1.Structure-activity Omics on Anti-inflammatory and Analgesic Effect of Cyperi Rhizoma in Qizhi Weitong Granules
Ying ZHENG ; Sicong LIU ; Xi LUO ; Bing QI ; Shuai WANG ; Yongrui BAO ; Tianjiao LI ; Liang WANG ; Dong YAO ; Xiansheng MENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):153-160
ObjectiveTo elucidate the pharmacodynamic substances responsible for the anti-inflammatory and analgesic effects of Cyperi Rhizoma by structure-activity omics. MethodOn the basis of the previous in vitro efficacy study by our research group, this study explored the in vivo efficacy of the flavonoids in Cyperi Rhizoma. The flavonoids in Cyperi Rhizoma and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper, Swiss TargetPrediction, and available articles. The targets of the anti-inflammatory and analgesic effects were collected from DisGeNET and Online Mendelian Inheritance in Man (OMIM). The common targets shared by flavonoids and the effects were selected as the direct targets of flavonoids endowing Cyperi Rhizoma with anti-inflammatory and analgesic effects, and protein-protein interaction (PPI) network of the core targets was constructed. The method of structure-activity omics was employed to correlate the structure and efficacy of one or more classes of chemical components in Cyperi Rhizoma with the targets as a bridge. The components were classified according to structure. Molecular docking of components to core targets was carried out via SYBYL-X 2.1.1, PyMol, and Discovery Studio 4.5 visualizer. Two targets with the highest binding affinity were selected to explore the relationship between compound structures and targets. ResultThe flavonoids in Cyperi Rhizoma exerted anti-inflammatory and analgesic effects on the mouse model of pain induced by formaldehyde. Eighteen components and 115 direct targets were screened out, and the core targets with high activities were protein kinase B1 (Akt1), interleukin-1β (IL-1β), cellular tumor antigen p53 (TP53), prostaglandin-endoperoxide synthase 2 (PTGS2), and matrix metalloproteinase-9 (MMP-9). According to the structures, the flavonoids in Cyperi Rhizoma were classified into bioflavonoids, flavonols, flavones, and flavanes. The molecular docking results showed that flavonoids of Cyperi Rhizoma had the highest binding affinity to TP53 and PTGS2. The results of structure-activity omics showed that bioflavonoids represented the best binding structure to the targets, while their polyhydroxyl etherification resulted in a significant decrease in the binding affinity to PTGS2. Glycosides had higher binding affinity to PTGS2. The introduction of the long-chain hydrocarbon group to the A ring of flavonols facilitated the binding to TP53, while the change of B ring substituents was not the main factor affecting the binding affinity. The 3,4-dihydroxyl flavane outperformed 3-hydroxyl flavane in the binding to TP53, while the two compounds showed similar binding affinity to PTGS2. ConclusionThe method of structure-activity omics was used to analyze the material basis for the anti-inflammatory and analgesic effects of flavonoids in Cyperi Rhizoma. Structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.
2.Structure-activity Omics on Anti-inflammatory and Analgesic Effect of Paeoniae Radix Alba in Qizhi Weitong Granules
Bing QI ; Xi LUO ; Ying ZHENG ; Ying MENG ; Shuai WANG ; Yongrui BAO ; Tianjiao LI ; Ling HAN ; Xinying SHU ; Xiansheng MENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):169-175
ObjectiveTo elucidate the active compounds for the anti-inflammatory and analgesic effects of Paeoniae Radix Alba from structure-activity omics. MethodOn the basis of the previous in vitro efficacy study by our research group, a mouse model of foot swelling was induced by methyl aldehyde and used to study the anti-inflammatory and analgesic effects of total glycosides of Paeoniae Radix Alba in vivo. The core targets of the active compounds for the anti-inflammatory and analgesic effects of Paeoniae Radix Alba were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian Inheritance in Man (OMIM), and Search Tool for Recurring Instances of Neighbouring Genes (STRING). Molecular docking was conducted for the total glucosides of Paeoniae Radix Alba with the core targets, and the key core targets with high binding affinity were screened out according to the comprehensive score of each target and active structure. The structure-activity relationship was analyzed with targets as a bridge through the combination of compound structures and pharmacological effects. ResultThe total glucosides of Paeoniae Radix Alba had good anti-inflammatory and analgesic effects in vivo. The core targets of 23 active components of Paeoniae Radix Alba were epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), vascular endothelial growth factor A (VEGFA), cellular tumor antigen p53 (TP53), and proto-oncogene transcription factor (JUN). According to the structure of the parent nucleus, there were 16 pinane monoterpene glycosides, 4 pinene monoterpene glycosides, 2 monoterpene lactone glycosides, and 1 monoterpene ketone. The key core targets screened out by molecular docking were EGFR and STAT3. The structure-activity analysis of the active compound structures and the key core targets showed that the introduction of ketone group and benzene ring group on the parent nucleus affected the binding activity. ConclusionThis study analyzed the material basis for the anti-inflammatory and analgesic effects of total glycosides of Paeoniae Radix Alba from structure-activity omics, providing new ideas and methods for revealing the pharmacodynamic substances in traditional Chinese medicine.
3.Structure-activity Omics of Traditional Chinese Medicine: A Case Study of Anti-inflammatory and Analgesic Effect of Qizhi Weitong Granules
Xiansheng MENG ; Ying ZHENG ; Ying MENG ; Bing QI ; Sicong LIU ; Xi LUO ; Xinpeng QIN ; Yongrui BAO ; Shuai WANG ; Tianjiao LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):129-135
The complex chemical composition and limited research ideas of traditional Chinese medicine (TCM) have led to the unclear material basis and mechanism of the medicinal effects, which is a common problem hindering the modernization of TCM in China. The introduction of computer virtual technology has provided a new perspective for TCM research. In this study, we established the research method of structure-activity omics to study the relationships between the structures and effects of different compounds in TCM based on the chemical structures of TCM components and to analyze and predict the material basis and multitarget synergistic mechanism of TCM. Furthermore, a structure-activity omics study was carried out with the anti-inflammatory and analgesic effects of Qizhi Weitong granules as an example. This study provides support for screening the pharmacodynamic components and analyzing the active ingredients of TCM and gives insights into the research on the material basis and mechanism of compound efficacy and the development of lead compounds of TCM, thus promoting the modern research and the innovative development of TCM.
4.Structure-activity Omics on Anti-inflammatory and Analgesic Effect of Bupleuri Radix in Qizhi Weitong Granules
Xi LUO ; Bing QI ; Ying MENG ; Xinpeng QIN ; Yongrui BAO ; Tianjiao LI ; Liang WANG ; Shuai WANG ; Xiansheng MENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):146-153
ObjectiveTo identify the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Bupleuri Radix by structure-activity omics. MethodA mouse model of pain was established with formaldehyde to examine the anti-inflammatory and analgesic effects of saikosaponins in vivo. The core targets of the active components in Bupleurum Radix for the anti-inflammatory and analgesic effects were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian Inheritance in Man (OMIM), and Search Tool for Recurring Instances of Neighbouring Genes (STRING). The key core targets with high binding affinity were screened based on the comprehensive score in the molecular docking between different types of saikosaponins and core targets. The structure-activity relationship was discussed and analyzed based on the binding of compounds to pharmacodynamic targets. ResultSaikosaponins alleviated the foot swelling induced by formaldehyde and reduced the content of prostaglandin E2 (PGE2) in the mouse model, showcasing a significant inhibitory effect on the inflammatory pain caused by PGE2. Nine components and 39 targets of saikosaponins, as well as 3 074 targets of anti-inflammatory and analgesic effects were screened out, and 22 common targets shared by saikosaponins and the effects were obtained as the direct targets. The protein-protein interaction (PPI) analysis showed that the main active components of Bupleurum Radix were saikosaponins a, b1, b2, b3, c, d, e, f, and v, and the key targets were fms-related receptor tyrosine kinase 1 (FLT1), kinase insert domain receptor (KDR), fibroblast growth factor 2 (FGF2), vascular endothelial growth factor A (VEGFA), and signal transducer and activator of transcription 3 (STAT3). Molecular docking between saikosaponins and the top 5 targets with high degrees in PPI network analysis revealed 25 highly active docks, including 6 docks with scores of 5-6 and 18 docks with scores above 6. ConclusionThis study adopted structural-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Bupleuri Radix in vivo, providing new ideas and methods for identifying the pharmacodynamic substances in traditional Chinese medicine.
5.Structure-activity Omics on Anti-inflammatory and Analgesic Effect of Aurantii Fructus in Qizhi Weitong Granules
Sicong LIU ; Xinpeng QIN ; Bing QI ; Xi LUO ; Tianjiao LI ; Yongrui BAO ; Shuai WANG ; Ling HAN ; Xiansheng MENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):154-161
ObjectiveTo explain the pharmacodynamic substances of Aurantii Fructus flavonoids that exert anti-inflammatory and analgesic effects using a structure-activity omics approach. MethodOn the basis of the previous in vitro pharmacological screening conducted by the research team, an in vivo pharmacological study of Aurantii Fructus flavonoids was carried out. Core targets of the anti-inflammatory and analgesic active components of flavonoids of Aurantii Fructus were identified using various network databases, including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the Online Mendelian Inheritance in Man (OMIM), and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Computer-aided virtual screening technology was used to dock different types of Aurantii Fructus flavonoids with core targets. The key core targets with high binding activity were selected based on the comprehensive scores of each target and the active structures. Using these targets as bridges, the structures of one or more types of chemical components in Aurantii Fructus were closely linked to pharmacological effects. The structure-activity relationship between the clear pharmacodynamic compounds and their effects was explored through the binding patterns of various structures with pharmacodynamic targets. ResultAurantii Fructus flavonoids demonstrated significant anti-inflammatory and analgesic effects on dextran sulfate sodium (DSS)-induced colitis in mice, which could improve symptoms and significantly reduce the levels of inflammatory factors interleukin-6 (IL-6) and interleukin-1β (IL-1β)(P<0.05). Twelve active components of Aurantii Fructus flavonoids were identified and categorized into nine dihydroflavonoids and three flavonoids based on their structures of the parent nuclei. Through Venn analysis, 167 anti-inflammatory and analgesic targets for Aurantii Fructus were identified. Based on degree value and molecular docking comprehensive scores, prostaglandin-endoperoxide synthase 2(PTGS2) and mitogen-activated protein kinase 3(MAPK3) were selected for further structural analysis. Structural analysis revealed that components containing glycoside structures exhibited higher binding activity with anti-inflammatory and analgesic targets. ConclusionThis study utilized a structure-activity omics approach based on in vivo pharmacodynamic experiments to analyze the material basis of the anti-inflammatory and analgesic effects of Aurantii Fructus flavonoids. The structure-activity omics approach provides new ideas and methods for elucidating the pharmacodynamic substances of Chinese medicine.
6.Research progress in biomimetic nano formulations of biofilms
Qiang ZHANG ; Xi LUO ; Yongrui BAO ; Shuai WANG ; Tianjiao LI ; Xiansheng MENG
Journal of China Pharmaceutical University 2023;54(5):544-552
Biomimetic nano formulations of biofilms have low immunogenicity, high targeting, and good biocompatibility, and can avoid being cleared by the endothelial reticular system, thus with in longer blood circulation time in the body.This article mainly reviews the main types as well as advantages and disadvantages of biomimetic nano formulations of biofilms, including tumor cell membranes, red blood cell membranes, platelet membranes, white blood cell membranes, stem cell membranes, extracellular vesicles (exosomes, microvesicles, and apoptotic bodies), endoplasmic reticulum membranes, and composite biofilms, with also a prospect of the challenges facing biomimetic nano formulations of biofilms and their future development based on their current research status, aiming to provide some insight for further research on biomimetic nano formulations of biofilms.
7.Efficacy of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei
Ziying LEI ; Binghui DING ; Qiyue WU ; Jiali LUO ; Zheng LI ; Tian WANG ; Yingsi WANG ; Yangxiao CHEN ; Lifeng HUANG ; Jinfu HE ; Xiansheng YANG ; Tianpei GUAN ; Qiang RUAN ; Jiahong WANG ; Hongsheng TANG ; Jin WANG ; Shuzhong CUI
Chinese Journal of Gastrointestinal Surgery 2023;26(12):1179-1186
Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.
8.Efficacy of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei
Ziying LEI ; Binghui DING ; Qiyue WU ; Jiali LUO ; Zheng LI ; Tian WANG ; Yingsi WANG ; Yangxiao CHEN ; Lifeng HUANG ; Jinfu HE ; Xiansheng YANG ; Tianpei GUAN ; Qiang RUAN ; Jiahong WANG ; Hongsheng TANG ; Jin WANG ; Shuzhong CUI
Chinese Journal of Gastrointestinal Surgery 2023;26(12):1179-1186
Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.
9.Ultrasound evaluation in recombinant human bonemorphogenic protein-2 ( rhBMP-2 ) artificial bone angiogenesis
Yin LING ; Shasha WANG ; Zepeng CHEN ; Yuanjun XIA ; Xiansheng ZHU ; Guoxin LUO ; Jun′er FAN
Chinese Journal of Ultrasonography 2017;26(12):1092-1096
Objective To evaluate the application value of ultrasound in vascularization of different artificial bones . Methods A total of 15 New Zealand rabbits were utilized for model establishment of classic segmental bone defect in bilateral radius . Recombinant human bonemorphogenic protein-2 ( rhBMP-2 ) coralline hydroxyapatite(CHA) and CHA were implanted into left and right limbs . Each CHA was divided into 4 equal parts which were examined with conventional ultrasonography and contrast-enhanced ultrasonography( CEUS ) on 3 d ,7 d ,11 d ,15 d ,30 d and 45 d respectively . CEUS quantitative was performed by time-intensity curve(TIC) ,which parameters including the basic intensity(BI) ,peak intensity (PI) ,increased signal intensity ( ΔSI) and time to peak ( TTP) . Then the results were analyzed and compared to pathology . Results Within the same duration ,the vascularization degree in rhBMP-2 group was stronger than that in the ordinary group with advanced vascularization time . Positive correlation was detected between ΔSI and time of both groups ( r =0 .938 ,0 .890 ;P =0 .000) ,and negative correlation was found between BI/PI or TTP and time ( BI/PI: r = -0 .798 ,-0 .899 ; P = 0 .000 ;TTP= r -0 .874 ,-0 .868 ;P = 0 .000 ) . No statistical significance was observed among four observation points of both CHA ,which indicated no obvious difference in vascularization degree of each observation point . Conclusions The structure of bone graft can be clearly displayed by conventional ultrasound ,and CEUS is able to show the early blood perfusion in two CHA grafts and to accurately evaluate the difference of CHA microvascular growth before and after rhBMP-2 application . The combination of these two techniques is a promising approach of evaluating bone graft vascularization in clinical practice .
10.Surfactant Protein A Polymorphism Is Associated with Susceptibility to Chronic Obstructive Pulmonary Disease in Chinese Uighur Population
GUAN JIAN ; LIU XIANSHENG ; XIE JUNGANG ; XU XILIN ; LUO SHUXIN ; WANG RAN ; XU YONGJIAN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(2):186-189
This study investigated the correlation between surfactant protein-A (SP-A) polymorphism and the susceptibility of chronic obstructive pulmonary disease (COPD) in Xinjiang Uighurs.Genomic DNA was extracted from peripheral blood of 194 COPD smokers and 201 healthy smokers of Uighur who were hospitalized in or paid a visit to one of the four Xinjiang-based hospitals involved in the study,from March 2009 to December 2010.Single nucleotide polymorphisms (SNPs) were studied at aa62 (CCA/CCG rs 1136451) and aa219 (CGG/rGG,rs4253527) in SP-A.Genotypes were determined by using the TaqMan polymerase chain reaction (PCR).Our results showed that genotype frequencies were different between the COPD and normal smokers in aa62 (x2=6.852,P=0.033).There were also significant differences in allele genotype frequencies between the COPD and the control and allele G might decrease the risk COPD (x2=6.545,P=0.011; OR=0.663; 95% CI:0.484-0.909).The result suggested that polymorphism of aa62 (CCA/CCG,rs1136451) of SP-A may be associated with the susceptibility to COPD in Xinjiang Uighurs.

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