New Isopropyl Chromone and Flavanone Glucoside Compounds from the Leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry and Their Inhibition of Nitric Oxide Production

A new isopropyl chromone ( 1 ) and a new flavanone glucoside ( 2 ) together with eleven known compounds ( 3–13 ) were isolated from the leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry. Their structures were elucidated as 5,7-dihydroxy-2-isopropyl-6,8-dimethyl-4H-chromen-4-one ( 1 ), 5,7-dihydroxyflavanone 7-O-β-D-(6′′-O-galloylglucopyranoside) ( 2 ), strobopinin ( 3 ), demethoxymatteucinol ( 4 ), pinocembrin-7-O-β-D-glucopyranoside ( 5 ), (2S)-hydroxynaringenin-7-O-β-D-glucopyranoside ( 6 ), afzelin ( 7 ), quercetin ( 8 ), kaplanin ( 9 ), endoperoxide G3 ( 10 ), grasshopper ( 11 ), vomifoliol ( 12 ), litseagermacrane ( 13 ) by the analysis of HR-ESI-MS, NMR, and CD spectral data. Compounds 1 , 2 , 5 , 6 and 10 inhibited NO production on LPS-activated RAW264.7 cells with IC₅₀ values of 12.28±1.15, 8.52±1.62, 7.68±0.87, 9.67±0.57, and 6.69±0.34 μM, respectively, while the IC₅₀ values of the other compounds ranging from 33.38±0.78 to 86.51±2.98 μM, compared to that of the positive control, N^G-monomethyl-L-arginine acetate (L-NMMA) with an IC₅₀ value of 32.50±1.00 μM.     

Novel (E)-3-(3-Oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides as Histone Deacetylase Inhibitors: Design,Synthesis and Bioevaluation

Herein, we report the design, synthesis and evaluation of novel (E)-3-(3-oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides ( 4 a – i , 7 a – g ) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC-3, prostate; NCI−H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a – i bearing the alkyl substituents seemed to be less potent than the benzyl-containing compounds 7 a – g in all biological assays. Compounds 7 e – f were found to be the most active HDAC inhibitors with IC₅₀ of 1.498±0.020 μM and 1.794±0.159 μM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC₅₀ values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity.     

Nitrate reductase deficient cell lines from haploid protoplast cultures ofNicotiana plumbaginifolia

Summary Nitrate reductase deficient (NR^-) cell lines were selected indirectly by their resistance to 40 mM chlorate in protoplast cultures of haploidNicotiana plumbaginifolia. Frequency of the chlorate resistant clones was 5.8×10^-5 in non-mutagenized cultures, which could be increased up to 25 times by treatment with N-ethyl-N-nitrosourea (NEU) or gamma irradiation.Out of 136 chlorate resistant clones 29 were fully deficient in nitrate reductase. The rest of the clones contained decreased or normal levels of NR activity (91 and 16 clones, respectively).Further characterization was carried out in 9 clones which were fully deficient in NR and in 2 clones containing resisdual (0–5%) NR activity. The clones were tentatively classified as defective in the apoenzyme (7 clones including the 2 with residual NR activity) or the cofactor (4 clones) of NR by the xanthine dehydrogenase activity and in vitro enzyme complementation. The cofactor defectives could be further classified into two groups. In one of these (2 clones) the NR activity could be partially restored by unphysiologically high (0.2–1 mM) molybdate in the culture medium. The other two are new types which have not been described in flowering plants.Plant regeneration was obtained only in the clones which contained residual NR activity.     

Monitoring occurrence,extinction, and colonization probabilities for gibbon populations

All gibbon species (Family: Hylobatidae) are considered threatened with extinction and recognized on the International Union for Conservation of Nature Red List of Threatened Species. Because gibbons are one of the most threatened families of primates, monitoring their status is now critically important. Long-term monitoring programs applying occupancy approaches, in addition to assessing occurrence probability, improves understanding of other population parameters such as site extinction or colonization probabilities, which elucidate temporal and spatial changes and are therefore important for guiding conservation efforts. In this study, we used multiple season occupancy models to monitor occurrence, extinction, and colonization probabilities for northern yellow-cheeked crested gibbon Nomascus annamensis in three adjacent protected areas in the Central Annamites mountain range, Vietnam. We collected data at 30 listening posts in 2012, 2014, and 2016 using the auditory point count method. Occurrence probabilities were highest in 2012 (0.74, confidence interval [CI]: 0.56–0.87) but slightly lower in 2014 (0.66, CI: 0.51–0.79) and 2016 (0.67, CI: 0.49–0.81). Extinction probabilities during the 2012–2014 and 2014–2016 intervals were 0.26 (0.14–0.44) and 0.25 (0.12–0.44), respectively. Colonization probabilities during 2012–2014 were 0.44 (0.19–0.73) and between 2014 and 2016 was 0.51 (0.26–0.75). Although local site extinctions have occurred, high recolonization probability helped to replenish the unoccupied sites and kept the occurrence probability stable. Long-term monitoring programs which use occurrence probability alone might not fully reveal the true dynamics of gibbon populations. We strongly recommend including multiple season occupancy models to monitor occurrence, extinction, and colonization probabilities in long-term gibbon monitoring programs.     

Soil and root nutrient chemistry structure root-associated fungal assemblages in temperate forests

Root-associated fungi (RAF) link nutrient fluxes between soil and roots and thus play important roles in ecosystem functioning. To enhance our understanding of the factors that control RAF, we fitted statistical models to explain variation in RAF community structure using data from 150 temperate forest sites covering a broad range of environmental conditions and chemical root traits. We found that variation in RAF communities was related to both root traits (e.g., cations, carbohydrates, NO₃⁻) and soil properties (pH, cations, moisture, C/N). The identified drivers were the combined result of distinct response patterns of fungal taxa (determined at the rank of orders) to biotic and abiotic factors. Our results support that RAF community variation is related to evolutionary adaptedness of fungal lineages and consequently, drivers of RAF communities are context-dependent.     

From geochemical background determination to pollution assessment of heavy metals in sediments and soils

Establishing geochemical background concentrations to distinguish the natural background from anthropogenic concentrations of heavy metals in sediments and soils is necessary to develop guidelines for environmental legislation. Due to the fact that the background concentrations strongly depend on geological characteristics such as mineral composition, grain size distribution and organic matter content, several normalization methods have been developed. Empirical (geochemical), theoretical (statistical) and integrated methods (combining both empirical and theoretical methods) are the main approaches described in literature for determination of geochemical background concentrations. In this review paper, the different approaches as well as the main normalization methods for heavy metal concentrations in sediments and soils will be discussed. Both geochemical background concentrations and added risk level (maximum permissible addition) should be taken into account for setting up legal threshold limits. Moreover, different approaches to evaluate the pollution status of heavy metals in sediments and soils, from Sediment/Soil Quality Guidelines to quantitative indices (Geo-accumulation Index-I_geo, Enrichment Factor-EF, Pollution Load Index-PLI and Risk assessment Code-RAC) will be presented. Although guidelines to establish whether a sediment or soil is polluted or not are generally only related to total metal concentrations, the available/reactive pool i.e., availability/reactivity of metals should be taken into account for sediment/soil pollution assessment.     

Diversity of Plant Methionine Sulfoxide Reductases B and Evolution of a Form Specific for Free Methionine Sulfoxide

Methionine can be reversibly oxidized to methionine sulfoxide (MetO) under physiological conditions. Organisms evolved two distinct methionine sulfoxide reductase families (MSRA & MSRB) to repair oxidized methionine residues. We found that 5 MSRB genes exist in the soybean genome, including GmMSRB1 and two segmentally duplicated gene pairs (GmMSRB2 and GmMSRB5, GmMSRB3 and GmMSRB4). GmMSRB2 and GmMSRB4 proteins showed MSRB activity toward protein-based MetO with either DTT or thioredoxin (TRX) as reductants, whereas GmMSRB1 was active only with DTT. GmMSRB2 had a typical MSRB mechanism with Cys121 and Cys 68 as catalytic and resolving residues, respectively. Surprisingly, this enzyme also possessed the MSRB activity toward free Met-R-O with kinetic parameters similar to those reported for fRMSR from Escherichia coli, an enzyme specific for free Met-R-O. Overexpression of GmMSRB2 or GmMSRB4 in the yeast cytosol supported the growth of the triple MSRA/MSRB/fRMSR (Δ3MSRs) mutant on MetO and protected cells against H₂O₂-induced stress. Taken together, our data reveal an unexpected diversity of MSRBs in plants and indicate that, in contrast to mammals that cannot reduce free Met-R-O and microorganisms that use fRMSR for this purpose, plants evolved MSRBs for the reduction of both free and protein-based MetO.     

Role of Insulin Resistance in the Alzheimer's Disease Progression

Recent studies continue to find evidence linking Type 2 diabetes (T2D) with Alzheimer's disease (AD), the most common cause of dementia, a general term for memory loss and other cognitive abilities serious enough to interfere with daily life. Insulin resistance or dysfunction of insulin signaling is a universal feature of T2D, the main culprit for altered glucose metabolism and its interdependence on cell death pathways, forming the basis of linking T2D with AD as it may exacerbate Aβ accumulation, tau hyperphosphorylation and devastates glucose transportation, energy metabolism, hippocampal framework and promulgate inflammatory pathways. The current work demonstrates the basic mechanisms of the insulin resistance mediates dysregulation of bioenergetics and progress to AD as a mechanistic link between diabetes mellitus and AD. This work also aimed to provide a potential and feasible zone to succeed in the development of therapies in AD by enhanced hypometabolism and altered insulin signaling.