Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells.     

Imaging evaluation of the liver using multi-detector row computed tomography in micropigs as potential living liver donors

The shortage of organ donors has stimulated interest in the possibility of using animal organs for transplantation into humans. In addition, pigs are now considered to be the most likely source animals for human xenotransplantation because of their advantages over non-human primates. However, the appropriate standard values for estimations of the liver of micropigs have not been established. The determination of standard values for the micropig liver using multi-detector row computed tomography (MDCT) would help to select a suitable donor for an individual patient, determine the condition of the liver of the micropigs and help predict patient prognosis. Therefore, we determined the standard values for the livers of micropigs using MDCT. The liver parenchyma showed homogenous enhancement and had no space-occupying lesions. The total and right lobe volumes of the liver were 698.57 ± 47.81 ml and 420.14 ± 26.70 ml, which are 51.74% and 49.35% of the human liver volume, respectively. In micropigs, the percentage of liver volume to body weight was approximately 2.05%. The diameters of the common hepatic artery and proper hepatic artery were 6.24 ± 0.20 mm and 4.68 ± 0.13 mm, respectively. The hepatic vascular system of the micropigs was similar to that of humans, except for the variation in the length of the proper hepatic artery. In addition, the diameter of the portal vein was 11.27 ± 0.38 mm. In conclusion, imaging evaluation using the MDCT was a reliable method for liver evaluation and its vascular anatomy for xenotransplantation using micropigs.     

The effect of Eucommia ulmoides leaf supplementation on the growth performance, blood and meat quality parameters in growing and finishing pigs

The aim of the present study was to investigate the effect of Eucommia ulmoides leaf (EUL) supplementation on the growth performance, blood and meat quality parameters in growing and finishing pigs. Ninety gilts (L × LW × D, 20 kg initialBW) were housed 10 per pen in a front‐open building with three replicate pens per treatment. Experimental treatment was started from the beginning of the growing stage (20 ± 3 kg) by supplementing EUL at 0(C), 3(T1) and 5% (T2) to the growing and finishing diet. Pigs were slaughtered by electrical stunning at 105 ± 3 kg live weight. Average daily feed intake (ADFI, kg/day) decreased (P < 0.05) by addition of EUL in growth performance, average daily gain (ADG, kg/day) was lower (P < 0.05) in T1 and T2 than in C. In hematology, leukocytes (WBC, 10³/mm³) decreased (P < 0.05) in T1 and T2 than in C. Erythrocytes (RBC, 10⁶/mm³), hemoglobin (HGB, g/dL) and hematocrit (HCT, %) increased (P < 0.05) in T1 and T2 than in C. Platelet (PLT, 10³/mm³) was lower (P < 0.05) in T2 than in C and T1. In biochemical composition of serum, total protein (g/dL), r‐GTP (μ/L), total cholesterol (mg/dL) and triglycerides (mg/dL) were lower (P < 0.05) in T1 and T2 than in C. On longissimus dorsi muscle, crude protein was higher (P < 0.05) in T1 than in C. Crude ash was higher (P < 0.05) in T1 and T2 than in C. Yellow to blue color scale (CIE b*) in meat color was higher (P < 0.05) in T2 than in C. CIE b* in back fat color was higher (P < 0.05) in T2 than in the other treatments. In sensory evaluation scores for fresh meat, the values of meat color, fat color, drip loss and marbling were not significantly affected by addition of EUL. In cooked meat, the values of chewiness and overall acceptability were higher (P < 0.05) in T1 and T2 than in C. The results indicate that the addition of EUL affected growth performance, blood parameters and meat quality parameters in growing and finishing pigs.     

Purification and characterization of an antifungal protein, C-FKBP, from Chinese cabbage

An antifungal protein was isolated from Chinese cabbage (Brassica campestris L. ssp. pekinensis) by buffer-soluble extraction and two chromatographic procedures. The results of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry revealed that the isolated Chinese cabbage protein was identical to human FK506-binding protein (FKBP). A cDNA encoding FKBP was isolated from a Chinese cabbage leaf cDNA library and named C-FKBP. The open reading frame of the gene encoded a 154-amino acid polypeptide. The amino acid sequence of C-FKBP exhibits striking degrees of identity with the corresponding mouse (61%), human (60%), and yeast (56%) proteins. Genomic Southern blot analyses using the full-length C-FKBP cDNA probe revealed a multigene family in the Chinese cabbage genome. The C-FKBP mRNA was highly expressed in vegetative tissues. We also analyzed the antifungal and peptidyl-prolyl cis-trans isomerase activity of recombinant C-FKBP protein expressed in Escherichia coli. This protein inhibited pathogenic fungal strains, including Candida albicans, Botrytis cinerea, Rhizoctonia solani, and Trichoderma viride, whereas it exhibited no activity against E. coli and Staphylococcus aureus. These results suggest that recombinant C-FKBP is an excellent candidate as a lead compound for the development of antifungal agents.     

Effects of Resistant Starch and Fiber from High‐Amylose Non‐Floury Corn on Tortilla Texture

A high‐amylose, non‐floury corn, a floury corn, and a 1:1 blend were made into masa and then tortillas. The masa flour made with the high‐amylose corn had a greater amount of resistant starch (RS 28.8%) and a greater amount of total dietary fiber (TDF 42.1%) than that with the floury corn (RS 2.9%, TDF 9.6%), producing a high‐fiber tortilla. The masa was evaluated for pasting properties using a Rapid ViscoAnalyser (RVA). The high‐amylose masa slurry gelatinized little at 95°C. The floury masa had the greatest peak viscosity, whereas the 1:1 blend was intermediate in value. Sensory evaluations of the tortillas for the textural attributes showed the floury tortillas to be chewier, more rollable, and grittier than the high‐amylose tortillas, whereas the blend tortillas were intermediate for most attributes. The cutting force of the high‐amylose tortillas, measured on a texture analyzer, was very low; the blend and floury tortillas required more force. Chewiness was correlated to rollability (r = 0.99, P = 0.05). The %RS and %TDF were correlated to rollability (r = –0.99), and cutting force (r = 0.99). The floury and blend tortillas had firm textures expected of desirable tortillas, whereas the high‐amylose tortillas broke under little force, and would not roll. The high‐amylose tortillas had high amounts of RS and TDF but poor texture. The blend tortillas retained most floury tortilla textural properties, making them suitable products for consumer use.     

Multi-Step Enzymatic Production and Purification of 2-Keto-3-Deoxy-Galactonate from Red-Macroalgae-Derived Agarose

2-keto-3-deoxy sugar acids, which have potential as precursors in medicinal compound production, have gained attention in various fields. Among these acids, 2-keto-3-deoxy-l-galactonate (KDGal) has been biologically produced from D-galacturonate originating from plant-derived pectin. KDGal is also found in the catabolic pathway of 3,6-anhydro-l-galactose (AHG), the main component of red-algae-derived agarose. AHG is converted to 3,6-anhydrogalactonate by AHG dehydrogenase and subsequently isomerized to KDGal by 3,6-anhydrogalactonate cycloisomerase. Therefore, we used the above-described pathway to produce KDGal from agarose. Agarose was depolymerized to AHG and to agarotriose (AgaDP3) and agaropentaose (AgaDP5), both of which have significantly higher molecular weights than AHG. When only AHG was converted to KDGal, AgaDP3 and AgaDP5 remained unreacted. Finally, KDGal was effectively purified from the enzymatic products by size-exclusion chromatography based on the differences in molecular weights. These results show that KDGal can be enzymatically produced and purified from agarose for use as a precursor to high-value products.     

Porphyra tenera Protects against PM2.5-Induced Cognitive Dysfunction with the Regulation of Gut Function

To evaluate the biological effects of Porphyra tenera (P. tenera), we tried to confirm the possibility that the intake of P. tenera could modulate cognitive and intestinal functions in PM_2.5-induced cognitive decline mice. P. tenera attenuated PM_2.5-induced learning and memory impairment through antioxidant and anti-inflammatory effects by regulating the mitochondrial function and TLR-initiated NF-κB signaling. In addition, P. tenera effectively alleviated Aβ production/tau phosphorylation by inhibiting the JNK phosphorylation. Also, the bioactive constituents of P. tenera determined the sulfated galactan, mycosporine-like amino acids (MAAs), and chlorophyll derivatives. Moreover, the bioactive compounds of P. tenera by gut fermentation protected against gut dysbiosis and intestinal tight junction damage with a decrease in inflammatory response and short-chain fatty acid production. Based on these results, our findings suggest that P. tenera with sulfated galactan and MAAs is a potential material for cognitive function improvement.     

Taeanamides A and B,Nonribosomal Lipo-Decapeptides Isolated from an Intertidal-Mudflat-Derived Streptomyces sp.

Two new lipo-decapeptides, namely taeanamides A and B (1 and 2), were discovered from the Gram-positive bacterium Streptomyces sp. AMD43, which was isolated from a mudflat sample from Anmyeondo, Korea. The exact molecular masses of 1 and 2 were revealed by high-resolution mass spectrometry, and the planar structures of 1 and 2 were elucidated using NMR spectroscopy. The absolute configurations of 1 and 2 were determined using a combined analysis of ¹H-¹H coupling constants and ROESY correlations, the advanced Marfey’s method, and bioinformatics. The putative nonribosomal peptide synthetase pathway for the taeanamides was identified by analyzing the full genome sequence data of Streptomyces sp. AMD43. We also found that taeanamide A exhibited mild anti-tuberculosis bioactivity, whereas taeanamide B showed significant bioactivity against several cancer cell lines.     

Regioselective Synthesis of 6-O-Acetyl Dieckol and Its Selective Cytotoxicity against Non-Small-Cell Lung Cancer Cells

Dieckol, a phlorotannin from Ecklonia cava, has shown potential for use as an anticancer agent that selectively kills cancer cells. However, it is necessary to amplify its potency without damaging its inherent safety in order to develop it as a competitive chemotherapeutic. Here, we explored the controlled O-acylations of dieckol. Acyl groups could be consistently introduced to the 6-O position of dieckol with a high regioselectivity, which was confirmed by NOESY, HMBC and HSQC spectroscopies. In cytotoxicity studies on the newly synthesized 6-O-acetyl, 6-O-benzoyl dieckols and previously synthesized 6-O-alkyl dieckols against A549 vs. normal cells, all of the derivatives showed low cytotoxicity in normal cells with an IC₅₀ of 481–719 μM, and highly structure-dependent cytotoxicity in A549 cells with an IC₅₀ of 7.02 (acetyl)−842.26 (benzyl) μM. The selectivity index also showed a large structure dependency in the range of 0.67 (benzyl)–68.58 (acetyl). An analysis of the structure–activity relationship indicated that the activity was dramatically reduced in the presence of a benzene ring and was highly increased in the presence of small polar substituents. Conclusions: Controlled mono-O-modifications of dieckol could be a powerful tool to enhance the anticancer activity of dieckol, thus contributing to the development strategy for dieckol-based chemotherapeutics.