AIM:To investigate the effect of keratinocyte growth factor(KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model.METHODS:The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 ...AIM:To investigate the effect of keratinocyte growth factor(KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model.METHODS:The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 mL 5%(v/v) acetic acid.Twenty-four hours after exposed to acetic acid,rats were divided into three experimental groups:control group,attenuated Salmonella typhimurium Ty21a strain(SP) group and SP strain carrying human KGF gene(SPK) group,and they were separately administered orally with 10% NaHCO3,SP or SPK.Animals were sacrificed and colonic tissues were harvested respectively on day 3,5,7 and 10 after administration.Weights of rats,colonic weight/length ratio and stool score were evaluated.Histological changes of colonic tissues were examined by hematoxylin and eosin(HE) staining method.The expression of KGF,KGF receptor(KGFR) and TNF-α were measured either by enzyme-linked immunosorbent assay or Western blotting.Immunohistochemistry was used to detect the cellular localization of KGFR and Ki67.In addition,superoxide dismutase(SOD) activity and malondialdehyde(MDA) contents in the homogenate were measured.RESULTS:Body weight and colonic weight/length ratio were declined in SPK group compared with SP and control groups(body weight:272.78 ± 17.92 g vs 243.72 ± 14.02 g and 240.68 ± 12.63 g,P < 0.01;colonic weight/length ratio:115.76 ± 7.47 vs 150.32 ± 5.99 and 153.67 ± 5.50 mg/cm,P < 0.01).Moreover,pathological changes of damaged colon were improved in SPK group as well.After administration of SPK strain,KGF expression increased markedly from the 3rd d,and remained at a high level till the 10th d.Furthermore,KGFR expression and Ki67 expression elevated,whereas TNF-α expression was inhibited in SPK group.In the group administered with SPK,SOD activity increased significantly(d 5:26.18 ± 5.84 vs 18.12 ± 3.30 and 18.79 ± 4.74 U/mg,P < 0.01;d 7:35.48 ± 3.35 vs 22.57 ± 3.44 and 21.69 ± 3.94 U/mg,P < 0.01;d 10:46.10 ± 6.23 vs 25.35 ± 4.76 and 27.82 ± 6.42 U/mg,P < 0.01) and MDA contents decreased accordingly(d 7:7.40 ± 0.88 vs 9.81 ± 1.21 and 10.45 ± 1.40 nmol/mg,P < 0.01;d 10:4.36 ± 0.62 vs 8.41 ± 0.92 and 8.71 ± 1.27 nmol/mg,P < 0.01),compared with SP and control groups.CONCLUSION:KGF gene therapy mediated by attenuated Salmonella ameliorates ulcerative colitis induced by acetic acids,and it may be a safe and effective treatment for ulcerative colitis.展开更多
AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood...AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were collected.After preparing tissue microarrays and blood smears HGFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were performed.Immunostained samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module software.For semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± SD were determined.In case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± SD) was determined.Using 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were collected.Gene expression analysis of HGFR,CDX2,CD133,leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).RESULTS:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HGFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P < 0.05),CDX2(blood:0 vs 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P < 0.05),CD133(blood:1.1 ± 0.72 vs 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P < 0.05)and Musashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to controls.HGFR/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P < 0.05)and Musashi-1/CDX2(blood and LP:0 vs scattered) coexpressions were found in blood and lamina propria of UC samples.HGFR/CD133 and CD133/CDX2 coexpressions appeared only in UC lamina propria samples.CDX2,Lgr5 and Musashi-1 expressions in UC blood samples were not accompanied by CK20 mRNA expression.CONCLUSION:In active UC,a portion of circulating HGFR-expressing cells are committed to the epithelial lineage,and may participate in mucosal regeneration by undergoing mesenchymal-to-epithelial transition.展开更多
Objective: To explore the comparative observation on nursing effect of nursing intervention and routine nursing in patients with renal calculi and gastric ulcer and the impacts on epidermal growth factor. Methods: A t...Objective: To explore the comparative observation on nursing effect of nursing intervention and routine nursing in patients with renal calculi and gastric ulcer and the impacts on epidermal growth factor. Methods: A total of 72 patients with renal calculi and gastric ulcer were selected and treated in our hospital from January 2018 to December 2018. They were divided into the observation group and the control group, 36 for each. Comprehensive nursing intervention was implemented in the observation group, whereas routine nursing was implemented in the control group. The level of epidermal growth factor, nursing satisfaction, renal calculi recurrence rate, average hospital stay and postoperative blood loss were compared between the two groups after nursing. Results: There was no significant difference in the level of epidermal growth factor between the two groups before nursing (P > 0.05), while after nursing, the level in the observation group was higher compared with the control group, and the difference between the two groups was significant (P Conclusion: With regard to patients with renal calculi and gastric ulcer, comprehensive nursing intervention can improve nursing satisfaction and quality of patients’ lives, reduce calculi recurrence rate, and increase the level of epidermal growth factor, which has clinical application value.展开更多
Objective: To observe the effect of acupuncture-moxibustion on the expression of insulin-like growth factor-I (IGF-I) and suppressor of cytokine signaling-2 (SOCS2) in colonic mucosa of rat models of ulcerative...Objective: To observe the effect of acupuncture-moxibustion on the expression of insulin-like growth factor-I (IGF-I) and suppressor of cytokine signaling-2 (SOCS2) in colonic mucosa of rat models of ulcerative colitis (UC), and explore the mechanism of acupuncture- moxibustion therapy in treating UC. Methods: The rats were randomized into a normal control (NC) group, a model control (MC) group, an herb-partitioned moxibustion (HPM) group and an electroacupuncture (EA) group, 8 in each group. The rat models of UC were established by immunological methods combined with local stimulation. The rats in the HPM and EA groups were given herb-partitioned moxibustion and electroacupuncture treatments respectively, once every day, lasting for 14 d. The morphological variations of rat's colonic mucosa were observed under light microscope; the colonic mucosal mucin was detected by PAS-AB and HID-AB staining methods; the expression of IGF-1 and SOCS2 was assayed by the immunohistochemical method. Results: In the rat models of UC, ulceration and inflammation of the colon were revealed by light microscope. The concentration of colonic mucosal mucin was reduced (P〈0.01), while the expression of IGF-1 had an increase (P〈0.01), and the expression of SOCS2 was reduced (P〈0.01). After HPM or EA treatment, the pathological injuries of colonic mucosa had improved, the concentration of mucin increased (P〈0.01), the expression of IGF-1 decreased (P〈0.01), and the expression of SOCS2 increased (P〈0.01). Conclusion: The secretion of mucosal mucin in rat UC decreased, the expression of IGF-1 was significantly higher, while the expression of SOCS2 was remarkably lower; both HPM and EA can help improve the damage of colonic mucosa in rat UC, and modulate the secretion of mucin, as well as regulate the expression of IGF-1 and SOCS2 in the colonic mucosa.展开更多
Objective: To observe the effect of moxibustion on the expressions of protein keratinocyte growth factor-1 (KGF-1), KGF-2, and interleukin-6 (IL-6) in colon of rats with ulcerative colitis (UC), and to explore ...Objective: To observe the effect of moxibustion on the expressions of protein keratinocyte growth factor-1 (KGF-1), KGF-2, and interleukin-6 (IL-6) in colon of rats with ulcerative colitis (UC), and to explore the action mechanism of moxibustion in treating UC. Methods: SD rats were randomized into a normal group, a model group, a herbs-partitioned moxibustion group, and a sulfasalazine (SASP) group. The rats in the herbs-partitioned group were treated with herbs-partitioned moxibustion at Tianshu (ST 25) and Qihai (CV 6), and those in the SASP group were treated by intragastric administration. After interventions, HE staining and light microscope were adopted in observing the histopathological changes of rat's colon, and immunohistochemical methods for detecting the expressions of KGF-1, KGF-2, and IL-6 proteins in rat's colon. Results: Compared with the model group, the rats' colons in the herbs-partitioned moxibustion group and the SASP group were histopathologically improved; compared with the normal group, the expressions of KGF-1, KGF-2, and IL-6 proteins increased significantly in the model group (P〈0.05); after intervened by herbs-partitioned moxibustion and SASP respectively, the expressions of KGF-1, KGF-2, and IL-6 proteins in rat's colon were decreased markedly (P〈0.05). Conclusion: Both herbs-partitioned moxibustion and SASP can down-regulate the expressions of KGF-1, KGF-2, and IL-6 proteins in rat's colon, which might be one of the mechanisms of herbs-partitioned moxibustion and SASP in treating UC.展开更多
AIM To determine whether recombinant human epidermal growth factor (rhEGF) can protect gastric mucosa against ethanol induced injury in rats. METHOD Fifty four SD rats weighing 200g - 500g each were divided ...AIM To determine whether recombinant human epidermal growth factor (rhEGF) can protect gastric mucosa against ethanol induced injury in rats. METHOD Fifty four SD rats weighing 200g - 500g each were divided into six groups after fasting for 24 hours. Three groups received different doses of oral rhEGF (30, 60 and 120μg·kg -1 ·d -1 ), one group was given cimetidine, one subcutaneous rhEGF (rhEGFⅣ) and one received saline as control. RESULTS Acute gastric dilatation developed in the control and cimetidine groups and bloody gastric juice was found in the control group. The ulcer index was 58 in control group, 53 in rhEGFⅠ, 46 in rhEGFⅡ ( P <0 01) , 11 in rhEGFⅢ ( P <0 01) , 19 in rhEGFⅣ ( P <0 01) , and 39 in cimetidine group ( P <0 05) . CONCLUSION rhEGF protected gastric mucosa against ethanol induced damage. The effect was dose dependent with blood levels of epidermal growth factor (EGF) at a dosage range of 60μg·kg -1 ·d -1 -120μg·kg -1 ·d -1 . It was more effective by injection than via oral route at the same dosage.展开更多
Objective:To observe the effect of moxibustion on the colonic mucosal barrier of rats with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS).Methods:Forty male Sprague-Dawley rats were randomly divided into...Objective:To observe the effect of moxibustion on the colonic mucosal barrier of rats with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS).Methods:Forty male Sprague-Dawley rats were randomly divided into a normal group and a modeling group,with 20 rats in each group.Rats in the modeling group were subjected to preparing experimental UC models by drinking 4%DSS for seven consecutive days.Two modeled rats and two normal rats were randomly selected for model identification.After the success of UC model was confirmed,the remaining 18 modeled rats were randomly divided into three groups,a model group,a model+herbal cake-partitioned moxibustion group,and a model+mild moxibustion group,with six rats in each group;the remaining normal rats were randomly divided into three groups,a normal group,a normal+herbal cake-partitioned moxibustion group,and a normal+mild moxibustion group,with six rats in each group.After 7 d of intervention with the herbal cake-partitioned moxibustion or the mild moxibustion,hematoxylin-eosin(HE)staining technique was used to observe the pathological changes of colon tissue under a light microscope;Western blotting and/or immunohistochemical techniques were used to detect the protein expression levels of Occludin,Claudin,junction adhesion molecular 1(JAM1),mucin 2(MUC2),and transforming growth factor beta1(TGF-β1)in rat colon tissue.Results:Compared with the normal group,the colon tissue was severely damaged,the pathological score was significantly increased,and the protein expression levels of Occludin,Claudin,JAM1,MUC2,and TGF-β1 were significantly decreased in the model group(P<0.01);while there were no significant differences in the colonic histopathological score,protein expression levels of Occludin,Claudin,JAM1,MUC2,and TGF-β1 in the normal+herbal cake-partitioned moxibustion group and the normal+mild moxibustion group(P>0.05).Compared with the model group,the model+herbal cake-partitioned moxibustion group and the model+mild moxibustion group showed repaired colon tissue,ulcer healing,significantly reduced pathological score,and significantly increased protein expression levels of JAM1,MUC2,and TGF-β1(P<0.05);the Occludin protein expression level in the colon tissue of the model+mild moxibustion group was increased(P<0.01).Conclusion:Neither herbal cake-partitioned moxibustion nor mild moxibustion influences the colonic histopathology and intestinal mucosal barrier-related protein expression in the normal rats;both herbal cake-partitioned moxibustion and mild moxibustion can up-regulate the protein expression levels of JAM1,MUC2,and TGF-β1 in the colon tissue of UC rats.Mild moxibustion can up-regulate Occludin protein expression.This may be a mechanism of moxibustion in reducing colonic mucosa inflammation in UC.展开更多
AIM:To investigate the role of epidermal growth factor receptor(EGFR) in colitis-associated dysplasia using the EGFR tyrosine kinase inhibitor erlotinib.METHODS:Sprague-Dawley rats received trinitrobenzene sulfonic ac...AIM:To investigate the role of epidermal growth factor receptor(EGFR) in colitis-associated dysplasia using the EGFR tyrosine kinase inhibitor erlotinib.METHODS:Sprague-Dawley rats received trinitrobenzene sulfonic acid(TNBS;30 mg in 50% ethanol,ic),followed 6 wk later by reactivation with TNBS(5 mg/kg,iv) for 3 d.To induce colitis-associated dysplasia,rats then received TNBS(iv) twice a week for 10 wk.One group received erlotinib(10 mg/kg,ip) for 1 wk before the start of the reactivation of the colitis and 2 wk after(21 d);the rest received the vehicle.After rats were euthanized,the colons were removed and analyzed for damage and expression of the EGFR downstream effectors Erk1/2 and c-Myc.RESULTS:Ninety percent of the vehicle-treated animals had dysplasia in any region of the colon.Erlotinib-treated animals had a significant decrease in the incidence of dysplasia compared to vehicle-treated animals in all regions of the colon(50.00% ± 11.47% vs 90.00% ± 10.00% in proximal,P < 0.05;15.00% ± 8.19% vs 50.00% ± 16.67% in mid,P < 0.05;and 20.00% ± 9.17% vs 70.00% ± 15.28% in distal,P < 0.01).Erlotinib-treated animals also had reduced cell proliferation,reduced active Erk1/2,and reduced c-Myc in colon epithelium compared with the vehicle-treated animals.In vitro,erlotinib treatment was shown to markedly decrease c-Myc and pErk1/2 levels in rat epithelial cells.Proliferation of rat epithelial cells was stimulated by epidermal growth factor and inhibited by erlotinib(P < 0.05).CONCLUSION:Erlotinib can decrease the development of colitis-associated dysplasia,suggesting a potential therapeutic use for erlotinib in patients with long-standing colitis.展开更多
BACKGROUND TreXTAM®is a combination of the key regulatory cytokine transforming growth factor beta(TGFβ)and all trans retinoic acid(ATRA)microencapsulated for oral delivery to immune structures of the gut.It is ...BACKGROUND TreXTAM®is a combination of the key regulatory cytokine transforming growth factor beta(TGFβ)and all trans retinoic acid(ATRA)microencapsulated for oral delivery to immune structures of the gut.It is in development as a novel treatment for inflammatory bowel disease(IBD).AIM To measure TGFβlevels in blood and tissue after oral administration of encapsulated TGFβ.METHODS Animals were orally administered encapsulated TGFβby gavage.Levels of drug substance in blood and in gut tissues at various times after administration were measured by ELISA.RESULTS We made the surprising discovery that oral administration of TreXTAM dramatically(approximately 50%)and significantly(P=0.025)reduced TGFβlevels in colon,but not small intestine or mesenteric lymph nodes.Similarly,levels in rat serum after 25 d of thrice weekly dosing with either TreXTAM,or microencapsulated TGFβalone(denoted as TPX6001)were significantly(P<0.01)reduced from baseline levels.When tested in the SCID mouse CD4+CD25-adoptive cell transfer(ACT)model of IBD,oral TPX6001 alone provided only a transient benefit in terms of reduced weight loss.CONCLUSION These observations suggest a negative feedback mechanism in the gut whereby local delivery of TGFβresults in reduced local and systemic levels of the active form of TGFβ.Our findings suggest potential clinical implications for use of encapsulated TGFβ,perhaps in the context of IBD and/or other instances of fibrosis and/or pathological TGFβsignaling.展开更多
In this study the w/o/w extraction–evaporation technique was adopted to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres loading recombinant human epidermal growth factor (rhEGF). The micro-spheres were char...In this study the w/o/w extraction–evaporation technique was adopted to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres loading recombinant human epidermal growth factor (rhEGF). The micro-spheres were characterized for morphology by transmission electron microscopy (TEM) and particle size distribution. The release performances, the proliferation effects and therapeutic effects of rhEGF-loaded PLGA microspheres were all studied. The results showed that these spherical micro-spheres had a narrow size distribution and a high drug encapsulation efficiency (85.6%). RhEGF-loaded microspheres enhanced the growth rate of fibroblasts and wound healing more efficiently than pure rhEGF. The number of the proliferating cell nuclear antigen (PCNA) in the epidermis layer with the mi-crosphere treatment was significantly larger than those of the control groups. Overall locally sustained delivery of rhEGF from biodegradable PLGA microspheres may serve as a novel therapeutic strategy for diabetic ulcer repair.展开更多
基金Supported by Postdoctoral Science Foundation of China,No.20060390192,200801243research grant from Science and Technology Department of Gansu Province,China,No.0708NKCA128
文摘AIM:To investigate the effect of keratinocyte growth factor(KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model.METHODS:The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 mL 5%(v/v) acetic acid.Twenty-four hours after exposed to acetic acid,rats were divided into three experimental groups:control group,attenuated Salmonella typhimurium Ty21a strain(SP) group and SP strain carrying human KGF gene(SPK) group,and they were separately administered orally with 10% NaHCO3,SP or SPK.Animals were sacrificed and colonic tissues were harvested respectively on day 3,5,7 and 10 after administration.Weights of rats,colonic weight/length ratio and stool score were evaluated.Histological changes of colonic tissues were examined by hematoxylin and eosin(HE) staining method.The expression of KGF,KGF receptor(KGFR) and TNF-α were measured either by enzyme-linked immunosorbent assay or Western blotting.Immunohistochemistry was used to detect the cellular localization of KGFR and Ki67.In addition,superoxide dismutase(SOD) activity and malondialdehyde(MDA) contents in the homogenate were measured.RESULTS:Body weight and colonic weight/length ratio were declined in SPK group compared with SP and control groups(body weight:272.78 ± 17.92 g vs 243.72 ± 14.02 g and 240.68 ± 12.63 g,P < 0.01;colonic weight/length ratio:115.76 ± 7.47 vs 150.32 ± 5.99 and 153.67 ± 5.50 mg/cm,P < 0.01).Moreover,pathological changes of damaged colon were improved in SPK group as well.After administration of SPK strain,KGF expression increased markedly from the 3rd d,and remained at a high level till the 10th d.Furthermore,KGFR expression and Ki67 expression elevated,whereas TNF-α expression was inhibited in SPK group.In the group administered with SPK,SOD activity increased significantly(d 5:26.18 ± 5.84 vs 18.12 ± 3.30 and 18.79 ± 4.74 U/mg,P < 0.01;d 7:35.48 ± 3.35 vs 22.57 ± 3.44 and 21.69 ± 3.94 U/mg,P < 0.01;d 10:46.10 ± 6.23 vs 25.35 ± 4.76 and 27.82 ± 6.42 U/mg,P < 0.01) and MDA contents decreased accordingly(d 7:7.40 ± 0.88 vs 9.81 ± 1.21 and 10.45 ± 1.40 nmol/mg,P < 0.01;d 10:4.36 ± 0.62 vs 8.41 ± 0.92 and 8.71 ± 1.27 nmol/mg,P < 0.01),compared with SP and control groups.CONCLUSION:KGF gene therapy mediated by attenuated Salmonella ameliorates ulcerative colitis induced by acetic acids,and it may be a safe and effective treatment for ulcerative colitis.
基金Cell Analysis Laboratory, 2nd Department of Internal Medicine, and the 1st Department of Pathology and Experimental Oncology, Semmelweis University for their technical support
文摘AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were collected.After preparing tissue microarrays and blood smears HGFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were performed.Immunostained samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module software.For semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± SD were determined.In case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± SD) was determined.Using 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were collected.Gene expression analysis of HGFR,CDX2,CD133,leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).RESULTS:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HGFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P < 0.05),CDX2(blood:0 vs 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P < 0.05),CD133(blood:1.1 ± 0.72 vs 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P < 0.05)and Musashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to controls.HGFR/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P < 0.05)and Musashi-1/CDX2(blood and LP:0 vs scattered) coexpressions were found in blood and lamina propria of UC samples.HGFR/CD133 and CD133/CDX2 coexpressions appeared only in UC lamina propria samples.CDX2,Lgr5 and Musashi-1 expressions in UC blood samples were not accompanied by CK20 mRNA expression.CONCLUSION:In active UC,a portion of circulating HGFR-expressing cells are committed to the epithelial lineage,and may participate in mucosal regeneration by undergoing mesenchymal-to-epithelial transition.
文摘Objective: To explore the comparative observation on nursing effect of nursing intervention and routine nursing in patients with renal calculi and gastric ulcer and the impacts on epidermal growth factor. Methods: A total of 72 patients with renal calculi and gastric ulcer were selected and treated in our hospital from January 2018 to December 2018. They were divided into the observation group and the control group, 36 for each. Comprehensive nursing intervention was implemented in the observation group, whereas routine nursing was implemented in the control group. The level of epidermal growth factor, nursing satisfaction, renal calculi recurrence rate, average hospital stay and postoperative blood loss were compared between the two groups after nursing. Results: There was no significant difference in the level of epidermal growth factor between the two groups before nursing (P > 0.05), while after nursing, the level in the observation group was higher compared with the control group, and the difference between the two groups was significant (P Conclusion: With regard to patients with renal calculi and gastric ulcer, comprehensive nursing intervention can improve nursing satisfaction and quality of patients’ lives, reduce calculi recurrence rate, and increase the level of epidermal growth factor, which has clinical application value.
文摘Objective: To observe the effect of acupuncture-moxibustion on the expression of insulin-like growth factor-I (IGF-I) and suppressor of cytokine signaling-2 (SOCS2) in colonic mucosa of rat models of ulcerative colitis (UC), and explore the mechanism of acupuncture- moxibustion therapy in treating UC. Methods: The rats were randomized into a normal control (NC) group, a model control (MC) group, an herb-partitioned moxibustion (HPM) group and an electroacupuncture (EA) group, 8 in each group. The rat models of UC were established by immunological methods combined with local stimulation. The rats in the HPM and EA groups were given herb-partitioned moxibustion and electroacupuncture treatments respectively, once every day, lasting for 14 d. The morphological variations of rat's colonic mucosa were observed under light microscope; the colonic mucosal mucin was detected by PAS-AB and HID-AB staining methods; the expression of IGF-1 and SOCS2 was assayed by the immunohistochemical method. Results: In the rat models of UC, ulceration and inflammation of the colon were revealed by light microscope. The concentration of colonic mucosal mucin was reduced (P〈0.01), while the expression of IGF-1 had an increase (P〈0.01), and the expression of SOCS2 was reduced (P〈0.01). After HPM or EA treatment, the pathological injuries of colonic mucosa had improved, the concentration of mucin increased (P〈0.01), the expression of IGF-1 decreased (P〈0.01), and the expression of SOCS2 increased (P〈0.01). Conclusion: The secretion of mucosal mucin in rat UC decreased, the expression of IGF-1 was significantly higher, while the expression of SOCS2 was remarkably lower; both HPM and EA can help improve the damage of colonic mucosa in rat UC, and modulate the secretion of mucin, as well as regulate the expression of IGF-1 and SOCS2 in the colonic mucosa.
基金supported by National Basic Research Program of China(973 Program,2009CB522900)Youth Fund Project of the National Natural Science Foundation of China(81001549)+1 种基金Shanghai Program for Cultivation of Elite in Health System(XYQ2011068)2nd Program for Cultivation of Xinglin Scholars by Shanghai University of Traditional Chinese Medicine
文摘Objective: To observe the effect of moxibustion on the expressions of protein keratinocyte growth factor-1 (KGF-1), KGF-2, and interleukin-6 (IL-6) in colon of rats with ulcerative colitis (UC), and to explore the action mechanism of moxibustion in treating UC. Methods: SD rats were randomized into a normal group, a model group, a herbs-partitioned moxibustion group, and a sulfasalazine (SASP) group. The rats in the herbs-partitioned group were treated with herbs-partitioned moxibustion at Tianshu (ST 25) and Qihai (CV 6), and those in the SASP group were treated by intragastric administration. After interventions, HE staining and light microscope were adopted in observing the histopathological changes of rat's colon, and immunohistochemical methods for detecting the expressions of KGF-1, KGF-2, and IL-6 proteins in rat's colon. Results: Compared with the model group, the rats' colons in the herbs-partitioned moxibustion group and the SASP group were histopathologically improved; compared with the normal group, the expressions of KGF-1, KGF-2, and IL-6 proteins increased significantly in the model group (P〈0.05); after intervened by herbs-partitioned moxibustion and SASP respectively, the expressions of KGF-1, KGF-2, and IL-6 proteins in rat's colon were decreased markedly (P〈0.05). Conclusion: Both herbs-partitioned moxibustion and SASP can down-regulate the expressions of KGF-1, KGF-2, and IL-6 proteins in rat's colon, which might be one of the mechanisms of herbs-partitioned moxibustion and SASP in treating UC.
文摘AIM To determine whether recombinant human epidermal growth factor (rhEGF) can protect gastric mucosa against ethanol induced injury in rats. METHOD Fifty four SD rats weighing 200g - 500g each were divided into six groups after fasting for 24 hours. Three groups received different doses of oral rhEGF (30, 60 and 120μg·kg -1 ·d -1 ), one group was given cimetidine, one subcutaneous rhEGF (rhEGFⅣ) and one received saline as control. RESULTS Acute gastric dilatation developed in the control and cimetidine groups and bloody gastric juice was found in the control group. The ulcer index was 58 in control group, 53 in rhEGFⅠ, 46 in rhEGFⅡ ( P <0 01) , 11 in rhEGFⅢ ( P <0 01) , 19 in rhEGFⅣ ( P <0 01) , and 39 in cimetidine group ( P <0 05) . CONCLUSION rhEGF protected gastric mucosa against ethanol induced damage. The effect was dose dependent with blood levels of epidermal growth factor (EGF) at a dosage range of 60μg·kg -1 ·d -1 -120μg·kg -1 ·d -1 . It was more effective by injection than via oral route at the same dosage.
文摘Objective:To observe the effect of moxibustion on the colonic mucosal barrier of rats with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS).Methods:Forty male Sprague-Dawley rats were randomly divided into a normal group and a modeling group,with 20 rats in each group.Rats in the modeling group were subjected to preparing experimental UC models by drinking 4%DSS for seven consecutive days.Two modeled rats and two normal rats were randomly selected for model identification.After the success of UC model was confirmed,the remaining 18 modeled rats were randomly divided into three groups,a model group,a model+herbal cake-partitioned moxibustion group,and a model+mild moxibustion group,with six rats in each group;the remaining normal rats were randomly divided into three groups,a normal group,a normal+herbal cake-partitioned moxibustion group,and a normal+mild moxibustion group,with six rats in each group.After 7 d of intervention with the herbal cake-partitioned moxibustion or the mild moxibustion,hematoxylin-eosin(HE)staining technique was used to observe the pathological changes of colon tissue under a light microscope;Western blotting and/or immunohistochemical techniques were used to detect the protein expression levels of Occludin,Claudin,junction adhesion molecular 1(JAM1),mucin 2(MUC2),and transforming growth factor beta1(TGF-β1)in rat colon tissue.Results:Compared with the normal group,the colon tissue was severely damaged,the pathological score was significantly increased,and the protein expression levels of Occludin,Claudin,JAM1,MUC2,and TGF-β1 were significantly decreased in the model group(P<0.01);while there were no significant differences in the colonic histopathological score,protein expression levels of Occludin,Claudin,JAM1,MUC2,and TGF-β1 in the normal+herbal cake-partitioned moxibustion group and the normal+mild moxibustion group(P>0.05).Compared with the model group,the model+herbal cake-partitioned moxibustion group and the model+mild moxibustion group showed repaired colon tissue,ulcer healing,significantly reduced pathological score,and significantly increased protein expression levels of JAM1,MUC2,and TGF-β1(P<0.05);the Occludin protein expression level in the colon tissue of the model+mild moxibustion group was increased(P<0.01).Conclusion:Neither herbal cake-partitioned moxibustion nor mild moxibustion influences the colonic histopathology and intestinal mucosal barrier-related protein expression in the normal rats;both herbal cake-partitioned moxibustion and mild moxibustion can up-regulate the protein expression levels of JAM1,MUC2,and TGF-β1 in the colon tissue of UC rats.Mild moxibustion can up-regulate Occludin protein expression.This may be a mechanism of moxibustion in reducing colonic mucosa inflammation in UC.
基金Supported by National Institutes of Health Grants, No.U56 CA126379 (to Isidro AA and Appleyard CB), No.CA118809 (to Wu J)a National Institutes of Health Predoctoral Fellowship No.F31 GM078951 (to Pagán B)
文摘AIM:To investigate the role of epidermal growth factor receptor(EGFR) in colitis-associated dysplasia using the EGFR tyrosine kinase inhibitor erlotinib.METHODS:Sprague-Dawley rats received trinitrobenzene sulfonic acid(TNBS;30 mg in 50% ethanol,ic),followed 6 wk later by reactivation with TNBS(5 mg/kg,iv) for 3 d.To induce colitis-associated dysplasia,rats then received TNBS(iv) twice a week for 10 wk.One group received erlotinib(10 mg/kg,ip) for 1 wk before the start of the reactivation of the colitis and 2 wk after(21 d);the rest received the vehicle.After rats were euthanized,the colons were removed and analyzed for damage and expression of the EGFR downstream effectors Erk1/2 and c-Myc.RESULTS:Ninety percent of the vehicle-treated animals had dysplasia in any region of the colon.Erlotinib-treated animals had a significant decrease in the incidence of dysplasia compared to vehicle-treated animals in all regions of the colon(50.00% ± 11.47% vs 90.00% ± 10.00% in proximal,P < 0.05;15.00% ± 8.19% vs 50.00% ± 16.67% in mid,P < 0.05;and 20.00% ± 9.17% vs 70.00% ± 15.28% in distal,P < 0.01).Erlotinib-treated animals also had reduced cell proliferation,reduced active Erk1/2,and reduced c-Myc in colon epithelium compared with the vehicle-treated animals.In vitro,erlotinib treatment was shown to markedly decrease c-Myc and pErk1/2 levels in rat epithelial cells.Proliferation of rat epithelial cells was stimulated by epidermal growth factor and inhibited by erlotinib(P < 0.05).CONCLUSION:Erlotinib can decrease the development of colitis-associated dysplasia,suggesting a potential therapeutic use for erlotinib in patients with long-standing colitis.
基金National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award,No.5R44AI080009.
文摘BACKGROUND TreXTAM®is a combination of the key regulatory cytokine transforming growth factor beta(TGFβ)and all trans retinoic acid(ATRA)microencapsulated for oral delivery to immune structures of the gut.It is in development as a novel treatment for inflammatory bowel disease(IBD).AIM To measure TGFβlevels in blood and tissue after oral administration of encapsulated TGFβ.METHODS Animals were orally administered encapsulated TGFβby gavage.Levels of drug substance in blood and in gut tissues at various times after administration were measured by ELISA.RESULTS We made the surprising discovery that oral administration of TreXTAM dramatically(approximately 50%)and significantly(P=0.025)reduced TGFβlevels in colon,but not small intestine or mesenteric lymph nodes.Similarly,levels in rat serum after 25 d of thrice weekly dosing with either TreXTAM,or microencapsulated TGFβalone(denoted as TPX6001)were significantly(P<0.01)reduced from baseline levels.When tested in the SCID mouse CD4+CD25-adoptive cell transfer(ACT)model of IBD,oral TPX6001 alone provided only a transient benefit in terms of reduced weight loss.CONCLUSION These observations suggest a negative feedback mechanism in the gut whereby local delivery of TGFβresults in reduced local and systemic levels of the active form of TGFβ.Our findings suggest potential clinical implications for use of encapsulated TGFβ,perhaps in the context of IBD and/or other instances of fibrosis and/or pathological TGFβsignaling.
基金the National Natural Science Foundation of China (Grant No. 50373033)the Applied Foundational Research Key Fund of Tianjin (Grant No. 05YFJZJC01001)the International Cooperative Fund of Tianjin (Grant No. 05YFGHHZ20070)
文摘In this study the w/o/w extraction–evaporation technique was adopted to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres loading recombinant human epidermal growth factor (rhEGF). The micro-spheres were characterized for morphology by transmission electron microscopy (TEM) and particle size distribution. The release performances, the proliferation effects and therapeutic effects of rhEGF-loaded PLGA microspheres were all studied. The results showed that these spherical micro-spheres had a narrow size distribution and a high drug encapsulation efficiency (85.6%). RhEGF-loaded microspheres enhanced the growth rate of fibroblasts and wound healing more efficiently than pure rhEGF. The number of the proliferating cell nuclear antigen (PCNA) in the epidermis layer with the mi-crosphere treatment was significantly larger than those of the control groups. Overall locally sustained delivery of rhEGF from biodegradable PLGA microspheres may serve as a novel therapeutic strategy for diabetic ulcer repair.