Glycerol Monolaurate Alleviates Oxidative Stress and Intestinal Flora Imbalance Caused by Salinity Changes for Juvenile Grouper.

Groupers with an initial body weight of 9.10 ± 0.03 g were selected to investigate whether dietary addition of 0 (G0) and 1800 mg/kg glycerol monolaurate (GML, G1800) could alleviate the oxidative stress response and intestinal flora imbalance after 0, 6, 12, and 24 h of salinity change in grouper. Experimental results show that the dietary addition of GML significantly reduced the liver MDA content and increased the SOD activity of grouper. The gene expression of CAT and SOD increased and then decreased with time after adding 1800 mg/kg GML, and the highest values were significantly higher than those of the control group. Salinity change had a slight effect on the top four intestinal flora composition of grouper at 0, 12, and 24 h, with changes occurring only at 6 h when Cyanobacteria replaced Actinobacteria. The addition of dietary GML slowed down the intestinal flora disorder, inhibited the colonization of harmful bacterium Vibrio, and promoted the abundance of beneficial bacterium Bacillus. In conclusion, dietary GML significantly reduced the oxidative damage caused by sudden changes in salinity, improved the antioxidant capacity, and alleviated the intestinal flora imbalance in juvenile grouper.

Effects of Plant-Derived Glycerol Monolaurate (GML) Additive on the Antioxidant Capacity, Anti-Inflammatory Ability, Muscle Nutritional Value, and Intestinal Flora of Hybrid Grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂).

In a context where the search for plant-derived additives is a hot topic, glycerol monolaurate (GML) was chosen as our subject to study its effect on grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂). Seven gradient levels of GML (0, 600, 1200, 1800, 2400, 3000, and 3600 mg/kg) were used for the experiment. Based on our experiments, 1800 mg/kg GML significantly increased the final body weight (FBW) and weight gain rate (WGR). GML increased the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased malondialdehyde (MDA). Adding 1800 mg/kg GML also significantly increased the levels of lauric acid (C12:0) (LA), n-3 polyunsaturated fatty acids (PFA), and the n-6 PFA-to-n-3/n-6 ratio, while significantly decreasing the levels of saturated fatty acids (SFA). Dietary supplementation with GML significantly inhibited the expression of pro-inflammatory factors and reduced the occurrence of inflammation. GML improved intestinal flora and the abundance of beneficial bacteria (Bacillus, Psychrobacter, Acinetobacter, Acinetobacter, Stenotrophomonas, and Glutamicibacter). It provides a theoretical basis for the application of GML in aquafeed and greatly enhances the possibility of using GML in aquafeed. Based on the above experimental results, the optimum level of GML in grouper feed is 1800 mg/kg.

Glycerol monolaurate (GML), a medium-chain fatty acid derivative, ameliorate growth performance, immune function, disease resistance and intestinal microbiota in juvenile hybrid grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂).

In order to evaluate the effects of glycerol monolaurate (GML) on the growth performance, immunology function, disease resistance and intestinal microbiota for hybrid groupers. Seven levels of GML (0, 600, 1200, 1800, 2400, 3000 and 3600 mg/kg) were added to diets and were noted as the G1 (control group), G2, G3, G4, G5, G6 and G7, respectively. Each experimental diet was fed to triplicate groups of 30 juvenile groupers for 8 weeks. The FBW, WGR and SGR were significantly higher and FCR was significantly lower in the G4 group compared to the G1 group (P < 0.05). Serum immune enzyme activities (ACP, AKP and LZM) rose and then fell and had the highest values in the G4 group (P < 0.05). The expression of TNF-α and IL6 in head kidney was significantly inhibited (P < 0.05), while the expression of TLR22 was increased (P < 0.05). After the Vibrio parahaemolyticus challenge test, ACP and AKP activities were increased in the G4 and G5 groups, while mortality was lower than in the G1 group (P < 0.05). GML significantly modulated the abundance of intestinal microbiota, with the G4 and G5 groups increasing the relative abundance of the Firmicutes and Bacillus, respectively (P < 0.05). The alpha diversity of the G5 group (Sob, Chao1 and ACE) was significantly higher than that of the G1 group (P < 0.05). In summary, the optimal level of GML was 1700 mg/kg according to the regression equation model fitted by the WGR index.

Dihydroartemisinin regulates apoptosis, migration, and invasion of ovarian cancer cells via mediating RECK.

BACKGROUND: Dihydroartemisinin (DHA) possesses an inhibitory effect on ovarian cancer and promotes reversion-inducing cysteine-rich protein with Kazal motifs (RECK) expression in glioma cells. This study explored the role of DHA and RECK on ovarian cancer. METHODS: The RECK level in ovarian cancer was analyzed under GEPIA 2 database and proved by RT-qPCR. After being treated with DHA or infected with siRECK lentivirus, the viability, apoptosis, migration, and invasion of ovarian cancer cells were evaluated by CCK-8, flow cytometry, wound healing, and transwell assays. Also, the expressions of factors related to apoptosis and epithelial-mesenchymal transition were measured by Western blot or RT-qPCR. RESULTS: DHA-treatment weakened the viability, migration, invasion, and enhanced apoptosis of ovarian cancer cells. DHA also down-regulated the levels of Bcl-2, N-cadherin, and Vimentin, and up-regulated the levels of Bax, C-caspase-3 and E-cadherin in ovarian cancer cells. RECK was lowly expressed in both ovarian cancer tissues and cells. siRECK not only had an effect opposite to DHA on the viability, apoptosis, migration, invasion, and related-factors of ovarian cancer cells but also offset the effect of DHA on ovarian cancer cells. CONCLUSION: DHA regulated apoptosis, migration, and invasion of ovarian cancer cells via mediating RECK.

MEHP promotes the proliferation of cervical cancer via GPER mediated activation of Akt.

Cervical cancer is the fourth leading cause of cancer death in females worldwide and the second leading cause of mortality among women. Estrogenic signals can regulate the progression of cervical cancer, however, little is known about the mono-2-ethyhexyl phthalate (MEHP), an environmental xenoestrogen, on the development of cervical cancers. Our present data showed that nanomolar concentrations of MEHP can trigger the proliferation, while not invasion, of cervical cancer HeLa and SiHa cells, which was confirmed by the results that MEHP can also increase the expression of proliferating cell nuclear antigen (PCNA). MEHP treatment can increase the phosphorylation and nuclear localization of Akt, while had no effect on the activation of ERK1/2 or p65. Targeted inhibition of Akt via its specific siRNA or inhibitor can reverse MEHP induced cell proliferation. In addition, the inhibitor of G protein coupled estrogen receptor (GPER), while not estrogen receptor α (ERα), can abolish MEHP induced phosphorylation of Akt and cell proliferation, suggesting that GPER is involved in MEHP induced activation of Akt. Collectively, our data showed that MEHP can trigger the progression of cervical cancer via activation of GPER/Akt. It suggested that MEHP exposure is also an important risk factor for development and progression of cervical cancers.

5-tert-Butyl-2-(4'-[18F]fluoropropynylphenyl)-1,3-dithiane oxides: potential new GABA A receptor radioligands.

As potential new ligands targeting the binding site of gamma-aminobutyric acid (GABA) receptor ionophore, trans-5-tert-butyl-2-(4'-fluoropropynylphenyl)-2-methyl-1,1-dioxo-1,3-dithiane (1) and cis/trans-5-tert-butyl-2-(4'-fluoropropynylphenyl)-2-methyl-1,1,3,3-tetroxo-1,3-dithiane (2) were selected for radiolabeling and initial evaluation as in vivo imaging agents for positron emission tomography (PET). Both compounds exhibited identical high in vitro binding affinities (K(i)=6.5 nM). Appropriate tosylate-substituted ethynyl precursors were prepared by multistep syntheses involving stepwise sulfur oxidation and chromatographic isolation of desired trans isomers. Radiolabeling was accomplished in one step using nucleophilic [(18)F]fluorination. In vivo biodistribution studies with trans-[(18)F]1 and trans-[(18)F]2 showed significant initial uptake into mouse brain and gradual washout, with heterogeneous regional brain distributions and higher retention in the cerebral cortex and cerebellum and lower retention in the striatum and pons-medulla. These regional distributions of the new radioligands correlated with in vitro and ex vivo measures of standard radioligands binding to the ionophore- and benzodiazepine-binding sites of GABA(A) receptor in rodent brain. A comparison of these results with previously prepared radiotracers for other neurochemical targets, including successes and failures as in vivo radioligands, suggests that higher-affinity compounds with increased retention in target brain tissues will likely be needed before a successful radiopharmaceutical for human PET imaging can be identified.

Site-specific labeling of annexin V with F-18 for apoptosis imaging.

Annexin V is useful in detecting apoptotic cells by binding to phosphatidylserine (PS) that is exposed on the outer surface of the cell membrane during apoptosis. In this study, we examined the labeling of annexin V-128, a mutated form of annexin V that has a single cysteine residue at the NH 2 terminus, with the thiol-selective reagent (18)F-labeling agent N-[4-[(4-[(18)F]fluorobenzylidene)aminooxy]butyl]maleimide ([(18)F]FBABM). We also examined the cell binding affinity of the (18)F-labeled annexin V-128 ([(18)F]FAN-128). [(18)F]FBABM was synthesized in two-step, one-pot method modified from literature procedure. (Toyokuni et al., Bioconjugate Chem. 2003, 14, 1253-1259). The average yield of [(18)F]FBABM was 23 +/- 4% (n = 4, decay-corrected) and the specific activity was approximately 6000 Ci/mmol. The total synthesis time was approximately 92 min. The critical improvement of this study was identifying and then developing a purification method to remove an impurity N-[4-[(4-dimethylaminobenzylidene)aminooxy]butyl]maleimide 4, whose presence dramatically decreased the yield of protein labeling. Conjugation of [(18)F]FBABM with the thiol-containing annexin V-128 gave [(18)F]FAN-128 in 37 +/- 9% yield (n = 4, decay corrected). Erythrocyte binding assay of [(18)F]FAN-128 showed that this modification of annexin V-128 did not compromise its membrane binding affinity. Thus, an in vivo investigation of [ (18)F]FAN-128 as an apoptosis imaging agent is warranted.

Resorcinarenes as templates: a general strategy for the synthesis of large macrocycles.

The concept that resorcinarenes can be used as templates for the synthesis of large macrocycles is introduced. By way of example, previously inaccessible, aromatic crown ethers compounds are synthesized.