The hallmark lesions of age-related macular degeneration (AMD) are drusen and basal linear deposit which are lipid substances deposited in Bruch membrane or the compartment on the Bruch membrane. There is a prevailing hypothesis that lipid and its oxidized derivant deposited in retina may have important roles in the pathogenesis of AMD. Lipid oxidation products are toxic, may affect the adjacent cells, induce inflammation, and trigger neovascularization.7-ketocholestoral (7KCh), a naturally occurring oxidized form of cholesterol, had been found to be toxic to retinal cells and able to induce chronic inflammation, which may play a critical role in the development of AMD. However the precise mechanism remains to be elucidated. Thus we will make a brief review of 7KCh and its association with AMD.
【Abstract】ObjectiveTo evaluate the relationships between the transporters BSEP， MRP2， MDR3 and cholesterol calculus formation. MethodsTwenty hepatic tissue specimens were taken from consented patients with cholesterol calculus during intraoperative liver biopsy, of which ten were taken from patients without cholesterol calculus. RNA of liver tissue from all the samples was extracted and ultraviolet spectrophotometry was used to measure the content and purity of it. The mRNA and protein expressions of BSEP, MRP2 and MDR3 were determined by reverse transcriptionpolymerase chain reaction (RTPCR) and Western blot analysis, respectively. ResultsRTPCR showed that the mRNA expressions of BSEP, MRP2 and MDR3 in liver were significantly lower in patients with cholesterol calculus （0.47±0.18, 1.12±0.39 and 1.02±0.24） than those in the liver of patients without calculus （0.90±0.42, 2.48±0.89 and 1.94±0.80）,P＜0.01. And Western blot also showed the protein expressions of these transporters were significantly lower in patients with cholesterol calculus （90.16±18.82, 45.43±22.77 and 61.08±14.77） than those in the liver of patients without calculus (186.17±4.34, 160.47±30.19 and 100.84±15.44). ConclusionThe decreased expression of BSEP, MRP2 and MDR3 may correlate with the formation of cholesterol calculus.
ObjectiveTo evaluate the relationship between low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) of preoperation (L/H value for short) and the pathological staging of colorectal cancer. MethodsThe clinical data of 187 patients with colorectal cancer who treated in PLA General Hospital from July 2009 to June 2014 were analyzed retrospectively. ResultsThere were statistical significance in L/H value among different TNM stagings, N stagings, and M stagings (P<0.05):L/H value of TNM Ⅳ staging was higher than those of TNM Ⅰ, Ⅱ, and Ⅲ staging, L/H values of N1 staging and N0 staging were lower than that of N2 staging, L/H value of M1 staging was higher than that of M0 staging. However, there was no statistical significance in L/H value among different T stagings of colorectal cancer (P>0.05). Logistic regression results showed that L/H value were positively associated with TNM staging (OR=4.34, 95% CI:2.837-6.644, P<0.000 1), T staging (OR=1.72, 95% CI:1.175-2.512, P=0.005 3), N staging (OR=2.15, 95% CI:1.422-3.254, P=0.000 3), and M staging (OR=3.04, 95% CI:1.733-5.332, P=0.000 1) of colorectal cancer, and patient with higher L/H value took more risk of progression of tumor, lymph node metastases, and distant metastasis. ConclusionsRaise of preoperative L/H value is an independent risk factor for the progression of TNM staging, T staging, N staging, and M staging in colorectal cancer.
ObjectiveTo summarize the remodeling of cholesterol metabolism in the occurrence and progression of pancreatic ductal adenocarcinoma (PDAC), and to review the research progress on targeted cholesterol metabolism in the treatment of PDAC. MethodRelevant literatures on cholesterol metabolism in the occurrence, development, and diagnosis and treatment of PDAC in recent years were searched and reviewed. ResultsMetabolites of PDAC tumor cells affected the expression of oncogenes or tumor suppressor genes. Signaling regulation within tumor cells affects cholesterol metabolism, characterized by increased de novo cholesterol synthesis and esterification, and reduced efflux. Tumor cells also regulated tumor immune microenvironment or tumor stroma formation through cholesterol metabolism. Inhibiting cholesterol metabolism could suppress the proliferation, invasion and migration of PDAC tumor cells, and combination therapy targeting cholesterol metabolism had a synergistic anti-PDAC effect. ConclusionsRemodeling of cholesterol metabolism occurs in both PDAC tumor cells and the tumor microenvironment, and is closely related to the occurrence, development, invasion, metastasis, and treatment response of PDAC. Targeting cholesterol metabolism or combined application with chemotherapy drugs can have anticancer effects. However, more research is needed to support the translation of cholesterol metabolism regulation into clinical treatment applications.
Objective To investigate the mRNA expressions of liver X receptor α (LXRα), farnesoid X receptor (FXR), steroid xenobiotic receptor (SXR) and liver receptor homolog 1 (LRH-1) gene in patients with cholesterol gallstone (CGS) disease in order to elucidate the biomolecular pathogenesis of gallstone formation. Methods Twenty-seven patients with CGS (CGS group) and 10 controls without gallstones (control group) were included in this study. Serum lipid composition (total cholesterol, triglyceride, high density lipoprotein cholesterol, apoprotein B, apoprotein A1), gallstone cholesterol concentration and biliary composition (cholesterol, bile salts, lecithin) were assayed. Biliary total lipid and cholesterol saturation index (CSI) were calculated. mRNA expressions of LRH-1, FXR, SXR and LXRα gene were determined by real-time polymorphism chain reaction. Results Serum high density lipoprotein cholesterol concentration was lower in CGS group than that in control group 〔(0.93±0.05) mmol/L vs (1.33±0.09) mmol/L, P＜0.001〕 and serum apoprotein A1 was also lower in CGS group than that in control group 〔(1.19±0.05) g/L vs (1.36±0.06) g/L, P＜0.05〕. There were no differences in serum total cholesterol, triglyceride and apoprotein B between two groups (Pgt;0.05). CSI was higher in CGS group than that in control group (1.17±0.02 vs 0.79±0.10), P＜0.001. Biliary cholesterol was also higher in CGS group than that in control group 〔(7.96±0.39) mol% vs (5.26±0.89) mol%, P＜0.01〕, while biliary total lipid was lower in CGS group than that in control group 〔(104.72±10.51) g/L vs (154.24±14.20) g/L, P＜0.05〕. There were no differences in bile salts and lecithin between two groups (Pgt;0.05). Expression of LRH-1 gene was higher in CGS group than that in control group (14.18±1.80 vs 7.22±2.22), the difference was statistically significant (P＜0.05). There were no differences in mRNA expressions of LXRα, FXR and SXR gene between two groups (Pgt;0.05). Conclusion CGS disease may be related to increased expression of LRH-1 gene.
Objective To study the latest research progress of the formation mechanism of cholesterol stone disease and forming factors of cholesterol stone disease and to provide new theoretical level and develop a new development direction for guiding clinical application. Methods The related literatures at home and abroad were analyzed, compared and summarized, and the current relevant research dynamic of cholesterol stone disease was sketched. Results The formation of cholesterol gallstone is closely related to the abnormal levels of serum lipids metabolism, bacterial and viral infection, and the expression of genes related to cholesterol gallstone. Conclusions The formation of cholesterol calculus disease is a kind of interaction and intricate disease process involving of environmental factors, genetic factors, and biological factors. Although there has been a lot of blood lipid, protein correlation research with cholesterol stone, there are also many studies such as using gene transplantation and gene knockout, but gene technology of cholesterol stone disease diagnosis and treatment is expected to become the new hot research topic.
ObjectiveTo observe the effects of oral Xiaoyan Lidan tablets(XYLDT) on the bile composition(total bile acids, cholesterol, phospholipids) in patients with intrahepatic duct stones after common bile duct exploration(CBDE) with T tube drainage, to explore its possible preventive effects on stone recurrence. MethodsForty consecutive patients with intrahepatic bile duct stones who underwent CBDE with T tube drainage were randomly divided into experi mental group and control group. XYLDT were administrated at day 4 after surgery in experimental group(n=20), while none of medication were given in control group(n=20). 2 mL of bile was collected through T tube in both groups at day 1, 2, 3, 7, 14, and 21 postoperatively. Total bile acids(TBA), cholesterol(CHO), and phospholipids(PLIP) in bile were measured, and TBA/CHO ratio and PLIP/CHO ratio were calculated respectively. The results were statistical analyzed. ResultsThe demographic data in both groups including age, gender, height, weight, preoperative concomitant diseases, operative time, postoperative complications, hospital stays, serum total bilirubin, direct bilirubin, alanine aminotransferase(ALT), aspartate aminotransferase(AST), and amylase were not significantly different(P > 0.05). The measurements of TBA, CHO, PLIP, and the ratio of TBA/CHO and PLIP/CHO in bile were not significant on day 1, 2, and 3 after surgery in both groups(P > 0.05). In experimental group, the TBA, CHO, and PLIP on day 7, 14, and 21 after surgery were significantly increased compared with the control group(P < 0.05). The ratio of TBA/CHO on day 7, 14, and 21 was 2.17±0.29, 2.29±0.44, and 2.59±0.58, the ratio of PLIP/CHO was 2.03±0.68, 2.84±0.64, and 2.86±0.77, respectively, which were also significantly increased compared with the control group(P < 0.05). ConclusionsOral XYLDT can increase the secretion of TBA, CHO, and PLIP, elevate the TBA/CHO and PLIP/CHO ratio, and change the bile composition which may increase the dissolution of cholesterol in the bile. Presumably, oral XYLDT may have preventive effects in the recurrence of intrahepatic bile duct stones.