1.BMP9 Regulates Osteogenic/Odontogenic Differentiation of Immortalized Stem Cells from the Apical Papilla via the ERK5 Pathway
Journal of China Medical University 2017;46(6):527-531
Objective The aim of this study was to investigate the effects of the ERK5 pathway on bone morphogenetic protein?9(BMP9)?regu?lated osteogenic/odontogenic differentiation of immortalized stern cells from the apical papilla(iSCAP). Methods BMP9 was introduced into the iSCAP by using recombinant adenoviruses,and the P?ERK5 protein expression was measured via western blotting. Then,the osteogenic/odontoblas?tic changes were analyzed by alkaline phosphatase(ALP)staining and Alizarin red staining,and the expression of osteogenic/odontoblast?associat?ed genes,such as Runx2,OCN,OPN,and DMP1 was measured by RT?PCR. Results BMP9 could up?regulate the phosphorylation of ERK5 in iSCAP. After using BIX02189,which was an inhibitor of ERK5,the phosphorylation of ERK5;the activity of ALP;the expression of Runx2, OCN,OPN,and DMP1;and the calcium deposition were all significantly inhibited. Conclusion The ERK5 signaling pathway plays an important role in BMP9?regulated osteogenic/odontogenic differentiation of iSCAP.
2.Metformin and rosiglitazone maleate tablets ameliorate insulin resistance and hyperandrogenism in obese and nonobese women with polycystic ovarian syndrome
Liangyan WU ; Lingjiao LIU ; Shan WANG ; Minxiang LEI ; Jing WU
Chinese Journal of Endocrinology and Metabolism 2014;30(12):1092-1096
Objective To evaluate the therapeutic effects of metformin hydrochloride and rosiglitazone maleate tablets on insulin resistance and androgen concentration in obese and nonobese women with polycystic ovarian syndrome (PCOS).Methods Seventy women with PCOS were enrolled into this study according to the diagnostic criteria of Rotterdam conference (2003).The women with PCOS were divided into the over weight/obese group (body mass index ≥ 25 kg/m2,n =34) and the nonobese group (body mass index<25 kg/m2,n =36).All women with PCOS took metformin hydrochloride and rosiglitazone maleate tablets twice daily for 3 months.The following indexes were measured before and after the treatment:height,weight,waist circumference,hip circumference,fasting plasma glucose,fasting plasma insulin,luteinizing hormone (LH),follicle stimulating hormone (FSH),total testosterone,free testosterone,follicular number and ovarian area,body mass index,waist to hip ratio,and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated.Results (1) Compared with the nonobese group,dramatic increases in HOMA-IR and follicle number were observed in over weight/obese group(P<0.05),while LH,LH/FSH,total testosterone,free testosterone showed no significant difference between two groups.(2) After the treatment with metformin hydrochloride and rosiglitazone maleate tablets,weight,body mass index,fasting plasma glucose,fasting plasma insulin,HOMA-IR significantly decreased in two groups (P < 0.05).There were also significant declines of LH,LH/FSH,free testosterone,ovarian area,follicular number,especially in the over weight/ obese women with PCOS (P<0.05),while total testosterone and FSH did not change significantly.(3) The incidence of gastrointestinal adverse reactions in nonobese and over weight/obese group was 9.3% and 6.3% respectively,and no liver toxicity,edema,hypoglycemia and other adverse reactions was observed during treatment.Conclusion Compared with the nonobese group,there were severer insulin resistance and more marked polycystic change of ovary in over weight/obese women with PCOS,while total testosterone and free testosterone showed no significant difference between two gruops.Metformin hydrochloride and rosiglitazone maleate tablets can ameliorate insulin resistance and polycystic ovary,and also reduce body mass index and free testosterone in women with PCOS particularly in the over weight/obese individuals.
3.Serum Levels of Hepatocyte Growth Factor and Granulocyte Macrophage-Colony Stimulating Factor in Patients with Psoriasis
Bing XU ; Yonggang WANG ; Wei WU ; Lingjiao WU
Chinese Journal of Dermatology 1995;0(03):-
Objective To investigate the serum levels of hepatocyte growth factor (HGF) and granulocyte macrophage-colony stimulating factor (GM-CSF) in patients with psoriasis. Methods Serum samples were collected from 68 patients with psoriasis vulgaris and 42 healthy controls. The serum concentrations of HGF and GM-CSF were measured by a dual antibody sandwich enzyme-linked immunosorbent assay (ELISA). Clinical severity of psoriasis vulgaris was assessed by psoriasis area and severity index (PASI) score. Results Serum concentration of HGF of patients with psoriasis vulgaris in progressive stage (653.35 ? 109.26 pg/mL) was significantly higher than that of the normal controls (353.85 ? 162.63 pg/mL) (P 0.05). The serum concentration of GM-CSF was significantly higher in the patients with psoriasis vulgaris of progressive stage (115.95 ? 25.72 pg/mL) than that in the patients of stable stage (68.28 ? 24.22 pg/mL) (P
4.Regulation Mechanism and Significance of TCMBu-Shen Gu-Jin Prescription on IL-1 and TNF-αof Knee Osteoarthritis
Chong ZHANG ; Hengshu WANG ; Lingjiao WANG ; Chunli ZHANG ; Yun HUANG ; Zhongqiu WU
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(6):1198-1202
This study was aimed to observe the effect of traditional Chinese medicine (TCM)Bu-Shen Gu-Jin Prescription (BSGJP) on the expression and action mechanism of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-α) in knee osteoarthritis (KOA) rabbit model. A total of 76 8-month healthy male New Zealand white rabbits were randomly divided into the control group, model group, TCM BSGJP group and western medicine group, with 19 rabbits in each group. Except the control group, improved Hulth modeling method was used in the animal model establishment. After 8-week consecutive medication, the serum, part of the synovial membrane tissues on the anterior side of the knee joint, articular cartilage and subchondral bone of the medial condyle of the femur were collected. Enzyme-linked immunosorbent assay (ELISA) was used in the content determination of IL-1 and TNF-α. The results showed that the narrowing of the joint space of the western medicine group were in between the model group and the TCM BSGJP group with obvious osteophyte formation. The TCM BSGJP group had slight narrowing of the joint space, mild rough of the articular cartilage surface, and slight osteophyte formation. The contents of IL-1 and TNF-α in the model group were higher than than of the control group (P < 0.01). Both medication groups were lower than the model group (P < 0.01). There was no significant difference between the two medication groups. It was concluded that BSGJP effectively reduced the secretion of IL-1 and TNF-α, delayed the deterioration of cartilage, which provided scientific experimental evidences for the clinical applications.
5.Inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis ;of human lung cancer xenografts in nude mice
Dongchang WANG ; Lingchan WANG ; Lingjiao WANG ; Gang CHEN ; Yunxia ZHAO ; Zhifang ZHAO ; Yahua LI
Chinese Journal of Oncology 2016;38(5):340-345
Objective To evaluate the inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung adenocarcinoma xenografts in nude mice, and to explore its possible mechanisms. Methods Human lung cancer A549 cells were injected into Bal B/c nude mice subcutaneously. Twenty?eight healthy male nude mice were randomly divided into 4 groups:the control group, imrecoxib group, lobaplatin group and imrecoxib combined with lobaplatin group. Each group was treated with appropriate drugs and the tumor size was measured every five days. The expression of ezrin and E?cadherin protein was detected by immunohistochemistry and flow cytometry. Ezrin and E?cadherin mRNA were detected by real?time PCR. Results The tumor inhibition rates of imrecoxib group, lobaplatin group and combination group were 36.7%, 54.6% and 69.2%, respectively. The tumor volumes of imrecoxib group [(905.33±113.31) mm3] and combination group [(507.74±77.50) mm3] were significantly lower than that of the control group (1355.33±189.04) mm3(P<0.05), and the tumor weights were significantly reduced [(1.13±0.14) g, (0.63±0.10) g respectively] vs. (1.69±0.24) g (P<0.05). The expressions of ezrin protein and mRNA in the imrecoxib group and combined treatment group were significantly lower than that of the control group (136.53±35.52, 74.72±19.48 vs. 175.62±21.16 for protein expression level;0.54± 0.03, 0.36±0.03 vs. 1.02±0.02 for mRNA expression level, respectively, P<0.05 for both), while the expression of E?cadherin protein and mRNA in the imrecoxib group and combined treatment group was significantly higher than that of the control group ( 253. 78 ± 38. 87, 308. 94 ± 24. 67 vs. 213. 66 ± 30. 31 for protein expression level;2.19±0.02, 3.02±0.02 vs. 1.05±0.03 for mRNA expression level, respectively, P<0.05 for both) . There was a significant negative correlation between ezrin protein and E?cadherin protein (r=-0.737, P<0.01), as well as between ezrin mRNA and E?cadherin mRNA (r=-0.977, P<0.01). Conclusions Administration of imrecoxib combined with lobaphatin has inhibitory effects on the growth of non?small cell lung cancer xenografts and lymph node metastasis via down?regulated ezrin and upregulated E?cadherin. Imrecoxib and lobaplatin have a synergistic antitumor effect.
6.Inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis ;of human lung cancer xenografts in nude mice
Dongchang WANG ; Lingchan WANG ; Lingjiao WANG ; Gang CHEN ; Yunxia ZHAO ; Zhifang ZHAO ; Yahua LI
Chinese Journal of Oncology 2016;38(5):340-345
Objective To evaluate the inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung adenocarcinoma xenografts in nude mice, and to explore its possible mechanisms. Methods Human lung cancer A549 cells were injected into Bal B/c nude mice subcutaneously. Twenty?eight healthy male nude mice were randomly divided into 4 groups:the control group, imrecoxib group, lobaplatin group and imrecoxib combined with lobaplatin group. Each group was treated with appropriate drugs and the tumor size was measured every five days. The expression of ezrin and E?cadherin protein was detected by immunohistochemistry and flow cytometry. Ezrin and E?cadherin mRNA were detected by real?time PCR. Results The tumor inhibition rates of imrecoxib group, lobaplatin group and combination group were 36.7%, 54.6% and 69.2%, respectively. The tumor volumes of imrecoxib group [(905.33±113.31) mm3] and combination group [(507.74±77.50) mm3] were significantly lower than that of the control group (1355.33±189.04) mm3(P<0.05), and the tumor weights were significantly reduced [(1.13±0.14) g, (0.63±0.10) g respectively] vs. (1.69±0.24) g (P<0.05). The expressions of ezrin protein and mRNA in the imrecoxib group and combined treatment group were significantly lower than that of the control group (136.53±35.52, 74.72±19.48 vs. 175.62±21.16 for protein expression level;0.54± 0.03, 0.36±0.03 vs. 1.02±0.02 for mRNA expression level, respectively, P<0.05 for both), while the expression of E?cadherin protein and mRNA in the imrecoxib group and combined treatment group was significantly higher than that of the control group ( 253. 78 ± 38. 87, 308. 94 ± 24. 67 vs. 213. 66 ± 30. 31 for protein expression level;2.19±0.02, 3.02±0.02 vs. 1.05±0.03 for mRNA expression level, respectively, P<0.05 for both) . There was a significant negative correlation between ezrin protein and E?cadherin protein (r=-0.737, P<0.01), as well as between ezrin mRNA and E?cadherin mRNA (r=-0.977, P<0.01). Conclusions Administration of imrecoxib combined with lobaphatin has inhibitory effects on the growth of non?small cell lung cancer xenografts and lymph node metastasis via down?regulated ezrin and upregulated E?cadherin. Imrecoxib and lobaplatin have a synergistic antitumor effect.
7.Intervention and therapeutic effect of siRNA-HDAC5 on abnormal histone modification in non-obese diabetic mice.
Lin OUYANG ; Yanfei WANG ; Lingjiao LIU ; Youming PENG ; Can HOU
Journal of Central South University(Medical Sciences) 2015;40(5):464-470
OBJECTIVE:
To evaluate therapeutic eff ect of siRNA-HDAC5 on non-obese diabetic (NOD) mice by using small interference RNA (siRNA) technique to knock down the expression of HDAC5 in spleen CD4+ T cells.
METHODS:
NOD mice, 12-weeks old, were randomly divided into 3 groups and were given normal saline, siRNA-Control or siRNA-HDAC5 through caudal vein injection. The spleens and other samples were collected at the 18th, 24th or 30th week. The blood glucose was tested by blood glucose meter. The urinary albumin and serum levels of IL-1, IL-6, IL-18, and TNF-α were detected by ELISA. The mRNA levels of CD11a, CCR5, and CX3CR1 in spleen CD4+ T cells were measured by quantitative Real-time PCR. The HDAC5 protein level in spleen CD4+ T cell was detected by Western blot.
RESULTS:
Compared with the control group, the siRNA-HDAC5 group showed a significant decrease in blood glucose, urine albumin excretion rate, serum cytokine and the mRNA levels of CD11a, CCR5, and CX3CR1, consist with the decrease in protein level of HDAC5.
CONCLUSION
Inhibition of HDAC5 expression in NOD mice could effectively alleviate the onset and development of kidney damage caused by diabetes.
Animals
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CD11a Antigen
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metabolism
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CD4-Positive T-Lymphocytes
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metabolism
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CX3C Chemokine Receptor 1
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Cytokines
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blood
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Diabetes Mellitus, Experimental
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genetics
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therapy
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Enzyme-Linked Immunosorbent Assay
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Histone Code
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Histone Deacetylases
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genetics
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Mice
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Mice, Inbred NOD
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RNA, Messenger
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metabolism
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RNA, Small Interfering
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genetics
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therapeutic use
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Random Allocation
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Real-Time Polymerase Chain Reaction
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Receptors, CCR5
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metabolism
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Receptors, Chemokine
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metabolism
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Spleen
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cytology
8.Effect of Anastrozole on Sex Hormone Levels and MCF-7 Cell Inhibition in Postmenopausal Women with Breast Cancer
Lingjiao FENG ; Danping WANG ; Weifang WU ; Haiqin CHEN
China Pharmacist 2017;20(10):1809-1812
Objective:To investigate the effect of anastrozole on sex hormone levels and michigan cancer foundation-7 ( MCF-7 ) cell inhibition in postmenopausal women with breast cancer. Methods: Totally 80 women with breast cancer were selected. Among them, 40 cases of patients received the routine management and tamoxifen treatment were included into the control group, and another 40 cases of patients received the routine management and anastrozole treatment were included into the observation group. The changes of sex hormone levels, effects and adverse drug reactions of two groups were compared between basetine and three months after treat-ment, meanwhile, the incidence of MCF-7 cell inhibition between two groups. Results:After treatment, the levels of estradiol( ER) , progesterone(PR) and luteotropic hormone(LH) were lower than baselime, however, the level of testosterone was contrary(P <0. 05). Meanwhile, the level of ER, PR and LH in control group were lower than baselime however, the level of testosterone was cont-ray (P<0. 05). The incidence of MCF-7 cell inhibillion between two grugs at time 72 h were higher than the 48 h, the incedence of MCF-7 cell inhibition in observation group were significantly higher than control groups at time 48 h and 72 h (P<0. 05). The rate of total effective in control group(45. 0%) was lower than the observation group(70. 0%)(P>0. 05). There was no significant differente in the micidence of adverse reactions. Conclusion:Anastrozole used for postmenopausal women with breast cancer has significant effi-cacy, high safety and promising inhibitory effect on MCF-7 cell. It can effectively adjust sex hormone level, reduce occurrence and transfer risks of breast cancer.
9.Effect of Anastrozole on Sex Hormone Levels and MCF-7 Cell Inhibition in Postmenopausal Women with Breast Cancer
Lingjiao FENG ; Danping WANG ; Weifang WU ; Haiqin CHEN
China Pharmacist 2017;20(10):1809-1812
Objective:To investigate the effect of anastrozole on sex hormone levels and michigan cancer foundation-7 ( MCF-7 ) cell inhibition in postmenopausal women with breast cancer. Methods: Totally 80 women with breast cancer were selected. Among them, 40 cases of patients received the routine management and tamoxifen treatment were included into the control group, and another 40 cases of patients received the routine management and anastrozole treatment were included into the observation group. The changes of sex hormone levels, effects and adverse drug reactions of two groups were compared between basetine and three months after treat-ment, meanwhile, the incidence of MCF-7 cell inhibition between two groups. Results:After treatment, the levels of estradiol( ER) , progesterone(PR) and luteotropic hormone(LH) were lower than baselime, however, the level of testosterone was contrary(P <0. 05). Meanwhile, the level of ER, PR and LH in control group were lower than baselime however, the level of testosterone was cont-ray (P<0. 05). The incidence of MCF-7 cell inhibillion between two grugs at time 72 h were higher than the 48 h, the incedence of MCF-7 cell inhibition in observation group were significantly higher than control groups at time 48 h and 72 h (P<0. 05). The rate of total effective in control group(45. 0%) was lower than the observation group(70. 0%)(P>0. 05). There was no significant differente in the micidence of adverse reactions. Conclusion:Anastrozole used for postmenopausal women with breast cancer has significant effi-cacy, high safety and promising inhibitory effect on MCF-7 cell. It can effectively adjust sex hormone level, reduce occurrence and transfer risks of breast cancer.
10.An investigation of iodine level in drinking water and children iodine nutritional status in Chaoyang, Beijing in 2017
Yan LIANG ; Jianxin MA ; Lingjiao FU ; Zheng ZHANG ; Shuo WANG ; Jinming WEI
Chinese Journal of Endemiology 2019;38(3):227-230
Objective In order to know the baseline data of water iodine and the iodine nutritional status of 8-10 years old children in Chaoyang District of Beijing,to evaluate the current status of iodine deficiency disorders so as to provide a basis for taking targeted preventive measure and adjusting the intervention strategies scientifically.Methods Multi-stages sampling method was used to select drinking water samples from 43 subdistricts or townships in Chaoyang,and the water iodine content in the drinking water was determined.A cluster sampling method was applied to select 8-10 years old children from primary schools in 5 subdistricts or townships,and the iodine contents of urine and salt were determined.And B ultrasonic examination was carried out for diagnosis of thyroid disease.Results The median iodine content of drinking water in Chaoyang was 4.85 μg/L,the iodine content of self-provided wells (5.65 μg/L) was higher than that of municipal water (3.80 μg/L,Z =-3.469,P < 0.05).The coverage rate of iodized salt was 88.06% (177/201) and the qualified rate of iodized salt was 81.59% (164/ 201).The median urinary iodine was 165.00 μ g/L,median urinary iodine in boys (174.00 μg/L) was higher than that of girls (146.00 μg/L Z =-2.434,P < 0.05).The goiter rate diagnosed by B ultrasound was 1.49% (3/201),the thyroid nodule rate was 24.88% (50/201).Conclusions The iodine content of drinking water in the Chaoyang District is low,and it is still in the external environment of iodine deficiency (< 10 μg/L).The 8-10 years old children of Chaoyang show a good iodine nutritional status,however,neither the coverage rate nor the qualified rate of iodized salt has reached the standard of elimination of iodine deficiency disorders,and scientific iodine can not be ignored.