Guirong Zhang

The aim of this study was to provide a practical experimental basis for the development of Neocryptotanshinone (NCTS) as an effective hypoglycemic drug and a theoretical method for the rapid screening of natural compounds with hypoglycemic effects. Molecular docking was used to screen the most suitable ligand. Hematoxylin and eosin, immunohistochemical staining, enzyme-linked immunosorbent assay and Western Blotting approved the hypoglycemic effect of NCTS. According to the free energy of binding, among 180 active compounds from the Traditional Chinese Medicine Integrated Database, NCTS was finally chose for investigation its hypoglycemic effects. In db/db mice, NCTS significantly reduced body weight and plasma glucose, improved glucose tolerance and levels of fasting plasma glucose and glycated hemoglobin A1c, and decreased insulin resistance after six-week administration. NCTS restored the pathological state in the liver of db/db mice and significantly decreased protein tyrosine phosphatase 1B (PTP1B) expression in the liver and muscle of db/db mice, which is related to the regulatory effect of NCTS on insulin receptor substrate 1. In conclusion, we successfully explored the hypoglycemic effect of NCTS in db/db mice via regulating the expression of PTP1B.

BACKGROUND: Giant cell tumor of bone (GC), osteosarcoma (OS) and Ewing’s sarcoma (ES) are three different types of bone cancer with common and specific pathology features. OBJECTIVE: The purpose of the study was to examine the relationship and differences of the three bone tumors using clinical samples. METHODS: Through screening the profiles of clinical samples from GC, OS and ES patients using a humanoncology array, we found 26, 25 and 15 tumorigenesis factors significantly increased in GS, OS and ES tissues compared to normal individuals. eNOS, endostatin, HIF-1α, IL-6, CCL2/MCP-1, CCL8/MCP-2, CCL7/MCP-3, Tie and VEGF directly or indirectly involve in the metastasis Therefore, expression levels of the 6 factors were further determined by Western blot. RESULTS: The results showed levels of MCP1, MCP2, MCP3 or IL-6 in the GS, OS and ES significantly increased, and the expression levels of angiogenesis and anti-angiogenesis factors containing eNOS, endostatin, HIF-1α, Tie or VEGF were enhanced. CONCLUSIONS: Our results suggest that eNOS, endostatin, HIF-1α, IL-6, CCL2/MCP-1, CCL8/MCP-2, CCL7/MCP-3, Tie and VEGF may play important roles in tumorigenesis, reveal the expression differences of tumor-associated cytokines and angiogenesis related factors, and provide clinical evidence for studying the mechanisms on the metastasis in GC, OS and ES.

Maize is the food crop with the highest total output in the world. However, corn bran is only a by‐product with low price. The 5,5′‐diferulic acid glucoside esters (DFG) were obtained from corn bran using the enzymatic method. DFG showed obvious antioxidant capacity in cell, Caenorhabditis elegans (C. elegans) and in mouse. DFG decreased ROS and MDA content in 500 μM H₂O₂ stimulated ARPE‐19 cells to 48.6% and 32.2%, respectively. DFG decreased ROS content in C. elegans to 49.1% and MDA content in acute ethanol (50%, 12 ml/kg) stimulated mouse to 30.4%. DFG also increased SOD protein content significantly in cell, C. elegans and mouse to 175.5%, 120.1%, and 126.2%, respectively. DFG significantly extended the lifespan of C. elegans both under heat stress and natural situation. The median survival time was prolonged to 133.3% and 116.7%, respectively. This capacity relied on the SIR‐2.1 activity. SIR‐2.1 is an ortholog of human Sirtuin‐1 (SIRT‐1). DFG also upregulated SIRT‐1 and PCG‐1α expression level obviously in H₂O₂‐stimulated ARPE‐19 cells (to 134.4% and 127.1%, respectively) and in acute ethanol stimulated mouse eyes (to 135.1% and 111.5%, respectively) and liver (to 123.3% and 113.6%, respectively). These results indicate that DFG has multiple bioactivities. Our research provides a new application prospect of corn bran. And to our best knowledge, this is the first time, the sirtuins‐relied lifespan extension activity of the 5,5′‐diferulic acid extracted from corn bran was reported. Practical applications The traditional method for extracting diferulic acid from corn bran is to use the strong alkali. Obviously, this is not welcomed by the food industry. We employed the biological enzyme method in a relatively mild pH range during the extraction process. It is more environmentally friendly and more economical. DFG can be added as a raw material for functional foods like yogurt, fruit juice, and cereals. As well, the solid precipitate obtained after extraction can also be used as high‐quality dietary fiber to produce functional food. Meanwhile, concerning for the 5,5′‐diferulic acid derived from corn bran, the relevant research is still not abundant. And to our best knowledge, we have reported for the first time about the effect of this kinds of diferulic acid on prolonging life span and its SIRT‐1‐dependent activity. It also provides a new perspective for the study of diferulic acid.

The improper usage of antibiotics is known to cause widespread antibiotic resistance. In this study, the antibacterial effects of a polypeptide-enriched extract from the skin of the amphibian Rana chensinensis (RCP) were evaluated against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus and the fungus Candida albicans. The mechanisms underlying these effects were also studied, and the minimum inhibitory concentration of RCP was determined for each species. Analyses of the levels of adenosine triphosphates (ATPases), including Na⁺/K⁺-ATPase and Ca²⁺-ATPase, and scanning electron microscopy confirmed that RCP damaged the microbial cell walls and membranes. RCP perturbed microbial metabolism and particularly affected the tricarboxylic acid cycle (TCA), suggesting that this agent downregulated the levels of succinate dehydrogenase, malate dehydrogenase and ATPase activity in cells. Furthermore, RCP caused the leakage of genetic material from all four microbial strains. In conclusion, RCP effectively inhibited the growth of Gram-negative and Gram-positive bacteria and a fungal species by disrupting energy metabolic processes.

Obesity in pregnant women presents a risk to fetal health, leading to numerous metabolic syndromes and chronic inflammation risks. Previously, physical exercise was considered to be one of the primary treatments for obesity. However, the effect of fat consumption throughout the life cycle on physical endurance capacity remains unknown. A total of two groups of female mice (age, 6 weeks; C57BL/6J) were fed with a normal chow diet and a moderate high fat diet (MHFD), during pregnancy and lactation (8 weeks), with the offspring receiving the same diet as the mother. When filial mice were 8, 16 and 24 weeks old, they were tested for endurance, blood pressure (BP) and glucose tolerance, as well as adipose tissue infiltration and macrophage subtype. Compared with the control group, filial mice in MHFD groups exhibited increased BP and glucose levels and larger adipose cells (similar to 4-fold). During adolescence, the obese filial mice demonstrated increased endurance compared with controls. Endurance declines in middle and old age; the endurance of aged obese mice was 29% that of lean ones. In addition, body coordination and movement memory did not notably change. The expression of cluster of differentiation 68, one of the most reliable markers of macrophages, increased by 2.48-fold, demonstrating that macrophages were recruited and underwent infiltration. In addition, increased tumor necrosis factor- and decreased interleukin-10 expression demonstrated that infiltrated macrophages are polarized to the M1 state, which weakens physical endurance and resists type M2 macrophages, which exhibit repairing functions. In conclusion, hereditary MHFD weakens physical endurance and alters the metabolic characteristics of C57BL/6 offspring.

Marasmius androsaceus is a medicinal fungus mainly used to treat various forms of pain in China. This study investigated the analgesic effects of an ethanol extract of M. androsaceus (MAE) and its potential molecular mechanisms. Oral administration of MAE (50, 200, and 1000 mg/kg) had significant analgesic effects in an acid-induced writhing test, a formalin test, and a hot-plate test, with effectiveness similar to tramadol (the positive control drug). The autonomic activity test showed that MAE had no harmful effects on the central nervous system in mice. MAE resulted in significantly enhanced levels of noradrenalin and 5-hydroxytryptamine in serum but suppressed both of these neurotransmitters in the hypothalamus after 30 s of hot-plate stimulation. Co-administration with nimodipine (10 mg/kg; a Ca²⁺ channel blocker) strongly enhanced the analgesic effect in the hot-plate test compared to MAE alone. Moreover, MAE down-regulated the expression of calmodulin-dependent protein kinase II (CaMKII) in the hypothalamus after a 30-s thermal stimulus. These results suggested that the analgesic ability of MAE is related to the regulation of metabolism by monoamine neurotransmitters and Ca²⁺/CaMKII-mediated signaling, which can potentially aid the development of peripheral neuropathic pain treatments obtained from M. androsaceus.

Cinnamyl acetate as an important fragrance ingredient could be synthesized by lipase-catalysed transesterification in organic systems, but enzyme proteins tended to denature and inactivate for no water lubrication. To improve the non-aqueous stability of lipases, absorbent cotton was taken as an alternative “water” phase to stabilize enzyme proteins. In a mass ratio of 1:1, Pseudomonas fluorescens lipase was immobilized on cotton fibres by physical absorption in a column glass bottle, forming a facile cotton-lipase bioreactor in which the transesterification between cinnamyl alcohol and vinyl acetate processed efficiently. From the molar conversions after reaction for 2 h at 37 °C and 160 rpm, the ability of cotton-lipase to transform substrate was more than 5-folds of native lipase. And even in static state and at 4 °C, the conversion of reaction catalysed by cotton-PFL had 11-fold increase relative to native lipase after 8 h. Recycles showed that the cotton-lipase had an extra-long half-life of activity (t_1/2 = 693 h) and a negligible decay rate in the ability to transform substrate (D_r = 0.08% h⁻¹). All these showed that this lipase had been effectively activated and stabilized by cotton fibres for the numerous hydroxyl groups and fluffy structure.

Corn bran dietary fibre (CF) was paid more attention for its anticancer and hypolipidemic activities. In this paper, corn bran was firstly decomposed to the threadlike fibre (CF₁) by multiple enzymes and then further modified to the granular fibre (CF₂) by alkali under high pressure and high temperature (APT). The two types of fibres were characterized by scanning electron microscope (SEM) and near-infrared spectrophotometer (IR), and investigated by hydration measurements and nitrite adsorption assays. The results showed that CF₂ had more much specific surface area, and displayed 4.7, 6.3 and 30-fold increases in water retention (WR), swelling capacity (SC) and nitrite absorption (NA), compared with CF₁, respectively. The rat feeding trials showed that the granular fibre could decrease total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol (LDLC) by 41.4 %, 20.7 % and 56.5 %, respectively. These excellent physiological activities indicate that CF₂ will be a potentially available dietary ingredient in functional food industries, and meanwile imply that the enzymochemical method is a desired strategy for CF processing.

To improve the activity and enantioselectivity of hyperthermophilic archaeon Aeropyrum pernix K1 esterase (APE1547) and its mutants, they were purified by acetone-treated method. It was found that the acetone treatment not only caused APE1547 and its mutants to display higher activity and enantioselectivity but also saved more than 90% of time spent in purifying them by Ni-chelating column. In hydrolysis of p-nitrophenyl caprylate, the acetone-treated APE1547 and mutant A containing the following substitutions R11G, L36P, V225A, I551L, and A564T showed 5.7- and 6.9-fold active increase, respectively. In the resolution of 2-octanol acetate, the acetone-treated mutant A had a 9-fold enantioselective increase relative to that purified by Ni-chelating column. In addition, the impact of pH, temperature, and chemical reagents on activity of APE1547 and mutant A was discussed in this paper.