Yulin Deng

DNA methylation, a hand behind neurodegenerative diseases

Epigenetic alterations represent a sort of functional modifications related to the genome that are not responsible for changes in the nucleotide sequence. DNA methylation is one of such epigenetic modifications that have been studied intensively for the past several decades. The transfer of a methyl group to the 5 position of a cytosine is the key feature of DNA methylation. A simple change as such can be caused by a variety of factors, which can be the cause of many serious diseases including several neurodegenerative diseases. In this review, we have reviewed and summarized recent progress regarding DNA methylation in four major neurodegenerative diseases: Alzheimers disease (AD), Parkinsons disease (PD), Huntingtons disease (HD), and amyotrophic lateral sclerosis (ALS). The studies of these four major neurodegenerative diseases conclude the strong suggestion of the important role DNA methylation plays in these diseases. However, each of these diseases has not yet been understood completely as details in some areas remain unclear, and will be investigated in future studies. We hope this review can provide new insights into the understanding of neurodegenerative diseases from the epigenetic perspective.

A Strategy for Precise and Large Scale Identification of Core Fucosylated Glycoproteins

Core fucosylation (CF) patterns of some glycoproteins are more sensitive and specific than evaluation of their total respective protein levels for diagnosis of many diseases, such as cancers. Global profiling and quantitative characterization of CF glycoproteins may reveal potent biomarkers for clinical applications. However, current techniques are unable to reveal CF glycoproteins precisely on a large scale. Here we developed a robust strategy that integrates molecular weight cutoff, neutral loss-dependent MS3, database-independent candidate spectrum filtering, and optimization to effectively identify CF glycoproteins. The rationale for spectrum treatment was innovatively based on computation of the mass distribution in spectra of CF glycopeptides. The efficacy of this strategy was demonstrated by implementation for plasma from healthy subjects and subjects with hepatocellular carcinoma. Over 100 CF glycoproteins and CF sites were identified, and over 10,000 mass spectra of CF glycopeptide were found. The scale of identification results indicates great progress for finding biomarkers with a particular and attractive prospect, and the candidate spectra will be a useful resource for the improvement of database searching methods for glycopeptides.

Chromatographic fingerprint analysis of Cephalotaxus sinensis from various sources by high-performance liquid chromatography-diodearray detection-electrospray ionization-tandem mass spectrometry

Selective and efficient analytical methods are required not only for quality assurance but also for authentication of Chinese herbal medicine. A simple, rapid and valid fingerprint method has been first carried out for the quality control of Cephalotaxus sinensis by using high-performance liquid chromatography (HPLC) coupled with photodiode array detection (DAD) and electrospray ionisation-tandem mass spectrometry (ESI-MS). The characteristic analytical fingerprints of this plant extract showed 18 common peaks, and out of these, 10 compounds involving 2 new compounds were identified by comparing the retention time, UV and ESI-MS/MS spectrum of each standard with those of each peak separated by on-line HPLC-DAD-MS/MS. Moreover, the effects of collecting locations, harvesting time, storage time, drying methods, and medicinal portions on herbal chromatographic fingerprints were examined by similarity analysis and principal component analysis (PCA) along with markers. Using the reference fingerprint along with markers, the best harvesting time, cultivation location and medicinal part were determined. The results obtained suggest that the chromatographic fingerprint combining similarity evaluation and PCA along with markers or pharmacologically active constituents can efficiently identify raw herb of Cephalotaxus sinensis from different sources, which provide helpful clues to the study of plants secondary metabolites and benefit quality control.

Reduction of nitro phenols using nitroreductase from E. coli in the presence of NADH.

The reductions of nitrophenols catalyzed by nitroreductase from E. coli in the presence of NADH were investigated in this paper. 4-Aminophenol and 4-hydroxylaminophenol were found in the reductive products of 4-nitrophenol and the maximum reductive ratio was about 83.49% when the reaction time was 70 min; 4,6-dinitro-2-pimelie kelone was found in the reductive products of 2,4-dinitrophenol and the maximum reductive ratio was about 75.28% when the reaction time was 80 min; 2,4-dinitrophenol and 4,6-dinitro-2-pimelie kelone were found in the reductive products of 2,4,6-trinitrophenol and the maximum reductive ratio was about 62.08% when the reaction time was 100 min. The similar reductive ratios of nitrophenols were obtained under aerobic and anaerobic conditions. The results indicated that nitroreductase was an oxygen-insensitive enzyme.

Potential Therapeutic Strategies for Alzheimer’s Disease Targeting or Beyond β-Amyloid: Insights from Clinical Trials

Alzheimers disease (AD) is a progressive neurodegenerative disorder with two hallmarks: β-amyloid plagues and neurofibrillary tangles. It is one of the most alarming illnesses to elderly people. No effective drugs and therapies have been developed, while mechanism-based explorations of therapeutic approaches have been intensively investigated. Outcomes of clinical trials suggested several pitfalls in the choice of biomarkers, development of drug candidates, and interaction of drug-targeted molecules; however, they also aroused concerns on the potential deficiency in our understanding of pathogenesis of AD, and ultimately stimulated the advent of novel drug targets tests. The anticipated increase of AD patients in next few decades makes development of better therapy an urgent issue. Here we attempt to summarize and compare putative therapeutic strategies that have completed clinical trials or are currently being tested from various perspectives to provide insights for treatments of Alzheimers disease.

Dragon's Blood extract has antithrombotic properties, affecting platelet aggregation functions and anticoagulation activities.

ETHNOPHARMACOLOGICAL RELEVANCE Dragons Blood from Dracaena cochinchinensis (Lour.) S.C. Chen (Yunnan, China), as a traditional Chinese medicinal herb, was shown to have certain antithrombotic effects. A new preparation process was used to extract effective components from Dragons Blood. A 95% ethanol extract A (EA) and a precipitate B (PB) fraction were obtained and compared. Reliability of the preparation process was validated by pharmacodynamic experiments. MATERIALS AND METHODS A rat/mouse thrombosis and blood stasis model was developed for this study, and EA and PB effects on thrombosis, platelet functions and blood coagulation activities were analyzed. RESULTS It was observed that the EA fraction had significantly better inhibitory effects than the PB fraction on thrombosis (p<0.05), platelet aggregation function (p<0.01) and anticoagulation activity (p<0.05-0.01). CONCLUSIONS The results obtained here showed that EA fraction from Dragons Blood contained pharmacologically effective compounds with antithrombotic effects, partially improving platelet function and anticoagulation activity.

Hypoglycemic effect of Belamcanda chinensis leaf extract in normal and STZ-induced diabetic rats and its potential active faction.

Belamcanda chinensis (Iridaceae) belongs to the family of iridaceae and its rhizoma has been widely used for the treatment of throat ailment. Here we report a new pharmacological activity of B. chinensis leaf extract (BCL), that is, the hypoglycemic effect in normal and STZ-induced diabetic rats. Animals either healthy or STZ-induced diabetic show significantly lowered fasting blood glucose levels after treatment with BCL. The serum insulin concentration in normal rats is also enhanced. Additionally, the increase in blood glucose levels after administration of various carbohydrates in normal rats is significantly decreased and the oral glucose tolerance (OGTT) of STZ-induced diabetic rats is largely improved by BCL treatment. However, co-administration of BCL with Nifedipine, a Ca(2+) ion channel blocker, or Nicorandil, an ATP-sensitive K(+) ion channel opener thoroughly abolishes the hypoglycemic effect of BCL. HPLC analysis and compound identification showed that several isoflavone glycosides with antidiabetic activities were contained in BCL while pharmacological experiment showed that the polysaccharide fraction of BCL had no significant hypoglycemic effect on normal rats. Therefore, the isoflavone glycosides but not polysaccharides might be the active fraction of BCL in diabetes treatment.

Appraisal of antinociceptive and anti-inflammatory potential of extract and fractions from the leaves of Torreya grandis Fort Ex. Lindl

Torreya grandis (Taxaceae) was studied for antinociceptive and anti-inflammatory effects. Leaves were extracted with 80% ethanol at 80 degrees C for 3h and fractionated with petroleum ether, chloroform, ethylacetate and n-butanol. The aqueous ethanolic extract (aq.EE), ethylacetate fraction (EaF) and butanol fraction (BtF) at the doses of (100 and 200mg/kg, i.g.) body weight were used for study. Evaluation of antinociceptive activity was carried out by acetic acid-induced writhing response and formalin-induced paw licking time in the first and second phases of mice. The paw edema induced by formalin- and xylene-induced ear edema were used to assess anti-inflammatory activity. It was found that Torreya grandis extract and fractions at the doses of (100 and 200mg/kg, i.g.) were significantly attenuated the writhing responses induced by acetic acid and second phase of pain response induced by subplantar injection of formalin in mice. In addition, these extract and fractions inhibiting the formaldehyde-induced arthritis as well as xylene-induces edema prolifically. From acute oral toxicity studies no mortality was pragmatic even at highest dose (2500 mg/kg, i.g.). Furthermore, our phytochemical studies indicated that the aq. ethanolic extract of leaves contains alkaloids, flavonoids, tannins, terpenoids and saponins. The results provide justification for the folkloric uses of Torreya grandis in the treatment of analgesic and inflammatory-based diseases across the China.

Switchable boronate affinity materials for thermally modulated capture, separation and enrichment of cis-diol biomolecules

A new thermoresponsive boronate affinity chromatographic material, P(N-isopropylacrylamide-4-vinylphenylboronic acid) P(NIPAAm-co-VPBA) grafted silica featuring a thermally switchable property, was prepared and successfully employed for the specific capture–release of cis-diol biomolecules with simpler adjustment to the temperature instead of the conventional need to change the pH of the mobile phase.

Lrrk2 interaction with α-synuclein in diffuse Lewy body disease

Mutations of the leucine-rich repeat kinase 2 (LRRK2) gene are the leading cause of genetically inherited Parkinsons disease (PD) and its more severe variant diffuse Lewy body disease (DLB). Pathological mutations in Lrrk2 are autosomal dominant, suggesting a gain of function. Mutations in alpha-synuclein also produce autosomal dominant disease. Here we report an interaction between Lrrk2 and alpha-synuclein in a series of diffuse Lewy body (DLB) cases and in an oxidative stress cell based assay. All five cases of DLB, but none of five controls, showed co-immunoprecipitation of Lrrk2 and alpha-synuclein in soluble brain extracts. Colocalization was also found in pathological deposits in DLB postmortem brains by double immunostaining. In HEK cells transfected simultaneously with plasmids expressing Lrrk2 and alpha-synuclein, co-immunoprecipitation of Lrrk2 and alpha-synuclein was detected when they were exposed to oxidative stress by H(2)O(2). Taken together, these results suggest the possibility that in PD and related synucleinopathies, oxidative stress upregulates alpha-syn and Lrrk2 expression, paving the way for pathological interactions. New therapeutic approaches to PD and the synucleinopathies may result from limiting the interaction between Lrrk2 and alpha-synuclein.