1.Metabolomics Analysis of Tupaia belangeri Breast Tumor Model
Xi FANG ; Qingqing AO ; Chunhong LI ; Yiqiang OUYANG ; Songchao GUO ; Bing HU
Laboratory Animal and Comparative Medicine 2024;44(1):52-61
ObjectiveTo explore the metabolic changes during the development of Tupaia belangeri breast tumors, to investigate the close relationship between the changes of serum metabolic substances and the occurrence and progression of tumors, and to screen for biomarkers reflecting the progression of breast tumors. MethodsBreast tumors in Tupaia belangeri were induced by orally administering 7,12-dimethylbenzoanthracene (DMBA) three times, with a 15-day interval between each administration, along with a high-fat and high-sugar diet. The DMBA-induced breast cancer group and the DMBA-inducedwithout breast cancer group were compared with the control group. Untargeted determination of serum metabolites was performed using gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) in DMBA-induced Tupaia belangeri with breast cancer, DMBA-induced without breast cancer and the control group. Multidimensional statistical analysis including unsupervised principal component analysis (PCA), and orthogonal partial least squares analysis (OPLS-DA) were conducted. Furthermore, t-test was used for intergroup differential comparison. Differential metabolites were screened under VIP>1 and P<0.05 conditions, and significantly changing differential metabolites were identified using the HMDB online database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database was utilized to enrich metabolic-related gene regulatory pathways. ResultsThe incidence of breast tumors was 40% in DMBA-induced Tupaia belangeri. Compared with the control group, 30 metabolic differential products were detected in the serum of the group with breast cancer, with 18 down-regulated and 12 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in four metabolic pathways: glutamate metabolism, glyceride metabolism, citric acid cycle, and alanine metabolism. Compared with the group without breast cancer, 18 metabolic differential products were detected, with 7 down-regulated and 11 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in the citric acid cycle and glutamate metabolism. Compared with the control group, 31 metabolic differential products were detected in the serum of the groups without breast cancer, with 14 down-regulated and 17 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in three metabolic pathways: glutamate metabolism, glyceride metabolism, and citric acid cycle. ConclusionMetabolomics analysis can reveal the characteristics of changes in metabolites in the serum of breast tumors. The results suggest that glutamate metabolism, glyceride metabolism, citric acid cycle, and alanine metabolism pathways are associated with the occurrence and development of DMBA-induced breast tumors in Tupaia belangeri. It provides a foundation for further research into the biological mechanism of breast cancer.
2.Effect of early inhibition of TLR4 on hippocampal immune function to adolescence after neonatal HIBD
Xiaoli Huang ; Zhicui Ouyang ; Xianghong Wu ; Yan Li ; Yun Huang ; Guoqiong Liu ; Shiwei Lu ; Zhen Tang
Acta Universitatis Medicinalis Anhui 2023;58(8):1317-1322
Objective :
To investigate the role of early inhibition of Toll⁃like receptor 4 (TLR4) in regulating hippampal neuroimmune responseto adolescent ratsafter neonatal hypoxic⁃ischemic brain damage(HIBD) .
Methods:
Postnatal day 7 rats were randomized into controlgroup , hypoxic ischemia (HI) group , and HI + TAK⁃242( the specific inhibitor of TLR4)(TAK⁃242) group. The expression of TLR4 in rat hippocampus was detected by immunohistochemistry at 3 days after HI. Immunofluorescence were used to determine the number of Iba⁃1 + , GFAP + , CD161 + , MPO + and CD3 + cells in the hippocampus at 21 days after HI. Immunohistochemistry was used to detect ICAM⁃1 and C3a expression in the hippocampal CA1 region ; and Western blot was used to detect tumor necrosis factor interleukin IL⁃1β , TNF⁃α and IL⁃10 expression.
Results :
Compared with control group , significantly raised TLR4 expression was observed in the left hippocampal CA1 , CA3 and DG regions(P < 0. 01 or P < 0. 05) , while the expression in the TAK⁃242 group lowered compared to the HI group (P < 0. 05) . The number of GFAP + cells in the CA1 area of the hippocampus in the TAK⁃242 group of neonatal rats decreased compared to which in the HI group at 21 days after HI(P < 0. 05) , but the number of CD3 + T lymphocytes in the hippocampal CA1 area of new born rats in the HI group increased compared to which in the Control group (P < 0. 05) , but the difference between TAK⁃242 and the Control group was not statistically significant. The number of Iba⁃1 + cells , MPO + cells , CD161 + cells , the expression of ICAM⁃1 and C3a in hippocampal CA1 region , and the expression of TNF⁃α , IL⁃1β and IL⁃10 in hippocampus of rats were not different among groups at 21 days after HIBD.
Conclusion
Early inhibition of TLR4 may ameliorate adolescent neuroimmune disorders by reducing the increase of hippocampal astrocytesafter neonatal HIBD.
3.Effect of Quercetin on Apoptosis of Platelets and Its Mechanism.
Qian XIAO ; Xiong-Yan CHEN ; Qing OUYANG ; Li-Xing JIANG ; Yi-Qian WU ; Yan-Fang JIANG
Journal of Experimental Hematology 2019;27(5):1612-1616
OBJECTIVE:
To investigate the effects of quercetin on the apoptosis of platelets and to analyze the intrinsic mechanism.
METHODS:
Firstly, the effects of quecetin on the apoptosis of platelets was detected by flow cytometry. Secondly, Western blot was used to detect the expression of apoptosis-related proteins in the platelets treated with quercetin for 2 and 4 day.
RESULTS:
By flow cytometry, it was found that the apoptosis of platelets in the quercetin-treated group (2, 4 and 8 μmol/L) was inhibited, the apoptosis rate of platelets in 2, 4 and 8 μmol/L quercetin group was 3.12%±0.32%, 2.89%±0.15% and 2.31%±0.28%, respectively, which were signigicantly lover than that in control group (P<0.01). With the increase of quecetin concentration, the proportion ratio of platelets significantly decreased in a concentration-dependent manner(r=-0.9985). Similar results were observed on the 4th day. Western blot showed that the treatment with quercetin (2, 4 and 8 μmol/L) promoted the expression of anti-apoptotic protein BCL-2, inhibited the expression of pro-apoptotic protein BAX, resulting in a significant increase in the ratio of BCL-2/BAX (P<0.01), thereby inhibiting the apoptosis of platelets. Similar results were observed on the 4th day.
CONCLUSION
Quercetin can inhibit platelet apoptosis by increasing the ratio of apoptosis-related protein BCL-2/BAX in a concentration-dependent manner.
Apoptosis
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Apoptosis Regulatory Proteins
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Blood Platelets
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Quercetin
4.Curative effect of micro-strip line anchors combined with posterior capsulorrhaphy in the treatment of first metacarpophalangeal joint dislocation in rheumatoid arthritis
Zhixing NIE ; Chenxin GAO ; Dapeng HAN ; Sheng DING ; Lingchun WANG ; Jianpo ZHANG ; Guilin OUYANG
Clinical Medicine of China 2019;35(1):49-53
Objective To study the short-term and medium-term effects of mini- strip anchor and capsulotomy in the treatment of first metacarpophalangeal joint dislocation in rheumatoid arthritis (RA). Methods From January 2015 to December 2016,fifty-eight RA patients with first metacarpophalangeal joint dislocation were randomly divided into study group (20 cases),joint replacement group (19 cases) and non-operation group (19 cases). Postoperative evaluation indexes: the wound healing was observed in accordance with "trial standard of functional evaluation of upper limbs of Chinese Medical Association Hand Surgery Society". The surgical outcomes of the three groups were compared. The hand function and quality of life were assessed by Michiga Hand Outcomes Questionnaire ( MHQ ) and arthritis impact measurement scale 2 (AIMS2) before treatment, 6 months after treatment and 12 months after treatment. Results All the patients in the study group and the joint replacement group healed by first intention without any early complications. According to the criteria of upper extremity functional evaluation of Chinese Medical Association,the curative effect of the operation was evaluated. In the study group,15 cases were excellent,3 cases were good,2 cases were poor,the excellent and good rate was 90. 0%. In the joint replacement group, 15 cases were excellent,3 cases were good,1 case was poor,and the excellent and good rate was 94. 7%. After treatment for 6months, the MHQ scores were improved significantly in the three groups (( 48. 36 ±8. 24) vs. (73. 06±10. 55); (47. 56±7. 75) vs. (81. 42±8. 54); (48. 75±8. 85) vs. (65. 91±8. 26)) (F=33. 19,35. 12,28. 42, P<0. 05). The MHQ scores of study group ( (73. 06±10. 55)points) and joint replacement group ( ( 81. 42 ± 8. 54) points) were significantly higher than those of non-operation group ((65. 91± 8. 26) points) ( P<0. 05), and the MHQ scores of joint replacement group were significantly higher than those of study group (P<0. 05). At 12 months after treatment,there was no significant difference in MHQ score between the study group ((82. 45±7. 18)points) and the arthroplasty group ((84. 36±6. 33) points) (P>0. 05) . At 6 and 12 months after treatment, AIMS2 scores of each group were significantly improved,but AIMS2 scores of study group (( 216. 51 ± 35. 28) points, ( 230. 28 ± 23. 51) points) and arthroplasty group ((221. 45±31. 63) points,(234. 15±21. 42) points) were significantly higher than those of non-operation group ((192.69±41.31) points,(200.43 ±28.42) points) (P<0.05).At 6 and 12 months after treatment,there was no significant difference in AIMS2 scores between the study group and the arthroplasty group ( P > 0. 05 ) . Conclusion Micro-strip line anchors combined with posterior capsulorrhaphy in the treatment of first metacarpophalangeal joint dislocation in rheumatoid arthritis can achieve good stability of articular reduction,significantly improve the joint function and quality of life and have ideal short-term and mid-term effect.
5.Total knee arthroplasty without the patellar replacement:knee function and incidence of anterior knee pain
Fei ZHU ; Yanxi CHEN ; Guilin OUYANG ; Qing XIA
Chinese Journal of Tissue Engineering Research 2015;(13):2000-2004
BACKGROUND:The incidence of patel ar complications is decreasing, however, the necessity of patel ar replacement remains unclear. OBJECTIVE:To investigate the incidence rate of anterior knee pain and postoperative pain score in total knee arthroplasty without the patel ar replacement and to provide a reference for the formulation of clinical operation scheme. METHODS:151 patients with 193 knees receiving total knee arthroplasty were involved in this study. Al the patients were treated with patel ar forming but not resurfacing of the patel a. The Western Ontario and McMaster University (WOMAC) Osteoarthritis Index and America Hospital for Special Surgery (HSS) score were used to evaluate patients before surgery and at 6 and 12 months after surgery. The function of knee joint, the incidence rate of anterior knee pain and visual analogous scale score before and after operation were compared. RESULTS AND CONCLUSION:After 6 and 12 months of total knee arthroplasty, WOMAC osteoarthritis index was significantly lower and HSS score was significantly higher than those before surgery (P<0.05). At 12 months post-operation, the incidence rate of anterior knee pain was 11.3%, which was significantly lower than the preoperative rate (94.5%) (P<0.05). At 12 months post-surgery, visual analogous scale scores were also significantly lower than the preoperative score (P<0.05). Total knee replacement without resurfacing of the patel a can effectively improve knee joint function in knee osteoarthritis or rheumatoid arthritis patients, ameliorate the symptoms of anterior knee pain, has a good clinical effect within short term post-operation. The middle-and long-term effects need further exploration.
6.Effects of early application of Tuina treatment on quadriceps surface myoelectricity in patients after total knee arthroplasty: a randomized controlled trial.
Nianhong WANG ; Juntao YAN ; Wuquan SUN ; Yongshan HU ; Jun XIA ; Licheng WEI ; Jie JIA ; Guilin OUYANG ; Yong HE ; Yanming GUO ; Jie XU
Journal of Integrative Medicine 2012;10(11):1247-53
Total knee replacement surgery is commonly used in end-stage diseases of the knee. It is important for improving surgical efficacy and patient satisfaction by promoting early rehabilitation of patients and improving knee function.
7.Effects of Chinese herbal medicine Qianggu Capsule on patients with rheumatoid arthritis-induced osteoporosis: a report of 82 cases.
Guilin OUYANG ; Xiaohui FENG ; Lianbo XIAO ; Zheng HUANG ; Qing XIA ; Fei ZHU
Journal of Integrative Medicine 2012;10(12):1394-9
Rheumatoid arthritis (RA) is a kind of chronic autoimmune disease and osteoporosis is one of its complications.
8.The experimental study on the effect of rhTNFR:Fc and methtotrexate-rhTNFR:Fc on joint destruction of collagen-induced arthritis rat
Junlin HU ; Guilin OUYANG ; Huali GAO ; Ningli LI ; Zhiming HUANG ; Zheng HUANG ; Jun XIE ; Baihua SHEN ; Li WANG ; Lianbo XIAO
Chinese Journal of Rheumatology 2011;15(12):843-845
Objective This study is aimed to explore the effect of rhTNFR:Fc and methotrexate (MTX)-rhTN FR:Fc on joint destruction of collagen-induced arthritis ( CIA ) rat by establishing CIA rat model which imitates pathogenic factors of rheumatoid arthritis (RA).Methods CIA rat model were developed by subcutaneous injection of bovine type Ⅱ collagen.The rats with inflammation scores of two or above were randomly divided into four groups:the sterilized water treatment group (0.4 ml/w,intra-peritoneal injection),the MTX treatment group (1 mg/w,intra-peritoneal injection),the rhTNFR:Fc treatment group(0.8 mg Biw,intra-peritoneal injection),the MTX + rhTNFR:Fc treatment group (MTX 1 mg/w and rhTNFR:Fc 0.8 mg Biw,intraperitoneal injection).After treatment for 8 weeks,the rats were sacrificed and took the ankle radiography.Micro-CT scan of proximal tibia was performed and hard-tissue slices were made,and then the ankle's bone damage of each group was observed in order to evaluate trabecular variation and bone quantity changes of proximal tibia.Statisstical analysis was conducted with ANK-q test.Results After treatment for 8 weeks,the percentage of trabecular area and the trabecular number of the rhTNFR:Fc treatment group and the MTX-rhTNFR:Fc treatment were [(29.1±0.3)%,(26.7±0.6)%,(4.4±0.5)/mm,(4.0±0.6)/mm] (P<0.01),which were evidently higher than the sterilized water treatment group and MTX treatment group (P<0.01).The trabecular separation of Etanercept treatment group and MTX-rhTNFR:Fc group was obviously less than the sterilized water treatment group and MTX treatment group [(12.9±0.5)%,(13.2±0.4)% vs (2.0±0.3)/mm,(2.2t0.2)/mm] (P<0.01).Conclusion rhTNFR:Fc and MTX-rhTNFR:Fc can remarkably inhibit joint destruction of CIA rat.And their effect on inhibiting of inflammation and increasing peri-articular bone quantity.In addition,they are effective on inhibiting the reduction of local trabecular structure and increase of trabecular separation.
9.Effects of Tuina and Chinese patent drug Shuxuetong injection on deep venous thrombosis and functional rehabilitation after total knee arthroplasty.
Junlin HU ; Guilin OUYANG ; Dapeng HAN ; Qing XIA ; Yong HE ; Zheng HUANG ; Fei ZHU ; Songtao SUN
Journal of Integrative Medicine 2011;9(10):1088-93
To evaluate the efficacy of Tuina and Chinese patent drug Shuxuetong injection in preventing patients undergoing total knee arthroplasty from deep venous thrombosis and in functional rehabilitation.
10.Primary total knee arthroplasty in treatment of stiff knees
Yong HE ; Guilin OUYANG ; Lianbo XIAO ; Junlin HU ; Qing XIA ; Zheng HUANG ; Dapeng HAN ; Fei ZHU ; Songtao SUN
Chinese Journal of Orthopaedics 2010;30(12):1175-1180
Objective To evaluate the outcome of primary total knee arthroplasty (TKA) in treatment of stiff knee, and discuss the key points of operative technique and rehabilitation. Methods From February 2005 to April 2009, 23 patients with 34 stiff knees were treated with primary TKA. The study included 3 males (4 knees) and 20 females (30 knees), with the mean age of 56.9 years. Primary disease of the patients included rheumatoid arthritis (26 knees in 15 cases) and osteoarthritis (8 knees in 8 cases). Varus deformity was found in 10 knees (5°-15°), and valgus was found in 5 knees (5°-10°). Evaluations included preoperative and postoperative range of motion (ROM) measurement, hospital for special surgery knee score (HSS), blood loss, operative time and assessment of postoperative complications. Results All patients were followed up. The mean follow-up time was 32.2 (range, 24 to 40) months. At the final follow-up visit, the HSS score increased from 42.9±5.2 preoperatively to 85.7±4.3, the range of motion increased from 42.6°±5.7° preoperatively to 89.2°±10.5°. Sixteen knees in 12 cases underwent manipulation at 3 to 8 weeks postoperatively for unsatisfied ROM, but ROM was still less than 90° in 8 knees at the last follow-up. The average blood loss were (632.4±180.2) ml in first 24 hours (450-850 ml) and the operative time were (98.1±18.6) min (80-150 min). Deep venous thrombosis was found in 3 patients. All the symptoms relieved after anticoagulant therapy. Postoperative varus deformity was seen in one patient, but the function of knee was good. No revision was needed. Conclusion Primary total knee arthroplasty is reliable method in treatment of stiff knees. Sufficient soft tissue release during the operation, postoperative muscle strength exercise and essential manipulation are key points for satisfactory outcomes.


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