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.
ObjectiveTo summarize progress of 25-hydroxycholesterol (25-OHC), 27-hydroxycholesterol(27-OHC), and 7α,25-hydroxycholesterol (7α,25-OHC) three oxidized cholesterols in inflammation and immunology and to provide evidence for related basic researches and diseases treatments.MethodThe relevant literatures about these three important oxidized cholesterols in the inflammation and immunology in recent years were reviewed.ResultsThe 25-OHC and 27-OHC could exert the antiviral effects by interfering with various viruses invading the host via various mechanisms. Moreover, the 25-OHC and 27-OHC also played the important regulatory roles in a variety of inflammatory processes and inflammatory diseases. The 7α,25-OHC played the important role in a variety of inflammatory processes by acting on the inflammatory and immune cell membrane receptor G-protein coupled receptor 183 (also known as Epstein-Barr virus-inducible receptor 2).Conclusion25-OHC, 27-OHC and 7α,25-OHC play an important roles in occurrence and development of various inflammatory and immune responses and diseases of inflammatory and immune by acting on a variety of nuclear receptors and membrane receptors.
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.
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.
Objective To discuss the changes of c-kit/scf mRNA and protein in guinea pig gallbladder fed on high cholesterol diet. Methods Twenty guinea pigs were divided into two equal groups of 10 each：the control group and lithogenic group. Normal diet and high cholesterol diet was given to each group respectively. The period of stone permeation was six weeks. RT-PCR and Western blot were used to determin the expressions of c-kit and scf mRNA and protein. Results RT-PCR results showed that the expressions of c-kit mRNA（t=6.985，P＜0.01） and scf mRNA （t=6.028， P＜0.01）decreased significantly in lithogenic group compared with the control group. Western blot results showed that the expressions of c-kit protein （t=10.256， P＜0.01） and scf protein （t=9.586， P＜0.01）decreased significantly in lithogenic group compared with the control group. Conclusions The expressions of c-kit/scf mRNA and protein decrease during the formation of cholesterol gallstones in guinea pigs fed on high cholesterol diet. Inhibition of c-kit/scf pathway may play a role in the formation of cholesterol gallstones.
ObjectiveTo conduct a systematical evaluation and meta-analysis of the relation between serum total cholesterol (TC) level and the risk of gastric cancer. MethodsThe PubMed, Embase, Web of Science, and Cochrane Library databases were searched from inception to March 5, 2023. Two independent reviewers performed the literature search, identification, and screening, as well as performed the quality assessment and data extraction. ResultsA total of 12 studies with 5 143 671 participants and 40 551 patients with gastric cancer were included in the meta-analysis. The results of meta analysis showed that 9 studies reported that the elevated serum TC level decreased the risk of gastric cancer [OR (95%CI) was 0.91 (0.85, 0.98)], and 5 studies reported that the decreased serum TC level increased the risk of gastric cancer [OR (95%CI) was 1.93 (1.17, 3.18)]. Also the results of the subgroup analyses showed that the decreased serum TC level increased the risk of gastric cancer in the studies with cohort study, larger overall sample sizes and gastric cancer sample sizes, with longer duration of follow-up, and in those with habits of alcohol and smoking [0.89 (0.87, 0.92), 0.90 (0.87, 0.94), 0.90 (0.87, 0.93), 0.86 (0.82, 0.90), 0.90 (0.87, 0.93), and 0.90 (0.87, 0.93), respectively] , which was consistent with the overall results. In contrast, there was no statistical difference in the relation between the elevated serum TC level decreased the risk of gastric cancer between male and female patients in the gender subgroup. ConclusionsThe results of this systematical evaluation and meta-analysis suggest that serum TC level [135–294 mg/dL (3.49–7.62 mmol/L)] may be a protective factor for gastric carcinogenesis. The risk of gastric carcinogenesis may be increased when serum TC level decreases, and this change is a long-term and insidious process.
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
Oncogene StarD4 had the function of promoting proliferation and metastasis of triple-negative breast cancer (TNBC), but its clinical value and molecular mechanism are unknown. This paper found that StarD4 was highly expressed in cancer tissues of TNBC patients, and higher expression level of StarD4 in TNBC patient resulted in poorer prognosis. Based on transcriptomics of MDA-MB-231 cell model, the results of bioinformatics analysis showed that down-regulated expression level of StarD4 led to overall downregulation of cholesterol-relative genes and significant enrichment of cancer mechanism and pathway. Further analysis and investigation verified that StarD4 might cross-promote the protein stability of receptor ITGA5 through the cholesterol pathway to enhance TNBC progression, which provides guidance for clinical application of TNBC diagnosis and treatment.
ObjectiveTo investigate the predictive value of a new nutritional index, triglycerides-total cholesterol-body mass index (TCBI), for prolonged postoperative hospital stay in patients undergoing coronary artery bypass grafting surgery (CABG). MethodsA retrospective analysis was conducted on the clinical data of CABG patients admitted to Wuhan Asian Heart Hospital, Wuhan University of Science and Technology from January 2022 to March 2024. Based on the postoperative hospital stay duration of CABG patients, they were divided into two groups: normal hospital stay group (≤14 days) and prolonged hospital stay group (>14 days). Univariate and multivariate logistic regression analyses were used to identify independent factors associated with prolonged postoperative hospital stay in CABG patients. The receiver operating characteristic (ROC) curve was employed to evaluate the predictive value of TCBI for prolonged postoperative hospital stay. ResultsA total of 460 patients were included, with 289 males (62.8%) and 171 females (37.2%), with an average age of 67 years (range 35-83 years). The TCBI level in the prolonged hospital stay group was significantly lower than that in the normal hospital stay group [1161.71 (825.36, 1511.78) vs. 1777.60 (1354.53, 2448.60), P<0.001]. Multivariate logistic regression analysis revealed that drinking history (OR=2.222, P=0.022), low absolute lymphocyte count (OR=0.169, P<0.001), low serum albumin (OR=0.624, P<0.001), and low TCBI (OR=0.816, P<0.001) were independent risk factors for prolonged postoperative hospital stay in CABG patients. ROC curve results showed that the area under the curve for TCBI to predict prolonged hospital stay was 0.808, with a sensitivity of 72.8% and specificity of 70.9% at a cutoff value of 1446.11. ConclusionTCBI is an effective predictive indicator for prolonged postoperative hospital stay in CABG patients, and the risk of prolonged postoperative hospital stay is higher in CABG patients with TCBI ≤1446.11.