1.Clinical characteristics and prognosis of ovarian juvenile granulosa cell tumors
Xiao MA ; Gongyi ZHANG ; Zhe LI
Chinese Journal of Obstetrics and Gynecology 2025;60(1):34-45
Objective:To analyze the clinical characteristics, treatments, and prognosis of patients with ovarian juvenile granulosa cell tumor (JGCT).Methods:Clinical and pathological data, and follow-up information of 34 patients diagnosed with JGCT from 2000 to 2021 were collected from the surveillance, epidemiology, and end results (SEER) database. A retrospective analysis was conducted to summarize the patients′ clinical and pathological characteristics, treatments, and prognosis. Propensity score matching (PSM) was used to match the JGCT cases with adult granulosa cell tumor (AGCT) cases in SEER database. A total of 96 patients with ovarian granulosa cell tumor (OGCT), including 32 cases of JGCT and 64 cases of AGCT, were enrolled in a matched cohort analysis. Univariate and multivariate Cox regression analysis were performed on the matched cohort to explore the risk factors for overall survival. Kaplan-Meier curves and the log-rank test were used to compare the survival outcomes between JGCT and AGCT.Results:(1) The median age at diagnosis for the 34 JGCT patients was 19.5 years (ranged: 1-48 years), with 3 patients aged ≤10 years, 16 patients aged 11-20 years, 11 patients aged 21-30 years, and 4 patients aged >30 years. Tumors originated unilaterally in 33 patients, with only 1 case originating bilaterally. The maximum tumor diameter was recorded in 26 patients, with a median size of 12.4 cm (ranged: 3.5-40.0 cm). According to the 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system, 19 patients were diagnosed with stage Ⅰ (including 10 cases with stage Ⅰa and 9 cases with stage Ⅰc), 4 patients with stage Ⅱ, 8 patients with stage Ⅲ, and 3 patients with stage Ⅳ. Two patients did not undergo surgery for the resection of lesions. Stage Ⅰ patients (15/19) underwent fertility-sparing surgery, while stage Ⅱ-Ⅲ patients underwent either fertility-sparing surgery or cytoreductive surgery (6 cases each). Stage Ⅳ patients underwent cytoreductive surgery (2 cases). Lymph node dissection was performed in 10 patients, among which only 1 patient with positive lymph nodes metastasis. None of the 34 patients received radiotherapy, while 18 patients received adjuvant chemotherapy (included neoadjuvant chemotherapy and postoperative adjuvant chemotherapy). The proportion of stage Ⅰ patients receiving adjuvant chemotherapy was relatively low, with only 4 out of 19 patients (including 2 out of 10 cases for stage Ⅰa and 2 out of 9 cases for stage Ⅰc). The proportions of patients receiving adjuvant chemotherapy for stages Ⅱ, Ⅲ and Ⅳ were 3 out of 4 cases, 8 out of 8 cases, and 3 out of 3 cases, respectively. The follow-up ended in December 2021, with 20 patients alive and 14 dead. The survival rate for ovarian JGCT patients was 59% (20/34). Among them, the survival rate for stage Ⅰ patients was 16/19, while for stage Ⅱ-Ⅳ patients, it was 4/15; there was a statistically significant difference ( P=0.002). Among stage Ⅱ-Ⅲ patients, the survival rate at the end of follow-up was 1/6 for those who underwent fertility-sparing surgery, compared to 3/6 for those who underwent cytoreductive surgery ( P=0.546). (2) For the 96 OGCT patients after matching using the PSM method, 64 ovarian AGCT patients had 5 deaths and 59 survivors during the follow-up period, the survival rate was 92% (59/64) at the end of follow-up. In contrast, among the 32 ovarian JGCT patients, 13 died and 19 survived, resulting in a survival rate of 59% (19/32) at the end of follow-up, which was statistically significant difference for the AGCT group ( P<0.001). Univariate Cox analysis revealed that histology, extent of surgery, chemotherapy, postoperative tumor residual status, and stage all significantly affected the survival outcomes of OGCT patients (all P<0.05). Multivariate Cox analysis revealed that variables with significant statistical differences were histology and stage. The median survival time for JGCT patients was 126 months, while AGCT patients median survival time was not reached with a statistically significant between the two groups ( P<0.001). Conclusions:Ovarian JGCT predominantly occur in adolescents and young women. Lymph node metastasis is relatively rare, and treatment primarily involves surgery and adjuvant chemotherapy. Most ovarian JGCT patients are diagnosed at stage Ⅰ, with a favorable prognosis. Fertility-preserving surgery is recommended, involving salpingo-oophorectomy on the affected side plus comprehensive staging surgery, or a second surgery to achieve comprehensive staging. For stage Ⅱ-Ⅳ ovarian JGCT patients, the prognosis is relatively poor, and fertility-preserving surgery should be considered with caution. The prognosis of ovarian JGCT patients is worse than that of ovarian AGCT patients.
2.Application of pedicle or perforator flaps transfer in the stage Ⅰ tissue defect repair after vulvar cancer surgery
Yufen CHEN ; Ping BAI ; Yuqiao ZHAO ; Linan CONG ; Nan LI ; Jing ZUO ; Gongyi ZHANG ; Yangchun SUN ; Shumin LI ; Qiang LI
Chinese Journal of Obstetrics and Gynecology 2025;60(2):136-143
Objective:To investigate the application of pedicled or perforator flaps transfer in the stage Ⅰ tissue defect repair after vulvar cancer surgery.Methods:From January 2005 to December 2023, 20 patients with vulvar cancer who underwent extensive episiectomy or extended episiectomy±inguinal lymph node resection+vulvar defect flap transfer were collected in Huanxing Cancer Hospital of Chaoyang District and Cancer Hospital and Peking Union Medical College, Chinese Academy of Medical Sciences. The survival status, appearance structure, sexual function satisfaction, tumor recurrence, and survival were analyzed.Results:(1) The median age of the 20 patients was 59 years (ranged: 29-73 years). There were 14 patients with recurrence and 6 patients with initial treatment. Pathological types: 14 cases of squamous cell carcinoma, 4 cases of Paget′s disease, 1 case of malignant melanoma, 1 case of adenoid cystic carcinoma (salivary gland type carcinoma). (2) Among the 20 patients, 6 cases underwent extensive episiotomy and 14 underwent extended episiotomy (1 of them underwent extensive excision of inguinal masses). Simultaneous inguinal lymphadenectomy (or dissection) were performed in 11 cases, including 7 cases of bilateral inguinal lymph node resection (or dissection) and 4 cases of unilateral inguinal lymph node resection (or dissection). Flap source: pedicled flap in 12 cases, perforator flap in 8 cases. All the 20 patients were removed at 10-14 days after operation, and all of them survived with rosy skin color and good elasticity. Seventeen cases of transferred flaps healed at stage Ⅰ, 2 cases healed at about 6 weeks due to incision leakage, and 1 case healed at 6 weeks after incision infection debridement. Six months after the operation, 2 cases felt that the pubic mound was thick and swollen. The other 18 cases showed vulva fullness and elasticity, no displacement of urethral opening, no deviation of urethra during urination, no stenosis of vaginal opening, no vulvar scar pain. In addition to 1 unmarried 29-year-old patient and 6 patients over 65 years old who had no sexual life before and after surgery, the other 13 patients had normal sexual life after surgery. (3) The follow-up period were 6 to 100 months, and 9 cases (45%, 9/20) relapsed during the follow-up period. There were 5 deaths (25%, 5/20), who were due to recurrence of vulvar cancer. The 5-year survival rate of 20 patients was 75%, including 83% in 6 patients with initial treatment and 71% in 14 patients with recurrence and reoperation.Conclusions:The combination of flap transfer for episioplasty with vulvar cancer surgery does not affect the wound healing. Because the external structure of the vulva is repaired, it could effectively improve the local wound healing ability and improve the organ function, and has good clinical application value.
3.Clinical characteristics and prognosis of ovarian juvenile granulosa cell tumors
Xiao MA ; Gongyi ZHANG ; Zhe LI
Chinese Journal of Obstetrics and Gynecology 2025;60(1):34-45
Objective:To analyze the clinical characteristics, treatments, and prognosis of patients with ovarian juvenile granulosa cell tumor (JGCT).Methods:Clinical and pathological data, and follow-up information of 34 patients diagnosed with JGCT from 2000 to 2021 were collected from the surveillance, epidemiology, and end results (SEER) database. A retrospective analysis was conducted to summarize the patients′ clinical and pathological characteristics, treatments, and prognosis. Propensity score matching (PSM) was used to match the JGCT cases with adult granulosa cell tumor (AGCT) cases in SEER database. A total of 96 patients with ovarian granulosa cell tumor (OGCT), including 32 cases of JGCT and 64 cases of AGCT, were enrolled in a matched cohort analysis. Univariate and multivariate Cox regression analysis were performed on the matched cohort to explore the risk factors for overall survival. Kaplan-Meier curves and the log-rank test were used to compare the survival outcomes between JGCT and AGCT.Results:(1) The median age at diagnosis for the 34 JGCT patients was 19.5 years (ranged: 1-48 years), with 3 patients aged ≤10 years, 16 patients aged 11-20 years, 11 patients aged 21-30 years, and 4 patients aged >30 years. Tumors originated unilaterally in 33 patients, with only 1 case originating bilaterally. The maximum tumor diameter was recorded in 26 patients, with a median size of 12.4 cm (ranged: 3.5-40.0 cm). According to the 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system, 19 patients were diagnosed with stage Ⅰ (including 10 cases with stage Ⅰa and 9 cases with stage Ⅰc), 4 patients with stage Ⅱ, 8 patients with stage Ⅲ, and 3 patients with stage Ⅳ. Two patients did not undergo surgery for the resection of lesions. Stage Ⅰ patients (15/19) underwent fertility-sparing surgery, while stage Ⅱ-Ⅲ patients underwent either fertility-sparing surgery or cytoreductive surgery (6 cases each). Stage Ⅳ patients underwent cytoreductive surgery (2 cases). Lymph node dissection was performed in 10 patients, among which only 1 patient with positive lymph nodes metastasis. None of the 34 patients received radiotherapy, while 18 patients received adjuvant chemotherapy (included neoadjuvant chemotherapy and postoperative adjuvant chemotherapy). The proportion of stage Ⅰ patients receiving adjuvant chemotherapy was relatively low, with only 4 out of 19 patients (including 2 out of 10 cases for stage Ⅰa and 2 out of 9 cases for stage Ⅰc). The proportions of patients receiving adjuvant chemotherapy for stages Ⅱ, Ⅲ and Ⅳ were 3 out of 4 cases, 8 out of 8 cases, and 3 out of 3 cases, respectively. The follow-up ended in December 2021, with 20 patients alive and 14 dead. The survival rate for ovarian JGCT patients was 59% (20/34). Among them, the survival rate for stage Ⅰ patients was 16/19, while for stage Ⅱ-Ⅳ patients, it was 4/15; there was a statistically significant difference ( P=0.002). Among stage Ⅱ-Ⅲ patients, the survival rate at the end of follow-up was 1/6 for those who underwent fertility-sparing surgery, compared to 3/6 for those who underwent cytoreductive surgery ( P=0.546). (2) For the 96 OGCT patients after matching using the PSM method, 64 ovarian AGCT patients had 5 deaths and 59 survivors during the follow-up period, the survival rate was 92% (59/64) at the end of follow-up. In contrast, among the 32 ovarian JGCT patients, 13 died and 19 survived, resulting in a survival rate of 59% (19/32) at the end of follow-up, which was statistically significant difference for the AGCT group ( P<0.001). Univariate Cox analysis revealed that histology, extent of surgery, chemotherapy, postoperative tumor residual status, and stage all significantly affected the survival outcomes of OGCT patients (all P<0.05). Multivariate Cox analysis revealed that variables with significant statistical differences were histology and stage. The median survival time for JGCT patients was 126 months, while AGCT patients median survival time was not reached with a statistically significant between the two groups ( P<0.001). Conclusions:Ovarian JGCT predominantly occur in adolescents and young women. Lymph node metastasis is relatively rare, and treatment primarily involves surgery and adjuvant chemotherapy. Most ovarian JGCT patients are diagnosed at stage Ⅰ, with a favorable prognosis. Fertility-preserving surgery is recommended, involving salpingo-oophorectomy on the affected side plus comprehensive staging surgery, or a second surgery to achieve comprehensive staging. For stage Ⅱ-Ⅳ ovarian JGCT patients, the prognosis is relatively poor, and fertility-preserving surgery should be considered with caution. The prognosis of ovarian JGCT patients is worse than that of ovarian AGCT patients.
4.Application of pedicle or perforator flaps transfer in the stage Ⅰ tissue defect repair after vulvar cancer surgery
Yufen CHEN ; Ping BAI ; Yuqiao ZHAO ; Linan CONG ; Nan LI ; Jing ZUO ; Gongyi ZHANG ; Yangchun SUN ; Shumin LI ; Qiang LI
Chinese Journal of Obstetrics and Gynecology 2025;60(2):136-143
Objective:To investigate the application of pedicled or perforator flaps transfer in the stage Ⅰ tissue defect repair after vulvar cancer surgery.Methods:From January 2005 to December 2023, 20 patients with vulvar cancer who underwent extensive episiectomy or extended episiectomy±inguinal lymph node resection+vulvar defect flap transfer were collected in Huanxing Cancer Hospital of Chaoyang District and Cancer Hospital and Peking Union Medical College, Chinese Academy of Medical Sciences. The survival status, appearance structure, sexual function satisfaction, tumor recurrence, and survival were analyzed.Results:(1) The median age of the 20 patients was 59 years (ranged: 29-73 years). There were 14 patients with recurrence and 6 patients with initial treatment. Pathological types: 14 cases of squamous cell carcinoma, 4 cases of Paget′s disease, 1 case of malignant melanoma, 1 case of adenoid cystic carcinoma (salivary gland type carcinoma). (2) Among the 20 patients, 6 cases underwent extensive episiotomy and 14 underwent extended episiotomy (1 of them underwent extensive excision of inguinal masses). Simultaneous inguinal lymphadenectomy (or dissection) were performed in 11 cases, including 7 cases of bilateral inguinal lymph node resection (or dissection) and 4 cases of unilateral inguinal lymph node resection (or dissection). Flap source: pedicled flap in 12 cases, perforator flap in 8 cases. All the 20 patients were removed at 10-14 days after operation, and all of them survived with rosy skin color and good elasticity. Seventeen cases of transferred flaps healed at stage Ⅰ, 2 cases healed at about 6 weeks due to incision leakage, and 1 case healed at 6 weeks after incision infection debridement. Six months after the operation, 2 cases felt that the pubic mound was thick and swollen. The other 18 cases showed vulva fullness and elasticity, no displacement of urethral opening, no deviation of urethra during urination, no stenosis of vaginal opening, no vulvar scar pain. In addition to 1 unmarried 29-year-old patient and 6 patients over 65 years old who had no sexual life before and after surgery, the other 13 patients had normal sexual life after surgery. (3) The follow-up period were 6 to 100 months, and 9 cases (45%, 9/20) relapsed during the follow-up period. There were 5 deaths (25%, 5/20), who were due to recurrence of vulvar cancer. The 5-year survival rate of 20 patients was 75%, including 83% in 6 patients with initial treatment and 71% in 14 patients with recurrence and reoperation.Conclusions:The combination of flap transfer for episioplasty with vulvar cancer surgery does not affect the wound healing. Because the external structure of the vulva is repaired, it could effectively improve the local wound healing ability and improve the organ function, and has good clinical application value.
5.Preparation and characterization of curcumin nanomicelles and evaluation of in vitro hepatoprotective activity against alcohol liver disease
Luhui LI ; Guangping GENG ; Lei XU ; Zhikun ZHANG ; Xiaohui PU
China Pharmacy 2024;35(10):1203-1208
OBJECTIVE To prepare and characterize curcumin nanomicelles (hereinafter referred to as Cur/mPEG-PBLA micelles), and to evaluate the in vitro hepatoprotective activity against alcohol liver disease (ALD). METHODS Cur/mPEG-PBLA micelles were prepared with the dialysis method using methoxy-poly(ethylene glycol)-poly(β-benzyl-L-aspartate) (mPEG-PLGA) as the carrier. The appearance and microscopic morphology of Cur/mPEG-PBLA micelles were observed, and particle size, polydispersity index, Zeta potential, encapsulation efficiency and drug loading content were all detected. The in vitro release, pH stability, thermal stability, dilution stability, storage stability, plasma stability tests, and hemolysis experiments were all performed. The cell model of ALD was established with anhydrous ethanol intervention using human liver cancer cells and normal liver cells as objects, Cur reference solution as reference, to evaluate in vitro preventive and ameliorative effects of Cur/mPEG- PBLA micelles on ALD. RESULTS The prepared Cur/mPEG-PBLA micelles exhibited a pale-yellow milky light, with a spherical shape and uniform distribution. The average particle size was about 140 nm, and the polydispersity index was less than 0.3. Zeta potential was (-8.15±0.05) mV; the encapsulation efficiency was (73.26±3.16)%, and the drug loading content was (4.87± 0.42)%. The cumulative release of Cur reference substance was close to 80% at 10 h; the cumulative release of Cur/mPEG-PBLA micelles at 8 h was 28.94% and only 48.25% at 48 h. pH stability and thermal stability of Cur/mPEG-PBLA micelles were better than those of Cur reference solution; Cur/mPEG-PBLA micelles showed good dilution stability, storage stability and plasma stability, and would not cause hemolysis. Cur reference solution and Cur/mPEG-PBLA micelles had varying degrees of in vitro preventive and ameliorative effects on ALD in two types of cells; after 48 h of application, the above effects of Cur/mPEG-PBLA micelles were significantly better than those of Cur reference solution at the same mass concentration (P<0.05). CONCLUSIONS Cur/mPEG-PBLA micelles can improve pH stability and thermal stability of Cur, delayits degradation rate, and have better in vitro hepatoprotective activity against ALD.
6.Histological evaluation and analysis of intestinal flora in a rat model of colitis-cancer transformation induced by azoxymethane/dextran sulfate sodium
Xiunan WEI ; Dajuan SUN ; Junwei LIANG ; Jiahui LIU ; Gongyi LI ; Lili CHI
Acta Laboratorium Animalis Scientia Sinica 2024;32(11):1369-1378
Objective The aim of this study was to establish a rat model of inflammation-cancer transformation of inflammatory bowel disease(IBD)and to explore the associated characteristics of the intestinal flora.Methods Adult male Wistar rats were divided randomly into control and model groups(M1,M2,M3)with different dextran sulfate sodium(DSS)intervention cycles.Colitis-cancer transformation was induced in all rats in the model group by a single intraperitoneal injection of azoxymethane(AOM)combined with free drinking of DSS in different cycles,and disease activity index(DAI)scores were recorded.Rats in the M1,M2 and M3 groups were killed at the end of the first,second,and third cycles of DSS,respectively,and spleen and colon tissues and colon contents were collected.Histological damage and colon carcinogenesis were evaluated in each group using hematoxylin and eosin staining and transmission electron microscopy.Characteristic changes in the intestinal flora were analyzed by 16S rRNA sequencing.Results AOM/DSS administration significantly increased the DAI score,shortened the colon,and increased the spleen index.The intestinal mucosal barrier was progressively destroyed from groups M1 to M3,and the pathological score was gradually increased.Abnormal crypt foci,polyps,low-and high-grade intraepithelial neoplasia,and mucosal carcinoma appeared in turn,while the pathological process showed similar characteristics to carcinogenesis in human inflammatory bowel disease.Screening using 16S rRNA sequencing with two differential abundance testing tools,Wilcoxon and ALDEx2,indicated that changes in flora abundance represented by Bacteroidetes and Monoglobus may be involved in the progression of colitis-cancer transformation.The functions of the differential flora were mainly enriched in metabolic pathways,such as lipid and carbohydrate metabolism.Conclusions The current rat model induced by AOM/DSS can dynamically simulate the pathological characteristics of colitis-cancer transformation,accompanied by changes in the abundance of specific intestinal flora,which may be closely related to the metabolic pathways mediated by the flora.
7.Histological evaluation and analysis of intestinal flora in a rat model of colitis-cancer transformation induced by azoxymethane/dextran sulfate sodium
Xiunan WEI ; Dajuan SUN ; Junwei LIANG ; Jiahui LIU ; Gongyi LI ; Lili CHI
Acta Laboratorium Animalis Scientia Sinica 2024;32(11):1369-1378
Objective The aim of this study was to establish a rat model of inflammation-cancer transformation of inflammatory bowel disease(IBD)and to explore the associated characteristics of the intestinal flora.Methods Adult male Wistar rats were divided randomly into control and model groups(M1,M2,M3)with different dextran sulfate sodium(DSS)intervention cycles.Colitis-cancer transformation was induced in all rats in the model group by a single intraperitoneal injection of azoxymethane(AOM)combined with free drinking of DSS in different cycles,and disease activity index(DAI)scores were recorded.Rats in the M1,M2 and M3 groups were killed at the end of the first,second,and third cycles of DSS,respectively,and spleen and colon tissues and colon contents were collected.Histological damage and colon carcinogenesis were evaluated in each group using hematoxylin and eosin staining and transmission electron microscopy.Characteristic changes in the intestinal flora were analyzed by 16S rRNA sequencing.Results AOM/DSS administration significantly increased the DAI score,shortened the colon,and increased the spleen index.The intestinal mucosal barrier was progressively destroyed from groups M1 to M3,and the pathological score was gradually increased.Abnormal crypt foci,polyps,low-and high-grade intraepithelial neoplasia,and mucosal carcinoma appeared in turn,while the pathological process showed similar characteristics to carcinogenesis in human inflammatory bowel disease.Screening using 16S rRNA sequencing with two differential abundance testing tools,Wilcoxon and ALDEx2,indicated that changes in flora abundance represented by Bacteroidetes and Monoglobus may be involved in the progression of colitis-cancer transformation.The functions of the differential flora were mainly enriched in metabolic pathways,such as lipid and carbohydrate metabolism.Conclusions The current rat model induced by AOM/DSS can dynamically simulate the pathological characteristics of colitis-cancer transformation,accompanied by changes in the abundance of specific intestinal flora,which may be closely related to the metabolic pathways mediated by the flora.
9.Glomuvenous malformation: a clinicopathological analysis of 31 cases.
Q Y LIU ; W J BAO ; C X LI ; S XUE ; Y Z DING ; D K LIU ; B X MA ; F F FU ; L F KONG
Chinese Journal of Pathology 2023;52(10):1001-1005
Objective: To investigate the clinicopathological features of glomuvenous malformation (GVM). Methods: Thirty-one cases of GVM diagnosed at the Henan Provincial People's Hospital from January 2011 to December 2021 were collected. Their clinical and pathological features were analyzed. The expression of relevant markers was examined using immunohistochemistry. The patients were also followed up. Results: There were 16 males and 15 females in this study, with an average age of 11 years (range, 1-52 years). The locations of the disease included 13 cases in the limbs (8 cases in the upper limbs, 5 cases in the lower limbs), 9 cases in the trunks, and 9 cases in the foot (toes or subungual area). Twenty-seven of the cases were solitary and 4 were multifocal. The lesions were characterized by blue-purple papules or plaques on the skin surface, which grew slowly. The lumps became larger and appeared to be conspicuous. Microscopically, GVM mainly involved the dermis and subcutaneous tissue, with an overall ill-defined border. There were scattered or clustered irregular dilated vein-like lumens, with thin walls and various sizes. A single or multiple layers of relatively uniform cubic/glomus cells were present at the abnormal wall, with scattered small nests of the glomus cells. The endothelial cells in the wall of abnormal lumen were flat or absent. Immunohistochemistry showed that glomus cells strongly expressed SMA, h-caldesmon, and collagen IV. Malformed vascular endothelial cells expressed CD31, CD34 and ERG. No postoperative recurrence was found in the 12 cases. Conclusions: GVM is an uncommon type of simple venous malformation in the superficial soft tissue and different from the classical glomus tumor. Morphologically, one or more layers of glomus cells grow around the dilated venous malformation-like lumen, which can be combined with common venous malformations.
Male
;
Female
;
Humans
;
Child
;
Glomus Tumor/surgery*
;
Endothelial Cells/pathology*
;
Paraganglioma, Extra-Adrenal/pathology*
;
Immunohistochemistry
10.Effects of centellaasiatica granule on the expression of Smad 2/3, Smad 7 and collagen Ⅳ in the mesangial cells stably expressed TGF-β1.
Ji-Wei MA ; Hong-Tian WANG ; Hao-Fei LIU ; Lei-Peng DONG ; Yuan DING ; Ji-Qiong BAI ; Zhu ZHANG ; Li-Jie DONG
Chinese Journal of Applied Physiology 2018;34(2):122-125
OBJECTIVES:
Stably expressed transforming growth factor -beta 1(TGF-β1)MCs were obtained and the effects of centellaasiatica (CA) granule on the expressions of Smad 2/3, Smad 7 and collagen Ⅳ and the level of Smad 2/3 phosphorylation were observed.
METHODS:
Lipofectin method was used to transfect TGF-β1 vector into MC, and the stably expressed TGF-β1 cell lines were selected by G418. The cells were divided into three groups. Control group:normal MC + RPMI 1640 + 10% normal rat serum; TGF-β1 group:stably expressed TGF-β1 MC + RPMI 1640 + 10% normal rat serum; CA group:stably expressed TGF-β1 MC + RPMI 1640 + 10% rat serum containing high CA. The experiments were repeated for five times. The contents of TGF-β1 and collagen Ⅳ in the culture medium were detected with ELISA, the expressions of mRNA and protein of TGF-β1, Smad 2/3, Smad 7 and the level of Smad 2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot.
RESULTS:
The contents of TGF-β1 and collagen Ⅳ in the culture medium of stably-expressed TGF-β1 MC were increased significantly, and the CA could reverse the effects of TGF-β1. The expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation were increased significantly in TGF-β1 transfected MC, and CA could dramatically reduce the expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation. The high expression of TGF-β1 decreased the expression of Smad 7 mRNA and protein, and the CA could antagonize the effect of mRNA expression.
CONCLUSIONS
The MCs stably-expressed TGF-β1 can activate the TGF-β1/Smad signal pathway and increase the expression of collagen Ⅳ. CA can decrease the occurrence of diabetic nephropathy(DN) by reducing the production of collagen Ⅳ through inhibiting the TGF-β1/Smad signal pathway.
Animals
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Cells, Cultured
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Centella
;
chemistry
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Collagen Type IV
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metabolism
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Drugs, Chinese Herbal
;
pharmacology
;
Mesangial Cells
;
drug effects
;
metabolism
;
Rats
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Signal Transduction
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Smad Proteins
;
metabolism
;
Smad2 Protein
;
metabolism
;
Smad3 Protein
;
metabolism
;
Smad7 Protein
;
metabolism
;
Transforming Growth Factor beta1
;
metabolism

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