Anti-aging derivatives of cycloastragenol produced by biotransformation.

In this study, the microbial transformation of cycloastragenol (CA) by the fungi Mucor subtilissimus AS 3.2456 and Aspergillus oryzae AS 3.407 yielded 19 metabolites. Their structures were established based on extensive NMR and HR-MS data analyses, and six of them are new compounds. The two fungal strains exhibited distinct biocatalytic features. M. subtilissimus could catalyse hydroxylation and carbonylation reactions meanwhile the fragile 9,19-cyclopropane ring remained intact. A. oryzae preferred to catalyse hydroxylation, acetylation and ring expansion reactions. These highly specific reactions are difficult to achieve by chemical synthesis, particularly under mild conditions. Furthermore, we found that most of the metabolites could significantly extend the lifespan of Caenorhabditis elegans at 50 µM. These biotransformed derivatives of CA could be potential anti-aging agents.

Biotransformation of betulin by Mucor subtilissimus to discover anti-inflammatory derivatives.

Biotransformation of lupane-type triterpenoid betulin was carried out with Mucor subtilissimus CGMCC 3.2456. Yielded nine previously undescribed hydroxylated compounds. M. subtilissimus biotransformation provided C-7, C-11, C-15 and C-24 hydroxylated compounds along with C-7 oxidized and C-28 acetylated derivatives. The structures of the metabolites were established based on extensive NMR and HR-ESI-MS data analyses. Furthermore, we found that most of the metabolites exhibited pronounced inhibitory activities on lipopolysaccharides-induced NO production in RAW264.7 cells.

Biotransformation of 20(R)-panaxatriol by the fungus Aspergillus flavus Link AS 3.3950.

Microbial transformation of 20(R)-panaxatriol by the fungus Aspergillus flavus Link AS 3.3950 was performed. Four new (1-4), along with two previously reported metabolites (5 and 6), were obtained. Their chemical structures were elucidated on the basis of extensive spectroscopic analyses. Furthermore, the inhibitory effects of those compounds on K562/ADR, Du-145, Hela, MCF-7 and HepG2 cell lines were evaluated by MTT assay. Among them, compound 15ß-hydroxy-20(R)-panaxatriol (4) exhibited selective inhibitory effects on human leukaemic progenitor cells K562/ADR through arresting cell cycle, which was associated with obvious decrease of cyclin B1, cyclin D1 and cyclin-dependent kinase (CDK) 1/2/4/6 protein expression.

Anti-Inflammatory 18ß-Glycyrrhetinin Acid Derivatives Produced by Biocatalysis.

In this study, the biocatalysis of 18ß-glycyrrhetinic acid by two strains of filamentous fungi, namely Rhizopus arrhizus AS 3.2893 and Circinella muscae AS 3.2695, was investigated. Scaled-up biotransformation reactions yielded 14 metabolites. Their structures were established based on extensive nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data analyses, and seven of them are new compounds. The two fungal strains exhibited distinct biocatalytic features. R. arrhizus could catalyze hydroxylation and carbonylation reactions, whereas C. muscae preferred to catalyze hydroxylation and glycosidation reactions. These highly specific reactions are difficult to achieve by chemical synthesis, particularly under mild conditions. Furthermore, we found that most of the metabolites exhibited pronounced inhibitory activities on lipopolysaccharides-induced nitric oxide production in RAW264.7 cells. These biotransformed derivatives of 18ß-glycyrrhetinic acid could be potential anti-inflammatory agents.

Microbial transformation of the anti-aging agent cycloastragenol by Mucor racemosus.

The microbial transformation of cycloastragenol (CA) by Mucor racemosus AS 3.20 was investigated. Seven isolated products were identified as (20R,24S)-3ß,6α,16ß,25- tetrahydroxy-20,24-epoxy-9,10-seco-cycloartan-9(11),10(19)-diene (1), (20R,24S)- 3ß,6α,16ß,25-tetrahydroxy-20,24-epoxy-9,10-seco-cycloartan-1(10),9(11)-diene (2), (20R,24S)-3ß,16ß,25-trihydroxy-6α,19α;20,24-diepoxy-9,10-seco-cycloartan-9(11)-ene (3), (20R,24S)-6α,16ß,25-trihydroxy-3ß,10ß;20,24-diepoxy-9,10-seco- cycloartan-11-one (4), (20R,24S)-16ß,25-dihydroxy-6α-methoxy-3ß,10ß;20,24- diepoxy-9,10-seco-cycloartan-7(8),9(11)-diene (5), (20R,24S)-6α,16ß,25-trihydroxy-3ß,10ß;20,24-diepoxy-9,10-seco-cycloartan-9(11)-ene (6), and (20R,24S)-3ß,6α,16ß,25-tetrahydroxy-19-acetoxy-ranunculan-9(10)-ene (7) by spectroscopic analysis. Among them, compounds 2 and 5 were new compounds. M. racemosus could catalyze ring expansion and epoxidation reactions to form 3ß,10ß-epoxy- or 6α,19α-epoxy-9,10-seco-cycloartane structures. These regio- and stereo-selective reactions are difficult to achieve by chemical means. In addition, the biological effects of isolated metabolites on increasing the lifespan of Caenorhabditis elegans were evaluated. Most of the metabolites could significantly extend the lifespan of C. elegans at 50 µM.

Laparoscopic versus open total gastrectomy for advanced proximal gastric carcinoma: a matched pair analysis.

PURPOSE: Laparoscopic total gastrectomy for advanced proximal gastric carcinoma is a complex and challenging procedure, limited to a few expert centers. This study analyzed the short- and long-term outcomes of laparoscopic total gastrectomy for advanced proximal gastric carcinoma compared with open gastrectomy. METHODS: From January 2008 to January 2015, 61 patients underwent laparoscopic total gastrectomy for advanced proximal gastric carcinoma. They were matched and compared to 61 patients who underwent a conventional open operation. Short-term operative and postoperative outcomes as well as long-term outcomes, including overall survival and disease-free survival rates, were assessed. RESULTS: Patients were well matched for several preoperative factors. Overall postoperative 30-day complication rates were significantly higher for the open group. No significant difference was seen in 5-year overall survival and 5-year disease-free survival between the open and laparoscopic groups. The same result was seen in subgroup analyses of TNM stage. CONCLUSION: This study shows the feasibility of laparoscopic total gastrectomy for advanced proximal gastric carcinoma compared to open resection in regard to both short- and long-term outcomes. Laparoscopic surgery offers many advantages commonly attributed to laparoscopy and is well suited for proximal gastric carcinoma when performed by experienced surgeons.

Determination of the intrinsic reactivities for carbon dioxide gasification of rice husk chars through using random pore model.

Rice husk is abundantly available and environmentally friendly, and char-CO2 gasification is of great importance for the biomass gasification process. The intrinsic reaction rates of carbon dioxide gasification with rice husk chars derived from different pyrolysis temperatures were investigated in this study by conducting thermogravimetric analysis (TGA) measurements. The effects of gasification temperature and reactant partial pressure on the char-CO2 gasification were investigated and the random pore model (RPM) was used to determine the intrinsic kinetic parameters based on the experimental data. The results obtained from this study show that the activation energy, reaction order and pre-exponential factor varied in the ranges of 226.65-232.28kJ/mol, 0.288-0.346 and 2.38×10(5)-2.82×10(5)1/sPa(n) for the rice husk chars pyrolyzed at 700-900°C, respectively. All the determination coefficients between the RPM predictions and experimental results were higher than 0.906, indicating the RPM is reliable for determining and evaluating the intrinsic reactivities of rice husk chars.

MutL homolog 1 expression in thyroid carcinoma and its clinical significance.

OBJECTIVE: The aim of this study was to evaluate the MutL homolog 1 (MLH1) protein expression in thyroid cancer patients and its association with clinical pathological characteristics. MATERIALS AND METHODS: Forty thyroid cancer tissues and 22 partial paired normal thyroid tissues from 40 thyroid cancer patients who received surgery were collected in this study. MLH1 protein expression was tested by immunohistochemical method for the 40 cancer tissues and 22 partial paired normal thyroid tissues. The positive expression rate of MLH1 was compared between cancer tissue and normal tissue. The association between clinical pathological features such as gender, age, pathology type, clinical stage, lymph node metastasis, and MLH1 protein expression was calculated. RESULTS: MLH1 protein was mainly expressed in the nucleus with a small amount of expression in cytoplasm. The MLH1-positive expression rates in cancer and normal tissue were 47.5% and 81.8%, respectively, with statistical difference (P = 0.008); MLH1 protein positive expression was correlated with clinical stage (P = 0.04) and cancer lymph node metastasis (P = 0.03). However, its expression was not associated with gender (P = 0.63), age (P = 0.77), and pathology type (P = 0.77). CONCLUSION: MLH1-negative expression may play an important role in thyroid cancer tissue development and lymph node metastasis.