Ursodeoxycholic acid lowers bile lithogenicity by regulating SCP2 expression in rabbit cholesterol gallstone models

Aims: We designed this study to get insight into the disorder of lipid metabolism during cholesterol gallstone formation and evaluate the effect of ursodeoxycholic acid on the improvement of bile lithogenicity and on expression of lipid related genes. Methods: Rabbit cholesterol gallstone models were induced by high cholesterol diet. Bile, blood and liver tissues were obtained from rabbits after 0, 1, 2, 3, 4 and 5 weeks. Bile and blood lipids were measured enzymatically. 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), cytochrome P450, family 7, subfamily A, polypeptide 1 (CYP7A1) and sterol carrier protein 2 (SCP2) mRNA expressions were detected by using quantitative real-time RT-PCR. Cholesterol saturation index (CSI) was calculated by using Carey table to represent the bile lithogenicity. Results: Rates of gallstone formation of the 4 and 5 week treatment groups were 100 %, but that of the ursodeoxycholic acid treatment group was only 33.3 %. Expression of HMGCR and SCP2 mRNA in the 4 week group was upregulated and that of CYP7A1 mRNA decreased as compared with the 0 week group. Ursodeoxycholic acid could significantly extend nucleation time of bile and lower CSI. Ursodeoxycholic acid could reduce the expression of SCP2, but couldn’t influence expression of HMGCR and CYP7A1. Conclusions: Abnormal expression of HMGCR, CYP7A1 and SCP2 might lead to high lithogenicity of bile. Ursodeoxycholic acid could improve bile lipids and lower bile lithogenicity, thereby reducing the incidence of gallstones. So it might be a good preventive drug for cholesterol gallstones

Overexpression of Sterol Carrier Protein 2 in Patients with Hereditary Cholesterol Gallstones

<p>Abstract</p> <p>Background</p> <p>Lithogenic bile is the major cause of cholesterol gallstone, but its pathogenesis is not well understood. The hypersecretion of biliary cholesterol is believed to be an important cause of lithogenic bile. Sterol Carrier Protein 2 (SCP2) participates in cholesterol trafficking and lipid metabolism in hepatocytes and may play a key role in cholesterol gallstone formation.</p> <p>Methods</p> <p>21 cholesterol gallstone genealogies were studied to investigate the expression of SCP2 gene in liver tissue of hereditary and non-hereditary cholesterol gallstone patients as well as non-gallstone patients. The mRNA expression of liver SCP2 in 28 hereditary patients, 30 non-hereditary cholesterol gallstone patients and 32 non-gallstone patients was measured by Reverse Transcription Polymerase Chain Reaction (RT-PCR). The protein expression of liver SCP2 was also detected in all the patients by Western blotting. At the same time, the bile was also analyzed with biochemical techniques and the Cholesterol Saturation Index (CSI) was calculated.</p> <p>Results</p> <p>The mRNA and protein expression of SCP2 was significantly increased in cholesterol gallstone patients compared to those of non-gallstone patients. Moreover, SCP2 was expressed at higher levels in hereditary cholesterol gallstone patients than that of non-hereditary cholesterol gallstone patients. There was significant difference observed in CSI between cholesterol gallstone patients and non-gallstone patients, but not in CSI between hereditary and non-hereditary cholesterol gallstone patients.</p> <p>Conclusions</p> <p>SCP2 was overexpressed in hereditary cholesterol gallstone patients compared to non-hereditary cholesterol gallstone patients. This finding indicated that SCP2 might be one of the genetic factors contributing to cholesterol gallstone formation, which was always accompanied by the increase of bile lithogenicity.</p

The Role of Autophagy and Autophagy Receptor NDP52 in Microbial Infections

Autophagy is a general protective mechanism for maintaining homeostasis in eukaryotic cells, regulating cellular metabolism, and promoting cell survival by degrading and recycling cellular components under stress conditions. The degradation pathway that is mediated by autophagy receptors is called selective autophagy, also named as xenophagy. Autophagy receptor NDP52 acts as a &lsquo;bridge&rsquo; between autophagy and the ubiquitin-proteasome system, and it also plays an important role in the process of selective autophagy. Pathogenic microbial infections cause various diseases in both humans and animals, posing a great threat to public health. Increasing evidence has revealed that autophagy and autophagy receptors are involved in the life cycle of pathogenic microbial infections. The interaction between autophagy receptor and pathogenic microorganism not only affects the replication of these microorganisms in the host cell, but it also affects the host&rsquo;s immune system. This review aims to discuss the effects of autophagy on pathogenic microbial infection and replication, and summarizes the mechanisms by which autophagy receptors interact with microorganisms. While considering the role of autophagy receptors in microbial infection, NDP52 might be a potential target for developing effective therapies to treat pathogenic microbial infections

Factors promoting thrombosis in essential thrombocythemia: a Meta-analysis

ObjectiveTo further understand the factors that promote thrombosis in essential thrombocythemia （ET） that were not included in IPSET-thrombosis （International Prognostic Score of Thrombosis for ET）. MethodsA systematic evaluation was conducted on 292 studies by retrieving PubMed，Web of Science, and The Cochrane Library. The incidence and relative risk ratio （RR） of thrombosis in ET patients with different risk factors were calculated. The confidence levels for the outcome were analyzed in combination with RR values and recommendation scores (RS) to find the thrombotic risk factors in ET patients. ResultsOut of 9 risk factors that promoted ET thrombosis, there were 4 factors in IPSET-thrombosis, including history of thrombosis （35.0%, RR=3.30, 95% CI : 2.30-4.75）, JAK2V617F positive （21.0%, RR=2.28, 95%CI : 1.14-4.56）, age over 60 years old （ 22.4% , RR=1.95, 95%CI : 1.17-3.23） and cardiovascular risk factors （17.7%, RR =1.90, 95%CI : 1.08-3.35）. The remaining five risk factors, not listed in IPSET-thrombosis, included monoclonal type of ET based on X-chromosome inactivation pattern （XCIP, 30.6%, RR=4.49, 95% CI: 1.58-12.77）, high JAK2V617F burden （33.9%, RR=3.69, 95%CI: 1.70-7.99）, leukocytosis （18.7%, RR=3.05, 95%CI: 1.81-5.13）, MPL mutation （22.1%, RR=2.40, 95%CI: 1.08-5.33） and splenomegaly （25.6%, RR=1.76, 95%CI：1.29-2.40）. ConclusionAmong the risk factors promoting thrombosis in ET patients, five thrombotic risk factors not included in the IPSET-thrombosis have been identified