Protective effects of ß- nicotinamide adenine dinucleotide against motor deficits and dopaminergic neuronal damage in a mouse model of Parkinson's disease.

The level of nicotinamide adenine dinucleotide (NAD) decreases in Parkinson's disease (PD), and its reduction has been reported to be involved in many age-associated neurodegenerative pathologies. Thus, we investigated whether NAD replenishment is beneficial in a 6-hydroxydopamine (6-OHDA)-induced mouse model of PD. Preinjection with NAD in the striatum ameliorated motor deficits and dopaminergic neuronal damage in the substantia nigra and striatum of a mouse model of PD. Moreover, preincubation with NAD protected PC12 cells against the loss of cell viability, morphological damage, oxidative stress and mitochondrial dysfunction caused by 6-OHDA. These results add credence to the beneficial role of NAD against parkinsonian neurodegeneration in mouse models of PD, provide evidence for the potential of NAD for the prevention of PD, and suggest that NAD prevents pathological changes in PD via decreasing mitochondrial dysfunctions.

Seasonal and tissue age influences on endophytic fungi of Pinus tabulaeformis (Pinaceae) in the Dongling Mountains, Beijing.

Endophytic fungi associated with Pinus tabulaeformis Carr. were investigated in the Dongling Mountains of Beijing. A total of 16,200 tissue segments of P. tabulaeformis from four sample collections were processed, and 10,659 fungal isolates were recovered. The overall colonization and isolation rates of endophytic fungi from high to low were spring > winter > autumn > summer and in different tissues were bark > needle > xylem, irrespective of sampling seasons. The colonization rates of endophytic fungi of needles increased with age in the four sample collections. There were no significant differences of the colonization rates of endophytic fungi among 1-, 2-, and 3-year-old bark and xylem, except for significantly lower colonization rates in 1-year-old bark than in 2- and 3-year-old bark in summer. A similar trend of the isolation rates of endophytic fungi occurred. A total of 24 fungal taxa were recorded, of these five taxa Alternaria alternata, Leptostroma sp., Pestalotiopsis besseyi, Phoma lingam, and Phomopsis archeri, were consistently isolated as the common fungi in each sample collection. Our results suggest that some fungi show a certain degree of tissue recurrence or specificity, and the composition of endophytic assemblages is not conspicuously influenced by the seasonal factor.

Annonaceous acetogenin mimics bearing a terminal lactam and their cytotoxicity against cancer cells.

Annonaceous acetogenins are a large class of naturally occurring polyketides exhibiting potent anticancer activities. Based on our previous discovery of AA005, a multi-ether mimic of natural acetogenins having potent antitumor activities and significant selectivity between normal cells and cancer cells, a new series of mimics containing a terminal lactam were designed, synthesized and evaluated. Bioactivity study against cancer cells shows that the N-methylated lactam-containing compounds 3, 4, and 5 exhibit comparable potencies to that of AA005, as well as the similar selectivity to cancer cells. Hydrocarbon-length effects of N-alkyl were further explored through synthesizing derivatives 24-26, and application of this derivation protocol to the fluorescent labeling was also investigated.

Induction of cell death of gastric cancer cells by a modified compound of the annonaceous acetogenin family.

Annonaceous acetogenins are a family of natural products with antitumor activities. The polyether mimic AA005 has been synthesized. The cytotoxic mechanism of AA005 was investigated. It was found that AA005 can induce the cell death of gastric tumor cells. Most AA005-induced cell death is due to necrosis but partial and p53-independent apoptosis is also detected. An expanded study with gastric tumor cells and a cell-free system indicates that AA005 affects NADH:ubiquinone oxidoreductase (complex I; NADH=nicotinamide adenine dinucleotide, reduced form) in the mitochondrial electron transport system. These results show for the first time that the polyether mimic AA005 acts on the same biological target as the natural annonaceous acetogenins.