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Anti-inflammatory properties of the short-chain fatty acids acetate and propionate:A study with relevance to inflammatory bowel disease 被引量:83
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作者 Sofia Tedelind Fredrik Westberg +1 位作者 Martin Kjerrulf Alexander Vidal 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第20期2826-2832,共7页
AIM: To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS: The effect of SCFAs on cytokine rel... AIM: To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS: The effect of SCFAs on cytokine release from human neutrophils was studied with EHSA. SCFA- dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. RESULTS: Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. CONCLUSION: In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD. 展开更多
关键词 NEUTROPHILS epithelial cells COLITIS Infla- mmation Short-chain fatty acids ACETATE PROPIONATE BUTYRATE NF-KB Cytokines
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Randomized Double-Blind Clinical Trial of Moluodan(摩罗丹)for the Treatment of Chronic Atrophic Gastritis with Dysplasia 被引量:67
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作者 唐旭东 周丽雅 +10 位作者 张澍田 徐有青 崔全才 李理 陆京京 李鹏 陆芳 王凤云 王萍 卞立群 卞兆祥 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2016年第1期9-18,共10页
Objective: To assess the efficacy and safety of Moluodan (摩罗丹~) in treating dysplasia in chronic atrophic gastritis (CAG) patients. Methods: This was a multi-centered, double-blind, randomized controlled tria... Objective: To assess the efficacy and safety of Moluodan (摩罗丹~) in treating dysplasia in chronic atrophic gastritis (CAG) patients. Methods: This was a multi-centered, double-blind, randomized controlled trial. The total of 196 subjects were assigned to receive either Moluodan or folic acid in a 2:1 ratio by blocked randomization. Mucosa marking targeting biopsy (MTB) was used to insure the accuracy and consistency between baseline and after 6-month treatment. Primary outcomes were histological score, response rate of pathological lesions and dysplasia disappearance rate. Secondary endpoints included gastroscopic findings, clinical symptom and patient reported outcome (PRO) instrument. Results: Dysplasia score decreased in Moluodan group (P=0.002), significance was found between groups (P=0.045). Dysplasia disappearance rates were 24.6% and 15.2% in Moluodan and folic acid groups respectively, no significant differences were found (P=0.127). The response rate of atrophy and intestinal metaplasia were 34.6% and 23.0% in Moluodan group, 24.3% and 13.6% in folic acid group. Moluodan could improve erythema (P=0.044), and bile reflux (P=0.059), no significance between groups. Moluodan was better than folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite (P〈0.05), with symptom disappearance rates of 37% to 83%. Conclusions: Moluodan improved dysplasia score in histopathology, and erythema and bile reflux score in endoscopy, and superior to folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite. 展开更多
关键词 gastric epithelial dysplasia chronic atrophic gastritis Moluodan folic acid randomized clinical trial
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Neurodegeneration:An early event of diabetic retinopathy 被引量:43
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作者 Marta Villarroel Andreea Ciudin +1 位作者 Cristina Hernández Rafael Simó 《World Journal of Diabetes》 SCIE CAS 2010年第2期57-64,共8页
Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyper... Diabetic retinopathy(DR) has been classically considered to be a microcirculatory disease of the retina caused by the deleterious metabolic effects of hyperglycemia per se and the metabolic pathways triggered by hyperglycemia.However,retinal neurodegeneration is already present before any microcirculatory abnormalities can be detected in ophthalmoscopic examination.In other words,retinal neurodegeneration is an early event in the pathogenesis of DR which predates and participates in the microcirculatory abnormalities that occur in DR.Therefore,the study of the mechanisms that lead to neurodegeneration will be essential to identify new therapeutic targets in the early stages of DR.Elevated levels of glutamate and the overexpression of the renin-angiotensin-system play an essential role in the neurodegenerative process that occurs in diabetic retina.Among neuroprotective factors,pigment epithelial derived factor,somatostatin and erythropoietin seem to be the most relevant and these will be considered in this review.Nevertheless,it should be noted that the balance between neurotoxic and neuroprotective factors rather than levels of neurotoxic factors alone will determine the presence or absence of retinal neurodegeneration in the diabetic eye.New strategies,based on either the delivery of neuroprotective agents or the blockade of neurotoxic factors,are currently being tested in experimental models and in clinical pilot studies.Whether these novel therapies will eventually supplement or prevent the need for laser photocoagulation or vitrectomy awaits the results of additional clinical research. 展开更多
关键词 Diabetic retinopathy Angiotensin II ERYTHROPOIETIN GLUTAMATE Retinal neurodegeneration NEUROPEPTIDES Pigment epithelial derived factor SOMATOSTATIN
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表皮生长因子在糖尿病足溃疡创面愈合过程中的作用观察及其机制探讨 被引量:38
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作者 刘如俊 赵文志 +1 位作者 张路 王国强 《大连医科大学学报》 CAS 2014年第4期322-327,共6页
目的探讨表皮生长因子(EGF)对糖尿病足溃疡创面愈合的治疗效果及其作用机制。方法将入选的32只糖尿病足新西兰兔随机分为2组:表皮生长因子组(A组)和对照组(B组),每组16只。将2组实验用兔大腿部切除10 mm×7 mm矩形区域全层皮肤,一... 目的探讨表皮生长因子(EGF)对糖尿病足溃疡创面愈合的治疗效果及其作用机制。方法将入选的32只糖尿病足新西兰兔随机分为2组:表皮生长因子组(A组)和对照组(B组),每组16只。将2组实验用兔大腿部切除10 mm×7 mm矩形区域全层皮肤,一组局部创口连续涂抹表皮生长因子(EGF),用量从始至终为1 mL,1次/d(A组);另一组不施加干预(B组)。15 d后沿超出创面外缘2 mm处取下创面新生肉芽组织并作Masson染色、HE染色、电镜观察及内源性EGFmRNA检测。结果 (1)光镜下A组可见大量成纤维细胞聚集成群,轮廓较清晰,细胞外基质丰富,胶原纤维束排列密集而有序,可见大量血管生成,组织分层愈合良好;B组可见创面愈合缓慢,胶原纤维稀疏,组织结构不明显。电镜下A组可见成纤维细胞体积大、形态完好、胞质内细胞器丰富,细胞周围可见大量胶原纤维排列整齐有序;B组成纤维细胞形态不规则,细胞内容物少,周围胶原纤维稀疏,排列混乱。(2)内源性EGFmRNA检测发现:A组EGFmRNA的灰度相对值为109.31±5.17;B组EGFmRNA的灰度相对值为61.59±4.61,两组比较,差异有显著性意义(P<0.01)。结论表皮生长因子能够促进糖尿病足溃疡创面的愈合,可能机制为外源性的EGF上调了局部组织中EGFmRNA的表达。 展开更多
关键词 表皮生长因子 糖尿病足 创面愈合 epithelial growth factor ( EGF)
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Cellular and molecular mechanisms of intestinal fibrosis 被引量:33
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作者 Silvia Speca Ilaria Giusti +1 位作者 Florian Rieder Giovanni Latella 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第28期3635-3661,共27页
Fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. Intestinal fibrosis may develop in s... Fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. Intestinal fibrosis may develop in several different enteropathies, including inflammatory bowel disease. It develops through complex cell, extracellular matrix, cytokine and growth factor interactions. Distinct cell types are involved in intestinal fibrosis, such as resident mesenchymal cells (fibroblasts, myofibroblasts and smooth muscle cells) but also ECM-producing cells derived from epithelial and endothelial cells (through a process termed epithelialand endothelial-mesenchymal transition), stellate cells, pericytes, local or bone marrow-derived stem cells. The most important soluble factors that regulate the activation of these cells include cytokines, chemokines, growth factors, components of the renin-angiotensin system, angiogenic factors, peroxisome proliferator-activated receptors, mammalian target of rapamycin, and products of oxidative stress. It soon becomes clear that although inflammation is responsible for triggering the onset of the fibrotic proc-ess, it only plays a minor role in the progression of this condition, as fibrosis may advance in a self-perpetuating fashion. Definition of the cellular and molecular mechanisms involved in intestinal fibrosis may provide the key to developing new therapeutic approaches. 展开更多
关键词 Inflammatory bowel disease Intestinal fibrosis Extracellular matrix Molecular mediators MYOFIBROBLASTS Inflammatory cells epithelial cells Mesenchymal cells Endothelial cells
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Astragalus mongholicus polysaccharide inhibits lipopolysaccharide-induced production of TNF-α and interleukin-8 被引量:30
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作者 Yuan Yuan Mei Sun Ke-Shen Li 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第29期3676-3680,共5页
AIM: To explore the effect of Astraga/us mongholicus polysaccharide (APS) on gene expression and mitogenactivated protein kinase (MAPK) transcriptional activity in intestinal epithelial cells (IEC). METHODS: I... AIM: To explore the effect of Astraga/us mongholicus polysaccharide (APS) on gene expression and mitogenactivated protein kinase (MAPK) transcriptional activity in intestinal epithelial cells (IEC). METHODS: IEC were divided into control group, lipopolysaccharide (LPS) group, LPS+ 50 μg/mL APS group, LPS+ 100 μg/mL APS group, LPS+ 200 μg/mL APS group, and LPS+ 500 μg/mL APS group. Levels of mRNAs in LPS-induced inflammatory factors, tumor necrosis factor (TNF)-α and interleukin (IL)-8, were measured by reverse transcription-polymerase chain reaction. MAPK protein level was measured by Western blotting. RESULTS: The levels of TNF-α and IL-8 mRNAs were significantly higher in IEC with LPS-induced damage than in control cells. APS significantly abrogated the LPS-induced expression of the TNF-α and IL-8 genes. APS did not block the activation of extracellular signal- regulated kinase or c Jun amino-terminal kinase, but inhibited the activation of p38, suggesting that APS inhibits LPS-induced production of TNF-α and IL-8 mRNAs, possibly by suppressing the p38 signaling pathway.CONCLUSION: APS-modulated bacterial productmediated p38 signaling represents an attractive strategy for prevention and treatment of intestinal inflammation. 展开更多
关键词 Astraga/us mongho/icus polysaccharide Intestinal epithelial cells Tumor necrosis factor-Q INTERLEUKIN-8 Extracellular signal-regulated kinase CJun amino-terminal kinase p38 kinase
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Experimental Study on the Molecular Mechanism of Anthraquinone Cathartics in Inducing Melanosis Coli 被引量:27
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作者 陈建永 潘锋 +2 位作者 张涛 夏瑾 李艳娟 《Chinese Journal of Integrative Medicine》 SCIE CAS 2011年第7期525-530,共6页
Objective:To explore the significance of colonic epithelial cell apoptosis and tumor necrosis factorα(TNF-α)changing in pathogenesis of melanosis coli(MC)in guinea pig and the molecular mechanism of rhubarb(Rh... Objective:To explore the significance of colonic epithelial cell apoptosis and tumor necrosis factorα(TNF-α)changing in pathogenesis of melanosis coli(MC)in guinea pig and the molecular mechanism of rhubarb(Rhu)in inducing the disease,by means of using different dosages of Rhu to induce the disease. Methods:One hundred and forty-four male guinea pigs,clean grade,were randomized according to their body weight into 5 groups,the untreated normal group and the 4 Rhu groups treated,respectively,with different doses of Rhu,3 g/kg·d for low dose(Rhu-I)group,6 g/kg·d for moderate dose(Rhu-m)group,12 g/kg·d for high dose(Rhu-h)group and 24 g/kg·d for super-high dose(Rhu-s)group via gastric infusion.All animals were sacrificed 60 days later,their viscera were taken for observing the pathologic and morphologic changes with HE, melanin and melatonin staining,and the apoptosis of colonic epithelial cells was detected with TUNEL stain and transmission electric microscopy.In addition,the levels of TNF-αin serum and colonic tissue were measured using ELISA and RT-PCR.Results:The pathological changes of MC could be found by naked eye in all Rhu groups,especially apparent at caecum and proximal end of colon,but did not found in gallbladder,jejunum and ileum.In normal guinea pigs,the colonic membrane was pink in color with no apparent pigment deposition. Membranous color deepened in the Rhu groups depending on the dosage of Rhu used.MC scoring showed the highest scores revealed in the Rhu-s group(6.00±0.00),which was significantly different to those in the Rhu-I (3.86±0.69),Rhu-m(4.43±0.79)and Rhu-h groups(4.88±0.35,all P0.05).Levels of cell apoptosis in colon and TNF-αin serum in all Rhu groups were higher than those in the normal group(P0.01),but showed no significant difference among the Rhu groups(P0.05).Moreover,a positive correlation was found in the degree of induced MC with apoptosis rate and TNF-αlevel.Conclusions:Rhu(anthraquinone purgatives)had 展开更多
关键词 ANTHRAQUINONE extract of rhubarb guinea pig melanosis coli colonic epithelial cell apoptosis tumor necrosis factor-α
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Chronic hepatitis B serum promotes apoptotic damage in human renal tubular cells 被引量:26
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作者 Cun-Liang Deng Xin-Wen song +3 位作者 Hai-Jun Liang Chen Feng Yun-Jian Sheng Ming-Yong Wang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第11期1752-1756,共5页
AIM: To investigate the effect of the serum of patients with chronic hepatitis B (CHB) on apoptosis of renal tubular epithelial cells in vitro and to study the role of hepatitis B virus (HBV) and transforming gro... AIM: To investigate the effect of the serum of patients with chronic hepatitis B (CHB) on apoptosis of renal tubular epithelial cells in vitro and to study the role of hepatitis B virus (HBV) and transforming growth factor-β1 (TGF-β1) in the pathogenesis of hepatitis B virus associated glomerulonephritis (HBV-GN). METHODS: The levels of serum TGF-β1 were measured by specific enzyme linked immunosorbent assay (ELISA) and HBV DNA was tested by polymerase chain reaction (PCR) in 44 patients with CHB ,and 20 healthy persons as the control. The normal human kidney proximal tubular cell (HK-2) was cultured together with the sera of healthy persons, CHB patients with HBV-DNA negative(20 cases) and HBV-DNA positive (24 cases) for up to 72 h. Apoptosis and Fas expression of the HK-2 were detected by flow cytometer. RESULTS: The apoptosis rate and Fas expression of HK-2 cells were significantly higher in HBV DNA positive serum group 19.01±5.85% and 17.58±8.35%, HBV DNA negative serum group 8.12±2.80% and 6.96 ± 2.76% than those in control group 4.25±0.65% and 2.33 ± 1.09%, respectively (P 〈 0.01). The apoptosis rate and Fas expression of HK-2 in HBV DNA positive serum group was significantly higher than those in HBV DNA negative serum (P 〈 0.01). Apoptosis rate of HK-2 cells in HBV DNA positive serum group was positively correlated with the level of HBV-DNA (r = 0.657). The level of serum TGF-β1 in CHB group was 163.05 ± 91.35 μg/L, signifi- cantly higher as compared with 81.40 ± 40.75 μg/L in the control group (P 〈 0.01).CONCLUSION: The serum of patients with chronic hepatitis B promotes apoptotic damage in human renal tubular cells by triggering a pathway of Fas up-regulation. HBV and TGF-β1 may play important roles in the mechanism of hepatitis B virus associated glomerulonephritis. 展开更多
关键词 Renal tubular epithelial cells HBV TGF-Β1 APOPTOSIS
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Moxibustion down-regulates colonic epithelial cell apoptosis and repairs tight junctions in rats with Crohn's disease 被引量:25
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作者 Chun-Hui Bao Lu-Yi Wu Yin Shi Huan-Gan Wu Hui-Rong Liu Rong Zhang Li-Qing Yu Jin-Hai Wang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第45期4960-4970,共11页
AIM: To investigate the effects of moxibustion on down-regulation of the colonic epithelial cell apoptosis and repair of the tight junctions in rats with Crohn's disease (CD). METHODS: Sixty male Sprague-Dawley ra... AIM: To investigate the effects of moxibustion on down-regulation of the colonic epithelial cell apoptosis and repair of the tight junctions in rats with Crohn's disease (CD). METHODS: Sixty male Sprague-Dawley rats were randomly divided into a normal control (NC) group, a model control (MC) group, an herbs-partitioned moxibustion (HPM) group, a mild-warm moxibustion (MWM) group and a salicylazosulphapyridine (SASP) group, with 12 rats in each group. The CD model rats were treated with trinitrobenzene sulphonic acid to induce intestinal inflammation. The rats in the HPM and MWM groups were treated at the Tianshu (ST25) and Qihai (CV6) acupoints once daily for 14 d, and the SASP group was fed SASP twice daily for 14 d. No additional treatment was given to the MC and NC groups. Themicrostructure of the colonic epithelium was observed under a transmission electron microscope, the transepithelial resistance was measured using a shortcircuit current, colonic epithelial cell apoptosis was determined by terminal deoxynucleotidyl transferasemediated dUTP-biotin nick end labelling assay, and the expression of occludin, claudin-1 and zonula occludens-l (ZO-1) in the colonic epithelial junction was determined by Western blotting and immunofluorescence staining. RESULTS: Compared with the MC group, the microstructure of the colonic epithelial barrier was signifi-cantly improved in rats treated with HPM, MWM or SASP, meanwhile, the current flow was reduced signifi-cantly, with values of 168.20 ± 6.14 vs 99.70 ± 3.13, 99.10 ± 4.28 and 120.30 ± 3.65 mA, respectively (P = 0.001). However, the HPM and MWM groups had higher current flow rates than the SASP group (99.70 ± 3.13, 99.10 ± 4.28 vs 120.30 ± 3.65 mA, P = 0.001). The number of the apoptotic colonic epithelial cells in HPM, MWM and SASP groups was largely reduced (61.5 ± 16.91 vs 15.5 ± 8.89, 14.8 ± 6.27 and 24.7 ± 9.68, respectively (P = 0.001); and the expression of occlu- din, claudin-1 and ZO-1 in the MWM and HPM groups was signifi cantly enhanced (0.48 ± 0 展开更多
关键词 MOXIBUSTION Colonic epithelial cells apoptosis Tight junctions Colonic epithelial barrier Crohn’s disease RATS
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Moxibustion combined with acupuncture increases tight junction protein expression in Crohn's disease patients 被引量:24
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作者 Hai-Xia Shang An-Qi Wang +6 位作者 Chun-Hui Bao Huan-Gan Wu Wei-Feng Chen Lu-Yi Wu Rong Ji Ji-Meng Zhao Yin Shi 《World Journal of Gastroenterology》 SCIE CAS 2015年第16期4986-4996,共11页
AIM:To investigate the effect of herb-partitioned moxibustion combined with acupuncture on the expression of intestinal epithelial tight junction(TJ) proteins.METHODS:Sixty patients diagnosed with mild to moderate Cr... AIM:To investigate the effect of herb-partitioned moxibustion combined with acupuncture on the expression of intestinal epithelial tight junction(TJ) proteins.METHODS:Sixty patients diagnosed with mild to moderate Crohn’s disease(CD)were allocated into the herb-partitioned moxibustion combined with acupuncture(HMA)group(n=30)or the mesalazine(MESA)group(n=30)using a parallel control method.There were 2 sets of acupoints used alternately for HMA treatment.The following points were included in Set A:ST25(Tianshu),RN6(Qihai),and RN9(Shuifen)for herb-partitioned moxibustion and ST36(Zusanli),ST37(Shangjuxu),LI11(Quchi),and LI4(Hegu)for acupuncture.The points for Set B included BL23(Shenshu)and BL25(Dachangshu)for herb-partitioned moxibustion and EX-B2 of T6-T1(Jiajixue)fo r acupuncture.The patients received the same treatment6 times a week for 12 consecutive weeks.The MESA group received 1 g of mesalazine enteric coated tablets4 times daily for 12 consecutive weeks.Intestinaltissues were stained and examined to compare the morphological and ultrastructural changes before and after the treatment session.Immunohistochemistry and in situ hybridization assays were used to detect the expression of intestinal epithelial TJ proteins zonula occludens-1(ZO-1),occludin,and claudin-1.The m RNA levels were also evaluated.RESULTS:After the treatment,both herb-partitioned moxibustion combined with acupuncture and mesalazine improved intestinal morphology and ultrastructure of CD patients;the patients treated with HMA showed better improvement.HMA significantly increased the expression of ZO-1(P=0.000),occludin(P=0.021),and claudin-1(P=0.016).MESA significantly increased the expression of ZO-1(P=0.016)and occludin(P=0.026).However,there was no significant increase in the expression of claudin-1(P=0.935).There was no statistically significant difference between the two groups for the expression of occludin and claudin-1(P>0.05).The HMA group showed a significant improvement in ZO-1 expression compared to the MESA group(2333.34±35 展开更多
关键词 Crohn's disease Herb-partitioned MOXIBUSTION ACUPUNCTURE Intestinal epithelial cells Tight junctionproteins
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Methionine-dependence and combination chemotherapy on human gastric cancer cells in vitro 被引量:24
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作者 Wei-Xin Cao Jing-Min Ou Xu-Feng Fei,Department of Clinical Nutrition,Shanghai Institute of Digestive Surgery,Ruijin Hospital,Shanghai Second Medical University,Shanghai 200025,China Zheng-Gang Zhu Hao-Ran Yin Min Yan Yan-Zhen Lin,Department of Surgery,Shanghai Institute of Digestive Surgery,Ruijin Hospital,Shanghai Second Medical University,Shangha 200025,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2002年第2期230-232,共3页
AIM: To elucidate whether human primary gastric cancer and gastric mucosa epithelial cells in vitro can grow normally in a methionine (Met) depleted environment, i.e. Met-dependence, and whether Met-depleting status c... AIM: To elucidate whether human primary gastric cancer and gastric mucosa epithelial cells in vitro can grow normally in a methionine (Met) depleted environment, i.e. Met-dependence, and whether Met-depleting status can enhance the killing effect of chemotherapy on gastric cancer cells. METHODS: Fresh human gastric cancer and mucosal tissues were managed to form monocellular suspensions, which were then cultured in the Met-free but homocysteine-containing (Met(-)Hcy(+)) medium, with different chemotherapeutic drugs. The proliferation of the cells was examined by cell counter, flow cytometry (FCM) and microcytotoxicity assay (MTT). RESULTS: The growth of human primary gastric cancer cells in Met(-)Hcy(+) was suppressed, manifested by the decrease of total cell counts [1.46 +/- 0.42 (x 10(9).L(-1)) in Met(-)Hcy(+) vs 1.64 +/-0.44(x 10(9).L(-1)) in Met(+)Hcy(-), P【0.01], the decline in the percentage of G(0)G(1) phase cells (0.69 +/- 0.24 in Met(-)Hcy(+) vs 0.80 +/- 0.18 in Met(+)Hcy(-), P【0.01) and the increase of S cells (0.24 +/- 0.20 in Met(-)Hcy(+) vs 0.17 +/- 0.16 in Met(+)Hcy(-), P【0.01); however, gastric mucosal cells grew normally. If Met(-)Hcy(+) medium was used in combination with chemotherapeutic drugs, the number of surviving gastric cancer cells dropped significantly. CONCLUSION: Human primary gastric cancer cells in vitro are Met-dependent; however, gastric mucosal cells have not shown the same characteristics. Met(-)Hcy(+) environment may strengthen the killing effect of chemotherapy on human primary gastric cancer cells. 展开更多
关键词 Antineoplastic Combined Chemotherapy Protocols Cells Cultured Culture Media epithelial Cells Gastric Mucosa Humans METHIONINE Research Support Non-U.S. Gov't Stomach Neoplasms
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Transplantation of human amniotic epithelial cells improves hindlimb function in rats with spinal cord injury 被引量:23
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作者 WU Zhi-yuan HUI Guo-zhen +2 位作者 LU Yi WU Xin GUO Li-he 《Chinese Medical Journal》 SCIE CAS CSCD 2006年第24期2101-2107,共7页
Background Human amniotic epithelial cells (HAECs), which have several characteristics similar to stem cells, therefore could possibly be used in cell therapy without creating legal or ethical problems. In this stud... Background Human amniotic epithelial cells (HAECs), which have several characteristics similar to stem cells, therefore could possibly be used in cell therapy without creating legal or ethical problems. In this study, we transplanted HEACs into the injured spinal cord of rats to investigate if the cells can improve the rats' hindlimb motor function. Methods HAECs were obtained from a piece of fresh amnion, labeled with Hoechst33342, and transplanted into the site of complete midthoracic spinal transections in adult rats. The rats (n=21) were randomly divided into three groups: Sham-operation group (n=7), cells-graft group (n=7), and PBS group (n=7). One rat of each group was killed for histological analysis at the second week after the transplantation. The other six rats of each group were killed for histological analysis after an 8-week behavioral testing. Hindlimb motor function was assessed by using the open-field BBB scoring system. Survival rate of the graft cells was observed at second and eighth weeks after the transplantation. We also detected the myelin sheath fibers around the lesions and the size of the axotomized red nucleus. A one-way ANOVA was used to compare the means among the groups. The significance level was set at P〈0.05. Results The graft HAECs survived for a long time (8 weeks) and integrated into the host spinal cord without immune rejection. Compared with the control group, HAECs can promote the regeneration and sprouting of the axons, improve the hindlimb motor function of the rats (BBB score: cells-graft group 9.0 ± 0.89 vs PBS group 3.7± 1.03, P〈0.01), and inhibit the atrophy of axotomized red nucleus [cells-graft group (526.47±148.42)μm^2 vs PBS group (473.69±164.73) μm^2, P〈0.01]. Conclusion Transplantation of HAECs can improve the hindlimb motor function of rats with spinal cord injury. 展开更多
关键词 spinal cord injury human amniotic epithelial cells TRANSPLANTATION
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Microbiota-host interactions in irritable bowel syndrome: Epithelial barrier, immune regulation and brain-gut interactions 被引量:24
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作者 Niall P Hyland Eamonn MM Quigley Elizabeth Brint 《World Journal of Gastroenterology》 SCIE CAS 2014年第27期8859-8866,共8页
Irritable bowel syndrome(IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to... Irritable bowel syndrome(IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to contribute to the genesis of symptoms in IBS, a search for an underlying aetiology has, to date, proven unsuccessful. Recently, attention has been focused on the microbiota as a possible factor in the pathogenesis of IBS. Prompted by a number of clinical observations, such as the recognition of the de novo development of IBS following enteric infections, as well as descriptions of changes in colonic bacterial populations in IBS and supported by clinical responses to interventions, such as antibiotics and probiotics, that modify the microbiota, various approaches have been taken to investigating the microbiota-host response in IBS, as well as in animal models thereof. From such studies a considerable body of evidence has accumulated to indicate the activation or upregulation of both factors involved in bacterial engagement with the host as well host defence mechanisms against bacteria. Alterations in gut barrier function, occurring in response, or in parallel, to changes in the microbiota, have also been widely described and can be seen to play a pivotal role in generating and sustaining host immune responses both within and beyond the gut. In this manner a plausible hypothesis, based on an altered microbiota and/or an aberrant host response, for the pathogenesis, of at least some instances of IBS, can be generated. 展开更多
关键词 MICROBIOTA Irritable bowel syndrome Tolllike receptor epithelial barrier Gut-brain axis
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Role of connective growth factor in plasminogen activator inhibitor-1 and fibronectin expression induced by transforming growth factor β1 in renal tubular cells 被引量:20
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作者 张春 孟宪芳 +2 位作者 朱忠华 杨晓 邓安国 《Chinese Medical Journal》 SCIE CAS CSCD 2004年第7期990-996,共7页
Background Connective tissue growth factor (CTGF) contributes greatly to renal tubulointerstitial fibrosis, which is the final event leading to end-stage renal failure. This study was designed to investigate the effe... Background Connective tissue growth factor (CTGF) contributes greatly to renal tubulointerstitial fibrosis, which is the final event leading to end-stage renal failure. This study was designed to investigate the effects of CTGF antisense oligodeoxynucleotides (ODNs) on the expressions of plasminogen activator inhibitor-1 (PAI-1) and fibronectin in renal tubular cells induced by transforming growth factor β1 (TGF-β1) in addition to the role of CTGF in the accumulation and degradation of renal extracellular matrix (ECM).Methods A human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODNs were transfected into HKC cells. After HKC cells were stimulated with TGF-β1 (5 μg/L), the mRNA levels of PAI-1 and fibronectin were measured by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 and fibronectin in the medium were determined by Western blot and ELISA, respectively.Results TGF-β1 was found to induce tubular CTGF, PAI-1, and fibronectin mRNA expression. PAI-1 and fibronectin mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODNs. CTGF antisense ODNs also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 and fibronectin protein secreted into the medium.Conclusions CTGF may play a crucial role in the accumulation and degradation of excessive ECM during tubulointerstitial fibrosis, and transfecting CTGF antisense ODNs may be an effective way to prevent renal fibrosis. 展开更多
关键词 connective tissue growth factor antisense oligodeoxynucleotide plasminogen activator inhibitor-1 FIBRONECTIN renal tubular epithelial cells
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Establishment of an untransfected human corneal epithelial cell line and its biocompatibility with denuded amniotic membrane 被引量:22
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作者 Ting-Jun Fan Bin Xu +3 位作者 Jun Zhao Hong-Shou Yang Rui-Xin Wang and Xiu-Zhong Hu 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2011年第3期228-234,共7页
AIM: To establish an untransfected human corneal epithelial (HCEP) cell line and characterize its biocompatibility with denuded amniotic membrane (dAM). METHODS: The torn HCEP pieces were primarily cultured in DMEM/F1... AIM: To establish an untransfected human corneal epithelial (HCEP) cell line and characterize its biocompatibility with denuded amniotic membrane (dAM). METHODS: The torn HCEP pieces were primarily cultured in DMEM/F12 media (pH 7.2) supplemented with 20% fetal bovine serum and other necessary factors, yielding an HCEP cell line which was its growth performance, chromosome morphology, tumorigenicity and expression of marker proteins analyzed. In addition, the biocompatibility of HCEP cells with dAM was evaluated through histological and immunocytochemistry analyses and with light, electron and slit-lamp microscopies. RESULTS: HCEP cells proliferated to confluence in 3 weeks, which have been subcultured to passage 160. A continuous untransfected HCEP cell line, designated as utHCEPC01, was established with a population doubling time of 45.42 hours as was determined at passage 100. The cells retained HCEP cell properties as were approved by chromosomal morphology and the expression of keratin 3. They, with no tumorigenicity, formed a multilayer epithelium-like structure on dAMs through proliferation and differentiation during air-liquid interface culture, maintained expression of marker proteins including keratin 3 and integrin p 1 and attached tightly to dAMs. The reconstructed HCEP was highly transparent and morphologically and structurally similar to the original. CONCLUSION: An untransfected and non-tumorigenic HCEP cell line was established in this study. The cells maintained expression of marker proteins. The cell line was biocompatible with dAM. It holds the potential of being used for in vitro reconstruction of tissue-engineered HCEP, promising for the treatment of diseases caused by corneal epithelial disorders. 展开更多
关键词 human corneal epithelial cell cell line untransfected BIOCOMPATIBILITY denuded amniotic membrane
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Telomere and telomerase in the initial stage of immortalization of esophageal epithelial cell 被引量:21
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作者 Zhong-Ying Shen Li-Yan Xu Wei-Jia Cai Min-Hua Chen Jian Shen,Department of Tumor Pathology,Medical College of Shantou University,Shantou 515031,Guangdong Province,China En-Min Li,Department of Biochemistry and Molecular Biology,Medical College of Shantou University,Shantou 515031,Guangdong Province,China Yi Zeng,Institute of Virology,Chinese Academy of Preventive Medicine,Beijing 100052,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2002年第2期357-362,共6页
AIM: To search for the biomarker of cellular immortalization, the telomere length, telomerase activity and its subunits in cultured epithelial cells of human fetal esophagus in the process of immortalization. METHODS:... AIM: To search for the biomarker of cellular immortalization, the telomere length, telomerase activity and its subunits in cultured epithelial cells of human fetal esophagus in the process of immortalization. METHODS: The transgenic cell line of human fetal esophageal epithelium (SHEE) was established with E(6)E(7) genes of human papillomavirus (HPV) type 18 in our laboratory. Morphological phenotype of cultured SHEE cells from the 6th to 30th passages, was examined by phase contrast microscopy, the telomere length was assayed by Southern blot method, and the activity of telomerase was analyzed by telomeric repeat amplification protocol (TRAP). Expressions of subunits of telomerase, hTR and hTERT, were assessed by RT-PCR. DNA content in cell cycle was detected by flow cytometry. The cell apoptosis was examined by electron microscopy (EM) and TUNEL label. RESULTS: SHEE cells from the 6th to 10th passages showed cellular proliferation with a good differentiation. From the 12th to the 16th passages, many senescent and apoptotic cells appeared, and the telomere length sharply shortened from 23kb to 17kb without expression of hTERT and telomerase activity. At the 20th passage, SHEE cells overcame the senescence and apoptosis and restored their proliferative activity with expression of telomerase and hTERT at low levels, but the telomere length shortened continuously to the lowest of 3kb. After the 30th passage cells proliferation was restored by increment of cells at S and G2M phase in the cell cycle and telomerase activity expressed at high levels and with maintenance of telomere length. CONCLUSION: At the early stage of SHEE cells, telomeres are shortened without expression of telomerase and hTERT causing cellular senescence and cell death. From the 20th to the 30th passages, the activation of telomerase and maintenance of telomere length show a progressive process for immortalization of esophageal epithelial cells. The expression of telomerase may constitute a biomarker for detection of immortalization of cells. 展开更多
关键词 Cell Transformation Neoplastic Apoptosis Cell Division Cell Line Cell Size epithelial Cells Esophagus Humans In Situ Nick-End Labeling Papillomavirus Human Research Support Non-U.S. Gov't TELOMERASE TELOMERE
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Drug resistance and combating drug resistance in cancer 被引量:21
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作者 Xuan Wang Haiyun Zhang Xiaozhuo Chen 《Cancer Drug Resistance》 2019年第2期141-160,共20页
Cancer is the second leading cause of death in the US.Current major treatments for cancer management include surgery,cytotoxic chemotherapy,targeted therapy,radiation therapy,endocrine therapy and immunotherapy.Despit... Cancer is the second leading cause of death in the US.Current major treatments for cancer management include surgery,cytotoxic chemotherapy,targeted therapy,radiation therapy,endocrine therapy and immunotherapy.Despite the endeavors and achievements made in treating cancers during the past decades,resistance to classical chemotherapeutic agents and/or novel targeted drugs continues to be a major problem in cancer therapies.Drug resistance,either existing before treatment(intrinsic)or generated after therapy(acquired),is responsible for most relapses of cancer,one of the major causes of death of the disease.Heterogeneity among patients and tumors,and the versatility of cancer to circumvent therapies make drug resistance more challenging to deal with.Better understanding the mechanisms of drug resistance is required to provide guidance to future cancer treatment and achieve better outcomes.In this review,intrinsic and acquired resistance will be discussed.In addition,new discoveries in mechanisms of drug resistance will be reviewed.Particularly,we will highlight roles of ATP in drug resistance by discussing recent findings of exceptionally high levels of intratumoral extracellular ATP as well as intracellular ATP internalized from extracellular environment.The complexity of drug resistance development suggests that combinational and personalized therapies,which should take ATP into consideration,might provide better strategies and improved efficacy for fighting drug resistance in cancer. 展开更多
关键词 Cancer stem cells epithelial mesenchymal transition ATP binding cassette transporters extracellular ATP MACROPINOCYTOSIS EPIGENETICS MICRORNA
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Research progress on the relationship between intestinal microecology and intestinal bowel disease 被引量:20
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作者 Qianhui Fu Tianyuan Song +1 位作者 Xiaoqin Ma Jian Cui 《Animal Models and Experimental Medicine》 CAS CSCD 2022年第4期297-310,共14页
Intestinal microecology is the main component of human microecology.Intestinal microecology consists of intestinal microbiota,intestinal epithelial cells,and intestinal mucosal immune system.These components are inter... Intestinal microecology is the main component of human microecology.Intestinal microecology consists of intestinal microbiota,intestinal epithelial cells,and intestinal mucosal immune system.These components are interdependent and establish a complex interaction network that restricts each other.According to the impact on the human body,there are three categories of symbiotic bacteria,opportunistic pathogens,and pathogenic bacteria.The intestinal microecology participates in digestion and absorption,and material metabolism,and inhibits the growth of pathogenic microorganisms.It also acts as the body’s natural immune barrier,regulates the innate immunity of the intestine,controls the mucosal barrier function,and also participates in the intestinal epithelial cells’physiological activities such as hyperplasia or apoptosis.When the steady-state balance of the intestinal microecology is disturbed,the existing core intestinal microbiota network changes and leads to obesity,diabetes,and many other diseases,especially irritable bowel syndrome,inflammatory bowel disease(IBD),and colorectal malignancy.Intestinal diseases,including tumors,are particularly closely related to intestinal microecology.This article systematically discusses the research progress on the relationship between IBD and intestinal microecology from the pathogenesis,treatment methods of IBD,and the changes in intestinal microbiota. 展开更多
关键词 inflammatory bowel disease intestinal epithelial barrier intestinal microbiota intestinal mucosal barrier
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Lactobacillus plantarum inhibits epithelial barrier dysfunction and interleukin-8 secretion induced by tumor necrosis factor-a 被引量:18
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作者 Jae Sung Ko Hye Ran Yang +1 位作者 Ju Young Chang Jeong Kee Seo 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第13期1962-1965,共4页
AIM: To determine whether Lactobacillus plantarum can modify the deleterious effects of tumor necrosis factor-α (TNF-α) on intestinal epithelial cells. METHODS: Caco-2 cells were incubated with TNF-α alone or i... AIM: To determine whether Lactobacillus plantarum can modify the deleterious effects of tumor necrosis factor-α (TNF-α) on intestinal epithelial cells. METHODS: Caco-2 cells were incubated with TNF-α alone or in the presence of L. plantarum. Transepithelial electrical resistance was used to measure epithelial barrier function. Interleukin 8 (IL-8) secretion by intestinal epithelial cells was measured using an ELISA. Cellular lysate proteins were immunoblotted using the anti-extracellular regulated kinase (ERK), anti-phospho- ERK and anti-IκB-α. RESULTS: A TNF-α-induced decrease in transepithelial electrical resistance was inhibited by L. plantarum. TNF- α-induced IL-8 secretion was reduced by L. plantarum. L. plantarum inhibited the activation of ERK and the degradation of IκB-α in TNF-a-treated Caco-2 cells. CONCLUSION: Induction of epithelial barrier dysfunction and IL-8 secretion by TNF-α is inhibited byL. plantarum. Probiotics may preserve epithelial barrier function and inhibit the inflammatory response by altering the signal transduction pathway. 展开更多
关键词 Lactobacillus plantarum Tumor necrosisfactor-α epithelial barrier INTERLEUKIN-8 ERK IΚB-Α
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Effect of Helicobacter pylori on gastric epithelial cells 被引量:19
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作者 Shatha Alzahrani Taslima T Lina +3 位作者 Jazmin Gonzalez Irina V Pinchuk Ellen J Beswick Victor E Reyes 《World Journal of Gastroenterology》 SCIE CAS 2014年第36期12767-12780,共14页
The gastrointestinal epithelium has cells with features that make them a powerful line of defense in innate mucosal immunity. Features that allow gastrointestinal epithelial cells to contribute in innate defense inclu... The gastrointestinal epithelium has cells with features that make them a powerful line of defense in innate mucosal immunity. Features that allow gastrointestinal epithelial cells to contribute in innate defense include cell barrier integrity, cell turnover, autophagy, and innate immune responses. Helicobacter pylori (H. pylori) is a spiral shape gram negative bacterium that selectively colonizes the gastric epithelium of more than half of the world&#x02019;s population. The infection invariably becomes persistent due to highly specialized mechanisms that facilitate H. pylori&#x02019;s avoidance of this initial line of host defense as well as adaptive immune mechanisms. The host response is thus unsuccessful in clearing the infection and as a result becomes established as a persistent infection promoting chronic inflammation. In some individuals the associated inflammation contributes to ulcerogenesis or neoplasia. H. pylori has an array of different strategies to interact intimately with epithelial cells and manipulate their cellular processes and functions. Among the multiple aspects that H. pylori affects in gastric epithelial cells are their distribution of epithelial junctions, DNA damage, apoptosis, proliferation, stimulation of cytokine production, and cell transformation. Some of these processes are initiated as a result of the activation of signaling mechanisms activated on binding of H. pylori to cell surface receptors or via soluble virulence factors that gain access to the epithelium. The multiple responses by the epithelium to the infection contribute to pathogenesis associated with H. pylori. 展开更多
关键词 Helicobacter pylori APOPTOSIS Gastric epithelial cells Proinflammatory cytokines Chronic inflammation Gastric diseases Gastric cancer
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