Simvastatin Blocks Blood-Brain Barrier Disruptions Induced by Elevated Cholesterol Both In Vivo and In Vitro

Background. Hypercholesterolemia and disruptions of the blood brain barrier (BBB) have been implicated as underlying mechanisms in the pathogenesis of Alzheimer's disease (AD). Simvastatin therapy may be of benefit in treating AD; however, its mechanism has not been yet fully understood. Objective. To explore whether simvastatin could block disruption of BBB induced by cholesterol both in vivo and in vitro. Methods. New Zealand rabbits were fed cholesterol-enriched diet with or without simvastatin. Total cholesterol of serum and brain was measured. BBB dysfunction was evaluated. To further test the results in vivo, rat brain microvascular endothelial cells (RBMECs) were stimulated with cholesterol in the presence/absence of simvastatin in vitro. BBB disruption was evaluated. Results. Simvastatin blocked cholesterol-rich diet induced leakage of Evan's blue dye. Cholesterol content in the serum was affected by simvastatin, but not brain cholesterol. Simvastatin blocked high-cholesterol medium-induced decrease in TEER and increase in transendothelial FITC-labeled BSA Passage in RBMECs. Conclusions. The present study firstly shows that simvastatin improves disturbed BBB function both in vivo and in vitro. Our data provide that simvastatin may be useful for attenuating disturbed BBB mediated by hypercholesterolemia

Characteristics and metabolic potential of biliary microbiota in patients with giant common bile duct stones

BackgroundEndoscopic retrograde cholangiopancreatography (ERCP) is an effective minimally invasive operation for the management of choledocholithiasis, while successful extraction is hampered by large diameter of stones. Emerging studies have revealed the close correlation between biliary microbiota and common bile duct stones (CBDS). In this study, we aimed to investigate the community characteristics and metabolic functions of biliary microbiota in patients with giant CBDS.MethodsEligible patients were prospectively enrolled in this study in First Affiliated Hospital of Soochow University from February 2022 to October 2022. Bile samples were collected through ERCP. The microbiota was analyzed using 16S rRNA sequencing. Metabolic functions were predicted by PICRUSTs 2.0 calculation based on MetaCyc database. Bile acids were tested and identified using ultra performance liquid chromatography-tandem mass spectrometry.ResultsA total of 26 patients were successfully included into final analysis, 8 in giant stone (GS) group and 18 in control group. Distinct biliary microbial composition was identified in patients with giant CBDS, with a significantly higher abundance of Firmicutes at phylum level. The unique composition at genus level mainly consisted of Enterococcus, Citrobacter, Lactobacillus, Pyramidobacter, Bifidobacterium and Shewanella. Pyramidobacter was exclusively found in GS group, along with the absence of Robinsoniella and Coprococcus. The contents of free bile acids were significantly higher in GS group, including cholic acid (98.39μmol/mL vs. 26.15μmol/mL, p=0.035), chenodesoxycholic acid (54.69μmol/mL vs. 5.86μmol/mL, p=0.022) and ursodeoxycholic acid (2.70μmol/mL vs. 0.17μmol/mL, p=0.047). Decreasing tendency of conjugated bile acids were also observed. Metabolic pathways concerning cholelithiasis were abundant in GS group, including geranylgeranyl diphosphate biosynthesis, gluconeogenesis, glycolysis and L-methionine biosynthesis.ConclusionsThis study demonstrated the community structure and metabolic potential of biliary microbiota in patients with giant CBDS. The unique biliary microbial composition holds valuable predictive potential for clinical conditions. These findings provide new insights into the etiology of giant CBDS from the perspective of biliary microbiota

Lithium Suppresses Astrogliogenesis by Neural Stem and Progenitor Cells by Inhibiting STAT3 Pathway Independently of Glycogen Synthase Kinase 3 Beta

Transplanted neural stem and progenitor cells (NSCs) produce mostly astrocytes in injured spinal cords. Lithium stimulates neurogenesis by inhibiting GSK3b (glycogen synthetase kinase 3-beta) and increasing WNT/beta catenin. Lithium suppresses astrogliogenesis but the mechanisms were unclear. We cultured NSCs from subventricular zone of neonatal rats and showed that lithium reduced NSC production of astrocytes as well as proliferation of glia restricted progenitor (GRP) cells. Lithium strongly inhibited STAT3 (signal transducer and activator of transcription 3) activation, a messenger system known to promote astrogliogenesis and cancer. Lithium abolished STAT3 activation and astrogliogenesis induced by a STAT3 agonist AICAR (5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside), suggesting that lithium suppresses astrogliogenesis by inhibiting STAT3. GSK3β inhibition either by a specific GSK3β inhibitor SB216763 or overexpression of GID5-6 (GSK3β Interaction Domain aa380 to 404) did not suppress astrogliogenesis and GRP proliferation. GSK3β inhibition also did not suppress STAT3 activation. Together, these results indicate that lithium inhibits astrogliogenesis through non-GSK3β-mediated inhibition of STAT. Lithium may increase efficacy of NSC transplants by increasing neurogenesis and reducing astrogliogenesis. Our results also may explain the strong safety record of lithium treatment of manic depression. Millions of people take high-dose (>1 gram/day) lithium carbonate for a lifetime. GSK3b inhibition increases WNT/beta catenin, associated with colon and other cancers. STAT3 inhibition may reduce risk for cancer

Gravity field recovery from GOCE orbits using the energy conservation approach

The sum of the dissipative energy and energy constant of the GOCE satellite is found by a priori gravity field model at first, and the GOCE dissipative energy is obtained by computing the adjacent epoch difference via the differential method. Then, a gravity field model GOCE-ECP01, which up to the degree and order 80, is recovered by the energy conservation approach from the 103-day precise orbital data of the GOCE satellite collected from November 1, 2009 to January 12, 2010. Finally, the model is compared with existing models EGM96, ITG-CHAMP05S, EIGEN-GRACE2010S, EIGEN-6C and GO_CONS_GCF_2_DIR_R3. The results show that at the same order and degree, the accuracy of model GOCE-EBP01 is higher than those of models EGM96 and ITG-CHAMP05S, but lower than those of models EIGEN-GRACE2010S, EIGEN-6C and GO_CONS_GCF_2_DIR_R3, which is mainly caused by the pole gap

Effects of phosphorus and nitrogen limitations on continuous production of glycerol in a multistage cascade bioreactor by Candida krusei

A multistage cascade culture was used for the continuous production of glycerol by an osmophilic yeast Candida krusei. The effects of phosphorus and nitrogen limitations on glycerol production were investigated. The results showed that the fermentation performance was improved under either phosphorus or nitrogen limitation. A maximum glycerol yield of 24.7% based on the glucose consumed and a maximum glycerol yield of 7.1 g g?1 based on the biomass were achieved under the optimum nitrogen limitation. The maximum productivity for the whole system under the optimum phosphorus limitation was 11.3% higher than that under the optimum nitrogen limitation. This indicated that the nitrogen limitation benefited the improvement of glycerol yield based on the glucose consumed and the production ability of glycerol per unit biomass but the phosphorus limitation favored the increase of productivity. The glycerol/glucose yield and the glycerol/biomass yield could be further improved under the dual limitations of phosphorus and nitrogen, but the biomass yield and the productivity were reduce

Glycerol production by Candida krusei employing NaCl as an osmoregulator in batch and continuous fermentations

Addition of 40 g NaCl l?1 to a chemically defined medium containing 140 g glucose l?1 in shake-flask culture improved glycerol production by Candida krusei from 16.5 g l?1 to 47.7 g l?1. With 40 g NaCl l?1 at a dilution rate of 0.065 h?1, glycerol concentration, glycerol yield (based on glucose consumed), and productivity in a four-stage cascade bioreactor were higher by 240%, 27% and 28%, respectively, than in a single-stage continuous culture system

Target Image Matching Algorithm Based on Binocular CCD Ranging

This paper proposed target image in a subpixel level matching algorithm for binocular CCD ranging, which is based on the principle of binocular CCD ranging. In the paper, firstly, we introduced the ranging principle of the binocular ranging system and deduced a binocular parallax formula. Secondly, we deduced the algorithm which was named improved cross-correlation matching algorithm and cubic surface fitting algorithm for target images matched, and it could achieve a subpixel level matching for binocular CCD ranging images. Lastly, through experiment we have analyzed and verified the actual CCD ranging images, then analyzed the errors of the experimental results and corrected the formula of calculating system errors. Experimental results showed that the actual measurement accuracy of a target within 3 km was higher than 0.52%, which meet the accuracy requirements of the high precision binocular ranging

Research on Adaptive Optics Image Restoration Algorithm by Improved Expectation Maximization Method

To improve the effect of adaptive optics images’ restoration, we put forward a deconvolution algorithm improved by the EM algorithm which joints multiframe adaptive optics images based on expectation-maximization theory. Firstly, we need to make a mathematical model for the degenerate multiframe adaptive optics images. The function model is deduced for the points that spread with time based on phase error. The AO images are denoised using the image power spectral density and support constraint. Secondly, the EM algorithm is improved by combining the AO imaging system parameters and regularization technique. A cost function for the joint-deconvolution multiframe AO images is given, and the optimization model for their parameter estimations is built. Lastly, the image-restoration experiments on both analog images and the real AO are performed to verify the recovery effect of our algorithm. The experimental results show that comparing with the Wiener-IBD or RL-IBD algorithm, our iterations decrease 14.3% and well improve the estimation accuracy. The model distinguishes the PSF of the AO images and recovers the observed target images clearly