Effect of dimethyl fumarate on rats with chronic pancreatitis

OBJECTIVE@#To discuss the effect of dimethyl fumarate (DMF) on rats with l-arginine induced chronic pancreatitis (CP).@*METHODS@#Male Wistar rats were given DMF treatment (25 mg/kg) by oral lavage method; then Wistar rats were given the intraperitoneal injection of l-arginine for 5 times (250 mg/100 kg, twice per time, each interval of 1 h) for building of CP model. Rats were divided into control group, CP group, DMF group and CP + DMF group. Rats in CP + DMF group were given the oral intragastric administration of DMF (25 mg/kg), while rats in control group and CP group were given the equal volume of normal saline. The weight of rats was evaluated and the intraperitoneal glucose tolerance test was performed (IPGTT, 2 g/kg). The islet of rats was isolated and then flow cytometry was employed to evaluate the quality and activity of islets. Meanwhile, the histology of non-endocrine tissues and levels of myeloperoxidase (MPO) and malondialdehyde (MDA) were detected.@*RESULTS@#Compared with control group, the weight of rats in CP group was significantly reduced at week 2, 4 and 6; the blood glucose significantly increased, AUC increased, the histopathological scores of pancreatic atrophy, acinar injury, edema and cellular infiltration increased, levels of MDA and MPO increased, the islet equivalent and islet activity decreased at 0, 30, 60, 120 and 180 min. Compared with CP group, the weight of rats in CP + DMF group significantly increased at week 2, 4 and 6; the blood glucose significantly decreased, AUC decreased, the histopathological scores of pancreatic atrophy, acinar injury, edema and cellular infiltration decreased, levels of MDA and MPO decreased, the islet equivalent and islet activity increased at 0, 30, 60, 120 and 180 min.@*CONCLUSIONS@#DMF treatment can improve CP induced by l-arginine and islet function in rats.

Effect of dimethyl fumarate on rats with chronic pancreatitis

Objective: To discuss the effect of dimethyl fumarate (DMF) on rats with l-arginine induced chronic pancreatitis (CP). Methods: Male Wistar rats were given DMF treatment (25 mg/kg) by oral lavage method; then Wistar rats were given the intraperitoneal injection of l-arginine for 5 times (250 mg/100 kg, twice per time, each interval of 1 h) for building of CP model. Rats were divided into control group, CP group, DMF group and CP + DMF group. Rats in CP + DMF group were given the oral intragastric administration of DMF (25 mg/kg), while rats in control group and CP group were given the equal volume of normal saline. The weight of rats was evaluated and the intraperitoneal glucose tolerance test was performed (IPGTT, 2 g/kg). The islet of rats was isolated and then flow cytometry was employed to evaluate the quality and activity of islets. Meanwhile, the histology of non-endocrine tissues and levels of myeloperoxidase (MPO) and malondialdehyde (MDA) were detected. Results: Compared with control group, the weight of rats in CP group was significantly reduced at week 2, 4 and 6; the blood glucose significantly increased, AUC increased, the histopathological scores of pancreatic atrophy, acinar injury, edema and cellular infiltration increased, levels of MDA and MPO increased, the islet equivalent and islet activity decreased at 0, 30, 60, 120 and 180 min. Compared with CP group, the weight of rats in CP + DMF group significantly increased at week 2, 4 and 6; the blood glucose significantly decreased, AUC decreased, the histopathological scores of pancreatic atrophy, acinar injury, edema and cellular infiltration decreased, levels of MDA and MPO decreased, the islet equivalent and islet activity increased at 0, 30, 60, 120 and 180 min. Conclusions: DMF treatment can improve CP induced by l-arginine and islet function in rats.

Effect of VEGF, P53 and telomerase on angiogenesis of gastric carcinoma tissue

OBJECTIVE@#To investigate the effect of vascular endothelial growth factor (VEGF), P53 and telomerase on angiogenesis in gastric carcinoma tissue.@*METHODS@#A total of 95 surgical resection samples of gastric cancer tissue after pathological diagnosis are collected to observe the VEGF, P53 and telomerase expression using immunohistochemical methods. Relationship between their expression and its influence on angiogenesis in gastric carcinoma tissue were analyzed.@*RESULTS@#Microvascular density (MVD) and the expression of VEGF, P53 and telomerase were positively correlated. Expression of VEGF and P53 protein were related to tumor type and lymph metastasis, and also a correlation was observed between P53 and VEGF. The telomerase expression had no correlation with VEGF, and P53.@*CONCLUSIONS@#VEGF angiogenesis has a angiogenesis promoting effect on gastric cancer tissue development and plays an important role in tumor generation and metastasis. Mutant P53 promotes the tumor angiogenesis generation by adjusting VEGF. Telomerase has a certain role in promoting activity of angiogenesis through different way rather than P53.

Effects of langchuangping granule on the expression of B lymphocyte activating factor in the peripheral blood B cells of BXSB lupus nephritis mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the expressions of B lymphocyte activating factor (BAFF) in the serum and peripheral blood B cells (PBBCs) of BXSB lupus nephritis mice, and to investigate the efficacy of Langchuangping Granule (LG).</p><p><b>METHODS</b>Eighteen 11-week-old male BXSB lupus mice were randomly divided into three groups, i.e., the lupus control group, the hormone treatment group, and the LG treatment group, 6 in each group. Besides, another 6 C57BL/6 male mice were recruited as the normal control group. The mice were given with normal sodium (10 mL/d), methylprednisolone (at the daily dose of 5 mg/kg), LG (at the daily dose of 4 g/kg), and the normal saline (10 mL/d) respectively by gastrogavage for 4 weeks. The urine protein, ds-DNA, and body weight were determined. The serum soluble BAFF (sBAFF), the expressions and changes of BAFF-mRNA in the PBBCs were detected using ELISA and RT-PCR respectively. The activity index (AI) and 24 h urine albumin excretion quantitation of renal pathological activities were observed. The correlation between ds-DNA and sBAFF were analyzed.</p><p><b>RESULTS</b>The level of sBAFF in serum, the BAFF mRNA level in PBBCs, 24 h urinary albumin excretion, and serum ds-DNA content increased more obviously in lupus mice than in the normal mice. After being treated by methylprednisolone or LG, the sBAFF and BAFF mRNA expressions decreased more obviously than before treatment, showing statistical difference (P<0.05). But there was no statistical difference in the sBAFF level or the BAFF mRNA expression (P>0.05). There was positive correlation between sBAFF and AI (r=0.8098, P<0.01), 24 h urinary albumin excretion (r=0.8220, P<0.01), and ds-DNA (r=0.8535, P<0.01).</p><p><b>CONCLUSIONS</b>BAFF plays an important role in the occurrence and development of lupus nephritis. It can be used in monitoring the disease progress and predicting its recurrence. It is one of ideal targets for treating lupus nephritis. LG could attenuate the renal injury via suppressing BAFF level. It is worth further clinical application.</p>

Langohuangping granule down-regulated monocyte chemoattractant protein-1 via suppressing nuclear factor kappa B signaling pathway in BXSB lupus nephritis mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study whether Langchuangping granule (LG) could exert its renal protection by down-regulating monocyte chemoattractant protein-1 (MCP-1) via suppressing nuclear factor kappa B (NF-kappaB) signaling pathway in BXSB lupus nephritis (LN) mice. Methods Eighteen male 11-week-old BXSB LN mice were randomly divided into three groups, i.e., the model group, the hormone group, and the Chinese medicine group, 6 in each. They were administered by gastrogavage with normal saline, methylprednisolone, and LG, respectively. Another six C57BL/6 male mice of the same age was taken as the normal control group, which was administered with normal saline by gastrogavage. All mice were treated once daily, for 4 successive weeks. The 24-h urine protein was determined. The mRNA and protein expressions of MCP-1 in the renal tissue were detected using RT-PCR and Western blot. The expression of NF-kappaB p65 in the renal tissue was detected using immunohistochemical assay. Activity index (AI) of the renal tissue was counted using PAS stain. The content of ds-DNA antibody was detected using ELISA. The correlations of the aforesaid indices were analyzed.</p><p><b>RESULTS</b>The 24-h urine protein level, serum ds-DNA antibody content, protein and mRNA expressions of MCP-1, NF-kappaB p65 expression level, and AI count were obviously higher in the model group than in the normal control group (P < 0.01). The aforesaid indices all obviously decreased after medication in the Chinese medicine group and the hormone group (P < 0.05). MCP-1 protein expression level was positively correlated with MCP-1 mRNA, NF-kappaB p65, AI, 24-h urine protein, and ds-DNA antibody of all LN mice (r= 0.984, 0.936, 0.887, 0.698, 0.679, all P < 0.01).</p><p><b>CONCLUSIONS</b>LG possibly played renal protection by down-regulating NF-kappaB-mediated MCP-1 expression levels. MCP-1 played important roles in the occurrence and development of LN, being one of ideal targets for LN treatment.</p>

Effects of K-ras gene mutation on colon cancer cell line Caco-2 metastasis by regulating E-cadherin/beta-catenin/p120 protein complex formation and RhoA protein activity / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the effects of K-ras gene mutation on colon cancer cell line Caco-2 metastasis by regulating E-cadherin/beta-catenin/p120 protein complex formation and RhoA protein activity.</p><p><b>METHODS</b>K-ras wild-type colon cancer cell line Caco-2 was transiently transfected by phr-GFP vector (control group), transfected by mutant K-ras gene phr-K-ras (Val12) vector (transfection group), transfected by mutant K-ras gene phr-K-ras (Val12) vector and treated by specific MAPK pathway inhibitor PD98059 (MAPK inhibition group), or transfected by mutant K-ras gene phr-K-ras (Val12) vector and treated by specific PI-3K pathway inhibitor LY294002 (PI-3K inhibition group), respectively. Cell migration was tested by Transwell experiment. E-cadherin and beta-catenin protein expression and intracellular location were detected by cell immunofluorescence method. Intracellular p120 protein expression was detected by Western blot. beta-catenin protein level which combined with E-cadherin was detected by immunoprecipitation. RhoA activity was analyzed by Pull-down assay.</p><p><b>RESULTS</b>The Caco-2 cell migration rate was (19.8 +/- 5.6) % in transfection group, which was significantly higher than that in control group [(14.0 +/- 4.2) %] (P = 0.001) and in MAPK inhibition group [(15.8 +/- 1.2) %] (P = 0.044), but was not significantly different from that in PI-3K inhibition group [(17.5 +/- 2.8) %] (P = 0.095). Immunofluorescence method showed that the E-cadherin and beta-catenin stain located in the cell membrane decreased in transfection group. Western blot showed that the total intracellular p120 protein decreased in transfection group and PI-3K inhibition group. Immunoprecipitation data showed that beta-catenin protein level combined with E-cadherin decreased in transfection group and PI-3K group. Pull-down test showed that RhoA protein activity was up-regulated in transfection group.</p><p><b>CONCLUSION</b>K-ras gene mutation stimulates the migration of colon cancer cell Caco-2, which may be achieved by decreasing the E-cadherin/beta-catenin/p120 protein complex formation via MAPK pathway and increasing the RhoA protein activity.</p>