Effect of Total Flavone of Haw Leaves on Nuclear Factor Erythroid-2 Related Factor and Other Related Factors in Nonalcoholic Steatohepatitis Rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of total flavone of haw leaves (TFHL) on the expression of nuclear factor erythroid-2 related factor (Nrf2) and other related factors in nonalcoholic steatohepatitis (NASH) rats induced by high-fat diet and then to further discuss the mechanism of TFHL's prevention against NASH.</p><p><b>METHODS</b>High-fat diet was fed to 40 rats to establish the NASH model. Then model rats were intragastrically administrated with 40, 80, 160 mg/(kg•day) TFHL, respectively. The pathological changes of liver tissues in NASH rats were detected by oil red O and hematoxylin-eosin (HE) stainings. The expression of Nrf2 in rat liver was examined through immunohistochemistry. The level of 8-iso-prostaglandin F2α in serum was detected through enzyme linked immunosorbent assay (ELISA). The mRNA and protein levels of Nrf2 and other related factors in liver tissue were measured by real-time reverse transcriptionpolymerase chain reaction and western blot.</p><p><b>RESULTS</b>Lipid deposition, hepatic steatosis, focal necrosis in lobular inflammation and ballooning degeneration were emerged in livers of NASH rats. The 8-iso-prostaglandin F2α in the serum of NASH rats increased significantly compared with the control group (P<0.05). The mRNA of Nrf2, hemeoxyenase1 (HO-1) and the mRNA and protein levels of quinine oxidoreductase (NQO1) in NASH rats liver tissue showed a striking increase, while the mRNA levels of Keap1, r-glutamylcysteine synthethase (rGCS) and glutathione S-transferase (GST) were significantly decreased compared with the control group (P<0.05). After TFHL treatment, 8-iso-prostaglandin F2α level in serum significantly decreased, and Nrf2 mRNA and protein levels in hepatocytes nucleus enhanced compared with the model group (P<0.05 or 0.01). Meanwhile the Keap1 mRNA, the mRNA and protein levels of HO-1, NQO1 antibody, rGCS antibody, GST increased after TFHL treatment (P<0.05 or 0.01).</p><p><b>CONCLUSIONS</b>Nrf2 and other related factors were involved in development of NASH, and they also served as an important part in its occurrence. By regulating expression of Nrf2 and other related factors, TFHL may play a role in antioxidative stress and prevention of NASH.</p>

Effect of Nrf2 and related factors on the progression of nonalcoholic steatohepatitis / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the role of NF-E2-related factor 2(Nrf2) and its related factors in the progression of nonalcoholi steatohepatitis (NASH) by investigating the alterations of lipid metabolism and liver histopathology as well as the changes of mRNA and protein expression levels of Nrf2 and its related factors in rats during NASH progression.</p><p><b>METHODS</b>Male SD rats were randomly divided into normal group and model group, which were administrated with high fat diet to establish nonalcoholic steatohepatitis model. The rats from both groups were randomly killed at the end of 4, 12 weeks respectively. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) were detected in the serum and liver tissue; Changes in fat deposition in liver tissue were determined by oil red O staining. HE staining were used to observe the pathological changes of liver tissue and to calculate nonalcoholic fatty liver disease (NAFLD) activity score (hepatic steatosis, inflammation and ballooning degeneration of liver cells). The expression of Nrf2 in liver was detected by immunohistochemical staining. The mRNA and protein levels of Nrf2 and related factors in liver were determined by Realtime PCR and Western blot, respectively.</p><p><b>RESULTS</b>After 4 weeks of high fat diet, the levels of ALT, AST, TC in rat serum and TC, TG, LDL-C in liver were significantly increased compared with that of the normal group (P < 0.01, P < 0.05). After 4 weeks of high fat diet, the levels of ALT, AST, TC, TG in serum and TC, TG, LDL- C in liver increased further (P < 0.01, P < 0.05). Until the 12th week, the content of HDL-C in liver was significantly lower than that of the normal group (P < 0.05). At the end of the 4th or the 12th week, lipid droplets in the model rat liver cells were heavily dyed red and hepatic steatosis increased severely, with ballooning degeneration of liver cells. With the extension of high fat diet feeding time, fat deposition in the liver tissue, hepatic steatosis, NAFLD score, Nrl2 expression were significantly increased (P < 0.01). Expression levels of mRNA and protein of Nrf2, heme oxyenase 1(HO1), NADPH quinone oxidoreductase 1(NQO1), γ-glutamylcysteine synthethase (γ-GCS), glutathione S-transferase (GST) in the model rats increased or decreased at the end of the 4th or the 12th week differentially, (P < 0.01, P < 0.05) with the more significant changes at the end of the 4th week than the 12th week.</p><p><b>CONCLUSION</b>Nrf2 and its related factors may be involved in the occurrence and development of nonalcoholic fatty liver disease, which may play an important role in the process of NASH formation.</p>

Study on treatment effect and mechanism of Hirsutella sinensis mycelium in idiopathic pulmonary fibrosis in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study and discuss the effect and mechanism of Hirsutella sinensis mycelium (HSM) on idiopathic pulmonary fibrosis in rats.</p><p><b>METHOD</b>Forty Wistar rats were divided into five groups: the normal control group, the model control group, the high-dose group (1.0 g x kg(-1) HSM), the low-dose group (0.5 g x kg(-1) HSM), and the positive control group (10 mg x kg(-1) hydrocortisone). In addition to rats in the normal control group, the pulmonary fibrosis model was established by injecting 5 mg x kg(-1) bleomycin into rat tracheas for consecutively 28 days, in order to observe their lung function, lung tissue hydroxyproline, cytokines and pathology.</p><p><b>RESULT</b>After rats were administered with HSM, 0.5 g x kg(-1) and 1.0 g x kg(-1) HSM could significantly decrease lung index and hydroxyproline content (P<0.01), while notably improving pulmonary function, alveolus inflammation and fibrosis degree (P<0.05, P<0.01); 1.0 g x kg(-1) HSM could decrease significantly protein expressions of TNF-alpha, IL-1beta and TGF-beta1 in lung tissues, while increasing significantly protein expressions of IFN-gamma (P<0.05).</p><p><b>CONCLUSION</b>HSM have better effect in treating idiopathic pulmonary fibrosis in rats. Its treatment effect and mechanism are related to the regulation of TNF-alpha, IL-1beta and TGF-beta1 and IFN-gamma imbalance.</p>

The mitogen-activated protein kinase phosphatase-1 (MKP-1) gene is a potential methylation biomarker for malignancy of breast cancer

The mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) belongs to the MAPK cascades which are central to cell proliferation and apoptosis. The carcinogenic role of MKP-1 has been reported in many types of cancer but it has rarely been investigated in breast cancer. The present study was designed to evaluate the MKP-1 mRNA expression and its possible regulation by methylation of MKP-1 promoter in the model of several breast cancer cell lines and tissues as well as controls. Our data demonstrate MKP-1 mRNA expression significantly decreased in five breast cancer cell lines compared to breast controls (P < 0.01). Using the methylation-specific PCR (MSP) analysis, the unmethylated reaction (U) is dominant in both normal cell lines and benign breast tumors (100% vs. 86.2%), whereas the methylated reaction (M) is dominant in both breast cancer cell lines and invasive breast tumors (100% vs. 57.2%). In terms of methylation ratio (M/M+U), methylation level in MKP-1 promoter is significantly higher in the invasive breast tumor tissues (n = 152) than in benign breast tumor tissues (n = 29) (P < 0.0001). Assessing the methylation ratio of the promoter of MKP-1 gene to diagnose the breast malignancy (invasive vs. benign), the area under the receiver-operating characteristic (ROC) curve was 0.809 (95% CI: 0.711-0.906, P < 0.001). The best performance for this prediction has a sensitivity of 76.32% and a specificity of 82.76% at the cutoff value of 0.38. Taken together, we firstly demonstrated that the promoter methylation of MKP-1 gene is a potential breast cancer biomarker for breast malignancy.

Effect of Tongxie Yaofang Granule in treating diarrhea-predominate irritable bowel syndrome / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the clinical effect of Tongxie Yaofang (TXYF) Granule in treating diarrhea-predominate irritable bowel syndrome (D-IBS) and its possible mechanism.</p><p><b>METHODS</b>A total of 120 patients were assigned to two groups using stratified block randomization, 80 in the intervention group and 40 in the control group. To the intervention group the TXYF granule was given at one package each time, twice a day; the control group was treated with Miyarisan three times a day, two tablets each time. The course of treatment was 4 weeks for both groups. The total efficacy in them was compared, and data of scoring on stool (Bristol method), abdominal pain, abdominal distension, and mental condition were collected before treatment and 2 and 4 weeks after treatment. The activation of mast cells (MCs) of six patients chosen from each group was detected as well before and after treatment.</p><p><b>RESULTS</b>No significant difference between the two groups in terms of the total efficacy or the scores of symptoms before and after treatment was found (P>0.05). The number of activated MCs was decreased in the intervention group after treatment, showing significant difference as compared with that before treatment as well as with that in the control group after treatment (P<0.01).</p><p><b>CONCLUSIONS</b>TXYF is an effective preparation for the treatment of D-IBS. It can quickly lessen abdominal pain and distention, improve the property of stool, and improve mental tension and depression in patients. Its mechanism of action might be through the adjustment of MCs activation to decrease visceral hypersensitivity.</p>