Studies on the metabolism of a triptolide derivative (5R)-5-hydroxytriptolide in vitro / 药学学报

The purpose of current study is to investigate the metabolic profile of a triptolide derivative (5R)-5-hydroxytriptolide in vitro. (5R)-5-Hydroxytriptolide was incubated with the hepatocytes of human, monkey, dog, rat or mouse, respectively. Compared with inactivated hepatocytes, four metabolites were identified in hepatocytes from all five species: oxidative ring-opening metabolite (M1), glutathione-conjugating metabolite (M2), and monooxidative combined with glutathione-conjugating metabolites (M3-1 and M3-2), respectively. In human or rat liver microsomes, seven metabolites of (5R)-5-hydroxytriptolide were found, dehydrogenated metabolite (M4) and monooxidative metabolites (M5-1–M5-6), respectively. Reference standards for the metabolites were obtained either through chemical semisynthesis or biotransformation through rat primary hepatocytes. The structures of five metabolites were confirmed, which were 12,13-epoxy ring-opening metabolite M1, 12-glutathione-conjugating metabolite M2, (16S)-, (2R)- and (19R)-monohydroxylated metabolites M5-1, M5-4, and M5-5, respectively. In vitro activity assay revealed that only (2R)-hydroxylated metabolite exhibited weak immunosuppressive activity with less than one-tenth the activity of its parent drug, and a significant decrease in toxicity was observed. It is suggested that (5R)-5-hydroxytriptolide might undergo metabolic inactivation and detoxification in vivo.

Biomechanical changes of sheep cervical spine after unilateral hemilaminectomy and different degrees of facetectomy / 北京大学学报(医学版)

OBJECTIVE@#To establish animal models and investigate the impact of unilateral hemilaminectomy (ULHL) and different degrees of facetectomy (FT) on the cervical spinal biomechanics.@*METHODS@#Twenty sheep were randomly and evenly divided into 4 groups. No operation was performed for group A, right C4-C6 ULHL was performed for group B, right C4-C6 ULHL and 50% ipsilateral C4-C5 FT was performed for group C, right C4-C6 ULHL and 100% ipsilateral C4-C5 FT was performed for group D. Animals of group A, B, C and D were sacrificed 24 weeks after operating and fresh cervical spine specimens were acquired, biomechanically tested and these data were compared to determine whether ULHL and different degrees of FT led to long-term differences in range of motion.@*RESULTS@#(1) Changes of the total range of motion of cervical spine 24 weeks after surgery: the total range of motion of group D (60.2°±8.6°) was significantly greater than group A (40.7°±6.4°) and group B (41.2°±13.1°) under flexion-extension station, the total range of motion of group D (81.5°±15.7°) was significantly greater than that of group A (56.7°±12.2°) and group B (57.7°±12.8°) under lateral bending station, and the total range of motion of group D (38.5°±17.5°) had no obvious increase compared with group A (26.4°±9.9°) and group B (27.1°±10.9°) under axial rotation station. The total range of motion of group C had no obvious increase compared with group A and group B under flexion-extension station (44.1°±11.7°), lateral bending station (73.6°±11.4°) and axial rotation station (31.3°±11.5°). (2) Changes of the intersegmental motion 24 weeks after surgery: the intersegmental motion of group D (20.3°±4.6°) at C4-C5 was significantly greater than that of group A (11.7°±3.4°) and group B (11.9°±2.1°) under flexion-extension station, the intersegmental motion of group D (26.8°±3.5°) at C4-C5 was significantly greater than that of group A (15.2°±3.1°) and group B (16.2°±3.2°) under lateral bending station, the intersegmental motion of group D (15.2°±3.5°) at C4-C5 was significantly greater than that of group A (6.6°±2.3°) and group B (7.1°±1.9°) under axial rotation station. The intersegmental motion of group C (21.2°±4.1°) at C4-C5 was significantly greater than that of group A and group B under lateral bending station, the intersegmental motion of group C at C4-C5 had no obvious increase compared with group A and group B under flexion-extension station (15.7°±3.7°) and axial rotation station (10.3°±3.1°).@*CONCLUSION@#ULHL does not affect cervical stability, ULHL and 50% ipsilateral FT does not affect the long-term cervical stability, ULHL and 100% ipsilateral FT can lead to long-term instability under lateral bending and flexion-extension station.

Relationship between mineral density and elastic modulus of human cancellous bone / 医用生物力学

Objective To measure the cancellous bone mineral density and axial elastic modulus from multiple anatomic sites, then build the constitutive equation between them, so as to provide specific data for finite element modeling of Chinese people. Methods Ten fresh adult cadavers were taken as sample sources. In every fresh cadaver, 5 different anatomic sites were selected: proximal tibia, greater trochanter, femoral neck, humeral head and lumbar vertebra. The raw samples were processed into standard specimens, which were approximately 6 mm in diameter and 30 mm or 40 mm in length. Both the size and volume for the cancellous bone specimens were measured, and their mineral densities were obtained with computed tomography. The mechanical properties of such specimens were tested with biomechanical testing machine for analyzing the elastic modulus of the cancellous bone at different anatomic sites. The linear and power regression between mineral density and axial elastic modulus were analyzed on SPSS 18.0. Results A total of 169 cancellous bone specimens which were availably tested were collected, including 52 proximal tibia, 31 greater trochanter, 15 femoral neck, 17 humeral head and 54 lumbar vertebrae. The analysis on measurement results showed that the mineral density and axial elastic modulus in cancellous bones from 5 anatomic sites were different, and had a solid linear relationship (0.850>r2>0.785), with 3 sites (proximal tibia, greater trochanter, lumbar vertebra) showing a solid power correlation (0.871>r2>0.825), and the other 2 sites (humeral head and femoral neck) showing relatively weak power correlation (0.671>r2>0.643). Conclusions There are solid linear and power relationship between mineral density and axial elastic modulus, while no significant difference is proved between the r2 values of the two regressions in this research. This discovery can be applied to detect patients’ bone quality in vitro and identify the precise position of bone loss, and further to predict fracture risk with the help of finite element modeling.

Advances in the study of steroidal inhibitors of cytochrome P45017alpha / 药学学报

The steroidal enzyme cytochrome P45017alpha catalyzes the conversion of progesterone and pregnenolone into androgens, androstenedione and dehydroepiandrosterone, respectively, the direct precursors of estrogens and testosterone. Dihydrotestosterone is the principal active androgen in the prostate, testosterone is also an active stimulant of the growth of prostatic cancer tissue. Inhibition of this enzyme as a mechanism for inhibiting androgen biosynthesis could be a worthwhile therapeutic strategy for the treatment of PCA. In this paper, four categories of steroidal inhibitors of cytochrome P45017alpha will be reviewed, a diverse range of steroidal inhibitors had been synthesized and shown to be potent inhibitors of P45017alpha.

Biomechanical advantages of medial support screws in locking plate for treating proximal humerus fractures / 医用生物力学

Objective To evaluate the biomechanical advantages of medial support screws (MSSs) in locking proximal humeral plate for treating proximal humerus fractures. Methods Thirty synthetic left humeri were randomly divided into 3 groups to establish the fracture models. Group A was fixed with a locking proximal humerus plate with medial cortical support, but without MSSs; group B was fixed with 3 MSSs, but without medial cortical support; group C was fixed with neither medial cortical support nor MSSs. Axial compression, torsion, shear stiffness and failure tests were applied on the specimens of the three groups. Results For axial compression tests, the maximum load of group A, B, C was (240.88±19.13), (169.04±19.26), (128.58±17.53) N, respectively; the axial stiffness of group A, B, C was (424.4±101.2), (230.7±40.54), (147.0±29.2) N/mm, respectively, showing significant differences (P0.05). For shear stiffness tests, the maximum load of group A, B, C was (444.71±20.87), (228.79±28.95), (188.73±26.15) N, respectively; the shear stiffness of group A, B, C was (70.0± 54.4), (183.89±29.64), (140.2±32.1) N/mm, respectively, showing significant differences (P0.05). Conclusions Using three MSSs in locking plate for proximal humerus fractures shows optimal biomechanical properties, as compared to the situation without restoration of the medial column support. The reconstruction of the medial cortical support or MSSs for proximal humerus fractures helps to enhance the mechanical stability of the humeral head and prevent failure after internal fixation.

Reinforcement property of collagen fibril in articular cartilage / 医用生物力学

Objective To evaluate and compare the differences in COSMOL articular cartilage (AC) simulation due to the application of collagen fibril reinforcement property. Methods Collagen fiber stress was modeled independently according to its orientation in AC and written into the original poro-elastic AC model. Function call was used to avoid quadric strain term. The iteration of solver was increased for better convergence. Results The initial superficial Y displacement of the reinforced model was 15 μm, which was 17.6% of the non-reinforced model. X normal strain of the reinforced model was 10% of that in the non-reinforced model, but the superficial X normal stress of the reinforced model was 10 times higher than that of the non-reinforced model. Conclusions The application of collagen fibril reinforcement property in COMSOL AC simulation is achieved, which provided the computational model and theoretical analysis for collagen fibril lesion. Lateral reinforcement of collagen fiber can constrain the vertical strain, by which enlarge AC load capacity and improve AC mechanical properties.

Multiscale computation on mechanical environment of chondrocytes / 医用生物力学

Objective To compare the mechanical environment of chondrocytes between superficial zone and deep zone by multiscale computation. Methods The chondrocyte biphasic model was set up and made the results of the articular cartilage (AC) biphasic model mapped to the corresponding borders of the chondrocyte model as the boundary condition. The chondrocyte model was computed to obtain the results of the mechanical environment of chondrocytes and analyzed. Results The results showed that the stress of chondrocytes at deep zone was half of that at superficial zone, but both were much smaller than those outside chondrocytes. The pericellular matrix (PCM) sustained the high stress outside chondrocytes and remarkably reduced the stress inside chondrocytes. Interstitial flow directions adjacent to two chondrocytes were totally the opposite.Conclusions The bearing property of AC reduced the stress near chondrocytes at deep zone prominently and protected the chondrocytes at deep zone and subchondral bone. PCM sustained the high stress outside chondrocytes to provide lower stress environment for chondrocytes living. The opposite interstitial flow direction of two chondrocytes supported the theory that synovia seepage from cartilage surface and nutrient pumped out from subchondral bone constitute the bidirectional nutrient supply in AC.

Diterpene constituents of Tripterygium willfordii (II) / 药学学报

In order to study the constituents and pharmacology of Tripterygium plants (Tripterygium willfordii Hook.f), a variety of chromatography methods were used. Four compounds were isolated from Tripterygium plant and their structures were elucidated by UV, IR, MS, HR-MS, 1H NMR, 13C NMR and 2D-NMR techniques. The isolated compounds were named as triptonide (1), neo-triptetraolide (2), 2alpha-hydroxytriptonide (3), and 15-hydroxytriptonide (4), separately. Compounds 3, 4 belong to new diterpenoids, which can inhibit the growth of K562 cells (leukemia cells) and HL60 cells (acute myeloid leukemia cells).

Articular cartilage simulation using depth-dependent mechanical parameters / 医用生物力学

Objective To evaluate the difference in articular cartilage simulation due to the application of either homogeneous or depth-dependent mechanical parameters. Method The nonlinear， biphasic， porous model of articular cartilage was built using poroelasticity module in COMSOL. Under the static load, the model was computed using homogeneous and depth dependent parameter, respectively. The difference between the results was analyzed. Results For the total stress of cartilage， there was no remarkable difference between two parameter configurations. However, for the analysis such as solid phase stress, fluid pressure and flow velocity， the difference between two parameter configurations must be considered. Conclusions Different parameter configuration has negligible effect on the total stress of cartilage, but it is influential to the flow velocity. Therefore， homogeneous mechanical parameters should be used in order to simplify the total stress computation problem. The other more detailed analysis should be based on the depth dependent parameters. These conclusions could be referred to for future cartilage modeling and numerical computation and thus laying a foundation for the design and computation of artificial joint.

Vitro antitumor activity and synthesis of the key intermediate of bakuchiol / 药学学报

The in vitro antitumor activity of bakuchiol was exploited, compared with tamoxifen. The result of biological activities showed that bakuchiol could inhibit human breast cancer and the IC50 values were 2.89 x 10(-5) mol L(-1) and 8.29 x 10(-3) mol L(-1) against the cells line T-47D and MDA-MB-231 respectively. On the other hand, the key intermediate to synthesize bakuchiol was obtained by the method of Ireland-Claisen rearrangement. Comparing with traditional Claisen rearrangement, the reaction conditions are milder and the reaction reagents are safer.

JCS-based method on coordinate transformation of attachment points between muscle and bone / 医用生物力学

Objective In order to avoid potential injuries imposed to human body, it can be feasible to use the musculoskeletal models which can be reconstructed from the cadaver color cryosection (CCC) images, computerized tomography (CT) images, magnetic resonance (MR) images or other images to analyze the dynamic properties of muscles in vivo during human movement. Methods We reconstruct the lower limb musculoskeletal model and define the uniform joint coordinate system (JCS) on the model and the subject. The coordinate transformation of the muscle attachment points both on the model and the subject is described in detail. Results The length and the moment arm of the biceps femoris (short head) during knee flexion are calculated and analyzed. Conclusion This method plays an important role in improving the kinematics and dynamic simulation and the muscle force estimation.

JCS-based method on coordinate transformation of attachment points between muscle and bone / 医用生物力学

Objective In order to avoid potential injuries imposed to human body,it could be feasible to use the musculoskeletal models which can be reconstructed from the cadaver color cryosection(CCC)images,computerized tomography(CT)images,magnetic resonance(MR)images or other images to analyze the dynamic properties of muscles in vivo during human movement.Mothod We reconstruct the lower limb musculoskeletal model and define the uniform ioint coordinate system(JCS)on the model and the subject.The coordinate transformation of the muscle attachment points both on the model and the subject is described in detail.Results The length and the moment arm of the biceps femoris(short head)during knee flexion are calculated and analyzed.Conclusion This method plays an important role in improving the kinematics and dynamic simulation and the muscle force estimation.

JCS-based method on coordinate transformation of attachment points between muscle and bone / 医用生物力学

Objective In order to avoid potential injuries imposed to human body,it could be feasible to use the musculoskeletal models which can be reconstructed from the cadaver color cryosection(CCC)images,computerized tomography(CT)images,magnetic resonance(MR)images or other images to analyze the dynamic properties of muscles in vivo during human movement.Mothod We reconstruct the lower limb musculoskeletal model and define the uniform ioint coordinate system(JCS)on the model and the subject.The coordinate transformation of the muscle attachment points both on the model and the subject is described in detail.Results The length and the moment arm of the biceps femoris(short head)during knee flexion are calculated and analyzed.Conclusion This method plays an important role in improving the kinematics and dynamic simulation and the muscle force estimation.

Chemical constituents in root of Hemerocallis fulva / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of the root of Hemerocallis fulva.</p><p><b>METHOD</b>Compounds were isolated by repeated silica gel, Sephadex LH-20, MCI gel, etc. column chromatography and their structures were determined by spectral analyses and physicochemical properties.</p><p><b>RESULT</b>From the n-butanol fraction of the EtOH extract of the roots of H. fulva, 9 glycosides were isolated and identified as sweroside (1), laganin (2), picraquassioside C (3), puerarin (4), 3'-methoxypuerarin (5), 7-hydro xylnaphthalide-O-beta-D-glucopyranoside (6), orcinol-3-O-beta-glucopyranoside (7), HN saponin F (8), hederagenin-3-0-beta D-glucopyranosyl-(1-3)-alpha-L-arabinopyranoside-28-O-beta-D-glucopyranosyl ester (9).</p><p><b>CONCLUSION</b>Compounds 1-9 were isolated from the genus Hemerocallis for the first time.</p>

Influence of Wnt-1 recombinant adenovirus on differentiation of human epidermal stem cells / 中华烧伤杂志

<p><b>OBJECTIVE</b>To observe the influence of Wnt-1 recombinant adenovirus on differentiation tendency of human epidermal stem cells.</p><p><b>METHODS</b>Wnt-1 recombinant adenovirus was transduced into hESCs (E group), while normal hESCs were used as control (C) group. The diameter, proliferation,and labeling molecular expression of hESC were determined. The content of MMP-2 and MMP-7 in supernate were also assayed.</p><p><b>RESULTS</b>There was no obvious difference in diameter of hESC between two groups. The density of hESC in E group was (1.45 +/- 0.09) x 10(5)/mL, which was obviously higher than that in C group [(1.18 +/- 0.10) x 10(5)/mL, P < 0.05]. There were no obvious differences in expression of markers between two groups,including keratin 5 (KS), K6, K7, KS, K14, CD44, carcinoembryonic-like antigen (CEAA), ER, PR (P > 0.05) ,while the expression of K 10 was different among groups [(60 +/- 3)% in E group, 0 in C group], also K18 [(34.3 +/- 2.1)% in E group vs. (13.8 +/- 1.7)% in C group, P < 0.05], and K19 [(17.1 +/- 1.8)% in E group vs. (24.4 +/- 1.5)% in C group, P < 0.05].The contents of MMP-2 and MMP-7 in E group were higher than those in C group (P < 0.01).</p><p><b>CONCLUSION</b>Wnt-1 recombinant adenovirus can induce the differentiation of hESCs to glandular epithelium-like cells.</p>

Isolation and structure identification of chemical constituents from Anabasis brevifolia / 药学学报

<p><b>AIM</b>To study the chemical consitituents of the n-butanol-extracts of Anabasis salsa and Various chromatographic techniques were used to the chloroform-extract of Anabasis brevifolia.</p><p><b>METHODS</b>separate and purify the constituents. Their physico-chemical properties and spectral data were used to elucidate their structures.</p><p><b>RESULTS</b>Five compounds were isolated and identified as 2-O-beta-D-glucopyranosyloxy-4,6-dimethoxy phenylenthanone (1), 2-O-(2)-beta-D-glucopyranosyloxy-4, 6-dimethoxy phenylenthanone (2), 3-methyl-but-2-enoic acid-[2-(4-methoxy phenyl)-ethyl]-amide (3), 5,6,7,2'-tetramethoxy isoflavonoid (4), 2'-hydroxy-5,6,7-trimethoxyisoflavonoid (5).</p><p><b>CONCLUSION</b>Compounds 2, 3, and 5 are new compounds. And the others were isolated from Anabasis L. for the first time.</p>

Diterpenes constituents of Tripterygium wilfordii / 药学学报

<p><b>AIM</b>To study the chemical constituents of Tripterygium wilfordii Hook. F.</p><p><b>METHODS</b>Various column chromatographies with silica gel were used for the isolation and purification. The structures of compounds were established on the basis of its IR, MS, UV, 1H NMR, 13C NMR and HRMS, 1H-1H COSY, 1H-13C COSY and NOESY.</p><p><b>RESULTS</b>Four diterpenoids were isolated: 16-hydroxytriptolide (I), triptolidenol (II), tripdiolide (III), 2-epitripdiolide (IV).</p><p><b>CONCLUSION</b>Compound IV is a new diterpenoid.</p>

Isolation and identification of two new epimer from the mother liquid of megestrol acetate / 药学学报

<p><b>AIM</b>To study the impurity in the drug megestrol acetate.</p><p><b>METHODS</b>Chromatography methods were used to separate the chemical constituents. Their structures were determined by NMR and MS spectral analysis.</p><p><b>RESULTS</b>Two new epimers were isolated from the mother liquid of the drug megestrol acetate.</p><p><b>CONCLUSION</b>These new epimers were identified as 17alpha-acetoxy-2beta,6alpha-dimethylprega-4-ene-3,20-dione (1) and 17alpha-acetoxy-2alpha,6alpha-dimethylprega-4-ene-3,20-dione (2).</p>

The isolation and identification of two new epimer from the mother liquid of testosterone / 药学学报

<p><b>AIM</b>To study the impurity of the drug testosterone.</p><p><b>METHODS</b>Chromatography methods were used to separate the chemical constituents. Their structures were determined by NMR and MS spectral analysis.</p><p><b>RESULTS</b>Two new epimers were isolated from the mother liquid of the drug.</p><p><b>CONCLUSION</b>These new epimers were identified as 3alpha-ethoxyandrost-4-en-17beta-ol, 3beta-ethoxyandrost-4-en-17beta-ol.</p>

Isolation and structure of wilfordlonging from Tripterygium wilfordii Hook. f / 药学学报

<p><b>AIM</b>To study the chemical composition of Tripterygirm wilfordii Hook. f.</p><p><b>METHODS</b>Colunm chromatography was used to separate the chemical constituents. UV, IR, MS, HRMS, 1HNMR, 13CNMR (COM and OFR), 1H-1H COSY, 1H-13C COSY, NOESY and COLOC spectra were used to determine the structures of the isolated constituents.</p><p><b>RESULTS</b>Two sesquiterpene alkaloids were isolated and their structures were elucidated as wilforgine and wilfordlongine on the basis of spectral evidence.</p><p><b>CONCLUSION</b>Wilfordclonine is a new sesquiterpene alkaloid.</p>