Objective:To investigate the expressions of caveolin-1,E-cadherin and β-catenin in gastric carcinoma,precancerous gastric and chronic non-atrophic gastritis tissues,and evaluate the correlation of these expressions w...Objective:To investigate the expressions of caveolin-1,E-cadherin and β-catenin in gastric carcinoma,precancerous gastric and chronic non-atrophic gastritis tissues,and evaluate the correlation of these expressions with the development of gastric cancer.Methods:The expressions of caveolin-1,E-cadherin and β-catenin were detected by biotin-streptavidin-peroxidase(SP) immunohistochemistry on 58 gastric cancer tissues,40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues.The correlation between the expressions of caveolin-1,E-cadherin and β-catenin,and the clinicopathologic parameters of gastric cancer was analyzed retrospectively.Results:The positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues(P<0.01).An abnormal rate of β-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues(P<0.01).Moreover,low expressions of caveolin-1,E-cadherin and β-catenin correlated with tumor size,depth of invasion,lymph node metastasis and TNM stage(P<0.05).The positive rates of caveolin-1 and E-cadherin expressions decreased(P<0.01),while an abnormal rate of β-catenin expression increased inversely,with the degree of atypical hyperplasia(P<0.01).Caveolin-1 expression correlated positively with E-cadherin(r=0.41,P<0.05).Caveolin-1(r= 0.36,P<0.05) and E-cadherin(r= 0.45,P<0.05) expressions negatively correlated with abnormal β-catenin expression.Conclusion: These results suggested that dysregulated expressions of caveolin‐1, E‐cadherin and β‐catenin correlated with the development of gastric cancer and its biological behavior.展开更多
AIM:To detect the expression of 60 microRNAs(miRNAs)in gastric cancer tissues and find new predictive biomarkers of gastric cancer with metastasis.METHODS:The expressions of 60 candidate miRNAs in 30 gastric cancer ti...AIM:To detect the expression of 60 microRNAs(miRNAs)in gastric cancer tissues and find new predictive biomarkers of gastric cancer with metastasis.METHODS:The expressions of 60 candidate miRNAs in 30 gastric cancer tissues and paired normal tissues were detected by stem-loop real-time reverse transcription-polymerase chain reaction.After primary screening of miRNAs expression,5 selected miRNAs were further testified in another 22 paired gastric tissues.Based on the expression level of miRNAs and the status of metastasis to lymph node(LN),receiver-operating-characteristic(ROC)curve were used to evaluate their ability in predicting the status of metastasis to LN.RESULTS:Thirty-eight miRNAs expressions in gastric cancer tissues were significantly different from those in paired normal tissues(P<0.01).Among them,31miRNAs were found to be up-expressed in cancer tissues and 1 miRNAs were down-expressed≥1.5 fold vs paired normal gastric tissue.Five microRNAs(miR-125a-3p,miR-133b,miR-143,miR-195 and miR-212)were differently expressed between different metastatic groups in 30 gastric cancer biopsies(P<0.05).Partial correlation analysis showed that hsa-mir-212 and hsa-mir-195 were correlated with the status of metastasis to LN in spite of age,gender,tumor location,tumor size,depth of invasion and cell differentiation.ROC analysis indicated that miR-212 and miR-195 have better sensi-tivities(84.6%and 69.2%,respectively)and specifici-ties(both 100%)in distinguishing biopsies with metastasis to LN from biopsies without metastasis to LN.CONCLUSION:miR-212 and miR-195 could be independent biomarkers in predicting the gastric cancer with metastasis to LN.展开更多
AIM: To investigate the implication of the hypoxia inducible factor HIF-1α mRNA in gastric carcinoma and its relation to the expression of vascular endothelial growth factor (VEGF) protein, tumor angiogenesis invasio...AIM: To investigate the implication of the hypoxia inducible factor HIF-1α mRNA in gastric carcinoma and its relation to the expression of vascular endothelial growth factor (VEGF) protein, tumor angiogenesis invasion/metastasis and the patient's survival. METHODS: In situ hybridization was used to examine expression of HIF-1α mRNA, and immunohistochemical staining was used to examine expression of VEGF protein and CD34 in 118 specimens from patients with gastric carcinoma. RESULTS: The positive rates of HIF-1α mRNA and VEGF protein were 49.15% and 55.92%, respectively. Positive expressions of HIF-1α and VEGF in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis were dramatically stronger than stage T1-T2 cases and those without vessel invasion, lymph node metastasis and distant metastasis. The mean microvascular density (MVD) in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis was significantly higher than stage T1-T2 tumors and those without vessel invasion, lymph node metastasis and distant metastasis. The mean MVD in tumors with positive HIF-1α and VEGF expression was significantly higher than that in tumors with negative HIF-1α and VEGF expression. The expression of HIF- 1α was positively correlated with VEGF protein. There were positive correlations between MVD and expressionof HIF-1α and VEGF. The mean survival time and the 5-year survival rate in cases with positive expression HIF-1α and VEGF and MVD value ≥ 41.5/0.72 mm2 were significantly lower than those with negative expression of HIF-1α and VEGF and MVD value < 41.5/0.72 mm2. CONCLUSION: Overexpression of HIF-1α is found in gastric carcinoma. HIF-1α may induce the angiogenesis in gastric carcinoma by upregulating the transcription of VEGF gene, and take part in tumor invasion and metastasis. They can be used as prognostic markers of gastric cancer in clinical practice.展开更多
AIM:To investigate the effect and mechanism of oridonin on the gastric cancer cell line HGC-27 in vitro.METHODS:The inhibitory effect of oridonin on HGC-27 cells was detected using the 3-(4,5-dimethylthiazol2-yl)-2,5-...AIM:To investigate the effect and mechanism of oridonin on the gastric cancer cell line HGC-27 in vitro.METHODS:The inhibitory effect of oridonin on HGC-27 cells was detected using the 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyl tetrazolium bromide assay.After treatment with 10 μg/mL oridonin for 24 h and 48 h,the cells were stained with acridine orange/ethidium bromide.The morphologic changes were observed under an inverted fluorescence microscope.DNA fragmen-tation(a hallmark of apoptosis) and lactate dehydrogenase activity were examined using DNA ladder assay and lactate dehydrogenase-release assay.After treated with oridonin(0,1.25,2.5,5 and 10 μg/mL),HGC-27 cells were collected for anexin V-phycoerythrin and 7-amino-actinomycin D double staining and tested by flow cytometric analysis,and oridonin-induced apoptosis in HGC-27 cells was detected.After treatment with oridonin for 24 h,the effects of oridonin on expression of Apaf-1,Bcl-2,Bax,caspase-3 and cytochrome c were also analyzed using reverse-transcript polymerase chain reaction(RT-PCR) and Western blotting.RESULTS:Oridonin significantly inhibited the proliferation of HGC-27 cells in a dose-and time-dependent manner.The inhibition rates of HGC-27 treated with four different concentrations of oridonin for 24 h(1.25,2.5,5 and 10 μg/mL) were 1.78% ± 0.36%,4.96% ± 1.59%,10.35% ± 2.76% and 41.6% ± 4.29%,respectively,which showed a significant difference(P < 0.05).The inhibition rates of HGC-27 treated with oridonin at the four concentrations for 48 h were 14.77% ± 4.21%,21.57% ± 3.75%,30.31% ± 4.91% and 61.19% ± 5.81%,with a significant difference(P < 0.05).The inhibition rates of HGC-27 treated with oridonin for 72 h at the four concentrations were 25.77% ± 4.85%,31.86% ± 3.86%,48.30% ± 4.16% and 81.80% ± 6.72%,with a significant difference(P < 0.05).Cells treated with oridonin showed typical apoptotic features with acridine orange/ethidium bromide staining.After treatment with oridonin,the cells became round,shrank,and developed small buds around the nuclear membrane while forming apoptotic bodies.Lactate dehydrogenase(LDH) release assay showed that after treated with 1.25 μg/mL and 20 μg/mL oridonin for 24 h,LDH release of HGC-27 caused by apoptosis increased from 22.94% ± 3.8% to 52.68% ± 2.4%(P < 0.001).However,the change in the release of LDH caused by necrosis was insignificant,suggesting thatthe major cause of oridonin-induced HGC-27 cell death was apoptosis.Flow cytometric analysis also revealed that oridonin induced significant apoptosis compared with the controls(P < 0.05).And the apoptosis rates of HGC-27 induced by the four different concentrations of oridonin were 5.3% ± 1.02%,12.8% ± 2.53%,28.5% ± 4.23% and 49.6% ± 3.76%,which were in a dose-dependent manner(P < 0.05).After treatment for 24 h,DNA ladder showed that oridonin induced a significant increase in DNA fragmentation in a dosedependent manner.RT-PCR revealed that mRNA expression levels were up-regulated compared with the controls in caspase-3(0.917 ± 0.103 vs 0.357 ± 0.019,P < 0.05),cytochrome c(1.429 ± 0.111 vs 1.002 ± 0.014,P < 0.05),Apaf-1(0.688 ± 0.101 vs 0.242 ± 0.037,P < 0.05) and Bax(0.856 ± 0.101 vs 0.278 ± 0.027,P < 0.05)(P < 0.05),whereas down-regulated in Bcl-2(0.085 ± 0.012 vs 0.175 ± 0.030,P < 0.05).Western blotting analysis also confirmed this result.CONCLUSION:Apoptosis of HGC-27 induced by oridonin may be associated with differential expression of Apaf-1,caspase-3 and cytochrome c,which are highly dependent upon the mitochondrial pathway.展开更多
AIM: To assess the value of plasma melatonin in pre-dicting acute pancreatitis when combined with the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and bedside index for severity in acute pancreatitis ...AIM: To assess the value of plasma melatonin in pre-dicting acute pancreatitis when combined with the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and bedside index for severity in acute pancreatitis (BISAP) scoring systems. METHODS: APACHEⅡ and BISAP scores were calculated for 55 patients with acute physiology (AP) in the first 24 h of admission to the hospital. Additionally, morning (6:00 AM) serum melatonin concentrations were measured on the first day after admission. According to the diagnosis and treatment guidelines for acute pancreatitis in China, 42 patients suffered mild AP (MAP). The other 13 patients developed severe AP (SAP). A total of 45 healthy volunteers were used in this study as controls. The ability of melatonin and the APACHEⅡ and BISAP scoring systems to predict SAP was evaluated using a receiver operating characteristic (ROC) curve. The optimal melatonin cutoff concentration for SAP patients, based on the ROC curve, was used to classify the patients into either a high concen-tration group (34 cases) or a low concentration group (21 cases). Differences in the incidence of high scores, according to the APACHEⅡ and BISAP scoring sys- tems, were compared between the two groups. RESULTS: The MAP patients had increased melatonin levels compared to the SAP (38.34 ng/L vs 26.77 ng/L) (P = 0.021) and control patients (38.34 ng/L vs 30.73 ng/L) (P = 0.003). There was no significant difference inmelatoninconcentrations between the SAP group and the control group. The accuracy of determining SAP based on the melatonin level, the APACHEⅡ score and the BISAP score was 0.758, 0.872, and 0.906, respectively, according to the ROC curve. A melatonin concentration ≤ 28.74 ng/L was associated with an increased risk of developing SAP. The incidence of high scores (≥ 3) using the BISAP system was significantly higher in patients with low melatonin concentration (≤ 28.74 ng/L) compared to patients with high melatonin concentration (> 28.74 ng/L) (42.9% vs 14.7%, P = 0.02). The incidence of high APACHEⅡ scores (≥ 10) between the two groups was not significantly different. CONCLUSION: The melatonin concentration is closely related to the severity of AP and the BISAP score. Therefore, we can evaluate the severity of disease by measuring the levels of serum melatonin.展开更多
Blue rubber bleb nevus syndrome(BRBNS)is a rare disease characterized by multiple venous malformations and hemangiomas in the skin and visceral organs.The lesions often involve the cutaneous and gastrointestinal syste...Blue rubber bleb nevus syndrome(BRBNS)is a rare disease characterized by multiple venous malformations and hemangiomas in the skin and visceral organs.The lesions often involve the cutaneous and gastrointestinal systems.Other organs can also be involved,such as the central nervous system,liver,and muscles.The most common symptoms are gastrointestinal bleeding and secondary iron deficiency anemia.The syndrome may also present with severe complications such as rupture,intestinal torsion,and intussusception,and can even cause death.Cutaneous malformations are usually asymptomatic and do not require treatment.The treatment of gastrointestinal lesions is determined by the extent of intestinal involvement and severity of the disease.Most patients respond to supportive therapy,such as iron supplementation and blood transfusion.For more significant hemorrhages or severe complications,surgical resection,endoscopic sclerosis,and laser photocoagulation have been proposed.Here we present a case of BRBNS in a 45-year-old woman involving 16sites including the scalp,eyelid,orbit,lip,tongue,face,back,upper and lower limbs,buttocks,root of neck,clavicle area,superior mediastinum,glottis,esophagus,colon,and anus,with secondary severe anemia.In addition,we summarize the epidemiology,clinical manifestations,diagnosis,differential diagnosis and therapies of this disease by analyzing all previously reported cases to enhance the awareness of this syndrome.展开更多
Minimally invasive endoscopic resection has become an increasingly popular method for patients with small(less than 3.5 cm in diameter) gastric subepithelial tumors(SETs) originating from the muscularis propria(MP) la...Minimally invasive endoscopic resection has become an increasingly popular method for patients with small(less than 3.5 cm in diameter) gastric subepithelial tumors(SETs) originating from the muscularis propria(MP) layer. Currently, the main endoscopic therapies for patients with such tumors are endoscopic muscularis excavation, endoscopic full-thickness resection, and submucosal tunneling endoscopic resection. Although these endoscopic techniques can be used for complete resection of the tumor and provide an accurate pathological diagnosis, these techniques have been associated with several negative events, such as incomplete resection, perforation, and bleeding. This review provides detailed information on the technical details, likely treatment outcomes, and complications associated with each endoscopic method for treating/removing small gastric SETs that originate from the MP layer.展开更多
AIM:To investigate the relationship between polymorphisms present in the vitamin D receptor(VDR) gene and colorectal cancer risk,a systematic meta-analysis of population-based studies was performed.METHODS:A total of ...AIM:To investigate the relationship between polymorphisms present in the vitamin D receptor(VDR) gene and colorectal cancer risk,a systematic meta-analysis of population-based studies was performed.METHODS:A total of 38 relevant reports published between January 1990 and August 2010 were identified,of which only 23 qualified for this meta-analysis based on our selection criteria.Five polymorphic variants of the VDR gene,including Cdx-2(intron 1e) and FokI(exon 2) present in the 5' region of the gene,and BsmI(intron 8),ApaI(intron 8),and TaqI(exon 9) sites present in the 3' untranslated region(UTR),were evaluated for possible associations with colorectalcancer risk.Review manager 4.2 was used to perform statistical analyses.RESULTS:In the meta-analysis performed,only the BsmI polymorphism was found to be associated with colorectal cancer risk.In particular,the BsmI B genotype was found to be related to an overall decrease in the risk for colorectal cancer [BB vs bb:odds ratio(OR) = 0.87,95% CI:0.80-0.94,P = 3 × 10-4;BB vs Bb + bb:OR = 0.90,95% CI:0.84-0.97,P = 5 × 10-4].Moreover,in subgroup analyses,the BsmI B genotype was significantly associated with colon cancer,and not rectal cancer.An absence of between-study heterogeneity was also observed.CONCLUSION:A meta-analysis of 23 published studies identified the BsmI polymorphism of the VDR gene to be associated with an increased risk of colon cancer.展开更多
AIM: To evaluate the relationship between the expression of cell adhesion molecules (CAMs) and the biological behavior of gastric carcinoma. METHODS: Expression of syndecan-1, E-cadherin and integrin β3 were evaluate...AIM: To evaluate the relationship between the expression of cell adhesion molecules (CAMs) and the biological behavior of gastric carcinoma. METHODS: Expression of syndecan-1, E-cadherin and integrin β3 were evaluated by immunohistochemical study in a total of 118 gastric carcinomas and 20 non- tumor gastric mucosas. RESULTS: The expressions of syndecan-1 and E-cadherin were significantly lower in gastric carcinoma compared to non-tumor gastric mucosa, and the low expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). However, the expression of integrin β3 was significantly higher in gastric carcinoma compared to non-tumor gastric mucosa, and the high expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). In addition, the three protein expressions were correlated to the tumor growth pattern (P < 0.01, P < 0.01, and P < 0.05 respectively), but not correlated to tumor differentiation (P > 0.05, P > 0.05 and P > 0.05 respectively). Positive correlation was observed between the expressions of syndecan-1 and E-cadherin, but they which were negatively correlated to the expression of integrin β3 (P < 0.01 in all cases). Univariate analysis demonstrated that the mean survival time and 5-year survival rate were lower in the cases with low expressions of syndecan-1 and E-cadherin and high expression of integrin β3 (P < 0.01, in all cases). COX multivariate analysis showed that the expression level of syndecan-1 could be an independent prognostic index of gastric carcinoma (P < 0.01), whereas E-cadherin and integrin β3 could not be independent indexes (P > 0.05, P > 0.05 respectively). CONCLUSION: The low expression of syndecan-1 and E-cadherin and the high expression of integrin β3 are significantly correlated with the invasion and metastasis of gastric carcinoma, and they are highly correlated with each other. Therefore they may serve as important prognostic markers of gastric carcinoma.展开更多
AIM:To compare the visual and optical performance of eyes with different corneal spherical aberration(SA) implanted with spherical aberration-free intraocular lens(IOLs).· METHODS:Thirty-six patients with differe...AIM:To compare the visual and optical performance of eyes with different corneal spherical aberration(SA) implanted with spherical aberration-free intraocular lens(IOLs).· METHODS:Thirty-six patients with different corneal SA had phacoemulsification with implantation of spherical aberration-free IOLs.Patients were divided into 3 groups according to the value of preoperative corneal SA.Eyes with corneal SA <0.10μm were assigned to group A,those with 0.10 ≤corneal SA <0.20μm to Group B,and those with 0.20≤corneal SA <0.35μm to Group C.Best-corrected visual acuity(BCVA),contrast sensitivity,corneal SA,total ocular aberrations,and depth of focus were recorded 3 months postoperatively.Distance-corrected near and intermediate visual acuity was studied to measure depth of focus.· RESULTS:BCVA and contrast sensitivity were similar between groups.There were no significant differences in distance-corrected near or intermediate visual acuity.Corneal SA was similar before and 3 months after surgery in the 3 groups.With a 5.0mm pupil diameter,root mean square values for total ocular higher-order aberrations(HOAs) were lower in groups A and B than in group C.Total ocular SA was lower in group A than in groups B and C.SA was also lower in group B than in group C.Coma and trefoil were similar between the groups.· CONCLUSION:Implantation of spherical aberration-free IOLs in eyes with different corneal SA results in similar visual performance at BCVA,contrast sensitivity and depth of focus.展开更多
Summary: The changes of tumor necrosis factor-α (TNF-α) and brain ultrastructure during cardiopulmonary resuscitation and the effects of ulinastation injection were observed, and the mechanism was investigated. Twen...Summary: The changes of tumor necrosis factor-α (TNF-α) and brain ultrastructure during cardiopulmonary resuscitation and the effects of ulinastation injection were observed, and the mechanism was investigated. Twenty-four adult healthy Sprague-Dawley rats were randomly divided into control group (8 rats), resuscitation group (8 rats) and ulinastatin (UTI) group (8 rats). Rats in control group underwent tracheotomy without clipping the trachea to induce circulatory and respiratory standstill. Rats in resuscitation and ulinastatin group were subjected to the procedure of establishing the model of cardiopulmonary cerebral resuscitation (CPCR). Rats in ulinastatin group were given with UTI 104 U/kg once after CPCR. In the control group, the plasma was collected immediate, 30 min, 2 h, 4 h, and 6 h after tracheotomy. In resuscitation group and UTI group, plasma was collected immediate after tracheotomy, 30 min, 2 h, 4 h and 6 h after successful resuscitation. The plasma levels of TNF-α were determined by radioimmunoassay (RIA). At the end of the experiment, 2 rats were randomly selected from each group and were decapitated. The cortex of the brain was taken out immediately to observe the ultrastructure changes. In control group, there were no significant differences in the level of TNF-α among different time points (P>0.05). In resuscitation group, the level of TNF-α was increased obviously after resuscitation (P<0.01) and reached its peak 2 h later after resuscitation. An increasing trend of TNF-α showed in UTI group. There were no differences in TNF-α among each sample taken after successful resuscitation and that after tracheotomy. The utrastructure of brains showed the injury in UTI group was ameliorated as compared with that in resuscitation group. In early period of CPCR, TNF-α was expressed rapidly and kept increasing. It indicated that TNF-α might take part in the tissue injury after CPCR. The administration of UTI during CACR could depress TNF-α and ameliorate brain injury. By regulating the expression of damaging mediator, UTI might provide a protective effect on the tissue injury after CPCR.展开更多
Objective: To investigate a possible mechanism responsible for anti-apoptotic effects of melatonin and provide theoretical evidences for clinical therapy. Methods: Ischemia-reperfusion mediated neuronal cell injury mo...Objective: To investigate a possible mechanism responsible for anti-apoptotic effects of melatonin and provide theoretical evidences for clinical therapy. Methods: Ischemia-reperfusion mediated neuronal cell injury model was constructed in cerebellar granule neurons (CGNs) by deprivation of glucose, serum and oxygen in media. After ischemia, melatonin was added to the test groups to reach differential concentration during reperfusion. DNA fragmentation, mitochondrial transmembrane potential, mitochondrial cytochrome c release and caspase-3 activity were observed after subjecting cerebellar granule neurons to oxy-gen-glucose deprivation (OGD). Results: The results showed that OGD induced typical cell apoptosis change, DNA ladder and apoptosis-related alterations in mitochondrial functions including depression of mitochondrial transmembrane potential (its maximal protection ratio was 73.26%) and release of cytochrome c (its maximal inhibition ratio was 42.52%) and the subsequent activation of caspase-3 (its maximal protection ratio was 59.32%) in cytoplasm. Melatonin reduced DNA damage and inhibited release of mitochondrial cytochrome c and activation of caspase-3. Melatonin can strongly prevent the OGD-induced loss of the mitochondria membrane potential. Conclusion: Our findings suggested that the direct inhibition of mitochondrial pathway might essentially contribute to its anti-apoptotic effects in neuronal ischemia-reperfusion.展开更多
Objective:To study the protective effect of resveratrol on lens epithelial cell apoptosis in diabetic cataract rat.Methods:A total of 84 Wistar rats were divided into 4 groups:12 in Group A(control group).24 in Group ...Objective:To study the protective effect of resveratrol on lens epithelial cell apoptosis in diabetic cataract rat.Methods:A total of 84 Wistar rats were divided into 4 groups:12 in Group A(control group).24 in Group B(diabetic cataract group),24 in Group C(therapeutic-dose of resveratrol group) and 24 in Group D(low-dose of resveratrol group).Rats in Group B-D were given with60 mg/kg streptozotocin through intraperitoneal injection.Rats in Group C were given with 100mg/kg resveratrol and rats in Group D were given with 20 mg/kg resveratrol.The caspase-3expression levels and apoptosis ratios of LEC among each group were observed:the degrees of lens opacity in Group B-D after 12 weeks were compared.Results:There were significant differences in caspase-3 expression levels,apoptosis ratios of T.F.C among groups at 4 w,8 w and12 w(P<0.05).After 12 weeks,in Group B the degree of lens opacity was as follow:0(0.00%) in grade Ⅰ,3(37.50%) in grade Ⅱ,2(25.00%)in grade Ⅲ,2(25.00%)grade Ⅳ,and 1(12.50%) in gradeⅤ:in Group C:2(25.00%)in grade Ⅰ,4(50.00%) in grade Ⅱ.2(25.00%)in grade Ⅲ,0(0.00%)gradeⅣ,and 0(0.00%) in grade Ⅴ;in Group D:1(12.50%)in grade Ⅰ,4(50.00%) in grade Ⅱ,2(25.00%)in grade Ⅲ,1(12.50%) grade Ⅳ,and 0(0.00%) in grade Ⅴ.The.difference among Group B-D was statistically significant(P<0.05).Conclusions:Resveratrol has protective effect on lens epithelial cell apoptosis in diabetic cataract rat,and the effect is relative to its dose.展开更多
Receptor imidazoline 2 (I2) is one of the imidazoline receptors with high affinity for 3H-idazoxan. Receptor I2,being classified into I2A and I2B subtypes,is mainly localized to the outer membrane of mitochondria in l...Receptor imidazoline 2 (I2) is one of the imidazoline receptors with high affinity for 3H-idazoxan. Receptor I2,being classified into I2A and I2B subtypes,is mainly localized to the outer membrane of mitochondria in liver,kidney and brain. Receptor I2,displaying high similarity of sequence with monoamine oxidase-B (MAO-B),is structurally related to MAO-B,but the I2 imidazoline binding site (I2BS) with ligand is distinct from the catalytic site of MAO-B. Agmatine is the endogenous ligand of receptor I2. Accumulating evidence have revealed that the activation of receptors I2 may produce neuroprotective effects by increasing expression of glial fibrillary acidic protein (GFAP) in astrocytes,inhibiting activity of MAO,reducing calcium overload in cells. Agmatine exerts neuroprotection against ischemia-hypoxia,injury,glutamate-induced neurotoxicity by activating imidazoline receptors,blocking N-methyl-D-aspartate (NMDA) receptor,inhibiting all isoforms of nitric oxide synthase (NOS),and selectively blocking the voltage-gated calcium channels (VGCC). It would be expected that agmatine is one of the potential neuroprotective agents.展开更多
AIM: To examine fibrinogen-like protein 2 (fgl2) expression during taurocholate-induced acute pancreatitis progression in rats and its correlation with pancreatic injury severity. METHODS: Forty-eight male Sprague-Daw...AIM: To examine fibrinogen-like protein 2 (fgl2) expression during taurocholate-induced acute pancreatitis progression in rats and its correlation with pancreatic injury severity. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into the severe acute pancreatitis (SAP) group (n = 24) and the sham operation (SO) group (n = 24). Sodium taurocholate (4% at doses of 1 mL/kg body weight) was retrogradely injected into the biliopancreatic ducts of the rats to induce SAP. Pancreatic tissues were prepared immediately after sacrifice. At the time of sacrifice, blood was obtained for determination of serum amylase activity and isolation of peripheral blood mononuclear cells (PBMCs). Pancreatic tissue specimens were obtained for routine light microscopy including hematoxylin and eosin staining, and the severity of pancreatic injury was evaluated 1, 4 and 8 h after induction. Expression of fgl2 mRNA was measured in the pancreas and PBMCs using reverse transcription polymerase chain reaction. Expression of fgl2 protein was evaluated in pancreatic tissues using Western blotting and immunohistochemical staining. Masson staining was also performed to observe microthrombosis. RESULTS: At each time point, levels of fgl2 mRNAs in pancreatic tissues and PBMCs were higher (P < 0.05) in the SAP group than in the SO group. For pancreatic tissue in SAP vs SO, the levels were: after 1 h, 3.911 ± 1.277 vs 1.000 ± 0.673; after 4 h, 9.850 ± 3.095 vs 1.136 ± 0.609; and after 8 h, 12.870 ± 3.046 vs 1.177 ± 0.458. For PBMCs in SAP vs SO, the levels were: after 1 h, 2.678 ± 1.509 vs 1.000 ± 0.965; after 4 h, 6.922 ± 1.984 vs 1.051 ± 0.781; and after 8 h, 13.533 ± 6.575 vs 1.306 ± 1.179. Levels of fgl2 protein expression as determined by Western blotting and immunohistochemical staining were markedly up-regulated (P < 0.001) in the SAP group compared with those in the SO group. For Western blotting in SAP vs SO, the results were: after 1 h, 2.183 ± 0.115 vs 1.110 ± 0.158; after 4 h, 2.697 ± 0.090 vs 0.947 ± 0.361; and after 8 h, 3.258 ± 0.094 vs 1.208 ± 0.082. For immunohistochemical staining in SAP vs SO, the results were: after 1 h, 1.793 ± 0.463 vs 0.808 ± 0.252; after 4 h, 4.535 ± 0.550 vs 0.871 ± 0.318; and after 8 h, 6.071 ± 0.941 vs 1.020 ± 0.406. Moreover, we observed a positive correlation in the pancreas (r = 0.852, P < 0.001) and PBMCs (r = 0.735, P < 0.001) between fgl2 expression and the severity of pancreatic injury. Masson staining showed that microthrombosis (%) in rats with SAP was increased (P < 0.001) compared with that in the SO group and it was closely correlated with fgl2 expression in the pancreas (r = 0.842, P < 0.001). For Masson staining in SAP vs SO, the results were: after 1 h, 26.880 ± 9.031 vs 8.630 ± 3.739; after 4 h, 53.750 ± 19.039 vs 8.500 ± 4.472; and after 8 h, 80.250 ± 12.915 vs 10.630 ± 7.003.CONCLUSION: Microthrombosis due to fgl2 overexpression contributes to pancreatic impairment in rats with SAP, and fgl2 level may serve as a biomarker during early stages of disease.展开更多
基金supported by Zhejiang Provincial Natural Science Foundation (No. Y206750)Zhejiang Foundation for Development of Science and Technology, China (No. 2008C33066)Wenzhou Foundation for Development of Science and Technology,China (No. H20060026)
文摘Objective:To investigate the expressions of caveolin-1,E-cadherin and β-catenin in gastric carcinoma,precancerous gastric and chronic non-atrophic gastritis tissues,and evaluate the correlation of these expressions with the development of gastric cancer.Methods:The expressions of caveolin-1,E-cadherin and β-catenin were detected by biotin-streptavidin-peroxidase(SP) immunohistochemistry on 58 gastric cancer tissues,40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues.The correlation between the expressions of caveolin-1,E-cadherin and β-catenin,and the clinicopathologic parameters of gastric cancer was analyzed retrospectively.Results:The positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues(P<0.01).An abnormal rate of β-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues(P<0.01).Moreover,low expressions of caveolin-1,E-cadherin and β-catenin correlated with tumor size,depth of invasion,lymph node metastasis and TNM stage(P<0.05).The positive rates of caveolin-1 and E-cadherin expressions decreased(P<0.01),while an abnormal rate of β-catenin expression increased inversely,with the degree of atypical hyperplasia(P<0.01).Caveolin-1 expression correlated positively with E-cadherin(r=0.41,P<0.05).Caveolin-1(r= 0.36,P<0.05) and E-cadherin(r= 0.45,P<0.05) expressions negatively correlated with abnormal β-catenin expression.Conclusion: These results suggested that dysregulated expressions of caveolin‐1, E‐cadherin and β‐catenin correlated with the development of gastric cancer and its biological behavior.
基金Supportedby Nature Science Foundation of Zhejiang Province No. Y2080978Wenzhou Science and Technology Bureau No. H20100028 and No. Y20070067
文摘AIM:To detect the expression of 60 microRNAs(miRNAs)in gastric cancer tissues and find new predictive biomarkers of gastric cancer with metastasis.METHODS:The expressions of 60 candidate miRNAs in 30 gastric cancer tissues and paired normal tissues were detected by stem-loop real-time reverse transcription-polymerase chain reaction.After primary screening of miRNAs expression,5 selected miRNAs were further testified in another 22 paired gastric tissues.Based on the expression level of miRNAs and the status of metastasis to lymph node(LN),receiver-operating-characteristic(ROC)curve were used to evaluate their ability in predicting the status of metastasis to LN.RESULTS:Thirty-eight miRNAs expressions in gastric cancer tissues were significantly different from those in paired normal tissues(P<0.01).Among them,31miRNAs were found to be up-expressed in cancer tissues and 1 miRNAs were down-expressed≥1.5 fold vs paired normal gastric tissue.Five microRNAs(miR-125a-3p,miR-133b,miR-143,miR-195 and miR-212)were differently expressed between different metastatic groups in 30 gastric cancer biopsies(P<0.05).Partial correlation analysis showed that hsa-mir-212 and hsa-mir-195 were correlated with the status of metastasis to LN in spite of age,gender,tumor location,tumor size,depth of invasion and cell differentiation.ROC analysis indicated that miR-212 and miR-195 have better sensi-tivities(84.6%and 69.2%,respectively)and specifici-ties(both 100%)in distinguishing biopsies with metastasis to LN from biopsies without metastasis to LN.CONCLUSION:miR-212 and miR-195 could be independent biomarkers in predicting the gastric cancer with metastasis to LN.
基金grant from Zhejiang Province Natural Science Foundation, No. M303843
文摘AIM: To investigate the implication of the hypoxia inducible factor HIF-1α mRNA in gastric carcinoma and its relation to the expression of vascular endothelial growth factor (VEGF) protein, tumor angiogenesis invasion/metastasis and the patient's survival. METHODS: In situ hybridization was used to examine expression of HIF-1α mRNA, and immunohistochemical staining was used to examine expression of VEGF protein and CD34 in 118 specimens from patients with gastric carcinoma. RESULTS: The positive rates of HIF-1α mRNA and VEGF protein were 49.15% and 55.92%, respectively. Positive expressions of HIF-1α and VEGF in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis were dramatically stronger than stage T1-T2 cases and those without vessel invasion, lymph node metastasis and distant metastasis. The mean microvascular density (MVD) in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis was significantly higher than stage T1-T2 tumors and those without vessel invasion, lymph node metastasis and distant metastasis. The mean MVD in tumors with positive HIF-1α and VEGF expression was significantly higher than that in tumors with negative HIF-1α and VEGF expression. The expression of HIF- 1α was positively correlated with VEGF protein. There were positive correlations between MVD and expressionof HIF-1α and VEGF. The mean survival time and the 5-year survival rate in cases with positive expression HIF-1α and VEGF and MVD value ≥ 41.5/0.72 mm2 were significantly lower than those with negative expression of HIF-1α and VEGF and MVD value < 41.5/0.72 mm2. CONCLUSION: Overexpression of HIF-1α is found in gastric carcinoma. HIF-1α may induce the angiogenesis in gastric carcinoma by upregulating the transcription of VEGF gene, and take part in tumor invasion and metastasis. They can be used as prognostic markers of gastric cancer in clinical practice.
基金Supported by Medical and Health Research Foundation of Zhejiang Province,No. 2009B019
文摘AIM:To investigate the effect and mechanism of oridonin on the gastric cancer cell line HGC-27 in vitro.METHODS:The inhibitory effect of oridonin on HGC-27 cells was detected using the 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyl tetrazolium bromide assay.After treatment with 10 μg/mL oridonin for 24 h and 48 h,the cells were stained with acridine orange/ethidium bromide.The morphologic changes were observed under an inverted fluorescence microscope.DNA fragmen-tation(a hallmark of apoptosis) and lactate dehydrogenase activity were examined using DNA ladder assay and lactate dehydrogenase-release assay.After treated with oridonin(0,1.25,2.5,5 and 10 μg/mL),HGC-27 cells were collected for anexin V-phycoerythrin and 7-amino-actinomycin D double staining and tested by flow cytometric analysis,and oridonin-induced apoptosis in HGC-27 cells was detected.After treatment with oridonin for 24 h,the effects of oridonin on expression of Apaf-1,Bcl-2,Bax,caspase-3 and cytochrome c were also analyzed using reverse-transcript polymerase chain reaction(RT-PCR) and Western blotting.RESULTS:Oridonin significantly inhibited the proliferation of HGC-27 cells in a dose-and time-dependent manner.The inhibition rates of HGC-27 treated with four different concentrations of oridonin for 24 h(1.25,2.5,5 and 10 μg/mL) were 1.78% ± 0.36%,4.96% ± 1.59%,10.35% ± 2.76% and 41.6% ± 4.29%,respectively,which showed a significant difference(P < 0.05).The inhibition rates of HGC-27 treated with oridonin at the four concentrations for 48 h were 14.77% ± 4.21%,21.57% ± 3.75%,30.31% ± 4.91% and 61.19% ± 5.81%,with a significant difference(P < 0.05).The inhibition rates of HGC-27 treated with oridonin for 72 h at the four concentrations were 25.77% ± 4.85%,31.86% ± 3.86%,48.30% ± 4.16% and 81.80% ± 6.72%,with a significant difference(P < 0.05).Cells treated with oridonin showed typical apoptotic features with acridine orange/ethidium bromide staining.After treatment with oridonin,the cells became round,shrank,and developed small buds around the nuclear membrane while forming apoptotic bodies.Lactate dehydrogenase(LDH) release assay showed that after treated with 1.25 μg/mL and 20 μg/mL oridonin for 24 h,LDH release of HGC-27 caused by apoptosis increased from 22.94% ± 3.8% to 52.68% ± 2.4%(P < 0.001).However,the change in the release of LDH caused by necrosis was insignificant,suggesting thatthe major cause of oridonin-induced HGC-27 cell death was apoptosis.Flow cytometric analysis also revealed that oridonin induced significant apoptosis compared with the controls(P < 0.05).And the apoptosis rates of HGC-27 induced by the four different concentrations of oridonin were 5.3% ± 1.02%,12.8% ± 2.53%,28.5% ± 4.23% and 49.6% ± 3.76%,which were in a dose-dependent manner(P < 0.05).After treatment for 24 h,DNA ladder showed that oridonin induced a significant increase in DNA fragmentation in a dosedependent manner.RT-PCR revealed that mRNA expression levels were up-regulated compared with the controls in caspase-3(0.917 ± 0.103 vs 0.357 ± 0.019,P < 0.05),cytochrome c(1.429 ± 0.111 vs 1.002 ± 0.014,P < 0.05),Apaf-1(0.688 ± 0.101 vs 0.242 ± 0.037,P < 0.05) and Bax(0.856 ± 0.101 vs 0.278 ± 0.027,P < 0.05)(P < 0.05),whereas down-regulated in Bcl-2(0.085 ± 0.012 vs 0.175 ± 0.030,P < 0.05).Western blotting analysis also confirmed this result.CONCLUSION:Apoptosis of HGC-27 induced by oridonin may be associated with differential expression of Apaf-1,caspase-3 and cytochrome c,which are highly dependent upon the mitochondrial pathway.
基金Supported by The Wenzhou Municipal Science and Technology Commission Major Projects Funds,No.20090006
文摘AIM: To assess the value of plasma melatonin in pre-dicting acute pancreatitis when combined with the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and bedside index for severity in acute pancreatitis (BISAP) scoring systems. METHODS: APACHEⅡ and BISAP scores were calculated for 55 patients with acute physiology (AP) in the first 24 h of admission to the hospital. Additionally, morning (6:00 AM) serum melatonin concentrations were measured on the first day after admission. According to the diagnosis and treatment guidelines for acute pancreatitis in China, 42 patients suffered mild AP (MAP). The other 13 patients developed severe AP (SAP). A total of 45 healthy volunteers were used in this study as controls. The ability of melatonin and the APACHEⅡ and BISAP scoring systems to predict SAP was evaluated using a receiver operating characteristic (ROC) curve. The optimal melatonin cutoff concentration for SAP patients, based on the ROC curve, was used to classify the patients into either a high concen-tration group (34 cases) or a low concentration group (21 cases). Differences in the incidence of high scores, according to the APACHEⅡ and BISAP scoring sys- tems, were compared between the two groups. RESULTS: The MAP patients had increased melatonin levels compared to the SAP (38.34 ng/L vs 26.77 ng/L) (P = 0.021) and control patients (38.34 ng/L vs 30.73 ng/L) (P = 0.003). There was no significant difference inmelatoninconcentrations between the SAP group and the control group. The accuracy of determining SAP based on the melatonin level, the APACHEⅡ score and the BISAP score was 0.758, 0.872, and 0.906, respectively, according to the ROC curve. A melatonin concentration ≤ 28.74 ng/L was associated with an increased risk of developing SAP. The incidence of high scores (≥ 3) using the BISAP system was significantly higher in patients with low melatonin concentration (≤ 28.74 ng/L) compared to patients with high melatonin concentration (> 28.74 ng/L) (42.9% vs 14.7%, P = 0.02). The incidence of high APACHEⅡ scores (≥ 10) between the two groups was not significantly different. CONCLUSION: The melatonin concentration is closely related to the severity of AP and the BISAP score. Therefore, we can evaluate the severity of disease by measuring the levels of serum melatonin.
文摘Blue rubber bleb nevus syndrome(BRBNS)is a rare disease characterized by multiple venous malformations and hemangiomas in the skin and visceral organs.The lesions often involve the cutaneous and gastrointestinal systems.Other organs can also be involved,such as the central nervous system,liver,and muscles.The most common symptoms are gastrointestinal bleeding and secondary iron deficiency anemia.The syndrome may also present with severe complications such as rupture,intestinal torsion,and intussusception,and can even cause death.Cutaneous malformations are usually asymptomatic and do not require treatment.The treatment of gastrointestinal lesions is determined by the extent of intestinal involvement and severity of the disease.Most patients respond to supportive therapy,such as iron supplementation and blood transfusion.For more significant hemorrhages or severe complications,surgical resection,endoscopic sclerosis,and laser photocoagulation have been proposed.Here we present a case of BRBNS in a 45-year-old woman involving 16sites including the scalp,eyelid,orbit,lip,tongue,face,back,upper and lower limbs,buttocks,root of neck,clavicle area,superior mediastinum,glottis,esophagus,colon,and anus,with secondary severe anemia.In addition,we summarize the epidemiology,clinical manifestations,diagnosis,differential diagnosis and therapies of this disease by analyzing all previously reported cases to enhance the awareness of this syndrome.
基金Supported by Project of the Zhejiang Province bureau of Health,No.2013KYA226 and No.2013KYA229Taizhou City science and Technology bureau(121ky08)
文摘Minimally invasive endoscopic resection has become an increasingly popular method for patients with small(less than 3.5 cm in diameter) gastric subepithelial tumors(SETs) originating from the muscularis propria(MP) layer. Currently, the main endoscopic therapies for patients with such tumors are endoscopic muscularis excavation, endoscopic full-thickness resection, and submucosal tunneling endoscopic resection. Although these endoscopic techniques can be used for complete resection of the tumor and provide an accurate pathological diagnosis, these techniques have been associated with several negative events, such as incomplete resection, perforation, and bleeding. This review provides detailed information on the technical details, likely treatment outcomes, and complications associated with each endoscopic method for treating/removing small gastric SETs that originate from the MP layer.
基金Supported by Zhejiang provincial top key discipline in surgery
文摘AIM:To investigate the relationship between polymorphisms present in the vitamin D receptor(VDR) gene and colorectal cancer risk,a systematic meta-analysis of population-based studies was performed.METHODS:A total of 38 relevant reports published between January 1990 and August 2010 were identified,of which only 23 qualified for this meta-analysis based on our selection criteria.Five polymorphic variants of the VDR gene,including Cdx-2(intron 1e) and FokI(exon 2) present in the 5' region of the gene,and BsmI(intron 8),ApaI(intron 8),and TaqI(exon 9) sites present in the 3' untranslated region(UTR),were evaluated for possible associations with colorectalcancer risk.Review manager 4.2 was used to perform statistical analyses.RESULTS:In the meta-analysis performed,only the BsmI polymorphism was found to be associated with colorectal cancer risk.In particular,the BsmI B genotype was found to be related to an overall decrease in the risk for colorectal cancer [BB vs bb:odds ratio(OR) = 0.87,95% CI:0.80-0.94,P = 3 × 10-4;BB vs Bb + bb:OR = 0.90,95% CI:0.84-0.97,P = 5 × 10-4].Moreover,in subgroup analyses,the BsmI B genotype was significantly associated with colon cancer,and not rectal cancer.An absence of between-study heterogeneity was also observed.CONCLUSION:A meta-analysis of 23 published studies identified the BsmI polymorphism of the VDR gene to be associated with an increased risk of colon cancer.
基金The Grant of Zhejiang Province Natural Science Foundation, No. M303843
文摘AIM: To evaluate the relationship between the expression of cell adhesion molecules (CAMs) and the biological behavior of gastric carcinoma. METHODS: Expression of syndecan-1, E-cadherin and integrin β3 were evaluated by immunohistochemical study in a total of 118 gastric carcinomas and 20 non- tumor gastric mucosas. RESULTS: The expressions of syndecan-1 and E-cadherin were significantly lower in gastric carcinoma compared to non-tumor gastric mucosa, and the low expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). However, the expression of integrin β3 was significantly higher in gastric carcinoma compared to non-tumor gastric mucosa, and the high expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). In addition, the three protein expressions were correlated to the tumor growth pattern (P < 0.01, P < 0.01, and P < 0.05 respectively), but not correlated to tumor differentiation (P > 0.05, P > 0.05 and P > 0.05 respectively). Positive correlation was observed between the expressions of syndecan-1 and E-cadherin, but they which were negatively correlated to the expression of integrin β3 (P < 0.01 in all cases). Univariate analysis demonstrated that the mean survival time and 5-year survival rate were lower in the cases with low expressions of syndecan-1 and E-cadherin and high expression of integrin β3 (P < 0.01, in all cases). COX multivariate analysis showed that the expression level of syndecan-1 could be an independent prognostic index of gastric carcinoma (P < 0.01), whereas E-cadherin and integrin β3 could not be independent indexes (P > 0.05, P > 0.05 respectively). CONCLUSION: The low expression of syndecan-1 and E-cadherin and the high expression of integrin β3 are significantly correlated with the invasion and metastasis of gastric carcinoma, and they are highly correlated with each other. Therefore they may serve as important prognostic markers of gastric carcinoma.
基金We would like to thank Dr HeinzAmheiter （NIH/NINDS） for generously contributing to the images, and Dr Laura Baxter and Dr Yingzi Yang （NIH/NHGRI） for thoughtful comments on the manuscript. We also acknowledge the support by the National Natural Science Foundation of China （30771149） and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health.
基金Science and Technology of Wenzhou City,China(No.Y20100040)
文摘AIM:To compare the visual and optical performance of eyes with different corneal spherical aberration(SA) implanted with spherical aberration-free intraocular lens(IOLs).· METHODS:Thirty-six patients with different corneal SA had phacoemulsification with implantation of spherical aberration-free IOLs.Patients were divided into 3 groups according to the value of preoperative corneal SA.Eyes with corneal SA <0.10μm were assigned to group A,those with 0.10 ≤corneal SA <0.20μm to Group B,and those with 0.20≤corneal SA <0.35μm to Group C.Best-corrected visual acuity(BCVA),contrast sensitivity,corneal SA,total ocular aberrations,and depth of focus were recorded 3 months postoperatively.Distance-corrected near and intermediate visual acuity was studied to measure depth of focus.· RESULTS:BCVA and contrast sensitivity were similar between groups.There were no significant differences in distance-corrected near or intermediate visual acuity.Corneal SA was similar before and 3 months after surgery in the 3 groups.With a 5.0mm pupil diameter,root mean square values for total ocular higher-order aberrations(HOAs) were lower in groups A and B than in group C.Total ocular SA was lower in group A than in groups B and C.SA was also lower in group B than in group C.Coma and trefoil were similar between the groups.· CONCLUSION:Implantation of spherical aberration-free IOLs in eyes with different corneal SA results in similar visual performance at BCVA,contrast sensitivity and depth of focus.
文摘Summary: The changes of tumor necrosis factor-α (TNF-α) and brain ultrastructure during cardiopulmonary resuscitation and the effects of ulinastation injection were observed, and the mechanism was investigated. Twenty-four adult healthy Sprague-Dawley rats were randomly divided into control group (8 rats), resuscitation group (8 rats) and ulinastatin (UTI) group (8 rats). Rats in control group underwent tracheotomy without clipping the trachea to induce circulatory and respiratory standstill. Rats in resuscitation and ulinastatin group were subjected to the procedure of establishing the model of cardiopulmonary cerebral resuscitation (CPCR). Rats in ulinastatin group were given with UTI 104 U/kg once after CPCR. In the control group, the plasma was collected immediate, 30 min, 2 h, 4 h, and 6 h after tracheotomy. In resuscitation group and UTI group, plasma was collected immediate after tracheotomy, 30 min, 2 h, 4 h and 6 h after successful resuscitation. The plasma levels of TNF-α were determined by radioimmunoassay (RIA). At the end of the experiment, 2 rats were randomly selected from each group and were decapitated. The cortex of the brain was taken out immediately to observe the ultrastructure changes. In control group, there were no significant differences in the level of TNF-α among different time points (P>0.05). In resuscitation group, the level of TNF-α was increased obviously after resuscitation (P<0.01) and reached its peak 2 h later after resuscitation. An increasing trend of TNF-α showed in UTI group. There were no differences in TNF-α among each sample taken after successful resuscitation and that after tracheotomy. The utrastructure of brains showed the injury in UTI group was ameliorated as compared with that in resuscitation group. In early period of CPCR, TNF-α was expressed rapidly and kept increasing. It indicated that TNF-α might take part in the tissue injury after CPCR. The administration of UTI during CACR could depress TNF-α and ameliorate brain injury. By regulating the expression of damaging mediator, UTI might provide a protective effect on the tissue injury after CPCR.
文摘Objective: To investigate a possible mechanism responsible for anti-apoptotic effects of melatonin and provide theoretical evidences for clinical therapy. Methods: Ischemia-reperfusion mediated neuronal cell injury model was constructed in cerebellar granule neurons (CGNs) by deprivation of glucose, serum and oxygen in media. After ischemia, melatonin was added to the test groups to reach differential concentration during reperfusion. DNA fragmentation, mitochondrial transmembrane potential, mitochondrial cytochrome c release and caspase-3 activity were observed after subjecting cerebellar granule neurons to oxy-gen-glucose deprivation (OGD). Results: The results showed that OGD induced typical cell apoptosis change, DNA ladder and apoptosis-related alterations in mitochondrial functions including depression of mitochondrial transmembrane potential (its maximal protection ratio was 73.26%) and release of cytochrome c (its maximal inhibition ratio was 42.52%) and the subsequent activation of caspase-3 (its maximal protection ratio was 59.32%) in cytoplasm. Melatonin reduced DNA damage and inhibited release of mitochondrial cytochrome c and activation of caspase-3. Melatonin can strongly prevent the OGD-induced loss of the mitochondria membrane potential. Conclusion: Our findings suggested that the direct inhibition of mitochondrial pathway might essentially contribute to its anti-apoptotic effects in neuronal ischemia-reperfusion.
基金supported by Wenzhou Science and Technology Project(Y20080087)
文摘Objective:To study the protective effect of resveratrol on lens epithelial cell apoptosis in diabetic cataract rat.Methods:A total of 84 Wistar rats were divided into 4 groups:12 in Group A(control group).24 in Group B(diabetic cataract group),24 in Group C(therapeutic-dose of resveratrol group) and 24 in Group D(low-dose of resveratrol group).Rats in Group B-D were given with60 mg/kg streptozotocin through intraperitoneal injection.Rats in Group C were given with 100mg/kg resveratrol and rats in Group D were given with 20 mg/kg resveratrol.The caspase-3expression levels and apoptosis ratios of LEC among each group were observed:the degrees of lens opacity in Group B-D after 12 weeks were compared.Results:There were significant differences in caspase-3 expression levels,apoptosis ratios of T.F.C among groups at 4 w,8 w and12 w(P<0.05).After 12 weeks,in Group B the degree of lens opacity was as follow:0(0.00%) in grade Ⅰ,3(37.50%) in grade Ⅱ,2(25.00%)in grade Ⅲ,2(25.00%)grade Ⅳ,and 1(12.50%) in gradeⅤ:in Group C:2(25.00%)in grade Ⅰ,4(50.00%) in grade Ⅱ.2(25.00%)in grade Ⅲ,0(0.00%)gradeⅣ,and 0(0.00%) in grade Ⅴ;in Group D:1(12.50%)in grade Ⅰ,4(50.00%) in grade Ⅱ,2(25.00%)in grade Ⅲ,1(12.50%) grade Ⅳ,and 0(0.00%) in grade Ⅴ.The.difference among Group B-D was statistically significant(P<0.05).Conclusions:Resveratrol has protective effect on lens epithelial cell apoptosis in diabetic cataract rat,and the effect is relative to its dose.
基金This work was supported by the National Natural Science Foundation of China （No. 30470611）the Natural Science Foundation of Zhejiang province （No.Y204133）.
文摘Receptor imidazoline 2 (I2) is one of the imidazoline receptors with high affinity for 3H-idazoxan. Receptor I2,being classified into I2A and I2B subtypes,is mainly localized to the outer membrane of mitochondria in liver,kidney and brain. Receptor I2,displaying high similarity of sequence with monoamine oxidase-B (MAO-B),is structurally related to MAO-B,but the I2 imidazoline binding site (I2BS) with ligand is distinct from the catalytic site of MAO-B. Agmatine is the endogenous ligand of receptor I2. Accumulating evidence have revealed that the activation of receptors I2 may produce neuroprotective effects by increasing expression of glial fibrillary acidic protein (GFAP) in astrocytes,inhibiting activity of MAO,reducing calcium overload in cells. Agmatine exerts neuroprotection against ischemia-hypoxia,injury,glutamate-induced neurotoxicity by activating imidazoline receptors,blocking N-methyl-D-aspartate (NMDA) receptor,inhibiting all isoforms of nitric oxide synthase (NOS),and selectively blocking the voltage-gated calcium channels (VGCC). It would be expected that agmatine is one of the potential neuroprotective agents.
文摘AIM: To examine fibrinogen-like protein 2 (fgl2) expression during taurocholate-induced acute pancreatitis progression in rats and its correlation with pancreatic injury severity. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into the severe acute pancreatitis (SAP) group (n = 24) and the sham operation (SO) group (n = 24). Sodium taurocholate (4% at doses of 1 mL/kg body weight) was retrogradely injected into the biliopancreatic ducts of the rats to induce SAP. Pancreatic tissues were prepared immediately after sacrifice. At the time of sacrifice, blood was obtained for determination of serum amylase activity and isolation of peripheral blood mononuclear cells (PBMCs). Pancreatic tissue specimens were obtained for routine light microscopy including hematoxylin and eosin staining, and the severity of pancreatic injury was evaluated 1, 4 and 8 h after induction. Expression of fgl2 mRNA was measured in the pancreas and PBMCs using reverse transcription polymerase chain reaction. Expression of fgl2 protein was evaluated in pancreatic tissues using Western blotting and immunohistochemical staining. Masson staining was also performed to observe microthrombosis. RESULTS: At each time point, levels of fgl2 mRNAs in pancreatic tissues and PBMCs were higher (P < 0.05) in the SAP group than in the SO group. For pancreatic tissue in SAP vs SO, the levels were: after 1 h, 3.911 ± 1.277 vs 1.000 ± 0.673; after 4 h, 9.850 ± 3.095 vs 1.136 ± 0.609; and after 8 h, 12.870 ± 3.046 vs 1.177 ± 0.458. For PBMCs in SAP vs SO, the levels were: after 1 h, 2.678 ± 1.509 vs 1.000 ± 0.965; after 4 h, 6.922 ± 1.984 vs 1.051 ± 0.781; and after 8 h, 13.533 ± 6.575 vs 1.306 ± 1.179. Levels of fgl2 protein expression as determined by Western blotting and immunohistochemical staining were markedly up-regulated (P < 0.001) in the SAP group compared with those in the SO group. For Western blotting in SAP vs SO, the results were: after 1 h, 2.183 ± 0.115 vs 1.110 ± 0.158; after 4 h, 2.697 ± 0.090 vs 0.947 ± 0.361; and after 8 h, 3.258 ± 0.094 vs 1.208 ± 0.082. For immunohistochemical staining in SAP vs SO, the results were: after 1 h, 1.793 ± 0.463 vs 0.808 ± 0.252; after 4 h, 4.535 ± 0.550 vs 0.871 ± 0.318; and after 8 h, 6.071 ± 0.941 vs 1.020 ± 0.406. Moreover, we observed a positive correlation in the pancreas (r = 0.852, P < 0.001) and PBMCs (r = 0.735, P < 0.001) between fgl2 expression and the severity of pancreatic injury. Masson staining showed that microthrombosis (%) in rats with SAP was increased (P < 0.001) compared with that in the SO group and it was closely correlated with fgl2 expression in the pancreas (r = 0.842, P < 0.001). For Masson staining in SAP vs SO, the results were: after 1 h, 26.880 ± 9.031 vs 8.630 ± 3.739; after 4 h, 53.750 ± 19.039 vs 8.500 ± 4.472; and after 8 h, 80.250 ± 12.915 vs 10.630 ± 7.003.CONCLUSION: Microthrombosis due to fgl2 overexpression contributes to pancreatic impairment in rats with SAP, and fgl2 level may serve as a biomarker during early stages of disease.
