Caffeic Acid Derivatives Inhibit the Growth of Colon Cancer: Involvement of the PI3-K/Akt and AMPK Signaling Pathways

The aberrant regulation of phosphatidylinositide 3-kinases (PI3-K)/Akt, AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (m-TOR) signaling pathways in cancer has prompted significant interest in the suppression of these pathways to treat cancer. Caffeic acid (CA) has been reported to possess important anti-inflammatory actions. However, the molecular mechanisms by which CA derivatives including caffeic acid phenethyl ester (CAPE) and caffeic acid phenylpropyl ester (CAPPE), exert inhibitory effects on the proliferation of human colorectal cancer (CRC) cells have yet to be elucidated

Determination of aflatoxin B1 level in rice (Oryza sativa L.) through near-infrared spectroscopy and an improved simulated annealing variable selection method

Direct quantification analysis of near-infrared (NIR) spectra is challenging because the number of spectral variables is usually considerably higher than the number of samples. To mitigate the so-called curse of dimensionality, var�iable selection is often performed before multivariate calibration. There has been much work in this regard, where the developed variable selection method can be categorized as individual variable selection, such as uninformative variable elimination or variable importance in projection, and continuous interval variable selection method such as interval partial least squares or moving window partial least squares. In this study, a new individual variable se�lection method, modified simulated annealing (MSA), was proposed and used in conjunction with the partial least squares regression (PLSR) model. The interpretability of the selected variables in the determination of aflatoxin B1 levels in white rice was assessed. The results revealed that the PLSR model combined with MSA not only yielded higher accuracy than the full-spectrum PLSR but also successfully shrank the variable space. The developed simplified PLSR model using MSA produced satisfactory performances, with root mean square error of calibration (RMSEC) of 0.11 μg/kg and 0.56 μg/kg, and root mean square error of prediction (RMSEP) of 7.16 μg/kg and 14.42 μg/kg, were obtained for the low-aflatoxin B1-level- and high-aflatoxin-B1-level samples, respectively. Specifically, the MSA-based models yielded improvements of 97.80% (calibration set) and 44.62% (prediction set) as well as 95.85% (calibration set) and 62.57% (prediction set) for both datasets when compared with the full-spectrum PLSR (low aflatoxin: RMSEC = 5.02 μg/kg, RMSEP = 12.93 μg/kg; high aflatoxin: RMSEC = 13.50 μg/kg, RMSEP = 38.53 μg/kg). Compared with the baseline method of simulated annealing (SA) (low aflatoxin: RMSEC = 0.21 μg/kg, RMSEP = 9.78 μg/kg; high aflatoxin: RMSEC = 12.27 μg/kg, RMSEP = 38.53 μg/kg), the MSA significantly improved the predictive performance of the regression models, with the number of selected variables being almost half of that in the SA. A comparison with other commonly used variable selection methods of selectivity ratio (low aflatoxin: RMSEC = 6.09 μg/kg, RMSEP = 13.75 μg/kg; high aflatoxin: RMSEC = 13.74 μg/kg, RMSEP = 41.13 μg/kg), unin�formative variable elimination (low aflatoxin: RMSEC = 0.32 μg/kg, RMSEP = 5.11 μg/kg; high aflatoxin: RMSEC = 3.80 μg/kg, RMSEP = 17.76 μg/kg), and variable importance in projection (low aflatoxin: RMSEC = 2.67 μg/kg, RMSEP = 10.71 μg/kg; high aflatoxin: RMSEC = 13.51 μg/kg, RMSEP = 32.53 μg/kg) also indicated the promising efficacy of the proposed MSA

Caffeic acid phenethyl amide ameliorates ischemia/reperfusion injury and cardiac dysfunction in streptozotocin-induced diabetic rats

BACKGROUND: Caffeic acid phenethyl ester (CAPE) has been shown to protect the heart against ischemia/reperfusion (I/R) injury by various mechanisms including its antioxidant effect. In this study, we evaluated the protective effects of a CAPE analog with more structural stability in plasma, caffeic acid phenethyl amide (CAPA), on I/R injury in streptozotocin (STZ)-induced type 1 diabetic rats. METHODS: Type 1 diabetes mellitus was induced in Sprague–Dawley rats by a single intravenous injection of 60 mg/kg STZ. To produce the I/R injury, the left anterior descending coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. CAPA was pretreated intraperitoneally 30 minutes before reperfusion. An analog devoid of the antioxidant property of CAPA, dimethoxyl CAPA (dmCAPA), and a nitric oxide synthase (NOS) inhibitor (Nω-nitro-l-arginine methyl ester [l-NAME]) were used to evaluate the mechanism involved in the reduction of the infarct size following CAPA-treatment. Finally, the cardioprotective effect of chronic treatment of CAPA was analyzed in diabetic rats. RESULTS: Compared to the control group, CAPA administration (3 and 15 mg/kg) significantly reduced the myocardial infarct size after I/R, while dmCAPA (15 mg/kg) had no cardioprotective effect. Interestingly, pretreatment with a NOS inhibitor, (l-NAME, 3 mg/kg) eliminated the effect of CAPA on myocardial infarction. Additionally, a 4-week CAPA treatment (1 mg/kg, orally, once daily) started 4 weeks after STZ-induction could effectively decrease the infarct size and ameliorate the cardiac dysfunction by pressure-volume loop analysis in STZ-induced diabetic animals. CONCLUSIONS: CAPA, which is structurally similar to CAPE, exerts cardioprotective activity in I/R injury through its antioxidant property and by preserving nitric oxide levels. On the other hand, chronic CAPA treatment could also ameliorate cardiac dysfunction in diabetic animals

Caffeic Acid Phenylethyl Amide Protects against the Metabolic Consequences in Diabetes Mellitus Induced by Diet and Streptozocin

Caffeic acid phenyl ester is distributed wildly in nature and has antidiabetic and cardiovascular protective effects. However, rapid decomposition by esterase leads to its low bioavailability in vivo. In this study, chronic metabolic and cardiovascular effects of oral caffeic acid phenylethyl amide, whose structure is similar to caffeic acid phenyl ester and resveratrol, were investigated in ICR mice. We found that caffeic acid phenylethyl amide protected against diet or streptozocin-induced metabolic changes increased coronary flow and decreased infarct size after global ischemia-reperfusion in Langendorff perfused heart. Further study indicated that at least two pathways might be involved in such beneficial effects: the induction of the antioxidant protein MnSOD and the decrease of the proinflammatory cytokine TNFα and NFκB in the liver. However, the detailed mechanisms of caffeic acid phenylethyl amide need further studies. In summary, this study demonstrated the protective potential of chronic treatment of caffeic acid phenylethyl amide against the metabolic consequences in diabetes mellitus

ITPKC Single Nucleotide Polymorphism Associated with the Kawasaki Disease in a Taiwanese Population

Kawasaki disease (KD) is characterized by systemic vasculitis with unknown etiology. Previous studies from Japan indicated that a gene polymorphism of ITPKC (rs28493229) is responsible for susceptibility to KD. We collected DNA samples from 1,531 Taiwanese subjects (341 KD patients and 1,190 controls) for genotyping ITPKC. In this study, no significant association was noted for the ITPKC polymorphism (rs28493229) between the controls and KD patients, although the CC genotype was overrepresented. We further combined our data with previously published case/control KD studies in the Taiwanese population and performed a meta-analysis. A significant association between rs28493229 and KD was found (Odds Ratio:1.36, 95% Confidence Interval 1.12–1.66). Importantly, a significant association was obtained between rs28493229 and KD patients with aneurysm formation (P = 0.001, under the recessive model). Taken together, our results indicated that C-allele of ITPKC SNP rs28493229 is associated with the susceptibility and aneurysm formation in KD patients in a Taiwanese population

Recombinant Trimeric HA Protein Immunogenicity of H5N1 Avian Influenza Viruses and Their Combined Use with Inactivated or Adenovirus Vaccines

[[abstract]]Background:The highly pathogenic avian influenza (HPAI) H5N1 virus continues to cause disease in poultry and humans. The hemagglutinin (HA) envelope protein is the primary target for subunit vaccine development.Methodology/Principal Findings:We used baculovirus-insect cell expression to obtain trimeric recombinant HA (rHA) proteins from two HPAI H5N1 viruses. We investigated trimeric rHA protein immunogenicity in mice via immunizations, and found that the highest levels of neutralizing antibodies resulted from coupling with a PELC/CpG adjuvant. We also found that the combined use of trimeric rHA proteins with (a) an inactivated H5N1 vaccine virus, or (b) a recombinant adenovirus encoding full-length HA sequences for prime-boost immunization, further improved antibody responses against homologous and heterologous H5N1 virus strains. Data from cross-clade prime-boost immunization regimens indicate that sequential immunization with different clade HA antigens increased antibody responses in terms of total IgG level and neutralizing antibody titers.Conclusion/Significance:Our findings suggest that the use of trimeric rHA in prime-boost vaccine regimens represents an alternative strategy for recombinant H5N1 vaccine development

Anesthetic Propofol Reduces Endotoxic Inflammation by Inhibiting Reactive Oxygen Species-regulated Akt/IKKβ/NF-κB Signaling

BACKGROUND: Anesthetic propofol has immunomodulatory effects, particularly in the area of anti-inflammation. Bacterial endotoxin lipopolysaccharide (LPS) induces inflammation through toll-like receptor (TLR) 4 signaling. We investigated the molecular actions of propofol against LPS/TLR4-induced inflammatory activation in murine RAW264.7 macrophages. METHODOLOGY/PRINCIPAL FINDINGS: Non-cytotoxic levels of propofol reduced LPS-induced inducible nitric oxide synthase (iNOS) and NO as determined by western blotting and the Griess reaction, respectively. Propofol also reduced the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 as detected by enzyme-linked immunosorbent assays. Western blot analysis showed propofol inhibited LPS-induced activation and phosphorylation of IKKβ (Ser180) and nuclear factor (NF)-κB (Ser536); the subsequent nuclear translocation of NF-κB p65 was also reduced. Additionally, propofol inhibited LPS-induced Akt activation and phosphorylation (Ser473) partly by reducing reactive oxygen species (ROS) generation; inter-regulation that ROS regulated Akt followed by NF-κB activation was found to be crucial for LPS-induced inflammatory responses in macrophages. An in vivo study using C57BL/6 mice also demonstrated the anti-inflammatory properties against LPS in peritoneal macrophages. CONCLUSIONS/SIGNIFICANCE: These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways

Studies on the Chemical Constituents of Derris laxiflora Benth.

疏花魚藤（Derris laxiflora Benth.）為荳科植物，並且是台灣特有種，此植物生長在臺灣低海拔1000公尺以下，此植物的根與莖曾經被使用作為農用殺蟲劑，而台灣原住民也常取其根部的汁液毒魚，作為捕魚的一種方法。 本研究將疏花魚藤，以甲醇浸泡得到之萃取物，運用矽膠薄層分析、矽膠管柱層析、高效率液相層析儀及再結晶等方法進行分離純化。單離之純化合物經測定紅外線光譜、氫核磁共振光譜、碳核磁共振光譜與質譜後，經推測若為已知化合物者，與文獻值比對確定其結構。若為新化合物，依需要進行二維核磁共振光譜實驗，配合化學反應等方法確定其結構。 本實驗鑑定得到共143個化合物，分別為： 一、芳香族類（Aromatic compounds）化合物13個 二、葉綠素（Chlorophyll）化合物5個 三、類黃酮類（Flavonoids）化合物25個 四、異黃酮類（Isoflavonoids）化合物13個 五、木酚素（Lignans）化合物12個 六、紫檀烷類（Pterocarpans）化合物10個 七、固醇類（Steroids）化合物21個 八、三萜類（Triterpenoids）化合物32個 九、其他類（Other compounds）化合物12個 共計有15個新化合物和7個首次自天然界分離得到之化合物。Derris laxiflora Benth., a member of the Leguminosae, endemic in Taiwan, distributed at altitudes of under 1000 meters. It's roots and the stems were once used as the agricultural pesticide. Taiwan aboriginals also took root's juice to poison fish. The components can be used to poison fish, but innocuous to mammalian. The methanol extract from D. laxiflora was concentrated to give a residue which was partitioned between ethyl acetate and H2O. The ethyl acetate layer was separated by column chromatography on silica gel, preparative thin layer chromatography, flash column chromatography, and high performance liquid chromatography (HPLC) to give one hundred and forty three compounds, including 13 aromatic compounds, 5 chlorophylls, 25 flavonoids, 13 isoflavonoids, 12 lignans, 10 pterocarpans, 21 steroids, 32 triterpenoids, and 12 other type compounds. Known compounds were identified by IR, NMR, and Mass spectral analysis and comparison with those of authentic samples or data reported in literatures. Structures of new compounds were further elucidated by 2D NMR spectral and chemical methods. Among these isolated compounds, there are fifteen new compounds, and seven of them were isolated for the first time from natural sources.中文摘要(Ⅰ) 英文摘要(Ⅱ) 第一章 緒論 第一節：緒言(1) 第二節：研究目的(1) 第三節：植物簡介(1) 第四節：魚藤屬植物的研究回顧(3) 第二章 結果與討論 第一節：萃取與分離(15) 第二節：芳香族類化合物與木酚素化合物構造鑑定(29) 化合物AR8之構造決定(30) 化合物AR9之構造決定(36) 化合物L12之構造決定(42) 第三節：類黃酮類化合物之構造鑑定(50) 化合物FL6之構造決定(51) 化合物FL10之構造決定(59) 化合物FL17之構造決定(67) 第四節：紫檀烷類化合物之構造鑑定(74) 化合物PT5之構造決定(75) 化合物PT9之構造決定(82) 化合物PT10之構造決定(90) 第五節：固醇類化合物之構造鑑定(97) 化合物ST12之構造決定(99) 第六節：三萜類（Glutinane）化合物之構造鑑定(108) 化合物TR5之構造決定(109) 第七節：三萜類（Cycloartane）化合物之構造鑑定(118) 化合物TR7之構造決定(119) 化合物TR13之構造決定(128) 第八節：三萜類（Oleanane）化合物之構造鑑定(137) 化合物TR16之構造決定(139) 化合物TR18之構造決定(148) 化合物TR27之構造決定(157) 化合物TR29之構造決定(166) 第九節：其他類化合物之構造鑑定(175) 化合物OT6之構造決定(176) 化合物OT8之構造決定(182) 化合物OT9之構造決定(188) 化合物OT11之構造決定(194) 化合物OT12之構造決定(201) 第三章 結論 第一節：化合物骨架之種類(208) 第二節：各類骨架的生合成推演(212) 第四章 實驗部份 第一節：實驗儀器與藥品(216) 第二節：實驗步驟(217) 第三節：已知化合物數據(222) 參考文獻(256

Tests of data quality, scaling assumptions, reliability, and construct validity of the SF-36 health survey in people who abuse heroin

Health-related quality of life (HRQOL) is considered an important outcome indicator in substances abuse studies. However, psychometric properties of HRQOL measures are largely unknown in people who abuse heroin. Therefore, the present study aimed to examine data quality, scaling properties, reliability, and construct validity of the 36-Item Short Form healthy survey (SF-36) in people who abuse heroin. Methods: A total of 469 people who abuse heroin participated in the study. Data quality was determined by data completeness. Scaling properties were evaluated by item frequency distribution, equivalence of item means and standard deviations, item-internal consistency, and item-discriminant validity (calculating scaling success). Internal consistency was examined using Cronbach's α. Construct validity was examined by investigating convergent validity and divergent validity among the eight scales of the SF-36. Results: The results of data quality showed low missing rates (0.0–3.8%) and high completion rates in the scales (91.9–98.7%). The results of scaling assumptions showed good item frequency distribution on each item, roughly equivalent item means and standard deviations within a scale, good item-internal consistency (>0.4) and good scaling success rates (77.5–100%), except on the two scales of bodily pain (BP) and social functioning (SF). Three scales showed ceiling and/or floor effects [i.e., physical functioning (PF), role limitations due to physical problems (RP), and role limitations due to emotional problems (RE)]. Cronbach's α was acceptable (>0.7), except for the BP and SF scales. Construct validity was partially supported by the results of convergent validity and divergent validity. Conclusion: The results confirmed good data quality; satisfactory scaling assumptions and internal consistency (except for the BP and SF scales); and generally acceptable construct validity. However, the PF, RP, and RE scales showed ceiling and/or floor effects. Therefore, the BP, SF, PF, RP, and RE scales should be used with cautions in measuring HRQOL in people who abuse heroin

Cultivation and Biorefinery of Microalgae (<i>Chlorella</i> sp.) for Producing Biofuels and Other Byproducts: A Review

Microalgae-based carbon dioxide (CO2) biofixation and biorefinery are the most efficient methods of biological CO2 reduction and reutilization. The diversification and high-value byproducts of microalgal biomass, known as microalgae-based biorefinery, are considered the most promising platforms for the sustainable development of energy and the environment, in addition to the improvement and integration of microalgal cultivation, scale-up, harvest, and extraction technologies. In this review, the factors influencing CO2 biofixation by microalgae, including microalgal strains, flue gas, wastewater, light, pH, temperature, and microalgae cultivation systems are summarized. Moreover, the biorefinery of Chlorella biomass for producing biofuels and its byproducts, such as fine chemicals, feed additives, and high-value products, are also discussed. The technical and economic assessments (TEAs) and life cycle assessments (LCAs) are introduced to evaluate the sustainability of microalgae CO2 fixation technology. This review provides detailed insights on the adjusted factors of microalgal cultivation to establish sustainable biological CO2 fixation technology, and the diversified applications of microalgal biomass in biorefinery. The economic and environmental sustainability, and the limitations and needs of microalgal CO2 fixation, are discussed. Finally, future research directions are provided for CO2 reduction by microalgae