1.Research progress on carrier-free and carrier-supported supramolecular nanosystems of traditional Chinese medicine anti-tumor star molecules
Zi-ye ZANG ; Yao-zhi ZHANG ; Yi-hang ZHAO ; Xin-ru TAN ; Ji-chang WEI ; An-qi XU ; Hong-fei DUAN ; Hong-yan ZHANG ; Peng-long WANG ; Xue-mei HUANG ; Hai-min LEI
Acta Pharmaceutica Sinica 2024;59(4):908-917
Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.
2. Expression change and role of myeloma cancer gene mRNA and the non-coding RNA in the hepatocyte cycle initiation and termination during the rat liver regeneration
Qi-Jie XUE ; Cui-Fang CHANG ; Zi-Hui WANG ; Xia-Yan ZANG ; Kai-Lin LIN ; Chun-Bo ZHANG ; Lu HAN ; Bing-Yu YE ; Cun-Shuan XU ; Qi-Jie XUE ; Cui-Fang CHANG ; Zi-Hui WANG ; Xia-Yan ZANG ; Kai-Lin LIN ; Chun-Bo ZHANG ; Lu HAN ; Bing-Yu YE ; Cun-Shuan XU
Acta Anatomica Sinica 2023;54(4):41-419
Objective To explore the role pathway and pattern of the myeloma cancer gene (MYC) and its mRNA interaction with the microRNAs(miRNAs) and circular RNA(circRNAs) at hour 0, hour 6 and hour 72 in the rat liver regeneration. Methods The rat 2/3 hepatectomy (PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al. The expression changes of mRNA, miRNA and circRNA [together named as competing endogenous RNA (ceRNA)] were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at hour 0 and hour 6 after PH, the ratio value of MYC mRNA showed 0.15±0.03 and 2.36±0.20, miR-134-5p indicated 3.22±0.61 and 0.08±0.02, circRNA_12112 displayed 0.68±0.21 and 13.35±3.53. At the same time, the cell cycle initiation-related genes ras association domain family member 1 (RASSF1), cyclin dependent kinase 2 (CDK2), superoxide dismutase 2 (SOD2), which were promoted in expression by MYC, were down-regulated at hour 0 after PH, but the cell cycle initiation-related genes nestin (NES), RAD21 cohesin complex component (RAD21), CUE domain containing 2 (CUEDC2), which are inhibieted in expression by MYC, had no meaningful express changes at hour 0 after PH. On the other hand, the cell cycle initiation-related gene SOD2, which was promoted in expression by MYC, was up-regulated at hour 6 after PH, but the cell cycle initiation-related genes NES, RAD21, CUEDC2, which are inhibieted in expression by MYC, were down-regulated at hour 6 after PH. In contrary, at hour 72 after PH, the ratio value of MYC mRNA showed 2.36±0.20, miR-880-3p indicated 0.54±0.01, circRNA_09599 displayd 0.54±0.16. At the same time, the cell cycle termination-related gene hepatocyte growth factor (HGF), which is promoted in expression by MYC, was up-regulated 72 hours after PH, the cell cycle termination-related genes MET proto-oncogene receptor tyrosine kinase (MET) and cyclin dependent kinase inhibitor 1A (CDKN1A), which are inhibieted in expression by MYC, were down-regulated 72 hours after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, MYC, its mRNA is inhibited by miRNAs, and the cell cycle initiation-related and cell cycle termination-related genes, which are regulated by MYC, are helpful for the hepatocyte to be in cell cycle initiation state at hour 6 after PH and to be in cell cycle termination state at hour 72 after PH.
3. Expression change and role of Kruppel-like factor 4 mRNA, microRNA-881-3p, circular RNA_20298 and circular RNA_14826 in the hepatocyte apoptosis during the rat liver regeneration
Kai-Lin LIN ; Xian-Guang YANG ; Zi-Hui WANG ; Xia-Yan ZANG ; Qi-Jie XUE ; Lu HAN ; Chun-Bo ZHANG ; Cun-Shuan XU ; Kai-Lin LIN ; Xian-Guang YANG ; Zi-Hui WANG ; Xia-Yan ZANG ; Qi-Jie XUE ; Lu HAN ; Chun-Bo ZHANG ; Cun-Shuan XU ; Zhi-Hu ZHAO
Acta Anatomica Sinica 2023;54(4):420-424
[ Abstract] Objective To explore the role pathway and pattern of the Kruppel-like factor 4 (KLF4) and its mRNA interaction with microRNA (miRNAs) and circular RNA (circRNAs) at 0 hour and the 120 th hour in the rat liver regeneration. Methods The rat 2 / 3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNA (ceRNA) were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3. 2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and the 120th hour PH, the ratio value of KLF4 mRNA showed 1. 00±0. 16 and 3. 14±0. 27, miR-881-3p displays 18. 30±1. 44 and 0. 47±0. 02, circRNA_20298 indicated 0. 32±0. 10 and 4. 24±0. 22, circRNA_14826 showed 0. 42±0. 13 and 0. 61±0. 08. At the same time, the four kinds of cell apoptosis-related genes adrenoceptor beta 2 (ADRB2), dimethylarginine dimethylaminohydrolase 2 (DDAH2), annexin A5 (ANXA5), ect, which were promoted in expression by KLF4, were down-regulated at 0 hour after PH, but the cell apoptosis-related genes synuclein gamma (SNCG), glutathione-disulfide reductase (GSR), FYVE, RhoGEF and PH domain containing 4 (FGD4), ect, which were inhibited in expression by KLF4, were up-regulated at 0 hour after PH. On the other hand, the cell apoptosis-related genes ANXA5 and thymosin beta 10 (TMSB10), which are promoted in expression by KLF4, were up-regulated at the 120th hour after PH, but the cell apoptosis-related genes chloride intracellular channel 4 (CLIC4) and ataxin 3 (ATXN3), ect, which were inhibited in expression by KLF4, were down-regulated at the 120th hour after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, KLF4, its mRNA is inhibited by miRNAs, and the cell apoptosis-related genes, which are regulated by KLF4, are helpful for the hepatocyte to be in active state 0 hour after PH and to be in apoptotic state 120-hour after PH.
4. Expression change and role of sex determining region box transcription factor 2 mRNA and the non-coding RNA in the hepatocyte stem changes during the rat liver regeneration
Zi-Hui WANG ; Jian-Lin GUO ; Xia-Yan ZANG ; Qi-Jie XUE ; Kai-Lin LIN ; Chun-Bo ZHANG ; Lu HAN ; Cun-Shuan XU ; Zi-Hui WANG ; Jian-Lin GUO ; Xia-Yan ZANG ; Qi-Jie XUE ; Kai-Lin LIN ; Chun-Bo ZHANG ; Lu HAN ; Cun-Shuan XU ; Jun-Tang LIN
Acta Anatomica Sinica 2023;54(2):202-207
Objective To explore the role pathway and pattern of the sex determining region box transcription factor 2 (SOX2) and its mRNA interaction with microRNA(miRNAs, miR) and circular RNA(circRNA) at 0 hour and 2 hours in the rat liver regeneration. Methods The rat 2/3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA [together named as competing endogenous RNAs(ceRNA)] were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and 2 hours after PH, the ratio value of SOX2 mRNA shows 1.00±0.09 and 2.15±0.48, miR-3558-3p displays 4.53± 0.10 and 0.81±0.16, circRNA_18404 shows 1.24±0.04 and 11.10±0.57, circRNA_18045 displays 1.97±0.47 and 4.44± 0.23. At the same time, the eight kinds of cell dedifferentiation-related genes AT-rich interaction domain 5A (ARID5A), activating transcription factor 3 (ATF3), BTG anti-proliferation factor 2 (BTG2), etc, which are prometed in expression by SOX2, were down-regulated at 0 h after PH, but the cell differentiation-related genes interferon regulatory factor 6 (IRF6) and somatostatin (SST), which are inhibited in expression by SOX2, were up-regulated at 0 hour after PH. On the other hand, the eight kinds of cell dedifferentiation-related genes ARID5A, ATF3, BTG2, etc, which are promoted in expression by SOX2, were up-regulated at 2 hours after PH, but the cell differentiation-related gene SST, which is inhibited in expression by SOX2, was down-regulated, and IRF6 had no meaningful changes in expression at 2 hours after PH. Conclusion The correlation in expression and role of the miRNA, which are inhibited by circRNA, SOX2, its mRNA is inhibited by miRNA, and the cell stem-related genes, which are regulated by SOX2, are helpful for the hepatocyte to be in differentiation state at 0 hour after PH and to be in stem state at 2 hours after PH.
5. Expression change and role of myeloma cancer gene mRNA, microRNA-540-3p, circular RNA-04996 in the liver inflammatory reaction during the rat liver regeneration
Chun-Bo ZHANG ; Gai-Ping WANG ; Zi-Hui WANG ; Xia-Yan ZANG ; Qi-Jie XUE ; Kai-Lin LIN ; Lu HAN ; Qi-Wen WANG ; Cun-Shua XU ; Chun-Bo ZHANG ; Gai-Ping WANG ; Zi-Hui WANG ; Xia-Yan ZANG ; Qi-Jie XUE ; Kai-Lin LIN ; Lu HAN ; Qi-Wen WANG ; Cun-Shua XU
Acta Anatomica Sinica 2023;54(1):70-74
Objective To explore the role pathway and pattern of the transcription factor myeloma cancer gene (MYC) and its mRNA interaction with microRNA(miRNA, miR) and ciccular RNA(circRNAs) at 0 hour and 6 hour in the rat liver regeneration. Methods The rat 2/3 hepatectomy (partial hepatectomy,PH) model was prepared as described by Higgins, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNAs(ceRNA) of remnant liver were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at 0 hour and 6 hours after PH, the ratio value of MYC mRNA showed 0.15±0.03 and 2.36±0.20, miR-540-3p displays 3.00±0.43 and 0.79±0.01, circRNA_04996 showed 1.43±0.43 and 3.14±0.94. At the same time, the four kinds of inflammatory reaction-related genes plasminogen activator urokinase receptor (PLAUR), tumor necrosis factor (TNF), interleukin 1 receptor type 2 (IL1R2), ect, which were prometed in expression by MYC, were down-regulated at 0 hour after PH, but the inflammatory reaction-related genes natriuretic peptide A (NPPA), nuclear receptor subfamily O group B member 2 (NROB2) and peroxisome proliferator activated receptor alpha (PPARA), which were inhibited in expression by MYC, were up-regulated at 0 hour after PH. On the other hand, the three kinds of inflammatory reaction-related genes PLAUR, TNF, IL1R2, ect, which are prometed in expression by MYC, were up-regulated at 6 hours after PH, but the inflammatory reaction-related genes NPPA, NROB2 and PPARA, which were inhibited in expression by MYC, were down-regulated at 6 hours after PH. Conclusion The correlation in expression and role of the miRNA, which are inhibited by circRNAs, MYC, its mRNA is inhibited by miRNAs, and the inflammatory reaction-related genes, which are regulated by MYC, and are helpful for the hepatocyte to be in non-inflammatory reaction state at 0 hour after PH and to be in inflammatory reaction state at 6 hours after PH.
6.Study on the application of model transfer technology in the extraction process of Xiao'er Xiaoji Zhike oral liquid
Xiu-hua XU ; Lei NIE ; Xiao-bo MA ; Xiao-qi ZHUANG ; Jin ZHANG ; Hai-ling DONG ; Wen-yan LIANG ; Hao-chen DU ; Xiao-mei YUAN ; Yong-xia GUAN ; Lian LI ; Hui ZHANG ; Xue-ping GUO ; Heng-chang ZANG
Acta Pharmaceutica Sinica 2023;58(10):2900-2908
The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.
7.Role of JAK2/STAT3 signaling pathway in ginsenoside Re pretreatment in prevention of isoproterenol-induced acute myocardial ischemia
Xue LENG ; Nan SONG ; yuan An ZANG ; fang Qi LI ; yan Li GU
Chinese Pharmacological Bulletin 2018;34(1):103-107
Aim To observe the protective effect of ginsenoside Re pretreatment on rats with isoproterenol-induced acute myocardial ischemia via JAK 2/STAT3 signaling pathway .Methods SD rat model with acute myocardial ischemia was established using isoprotere-nol.Seventy-five rats were randomly divided into five groups: control group, model group , puerarin group (PUE), high dose group (Re-H, 20 mg· kg -1) and Re low-dose group ( Re-L, 10 mg kg -1 ) .The blood flow on the heart surface of rats in each group was ob-served by moor laser blood flow imaging system .The levels of CK , LDH, SOD, MDA and GSH in myocar-dium were measured by ELISA .The expressions of Bax and Bcl-2 proteins were detected by immunohistochem-istry.The expressions of JAK , p-JAK, STAT3 and p-STAT3 proteins were detected by Western blot .Re-sults Compared with the control group , the mean blood flow on the heart surface of rats in the model group significantly decreased , the levels of CK , LDH and MDA in the myocardium increased , the levels of GSH and SOD decreased , the ratio of Bcl-2/Bax de-creased ( P <0.05 ) , and the expression of JAK 2/STAT3 pathway related proteins was enhanced ( P <0.05 ) . The mean blood flow on the heart surface markedly increased , the levels of CK , LDH and MDA decreased , the level of GSH-Px increased , the ratio of Bcl-2/Bax increased, and the expression of JAK2/STAT3 pathway proteins evidently increased in the Re-H group compared with those of the model group ( P<0.05 ) .Conclusion Ginsenoside Re pretreatment has a good protective effect on the myocardium in rats with acute myocardial ischemia , which may be related to the activation of JAK2/STAT3 signaling pathway .
8.Study on early screening of high saponin ginseng lines.
Li-Shan HAO ; Yu-Gang GAO ; Pu ZANG ; Yan ZHAO ; Zhong-Mei HE ; Hong-Yan ZHU ; He YANG ; Shang-Li LIU ; Jing-Ting LIU ; Lian-Xue ZHANG
China Journal of Chinese Materia Medica 2017;42(24):4775-4781
The study aims at screening the specific bands by PCR, quickly and accurately evaluating the quality of ginseng seeding, accelerating the process of ginseng breeding. Based on the correlation of genetic differences and saponin content between individuals, a pair of specific primer GC1 was screened by PCR. According to the experiment by L16 (45) orthogonal test, a PCR system most suitable for GC1 was established, which came out total 25 μL reaction system containing DNA 2.60 mg•L⁻¹, Mg²⁺ 1.44 mmol•L⁻¹, dNTP 0.19 mmol•L⁻¹, primer 0.32 μmol•L⁻¹ and Taq enzyme concentration 0.076 U•μL⁻¹. By comparing the saponin content and the GC1 PCR electrophoretogram of samples, the ginseng, with 1 200 bp specific band by PCR of GC1, the contents of 9 monosodium saponins and their additions were higher than others, which provided a reliable method for accelerating the process of ginseng breeding. The sequence was sequenced and 99% homologous to glycerol-3-phosphate dehydrogenase.
9.Expression and roles of long non-coding RNA ZFAS1 in non-small cell lung cancer
Xu ZHANG ; yan Xue ZANG ; mei Jian GU ; Peng ZHANG ; Wei LIANG ; yan Jing CHEN ; Lei PAN ; Hui QIAN ; rong Wen XU
Chinese Journal of Clinical Laboratory Science 2017;35(11):813-817,848
Objective To determine the expression levels of zinc finger antisense 1 (ZFAS1) in tumor tissues of non-small cell lung cancer (NSCLC) and investigate the biological roles of ZFAS1 in NSCLC.Methods The relative expression levels of ZFAS1 in tumor tissues of NSCLC patients were determined by using real-time fluorescent qRT-PCR.RNA interference was used to knock down ZFAS1 expression in A549 cells.The proliferations of A549 cells with ZFAS1 knockdown were determined by cell counting and cell colony formation assays.Flow cytometric analysis was used to determine the cellular cycle distribution and apoptosis of the A549 cells with ZFAS1 knockdown.Transwell migration and matrigel invasion assays were used to determine the migration and invasion of the A549 cells with ZFAS1 knockdown.The gene expression levels of cyclin D1,Bcl2,N-cadherin,ZEB1,Slug and Twist were determined by real-time fluorescent qRT-PCR.Results The mean expression levels of ZFAS1 in tumor tissues of NSCLC patients [0.01 (0.002 to 0.054)] were significantly higher than those in the adjacent non-cancerous tissues [0.002 (0.001 to 0.012)] (Z =-2.638;P < 0.01).After ZFAS1 knockdown,the proliferation of A549 cells was remarkably retarded (P < 0.01).The percentage of cells at G1 phase was increased while the cells at S phase was decreased (P < 0.01).The rate of apoptotic cells was significantly increased in A549 cells with ZFAS1 knockdown (P < 0.01).A549 cells showed decreased migration and invasion abilities after ZFAS1 knockdown (P <0.01).The expression levels of cyclin D1,Bcl2,N-cadherin,ZEB1,Slug and Twist genes were decreased in ZFAS1 knockdown A549 cells (P < 0.05).Conclusion ZFASI was highly expressed in the tumor tissues of NSCLC patients.ZFAS1 knockdown induced cell cycle arrest,cell apoptosis and suppression of epithelial-mesenchymal transition (EMT),leading to the inhibition of proliferation,migration,and invasion of NSCLC cells.
10.Application status of small interfering RNA in spinal cord injury
Jun ZHAO ; Hong-Jie XIN ; Hui-Qin XUE ; Yuan-Tong ZANG ; Jin-Yu YAN ; Jian-Feng LI
Chinese Journal of Tissue Engineering Research 2017;21(36):5892-5897
BACKGROUND:The connection between high-level central nervous system and spinal cord and peripheral nerve under injury level is blocked by traumatic spinal cord injury,and the whole function of the body is thereby influenced.The loss of motor function and feeling both severely affect the patient's life quality in views of physiology,psychology,function and social economics.RNA interference is an effective method to silence target genes,which provides a new treatment strategy for spinal cord injury.OBJECTIVE:To explore the application status of RNA interference in spinal cord injury.METHODS:PubMed and CNKI databases were retrieved using the keywords of "RNA interference,RNAi,spinal cord injury" in English and Chinese,respectively.The articles addressing the application of RNA interference in spinal cord injury were collected and reviewed.RESULTS AND CONCLUSION:Totally 44 articles were enrolled.It is urgent to find a new way to treat spinal cord injury.Compared with the traditional gene silencing technology,RNA interference owing to high specificity,high efficiency,high stability and high penetrability is considered to be a new direction for the studies on the pathogenesis and treatment of spinal cord injury.

Result Analysis
Print
Save
E-mail