MRSA by Using Decision Tree Model
Chun HUANG ; Fanlu MO ; Xingnan QIN ; Hongliang ZHANG
China Pharmacy 2019;30(9):1256-1259
OBJECTIVE: To analyze effectiveness and economy of domestic vancomycin hydrochloride for injection (trade name: Laikexin) vs. imported vancomycin hydrochloride for injection (trade name: Vancocin) in treatment of intracranial infection induced by MRSA, and to provide decision-making reference for the selection of clinical drugs. METHODS: Clinical data of patients with suspected MRSA intracranial infections receiving Laikexin or Vancocin were collected by retrospective study method from neurosurgery department of our hospital during Jan. 2016 to Jun. 2017, including 115 cases of Laikexin and 42 cases of Vancocin. Using response rate (including clinical cure and clinical improvement) as indexes, cost-effectiveness analysis was performed for Laikexin and Vancocin in the treatment of intracranial infection induced by MRSA by using decision tree model. Sensitivity analysis was conducted for 10% decrease of cost and response rate. RESULTS: Response rate and excepted cost of Laikexin were 85.21% and 13 125.96 yuan, cost-effectiveness ratio (CER) was 15 404.25. Response rate and excepted cost of Vancocin were 78.57% and 15 619.17 yuan, CER was 19 879.31. There was no statistical significance in response rate between Laikexin and Vancocin (P<0.05). There was no difference between sensitivity analysis and cost-effectiveness analysis. CONCLUSIONS: The efficacy of Laikexin and Vancocin in the treatment of MRSA intracranial infection is similar, but the CER of Laikexin is lower than that of Wenkexin.
6.The role of lung type Ⅱ epithelial stem cell differentiation in radiation-induced pulmonary fibrosis
Ziting XIAO ; Jian TIAN ; Yanyan ZHU ; Chaojie WANG ; Ning MA ; Xingnan ZHANG ; Yun ZHOU ; Jianwei ZHOU
Chinese Journal of Radiation Oncology 2020;29(12):1102-1109
Objective:To determine the role of type Ⅱ alveolar epithelial stem cells (AEC Ⅱ) in radiation-induced pulmonary injury and investigate the potential mechanism by observing the dynamic changes in the expression levels of anti-prosurfactant protein C (proSP-C) proSP-C (AEC Ⅱ biomarker), homeobox only protein X (HOPX, type I alveolar epithelial cell biomarker) or vimentin (a mesenchymal marker) and transforming growth factor β 1(TGF-β 1), a profibrotic cytokine. Methods:Eight-week old C57BL/6j female mice were exposed to X-ray thoracic irradiation. Mouse lungs were collected at 8 different time points of 24 h, 1 week, 1 to 6 months after irradiation. The histopathological changes of the lungs at different time points were observed with H& E staining to determine the time of formation of pulmonary fibrosis. In addition, the co-expression of proSP-C with HOPX or vimentin in AEC Ⅱ was confirmed by immunofluorescence staining to track AEC Ⅱ phenotypes at different injury phases following thoracic irradiation. The expression levels of those proteins and TGF-β 1 were quantitatively detected by Western blot. Results:After thoracic exposure to a single dose of 20 Gy X-ray for 3 months, the fibrotic lesions in the lungs could be noted. The co-expression of proSP-C with vimentin or HOPX could be observed in AEC Ⅱ. Western blot demonstrated that the expression levels of TGF-β 1 and those proteins were also changed along with the lung injury. Conclusion:AEC Ⅱ can be differentiated into mesenchymal-like cells after X-ray irradiation due to the up-regulated expression of TGF-β 1, which is a potential cause of radiation-induced pulmonary fibrosis.