Theory of pleiotropic action of biologically active compounds and medicines—Basic principles and practical application

This article represents the main positions of the theory of pleiotropic action of biologically active compounds (BACs) and medicines, which has been designed by the author based on her own experimental researches. The term “pleiotropy” means the ability of the BACs and medicines to implement more than one mechanism of action resulting in the specific biological (pharmacological) effect. The interaction of these mechanisms forms a distinct pattern of biological response (pleiotropic pattern), which reflects the change in his character with the increased dose (concentration)-dependent efficacy of BACs and medicines. The article consists of description of different pleiotropic patterns established in experiments on the model of reactive oxygen species (ROS) generation by macrophages dependent on activity of specialized enzyme called Nox2-NAD(P)H oxidase (Nox2, EC 1.6.3.1). Moreover, it consists of explanation of pharmacodynamic nature of pleiotropic patterns by means of application Chou-Talalay median effect equalization and combination index (CI) theory. The novel theory explains unsolved until now universal aspects of activity BACs and medicines, such as slope angles of “dose-effect” dependences in the conditions relevant in vivo, and it is of fundamental interest. However, it has applications in experimental pharmacology, as it allows defining the choice of the individual compounds and combinations, modulating the trust effect selectively and efficiently. This knowledge opens up new approaches to medicines discovery and evaluation, their rational dosing and combining.

2-芳基-5-(5-苯基-2H-四唑-2-亚甲基)-1,3,4-噁二唑类化合物的研究

作者曾研究2-芳基-5-(2-苯基-4-喹啉基)-1,3,4-噁二唑类衍生物,并发现它们具有促进小麦发芽生长的功效。

Recent Progress,Challenges,and Prospects in Two‑Dimensional Photo‑Catalyst Materials and Environmental Remediation

The successful photo-catalyst library gives significant information on feature that affects photo-catalytic performance and proposes new materials.Competency is considerably significant to form multi-functional photo-catalysts with flexible characteristics.Since recently,two-dimensional materials(2DMs)gained much attention from researchers,due to their unique thickness-dependent uses,mainly for photo-catalytic,outstanding chemical and physical properties.Photo-catalytic water splitting and hydrogen(H2)evolution by plentiful compounds as electron(e−)donors is estimated to participate in constructing clean method for solar H2-formation.Heterogeneous photocatalysis received much research attention caused by their applications to tackle numerous energy and environmental issues.This broad review explains progress regarding 2DMs,significance in structure,and catalytic results.We will discuss in detail current progresses of approaches for adjusting 2DMs-based photo-catalysts to assess their photo-activity including doping,hetero-structure scheme,and functional formation assembly.Suggested plans,e.g.,doping and sensitization of semiconducting 2DMs,increasing electrical conductance,improving catalytic active sites,strengthening interface coupling in semiconductors(SCs)2DMs,forming nano-structures,building multi-junction nano-composites,increasing photo-stability of SCs,and using combined results of adapted approaches,are summed up.Hence,to further improve 2DMs photo-catalyst properties,hetero-structure design-based 2DMs’photo-catalyst basic mechanism is also reviewed.

Catalyst Free One-Pot Synthesis of Chromeno Quinolines and Their Antibacterial Activity

An efficient greener one pot synthesis of dimethyl-dihydro-7H-chromeno[3, 2-h]quinolin-8(9H)-one derivatives has been synthesized through cyclization of aromatic aldehyde, dimidone and 8-hydroxy-quinoline through one-pot condensation method is described. The synthesized compounds are screened for further biological activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Bacillus using cut plate method and disc diffusion method.

不同时间脱蛋白异种骨抗原性和生物力学相关性研究

目的 研究脱脂脱蛋白处理异种骨的抗原性和生物力学强度与 30 %H2 O2 处理时间的关系 ,选择最佳处理时间 ,使骨的抗原性降至最低 ,又尽可能地保留其生物力学强度。方法 将牛松质骨脱脂脱蛋白处理 ,30 %H2 O2 浸泡时间分别为 0h ,8h ,16h和 48h。进行淋巴细胞转化实验、组织学观察和生物力学测定。结果 30 %H2 O2 浸泡 8h组的淋巴细胞转化实验刺激指数和局部组织学反应明显低于 0h组 ,与 16h和 48h组相同 ;30 %H2 O2 浸泡 8h组的弹性模量明显低于 0h组 ,但显著高于16h和 48h组。结论 牛松质骨经 30 %H2 O2 处理 8h为最佳处理时间 ,可使抗原性降至最低 ,最大程度上保留生物力学强度。

Significance of the carbon sink produced by H_2O–carbonate–CO_2–aquatic phototroph interaction on land

One of the most important questions in the science of global change is how to balance the atmospheric CO2 budget. There is a large terrestrial missing carbon sink amounting to about one billion tonnes of carbon per annum. The locations, magnitudes, variations, and mechanisms responsible for this terrestrial missing carbon sink are uncertain and the focus of much continuing debate. Although the positive feedback between global change and silicate chemical weathering is used in geochemical models of atmospheric CO2, this feedback is believed to operate over a long timescale and is therefore generally left out of the current discussion of human impact upon the carbon budget. Here, we show, by synthesizing recent findings in rock weathering research and studies into biological carbon pump effects in surface aquatic ecosystems, that the carbon sink produced by carbonate weathering based on the H2O- carbonate-CO2-aquatic phototroph interaction on land not only totals half a billion tonnes per annum, but also displays a significant increasing trend under the influence of global warming and land use change; thus, it needs to be included in the global carbon budget.

A New Approach to the Asymmetric Reaction of the Chiron 5-L-Menthyloxy-2(5H)-furanones with Horner-Emmons Reagent

The asymmetric reaction of the chiron 2(5H)-furanones (4a-4c) with the Homer-Emmons reagents (5a-5b) has been investigated. The newly chiral organophosphorus derivatives 6 and 7 were obtained using the phosphoryl-stabilized carbanion as a building block in DMSO under mild conditions. Through the asymmetric introduction, the Horner-Emmons reagent could be transformed to a chiral building block to afford the novel functionalized phosphorus derivatives. The structures of the synthesized compounds 6 and 7 were identified on the basis of their elementary and spectroscopic data, such as IR, 1H NMR, 13C NMR, MS and X-ray crystallography. These results provided a valuable approach to the synthesis of potentially interesting chiral organophosphorus derivatives and probing their biological activities.

Sensitivity of MCF-7 mammosphere CSCs to neutron radiation

Aim:Cancer stem cells(CSCs)are highly resistant to chemotherapy andγ-irradiation.Neutrons have a high linear energy transfer,which can lead to extensive damage to the DNA of tumor cells and CSCs.The aim of this work was to compare the sensitivity of MCF-7 human breast adenocarcinoma cells and CSCs toγ-andγ,n-irradiation.Methods:To increase the number of CSCs,MCF-7 cells were cultured as mammospheres.γ-irradiation was carried out in a GUT-200M device(^(60)Co source)in the dose range of 1-8 Gy at a dose rate of 0.75 Gy/min.γ,n-irradiation was carried out in an IR-8 reactor in the dose range of 0.05-2 Gy at a dose rate of 0.06 Gy/min.DNA DSB formation was assessed by the level ofγH2AX foci using fluorescence microscopy and flow cytometry.CSCs were identified by flow cytometry as CD44^(+)/CD24^(-/low) cells.Results:We showed thatγ,n-irradiation induced the formation ofγH2AX foci of a larger size than didγ-irradiation and led to more severe DNA damage per 1 Gy.Moreover,γ,n-radiation was found to have a high relative biological effectiveness(RBE)as assessed by the cell survival rate,the number of CSCs in culture,and the ability of CSCs to repopulate.The highest RBE of neutron radiation was observed at low doses,when cell survival rate decreased by only 5%-10%.With an increase in the radiation dose,the RBE value decreased for all studied parameters,but it remained as high as 5.Conclusion:γ,n-radiation is highly effective against CSCs.Our results explain the efficacy of neutron therapy for resistant forms of breast cancer.