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.
ObjectiveTo investigate the association of high density lipoprotein cholesterol (HDL-C) and cholesterol ester transfer protein (CETP) TaqIB mutation with non-arteritic anterior ischemic optic neuropathy (NA-AION) in the Shaanxi Han ethnic population. MethodsThe study cohort consisted of 45 individuals that had been diagnosed with NA-AION and 45 healthy controls (matched for age, gender). None of the cases or controls had a history of diabetes, serious cardio-cerebral vascular diseases, liver and kidney dysfunction that might influence plasma lipid levels. Plasma HDL-C was detected by enzyme-linked immunosorbent one-step, through the Toshiba TBA-40FR automatic biochemical analyzer. CETP TaqIB gene polymorphism was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques for analysis. B2B2 genotype was only a fluorescence band with 535 bp; B1B1 genotype was 2 fluorescence bands with 361, 174 bp; B1B2 genotype was 3 fluorescence bands with 535, 361, 174 bp. The relative risk of genotype, HDL-C and disease occurrence was analyzed by logistics regression analysis. ResultsThere have no significant difference between NA-AION patients and controls about plasma total cholesterol level and triglyceride level (t=1.907, 1.877; P > 0.05). The plasma HDL-C levels were significantly lower in NA-AION patients than in controls (t=2.367, P=0.022). Compared with controls, the prevalence of B1B1 genotype and B1 allele was higher (χ2=17.289, P=0.001), the prevalence of B2 allele (χ2=15.648, P=0.000) was lower in NA-AION patients. The lower concentration of HDL-C was risk factor of NA-AION (odds ratio=6.143, 95% confidence interval 1.262-29.895, χ2=27.676;P=0.013). The proportion of B1B1 genotype was significantly higher in NA-AION patients than in controls (odds ratio=2.24, 95% confidence interval 2.427-36.323, χ2=10.526; P=0.001). ConclusionsThe low plasma HDL-C is independent risk factor for NA-AION and is associated with the development of NA-AION in the Shaanxi Han ethnic population. CETP TaqIB mutation is associated with low plasma HDL-C in NA-AION in the Shaanxi Han ethnic population.
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.
To declare the clinical value of lowing serum LDL-C level in coronary heart disease by reviewing the history of its clinical trials in the last 4 decades.
Objective To investigate the correlation between the uric acid to high-density lipoprotein cholesterol ratio (UHR) and the presence of atherosclerotic stenosis in both intracranial and extracranial arteries among patients who have experienced cerebral infarction. Methods Patients with cerebral infarction admitted to the Department of Neurology of Sichuan Provincial People’s Hospital between January 2021 and June 2024 were retrospective selected. According to the digital subtraction angiography (DSA) performance, patients were divided into cerebral atherosclerotic stenosis group and no cerebral atherosclerotic stenosis group. According to the location of atherosclerotic stenosis, patients were divided into extracranial atherosclerotic stenosis group, intracranial atherosclerotic stenosis group, intracranial and extracranial atherosclerotic stenosis group. According to the severity of atherosclerotic stenosis, patients were divided into mild group, moderate group and severe group. Clinical data and laboratory indicators were collected. Multifactorial regression was used to analyze the risk factors, Spearman correlation analysis was used to evaluate the relationship between UHR and the degree of stenosis, and the predictive value of UHR for intracranial and extracranial atherosclerotic stenosis was analyzed by the receiver operating characteristic curve. Results A total of 388 patients were included. Among them, 291 cases in cerebral atherosclerotic stenosis group and 97 cases in no cerebral atherosclerotic stenosis group; 85 cases in the intracranial atherosclerotic stenosis group, 123 cases in the extracranial atherosclerotic stenosis group, and 83 cases in the intracranial and extracranial atherosclerotic stenosis group; There were 104 cases in the mild group, 81 cases in the moderate group, and 106 cases in the severe group. The results of multiple logistic regression analysis showed that age, hypertension, UHR and uric acid were independent influencing factors associated with atherosclerotic stenosis of intracranial and extracranial arteries. Furthermore, the uric acid and UHR were also risk factors for the degree of stenosis (P<0.05). Spearman correlation analysis results showed that UHR was positively correlated with the degree of stenosis (r=0.516, P < 0.001). Receiver operating characteristic curve showed that the predictive value of UHR (area under the curve was 0.724) was superior to that of uric acid (area under the curve was 0.638) or HDL-C (area under the curve was 0.709). It also showed good predictive value for stenosis in different locations of intracranial and extracranial arteries. Conclusion UHR is an independent risk factor for intracranial and extracranial atherosclerotic stenosis with notabla predictive value
ObjectiveTo explore the expressions of transthyretin(TTR) mRNA and its protein in tissues of human gallbladder with cholesterol gallstones, and to explore its role in the formation of cholesterol gallstones. MethodsGallbladder were got from cases of cholesterol gallstones(cholesterol gallstones group, n=25) and cases underwent liver transplantation with normal gallbladder(normal control group, n=9) respectively, who were treated in Ren Ji Hospital and Huashan Hospital. Real time PCR(RT-PCR) and Western blot method were used to determine the expressions of TTR mRNA and its protein respectively. In addition, 2 kinds of artificial model bile system were established to test nucleation time(NT) and nucleation activity, which added TTR and albumin(ALB). ResultsThe expression levels of TTR mRNA and protein in cholesterol gallstones group were 1.51±0.78 and 3.95±0.09 respectively, which were both higher than those of normal control group(P<0.05). The NT were(14.5±1.3)d and(18.0±0.8)d in TTR group and ALB group in small model bile system(P<0.01), which was similar with comprehensive model bile system[(13.5±0.6)d vs. (18.5±1.3)d]. The nucleation activity were 0.81 and 0.73 in small model bile system and comprehensive model bile system respectively. ConclusionsExpression of TTR up-regulates in human gallbladder tissues of patients with cholesterol gallstones, and TTR plays role of nucleation in model bile system, which is related to the formation of cholesterol gallstones.
【Abstract】Objective To explore the relationship between the expression of MDR1 gene in liver cell and the formation of cholesterol calculus in gallbladder.Methods The mRNA expression level of MDR1 gene in liver cell of the cholesterol calculus group and the normal control group were measured through reverse transcriptionpolymerase chain reaction (RT-PCR)， and microglobulin β2 was used as internal contrast.Results The MDR1 mRNA expression level of the cholesterol calculus group was lower than that of the normal control group(1.30±0.19 vs 2.25±0.28, P＜0.01). Conclusion The formation of cholesterol calculus in gallbladder is related to the reducd expression level of MDR1 gene in liver cell.