PPAR-α Agonist GW7647 Protects Against Oxidative Stress and Iron Deposit via GPx4 in a Transgenic Mouse Model of Alzheimer's Diseases.

Alzheimer's disease (AD) is a neurodegenerative disease caused by lipid peroxidation and iron hemostasis of the brain. PPAR-α is regarded as the most encouraging therapeutic approach of several neurodegenerative and metabolic disorders, due to its potent regulatory effects. In this study, we examined the ameliorative effect and the mechanisms of a PPAR-α agonist, GW7647, on the established AD models using APP/PS1 mice and APPsw/SH-SY5Y cells. Through Aß quantification and behavioral test, we found that GW7647 reduced Aß burden and improved cognitive defect in APP/PS1 mice. Liquid chromatography-mass spectrometry analysis indicated that GW7647 could enter the brain after oral administration. Neuronal cell death and iron deposit were inhibited, accompanied by decreased lipid peroxidation and inflammation. In an in vitro study of APPsw cells, we found that PPAR-α directly bound with GPx4 intron3 to promote GPx4 transcription and reduced the iron transport capability. Our data suggested that activation of PPAR-α by GW7647 improved the disruption of iron homeostasis in the brain of APP/PS1 mice and alleviated neuronal inflammation and lipid peroxidation, which was possibly related to the upregulated transcription of GPx4 mediated by the interaction of GPx4 noncoding region and the PPAR-α.

Value of Ultrasonic Elastography and Conventional Ultrasonography in the Differential Diagnosis of Non-Mass-like Breast Lesions.

The purpose of this study was to evaluate the diagnostic value of ultrasonic elastography (UE) and conventional ultrasonography (CUS) in the differential diagnosis of non-mass-like (NML) breast lesions. Static sonograms of 39 pathologically diagnosed NML breast lesions were reviewed. Lesions were evaluated by CUS and UE using CUS subjective ratings (benign, malignant or indeterminate), a 5-point subjective elasticity scoring system and the quantitative strain ratio (SR). Receiver operating characteristic curves and diagnostic tests were used to assess the diagnostic value of CUS and UE. Areas under the receiver operating characteristic curves (Az) of the CUS, 5-point elasticity and SR methods were 0.848 (p < 0.001), 0.895 (p < 0.001) and 0.943 (p < 0.001), respectively. In diagnosing NML breast lesions, there was no significant difference between the 5-point elasticity and CUS methods. The combination of UE and CUS helps to improve the accuracy of the ultrasonic diagnosis of NML breast lesions.

Copper-catalyzed Direct 2-Arylation of Benzoxazoles and Benzoimidazoles with Aryl Bromides and Cytotoxicity of Products.

An efficient copper-catalyzed direct 2-arylation of benzoxazoles and benzoimidazoles with aryl bromides is presented. The CuI/PPh3-based catalyst promotes the installation of various aryl and heteroaryl groups through a C-H activation process in good to excellent yields. The cytotoxicity of obtained 2-aryl benzoxazoles (benzoimidazoles) was also evaluated and 1-methyl-2-(naphthalen-1-yl)benzoimidazole showed potential cytotoxicity.

Recent advances in design, synthesis and bioactivity of paclitaxel-mimics.

Taxane-type anticancer drugs, including paclitaxel and its semi-synthetic derivatives docetaxel and cabazitaxel, are widely applied to chemotherapy of malignancy like breast cancer, ovarian cancer, non-small cell lung cancer and prostate cancer. However, their clinical applications are generally limited by scarce natural resources, various side effects and multidrug resistance. Therefore, it is significant to develop paclitaxel-mimics with simplified structure, fewer side effects and improved pharmaceutical properties. Based on our investigation on chemistry of paclitaxel, the current review summarized the most recent advances in the design, synthesis and biological activities of paclitaxel-mimics, which could be appealing to researchers in the field of medicinal chemistry and oncology. Meanwhile, smart design, interesting synthesis and potential bioactivities of these novel compounds may also provide valuable reference for the wider scientific communities.

Microwave-assisted extraction of polysaccharides from Yupingfeng powder and their antioxidant activity.

BACKGROUND: Microwave-assisted reflux extraction of polysaccharides YPF-P from the famous Chinese traditional drug, Yupingfeng powder, optimization of extracting conditions and evaluation of their antioxidant activity were conducted in this study. RESULTS: Single factor effect trends were achieved through yields and contends of YPF-P obtained from different extracting conditions. Then through a three-level, four-variable Box-Behnken design of response surface methodology adopting yield as response, the optimal conditions were determined as follows: Material/solvent ratio 1:23.37, microwave power 560 W, Extraction temperature 64°C, and extraction time 9.62 min. Under the optimal conditions, the YPF-P extraction yield was 3.23%, and its content was detected as 38.52%. In antioxidant assays, the YPF-P was tested to possess 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities with an IC50 value of 0.262 mg/ml. In addition, YPF-P was also proved to have relatively low ferric reducing antioxidant power (FRAP), compared to Vc, through FRAP assay. CONCLUSION: In the microwave assisted reflux extraction research, good YPF-P yield was achieved from materials with relatively low YPF-P content. And for the first time, both DPPH and FRAP assays were conducted on YPF-P, which proved that the antioxidant activity of YPF-P contributed to the functions of this medicine.

[Dissolved organic matter release of Zizania caduciflora and Phragmites australis from Lake Dianchi].

Ground dry leaves of two emerged macrophytes Zinania Caduciflora and Phragmites australis from Lake Dianchi were soaked in distilled water in laboratory to track their DOM release process. The results showed that: (1) during soaking, concentration of DOM which was released to the overlying water by the two species increased at first, then decreased and increased again at last. Concentrations of DOC, DON, and DOP released by both species reached their peaks at the 8th, 8th, and 24th hour, respectively; (2) the two species showed the same DOM release trend, i.e., release rates and intensities of DOC, DON, and DOP by both species reached the peaks at the 8th hour, and for both of them, the release rates and intensities of DOC, DON, and DOP at the 8th hour followed the order of DOC > DON > DOP; (3) the SUVA254 value obtained by the UV-visible spectroscopy increased at first and then decreased; (4) Fourier transform infrared (FT-IR) spectroscopy showed that the characteristic peak -OH disappeared during the decomposition process; (5) intensity of the humic-acid fluorescence peak as showed by the 3D-EEM fluorescence intensity (F/DOC) increased along with degradation.

Ectopic expression of Arabidopsis glycosyltransferase UGT85A5 enhances salt stress tolerance in tobacco.

Abiotic stresses greatly influence plant growth and productivity. While glycosyltransferases are widely distributed in plant kingdom, their biological roles in response to abiotic stresses are largely unknown. In this study, a novel Arabidopsis glycosyltransferase gene UGT85A5 was identified as significantly induced by salt stress. Ectopic expression of UGT85A5 in tobacco enhanced the salt stress tolerance in the transgenic plants. There were higher seed germination rates, better plant growth and less chlorophyll loss in transgenic lines compared to wild type plants under salt stress. This enhanced tolerance of salt stress was correlated with increased accumulations of proline and soluble sugars, but with decreases in malondialdehyde accumulation and Na(+)/K(+) ratio in UGT85A5-expressing tobacco. Furthermore, during salt stress, expression of several carbohydrate metabolism-related genes including those for sucrose synthase, sucrose-phosphate synthase, hexose transporter and a group2 LEA protein were obviously upregulated in UGT85A5-expressing transgenic plants compared with wild type controls. Thus, these findings suggest a specific protective role of this glycosyltransferase against salt stress and provide a genetic engineering strategy to improve salt tolerance of crops.

Differential Notch1 and Notch2 expression and frequent activation of Notch signaling in gastric cancers.

CONTEXT: The biologic effects of Notch1 and Notch2 vary with cancer types and their potential role(s) in gastric cancers (GCs) remains largely unknown. OBJECTIVES: This study aimed to address the previously mentioned issue by checking the expression of Notch1, Notch2, and Notch target gene Hes1 in GCs, premalignant gastric lesions, and noncancerous endoscopic gastric mucosa and by inhibiting Notch signal transduction in GC cells. DESIGN: The status of Notch1, Notch2, and Hes1 expression in 74 GC surgical specimens, 10 endoscopic samples, and 4 human GC cell lines was evaluated by tissue microarray-based immunohistochemical staining, Western blotting, and reverse transcription-polymerase chain reaction, and the importance of Notch signaling was elucidated by treating 2 GC cell lines with 2 γ-secretase inhibitors. RESULTS: Notch1 was undetectable in noncancerous gastric mucosa but was expressed with nuclear translocation in 16.7% (4 of 24) of chronic gastritis, 50.0% (9 of 18) of intestinal metaplasia, 54.2% (26 of 48) of intestinal GC, and 23.1% (6 of 26) of diffuse GC, showing distinct differences of Notch1 detection rates between either intestinal metaplasia and chronic gastritis or intestinal GCs and diffuse GCs (P  =  .03; P  =  .005, respectively). Notch2 nuclear translocation frequencies were 10.0% (1 of 10) in noncancerous endoscopic mucosa, 71.4% (30 of 42) in premalignant lesions, and 97.3% (72 of 74) in GC tissues, demonstrating a correlation of Notch2 expression with both intestinal GC and diffuse GC formation (P < .001). The rates of nuclear-Hes1 labeling were 1 of 10 among noncancerous, 42.9% premalignant, and 81.1% cancer tissues, which were closely correlated with Notch2 (P < .001) rather than Notch1 (P  =  .42) nuclear translocation. Only Notch2 was expressed accompanied with Hes1 nuclear labeling in the 4 GC cell lines established from diffuse GC cases. Inhibition of Notch signaling with γ-secretase inhibitors, L-685,458 and DAPT, prevented Hes1 nuclear translocation but neither suppressed growth nor induced cell death. CONCLUSIONS: This study demonstrated a close correlation of Notch2 expression with GC formation and the potential link of Notch1 upregulation with intestinal-like phenotypes of gastric lesions. Although inhibition of Notch activity failed to achieve anti-GC effects, the activated Notch signaling may reflect a potential GC risk.

Effect of temperature, light and salinity on seed germination and radicle growth of the geographically widespread halophyte shrub Halocnemum strobilaceum.

BACKGROUND AND AIMS: The small leafy succulent shrub Halocnemum strobilaceum occurs in saline habitats from northern Africa and Mediterranean Europe to western Asia, and it is a dominant species in salt deserts such as those of north-west China. The effects of temperature, light/darkness and NaCl salinity were tested on seed germination, and the effects of salinity were tested on seed germination recovery, radicle growth and radicle elongation recovery, using seeds from north-west China; the results were compared with those previously reported on this species from 'salt steppes' in the Mediterranean region of Spain. METHODS: Seed germination was tested over a range of temperatures in light and in darkness and over a range of salinities at 25 degrees C in the light. Seeds that did not germinate in the NaCl solutions were tested for germination in deionized water. Seeds from which radicles had barely emerged in deionized water were transferred to NaCl solutions for 10 d and then back to deionized water for 10 d to test for radicle growth and recovery. KEY RESULTS: Seeds germinated to higher percentages in light than in darkness and at high than at low temperatures. Germination percentages decreased with an increase in salinity from 0.1 to 0.75 M NaCl. Seeds that did not germinate in NaCl solutions did so after transfer to deionized water. Radicle elongation was increased by low salinity, and then it decreased with an increase in salinity, being completely inhibited by > or = 2.0 M NaCl. Elongation of radicles from salt solutions < 3.0 M resumed after seedlings were transferred to deionized water. CONCLUSIONS: The seed and early seedling growth stages of the life cycle of H. strobilaceum are very salt tolerant, and their physiological responses differ somewhat between the Mediterranean 'salt steppe' of Spain and the inland cold salt desert of north-west China.