Mechanism of endometrial MUC2 in reproductive performance in mice through PI3K/AKT signaling pathway after lipopolysaccharide treatment.

The objective of this study was to investigate the effects of exposure to endotoxin on the reproductive performance of humans and animals in pregnancy and delivery period. Mucin is considered to play a critical role in protecting the tissue epithelium. At pregnancy period, the MUC2 expression of uterus in the High LPS group was significantly higher than that in the Control group. The glycosaminoglycans of gland cells were secreted into the uterine cavity to protect the uterus. Then, the MUC2 layer became thinner, and LPS entered the lamina propria of the uterus. The mRNA expression of tight junction proteins showed a marked drop, and morphological damage of the uterus occurred. Subsequently, the glycosaminoglycans of gland cells in the High LPS and Low LPS groups increased with the increasing LPS dose, and the damage to the endometrial epithelium was repaired in female mice at Day 5 postdelivery. A low dose of LPS activated the PI3K/AKT signaling pathways to increase the glycosaminoglycans particles, while a high dose of LPS inhibited the PI3K/AKT signaling pathway to decrease the glycosaminoglycans particles. Taken together, our results suggest that gland cells secreted glycosaminoglycans particles into the uterine cavity by exocytosis to increase the thickness of the mucus layer to protect the uterus and that this process was regulated by PI3K/AKT signaling pathways.

Fear Erasure Facilitated by Immature Inhibitory Neuron Transplantation.

Transplantation of embryonic γ-aminobutyric acid (GABA)ergic neurons has been shown to modify disease phenotypes in rodent models of neurologic and psychiatric disorders. However, whether transplanted interneurons modulate fear memory remains largely unclear. Here, we report that transplantation of embryonic interneurons into the amygdala does not alter host fear memory formation. Yet approximately 2 weeks after transplantation, but not earlier or later, extinction training produces a marked reduction in spontaneous recovery and renewal of fear response. Further analyses reveal that transplanted interneurons robustly form functional synapses with neurons of the host amygdala and exhibit similar developmental maturation in electrophysiological properties as native amygdala interneurons. Importantly, transplanted immature interneurons reduce the expression of perineuronal nets, promote long-term synaptic plasticity, and modulate both excitatory and inhibitory synaptic transmissions of the host circuits. Our findings demonstrate that transplanted immature interneurons modify amygdala circuitry and suggest a previously unknown strategy for the prevention of extinction-resistant pathological fear.

Gold catalyzed enantioselective intermolecular [3+2] dipolar cycloaddition of N-allenyl amides with nitrones.

A gold catalyzed enantioselective [3+2] dipolar cycloaddition of N-allenyl amides with nitrones was developed to give chiral 4-alkylidenyl isoxazolidine derivatives in high yields and excellent enantioselectivities by using BINOL derived chiral phosphoramidate Au(I) catalysts.

Azepine synthesis from alkyl azide and propargylic ester via gold catalysis.

An efficient new method was developed to synthesize multisubstituted 4,5-dihydro-1H-azepine derivatives through the gold-catalyzed reaction of two molecules of propargylic esters with one molecule of alkyl azide. It was proposed that vinyl gold carbenoid, in situ generated from propargylic ester through gold-catalyzed 1,2-rearrangement, was trapped by alkyl azide to give vinyl imine intermediate. These, in turn, could undergo a formal [4 + 3] cycloaddition with another molecule of vinyl gold carbenoid to afford the desired azepine product.

Beta-arrestin-1 protein represses adipogenesis and inflammatory responses through its interaction with peroxisome proliferator-activated receptor-gamma (PPARgamma).

One of the master regulators of adipogenesis and macrophage function is peroxisome proliferator-activated receptor-γ (PPARγ). Here, we report that a deficiency of ß-arrestin-1 expression affects PPARγ-mediated expression of lipid metabolic genes and inflammatory genes. Further mechanistic studies revealed that ß-arrestin-1 interacts with PPARγ. ß-Arrestin-1 suppressed the formation of a complex between PPARγ and 9-cis-retinoic acid receptor-α through its direct interaction with PPARγ. The interaction of ß-arrestin-1 with PPARγ repressed PPARγ/9-cis-retinoic acid receptor-α function but promoted PPARγ/nuclear receptor corepressor function in PPARγ-mediated adipogenesis and inflammatory gene expression. Consistent with these results, a deficiency of ß-arrestin-1 binding to PPARγ abolished its suppression of PPARγ-dependent adipogenesis and inflammatory responses. These results indicate that the regulation of PPARγ by ß-arrestin-1 is critical. Furthermore, in vivo expression of ß-arrestin-1 (but not the binding-deficient mutant) significantly repressed adipogenesis, macrophage infiltration, and diet-induced obesity and improved glucose tolerance and systemic insulin sensitivity. Therefore, our findings not only reveal a molecular mechanism for the modulation of obesity by ß-arrestin-1 but also suggest a potential tactical approach against obesity and its associated metabolic disorders.

Beta-arrestin-1 protein represses diet-induced obesity.

Diet-related obesity is a major metabolic disorder. Excessive fat mass is associated with type 2 diabetes, hepatic steatosis, and arteriosclerosis. Dysregulation of lipid metabolism and adipose tissue function contributes to diet-induced obesity. Here, we report that ß-arrestin-1 knock-out mice are susceptible to diet-induced obesity. Knock-out of the gene encoding ß-arrestin-1 caused increased fat mass accumulation and decreased whole-body insulin sensitivity in mice fed a high-fat diet. In ß-arrestin-1 knock-out mice, we observed disrupted food intake and energy expenditure and increased macrophage infiltration in white adipose tissue. At the molecular level, ß-arrestin-1 deficiency affected the expression of many lipid metabolic genes and inflammatory genes in adipose tissue. Consistently, transgenic overexpression of ß-arrestin-1 repressed diet-induced obesity and improved glucose tolerance and systemic insulin sensitivity. Thus, our findings reveal that ß-arrestin-1 plays a role in metabolism regulation.

(1SR,2RS,3SR,5SR,6RS)-6-[(Z)-1-Acet-oxy-2-phenyl-ethen-yl]-3-eth-oxy-2-phenyl-bicyclo-[3.1.0]hexan-1-yl acetate.

The mol-ecule of the title compound, C(26)H(28)O(5), is chiral with five stereogenic centres; however, the centrosymmetric triclinic group gives a racemic crystal. The fused ring system adopta boat conformation in which the cyclo-propane ring plane is roughly perpendicular to the styryl group plane, forming a dihedral angle of 74.78 (19)°. The dihedral angle between the two benzene rings is 77.24 (6)°.

[Effects of Huanglian Jiedu Decoction on blood lipid metabolism and its related gene expressions in rats with hyperlipidemia].

OBJECTIVE: To observe the effects of Huanglian Jiedu Decoction (HJD), a compound traditional Chinese herbal medicine, on lipid metabolism and its related gene expressions in rats with hyperlipidemia. METHODS: Fifty SD rats were randomly divided into normal control group, untreated group, Lipitor (atorvastatin) group, and low- and high-dose HJD groups. Except the normal control group, rats in the other groups were fed with high-fat diet to induce hyperlipidemia. Then the rats were administered with corresponding drugs for 8 weeks. After treatment, the serum levels of total cholesterol (TC), triacylglycerol (TAG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assayed. The activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in liver tissues were measured. Low-density lipoprotein receptor (LDLR) and peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA expressions in liver tissues were determined by reverse transcription-polymerase chain reaction. RESULTS: Compared with the normal control group, the levels of serum TC, TAG and LDL-C in the untreated group were increased and the level of serum HDL-C was reduced. The activities of LPL and HL and expressions of LDLR and PPARgamma mRNAs in the untreated group were lower than those in the normal control group. After treatment, high-dose HJD significantly improved hyperlipemia by decreasing TC, TAG and LDL-C and increasing HDL-C. The activities of LPL and HL and expression levels of LDLR and PPARgamma mRNAs in liver tissues were also markedly enhanced in the high-dose HJD group as compared with those in the untreated group. CONCLUSION: HJD can activate the activity of lipid metabolism enzyme, and enhance the expressions of LDLR and PPARgamma mRNAs to modulate the lipid metabolic disorders in rats with hyperlipidemia.

Neuroprotection of ginsenoside Re in cerebral ischemia-reperfusion injury in rats.

In the present study, we have investigated the neuroprotective potential of ginsenoside Re (Re) in the middle cerebral artery occlusion model in Sprague-Dawley rats. Adult male Sprague-Dawley rats were treated with Re (5, 10 or 20 mg kg(- 1), P.O. for 7 days, once a day) prior to occlusion. There was a significant increase in the neurological symptoms in ischemic animals as compared with the sham group animals. These effects were attenuated by 10 and 20 mg kg(- 1) Re, P.O. There was a significant increase in the level of malondialdehyde (MDA) in ischemic animals indicating oxidative stress. An elevated level of MDA in ischemic animals was reduced by 10 and 20 mg kg(- 1) Re, P.O., respectively. It was observed that Re significantly decreased mitochondrial swelling, thereby preventing the reduction of H(+)-ATPase activity. This study demonstrates the neuroprotective potential of Re in cerebral ischemia-reperfusion injury in rats.

[Proceedings on the toxicity of a new hydroxylammonium nitrate (HAN)-based liquid propellant].

Hydroxylammonium nitrate (HAN) is the main active toxic component of the new HAN-based liquid propellant. It is a moderately toxic and caustic substance to animals, and can be administrated through dermal, oral or respiratory route. HAN causes severe damage to skins, eyes, and red blood cells of the hematologic system. Significant signs of HAN poisoning include hemolytic anemia, methemoglobinemia, splenomegaly, erythrocyte destruction and Heinz body formation. This review summarize the toxicity of hydroxylammonium nitrate, and discuss the primary protection methods.