1.Bie Jia Jian Pill Combined with Bone Mesenchymal Stem Cells Regulates microRNA-140 to Suppress Hepatocellular Carcinoma Stem Cells
Huang JINGJING ; Huang HONGNA ; Zhang WENFU ; Lv JIANLIN ; Huang GUOCHU ; Lin YUANJIA ; Chen SONGLIN ; Hu YUEQIANG
International Journal of Stem Cells 2021;14(3):275-285
Background and Objectives:
Cancer stem cells (CSCs) with tumorigenic potential are reported as the crucial factors of hepatocellular carcinoma (HCC) recurrence and therapy resistance. Bone mesenchymal stem cells (BMSCs) are documented to play an important role in the protection of hepatocytes. Bie Jia Jian pill (BJJP), a Traditional Chinese Medicine, has been used to treat liver fibrosis and liver cancer. This study aimed to explore the potential role of combined use of BJJP with BMSCs in HCC cell lines.
Methods:
and Results: Flow cytometry was used to identify BMSCs isolated from BALB/c mice and CSCs enriched from Huh7 cells by measuring CD24, CD133, CD44, CD73, CD105, CD166, CD29, CD14 and CD34. Differentiation potential of BMSCs was also determined. Cell viability and proliferation ability of CSCs were determined by CCK-8 assay and clone formation assay. The expressions of CSCs biomarkers and Wnt/β-catenin signal pathway related proteins were determined by PCR and western blot. TOP-Flash/FOP-Flash luciferase assay was applied to measure the activity of β-catenin/TCF. Compared with untreated CSCs, BJJP or BMSCs treatment alone on CSCs lead to increased miR-140 expression and cell apoptosis, as well as decreased expressions of CD24, CD133, EpCAM and cell viability.Downregualted expressions of Wnt/β-catenin signal pathway related proteins, Wnt3a and β-catenin were found in response to BJJP or BMSCs treatment alone. The combination of BJJP+BMSCs treatment on CSCs could further enhance the suppressive effect on CSCs. Down-regulation of miR-140 in CSCs partially blocked the effects of BMSCs or BMSCs+BJJP on the expressions of Wnt3a and β-catenin as well as the cell viability and apoptosis of CSCs.Reversed expression pattern was found in CSCs transfected with miR-140 overexpression.
Conclusions
Taken together, we demonstrate that BJJP+BMSCs together could further enhance the suppressive effect on CSCs through regulating miR-140 and suppressing Wnt/β-catenin signal pathway. This study demonstrated the potential of BJJP+BMSCs in therapeutic treatment of HCC.
2.Bie Jia Jian Pill Combined with Bone Mesenchymal Stem Cells Regulates microRNA-140 to Suppress Hepatocellular Carcinoma Stem Cells
Huang JINGJING ; Huang HONGNA ; Zhang WENFU ; Lv JIANLIN ; Huang GUOCHU ; Lin YUANJIA ; Chen SONGLIN ; Hu YUEQIANG
International Journal of Stem Cells 2021;14(3):275-285
Background and Objectives:
Cancer stem cells (CSCs) with tumorigenic potential are reported as the crucial factors of hepatocellular carcinoma (HCC) recurrence and therapy resistance. Bone mesenchymal stem cells (BMSCs) are documented to play an important role in the protection of hepatocytes. Bie Jia Jian pill (BJJP), a Traditional Chinese Medicine, has been used to treat liver fibrosis and liver cancer. This study aimed to explore the potential role of combined use of BJJP with BMSCs in HCC cell lines.
Methods:
and Results: Flow cytometry was used to identify BMSCs isolated from BALB/c mice and CSCs enriched from Huh7 cells by measuring CD24, CD133, CD44, CD73, CD105, CD166, CD29, CD14 and CD34. Differentiation potential of BMSCs was also determined. Cell viability and proliferation ability of CSCs were determined by CCK-8 assay and clone formation assay. The expressions of CSCs biomarkers and Wnt/β-catenin signal pathway related proteins were determined by PCR and western blot. TOP-Flash/FOP-Flash luciferase assay was applied to measure the activity of β-catenin/TCF. Compared with untreated CSCs, BJJP or BMSCs treatment alone on CSCs lead to increased miR-140 expression and cell apoptosis, as well as decreased expressions of CD24, CD133, EpCAM and cell viability.Downregualted expressions of Wnt/β-catenin signal pathway related proteins, Wnt3a and β-catenin were found in response to BJJP or BMSCs treatment alone. The combination of BJJP+BMSCs treatment on CSCs could further enhance the suppressive effect on CSCs. Down-regulation of miR-140 in CSCs partially blocked the effects of BMSCs or BMSCs+BJJP on the expressions of Wnt3a and β-catenin as well as the cell viability and apoptosis of CSCs.Reversed expression pattern was found in CSCs transfected with miR-140 overexpression.
Conclusions
Taken together, we demonstrate that BJJP+BMSCs together could further enhance the suppressive effect on CSCs through regulating miR-140 and suppressing Wnt/β-catenin signal pathway. This study demonstrated the potential of BJJP+BMSCs in therapeutic treatment of HCC.
3.Relationship between the changes of plasma levels of leptin and obesity in patients with insulinoma
Shuang YU ; Haiyan WU ; Ming LI ; Qiang WANG ; Liming ZHU ; Yuanjia CHEN
Chinese Journal of Digestion 2019;39(8):545-548
Objective To analyze the relationship between the changes of fasting plasma level of leptin and obesity in patients with insulinoma before operation.Methods From January 2003 to May 2008,40 patients with insulinoma diagnosed at Peking Union Medical College Hospital were selected.Preoperative fasting plasma samples of them were collected.From January 2003 to May 2008,the plasma samples of 28 volunteers matched with age,gender and body weight matched with the patients were collected as the controls.All the subjects were divided into overweight-obesity group and normal weight group according to their body mass index (BMI).Plasma levels of leptin of all the subjects were measured by enzyme linked immunosorbent assay (ELISA).The Mann-Whitney U test and the correlation coefficient test were used for statistical analysis.Results The plasma leptin level of patients with insulinoma was 0.35 ng/mL (0.25 ng/mL to 1.13 ng/mL),which was higher than that of the control group (0.29 ng/mL,0.25 ng/mL to 1.15 ng/mL),and the difference was statistically significant (U =324.50,P =0.003).In the normal-weight group,the plasma leptin level of the patients with insulinoma was 0.35 ng/mL (0.27 ng/mL to 0.62 ng/mL),which was higher than that of the control group (0.28 ng/mL,0.25 ng/mL to 0.37 ng/mL),and the difference was statistically significant (U =28.000,P =0.001).While in the overweight-obesity group,the plasma leptin levels of the patients with insulinoma and the controls were 0.35 ng/mL (0.25 ng/mL to 1.13 ng/mL) and 0.34 ng/mL (0.26 ng/mL to 1.15 ng/mL),respectively,and the difference was not statistically significant (U =153.500,P =0.525).Plasma leptin levels in both the patients with insulinoma and the controls,were correlated with BMI (r =0.355,P =0.025;r =0.571,P =0.001,respectively).Conclusion Preoperative fasting plasma level of leptin increase in patients with insulinoma which is correlated with BMI.
4.Recent advance in role of prefrontal cortex in pathogenesis of schizophrenia
Jinglan YAN ; Xiaorong ZHENG ; Yuanjia ZHENG ; Jiang HE ; Yongjun CHEN
Chinese Journal of Neuromedicine 2019;18(2):194-198
Schizophrenia is a serious neurological disorder characterized by incoordination among thinking, cognition, emotion and behavior, and its pathogenesis remains unclear now. In recent years, an increasing number of reports have found that the occurrence of schizophrenia shares a close relationship with prefrontal cortex (PFC), while the later plays an important role in numerous advanced cognitive functions, including working memory, learning and decision making. This review focuses on the recent development of neural circuits, including neurodevelopment, neurotransmitters, synaptic transmission, functional connectivity of brain regions and neural synchrony oscillation in PFC. Hopefully, this review will help to elucidate the pathogenesis of schizophrenia, and provide approaches and ideas for the treatment of relevant psychiatric disorders.
5.Comparative Analysis of Volatile Components in Different Parts of Stelleropsis Tianschanica
Leiling SHI ; Yuanjia MA ; Yongqiang GUAN ; Xiongfei GUO ; Gang CHEN ; Fanghua LIN
China Pharmacist 2018;21(2):215-223
Objective:To compare and analyze the chemical constituents of volatile oils extracted from the different parts ( flow-ers,leaves and roots) of Stelleropsis tianschanica by chromatography-mass spectrometry (GC-MS). Methods:The volatile oil was ex-tracted by diethyl ether-Soxhlet extraction method and analyzed by GC-MS with a capillary gas chromatographic column. The relative contents of the volatile compounds were calculated by chromatographic peak area normalization method.Results: Totally 179 volatile constituents in the different parts of Stelleropsis tianschanica were identified. Among them,81 compounds were identified in leaves,and the relative content accounted for 82.77% of the total volatile compounds;108 compounds were identified in flowers,and the relative content accounted for 82.85% of the total volatile compounds;112 compounds were identified in roots, and the relative content ac-counted for 85.98% of the total volatile compounds. Totally 33 compounds existed in all the three parts,and the content accounted for 39.24% of the total volatile components in leaves,35.86% in flowers and 48.89% in roots. The relative content of(Z,Z)-9,12-oc-tadecadienoic acid in leaves,flowers and roots of S. tianschanica was the highest,which accounted for 11.12%,9.8% and 22.49%, respectively. Conclusion:The different parts of S. tianschanica have similar volatile components, while the specific substances and the contents are different.
6.Network Pharmacological Analysis of Yi-Guan Decoction on "Different Diseases with Same Treatment"
Mengdie YANG ; Feifei CAI ; Rong WU ; Xiaole CHEN ; Qiusha PAN ; Yuanjia HU ; Shibing SU
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(12):1912-1919
This study was aimed to predict active compounds,drug targets and potential diseases of Yi-Guan decoction (YGD) by network pharmacological technology,and to clarify molecular mechanisms of YGD efficiency on different diseases with liver and kidney yin deficiency syndrome (LKYDS).Chemistry compounds,targets and related diseases from YGD were collected from TCMSP,TCM Database@Taiwan,TCMID,HIT,Drugbank,PubChem and TTD databases.The YGD compounds-targets-diseases network was constructed.The network topology was analyzed by Cytoscape software.The analysis of GO biological processes and KEGG pathways enrichment were performed by DAVID website.The results showed that 849 chemical compounds were identified from Beishashen,Maidong,Danggui,Shengdihuang,Chuanlianzi and Gouqizi.There were 49 active CHM compounds that were both oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18,corresponding to 200 target proteins and 264 diseases.The top three GO biological processes were response to organic substance,regulation of cell proliferation,and response to endogenous stimulus,respectively.The top three KEGG pathways were pathways in cancer,hepatitis B,and prostate cancer,respectively.It was concluded that the analysis on YGD was conducted based on network pharmacology,and the compound-target-disease network was built,which may help to clarify the mechanisms of YGD efficiency on different diseases with LKYDS.It can provide clues to find new potential clinical adaptation of disease and new drugs.
7.Expression of microtubule-associated protein 2 correlates with better prognosis of pancreatic neuroendocrine tumors
Tiantian SONG ; Yu XIAO ; Chunmei BAI ; Naishi LI ; Jie CHEN ; Dachun ZHAO ; Yuli SONG ; Kaizhou JIN ; Liming ZHU ; Run YU ; Xianjun YU ; Yuanjia CHEN
Chinese Journal of Clinical Oncology 2017;44(11):532-538
Objective: To determine whether microtubule-associated protein 2 (MAP2) and microtubule-associated protein 1B (MAP1B) could be prognostic biomarkers for patients with pancreatic neuroendocrine tumors (PNETs). Methods:With immunohisto-chemical staining, the expressions of MAP2 and MAP1B were examined in 193 and 120 primary tumors and peritumoral tissues, re-spectively. Then, the relationship between the expression of each protein and clinicopathological characteristics, including prognosis was analyzed. Results:MAP2 and MAP1B were expressed in 88 of 193 (45.6%) and 77 of 120 (64.2%) tumors, respectively. The expres-sion of MAP2 was significantly associated with the favorable overall survival of patients with PNETs (P=0.012). Moreover, MAP2 expres-sion was associated with the improved overall survival in a subset of patients with stageⅡand stageⅢtumors (P=0.017). The MAP1B expression did not correlate with other clinicopathological features and prognosis. Conclusion:MAP2 could be a novel, independent prognostcbiomarker for PNETs.
8.Traditional Interpretation of Modern Medicine: An Effective Approach for Promoting Traditional Chinese Medicine Development
Xiaole CHEN ; Mengdie YANG ; Yuanjia HU ; Shibing SU
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(3):381-386
In the long course of traditional Chinese medicine (TCM) development history,generations of physicians in their long-term medical practice,have paid attention to assimilate and apply new technology and new theory,constantly enrich and perfect the medical technologies,methods and theory systems.It is particularly important to promote the innovation of TCM theory and guide the clinical application of TCM through the learning and absorption of advantages from modern technologies and biomedicine to transform as part of TCM,and then,to expatiate with TCM language.It is especially important in the promotion of TCM theory innovation and clinical guidance of TCM practice.This paper overviewed the common points between TCM and modern medicine from the aspects of balance and steady state of organism,zangfu-organ relationship,etiology and pathogenesis,syndrome differentiation methods,compatibility of Chinese herbal medicine and formula,medicinal properties and pharmacology,etc.The feasibility of applying modern medicine in the interpretation of TCM and its development prospects was expatiated.It provided new ideas and new methods in TCM development.
9.Basic and translational research progress of gastrointestinal neuroendocrine neoplasmas.
Yuli SONG ; Xiaoyi LI ; Tiantian SONG ; Guole LIN ; Yuanjia CHEN
Chinese Journal of Gastrointestinal Surgery 2016;19(11):1217-1221
Gastrointestinal neuroendocrine tumors are a group of highly heterogeneous tumors. Their incidences have increased in the Western countries as well as in Asia for years. In recent years, predominant progression has been made in the basic and translational studies on gastrointestinal neuroendocrine tumors. Gastric neuroendocrine neoplasmas are classified as four types: type I( occurs on the basis of autoimmune atrophic gastritis, type II( clinically manifests as multiple endocrine tumor type I( and Zollinger-Ellison syndrome, type III( is sporadic neuroendocrine neoplasmas, and type IIII( is neuroendocrine carcinoma. According to the location of primary tumor, intestinal neuroendocrine neoplasmas are classified as small intestine neuroendocrine neoplasmas and colorectal neuroendocrine neoplasmas. The latest finding shows that familial type I( gastric neuroendocrine neoplasmas exists homozygous missense mutation (c.2107C>T) of ATP4A gene. A number of researches focus on small intestine neuroendocrine neoplasmas recently. The chromosome instability, whole genome low methylation and abnormal expression of microRNA can be found in small intestine neuroendocrine neoplasmas. Part of them presents heterozygous mutations and loss of heterozygosity of CDKN1B gene. A recent study showed the heterozygous mutations of IPMK gene (c.990-993del) in familial small intestinal neuroendocrine neoplasmas. PROX1 and Annexin A1 may be involved in the malignant progression of rectal neuroendocrine neoplasmas via the Wnt pathway. The molecular mechanism of gastrointestinal neuroendocrine carcinoma is significantly different from gastrointestinal neuroendocrine tumors. The expression of mTOR, thymidylate synthase and PD-L1 protein, and gene mutation of BRAF V600E and KRAS have been exclusively found in gastrointestinal neuroendocrine carcinoma. The expression of thymidylate synthase, p27, p16, Gα15, PROX1 and Annexin A1 in gastrointestinal neuroendocrine neoplasmas is associated with the prognosis of these patients. Neurokinin A is a specific peripheral blood tumor biomarker for the prognosis and response to the treatment of patients with small intestinal neuroendocrine neoplasmas. INSL5 can be used as a unique biomarker for rectal neuroendocrine neoplasmas.
Biomarkers, Tumor
;
Carcinoma, Neuroendocrine
;
Gastrointestinal Neoplasms
;
Humans
;
Intestine, Small
;
Mutation
;
Neuroendocrine Tumors
;
Prognosis
;
Translational Medical Research
10.Analysis on layout of traditional Chinese medicine industry based on location quotient.
Cong CHEN ; Yuanyuan YU ; Yuanjia HU ; Yitao WANG
China Journal of Chinese Materia Medica 2012;37(5):549-552
To observe the layout and evolution of the traditional Chinese medicine (TCM) medical industry, classify the industry by region and conduct a preliminary study on its professional advantages, competitiveness and possible cause by using the theory of location quotient in regional economics, in order to provide suggestions for the layout of the TCM medical industry.
Drug Industry
;
Medicine, Chinese Traditional

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