Bile acids are the main products of the cholesterol degradation in the liver. They promote the absorption and transportation of the intestinal lipids. Diverse bile acid receptors are widely distributed in human tissues and organs, including farnesoid X receptor (FXR) and Takeda G protein receptor (TGR5). The expression pattern of different bile acid receptors and their different affinities to various bile acids as their ligands determines their pleiotropic downstream effects, including regulating bile acid synthesis and transportation, immune and metabolism homeostasis. In addition, the bile acid pool includes components derived from both host and gut microbiota, which collaboratively contribute to the bile acid signaling activation in different compartments. Therefore, bile acid pool represents an information hub allowing the crosstalk between the host and gut microbiome and hereby modulating host metabolic homeostasis and gut microbiome symbiosis. This article reviews the recent advances in the field of bile acid regulation and the related mechanisms of bile acid signaling pathway to maintain metabolic homeostasis.

Objective: To explore the safety of elective therapeutic cardiac catheterization in congenital heart disease (CHD) children with recent upper respiratory tract infection (URI) (within two weeks), so as to provide guidance for clinical anesthesia management. Methods: A total of 140 CHD children of American Society of Anesthesiologist (ASA) II~III undergoing tracheal intubation general anesthesia for elective therapeutic cardiac catheterization, aged 3 months to 15 years, were divided into URI group and non-URI group according to history of recent URI. The incidence of perioperative respiratory adverse events (PRAEs) [i.e. laryngospasm, bronchospasm, breath holding ≥ 15 s, pulse blood oxygen saturation (SpO2)<95%( ≥ 10 s), cough, and glossoptosis] and postoperative dysphoria, fever, copious sputum, and vomiting within 24 h after operation were observed and compared. Results: Compared with non-URI group, recent URI increased significantly the overall incidence of PRAEs (any complications of PRAEs) (P=0.001), particularly the incidence of SpO2<95% (P=0.014) and cough (P=0.000). Compared with children aged from 4-15 in URI group, the overall incidence of PRAEs (P=0.003), SpO2<95% (P=0.018), and cough (P=0.027) of children younger than 3 years increased significantly. Besides, compared with non-URI group, recent URI increased significantly the incidence of postoperative copious sputum (P=0.002). Conclusion: Recent URI increases significantly the incidence of perioperative complications in CHD children undergoing elective therapeutic cardiac catheterization. These complications are short and easily managed, and no serious adverse events occurred in CHD children.

Objective To study the correlation between level of nitric oxide/ nitricoxide synthase(NO/NOS) on placenta homogenate and ultra-structure changes of placenta in pregnancy lead exposure in rats.Methods Seventeen normal pregnant rats and 46 rats of exposured in lead which were divided into A,B,C groups were studied.The level of NO/NOS of placenta were measured by nitrate reductase and NOS kit.Placentas were randomly selected from each group to detect ultra-structure by electron-microscope.Results There were significant difference among A,B and control groups on level of NO/NOS(all P0.05).Compensation hyperplasy or minor injury were observed in lead exposure of stage groups.Lead exposure during whole gestation period,the lead level was maxmum,and decompensation were observed on placental construction.Conclusions There is a close correlations between level of lead,NO/NOS and pathological change of placental tissue,and both of them may play an important role in the pathogenesis of peripartum lead exposure.

OBJECTIVETo investigate the feasibility of real-time elastography for quantitative evaluation of liver fibrosis in a rat model.

METHODSA total of 70 male Wistar rats were included in the group for dimethylnitrosamine (DMN)-induced liver injury, and 10 saline-injected rats were used as normal control. Hepatic injury was induced by a single intraperitoneal injection of DMN at a dose of 50 mg/kg of body weight. Nine or ten rats in the group with DNM injected and one or two rats in the normal control group were randomly selected and sacrificed at each of the following post-injection time: day 5, 7, 10, 14, 21, 24, and 28. And their livers were taken for pathology analysis. All the rats underwent real-time elastography before sacrificed in order to acquire area ratio of low-strain region (% AREA) and liver fibrosis index (LF index) which were compared with the stage of liver fibrosis and grade of necroinflammatory pathologically. By the different data, Spearman correlation analysis, rank-sum test or receiver operating characteristic curve was used.

RESULTSAmong 58 successfully modeled rats, there were nine, 13, 14 and 12 rats of S1, S2, S3 and S4 liver fibrosis on pathology, respectively, which were with or without mild necroinflammatory. The other 10 rats were found to be S0 with severe necroinflammatory. Values of LF index and % AREA both increased with liver fibrosis stage (P less than 0.05). There was certain correlation between LF index and liver fibrosis stage (r=0.643, P=0.000), so was % AREA and liver fibrosis stage (r=0.662, P=0.000). As for LF index, Areas under the receiver operating characteristic curve (Az) was 0.943, 0.890, 0.743 and 0.821 for the diagnosis of hepatic fibrosis S1 or higher, S2 or higher, S3 or higher and S4, respectively; as for % AREA, they were 0.948, 0.883, 0.772 and 0.842, respectively. However, we found a significant difference for LF index or % AREA between S0 with and without severe inflammatory activity rats (P=0.005 and P=0.017).

CONCLUSIONReal-time elastography is available for quantitative assessment of liver fibrosis in rats induced by DMN, but severe inflammatory activity can affect its accuracy.

Animals ; Dimethylnitrosamine ; adverse effects ; Elasticity Imaging Techniques ; Liver ; pathology ; Liver Cirrhosis, Experimental ; chemically induced ; pathology ; Male ; Rats ; Rats, Wistar

ObjectiveTo explore the effects of metformin （Met） on amyloid-β （Aβ） in AD cell model M146L and the underlying mechanism. MethodsMTT assay was performed to determine the optimal concentration of Met. Western blotting was performed to measure the protein levels of Aβ₄₂， amyloid precursor protein （APP） ， β-site APP-cleaving enzyme （BACE）and proteolytic enzymes including insulin-degrading enzyme （IDE）， neprilysin （NEP）， and light chain 3 Ⅱ/Ⅰ （LC3 Ⅱ/Ⅰ）； Immunofluorescence was performed to visualize how Aβ₄₂ peptides and IDE were affected by Met. Western blotting was performed to test levels of IDE and Aβ₄₂ after treatment of Met and Bacitracin （Bac）， a special inhibitor of IDE. ResultsIn this study， we showed that the levels of Aβ₄₂ were down-regulated by the Met treatment （P<0.05）. No effect was observed on the expression of APP and BACE， both of which are related to the production of Aβ， after Met treatment in M146L cells （P＞0.05）. Furthermore， levels of proteolytic enzymes including IDE， NEP， and LC3Ⅱ/Ⅰ levels were markedly decreased in the M146L cells compared to the CHO cells （P<0.05） ， and only the level of IDE was reversed after the Met treatment for 24 h （P<0.05）. Importantly， Met-mediated Aβ₄₂ degradation in M146L cells was completely blocked by the Bac （P<0.05）. ConclusionsThis study clarifies the ameliorating effect of Met on the abnormal accumulation of Aβ₄₂ in M146L cells， and that the underlying mechanism is mediated by the increased expression of IDE in the Aβ degradation pathway， providing an experimental basis for the T2DM drug metformin as a potential therapeutic target for AD.

ObjectiveTo investigate the effect of the M2 microglia marker Arginase1 （Arg1） knockdown on cognitive function in APP/PS1 transgenic mouse model of Alzheimer's disease （AD）. MethodsArginase1 genetically engineered mice were used and divided into C57BL/6 control group （WT）， Arginase1 low expression group （Arg1^+/-）， Alzheimer's disease mouse model group （APP/PS1）， Arginase1， APP/PS1 transgenic mice Arginase1 low expression group （Arg1^+/-； APP/PS1）. We used open field test （OFT） to assess the autonomous activity and adaptive capacity of mice； morris water maze experiment （MWM） to evaluate learning and memory function of mice； thioflavine-S staining to observe the brain amyloid β-protein （Aβ） deposition in mice； immunofluorescence staining to detect the expression of microglia markers ionized calcium-binding adaptor molecule 1 （Iba1）， transmembrane protein 119 （Tmem119） and lysosomal protein （CD68）； Elisa to determine Aβ_1-40 and Aβ_1-42 expression in hippocampal and cortical tissues； and protein immunoblot （Western blot） to measure the expression of amyloid precursor protein （APP）， beta-site APP-cleaving enzyme （BACE）， enkephalinase （NEP）， and interleukin-1β （IL-1β）. ResultsCompared with APP/PS1 group， Arg1^+/-； APP/PS1 group showed significantly increased duration and frequency in central area （P<0.00 1）； significantly reduced escape latency （P<0.001）， significantly increased dwell time， path length in the target quadrant and times of crossing the platform （all P<0.05）； significant decrease of Aβ deposition in the hippocampus （P<0.000 1） and significant increased expression of CD68 by microglia in the hippocampal region （P=0.039 2， P=0.000 3）； decreased levels of Aβ_1-40， Aβ_1-42， APP， IL-1β and increased expression of NEP protein （P<0.000 1）. No significant difference in BACE protein expression （P=0.497 7） was found. ConclusionDown-regulation of Arg1 may promote microglia activation in the brain， up-regulate the level of Aβ-degrading enzyme NEP， reduce Aβ deposition and neuroinflammation in the brain， thus improve the spatial learning capacity of APP/PS1 mouse model of AD.

Talaromyces marneffei is the only dimorphic species in its genus and causes a fatal systemic mycosis named talaromycosis. Our previous study indicated that knockdown of AcuD gene (encodes isocitrate lyase of glyoxylate bypass) of T. marneffei by RNA interference approach attenuated the virulence of T. marneffei, while the virulence of the AcuD knockout strains was not studied. In this study, T. marneffei-zebrafish infection model was successfully established through hindbrain microinjection with different amounts of T. marneffei yeast cells. After co-incubated at 28°C, the increasing T. marneffei inoculum doses result in greater larval mortality; and hyphae generation might be one virulence factor involved in T. marneffei-zebrafish infection. Moreover, the results demonstrated that the virulence of the ΔAcuD was significantly attenuated in this Zebrafish infection model.
Gene Knockout Techniques ; Hyphae ; Isocitrate Lyase ; Microinjections ; Mortality ; Rhombencephalon ; RNA Interference ; Talaromyces ; Virulence ; Yeasts ; Zebrafish

Metastasis is a multistep process involving modification of morphology to suit migration, reduction of tumor cell adhesion to the extracellular matrix, increase of cell mobility, tumor cell resistance to anoikis, and other steps. MicroRNAs are well-suited to regulate tumor metastasis due to their capacity to repress numerous target genes in a coordinated manner, thereby enabling their intervention at multiple steps of the invasion-metastasis cascade. In this study, we identified a microRNA exemplifying these attributes, miR-124, whose expression was reduced in aggressive MDA-MB-231 and SK-3rd breast cancer cells. Down-regulation of miR-124 expression in highly aggressive breast cancer cells contributed in part to DNA hypermethylation around the promoters of the three genes encoding miR-124. Ectopic expression of miR-124 in MDA-MB-231 cells suppressed metastasis-related traits including formation of spindle-like morphology, migratory capacity, adhesion to fibronectin, and anoikis. These findings indicate that miR-124 suppresses multiple steps of metastasis by diverse mechanisms in breast cancer cells and suggest a potential application of miR-124 in breast cancer treatment.
Anoikis ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Cell Adhesion ; Cell Line, Tumor ; Cell Movement ; Connective Tissue Growth Factor ; metabolism ; DNA Methylation ; Down-Regulation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; genetics ; metabolism ; Neoplasm Metastasis ; rho GTP-Binding Proteins ; metabolism ; rho-Associated Kinases ; metabolism

OBJECTIVETo investigate the effects of lead exposure to rat placenta and pups during different gestation periods.

METHODSAll 108 Wistar rats (72 females, 36 males) were randomly divided into four groups. All rats were orally fed with 0.025% lead acetate during different gestation periods. Blood was obtained from the abdominal vena cava and the lead level in maternal blood was measured by means of atomic absorption spectrometry at the end of the pregnancy. The number of pups, their body weight, body length and tail length were measured. The effects of lead to rat placenta were observed by level of microscopy, optical microscopy and electronic microscopy.

RESULTSExperimental groups the blood lead level at the end of gestation were above 0.483 micromol/L. There were significant differences among, of pups, during different groups (P < 0.01). Among them the drinking lead group of whole distant was the lowest in placenta weight [(0.31 +/- 0.13) g] body weight of pups [(2.08 +/- 0.88) g] length and tail length of pups [(2.37 +/- 0.32) cm, (0.98 +/- 0.09) cm]. There were significantly differences between the experimental groups and controls. Maternal blood lead level was negatively related to placenta weight (r = 0.652, P < 0.01), and had no relation with the body weight of pups (r = -0.107, P = 0.46). In the experimental groups of lead poisoned rats, the placenta showed focus necrosis in the deciduas, and increased the trophoblastic giant cells and light staining cells in the trophospongium. Trophoblast in the labyrinth and trophospongium showed degeneration; fibrin deposition around the villi was increased. Microvilli around the trophoblast were shorter and less, mitochondrion was swollen and decreased in number, rough endoplasmic reticulum was distended and ribosomal number on membrane decreased.

CONCLUSIONLead exposure during different gestation periods should have a traumatic effect on the trophoblast, leading to interference of nutrition and oxygen exchange. Furthermore, the blood supply to the placenta and nutrition and oxygen exchange between mother and pups were also interfered, leading to reduction of placenta weight and retardation of development of pups.

Animals ; Environmental Exposure ; adverse effects ; Female ; Lead ; toxicity ; Male ; Organ Size ; drug effects ; Placenta ; drug effects ; Pregnancy ; Rats ; Rats, Wistar

Preimplantation genetic diagnosis is a very early form of prenatal diagnosis aimed at eliminating embryos carrying serious genetic diseases before implantation. The basic techniques currently used involve embryo biopsy, the polymerase chain reaction and fluorescence in situ hybridization. In the current review, a number of problems arising from the use of these technologies as well as the possible solutions and new developments are discussed.
Cytogenetic Analysis ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Pregnancy ; Preimplantation Diagnosis ; Primed In Situ Labeling