1.In vitro arsenic trioxide induces apoptosis in T cells of asthmatic patients by a Bcl-2 related mechanism
Dongyun QIN ; Ren HUANG ; Tie WU
Acta Pharmaceutica Sinica 2008;43(1):35-43
This study examined the effects of arsenic trioxide on apoptosis and interleukin4 release in T cells of asthmatic patients in vitro and investigated the role of Bcl2 in the active mechanism. Tcells were isolated from asthmatic patients (n=21) and healthy controls (n=20), and then treated with arsenic trioxide and dexamethasone. Cell apoptosis was measured using fluorescence microscopy, flow cytometry and a cytochrome c ELISA kit. Interleukin4 levels in the serum and in supernatants from T cells were quantified by ELISA. Flow cytometric analysis and immunofluorescence studies were performed to determine Bcl 2 expression. Tcells of the asthmatic patients (I.e. without treatment) exhibited decelerated spontaneous apoptosis after 24 h incubation in vitro when compared to T cells of the healthy controls. With dexamethasone treatment, an increase in apoptosis of Tcells was not significantly different between both groups, irrespective of the method used. Arsenic trioxide treatment, however, significantly increased the apoptosis of T cells of the asthmatic group and showed a slight effect on the control group. In asthmatic patients, elevated levels of interleukin 4 and upregulated Bcl 2 expression were detected. Moreover, in vitro, T cells of asthmatic patients spontaneously released more interleukin4 and exhibited more Bcl 2 expression than T cells from the control group. Arsenic trioxide treatment significantly decreased interleukin4 release and downregulated Bcl 2 expression in asthmatic patients, while it only slightly affected healthy controls. Dexamethasone treatment decreased interleukin4 release in both groups examined. It did not significantly influence Bcl2 expression. These results suggest that arsenic trioxide induces T cell apoptosis and decreases interleukin4 release in T cells of asthmatic patients in vitro and that downregulation of Bcl2 expression may be an important mechanism.
2.Effects of arsenic trioxide on apoptosis and interleukin-4 release of peripheral T cells from asthmatic patients in vitro
Dongyun QIN ; Ren HUANG ; Tie WU
Chinese Journal of Pharmacology and Toxicology 2007;21(6):470-475
AIM To study the possible mechanism of the treatment of arsenic trioxide on asthma. METHODS T cells isolated from 21 asthmatic patients and 20 healthy controls were treated with arsenic trioxide (0.1 mg·L-1) or dexamethasone (5 mg·L-1),in vitro, for 24 h. Interleukin-4 (IL-4) levels in supernatants from T cells were quantified with ELISA. Cell apoptosis was measured by using fluorescence microscopy, flow cytometry and cytochrome c ELISA kit. RESULTS T cells of asthmatic patients spontaneously released more IL-4 than that of healthy controls. Arsenic trioxide significantly decreased IL-4 release of T cells from asthmatic patients, which was more obvious compared with healthy controls. Dexamethasone decreased IL-4 release in both groups. Apoptosis percentage and cytochrome c content in cytoplasm of T cells from asthmatic patients were lower than those from healthy controls. Arsenic trioxide significantly increased the apoptosis percentage and cytochrome c content in cytoplasm of T cells in the asthmatic group, and had slighter effects on that in healthy controls. Dexamathasone increased the apoptosis percentage and cytochrome c content of T cells in both groups. CONCLUSION The mechanism of the treatment of arsenic trioxide on asthma involves the induction of T cell apoptosis and decrease of IL-4 release in asthmatic patients.
3.Thrombosis prediction within short time after total knee arthroplasty: dynamic monitoring of D-Dimer and fibrin degradation products
Wei YUAN ; Huasong MA ; Xiaoping WANG ; Zhiming CHEN ; Ming LU ; Qiming XU ; Dongyun REN
Chinese Journal of Tissue Engineering Research 2015;19(17):2661-2666
BACKGROUND:Deep vein thrombosis after total knee arthroplasty has attracted increasing attention in recent years,but how to detect deep vein thrombosis in the early time in clinical practice remains unclear.Whether it is necessary to perform type-B ultrasonic or other invasive examination in lower limbs has become a hot issue.OBJECTIVE:To explore the significance of D-Dimer and fibrin degradation products in the prediction of deep vein thrombosis after total knee arthroplasty.METHODS:56 patients received total knee arthroplasty were colected from Department of Orthopedics,The 306th Hospital of Chinese PLA,between December 2012 and February 2014.The D-Dimer and fibrin degradation products were dynamicaly monitored before operation and at 1,3,5,7,10 days post-operation.Al the patients received type-B ultrasonic examination in double lower limbs at 10 days post-operation,and divided into thrombus group and non-thrombus group.The D-Dimer and fibrin degradation products in the two groups were compared.RESULTS AND CONCLUSION:Deep vein thrombosis was found in 13 cases by ultrasonic-B postoperation,D-Dimer and fibrin degradation products showed no significant difference between the two groups at 1 week after operation (P>0.05),but the difference was significant at 10 days (P<0.01).D-Dimer and fibrin degradation products index should be monitored dynamicaly for at least 10 days after operation,which is helpful for the earlydiagnosis of thrombosis.
4.Effects of simulated weightlessness on biomechanics of motion unit of rhesus monkey lumbar vertebra
Xiaoping WANG ; Ming LU ; Pei MA ; Zhiming CHEN ; Wei YUAN ; Fujiang ZHAO ; Hao ZHAO ; Dongyun REN ; Huasong MA ; Zhihong WU
Chinese Journal of Tissue Engineering Research 2016;20(26):3843-3848
BACKGROUND:It is generaly believed that the spine wil be extended, and vertebral muscle atrophy, bone loss of vertebral body, increased height and area of intervertebral disc, changes of composition of intervertebral disc wil occur in the condition of weightlessness. These are likely to be the cause of high incidence of low back pain. OBJECTIVE:To observe changes in lumbar spine bone microstructure analysis of simulated weightlessness on rhesus lumbar spine biomechanics. METHODS:Fourteen young rhesus monkeys were randomly divided into two groups: control group (n=7;free activities in the cage during the experiment), and experimental group (n=7; the use of head-down-10° on a special bed by bundle lying to simulate weightlessness). RESULTS AND CONCLUSION:(1) The results of Micro-CT examination: in the experimental group, structure model index in trabecular bone of increased. Trabecular bone changed from plate-like to the rod-like change. The intersection number of bone tissue in unit length to non-bone tissue declined. The average width of the canal between the trabecular bone increased, suggesting that there have been signs of osteoporosis in the experimental group. (2) Under an optical microscope, in the experimental group, bone hyperplasia line was disordered and irregular. Thick endplate trabecularbone became smal, shalow, and arranged substantialy perpendicular to the direction of trabecular bone and cartilage endplate. The closer the endplate surface, the smaler trabecular bone was. Compared with the control group, these smal trabecular bones were thin and curved. Bone marrow cavity was oval. The degree of the connection between the trabecular bones is poor, reflecting the structural characteristics of significant osteoporosis. (3) It is indicated that weightlessness affected the biomechanical properties of rhesus lumbar motion unit.
5.Bilateral pedicle screw and echelon tight closure spinal cord technique combined with implant fixations for correcting stiff spinal angular kyphosis
Huasong MA ; Xiaoping WANG ; Rong TAN ; Zhiming CHEN ; Ming LU ; Wei YUAN ; Qiming XU ; Dongyun REN ; Wei MA ; Long LI ; Jiajian WU ; Jing ZHANG ; Rui ZHENG ; Shen XIN
Chinese Journal of Tissue Engineering Research 2014;(31):4992-4997
BACKGROUND:The treatment difficulties of thoracolumbar angular kyphosis surgery are:low correction rate, hard to rebuild sagittal plane, easily induce neurological complications, postoperative loss of balance, high incidence of pseudarthrosis and postoperative loss of correction degree.
OBJECTIVE:To explore the safety and efficacy of modified posterior vertebral column resection osteotomy and bilateral pedicle screw combined with echelon tight closure spinal cord technique and implant fixation for severe spinal angular kyphosis.
METHODS:A total of 87 severe spinal angular kyphosis patients, 36 males and 51 females, who were treated in the Department of Orthopedics, the 306 Hospital of Chinese PLA from January 2006 to December 2013, were enrol ed in this study. They underwent posterior vertebral column resection, bilateral pedicle screw combined with echelon tight closure spinal cord, and implant fixation. Kyphosis, spinal sagittal imbalance, offset rate towards trunk side, operation time and intraoperative blood loss were observed before and after treatment.
RESULTS AND CONCLUSION:The preoperative average kyphosis was 90.1° (31°-138°). The postoperative average kyphosis was 27.9° (15°-57°). The improvement rate was 76%. The improvement rate of trunk sagittal offset was 76%. Intraoperative blood loss was 800-3 000 mL, and average blood loss was 2 300 mL. The operation time was 5-7 hours, averagely 5.9 hours. Before treatment, two patients affected neurologic symptoms in double lower extremity, and their Frankel classification was grade C and became grade E after treatment. Al patients were fol owed up for 9-57 months. Bony fusion was achieved in al patients. No complications of spinal cord injury appeared, and no orthopedic angle missing occurred. These results indicate that during posterior vertebral column resection for treating severe angular stiffness of the thoracic kyphosis, blood vessels could be maintained greatly. Blood vessel injury-induced ischemic changes in spinal cord and ischemic reperfusion injury could be avoided. To reduce hemorrhage and to keep effective blood volume in patients with low body mass are effective for early recovery after treatment. Bilateral pedicle screw combined with echelon tight closure spinal cord technique greatly protected spinal cord cells against injury. We should pay attention to the protection and loose of nerve root to avoid postoperative nerve root irritation. Sufficient bone fusion ensures kyphosis correction, avoids spine lateral offset, and plays a key role in spinal function and postoperative orthopedic effect.
6.Long-segment pedicle screw fixation and individual osteotomy in the treatment of ankylosing spondylitis with kyphosis
Xiaoping WANG ; Ming LU ; Huasong MA ; Jianwei ZHOU ; Wei YUAN ; Yang CHEN ; Jing NIU ; Dongyun REN ; Liuhua QIN ; Rui ZHENG ; Jing ZHANG
Chinese Journal of Tissue Engineering Research 2013;(52):8999-9004
BACKGROUND:Orthopedic osteotomy at the apex of kyphosis is best for treatment of ankylosing spondylitis from a biomechanical aspect, but there is a high risk for intraoperative spinal cord injury.
OBJECTIVE:To explore the clinical efficacy of vertebral plate osteotomy+vertebra osteotomy+long-segment pedicle screw fixation in the treatment of ankylosing spondylitis with kyphotic deformity.
METHODS:Thirty-six patients with ankylosing spondylitis were subjected to pedicle subtraction osteotomy and Smith-Peterson osteotomy, and then fol owed up for 3 months to 2 years.
RESULTS AND CONCLUSION:After implantation, sagittal imbalance did not occur in 36 patients, and the improvement rate of sagittal imbalance was 64%. The improvement rates of thoracolumbar kyphosis and chin-brow vertical angle were 60%and 98%, respectively. The pain relief rate was 64%, and the Oswestry Disability Index was 95%. There were no pul ed nails, broken nails and broken robs after implantation. These findings indicate that the combination of selective osteotomy technique and long-segment internal fixation can achieve stable fixation effects, prevent sagittal imbalance, and avoid the occurrence of pul ing nails, breaking nails and breaking robs caused by osteoporosis.
7.Posterior vertebral column resection osteotomy combined with step correction in treatment of stiff angular kyphosis:a biomechanical analysis
Huasong MA ; Xiaoping WANG ; Rong TAN ; Zhiming CHEN ; Ming LU ; Wei YUAN ; Qiming XU ; Dongyun REN ; Wei MA ; Long LI ; Jing ZHANG ; Rui ZHENG ; Xin XIN
Chinese Journal of Tissue Engineering Research 2014;(35):5647-5653
BACKGROUND:Severe spinal angular kyphosis aggravated spinal cord injury and early degeneration, even caused incomplete paralysis or complete paralysis. Surgical treatment is the only solving approaches and method, but it is difficult, exhibits high risk, and easily affects postoperative complications. OBJECTIVE:To analyze the science and effectiveness of posterior vertebral column resection osteotomy combined with step correction in treatment of stiff angular kyphosis based on biomechanical principle. METHODS:A total of 90 cases underwent posterior vertebral column resection osteotomy combined with bilateral pedicle screw spinal cord gradual y shortening echelon tight closure and orthopedic fixation were selected, including 37 males and 52 females, at the average age of 47 years. Kyphotic angle, spinal sagittal imbalance, trunk side offset rate, operation time, intraoperative blood loss were compared and analyzed before and after treatment. RESULTS AND CONCLUSION:The kyphotic angles were 31°-138° (averagely 90.1°) preoperatively and 10°-90° (averagely 41.6°) postoperatively, with an improvement rate of 65%. The distance from C 7 plumb line to the S 1 upper edge was averagely 5.2 mm, with a correction rate of 73%. Intraoperative blood loss was 1 200-6 000 mL, averagely 2 089 mL. Operation time was 212-470 minutes, averagely 326 minutes. The patients were fol owed up for 20 to 35 months after the surgery. Osteotomy segments had achieved bone fusion in al patients, and no complications of spinal cord injury or orthopedic angle loss appeared. These data verified that in the accordance with cellbiomechanics and spinal biomechanical principles, bilateral pedicle screw spinal cord gradual y shortening echelon tight closure and orthopedic fixation protected utmost spinal cord cells against injury in the correction of thoracolumbar angular kyphosis. There is sufficient basis for cellphysiology and it accorded biomechanical and physiological characteristics. During the surgery, we should pay attention to protection and release of nerve root and avoid postoperative corresponding nerve root irritation. Ful fusion ensures kyphosis correction and avoids spine lateral offset, is an effective safeguard for the recovery of spinal function and postoperative orthopedic effect.
8.Equisetin is an anti-obesity candidate through targeting 11β-HSD1.
Zhenlu XU ; Dongyun LIU ; Dong LIU ; Xue REN ; Haibo LIU ; Guihong QI ; Yue ZHOU ; Chongming WU ; Kui ZHU ; Zhongmei ZOU ; Jing YUAN ; Wenhan LIN ; Peng GUO
Acta Pharmaceutica Sinica B 2022;12(5):2358-2373
Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin (EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate. We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1's substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess 11β-HSD1 products, EQST's anti-obesity effects disappeared. Furthermore, EQST directly bond to 11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.