1.Exploring the Mechanism of Cichorium Glandulosum in the Treatment of Liver Fibrosis Based on Network Pharmacology and Experimental Validation
Jianhua YANG ; Ruoyu GENG ; Wei ZANG ; Qian LI ; Chao DU ; Junping HU
Chinese Journal of Modern Applied Pharmacy 2024;41(3):303-312
OBJECTIVE
To investigate the mechanism of Cichorium glandulosum in the treatment of liver fibrosis by using network pharmacology and experimental validation.
METHODS
A "component-target-pathway" network was constructed with the help of TCMSP, Pubchem, SwissTargetPrediction and Genecards databases, and the STRING database was used to predict the targets of Cichorium glandulosum against liver fibrosis. KEGG and GO enrichment analysis was performed in the DAVID database, and molecular docking of active ingredients and key targets was docked in AUTODOCK. PDGF-BB was used to induce activation of cells and verify the effects of six compounds, including quercetin, quercetin, chicoric acid, caffeic acid, chlorogenic acid, and isochlorogenic acid, on the proliferation, apoptosis, and liver fibrosis indicators of HSC-T6 cells. Western blotting was used to detect the expression of Ras, ERK1, ERK2, C-fos, and JNK proteins in HSC-T6 cells.
RESULTS
Network pharmacology screened 239 common targets between the components and liver fibrosis, PPI analysis showed that SRC, STAT3, HSP90AA1 and other targets were key targets, KEGG analysis showed that the pathways affected by Cichorium glandulosum included cancer pathways, metabolic pathways, etc. GO analysis predicted that Cichorium glandulosum mainly affected processes such as signal transduction. The molecular docking results showed that the target that could bind well with the components MAPK1, and the components that could bind well with the target aesculetin, caffeic acid and chlorogenic acid. Compared with the model group, the inhibition effect of the six compounds on PDGF-BB-induced HSC-T6 cell activation was stronger, and all 6 compounds had the effects to reverse the index of liver fibrosis, in which aesculetin had the strongest activity(P<0.01). The expression of Ras, ERK1, ERK2, C-fos, and JNK in HSC-T6 cells decreased after the interventions of 6 compounds.
CONCLUSION
Each component of Cichorium glandulosum has different anti liver fibrosis effects, which are related to the inhibition of ERK/RAS pathway activation.
2.Effect of silencing MPZL1 on tumor cell stemness and drug resistance of A549 / Tax cells via β-catenin signaling
Chao Zang ; Qiao Ge ; Chao Li ; Haining Hong ; Wei Li
Acta Universitatis Medicinalis Anhui 2024;59(1):99-105
Objective :
To explore the effect of MPZL1 knockdown in A549 Taxol resistant (A549 / Tax) cells and whether it affect drug resistance and tumor cell stemness by regulating β-catenin.
Methods :
A549 and A549 / Tax cells were treated with different concentrations of doxorubicin and paclitaxel to observe the differences in drug resist- ance between the two cells.Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the MP- ZL1 expression level in A549 and A549 / Tax cells. After knockdown or overexpression of MPZL1 in A549 / Tax cells,cells were divided into control group,small hairpin RNA negative control ( sh-NC) group,MPZL1 knock- down(sh-MPZL1) group,overexpression negative control ( OE-NC) group,MPZL1 overexpression ( OE-MPZL1) group.Cell counting kit-8 ( CCK-8 ) and clone formation assay were utilized to investigate cell proliferation and clone formation ablity.Western blot assay was used to detect the protein expression after the cells treated with Wnt / β-catenin signaling inhibitor XAV939 and activator CHIR-99201 .
Results :
The half inhibitory concentration ( IC50 ) of doxorubicin and paclitaxel in A549 / Tax cells significantly increased compared to A549 cells(P<0. 01) . MPZL1 presented a higher expression trend in A549 / Tax cells.The IC50 values of A549 / Tax for doxorubicin and paclitaxel were 2. 731 mg / ml and 4. 939 μg / ml after MPZL1 knockdown,compared to 4. 541 mg / ml and 13. 55 μg / ml in the NC group (P<0. 01) .The results of CCK-8 and clone formation assay showed that the knockdown of MPZL1 reduced the viability of cells proliferation and clonal formation ability (P<0. 05) .Western blot results in- dicated that the expression levels of MPZL1 protein,tumor cell stemness associated proteins ( CD44,CD133) ,β - catenin and multidrug resistance protein 1 (MDR1) ,lung resistance-related protein ( LRP) were significantly re- duced in the sh-MPZL1 group. Furthermore ,XAV939 could inhibit the expression levels of MPZL1 ,CD44, CD133,MDR1,LRP and β-catenin(P<0. 01) .The inhibitory effect of knockdown MPZL1 on the aforementioned proteins was significantly reversed by CHIR-99201 treatment.
Conclusion
MPZL1 is highly expressed in A549 / Tax cells.Knockdown MPZL1 suppresses the tumor cell stemness and proliferation,thereby reversing the drug re- sistance of doxorubicin and paclitaxel in A549 / Tax cells.
3.Application of Hisense computer-assisted surgery system in perioperative period of laparoscopic hepatectomy for liver cancer
Xin-Yu LI ; Zi-Qi ZANG ; Qi-Sheng HAO ; Li-Chao CHA ; Ming-Kai GONG ; Guo-Fei DONG ; Qing-Ze LI ; Lan-Tian TIAN
Chinese Journal of Current Advances in General Surgery 2024;27(6):435-441
Objective:To explore the clinical application of Hisense Computer-Assisted Sur-gery System(CAS)in the perioperative period of hepatectomy for liver cancer.Methods:Clinical data of patients undergoing laparoscopic hepatectomy(LH)for liver cancer from January 2021 to December 2022 were collected.Patients were divided into three groups based on surgical difficulty(low,medium,high)and further stratified into CAS-assisted subgroup and control subgroup ac-cording to whether the CAS system was used.Demographic and perioperative data were com-pared among different groups.Results:A total of 317 patients'clinical data were collected,in-cluding 31 cases in the low difficulty group,132 cases in th medium difficulty group,and 154 cases in the high difficulty group,with 108 cases(34.1%)in the CAS-assisted subgroup and 209 cases(65.9%)in the control group.In the medium difficulty group,the CAS-assisted subgroup had shorter operation time,drainage tube duration,and postoperative hospital stay compared to the control group(P<0.001),and the AFP levels at 1 month postoperatively in the CAS-assisted sub-group were lower than those in the control group(P<0.001).In the high difficulty group,the CAS-assisted subgroup showed shorter operation time,drainage tube duration,and postoperative hospi-tal stay,less intraoperative blood loss,and lower AFP levels 1 month post-operation compared to the control group(P<0.001 for all).Conclusion:Preoperative CAS in medium and high difficulty laparoscopic liver resections improves perioperative outcomes.Hisense CAS effectively assists general surgeons in accurately identifying the anatomical site of liver tumors,providing precise pre-operative simulation and intraoperative navigation,thereby optimizing surgical strategies for pa-tients.
4.Research and application of membrane sealing device for medical blood collection sample tube
Zongpin JIANG ; Xingsen ZANG ; Peng ZHAO ; Chao WANG
China Medical Equipment 2024;21(9):178-180
Medical blood collection tubes need to be sealed and stored after testing.To solve the problem that the traditional plastic plug sealing device was not compatible with different sizes and specifications of blood collection tube sealing,a hospital blood collection tube sealing device was designed,including a track component,a blocking component,a clamping component,a film feeding component,a film sealing and folding component.Combined with the selection of sealing parameters and fatigue test,it was shown that the blood collection tube sealing device could achieve high compatibility,high efficiency,simple structure and high reliability for sealing blood collection tubes and meet the needs of clinical testing.
5.Performance evaluation of nucleic acid testing system for blood screening in high-altitude areas
Liang ZANG ; Lei ZHOU ; Ji DUO ; Hao LIN ; Rui BAI ; Mei YANG ; Chao DAN ; Yaxin FAN
Chinese Journal of Blood Transfusion 2023;36(10):935-939
【Objective】 To validate the performance of a nucleic acid testing(NAT) system for blood screening in the high-altitude Nagqu region of Tibet, in order to assess the capability of NAT in high-altitude areas and further enhance blood safety. 【Methods】 Various methods were employed to evaluate the analytical sensitivity, reproducibility, ability to prevent cross-contamination, and comparison between different NAT systems. 【Results】 The NAT system in the Nagqu region of Tibet achieved a 100% detection rate for high-concentration HBV DNA and HIV-1 RNA samples, and over 90% for medium-concentration samples. PROBIT analysis revealed the lower limits of detection (LOD) for HBV DNA and HIV-1 RNA to be 8.29 IU/mL (95% CI, 5.88~20.55 IU/mL) and 40.52 IU/mL (95% CI, 30.26~85.92 IU/mL), respectively. For HCV RNA genotype 2a, the LOD was 97.14 IU/mL (95% CI, 71.00~182.67 IU/mL), all of which were lower than the declared minimum detectable concentrations in the instructions. Reproducibility analysis demonstrated a 100% level of consistency within the system. Cross-contamination performance verification showed a strong ability to resist cross-contamination. Comparative analysis of repeated testing of low-concentration HBV DNA samples and multi-system testing in plain areas revealed consistency rates of 77.78%(14/18) and 77.27%(17/22), respectively, indicating certain differences between the NAT system in Nagqu region and other systems. 【Conclusion】 The NAT system exhibited excellent performance in blood screening at high altitudes. The results of performance validation in high-altitude blood screening NAT systems were largely consistent with those in plain areas, providing a reliable basis for enhancing blood safety in high-altitude regions.
6.Enzalutamide and olaparib synergistically suppress castration-resistant prostate cancer progression by promoting apoptosis through inhibiting nonhomologous end joining pathway.
Hui-Yu DONG ; Pan ZANG ; Mei-Ling BAO ; Tian-Ren ZHOU ; Chen-Bo NI ; Lei DING ; Xu-Song ZHAO ; Jie LI ; Chao LIANG
Asian Journal of Andrology 2023;25(6):687-694
Recent studies revealed the relationship among homologous recombination repair (HRR), androgen receptor (AR), and poly(adenosine diphosphate-ribose) polymerase (PARP); however, the synergy between anti-androgen enzalutamide (ENZ) and PARP inhibitor olaparib (OLA) remains unclear. Here, we showed that the synergistic effect of ENZ and OLA significantly reduced proliferation and induced apoptosis in AR-positive prostate cancer cell lines. Next-generation sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the significant effects of ENZ plus OLA on nonhomologous end joining (NHEJ) and apoptosis pathways. ENZ combined with OLA synergistically inhibited the NHEJ pathway by repressing DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and X-ray repair cross complementing 4 (XRCC4). Moreover, our data showed that ENZ could enhance the response of prostate cancer cells to the combination therapy by reversing the anti-apoptotic effect of OLA through the downregulation of anti-apoptotic gene insulin-like growth factor 1 receptor ( IGF1R ) and the upregulation of pro-apoptotic gene death-associated protein kinase 1 ( DAPK1 ). Collectively, our results suggested that ENZ combined with OLA can promote prostate cancer cell apoptosis by multiple pathways other than inducing HRR defects, providing evidence for the combined use of ENZ and OLA in prostate cancer regardless of HRR gene mutation status.
Male
;
Humans
;
Prostatic Neoplasms, Castration-Resistant/genetics*
;
Drug Resistance, Neoplasm/genetics*
;
Cell Line, Tumor
;
Receptors, Androgen/genetics*
;
Nitriles
;
Apoptosis
7.FNDC1 is highly expressed in lung adenocarcinoma and closely related with poor prognosis.
Hai Ning HONG ; Hao Nan ZHU ; Chao LI ; Chao ZANG ; Hai Wei SANG ; Li Wei CHEN ; An Sheng WANG
Journal of Southern Medical University 2022;42(8):1182-1190
OBJECTIVE:
To explore the expression of fibronectin type Ⅲ domain containing 1(FNDC1) protein in lung adenocarcinoma and its prognostic significance.
METHODS:
The expression of FNDC1 in lung adenocarcinoma was predicted by analysis of data from GEO database and GEPIA, and the results were verified by immunohistochemical staining in 92 pairs of clinical specimens of lung adenocarcinoma and adjacent tissues.We further analyzed the correlation of FNDC1 expression with the clinicopathological features of the patients, and evaluated its prognostic value using Cox survival analysis.
RESULTS:
Analysis of the data form GEO database and GEPIA showed a significantly higher expression level of FNDC1 in lung adenocarcinoma than in matched normal tissues (P < 0.05).Kaplan-Meier survival analysis suggested that a high expression of FNDC1 protein was associated with a significantly shorter overall survival time of the patients (P < 0.05).Immunohistochemistry of the clinical specimens also showed a significantly higher protein expression of FNDC1 in lung adenocarcinoma tissues than in paired adjacent tissues (P < 0.001).A high expression of FNDC1 protein was significantly correlated with advanced clinical stage, T stage and N stage (P < 0.05).Cox univariate and multivariate regression survival analysis indicated that an increased expression of FNDC1 was an independent risk factor for poor prognosis of the patients with lung adenocarcinoma (P < 0.05).
CONCLUSION
FNDC1 protein is highly expressed in patients with lung adenocarcinoma and in closely related with the occurrence, progression and prognosis of the tumor, suggesting the value of FNDC1 protein as a potential biomarker for assessment of the survival and prognosis of patients with lung adenocarcinoma.
Adenocarcinoma of Lung/metabolism*
;
Humans
;
Kaplan-Meier Estimate
;
Lung Neoplasms/metabolism*
;
Neoplasm Proteins/genetics*
;
Prognosis
;
Proteins
8.Application value of triangular modal construed for planning approach of laparoscopic local resection of liver tumors located in superior part of central liver lobe
Ning FAN ; Yuan GUO ; Liqun WU ; Guofang LIU ; Qinghui NIU ; Chao LIU ; Yang XIN ; Zengqiang DAI ; Yanrong ZHAO ; Yan WANG ; Cong LI ; Yunjin ZANG ; Jinzhen CAI
Chinese Journal of Digestive Surgery 2021;20(8):906-912
Objective:To investigate the application value of triangular modal construed for planning approach of laparoscopic local resection of liver tumors located in superior part of central liver lobe.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 patients who underwent local laparoscopic resection of liver tumors located in superior part of central liver lobe at the Affiliated Hospital of Qingdao University from January to June 2020 were collected. There were 6 males and 4 females, aged from 41 to 63 years, with a median age of 54 years. Preoperative triangular model was constructed for all patients to plan approach of laparoscopic local resection of liver tumors located in superior part of central liver lobe. Observation indicators: (1) preoperative general situations of patients; (2) surgical situations; (3) follow-up. Follow-up was conducted by outpatient examination or telephone interview to detect tumor recurrence and survival of patients up to February 2021. Measurement data with normal distribution were expressed as Mean± SD. Count data were expressed was absolute numbers. Results:(1) Preoperative general situations of patients: hepatocellular carcinoma was found in 7 cases, inthahepatic cholangiocarcinoma was found in 2 cases and ovarian cancer with liver metastasis was found in 1 case. Three cases had tumors located in S4a segment, 2 cases had tumors located in ventral subsegment of S8 segment, 2 cases had tumors located in dorsal subsegment of S8 segment, and 3 cases had tumors across the ventral segment of S4a+S8. The diameter of tumors was (3.4±1.0)cm. (2) Surgical situation: all the 10 patients underwent R 0 resection successfully, with no intraoperative blood transfusion or conversion to open surgery. The operation time of 10 patients was (149±59)minutes, the volume of intraoperative blood loss was (294±163)mL, the minimum surgical margin of specimen was (1.1±0.2)cm. The alanine aminotransferase was (324±151)U/L on the postoperative first day, the aspartic aminotransferase was (401±113)U/L on the postoperative first day, and the duration of postoperative hospital stay was (9±4)days. No bile leakage, hemorr-hage, reoperation or other complications occurred in all patients. (3) Follow-up: 10 patients were followed up for 7?13 months, with a median follow-up time of 11 months. All patients had no margin recurrence or distant metastasis. Conclusion:It is safe and feasible to construct triangular modal for planning approach of local laparoscopic resection of liver tumors located in superior part of central liver lobe.
9.A preliminary pharmacophylogenetic study of Solanaceae medicinal plants containing tropane alkaloids.
Er-Huan ZANG ; Qin-Yu LI ; Jin-Fan XU ; Yi ZHANG ; Lin-Lin JIANG ; Xue LI ; Ming-Xu ZHANG ; Yu-Chao LIU ; Qing-Jiang WU ; Zhao-Hua LIU ; Min-Hui LI ; Pei-Gen XIAO
China Journal of Chinese Materia Medica 2021;46(17):4344-4359
The Solanaceae plants distributed in China belong to 105 species and 35 varietas of 24 genera. Some medicinal plants of Solanaceae are rich in tropane alkaloids(TAs), which have significant pharmacological activities. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, pharmacological activities, and biosynthetic pathways of TAs in Solanaceous plants were summarized. Besides, the phylogeny of medicinal plants belonging to Solanaceae was visualized by network diagram. Fourteen genera of Solanaceae plants in China contain TAs and have medical records. TAs mainly exist in Datura, Anisodus, Atropa, Physochlaina, and Hyoscyamus. The TAs-containing species were mainly concentrated in Southwest China, and the content of TAs was closely related to plant distribution area and altitude. The Solanaceae plants containing TAs mainly have antispasmodic, analgesic, antiasthmatic, and antitussive effects. Modern pharmacological studies have proved the central sedative, pupil dilating, glandular secretion-inhibiting, and anti-asthma activities of TAs. These pharmacological activities provide a reasonable explanation for the traditional therapeutic efficacy of tropane drugs. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, and modern pharmacological activities of TAs-containing species in Solanaceae were analyzed for the first time. Based on these data, the genetic relationship of TAs-containing Solanaceae species was preliminarily discussed, which provided a scientific basis for the basic research on TAs-containing solanaceous species and was of great significance for the development of natural medicinal plant resources containing TAs.
Biosynthetic Pathways
;
Phylogeny
;
Plants, Medicinal
;
Solanaceae/genetics*
;
Tropanes
10.Comparative analysis on the management of vaccine distribution in China and some other Asian countries
Zhao-yan ZANG ; Wei WANG ; Fei YAN ; Ke-zhong A ; Chao-wei FU
Shanghai Journal of Preventive Medicine 2021;33(3):243-
Objective To compare the framework of immunization programme and management of vaccine distributionin in China and some Asian countries, and further improve the immunization policy in China. Methods Using literature review, we compared the current status of immunization programme and vaccine distribution in China, Japan, Thailand, and Vietnam. Results Vaccine distribution has its own characteristics among Asian countries. Japan started early with a complete supervision system and compensation system. Thailand and Vietnam have also formed an efficient and complete cold chain transportation mode after implementing Expanded Programme on Immunization. Conclusion China can refer to the typical framework of immunization and experience of vaccine distributionfromsome Asian countries, which may improve vaccine accessand production links, standardize vaccine circulation market, and establish an efficient vaccine supervision and traceability system.


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