Synthesis of Optically Active Organofluorides by Ring Opening of Oxazolidinone-Fused Aziridines.

A general method for synthesizing optically active, primary, secondary, and tertiary organofluorides was developed. This chiral pool synthesis utilized the skeleton of arabinose to generate diastereomerically pure 2-oxazolidinone-fused aziridines, which underwent ring opening with a fluoride anion. The adducts, polyoxygenated organofluorides, were useful precursors to various fluorinated compounds, such as fluorinated amino acids.

Protective effects of corni fructus extract in mice with potassium oxonate-induced hyperuricemia.

Corni fructus is consumed as food and herbal medicine in Chinese culture. Studies have revealed that corni fructus exhibits potent antioxidant activity; however, few studies have investigated the ability of corni fructus to lower uric acid concentrations. In this study, the xanthine oxidase (XO) inhibition and uric acid-lowering effect of corni fructus extract (CFE) were evaluated in mice with potassium oxonate-induced hyperuricemia. Hyperuricemia is a chronic disease prevalent worldwide and is associated with high recurrence rates. In addition, drugs used to treat hyperuricemia induce side effects that discourage patient compliance. Hyperuricemia induces metabolic imbalances resulting in accumulative uric acid deposition in the joints and soft tissues. Hyperuricemia not only induces gout but also interrupts hepatic and renal function, thereby trigging severe inflammation and various complications, including obesity, nonalcoholic fatty liver disease, diabetes, and metabolic diseases. In this study, the ethyl acetate fraction (EAF) of CFE resulted in yields of antioxidant photochemical components significantly higher than those of CFEs formed using other substances. The EAF of CFE exhibited high free radical scavenging activity and XO inhibition and effectively lowered uric acid concentrations in the animal model of chemically induced hyperuricemia. The results of this study can serve as a reference for the prevention of preclinical gout as well as for functional food research.

Cyano Derivatives of 7-Aminoquinoline That Are Highly Emissive in Water: Potential for Sensing Applications.

6-Cyano-7-aminoquinoline (6CN-7AQ) and 3-cyano-7-aminoquinoline (3CN-7AQ) were synthesized and found to exhibit intense emission with quantum yield as high as 63 % and 85 %, respectively, in water. Conversely, their derivatives 6-cyano-7-azidoquinoline (6CN-7N3 Q) and 3-cyano-7-azidoquinoline (3CN-7N3 Q) show virtually no emission, which makes them suitable to be used as recognition agents in azide reactions based on fluorescence recovery. Moreover, conjugation of 6CN-7AQ with a hydrophobic biomembrane-penetration peptide PFVYLI renders a nearly non-emissive 6CN-7AQ-PFVYLI composite, which can be digested by proteinase K, recovering the highly emissive 6CN-7AQ with ∼200-fold enhancement. The result provides an effective early confirmation for RT-qPCR in viral detection.

Effect of Quercetin on Dexamethasone-Induced C2C12 Skeletal Muscle Cell Injury.

Glucocorticoids are widely used anti-inflammatory drugs in clinical settings. However, they can induce skeletal muscle atrophy by reducing fiber cross-sectional area and myofibrillar protein content. Studies have proven that antioxidants can improve glucocorticoid-induced skeletal muscle atrophy. Quercetin is a potent antioxidant flavonoid widely distributed in fruits and vegetables and has shown protective effects against dexamethasone-induced skeletal muscle atrophy. In this study, we demonstrated that dexamethasone significantly inhibited cell growth and induced cell apoptosis by stimulating hydroxyl free radical production in C2C12 skeletal muscle cells. Our results evidenced that quercetin increased C2C12 skeletal cell viability and exerted antiapoptotic effects on dexamethasone-treated C2C12 cells by regulating mitochondrial membrane potential (ΔΨm) and reducing oxidative species. Quercetin can protect against dexamethasone-induced muscle atrophy by regulating the Bax/Bcl-2 ratio at the protein level and abnormal ΔΨm, which leads to the suppression of apoptosis.

Autophagy and apoptotic machinery caused by Polygonum cuspidatum extract in cisplatin­resistant human oral cancer CAR cells.

Polygonum cuspidatum (Hu Zhang) is a traditional Chinese medicine (TCM) and has been revealed to exert anticancer, anti­angiogenesis, anti­human immunodeficiency virus (HIV), anti­hepatitis B virus, anti­microbial, anti­inflammatory, and neuro­protective bio­activities. However, the effect of P. cuspidatum extract (PCE) on drug­resistant human oral cancer cells regarding cell death is not fully understood yet. The present study was undertaken to explore the induction of autophagic and apoptotic cell death and to investigate their underlying molecular mechanisms in PCE­treated cisplatin­resistant human oral cancer CAR cells. Our results revealed that PCE was determined via HPLC analytic method, and it was revealed that resveratrol may be a major compound in PCE. The data also demonstrated that PCE reduced CAR cell viability in a concentration­ and time­dependent response via an MTT assay. PCE had an extremely low toxicity in human normal gingival fibroblasts (HGF). Autophagic and apoptotic cell death was found after PCE treatment by morphological determination. PCE was revealed to induce autophagy as determined using acridine orange (AO), LC3­GFP, monodansylcadaverine (MDC) and LysoTracker Red staining in CAR cells. In addition, PCE was revealed to induce apoptosis in CAR cells via 4',6­diamidino­2­phenylindole (DAPI)/terminal deoxynucleotidyl transferase dUTP nick­end labeling (TUNEL) double staining. PCE significantly stimulated caspase­9 and ­3 activities as revealed using caspase activity assays. PCE markedly increased the protein levels of Atg5, Atg7, Atg12, Beclin­1, LC3, Bax and cleaved caspase­3, while it decreased the protein expression of Bcl­2 in CAR cells as determined by western blotting. In conclusion, our findings are the first to suggest that PCE may be potentially efficacious for the treatment of cisplatin­resistant human oral cancer.

Quantitative assessment of hepatic fat of intact liver tissues with coherent anti-stokes Raman scattering microscopy.

A fatty liver might progress from being a benign fatty liver, to steatohepatitis, cirrhosis, or even hepatocellular carcinoma. The great prevalence and severe outcome have warranted much investigation of the pathology and the development of effective therapies, which involve animal studies requiring critical evaluation of the hepatic fatty change. Histological examination and wet chemical analysis of liver biopsy specimens are generally employed for this purpose despite numerous procedures being involved. Using coherent anti-Stokes Raman scattering (CARS) microscopy, we have demonstrated the specific imaging of fat droplets in intact liver tissues and extracted the hepatic fat content through image analysis while eliminating laborious procedures required by traditional histopathological examination. The content of hepatic fat measured with CARS imaging was correlated strongly with that determined by biochemical analysis (R(2) = 0.89) over a pathologically significant range of the hepatic fat (from 2% to 20% of the total mass of tissue). Our work validates the quantitative assessment of fat in intact tissue through the use of CARS microscopy. When combined with the increasingly diverse animal models of diseases related to metabolic disorders of lipids, our approach is extensible to enable acquiring important insight into the genetic, environmental, and dietary factors affecting the uptake and accumulation of fat within tissues.

Integrated multiple multi-photon imaging and Raman spectroscopy for characterizing structure-constituent correlation of tissues.

Histopathological imaging of tissues often requires extensive sample preparation including fixation and staining in order to highlight characteristic alterations associated with diseases. Herein, we report an integrated spectro-microscopy approach based on a combination of multi-modal multi-photon imaging and Raman micro-spectroscopy and demonstrate label-free characterization of the structure-constituent correlation of porcine skin. The multi-modal imaging allows the visualization of dermatological features whereas Raman micro-spectroscopy enables the identification of their 'molecular fingerprints'. By obtaining both structural and molecular-level information of tissue constituents, this integrated approach can offer new insight into the patho-physiological status of tissues.