Eleven authenticated botanicals used in the traditional Chinese medicine Huo-Luo-Xiao-Ling Dan were screened for ligands to cyclooxygenase (COX) using pulsed ultrafiltration liquid chromatography-mass spectrometry, and a mass spectrometry-based enzyme assay was used to determine the concentration of each of 17 ligands that inhibited COX-1 or COX-2 by 50% (IC 50 ). Acetyl-11-keto-β-boswellic -boswellic acid, acid, acetyl-α-boswellic acid, acetyl-β-boswellic acid, and betulinic acid were COX-1 selective inhibitors with IC 50 values of approximately 10 μM. Senkyunolide O and cryptotanshinone were COX-2 selective inhibitors with IC 50 values of 5 and 22 μM, respectively. Roburic acid and phenethyl-trans-ferulate inhibited COX
Bacillus subtilis strain B154, isolated from Agaricus bisporus mushroom 12 compost infected by red bread mold, exhibited antagonistic activities against Neurospora 13 sitophila. Antifungal activity against phytopathogenic fungi was also observed. The 14 maximum antifungal activity was reached during the stationary phase. This antifungal 15 activity was stable over a wide pH and temperature range, and was not affected by 16proteases. Assay of antifungal activity in vitro indicated that a purified antifungal 17 substance could strongly inhibit mycelia growth and spore germination of N. sitophila. In 18 addition, treatment with strain B154 in A. bisporus mushroom compost infected with N. 19 sitophila significantly increased the yield of bisporus mushrooms. Ultraviolet scan 20 spectroscopy, tricine sodium dodecyl sulfate-polyacrylamide gel electrophoresis 21 (tricine-SDS-PAGE), matrix-associated laser desorption ionization time of flight mass 22 spectrometry (MALDI-TOF-MS), and electrospray ionization tandem mass spectrometry 23 (ESI-MS/MS) analyses revealed a molecular weight consistent with 1498.7633 Da. The 24 antifungal compound might belong to a new type of lipopeptide fengycin. 25
Vesicular monoamine transporter 2 (VMAT2) is responsible for sequestering cytosolically toxic dopamine into intracellular secretory vesicles. Animal genetic studies have suggested that reduced VMAT2 activity contributes to the genetic etiology of Parkinson's disease (PD), but this role has not been established in humans. Based on human genetic association and meta-analysis, we first confirm the human VMAT2 (hVMAT2 or SLC18A2) promoter as a risk factor for PD in both family and unrelated US white people: marker rs363324 at -11.5 kb in the hVMAT2 promoter is reproducibly associated with PD in a cohort of nuclear families (p = 0.04506 in early-onset PD) and 3 unrelated US white people (meta-analysis p = 0.01879). In SH-SY5Y cells, low activity-associated hVMAT2 promoter confers high methylpiperidinopyrazole iodide cytotoxicity, which is likely attributed to functional polymorphisms bound by nuclear proteins. Interestingly, treatments with the dopamine neuron-protecting agent puerarin upregulates the promoter activity in a haplotype- and cell line-dependent manner. These pharmacogenetic findings suggest that hVMAT2 could be a risk factor and imply it as a target of genetic medications for PD.
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