1.Screening for selective TGF-βⅠinhibitors and structure-activity relationship analysis
Long LONG ; Feifei LI ; Xingzhou LI ; Wei CHEN ; Wei LI ; Lili WANG
Journal of International Pharmaceutical Research 2017;44(6):544-550
Objective To screen for selective transforming growth factor β(TGF-β)inhibitors from the compound library, and analyze their structure-activity relationship. Methods The inhibiting activities of 170 compounds to TGF-βpathway were evaluat-ed by the SMAD3 luciferase reporter system;the positive hits were examined for their selectivity towards activin receptor like kinase (ALK)4、ALK5 or ALK7 by a molecule based screening system composed of SMAD3,ATP and the purified kinase domain for ALK4, ALK5 or ALK7;the EGFP-SMAD2 fusion protein redistribution assay was used to confirm the inhibiting effects of positive hits. The structure-activity relationship was analyzed by comparing the docking module of SB431542 with ALK5 kinase domain. Results Fif-teen compounds were found capable of inhibiting luciferase expression downstream of SMAD3 with≥25%inhibitory rate;several of them showed different selectivity towards ALK4,ALK5 and ALK7. Compound 63 selectively inhibited the activity of ALK4 and ALK7 with IC500.234 and 0.370μmol/L,respectively,while compound 64 showed inhibiting activity towards all three kinases with the IC50 values 10,6 and 85 nmol/L for ALK4、ALK5 and ALK7,respectively. In addition,compounds 63 and 64 further inhibited the TGF-β1 induced EGFP-SMAD2 nuclear translocation,with the IC50 values of 0.45 and 6.30μmol/L,respectively. The MTT anti-proliferative assay indicated that compounds 63 and 64 exerted these activities at non-toxic concentrations. The analysis of structure-activity rela-tionship indicated that the compounds sharing a core structure,the 1,2,4-triarylimizazole or 1,3,5-triarylpyrazoline,with the 3,4 methyoenedioxyphenyl,6-methylpyridine and 4-aminocarboxyl substitution groups tended to exhibit better activities. Conclusion The two potent TGF-βpathway inhibitors,63 and 64 are identified through this screening project,of which,63 selectively inhibited the ALK4 and ALK7 activity,while 64 showed inhibiting activity towards all three tested types of ALKs.
2.Advances in the relationships between gastrointestinal microbiota and cancer
Haiyan LI ; Long CHU ; Wei LI ; Zhi XIONG ; Xinya LI
Chinese Journal of Microbiology and Immunology 2016;36(6):477-480
Commensal microorganisms that colonize barrier surfaces of all multicellular organisms exist in harmony with their hosts and have an important effect on both immune and non-immune functions of their hosts. Numerous researches have shown that gastrointestinal microbiota being one of the most important commensal microorganisms plays a critical role in the occurrence, development and treatment of cancer. As-signing causal roles in cancer to specific microbes and microbiotas, unraveling host-microbiota interactions with environmental factors in carcinogenesis, and applying such knowledge to cancer diagnosis and treatment are areas of intensive interest. This review considers how microbes and the microbiota may amplify or miti-gate carcinogenesis, responsiveness to cancer therapeutics, and cancer-associated complications.
3.Relationships among posttraumatic growth, social support, and coping style in women with infertility
Yongju YU ; Li PENG ; Long CHEN ; Ling LONG ; Wei HE ; Jing LI ; Min LI
Chinese Journal of Behavioral Medicine and Brain Science 2013;22(8):707-709
Objective To explore the relationships among posttraumatic growth (PTG),social support,and coping style in women with infertility.Methods 182 women with infertility were recruited in one public hospital department of assisted reproduction technology.Measures included Posttraumatic Growth Inventory (PTGI),Perceived Social Support Scale (PSSS),and Simplified Coping Style Questionnaire (SCQ).Results ① The PTG score of women with infertility was 42.55 ± 16.83,lower than the average level.② Compared with the lower PTG group,the higher PTG group scored significantly higher in social support,positive coping,and negative coping (t =3.867,P< 0.01 ; t =8.452,P< 0.01 ; t =2.817,P< 0.01).③ There were significantly positive correlations among PTG,social support and positive coping (r =0.295-0.515,P < 0.01).④ Positive coping served as a total mediator in the relationship between social support and PTG.Conclusion There are closely correlations among PTG,social support,and positive coping style.Positive coping style significantly mediate the relationship between social support and PTG.
4.Effects of hydrogen-rich saline on expression of phosphor-p38MAPK during cerebral ischemia-reperfusion in rats
Da LI ; Yanqiu AI ; Feng JIN ; Long HE ; Wei ZHANG
Chinese Journal of Anesthesiology 2015;35(3):370-372
Objective To evaluate the effect of hydrogen-rich saline on the expression of phosphor-p38 mitogen-activated protein kinase (p-p38MAPK) during cerebral ischemia-reperfusion (I/R) in rats.Methods Seventy-two adult male Sprague-Dawley rats,weighing 220-250 g,were randomly divided into 3 groups (n =20 each) using a random number table:sham operation group (group S),I/R group and hydrogen-rich saline group (group I/RH).Cerebral ischemia was induced in chloral hydrate-anesthetized rats by 2 h middle cerebral artery occlusion in I/R and I/RH groups.The artery was only exposed but not occluded in group S.At 3 days before operation and immediately after onset of reperfusion,hydrogen-rich saline (0.6 mmol/L) 10 ml/kg was intraperitoneally injected in group I/RH,while the equal volume of normal saline was given in S and I/R groups.Neurological deficits were blindly assessed and scored at the end of 24 h reperfusion.The animals were then sacrificed,and brains were removed for microscopic examination and for determination of the cerebral infarct size (by TTC),brain water content,cell apoptosis (by TUNEL),and expression of p38MAPk and phosphor-p38MAPK (p-p38MAPK) (by immunohistochemistry and Western blot).Apoptosis index was calculated.Results Compared with group S,neurological deficit score,apoptosis index,brain water content and cerebral infarct size were significantly increased,and the expression of p38MAPK and p-p38MAPK was up-regulated in I/R and I/RH groups.Compared with group I/R,neurological deficit score,apoptosis index,brain water content and cerebral infarct size were significantly decreased,and the expression of p38MAPK and p-p38MAPK was down-regulated in group I/RH.The pathological changes of cerebral tissues were significantly attenuated in group I/RH as compared with group I/R.Conclusion Hydrogen-rich saline can reduce cell apoptosis through inhibiting p-p38MAPK expression,thus attenuating cerebral I/R injury in rats.
5.Design and clinical application of HZ-01-A level detector and pressure monitor
Jingwen LI ; Cun LONG ; Song LOU ; Xiguang WEI
Chinese Journal of Tissue Engineering Research 2010;14(30):5686-5689
BACKGROUND: Mortality related to cardiopulmonary bypass can be lowered by intra-operative monitoring system.Monitoring liquid level and pressure is extremely indispensable for examination of cardiopulmonary bypass(CPB).OBJECTIVE: To design a CPB safety system including an arterial line pressure monitor and low-level sensor,and to evaluate its safety and effects in clinical settings.METHODS: The safety system was composed of pressure transducer,photoelectric transmitter,photoelectric detector,core controller,and liquid crystal display.The principles of reflection and refraction were applied to the design of level sensor.The pressure measurements were converted into electronic signals and processed.According to two principles above-mentioned,fluid level detector and pressure monitor were designed.Thirty patients with the age of 1-75 years receiving cardiac surgery with cardiopulmonary bypass were enrolled.The arterial line pressure at different pump flows was measured and the alarm function of the level sensor was also validated.RESULTS AND CONCLUSION: Cardiopulmonary bypass arterial line pressure increased with the pump flow.Arterial line pressure detected by HZ-01-A safety system also increased with the pump flow increasing,which was highly related to the pump pressure.HZ-01-A safety system could alarm when the arterial line pressure and reservoir level exceeded the pre-determined thresholds.HZ-01-A safety system could be safely and effectively applied to clinical cardiopulmonary bypass and improve bypass safety by accurately detecting the pressure and reservoir level.
6.Application of diffusion tensor imaging in brain tumors
Wei LI ; Wansheng LONG ; Xuemao LUO ; Xiaoqin CAI ; Manqiong CHEN
Journal of International Oncology 2011;38(10):797-800
Objective To study the characteristics of diffusion tensor imaging (DTI) in brain tumor and it's diagnosis and differential diagnosis value.Methods Thirty-nine patients with brain tumors proven by pathologically (10 meningioma,17 glioma,12 metastatic tumors) were enrolled,by using Philips Achieva 1.5 T MRI,conventional MRI and DTI were underwent on them,fractional anisotropy (FA) maps,apparent diffusion coefficient (ADC) maps and three dimensional white matter fiber bundle map were reconstructed in the workstation.The core substance of the tumor area and the contralateral mirror area were selected as the region of interest,and FA and ADC values of them were measured,and t test was performed.Results The FA values of meningioma,metastases tumors and gliomas were 0.36 ± 0.08,0.28 ± 0.03,0.18 ± 0.06,respectively,and the differences among them were significant( P < 0.05).The ADC values of meningioma,metastases tumors and gliomas were 1.72 ± 0.10,1.52 ± 0.22,1.34 ± 0.14,respectively,and the differences among them were significant( P < 0.05).Conclusion DTI has high clinical value in identification of meningiomas,metastatic tumors and glioma.
7.The study of dual energy X-ray absorptiometry on body composition components in obesity
Zhongkui HUANG ; Wei CHEN ; Liling LONG ; Xiaoyang LI
Chinese Journal of Radiology 2009;43(6):579-584
Objective To study the correlation of the bone mineral density (BMD) and the body composition components of body mass index (BMI), FAT and LEAN in Chinese obesity. Methods There were 150 cases in obesity group diagnosed by BMI, including 75 males[ median age 46 years, mean weight (89. 64±8. 33) kg] and 75 females[ median age 45 years, mean weight (77.23±6. 85) kg]. There were 150 persons with normal BMI in the control group, including 75 males [ ( median age 47 years, mean weight (62. 34±5.72) kg] and 75 females [ median age 45 years, mean weight (50. 16±5.06) kg]. The body height and weight of 300 persons in two groups were measured respectively and, simultaneously calculated the BMI. These data and the body composition parameters measured by the dual energy X-ray absorptiometry (DEXA) in these two groups were compared and analyzed. The data obtained used two-sample t-test analysis, bi-variable correlation used Pearson linear correlation analysis and multi-variable correlation used multiple linear regression analysis. Results FAT of arms, legs, trunk and total body of male cases in obesity group was (2.90±0.57), (7.48±1.46), ( 15.67±3.05 ), ( 30.92±5.94 ) kg respectively, FAT% was ( 30.9±5.1 ) %, ( 30.6±5.8 ) %, ( 37. 3±4.7 ) %, ( 35.1±4.4 ) % respectively, it was significantly higher than that in control group [ FAT was ( 1.12±0. 64 ), (3.27±1.22), (6. 71±3. 29 ), ( 11.61± 5. 16) kg respectively,FAT% was( 15.4±4. 8)%, ( 16. 5±5.0)%, (21.8±5.8)%, ( 18.6±5. 3)% respectively] ,P <0. 01 ;LEAN of trunk and total body of male cases in obesity group was (27.65±4. 08), (57. 09±7.08 ) kg respectively ; BMD was ( 0. 99±0. 09 ), ( 1.22±0. 09 ) g/cm2 respectively, it was significantly higher than that in control group [ LEAN was ( 22. 89±1.68 ), (48.89 s 3.72 ) kg respectively, BMD was( 0. 89±0. 07 ), ( 1.15±0. 06 ) g/em2 respectively ], P < 0. 01 ; LEAN of arms and legs of male cases in obesity group was(6.22±0.92), (17.31±2.65) kg respectively; BMD was(0.92±0. 04), (1.31±0. 09)g/cm2 respectively,and there were no statistical significance compared with those in control group [ LEAN was ( 5.99±0. 72 ), ( 16. 83±1.67 ) kg respectively, BMD was ( 0. 90±0. 08 ), ( 1.29± 0.09) g/cm2 respectively]. FAT of arms, legs, trunk and total body of females in obesity group was (3.78±1.53), ( 12. 61±3.72), ( 17. 56±2. 59), (33.71±6. 96) kg respectively, FAT% was (33.8± 4.0)%,(40. 1±6.9)%,(43.9±4.9)%, (43.5±4.2)% respectively, LEAN was(7.28±0.94), ( 14. 40 ±2. 05 ), ( 20. 71±3.08 ), ( 43.43±5.69 ) kg respectively, BMD was ( 0. 86±0. 08 ), ( 1.27± 0. 12),(0.95±0. 14), (1.19±0.09)g/cm2 respectively, they were significantly higher than those in control group [ FAT was(2. 04±0. 79), (3.79±0. 94), (6. 89±2. 56), ( 14. 68±3.57) kg respectively, FAT% was (27. 2±4. 5 ) %, ( 29. 6±3.9 ) %, ( 31.0±3.8 ) %, ( 25.9±4. 9 ) % respectively, LEAN was (5. 25±0. 63), ( 10. 65±1.44), ( 16. 65±1.50), (33. 10±3.22) kg respectively, BMD was (0. 78± 0. 04), ( 1.11±0. 09), ( 0. 82±0. 07 ), ( 1.05±0. 07 ) g/cm2 respectively ], P < 0. 01. Conclusion The significantly increasing of fat tissue in all parts of body is a major cause of change of body composition components in obesity. FAT in the trunk increases more obviously than that in other parts of the body in both males and females. The change of distribution of FAT and LEAN can obviously influence BMD.
8.2D-FIESTA Sequence of MRI in the Evaluation of the Biliary Tract for the Infants and Young Children
Xiaoying WANG ; Liuming HUANG ; Long LI ; Wei SUN ; Xuexiang JIANG
Journal of Practical Radiology 2001;0(01):-
Objective To evaluate the diagnostic value of 2D-FIESTA sequence of MRI in the detection of the biliary tract lesions in infant and young children patients(less than 3 years).Methods 8 infant and young children patients were examined by MRI to evaluatetheir biliary tract.Images were obtained with a 1.5T whole body MRI system(GE Medical System,Milwakee,Wis,USA),using theCARDIAC coil.The patients were sedated by chloral hydrate orally or by pentobarbital sodium intravenously.No contrast agents wererequired.All of the axial,coronal and sagittal images were reviewed on an independent workstation and maximum intensity projection(MIP) and multiplanar reformations(MPR) techniques were applied.Results The 2D-FIESTA pulse sequence results in images in which the hepatic vascular structures and the biliary tract were highlighted.In this way,a clear visualization of the hepatic vessels and biliarytract could be obtained in all 8 cases.MRI could demonstrate the anatomy and pathology of post-transplantation changes in 3 patients,choledochal cysts in 2 patients,anomalous connection between the bile and pancreatic ducts in 1 patient.All the abnormalities were proved by operation.2 examinees were diagnosed normal by MRI and were confirmed by follow-up.Conclusion 2D-FIESTA is a fast sequence that allows the high quality images to be generated without breath-hold and without administration of contrast material.It has a potential wide application in the evaluation of biliary tract in the infant patients.
9.Evaluation of ligamentum teres hepatis with multi-slice spiral CT:an initial experience
Wei CHEN ; Xueying LONG ; Wenzheng LI ; Xiaojun LIU
Chinese Journal of General Surgery 2001;0(08):-
Objective To recognize the features of the ligamentum teres hepatic(LTH) in multi-slice spiral CT,and to preliminarily explore its clinical value.Methods A total of 130 patients without liver disease underwent abdominal scanning with a 16-slice spiral CT scanner.LTHs,as focused points,were observed by using postprocessing techniques such as multi-planar reformation(MPR),slab maximum intensity projection(slab-MIP) and slab volume rendering(slab-VR).Results The LTH was detected by multi-slice spiral CT in 90.8%(118/130).On these oblique-sagittal MPR,slab-MIP and slab-VR images,LTH presentedas slightly high density smooth cord-like structure in accordance with its anatomical morphology and position.The mean diameter of fissure portion of normal LTH was(5.44?0.96) mm(range 3.2-7.2 mm) measured at its middle region,and that of free portion of normal LTH was(3.43?0.91) mm(range 1.6-6.0 mm).Conclusions Multi-slice spiral CT demonstrates the LTH clearly,and has a potentialto evaluate the LTH before abdominal operation in which the LTH is to be used as an autogenous repairmaterial.
10.Effect of hydrogen on activation of caspase-3 in brain tissues during cerebral ischemia-reperfusion in rats
Feng JIN ; Long HE ; Yanqiu AI ; Da LI ; Wei ZHANG
Chinese Journal of Anesthesiology 2017;37(3):305-307
Objective To evaluate the effect of hydrogen on the activation of caspase-3 in brain tissues during cerebral ischemia-reperfusion (I/R) in rats.Methods Thirty-six healthy adult male Sprague-Dawley rats,weighing 220-250 g,were divided into 3 groups (n=12 each) using a random number table:sham operation (group S),I/R group and hydrogen group (group H).Cerebral ischemia was induced by occlusion of the middle cerebral artery followed by reperfusion in I/R and H groups.In group H,hydrogen-rich saline 5 ml/kg (0.6 mmol/L) was injected intraperitoneally at 3 days before establishment of the model and immediately after the onset of reperfusion.At 24 h of reperfusion,the rats were sacrificed,and hippocampal tissues were obtained for determination of neuroapoptosis (by TUNEL),apoptotic neuron count and expression of activated caspase-3 (by Western blot).The brain tissues in the ischemic area were obtained and stained with haematoxylin and eosin for examination of the pathological changes.Results Compared with group S,the expression of activated caspase-3 was significantly up-regulated,and the apoptotic neuron count was increased in I/R and H groups (P<0.05).Compared with group I/R,the expression of activated caspase-3 was significantly down-regulated,the apoptotic neuron count was decreased (P<0.05),and the pathological changes of brain tissues were significantly reduced in group H.Conclusion The mechanism by which hydrogen inhibits neuroapoptosis during cerebral I/R is probably related to inhibited activation of caspase-3 in brain tissues of rats.