Structure-antioxidant and anti-tumor activity of Teucrium polium phytochemicals

Chemical characterization as well as antioxidant and anti-tumor activity are reported for isolated metabolites from Teucrium polium L. (Lamiaceae). Structures were identified using standard MS and NMR spectroscopic methods. Sesquiterpene absolute stereochemistry was determined based on a modified Mosher’s reaction. Biological activity was evaluated by a cupric reducing antioxidant capacity (CUPRAC) assay and select compounds screened for anti-tumor activity. (1R,4S,10R) 10,11-dimethyl-dicyclohex-5(6)-en-1,4-diol-7-one and (R)-mandelonitrile-β-laminaribioside, together with ten previously reported compounds were identified. Antioxidant versus tumor-inhibition relationships was examined.     

Law and ‘race’ in the citizenship spaces of Myanmar: spatial strategies and the political subjectivity of the Burmese Chinese

As Myanmar undergoes political and societal transition, observers are asking questions about citizenship and ethnic identity. How does one think about citizenship and people's negotiations with law in political-legal regimes that do not subscribe to liberal democratic norms? This paper investigates how law marginalizes the Burmese Chinese minority in Myanmar and the nature of their legal participation. Since law asserts cultural power impacting the way people think and behave, we engage with the concept of legal consciousness to understand how perceptions of legal vulnerability shape political subjectivity ambivalently. The paper highlights the spatial strategies and everyday practices that the Burmese Chinese deploy to navigate oppressive laws, but signals that internal social divisions and geopolitical considerations deter collective action towards rights assertion. It argues that studying the multiple sites and scales through which law is engaged contributes towards recovering citizenship aspirations where engagement with power and authority are articulated differently from Western norms.     

Design,synthesis, and evaluation of guanylhydrazones as potential inhibitors or reactivators of acetylcholinesterase

Analogs of pralidoxime, which is a commercial antidote for intoxication from neurotoxic organophosphorus compounds, were designed, synthesized, characterized, and tested as potential inhibitors or reactivators of acetylcholinesterase (AChE) using the Ellman’s test, nuclear magnetic resonance, and molecular modeling. These analogs include 1-methylpyridine-2-carboxaldehyde hydrazone, 1-methylpyridine-2-carboxaldehyde guanylhydrazone, and six other guanylhydrazones obtained from different benzaldehydes. The results indicate that all compounds are weak AChE reactivators but relatively good AChE inhibitors. The most effective AChE inhibitor discovered was the guanylhydrazone derived from 2,4-dinitrobenzaldehyde and was compared with tacrine, displaying similar activity to this reference material. These results indicate that guanylhydrazones as well as future similar derivatives may function as drugs for the treatment of Alzheimer's disease.     

Trinucleotide’s quadruplet symmetries and natural symmetry law of DNA creation ensuing Chargaff’s second parity rule

For almost 50 years the conclusive explanation of Chargaff’s second parity rule (CSPR), the equality of frequencies of nucleotides A=T and C=G or the equality of direct and reverse complement trinucleotides in the same DNA strand, has not been determined yet. Here, we relate CSPR to the interstrand mirror symmetry in 20 symbolic quadruplets of trinucleotides (direct, reverse complement, complement, and reverse) mapped to double-stranded genome. The symmetries of Q-box corresponding to quadruplets can be obtained as a consequence of Watson–Crick base pairing and CSPR together. Alternatively, assuming Natural symmetry law for DNA creation that each trinucleotide in one strand of DNA must simultaneously appear also in the opposite strand automatically leads to Q-box direct-reverse mirror symmetry which in conjunction with Watson–Crick base pairing generates CSPR. We demonstrate quadruplet’s symmetries in chromosomes of wide range of organisms, from Escherichia coli to Neanderthal and human genomes, introducing novel quadruplet-frequency histograms and 3D-diagrams with combined interstrand frequencies. These “landscapes” are mutually similar in all mammals, including extinct Neanderthals, and somewhat different in most of older species. In human chromosomes 1–12, and X, Y the “landscapes” are almost identical and slightly different in the remaining smaller and telocentric chromosomes. Quadruplet frequencies could provide a new robust tool for characterization and classification of genomes and their evolutionary trajectories.     

Water-soluble ferulic acid derivatives improve amyloid-β-induced neuronal cell death and dysmnesia through inhibition of amyloid-β aggregation

Ferulic acid (FA) has been reported to exhibit protective effects against amyloid-β (Aβ)-induced neurodegeneration in vitro and in vivo. Recently, we developed two water-soluble FA derivatives: 1-feruloyl glycerol and 1-feruloyl diglycerol. In this study, we examined the neuroprotective effects of these water-soluble FA derivatives on Aβ-induced neurodegeneration both in vitro and in vivo. FA and water-soluble FA derivatives inhibited Aβ aggregation and destabilized pre-aggregated Aβ to a similar extent. Furthermore, water-soluble FA derivatives, as well as FA, inhibited Aβ-induced neuronal cell death in cultured neuronal cells. In in vivo experiments, oral administration of water-soluble FA derivatives to mice improved Aβ-induced dysmnesia assessed by contextual fear conditioning test and protected hippocampal neurons against Aβ-induced neurotoxicity. This study provides useful evidence suggesting that water-soluble FA derivatives are expected to be effective neuroprotective agents.     

Intestinal immunostimulatory activity of neutral polysaccharide isolated from traditionally fermented Korean brown rice vinegar

In this study, diverse intestinal immunostimulatory activities were demonstrated for polysaccharides (KBV-CP) isolated from Korean brown rice vinegar. Monosaccharide composition analysis indicated that KBV-CP was composed mainly of neutral sugar units, primarily glucose and mannose. In vitro, KBV-CP significantly augmented the productions of immunoglobulin A (IgA) and IgA-related cytokines such as interleukin-6 (IL-6) and transforming growth factor-β (TGF-β) in a dose-dependent manner. Furthermore, results of an in vitro co-culture system of intestinal Caco-2 cells and RAW 264.7 macrophage cells suggested that KBV-CP is not only cytotoxic to Caco-2 cells but also capable of being transported across the small intestinal barrier. Oral administration of KBV-CP every other day for 20 days induced the IgA production by Peyer’s patch cells as well as in intestinal fluid and fecal extract. In addition, the production of IgA-related cytokines such as TGF-β and IL-6, and granulocyte macrophage colony-stimulating factor was triggered.     

湖南八面山银杉群落特征及其残遗性和保守性分析

为了解中国特有孑遗植物银杉( Cathaya argyrophylla Chun et Kuang)的生存现状,对位于湖南八面山脚盆辽的银杉+南方铁杉﹝Tsuga chinensis var. tchekiangensis ( Flous) Cheng et L. K. Fu﹞+甜槠﹝Castanopsis eyrei ( Champ.) Tutch.﹞-猴头杜鹃( Rhododendron simiarum Hance)群落进行调查,分析其群落特征及种群年龄结构,比较分布在不同区域的6个银杉群落中种子植物属的分布区类型及其相似性系数;在此基础上,讨论了银杉群落的残遗性特征。结果显示：脚盆辽银杉群落共有维管植物66种,包括蕨类植物4种和种子植物62种(裸子植物4种、被子植物58种);该群落乔木层的主要优势种为甜槠、猴头杜鹃、银杉和南方铁杉,重要值分别为13.12%、9.28%、8.86%和7.49%;该群落的Simpson和Shannon-Wiener多样性指数分别为0.94和3.20, Pielou均匀度指数Jsw和Jsi分别为0.81和0.92,说明该群落物种多样性偏低但物种分布均匀,与中亚热带山地的暖性针阔叶混交林特征一致。从生活型谱看,该群落中各频度百分比由高至低依次为A级、B级、C级、D级、E级,与Raunkiaer标准频度图谱基本一致,表明该群落整体上处于较为稳定的亚顶极状态。从银杉种群年龄结构看,种群中幼龄个体占一定比例,但80~180 a的中龄个体比例偏低;从该群落优势种的径级结构看,甜槠、猴头杜鹃和鹿角杜鹃( Rhododendron latoucheae Franch.)种群为增长型种群,而银杉、南方铁杉和福建柏﹝Fokienia hodginsii ( Dunn) Henry et Thomas﹞种群为衰退型种群。从脚盆辽银杉群落种子植物属的分布区类型看,温带分布型属占51.06%,略高于热带分布型属(占48.94%),说明该区域属于热带亚热带过渡区;除纬度外,海拔也能够在一定程度上影响其分布区类型组成。在处于粤北、粤桂山地和贵州高原3个植物区系亚地区的6个银杉群落中,种子植物属分布区类型的相似性系数为0.35~0.67,群落建群种所在属如铁杉属﹝Tsuga ( Endlicher) Carrière﹞、润楠属( Machilus Nees)、水青冈属( Fagus Linn.)和福建柏属( Fokienia Henry et Thomas)等在各群落间有相似性和共通性,且多为古老成分和孑遗成分,表明现存的银杉群落具有相近的变迁历史,分布地域具有明显的亚热带山地避难所特征,体现出其演替过程的残遗性和保守性。研究结果表明：在银杉群落中适度疏通林窗,降低林下郁闭度,有利于银杉幼树的生长,使银杉种群得到可持续更新和演替。     

8-Substituted 1,3-dimethyltetrahydropyrazino[2,1-f]purinediones: Water-soluble adenosine receptor antagonists and monoamine oxidase B inhibitors

Multitarget approaches, i.e., addressing two or more targets simultaneously with a therapeutic agent, are hypothesized to offer additive therapeutic benefit for the treatment of neurodegenerative diseases. Validated targets for the treatment of Parkinson’s disease are, among others, the A_2A adenosine receptor (AR) and the enzyme monoamine oxidase B (MAO-B). Additional blockade of brain A₁ ARs may also be beneficial. We recently described 8-benzyl-substituted tetrahydropyrazino[2,1-f]purinediones as a new lead structure for the development of such multi-target drugs. We have now designed a new series of tetrahydropyrazino[2,1-f]purinediones to extensively explore their structure–activity-relationships. Several compounds blocked human and rat A₁ and A_2AARs at similar concentrations representing dual A₁/A_2A antagonists with high selectivity versus the other AR subtypes. Among the best dual A₁/A_2AAR antagonists were 8-(3-(4-chlorophenyl)propyl)-1,3-dimethyl-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (41, K_i human A₁: 65.5 nM, A_2A: 230 nM; K_i rat A₁: 352 nM, A_2A: 316 nM) and 1,3-dimethyl-8-((2-(thiophen-2-yl)thiazol-4-yl)methyl)-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (57, K_i human A₁: 642 nM, A_2A: 203 nM; K_i rat A₁: 166 nM, A_2A: 121 nM). Compound 57 was found to be well water-soluble (0.7 mg/mL) at a physiological pH value of 7.4. One of the new compounds showed triple-target inhibition: (R)-1,3-dimethyl-8-(2,1,3,4-tetrahydronaphthalen-1-yl)-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione (49) was about equipotent at A₁ and A_2AARs and at MAO-B (K_i human A₁: 393 nM, human A_2A: 595 nM, IC₅₀ human MAO-B: 210 nM) thus allowing future in vivo explorations of the intended multi-target approach.     

Synthesis and evaluation of 6-(3-[18F]fluoro-2-hydroxypropyl)-substituted 2-pyridylbenzothiophenes and 2-pyridylbenzothiazoles as potential PET tracers for imaging Aβ plaques

3-[¹⁸F]Fluoro-2-hydroxypropyl substituted compounds were synthesized and evaluated as novel ¹⁸F-labeled PET tracers for imaging Aβ plaque in a living brain. All compounds exhibited high binding affinities toward the synthetic Aβ_1–42 aggregate and/or Alzheimer’s disease brain homogenate. In the microPET study with normal mice, the 3-[¹⁸F]fluoro-2-hydroxypropyl substituted compounds resulted in fast brain washout by reducing the lipophilicities of the compounds. Intriguingly, (S)-configured PET tracers, (S)-[¹⁸F]1b and (S)-[¹⁸F]1c, exhibited a 2.8 and 4.0-fold faster brain washout rate at a peak/30 min in the mouse brain than the corresponding (R)-configured PET tracers despite there being no meaningful difference in binding affinities toward Aβ plaque. A further evaluation of (S)-[¹⁸F]1c with healthy rhesus monkeys also revealed excellent clearance from the frontal cortex with ratios of 7.0, 16.0, 30.0 and 49.0 at a peak/30, 60, 90, and 120 min, respectively. These results suggest that (S)-[¹⁸F]1c may be a potential PET tracer for imaging Aβ plaque in a living brain.