1.Protective Effect and Mechanism of Rebamipide on Injury of Human Colon Cancer Cell Line Caco-2 Induced by Aspirin
Fangcen YUAN ; Zhenyu ZHANG ; Zhaotao DUAN ; Zongdan JLANG
Chinese Journal of Gastroenterology 2015;(5):272-277
Background:With the development of capsule endoscopy,small intestinal injury induced by non-steroidal anti-inflammatory drugs( NSAIDs)has become an issue of growing concern. Although there are a variety of drugs used for NSAIDs-induced gastric mucosal injury,small intestinal injury caused by NSAIDs is lack of effective prevention and treatment modalities. Aims:To investigate the protective effect and possible mechanism of rebamipide on human colon cancer cell line Caco-2 injury induced by aspirin. Methods:In aspirin group,Caco-2 cells were treated with aspirin 10 mmol/L;in rebamipide group,Caco-2 cells were treated with aspirin and different concentrations of rebamipide(0. 1, 0. 5,1. 0 mmol/L),and a negative control group was established. Cell proliferation inhibition was measured by MTT assay. Cell apoptosis was determined by flow cytometry. Morphological changes of cells were observed under inverted phase contrast microscope. Permeability of cells was assessed by Transwell assay. Expressions of tight junction proteins occludin and zonula occluden-1(ZO-1),as well as mitogen activated protein kinase(MAPK)signaling pathway-associated proteins including extracellular signal-regulated kinase(ERK)1/2,phosphorylated ERK1/2(p-ERK1/2),p38,p-p38,c-Jun N-terminal kinase( JNK),and p-JNK,were determined by Western blotting. Results:Proliferation inhibition rate,apoptosis rate and permeability of Caco-2 cells in rebamipide 0. 1,0. 5,1. 0 mmol/L groups were significantly lower than those in aspirin group in a dose-dependent manner(P<0. 05). Injuries of Caco-2 cells were seen in aspirin group by inverted phase contrast microscope and rebamipide could reduce these injuries. Expressions of occludin,ZO-1 and p-JNK were significantly higher and expressions of p-p38 and p-ERK1/2 were significantly lower in rebamipide 0. 1,0. 5,1. 0 mmol/L groups than those in aspirin group in a dose-dependent manner(P<0. 05). Conclusions:Rebamipide have a protective effect against aspirin-induced Caco-2 cell injury,probably through regulating MAPK signaling pathway( inhibiting p38 and ERK1/2 phosphorylation,stimulating JNK phosphorylation),and subsequently up-regulating the expressions of tight junction proteins and decreasing the permeability of cells.
2.Protective effects and its mechanism of rebamipide on aspirin-induced injury in human gastric mucosal epithelium cells
Zhaotao DUAN ; Zhenyu ZHANG ; Hailu WU ; Fangcen YUAN ; Zongdan JIANG ; Bangshun HE ; Shukui WANG
Chinese Journal of Digestion 2014;34(7):453-457
Objective To investigate the protective effects and its mechanism of rebamipide on aspirin-induced injury in human gastric mucosal epithelium cells (GES-1).Methods GES-1 cells monolayer culture model was established in vitro.Then the cells were divided into negative control group,aspirin injured group and combination of rebamipide at different concentration (0.2,0.5,1.0 mrnol/L) and aspirin groups.The cell proliferation,the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) of each group were detected.The ultrastructural changes of each group were observed by transmission electron microscopy (TEM).The expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) at protein level in the cells of each group were detected by Western blot.Nrf2 interfering suppression test was performed and then the influence of Nrf2 small interfering RNA (siRNA) on the expression of HO-1 protein was observed.One-way analysis of variance was performed for comparison among multi-groups and t-test was used for comparison between the two groups.Results The cell viability of aspirin injured group and combination of rebamipide at different concentration (0.2,0.5,1.0 mmol/L) and aspirin groups were (49.56±3.88)%,(59.34±4.36) %,(70.79 ± 5.96) % and (86.07 ± 5.20) %,respectively,and the difference was statistically significant (F=30.634,P< 0.01).Compared with aspirin injured group,the content of MDA significantly lowered in combination of rebamipide at different concentration (0.2,0.5,1.0 mmol/L) and aspirin groups ((2.26±0.25) nrnol/rng vs (1.85±0.13) nmol/mg vs (1.62±0.11) nmol/mg vs (1.13±0.15) nmol/mg),and the difference was statistically significant (F=23.821,P<0.05).Compared with aspirin injured group,the activity of SOD significantly increased in combination of rebamipide at 0.5 and 1.0 mmol/L and aspirin groups ((8.49±0.89) U/rng vs (11.50±1.03) U/mg vs (13.74±0.76) U/mg),the difference was statistically significant (F=25.666,P<0.05).Under TEM,the cell ultrastrucmral was obviously inured in aspirin treated,while rebamipide could relieve the injury.The differences of relative expression quantity of Nrf2 and HO-1 at protein level among combination of rebamipide at 0.2,0.5 and 1.0 mmol/L and aspirin groups and aspirin injured group were statistically significant (0.35±0.04 vs 0.46± 0.05 vs 0.84±0.08 vs 0.15±0.02,0.72±0.09 vs 0.93±0.11 vs 1.29±0.14 vs 0.39±0.07,F=92.550and 38.235,both P<0.05).After transfected with Nrf2 siRNA,the expression of HO-1 was 0.38±0.04 in aspirin injured group and 0.62±0.08 in combination of rebamipide and aspirin group,which was lower than that before transfection (0.61 ± 0.05,1.33± 0.09),respectively.The differences were statistically significant (t =6.276 and 10.444,both P<0.05).Conclusion Rebamipide may activate Nrf2/HO-1 pathway and relieve aspiriwinduced oxidative stress in GF1 ceils.
3.The correlation between different smoking status and serum uric acid in a middle-aged male population
Jing FEI ; Yun LU ; Yang HUANG ; Feng LI ; Yinbo FENG ; Fangcen YUAN ; Mengqian ZHANG ; Cheng SONG ; Zhenhai SHEN
Chinese Journal of Geriatrics 2020;39(2):151-154
Objective:To explore the correlation between different smoking status and serum uric acid(SUA)in a middle-aged male in health check-up population.Methods:In this cross-sectional study, a total of 26701 middle-aged men who underwent health check-up in Taihu Sanatorium of Jiangsu Province from January 2014 to June 2015 were studied.The correlation between smoking status and SUA was analyzed by questionnaires, physical examination and serum biochemical assay.Smoking state was divided into no smoking, a occasional smoking and smoking groups.Results:With the increase of age, there was a downward trend of SUA( F=7.38, P=0.000). Among the three smoking groups, the group with occasional smoking had the highest level of SUA.The smoking group had lower level of SUA than the non-smoking group and occasional smoking group( P=0.000 and 0.005). In the non-smoking group, the fourth quartile of SUA(41.5%)had a higher percentage than that in first quartile of SUA(38.4%)( χ2=12.266, P=0.000). In the smoking group, the fourth quartile of SUA(54.9%)had lower percentage than that in the first quartile of SUA(58.4%)( χ2=7.049, P=0.008). Compared with the non-smoking group, the prevalence of hyperuricemia(HUA)in smoking group was lower( OR=0.872, 95% CI: 0.821~0.927, P=0.000), the prevalence of HUA in occasional smoking group was higher( OR=1.194, 95% CI: 1.013~1.408, P=0.035). Conclusions:As compared with the non-smoking group, the prevalence of HUA is lower in smoking group and is higher in occasional smoking group.
4.Impact of different lifestyle indexes on serum uric acid levels in young and middle-aged men
Hongwei LI ; Zhenhai SHEN ; Bing JIA ; Tong ZHANG ; Shaolei LI ; Ping ZHANG ; Fangcen YUAN ; Yun LU
Chinese Journal of Endocrinology and Metabolism 2022;38(12):1034-1039
Objective:To investigate the impact of lifestyle index (LSI) on serum uric acid levels in young and middle-aged men.Methods:This was a cross sectional study. A total of 8 067 subjects underwent check-up in Taihu Sanatorium of Jiangsu Province from March 2020 to June 2021 were enrolled, average age were(46.46±8.81) years. According to age, subjects were divided into young male group (18-44 years old, n=3 269) and middle-aged male group (45-60 years old, n=4 798). Height, weight, body mass index, alcohol drinking, smoking, diet, exercise, fasting blood glucose, total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol(LDL-C), serum uric acid and other data in all cases were measured and recorded. Results:The serum uric acid level in allsubjects was (376.80±74.43)μmol/L and the prevalence of hyperuricemia was 25.7%.The serum uric acid level in the young male group was higher than that in the middle-aged male group [(381.86±74.32)μmol/L vs (373.34±74.32)μmol/L, P<0.001]. The prevalence of hyperuricemia in the young male group was higher than that in the middle-aged male group (27.4% vs 24.5%), and the difference was statistically significant ( P<0.001). With the improvement of LSI scores, the serum uric acid levels in young and middle-aged men showed a decreasing trend ( P<0.01). Logistic regression analysis showed that after adjusting for age, fasting blood glucose, total cholesterol, triglyceride, HDL-C, LDL-C, hypertension, and diabetes, LSI was an independent factor for serum uric acid levels in young and middle-aged men. The risk of hyperuricemia in young and middle-aged male decreased ( OR 0.83 and 0.84, respectively, P<0.01) for every 1-point increase in LSI. Exercise and body mass index were independently associated with hyperuricemia in the young male group ( OR 0.83 and 0.54, respectively, P<0.05). Exercise, body mass index, and alcohol drinking were independently associated with hyperuricemia in the middle-aged male group ( OR 0.85, 0.51 and 0.65, respectively, P<0.05). Conclusion:LSI is an independent factor associated with hyperuricemia in young and middle-aged men and a healthy lifestyle has a protective effect on serum uric acid levels in young and middle-aged men.
5.Effects of regular aerobic exercise on brachial ankle pulse wave velocity in middle-aged and elderly people
Hongwei LI ; Zhenhai SHEN ; Bing JIA ; Ping ZHANG ; Fangcen YUAN ; Yun LU
Chinese Journal of Geriatrics 2022;41(2):151-157
Objective:To investigate the effects of regular aerobic exercise on brachial ankle pulse wave velocity(baPWV)in middle-aged and elderly people.Methods:This was a cross-sectional study.A total of 7993 subjects receiving health examination at the Taihu Sanatorium of Jiangsu Province were enrolled, including 4 371 males and 3 622 females, with an average age of 55.8 years(±7.9).Information on exercise, alcohol consumption, smoking, body mass index, baPWV, blood pressure, resting heart rate, fasting blood glucose, total cholesterol(TC), triglycerides(TG), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C)and uric acid in all subjects were collected and recorded.Based on exercise habits, subjects were divided into the no exercise group(n=489), the occasional exercise group(n=3 222, exercise<3 times or<90 min per week)and regular exercise group(n=4 282, exercise 3-5 times or >90 min per week).Results:For male subjects, differences in baPWV between the no exercise group(1 747.37±346.07 cm/s), the occasional exercise group(1 486.77±195.15 cm/s)and the regular exercise group(1 449.77±219.50 cm/s)were statistically significant( P<0.05).For female subjects, difference in baPWV between the no exercise group(1865.05±120.19)cm/s, the occasional exercise group(1 593.18±332.51)cm/s and the regular exercise group(1 227.81±150.89)cm/s were also statistically significant( P<0.05).With increased time of exercise per week, the levels of systolic blood pressure, diastolic blood pressure, resting heart rate, fasting blood glucose, TG and uric acid in different exercise groups decreased gradually for both men and women.Multivariate linear regression analysis showed that exercise, alcohol consumption, systolic blood pressure, diastolic blood pressure and fasting blood glucose were independent risk factors for baPWV in men(all P<0.05)and that exercise, systolic blood pressure, diastolic blood pressure, resting heart rate and fasting blood glucose were the independent risk factors for baPWV in women(all P<0.05).Trend analysis showed that with increased time of exercise per week, the rate of abnormal baPWV decreased gradually in both men and women( χ2 values were 74.67 and 1545.54, respectively, P<0.01). Conclusions:Regular aerobic exercise can improve baPWV, systolic blood pressure, diastolic blood pressure, resting heart rate, fasting blood glucose, TG and uric acid in middle-aged and elderly people.Exercise is an independent influencing factor for baPWV in middle-aged and elderly people and exercise 3-5 times or more than 90 min per week is beneficial to cardiovascular health in middle-aged and elderly people.
6.Effects of cardiovascular health behaviors and factors on postmenopausal osteoporosis in Suxichang area of Jiangsu province
Bing JIA ; Zhenhai SHEN ; Hongwei LI ; Ping ZHANG ; Fangcen YUAN ; Yun LU
Chinese Journal of Geriatrics 2022;41(10):1215-1219
Objective:To explore the relationship of cardiovascular health behavior and factors with development of bone mass loss and postmenopausal osteoporosis in Suxichang area of Jiangsu province.Methods:In the across sectional study, a total of 2 423 postmenopausal women receiving health check-up from March 2019 to June 2020 in our hospital were enrolled.The seven variable factors included cardiovascular health behavior(body mass index, exercise, healthy diet and smoking state)and cardiovascular health-influencing factors(blood pressure, fasting blood glucose and total cholesterol). The information of the seven factors and bone mineral density were recorded.The seven factors were classified as ideal, average and poor, according to the level of bone mineral density.All individuals were divided into three groups: normal bone mass(n=1 305), osteopenia(n=290)and osteoporosis(n=828).Results:There were statistically significant differences in age, fasting blood glucose, systolic blood pressure, diastolic blood pressure, total cholesterol and exercise between osteoporosis and normal bone mass group( P<0.05). As the number of ideal cardiovascular health behaviors and factors increased, the proportion of bone mass loss and osteoporosis gradually decreased( P<0.05). Multiple logistic regression analysis showed that ageing, increased total cholesterol and fasting blood glucose levels were the independent risk factors of osteoporosis.The exercise and normal body mass index were the protective factors for osteoporosis.For each 1 unit increment in age, total cholesterol, body mass index and fasting blood glucose, the OR values for bone mineral density decrement by 1 grade were 1.17, 1.25, 0.92 and 1.23, respectively(all P<0.05). The OR value for bone mineral density decrement by 1 grade was 0.58( P<0.05)when exercise decreased by 1 grade. Conclusions:Postmenopausal women should positively control the levels of total cholesterol and fasting blood glucose, maintain reasonable body weight and conduct regular exercise, which are conductive to the prevention and treatment of postmenopausal osteoporosis.