Borylative Cyclization of 1,6-Allenynes Driven by BCl3.

A metal-free intramolecular borylative cyclization of 1,6-allenynes driven by BCl3 was developed. This method provides a general and practical strategy to construct valuable pyrrolidines containing all-carbon quaternary centers or 3,5-dihydroazepine derivatives depending on the substituents of the allene, with conjugative and sterically hindered phenyl groups favoring the latter.

Fabrication of Microspheres by Nano-TS-1 Crystals via a Spray-Forming Process: From Screening to Scale-up.

The spray-forming process of the nano-titanium silicalite (TS-1) zeolite was investigated and optimized in the lab in order to obtain materials with microsphere morphology and superior catalytic activity in cyclohexanone ammoximation on the industrial scale. The effects of spray-forming parameters, such as the state of the TS-1 raw material, load ratio, solid content, binder content, and calcination temperature, on the physicochemical and catalytic properties of TS-1 microspheres were investigated in detail. It was interesting to find that the shape of the spray-forming sample formed by wet powders was more intact than the sample formed by dried powders. Furthermore, the spray-forming process was successfully scaled up to a large spray device (LGZ-1000) according to the similarity principle of load ratio, and the shape of the TS-1 microspheres was as perfect as the spray-forming samples in the lab. The similarity principle of the load ratio for the spray-forming of titanium silicate was established and verified for the first time. The spray-forming TS-1 microspheres produced in the industry were used in cyclohexanone ammoximation, and ketone conversion and oxime selectivity were as high as 99.9 and 99.4%, respectively.

Resistin Induces Hypertension and Insulin Resistance in Mice via a TLR4-Dependent Pathway.

Resistin, an adipokine involved in insulin resistance (IR) and diabetes, has recently been reported to play a role in cardiovascular events. However, its effect on blood pressure (BP) and the underlying mechanisms remain unclear. In the present study, we showed that resistin induces hypertension and IR in wild type (WT) mice, but not in tlr4(-/-) mice. Resistin upregulated angiotensinogen (Agt) expression in WT mice, whereas it had no effect on tlr4(-/-) mice, or in mice treated with the angiotensin-converting enzyme inhibitor perindopril. Real-time PCR and chromatin immunoprecipitation further confirmed that resistin activates the renin-angiotensin system (RAS) via the TLR4/P65/Agt pathway. This finding suggested an essential role of resistin in linking IR and hypertension, which may offer a novel target in clinic on the study of the association between diabetes and hypertension.

[Intervention effect and mechanism of compound Ginkgo biloba preparations on nonalcoholic fatty liver].

OBJECTIVE: To investigate the intervention effect and mechanism of compound Ginkgo biloba (CGB) preparations on nonalcoholic fatty liver disease (NAFLD). METHOD: The C57BL/6 mouse NAFLD model was induced with high fat diets. Since the 2nd week after modeling, the mice were orally administered with 600 and 200 mg x kg(-1) x d(-1) CGB for eight weeks. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), cholesterol (CHOL) and LPS in serum, as well as pathological changes and expression of tumor necrosis factor-alpha (TNF-alpha) in hepatic tissues were observed. Changes in intestinal tight junction proteins ZO-1, Occludin, Claudin-1 in intestinal tissues were determined under microscopy. RESULT: Compared with the normal group, the model group showed obvious fatty degeneration in rat livers, with notable increase in TNF-alpha expression (P < 0.01), significant increases in ALT, AST, TG, CHOL and LPS in serum (P < 0.01, P < 0.05), injury in intestinal tight junction proteins, and remarkable declines in ZO-1, Occludin and Claudin-1 (P < 0.01). Compared with the model group, CGB high and low dose groups showed obvious relieves in fatty degeneration in rat livers and injury in intestinal tight junction proteins, significant reductions in TNF-alpha expression (P < 0.01, P < 0.05) and AST, TG, CHOL and LPS in serum (P < 0.01, P < 0.05) and remarkable increases in ZO-1 and Occludin expressions (P < 0.05). CONCLUSION: CGB can protect intestinal tight junction proteins, reduce intestinal leakage, relieve fatty degeneration and inflammations in livers and prevent NAFLD occurrence and development.

Herbal SGR Formula Prevents Acute Ethanol-Induced Liver Steatosis via Inhibition of Lipogenesis and Enhancement Fatty Acid Oxidation in Mice.

Our previous study indicated that herbal SGR formula partially attenuates ethanol-induced fatty liver, but the underlying mechanisms remain unclear. In the present study, mice were pretreated with SGR (100 and 200 mg/kg/d bw) for 30 d before being exposed to ethanol (4.8 g/kg bw). The biochemical indices and histopathological changes were examined to evaluate the protective effects and to explore potential mechanisms by investigating the adiponectin, tumor necrosis factor-α (TNF-α), peroxisome proliferators-activated receptor-α (PPAR-α), sterol regulatory element binding protein-1c (SREBP-1c), adenosine monophosphate-activated protein kinase (AMPK), and so forth. Results showed that SGR pretreatment markedly inhibited acute ethanol-induced liver steatosis, significantly reduced serum and hepatic triglyceride (TG) level, and improved classic histopathological changes. SGR suppressed the protein expression of hepatic SREBP-1c and TNF-α and increased adiponectin, PPAR-α, and AMPK phosphorylation in the liver. Meanwhile, acute toxicity tests showed that no death or toxic side effects within 14 days were observed upon oral administration of the extracts at a dose of 16 g/kg body wt. These results demonstrate that SGR could protect against acute alcohol-induced liver steatosis without any toxic side effects. Therefore, our studies provide novel molecular insights into the hepatoprotective effect of SGR formula, which may be exploited as a therapeutic agent for ethanol-induced hepatosteatosis.

Effects of compound Ginkgo biloba on intestinal permeability in rats with alcohol-induced liver injury.

This study aimed to investigate the effects of Compound Ginkgo biloba (CGB) on alterations in intestinal permeability and inflammation caused by endotoxin in chronic alcohol-induced liver injury. CGB was prepared by Ginkgo biloba extract and Rosa roxburghii in a 1 : 1 proportion. Rats were divided into four groups: control, ethanol, high-dosage CGB (0.6 g kg(-1) d(-1)) and low-dosage CGB (0.2 g kg(-1) d(-1)) group. Rats in the control group ingested a Lieber-DeCarli control liquid diet, while rats in the ethanol and CGB-treated groups ingested a Lieber-DeCarli alcohol liquid diet for eight weeks. CGB was orally administered from the beginning of the third week until the end of the experiment. CGB was observed to significantly reduce the activities of serum ALT, AST, diamine oxidase (DAO) as well as levels of serum TG, D-lactic acid and plasma endotoxin in rats fed with Lieber-DeCarli ethanol liquid. Further, the hepatic steatosis was improved and the damage to intestinal tight junctions was also relieved effectively after CGB administration. Moreover, CGB significantly downregulated the expressions of TNF-α, lipopolysaccharide binding protein (LBP), CD14 and TLR4 in the liver and upregulated the expressions of tight junction proteins including ZO-1, occludin and claudin-1. In summary, this study demonstrated that CGB alleviated alcohol-induced liver injury and hepatic lipopolysaccharide signaling as well as gut barrier dysfunction through restoring tight junctions.

Resistin reduces mitochondria and induces hepatic steatosis in mice by the protein kinase C/protein kinase G/p65/PPAR gamma coactivator 1 alpha pathway.

UNLABELLED: Obesity is associated with many severe chronic diseases and deciphering its development and molecular mechanisms is necessary for promoting treatment. Previous studies have revealed that mitochondrial content is down-regulated in obesity, diabetes, and nonalcoholic fatty liver disease (NAFLD) and proposed that NAFLD and diabetes are mitochondrial diseases. However, the exact mechanisms underlying these processes remain unclear. In this study, we discovered that resistin down-regulated the content and activities of mitochondria, enhanced hepatic steatosis, and induced insulin resistance (IR) in mice. The time course indicated that the change in mitochondrial content was before the change in fat accumulation and development of insulin resistance. When the mitochondrial content was maintained, resistin did not stimulate hepatic fat accumulation. The present mutation study found that the residue Thr464 of the p65 subunit of nuclear factor kappa B was essential for regulating mitochondria. A proximity ligation assay revealed that resistin inactivated peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α) and diminished the mitochondrial content by promoting the interaction of p65 and PGC-1α. Signaling-transduction analysis demonstrated that resistin down-regulated mitochondria by a novel protein kinase C/protein kinase G/p65/PGC-1α-signaling pathway. CONCLUSION: Resistin induces hepatic steatosis through diminishing mitochondrial content. This reveals a novel pathway for mitochondrial regulation, and suggests that the maintenance of normal mitochondrial content could be a new strategy for treatment of obesity-associated diseases.

C/EBPα promotes transcription of the porcine perilipin5 gene.

PERILIPIN5 (PLIN5) is a newly discovered member of the PAT family that regulates cellular neutral lipid stores and use. It is expressed in highly oxidative tissues and is induced during fasting. Like other members of the PAT family, PERILIPIN5 expression is also regulated by PPARα. However, its induction by fasting is PPARα-independent. So far, the transcriptional regulation of perilipin5, apart from PPARα, remains unclear. In the present study, we investigated the transcriptional regulation of pig perilipin5 and revealed that its promoter activity was up-regulated by C/EBPα. By constructing various progressive deletions and mutants, the binding region of C/EBPα was discovered. Furthermore, the binding site was identified by chromatin immunoprecipitation and luciferase reporter assays. Moreover, over-expression of C/EBPα induced endogenous perilipin5 expression in the pig kidney cell line IBRS2. Data from arrays showed that C/EBPα expression was induced during fasting. Taken together, our results indicate that C/EBPα is an essential regulatory factor for perilipin5 transcription and suggest that fasting stimulates perilipin5 transcription through influencing C/EBPα expression.

A novel process for recovery and refining of L-lactic acid from fermentation broth.

This paper introduces a novel process for recovery and refining of L-lactic acid from a fermentation broth. The use of a solvent extraction step, in the novel approach, has significant impacts on the following centrifugal short-path distillation conditions (operating pressure, evaporator temperature and feed flow rate). As the conditions were varied, the l-lactic acid purity and yield in the distillate were monitored. For the purpose of comparison, a series of experiments were also carried out using the existing purification process. The results showed that both of the two processes can obtain l-lactic acid with a high purity around 91.3%, while the yield obtained using the novel process reached 61.73%, which was about 20.43% higher than that using the existing process. Additionally, multiple-pass distillation observed special attention by improving the yield up to 74.63%.