1.Clinical efficacy of split liver transplantation in the treatment of children with biliary atresia.
Bin Sheng FU ; Shu Hong YI ; Hui Min YI ; Xiao FENG ; Tong ZHANG ; Qing YANG ; Ying Cai ZHANG ; Jia YAO ; Hui TANG ; Kai Ning ZENG ; Xiao Bin LI ; Zhou YANG ; Lei LYU ; Gui Hua CHEN ; Yang YANG
Chinese Journal of Surgery 2022;60(10):900-905
		                        		
		                        			
		                        			Objective: To compare the clinical efficacy of split liver transplantation (SLT) and living donor liver transplantation(LDLT) in the treatment of children with biliary atresia. Methods: The clinical data of 64 children with biliary atresia who underwent SLT and 44 children who underwent LDLT from June 2017 to May 2022 at Liver Surgery & Liver Transplantation Center,the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. Among the children who received SLT, there were 40 males and 24 females. The median age at transplantation was 8 months (range:4 to 168 months). Among the patients who received LDLT, there were 24 males and 20 females. The age at transplantation ranged from 4 to 24 months,with a median age of 7 months. Sixty-four children with biliary atresia were divided into two groups according to the SLT operation time: 32 cases in the early SLT group(June 2017 to January 2019) and 32 cases in the technically mature SLT group (February 2019 to May 2022). Rank sum test or t test was used to compare the recovery of liver function between the LDLT group and the SLT group,and between the early SLT group and the technically mature SLT group. The incidence of postoperative complications was compared by χ2 test or Fisher exact probability method. Kaplan-Meier method and Log-rank test were used for survival analysis. Results: The cold ischemia time(M (IQR)) (218 (65) minutes), intraoperative blood loss(175 (100) ml) and graft-to-recipient body weight ratio (3.0±0.7) in the LDLT group were lower than those in the SLT group(500 (130) minutes, 200 (250) ml, 3.4±0.8) (Z=-8.064,Z=-2.969, t=-2.048, all P<0.05). The cold ischemia time(457(158)minutes) and total hospital stay ((37.4±22.4)days) in the technically mature SLT group were lower than those in the early SLT group(510(60)minutes, (53.0±39.0)days).The differences were statistically significant (Z=-2.132, t=1.934, both P<0.05).The liver function indexes of LDLT group and SLT group showed unimodal changes within 1 week after operation. The peak values of ALT, AST, prothrombin time, activeated partial thromboplasting time, international normalized ratio, fibrinogen and creatinine all appeared at 1 day after operation, and the peak value of prothrombin activity appeared at 3 days after operation. All indicators returned to normal at 7 days after operation. The 1-,2-,and 3-year overall survival rates were 95.5% in LDLT group and 93.5% in the technically mature SLT group, and the difference was not statistically significant. The 1-,2-,and 3-year overall survival rates were 90.2% in the early SLT group and 93.5% in the technically mature SLT group, and there was no significant difference between the two groups(P>0.05). The main complications of the early SLT group were surgery-related complications(28.1%,9/32), and the main complications of the technically mature SLT group were non-surgery-related complications(21.9%,7/32). There were 5 deaths in the SLT group,including 4 in the early SLT group and 1 in the technically mature SLT group. Conclusion: The survival rate of SLT in the treatment of biliary atresia is comparable to that of LDLT.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Biliary Atresia/surgery*
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Child, Preschool
		                        			;
		                        		
		                        			Creatinine
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Fibrinogen
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Infant
		                        			;
		                        		
		                        			Liver Transplantation/methods*
		                        			;
		                        		
		                        			Living Donors
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Postoperative Complications/epidemiology*
		                        			;
		                        		
		                        			Prothrombin
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
2.Efficacy and safety of neoadjuvant toripalimab combined with nimotuzumab and chemotherapy in patients with unresectable stage Ⅳ squamous cell carcinoma of penis.
Ru YAN ; Sheng Jie GUO ; Xin AN ; Li Juan JIANG ; Ting Yu LIU ; Ting XUE ; Hua Li MA ; Kai YAO ; Yan Xia SHI ; Hui HAN
Chinese Journal of Surgery 2022;60(12):1093-1099
		                        		
		                        			
		                        			Objective: To compare the efficacy and safety of neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab in patients with unresectable locally advanced or metastatic squamous cell carcinoma of penis. Methods: A total of 33 patients with unresectable squamous cell carcinoma of penis undergoing neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab at Sun Yat-sen University Cancer Center from May 2015 to June 2021 were enrolled retrospectively. All the patients were male, with a median age (M(IQR))of 49.0 (13.5) years (range: 30 to 70 years). According to the therapy protocols, patients were divided into the chemotherapy group (16 cases) and the triple combination group (17 cases). Log-rank test was used to compare the progression-free survival and overall survival. χ2 test or Fisher exact method was used to compare the objective response rate, pathological down-stage rate and adverse events between these two groups. Results: The follow-up time was 28.1(19.2) months (range: 1.5 to 33.4 months). Patients of triple combination group were observed significantly longer progression-free survival (30.0 months vs. 8.2 months, χ²=3.998, P=0.046) than those of chemotherapy group. The median overall survival of the triple combination group and chemotherapy group were not reached and 15.2 months (χ²=3.298, P=0.069), respectively. Although there was no significant difference in the subsequent surgical resection rate between these two groups (12/17 vs.11/16, P=1), the objective response rate and the pathological complete response rate in triple combination group were significantly higher than in chemotherapy group (13/17 vs. 6/16, χ²=5.125, P=0.024; 6/7 vs. 0, P=0.001). The main common grade 1 to 2 adverse events in the triple combination group were alopecia (16 cases), anemia (15 cases), and nausea (14 cases). The main common grade 1 to 2 adverse events in the chemotherapy group were anemia (14 cases), alopecia (12 cases), decreased appetite (12 cases), and nausea (11 cases). The incidence of adverse events ≥grade 3 was similar in the triple combination group and chemotherapy group (8/17 vs. 6/16, χ²=0.308, P=0.579). There was no grade 3 adverse event in both groups. Conclusion: Compared with traditional chemotherapy alone, chemotherapy combined with toripalimab and nimotuzumab provides longer progression-free survival and similar toxicity for unresectable stage Ⅳ squamous cell carcinoma of penis.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Neoadjuvant Therapy
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Carcinoma, Squamous Cell/drug therapy*
		                        			;
		                        		
		                        			Alopecia
		                        			;
		                        		
		                        			Anemia
		                        			
		                        		
		                        	
3.Questionnaire investigation of radiation rectal injury with anxiety, depression and somatic disorder.
Bo LIAN ; Xin Ping CAO ; Hai Jun DENG ; Jun JIANG ; Ke Wei JIANG ; Xin Xiang LI ; You Sheng LI ; Guo Le LIN ; Ji Hong LIU ; Shou Min BAI ; Feng WANG ; Zi Qiang WANG ; Ai Wen WU ; Yi XIAO ; Hong Wei YAO ; Wei Tang YUAN ; Wei ZHANG ; Zhen ZHANG ; Yan Bing ZHOU ; Teng Hui MA ; Qing Chuan ZHAO
Chinese Journal of Gastrointestinal Surgery 2021;24(11):984-990
		                        		
		                        			
		                        			Objective: To observe the incidence and treatment of radiation rectal injury complicated with anxiety, depression and somatic symptom disorder. Methods: A cross-sectional survey research method was carried out. Patients with radiation rectal injury managed by members of the editorial board of Chinese Journal of Gastrointestinal Surgery were the subjects of investigation. The inclusion criteria of the survey subjects: (1) patients suffered from pelvic tumors and received pelvic radiotherapy; (2) colonoscopy showed inflammatory reaction or ulcer in the rectum. Exclusion criteria: (1) patient had a history of psycho-somatic disease before radiotherapy; (2) patient was unable to use a smart phone, unable to read and understand the questions in the questionnaire displayed on the phone; (3) patient refused to sign an informed consent form. According to the SOMA self-rating scale, PHQ-15 self-rating scale, GAD-7 and PHQ-9 self-rating scale, the electronic questionnaire of "Psychological Survey of Radiation Proctitis" was designed. The questionnaire was sent to patients with radiation rectal injury managed by the committee through the WeChat group. Observational indicators: (1) radiation rectal injury symptom assessment: using SOMA self-rating scale, radiation rectal injury symptom classification: mild group (≤3 points), moderate group (4-6 points) and severe group (> 6 points); (2) incidence of anxiety, depression and physical disorder: using GAD-7, PHQ-9 and PHQ-15 self-rating scales respectively for assessment; (3) correlation of radiation rectal injury symptom grading with anxiety, depression, and somatic symptom disorder. Results: Seventy-one qualified questionnaires were collected, of which 41 (56.9%) were from Guangzhou. Among the 71 patients, 6 were males and 65 were females; the mean age was (55.7±9.3) years old and 48 patients (67.6%) were less than 60 years old; the median confirmed duration of radiation rectal injury was 2.0 (1.0, 5.0) years. (1) Evaluation of symptoms of radiation rectal injury: 18 cases of mild (25.4%), 27 cases of moderate (38.0%), and 26 cases of severe (36.6%). (2) Incidence of anxiety, depression and somatic disorder: 12 patients (16.9%) without comorbidities; 59 patients (83.1%) with anxiety, depression, or somatic disorder, of whom 2 patients only had anxiety, 1 patient only had depression, 9 only had somatic disorder, 2 had anxiety plus depression, 4 had anxiety plus somatic disorder, 2 had depression plus somatic disorder, and 40 had all three symptoms. (3) correlation of radiation rectal injury grading with anxiety, depression, and somatic symptom disorder: as compared to patients in mild group and moderate group, those in severe group had higher severity of anxiety and somatic symptom disorder (Z=-2.143, P=0.032; Z=-2.045, P=0.041), while there was no statistically significant difference of depression between mild group and moderate group (Z=-1.176, P=0.240). Pearson correlation analysis revealed that radiation rectal injury symptom score was positively correlated with anxiety (r=0.300, P=0.013), depression (r=0.287, P=0.015) and somatic symptom disorder (r=0.344, P=0.003). Conclusions: The incidence of anxiety, depression, and somatic symptom disorder in patients with radiation rectal injury is extremely high. It is necessary to strengthen the diagnosis and treatment of somatic symptom disorder, so as to alleviate the symptoms of patients with pelvic perineum pain and improve the quality of life.
		                        		
		                        		
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Anxiety
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			Depression
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Quality of Life
		                        			;
		                        		
		                        			Rectum
		                        			;
		                        		
		                        			Surveys and Questionnaires
		                        			
		                        		
		                        	
4.Anatomical characteristics of patients with symptomatic severe aortic stenosis in China.
Tian-Yuan XIONG ; Yi-Ming LI ; Yi-Jun YAO ; Yu-Heng JIA ; Kai XU ; Zhen-Fei FANG ; Jun JIN ; Guo-Sheng FU ; Yi-Ning YANG ; Lei JIANG ; Wei-Dong LI ; Yan-Qing WU ; Yan-Song GUO ; Ran GUO ; Yun-Dai CHEN ; Yi LI ; Yi-Bing SHAO ; Yi ZHANG ; Bo-Sen YANG ; Yi-Ke ZHANG ; Jing-Jing HE ; Kai-Yu JIA ; Sheng-Hu HE ; Fa-Xin REN ; Jian-Cheng XIU ; Xing-Hua GU ; Liang-Long CHEN ; Ke HAN ; Yuan FENG ; Mao CHEN
Chinese Medical Journal 2021;134(22):2738-2740
5.Development and Validation of Web-Based Nomograms to Precisely Predict Survival Outcomes of Non-metastatic Nasopharyngeal Carcinoma in an Endemic Area
Ji-Jin YAO ; Li LIN ; Tian-Sheng GAO ; Wang-Jian ZHANG ; Wayne R. LAWRENCE ; Jun MA ; Ying SUN
Cancer Research and Treatment 2021;53(3):657-670
		                        		
		                        			Purpose:
		                        			This study aimed to develop web-based nomograms to precisely predict survival outcomes in patients with non-metastatic nasopharyngeal carcinoma (NPC) in an endemic area. 
		                        		
		                        			Materials and Methods:
		                        			A total of 10,126 patients who underwent radical intensity-modulated radiotherapy at Sun Yat-sen University Cancer Center (SYSUCC) from 2009 to 2015 were analyzed. We assigned patients into a training cohort (SYSUCC-A, n=6,751) and an internal validation cohort (SYSUCC-B, n=3,375) based on computer-generated random numbers. Patients collected from Wuzhou Red Cross Hospital (WZRCH) between 2012 and 2015 were used as the independent external validation cohort (WZRCH, n=450). Concordance index (C-index) was used to determine predictive accuracy and discriminative ability for the nomogram. The web-based clinicopathologic prediction models for predicting survival were based on Cox regression. 
		                        		
		                        			Results:
		                        			The C-indexes for SYSUCC-A, SYSUCC-B, and WZRCH cohorts for the established nomograms to predict 3-year overall survival (OS) was 0.736, 0.715, and 0.691. Additionally, C-indexes to predict 3-year distant metastasis-free survival (DMFS) was 0.717, 0.706, and 0.686, disease-free survival (DFS) was 0.713, 0.697, and 0.656, local relapse-free survival was 0.695, 0.684, and 0.652, and regional relapse-free survival was 0.672, 0.650, and 0.616. The calibration plots showed great agreement between nomogram-predicted 3-year survival outcomes and actual 3-year survival outcomes. Moreover, C-indexes of the nomograms for OS, DMFS, and DFS were significantly superior than TNM stage (p< 0.001 for all). 
		                        		
		                        			Conclusion
		                        			These user-friendly nomograms can precisely predict survival endpoints in patients with non-metastatic NPC. They may serve as a useful tool for providing patient counseling and help physicians to make individual follow-up plans.
		                        		
		                        		
		                        		
		                        	
6.Development and Validation of Web-Based Nomograms to Precisely Predict Survival Outcomes of Non-metastatic Nasopharyngeal Carcinoma in an Endemic Area
Ji-Jin YAO ; Li LIN ; Tian-Sheng GAO ; Wang-Jian ZHANG ; Wayne R. LAWRENCE ; Jun MA ; Ying SUN
Cancer Research and Treatment 2021;53(3):657-670
		                        		
		                        			Purpose:
		                        			This study aimed to develop web-based nomograms to precisely predict survival outcomes in patients with non-metastatic nasopharyngeal carcinoma (NPC) in an endemic area. 
		                        		
		                        			Materials and Methods:
		                        			A total of 10,126 patients who underwent radical intensity-modulated radiotherapy at Sun Yat-sen University Cancer Center (SYSUCC) from 2009 to 2015 were analyzed. We assigned patients into a training cohort (SYSUCC-A, n=6,751) and an internal validation cohort (SYSUCC-B, n=3,375) based on computer-generated random numbers. Patients collected from Wuzhou Red Cross Hospital (WZRCH) between 2012 and 2015 were used as the independent external validation cohort (WZRCH, n=450). Concordance index (C-index) was used to determine predictive accuracy and discriminative ability for the nomogram. The web-based clinicopathologic prediction models for predicting survival were based on Cox regression. 
		                        		
		                        			Results:
		                        			The C-indexes for SYSUCC-A, SYSUCC-B, and WZRCH cohorts for the established nomograms to predict 3-year overall survival (OS) was 0.736, 0.715, and 0.691. Additionally, C-indexes to predict 3-year distant metastasis-free survival (DMFS) was 0.717, 0.706, and 0.686, disease-free survival (DFS) was 0.713, 0.697, and 0.656, local relapse-free survival was 0.695, 0.684, and 0.652, and regional relapse-free survival was 0.672, 0.650, and 0.616. The calibration plots showed great agreement between nomogram-predicted 3-year survival outcomes and actual 3-year survival outcomes. Moreover, C-indexes of the nomograms for OS, DMFS, and DFS were significantly superior than TNM stage (p< 0.001 for all). 
		                        		
		                        			Conclusion
		                        			These user-friendly nomograms can precisely predict survival endpoints in patients with non-metastatic NPC. They may serve as a useful tool for providing patient counseling and help physicians to make individual follow-up plans.
		                        		
		                        		
		                        		
		                        	
7.INI1 Induces Adipocytic Differentiation of Epithelioid Sarcoma Cells
Xian-biao XIE ; Li-li WEN ; Dong-ming LV ; Yu-tong ZOU ; Hao YAO ; Ting-sheng PENG
Journal of Sun Yat-sen University(Medical Sciences) 2020;41(5):690-696
		                        		
		                        			
		                        			【Objective】 To study the function and mechanism of INI1 in human epithelioid sarcoma cells. 【Methods】 Western blotting was used to test the expressionlevel of INI1in epithelioid sarcoma cells. The expression of INI1 in clinical specimens of epithelioid sarcoma was detected by immunohistochemistry. Tet-on system was used to establish the expression of INI1 in epithelioid sarcoma cells. Following the induction of INI1 expression, the cell morphology, proliferation and the molecular markers of adipocytic differentiation were detected. Then western blot was employed to detect the transcription factors of adipocytic differentiation, and oil red O staining was also tested. 【Results】 The expression of INI1 was absent in both epithelioid sarcoma cells and clinical tissues(P<0.05). The INI1 expression in the epithelioid sarcoma cells was successfully established by Tet-on system. After induction by doxycycline, the expression of INI1 was up-regulated. With continuous expression of INI1, the morphology of VA-ES-BJ cells was changed, with the appearance of abundant vacuoles in the cytoplasm. The cell proliferation was obviously inhibited(P<0.05). Epithelial cell marker Cytokeratin was found significantly reduced(P<0.05). In addition, the adipocyte markers, leptin, adiponectin and lipoprotein lipase were significantly up-regulated(P<0.05). The adipogenic transcriptional factors PPAR-γ and CEBP-α were found upregulated(P<0.05) and the oil red staining was significantly positive. 【Conclusions】 The expression of INI1 was absent in epithelioid sarcoma. Reconstruction of the expression of INI1 could induce adipocytic differentiation via upregulation of transcriptional factors PPAR-γand CEBP-αin epithelioid sarcoma cells.
		                        		
		                        		
		                        		
		                        	
8. Effectiveness of glucocorticoid therapy in patients with severe novel coronavirus pneumonia: protocol of a randomized controlled trial
Yi-Hong ZHOU ; Yuan-Yuan QIN ; Yan-Qiu LU ; Feng SUN ; Sen YANG ; Vijay HARYPURSAT ; Sheng-Quan TANG ; Yin-Qiu HUANG ; Xiao-Qing HE ; Yan-Ming ZENG ; Yao LI ; Xiao-Lei XU ; Ting ZHAO ; Yao-Kai CHEN
Chinese Medical Journal 2020;133(0):E020-E020
		                        		
		                        			 Background:
		                        			At the end of 2019, a novel coronavirus outbreak emerged in Wuhan, China, and its causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The virus has since rapidly spread to all provinces and autonomous regions of China, and to countries outside of China. Patients who become infected with 2019-nCoV may initially develop mild upper respiratory tract symptoms. However, a significant fraction of these patients goes on to subsequently develop serious lower respiratory disease. The effectiveness of adjunctive glucocorticoid therapy uses in the management of 2019-nCoV infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation.
		                        		
		                        			Methods:
		                        			The present study will be conducted as an open-labelled, randomised controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at 4 consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks.
		                        		
		                        			Discussion:
		                        			The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in severe coronavirus disease 2019 (COVID-19) patients.
		                        		
		                        			Trial registration
		                        			ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777. 
		                        		
		                        		
		                        		
		                        	
9.BAX Gene Deletion Reduces the Sensitivity of BCR-ABL-Induced B-ALL Cells of Mice to Imatinib.
Liang SHI ; Yuan-Yuan LONG ; Xi LUO ; Qiong SU ; Pei HUANG ; Sheng-Sen YAO ; Yan CHEN
Journal of Experimental Hematology 2019;27(6):1749-1753
		                        		
		                        			OBJECTIVE:
		                        			To investigate the effect of BAX gene deletion on the sensitivity of BCR-ABL-induced B-ALL cells of mice to imatinib and the related mechanism.
		                        		
		                        			METHODS:
		                        			The target gene-knock out (BAX) mice were used as bone marrow cell donors; the wild type bone marrow cells(B6BM) and BAX bone marrow cells(B6BM-BAX) of mice were transfected by using reverse transcription virus, then the BCR-ABL transfected B6BM cells and B6BM-BAX cells were treated with imatinib at different concentration (0,0.5, 1.0 and 2.0 μmol/L) for 48 hours. The number of viable cells was detected by trypan blue, the flow cytometry was used to detect the cell apoptosis, the Western blot was used to detect the changes of BAX, Caspase expression.
		                        		
		                        			RESULTS:
		                        			In BCR-ABL transfected bone marrow cells treated with imatinib, the numbers of viable cells of BAX deletion group was significantly higher than that of wild type groups with statristcal difference(P<0.05), and effect- and dose-dependency(r=-0.9533 for BAX deletion group, and r=-0.9812 for wild type group). The flow cytometry showed that the cell apoptosis in BAX deletion group signifincantly decreased, compared with wild type group(P<0.05). The Western blot showed that the expression of apoptotic protein Caspase 3 in BAX deletion group was significantly higher than that in wild type group(P<0.05).
		                        		
		                        			CONCLUSION
		                        			BAX deletion can reduce the sensitivity of BCR-ABL-induced B-ALL cells to imatinib.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Apoptosis
		                        			;
		                        		
		                        			Drug Resistance, Neoplasm
		                        			;
		                        		
		                        			Fusion Proteins, bcr-abl
		                        			;
		                        		
		                        			Gene Deletion
		                        			;
		                        		
		                        			Imatinib Mesylate
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Piperazines
		                        			;
		                        		
		                        			Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			bcl-2-Associated X Protein
		                        			
		                        		
		                        	
10.Pyridocarbazole alkaloids from Ochrosia borbonica: lipid-lowering agents inhibit the cell proliferation and adipogenesis of 3T3-L1 adipocyte via intercalating into supercoiled DNA.
Yao-Hao XU ; Wei LI ; Yong RAO ; Zhi-Shu HUANG ; Sheng YIN
Chinese Journal of Natural Medicines (English Ed.) 2019;17(9):663-671
		                        		
		                        			
		                        			Bioassay-guided fractionation of an ethanolic extract of Ochrosia borbonica led to the isolation of two known pyridocarbazole alkaloids, ellipticine (1) and 9-methoxyellipticine (2), and six known monoterpenoid indole alkaloids (3-8). Lipid-lowering assay in 3T3-L1 cell model revealed that 1 and 2 could significantly inhibit the lipid droplet formation (EC = 0.41 and 0.92 μmol·L, respectively) and lower triglyceride levels by 50%-60% at the concentration of 1 μmol·L, being more potent than the positive drug luteolin (EC = 2.63 μmol·L). A mechanistic study indicated that 1 and 2 could intercalate into supercoiled DNA, which consequently inhibited the mitotic clonal expansion of 3T3-L1 cells at the early differentiation phase, leading to the retardance of following adipogenesis and lipogenesis. These findings suggest that 1 and 2 may serve as promising leads for further development of anti-obesity drugs.
		                        		
		                        		
		                        		
		                        	
            
Result Analysis
Print
Save
E-mail