Inhibitory effect of lignin by-products of pulping on yeast growth

The antimicrobial properties of lignin by-products obtained by organic solvent, neutral sulfite semichemical and kraft pulping were shown in a series of yeasts. Lignin can act as an inhibitor of growth ofSporobolomyces roseus, Candida tropicalis, Trichosporon cutaneum andCandida albicans. Oxidation of all lignin samples tested depresses their inhibitory effects.     

Antimicrobial treatment of grapes using sodium hypochlorite in winemaking and its effects on the chemical and sensory characteristics of wines

This study was performed to examine the use of NaOCl as an alternative antimicrobial compound in winemaking because of the potential health problems that may arise as a result of the use of SO2. For this, the blank (non-treated), control (SO2-added), and sample (NaOCl-treated) wines were made, and microbial and chemical changes including sensory characteristics were analyzed during the fermentation periods. Treatment of grapes with NaOCl decreased the initial contaminating microbial population in grape must, resulting in higher growth of yeast and lactic acid bacteria. After 200 days of fermentation, the chemical analysis of sample wine revealed that it had higher ethanol content, redness (a*), and concentrations of fruity ester compounds and lower total acidity than the control. In the sensory analyses, the sample wine obtained a higher overall acceptability score (5.70) than the control (4.26). This result reveals that NaOCl can be used as an alternative to SO2 in winemaking for inhibiting the growth of contaminating microorganisms.     

Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors

LAF389 is a synthetic analogue of bengamides, a class of marine natural products that produce inhibitory effects on tumor growth in vitro and in vivo. A proteomics-based approach has been used to identify signaling pathways affected by bengamides. LAF389 treatment of cells resulted in altered mobility of a subset of proteins on two-dimensional gel electrophoresis. Detailed analysis of one of the proteins, 14-3-3gamma, showed that bengamide treatment resulted in retention of the amino-terminal methionine, suggesting that bengamides directly or indirectly inhibited methionine aminopeptidases (MetAps). Both known MetAps are inhibited by LAF389. Short interfering RNA suppression of MetAp2 also altered amino-terminal processing of 14-3-3gamma. A high resolution structure of human MetAp2 co-crystallized with a bengamide shows that the compound binds in a manner that mimics peptide substrates. Additionally, the structure reveals that three key hydroxyl groups on the inhibitor coordinate the di-cobalt center in the enzyme active site.     

Low Hemoglobin Level Is Associated with the Development of Delirium after Hepatectomy for Hepatocellular Carcinoma Patients

Background

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and liver resection is the only potential curative treatment option for those patients. Postoperative complications specific to elderly surgical patients such as delirium will be increasingly relevant in the coming decades. Herein, we aimed to investigate the risk factors for postoperative delirium in patients who have received hepatectomy for HCC.

Methods

This is a single medical center observational study and the study subjects comprised 401 individuals who underwent liver resection for hepatocellular carcinoma during January 2009 to October 2013. Multivariate analysis was used to examine whether preoperative, intra-operative, or postoperative variables were associated with the development of delirium.

Results

Of the 401 patients who underwent hepatectomy, 34 developed postoperative delirium (8.4%). In the majority of those patients, symptoms and signs of the syndrome occurred on postoperative day 2 and the mean duration of symptoms was 3.61 ± 3.71 days. Multivariate analysis revealed that advanced age (>71 years) [odds ratio (OR) = 1.133, 95% confidence interval (CI): 1.071–1.200, p<0.001], prolonged operative time (>190 minutes) (OR = 1.009, 95% CI: 1.000–1.017, p = 0.038), a decreased postoperative hemoglobin level (< 10.16 g/dL) (OR = 0.777, 95% CI: 0.613–0.983, p = 0.036), and history of hypnotic drug use (OR = 3.074, 95% CI: 1.045–9.039, p = 0.041) were independent risk factors for the development of postoperative delirium after hepatectomy.

Conclusions

Although the mechanism of postoperative delirium is not well understood, numbers of studies have shown that patients with postoperative delirium tend to have prolonged hospital stay, worse postoperative outcome and an increased risk of short- and long-term mortality. In this study, we found that advanced age, prolonged operative time, postoperative low hemoglobin level and history of hypnotic drug use are independent risk factors for postoperative delirium.     

Crystal structure of the serine protease domain of prophenoloxidase activating factor-I

A family of serine proteases (SPs) mediates the proteolytic cascades of embryonic development and immune response in invertebrates. These proteases, called easter-type SPs, consist of clip and chymotrypsin-like SP domains. The SP domain of easter-type proteases differs from those of typical SPs in its primary structure. Herein, we report the first crystal structure of the SP domain of easter-type proteases, presented as that of prophenoloxidase activating factor (PPAF)-I in zymogen form. This structure reveals several important structural features including a bound calcium ion, an additional loop with a unique disulfide linkage, a canyon-like deep active site, and an exposed activation loop. We subsequently show the role of the bound calcium and the proteolytic susceptibility of the activation loop, which occurs in a clip domain-independent manner. Based on biochemical study in the presence of heparin, we suggest that PPAF-III, highly homologous to PPAF-I, contains a surface patch that is responsible for enhancing the catalytic activity through interaction with a nonsubstrate region of a target protein. These results provide insights into an activation mechanism of easter-type proteases in proteolytic cascades, in comparison with the well studied blood coagulation enzymes in mammals.     

Molecular characterization of flavonol synthase from poplar and its application to the synthesis of 3-<Emphasis Type="Italic">O</Emphasis>-methylkaempferol

Biosynthesis of flavonoid derivatives requires enzyme(s) having high reactivity as well as regioselectivity. We have synthesized 3-O-kaempferol from naringenin using two enzymes. The first reaction, in which naringenin is converted to kaempferol, is mediated by flavonol synthase (FLS). An FLS (PFLS) with strong catalytic activity was cloned and characterized from the genome sequence of the poplar (Populus deltoides). PFLS consists of a 1,008 bp ORF encoding a 38 kDa protein. PFLS was expressed in Escherichia coli with a glutathione-S-transferase (GST) tagging. The purified recombinant PFLS was characterized. Catalytically, it was more efficient than the previously characterized FLSs. A mixture of two E. coli transformants harboring either PFLS or ROMT9 (a kaempferol 3-O-methyltransferase) converted naringenin into 3-O-methylkaempferol.     

Design, synthesis and evaluation of novel hydroxyamides as orally available anticonvulsants

Themisone, also known as Atrolactamide, was found, in the 1950s, to be a very potent anticonvulsant. It was hypothesized that the -CF(3) substitution would maintain the anticonvulsant activity. Anticonvulsant testing of our novel compounds by the National Institute of Health's Anticonvulsant Screening Project of the Antiepileptic Drug Discovery Program identified analogue 1, 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide, to have potent anticonvulsant activity (MES ED(50) of 9.9 mg/kg, ScMET ED(50) of 34 mg/kg and TD(50) of 100 mg/kg). Therefore, a diverse range of analogues were synthesized utilizing multiple synthetic pathways to explore the structure-activity relationship. Patch clamp electrophysiology experiments demonstrate that compound 1 is an effective T-type calcium channel blocker. Altogether, these results suggest these compounds as a class of orally available anticonvulsants.     

TRIM46 activates AKT/HK2 signaling by modifying PHLPP2 ubiquitylation to promote glycolysis and chemoresistance of lung cancer cells

The incidence of lung cancer is increasing worldwide. Although great progress in lung cancer treatment has been made, the clinical outcome is still unsatisfactory. Tripartite motif (TRIM)-containing proteins has been shown to be closely related to tumor progression. However, the function of TRIM46 in lung cancer is largely unknown. Here, TRIM46 amplification was found in lung adenocarcinoma (LUAD) tissues and TRIM46 amplification was significantly associated with a poor survival rate. Overexpression of wild type TRIM46 increased the proliferation of LUAD cells and glycolysis, promoted xenografts growth, and enhanced cisplatin (DDP) resistance of LUAD cells via increased ubiquitination of pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) and upregulation of p-AKT. In contrast, overexpression of RING-mutant TRIM46 did not show any effects, suggesting the function of TRIM46 was dependent on the E3 ligase activity. Furthermore, we found that TRIM46 promoted LUAD cell proliferation and DDP resistance by enhancing glycolysis. PHLPP2 overexpression reversed the effects of TRIM46 overexpression. Amplification of TRIM46 also promoted LUAD growth and enhanced its DDP resistance in a patient-derived xenograft (PDX) model. In conclusion, our data highlight the importance of TRIM46/PHLPP2/AKT signaling in lung cancer and provide new insights into therapeutic strategies for lung cancer.Subject terms: Cancer, Biomarkers