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1.
Journal of Clinical Hepatology ; (12): 865-871, 2022.
Article in Chinese | WPRIM | ID: wpr-923294

ABSTRACT

Objective To investigate the effect of Yipi Yanggan prescription on the malignant transformation of liver stem cells in liver precancerous lesion induced by diethylnitrosamine (DEN) and its possible molecular mechanism. Methods A total of 35 male Sprague-Dawley rats were randomly divided into normal control group (blank group), DEN model group (model group), DEN+Yipi Yanggan prescription group (Yipi Yanggan prescription group), and DEN+Hugan tablet group (Hugan tablet group), with 5 rats in the blank group and 10 rats in the other three groups. Intraperitoneal injection of DEN was performed to establish a model of liver precancerous lesion, the rats were sacrificed after 16 weeks of administration. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (Alb) were measured; liver tissue was collected to observe the changes in size and appearance and calculate liver weight ratio (liver index); HE staining and Sirius Red staining were used to observe the pathological and morphological changes of rat liver tissue; immunohistochemistry was used to measure the expression of OV6 and glutathione S-transferase-Pi (GST-Pi); RT-PCR was used to measure the mRNA expression of EpCAM, CD133, and CD90, and Western blot was used to measure the protein expression of PI3K, Akt, and mTOR and their phosphorylation level. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the model group, the Yipi Yanggan prescription group and the Hugan tablet group had significant improvements in liver pathology and morphology, significant reductions in liver index and the levels of ALT and AST, and a significant increase in the level of Alb (all P < 0.05), as well as significant reductions in the protein expression levels of GST-Pi, OV6, p-PI3K, p-Akt, and p-mTOR and the mRNA expression levels of EpCAM, CD133, and CD90 (all P < 0.05). Compared with the Hugan tablet group, the Yipi Yanggan prescription group showed a more significant protective effect on the liver, with significant reductions in liver index and the levels of ALT and AST, and a significant increase in the level of Alb (all P < 0.05), as well as significant reductions in the protein expression levels of GST-Pi, OV6, p-PI3K, p-Akt, and p-mTOR and the mRNA expression levels of EpCAM, CD133, and CD90 (all P < 0.05). Conclusion Yipi Yanggan prescription can improve liver precancerous lesion induced by DEN in rats by inhibiting the malignant transformation of liver stem cells, and its mechanism of action may be associated with the PI3K/Akt/mTOR signaling pathway.

2.
Journal of Clinical Hepatology ; (12): 2621-2625, 2020.
Article in Chinese | WPRIM | ID: wpr-829655

ABSTRACT

Autophagy can regulate liver physiology and balance liver metabolism. Autophagy activation has a double-sided and complex effect on liver injury, and it is regulated by many factors and is associated with many protein pathways. This article summarizes the role of mTOR in the regulation of autophagy, which can inhibit or enhance autophagy through the PI3K/Akt upstream signaling pathway and participate in the physiological and pathological changes of related liver diseases. Therefore, this article reviews the research advances in the mTOR/PI3K/Akt autophagy pathway in liver injury, in order to provide new therapeutic targets for related liver diseases.

3.
Journal of Clinical Hepatology ; (12): 2349-2352, 2020.
Article in Chinese | WPRIM | ID: wpr-829416

ABSTRACT

Excessive lipid deposition, liver injury, and insulin resistance are hallmarks in the development and progression of nonalcoholic fatty liver disease (NAFLD). Liver X receptor (LXR) is a transcriptional regulator, and its two cell subtypes, LXRα and LXRβ, play a key role in regulating cholesterol metabolism, inducing anti-inflammation, and reducing insulin resistance. This article reviews the structure and function of LXR and its association with the pathogenesis of NAFLD, in order to provide new ideas and methods for the prevention and treatment of NAFLD.

4.
Journal of Clinical Hepatology ; (12): 1650-1654, 2020.
Article in Chinese | WPRIM | ID: wpr-822912

ABSTRACT

The development and progression of liver cancer have the stages of hepatitis, liver cirrhosis, precancerous lesion, and liver cancer, among which the malignant transformation of precancerous lesions of liver cancer is closely associated with the activation of hepatic stellate cells (HSC). By describing the activation of HSC, the generation of precancerous cells of liver cancer, the formation of inflammatory fibrotic microenvironment, and the association between HSC activation and precancerous lesion, this article points out that microRNAs can affect the malignant transformation of precancerous lesion of liver cancer by regulating the expression of related target genes and HSC activation, and the research in this field is expected to provide new ideas and targets for the prevention and treatment of liver cancer.

5.
Article in Chinese | WPRIM | ID: wpr-813033

ABSTRACT

Ulcerative colitis is an intestinal inflammatory disease characterized by diarrhea, abdominal pain and purulent stool. Uncontrolled inflammation caused by macrophage hyper-activation is an important cause of ulcerative colitis. Therefore, inhibiting macrophage hyper-activation is an effective way to treat ulcerative colitis. Notch signaling pathway is involved in regulating the immune response of macrophages and promoting inflammation. NF-κB signaling pathway is the "star pathway" involved in inflammation. NLRP3 inflammatory body is involved in the activation of macrophages. Notch, NF-κB and NLRP3 inflammatory bodies constitute the upstream and downstream signal pathways in the existing immune inflammatory diseases. Notch signal pathway can regulate the activation of macrophage via NF-κB/NLRP3 inflammatory body signaling pathway.


Subject(s)
Colitis, Ulcerative , Cytokines , Humans , Macrophage Activation , NF-kappa B , NLR Family, Pyrin Domain-Containing 3 Protein , Receptors, Notch , Signal Transduction
6.
Article in Chinese | WPRIM | ID: wpr-614267

ABSTRACT

Tongxie Yaofang is a classic formula in the treatment of diarrhea caused by liver wood restricts earth, but the clinical application is not confined to diarrhea with pain. According to TCM thought of treating different diseases with the same method, it can also be used for the treatment of constipation caused by liver and spleen discord. Combining modern study and linking clinic, this article discussed the mechanism of this formula for the treatment of constipation, with a purpose to inspire thought and expand its clinical application range.

7.
Article in Chinese | WPRIM | ID: wpr-607034

ABSTRACT

Objective To clarify the active ingredients of Guanxin Qiwei tablet,and to explore the potential target for its efficacy.Methods We studied the interaction between Chinese medicine ingredients in the Guanxin Qiwei tablet and the therapy targets using a network pharmacology model,which was developed by integrating oral bioavailability prediction,druggability analysis,principal component analysis,molecular docking simulation and network of pharmacophore-target-disease analysis.Results Eighteen principal compounds had high-degree network with 41 therapy targets for coronary heart disease (CHD),and had higher affinity with 18 potential targets via the calculation of molecular docking.Further analysis showed that 7 key targets were closely related to the treatment of CHD.Conclusion We have screened 18 possible active molecules in Guanxin Qiwei tablet and 7 key therapy targets,and preliminarily elucidate the molecular mechanism based on the multi-ingredient,multi-target,and synergistic effect.

8.
Article in Chinese | WPRIM | ID: wpr-815114

ABSTRACT

To observe the effect of vasoactive intestinal peptide (VIP) on the metabolism of intestinal fluid and cyclic AMP protein kinase A signaling pathway (cAMP-PKA) and water channel protein 3 (AQP3) in rats with constipation, and to explore the mechanism of VIP in the treatment of constipation.
 Methods: A total of 45 healthy adult rats were randomly divided into a control group, a model group, a model +VIP group. After 4 weeks of VIP treatment, the first black stool time were examined with the ink gastric method; the water content in feces was calculated; the morphological changes in colonic tissues were observed by HE staining. The expression of VIP and AQP3 protein levels in colon tissues were detected by Western blot; and the cAMP, PKA, AQP3 mRNA expression levels were detected by quantitative real time polymerase chain reaction (qPCR). 
 Results: Compared with the control group, the first black stool time was prolonged, the water content of fecal decreased significantly (both P<0.01); part of the colon mucosa epithelial cells were destructed; the goblet cell volume decreased and quantity was reduced; the contents of AQP3 and VIP in colon tissues were significantly decreased, and the cAMP, PKA and AQP3 mRNA levels were decreased in the model group (all P<0.05). Compared with the model group, the first black stool time in the model +VIP group was shortened, the fecal water content increased significantly (both P<0.05); the mucosal epithelium integrity improved, the number of goblet cells increased; the content of AQP3 and VIP in colon tissues was increased, and the cAMP, PKA, and AQP3 mRNA levels were elevated (all P<0.05).
 Conclusion: Intravenous injection of VIP can regulate intestinal fluid metabolism and improve the symptoms of constipation in rats, which might be related to the regulation of VIP-cAMP-PKA-AQP3 signaling pathway.


Subject(s)
Animals , Aquaporin 3 , Physiology , Aquaporins , Blotting, Western , Colon , Chemistry , Pathology , Constipation , Therapeutics , Cyclic AMP , Physiology , Defecation , Epithelial Cells , Pathology , Feces , Chemistry , Goblet Cells , Pathology , Intestinal Mucosa , Metabolism , Pathology , RNA, Messenger , Rats , Signal Transduction , Vasoactive Intestinal Peptide , Physiology , Therapeutic Uses
9.
Cancer Research and Clinic ; (6): 247-249,254, 2010.
Article in Chinese | WPRIM | ID: wpr-596942

ABSTRACT

Objective To detect the expression of multidrug resistance proteins P-gp, LRP, MRP, and analyze the relationship between them and the clinicopathological factors. Methods The expression of P-gp,LRP, MRP in formalin-fixed paraffin-embedded tissue sections was determined by a labelled StreptavidinPeroxidase (SP) immunohistochemical technique, and the results were analyzed in correlation with clinicopathological data. None of these patients received chemotherapy prior to surgery. Results The positive rates of P-gp, LRP, MRP were 86.4 %, 84.7 % and 27.1%, respectively. The difference between the positive rate of P-gp and MRP was significant statistically, as well as the difference between the expression of MRP and LRP. No significant difference was observed between P-gp and LRP, but the positively correlation between the expression of P-gp and LRP was observed. No significant correlation between the expression of P-gp, LRP, MRP and the grade of differentiation were observed. The expression of P-gp was correlated with clinical stages positively (r=0.742), but the difference with the expression of P-gp in different stages was not significant. Conclusion The expression of P-gp, LRP, MRP in patients with gastric cancer without prior chemotherapy are high and indicates that innate drug resistance may exist in gastric cancer.

10.
Cancer Research and Clinic ; (6): 690-694, 2008.
Article in Chinese | WPRIM | ID: wpr-381815

ABSTRACT

Objective To investigate the gene variation and the dependability and to evaluate the possible tumor suppressor genes on chromosome 9 in the development and progression of EC. Methods LOH was detected in normal esophageal mucosa, high-grade squamous dysplasia and esophageal squamous cell carcinoma by microdissection, polymerase chain reaction, denaturing polyacrylamide gel eleetrophoresis and silver nitrate staining technology. The changes of LOH at six microsatellite markers and the relationship between LOH rate were analyzed. Results In the informative cases, total frequency of LOH was 17.2 % in high-grade squamous dysplasia and 24.9 % in esophageal squamous cell carcinoma. In high grade squamous dysplasia and squamous cell carcinoma, LOH was detected at marker D9S162 (20.8 %, 36.7 %), D9S171 (33.3 %, 36 %), D9S753(34.8 %, 46.2 %), D9S1748(4.2 %, 13.8 %), D9S242(14.3 %, 21.2 %), D9S43(0, 0). The frequency of LOH showed significant difference among the six microsatellite markers (X2=17.26, P< 0.005; X2=22.66,P<0.005). Conclusion The progression from normal squamous epithelium to high-grade Squamous dysplasia and subsequently to squamous cell carcinoma of the esophagus is associated with accumulation of chromosomal change. The situs of D9S171, D9S162, D9S242, D9S753 exist higher LOH and all exceed 20 %. Possible tumor suppressor genes at or near D9S171, D9S162, D9S242, D9S753 may be related to the progression of esophageal squamous cell carcinoma.

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