共查询到20条相似文献,搜索用时 15 毫秒
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Network medicine has been applied successfully to elicit the structure of large-scale molecular interaction networks. Its main proponents have claimed that this approach to integrative medical investigation should make it possible to identify functional modules of interacting molecular biological units as well as interactions themselves. This paper takes a significant step in this direction. Based on a large-scale analysis of the nervous system molecular medicine literature, this study analyzes and visualizes the complex structure of associations between diseases on the one hand and all types of molecular substances on the other. From this analysis it then identifies functional co-association groups consisting of several types of molecular substances, each consisting of substances that exhibit a pattern of frequent co-association with similar diseases. These groups in turn exhibit interlinking in a complex pattern, suggesting that such complex interactions between functional molecular modules may play a role in disease etiology. We find that the patterns exhibited by the networks of disease – molecular substance associations studied here correspond well to a number of recently published research results, and that the groups of molecular substances identified by statistical analysis of these networks do appear to be interesting groups of molecular substances that are interconnected in identifiable and interpretable ways. Our results not only demonstrate that networks are a convenient framework to analyze and visualize large-scale, complex relationships among molecular networks and diseases, but may also provide a conceptual basis for bridging gaps in experimental and theoretical knowledge. 相似文献
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Alois Strasser Mirja Carra Khaled Ghareeb Wageha Awad Josef Böhm 《Mycotoxin Research》2013,29(3):203-208
As contradictory results have been reported on the immunotoxic properties of deoxynivalenol (DON) in animal studies, we introduced a lymphoblast cell culture model in order to examine the effects of DON on lymphoblastic cell growth and metabolism as well as the preventive properties of free radical scavenger molecules against the DON-induced cell damage. Murine YAC-1 lymphoma cells were used because lymphoblasts have been shown to be sensitive to DON-induced immunotoxicity. Cells were quantified and their proliferative activity was measured by a proliferation test. Lipid peroxidation and protein oxidation were determined using assays quantifying thiobarbituric acid reactive substances (TBARS) and carbonylated proteins. Severely reduced cell counts were detected in DON-treated samples, confirmed by a 5–10 times lower proliferative activity. Significant increases in lipid peroxidation and protein oxidation were found in parallel incubated samples. The pre-incubation with free radical scavengers significantly reduced DON-induced changes to proteins and lipids as well as the tarnished cell viability and cell proliferation. These results suggest that YAC-1 lymphoma cells are a suitable model to investigate and elucidate the basic molecular and cellular mechanisms for possible immunotoxic effects of DON. With regard to the impact of free radical scavengers, the applied in-vitro model might enable the investigation of potential prophylactic and therapeutic effects before or even without harmful animal experiments and cost- and time-intensive expenses. 相似文献
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M Hein C Madefessel B Haag K Teichmann A Post H J Galla 《Chemistry and physics of lipids》1992,63(3):223-233
The transepithelial resistance of confluent epithelial cell monolayers was monitored to investigate the influence of basic amino acids, Ca2+, protamine and protons on tight junction electrical resistance. In an accompanying paper we investigated the effect of these substances on the lamellar/hexagonal II phase transition in reconstituted phospholipid membranes containing phosphatidylserine and phosphatidylethanolamine. We conclude that the permeability of tight junctions may be described by a lipid phase equilibrium where the lamellar phase corresponds to an open state and the hexagonal lipid phase to the closed state of the cell contact. This dynamic lipid model is well suited to describe the morphological as well as functional properties of the tight junctions. 相似文献
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Artiukhov VG Nakvasina MA Lysenko IuA Agisheva NV 《Ukrainski? biokhimicheski? zhurnal》2001,73(1):29-42
The investigation results on the UV-induced changes of lactate dehydrogenase structural and functional properties in the presence of some chemical substances, which are able to interact with the oxygen active forms have been summarized. As well the kinetic characteristics of the photoinactivation processes for heart and muscle LDH types in free state and in the complex with the exogenous agents have been studied. Singlet molecular oxygen has been shown to play an important role in the process of UV-modification of different protein isoforms. The scheme of probable physical and chemical processes, leading to the inactivation of lactate dehydrogenase molecules, has been suggested. 相似文献
6.
The results of investigations of the electrokinetic properties of cell nuclei in various functional states were summarized. A positive correlation between the value of the electrostatic charge on the nuclear membrane surface and the functional state of the genetic apparatus upon activation was established. It was shown that the value of the electrokinetic potential reflects differences in the mechanisms of action of biologically active substances, and that this may be related to the peculiarity of their action on both membrane surface and the cell genome. It is concluded that the electrokinetic properties of the nuclear membrane reflect changes occurring in the genome of the eukaryotic cell nucleus, and from the value of surface charge density, the extent of involvement of the genome under various influences can be determined. 相似文献
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Barrett I Meegan MJ Hughes RB Carr M Knox AJ Artemenko N Golfis G Zisterer DM Lloyd DG 《Bioorganic & medicinal chemistry》2008,16(21):9554-9573
The estrogen receptors ERalpha and ERbeta are recognized as important pharmaceutical targets for a variety of diseases including osteoporosis and breast cancer. A series of novel benzoxepin-derived compounds are described as potent selective modulators of the human estrogen receptor modulators (SERMs). We report the antiproliferative effects of these compounds on human MCF-7 breast tumor cells. These heterocyclic compounds contain the triarylethylene arrangement as exemplified by tamoxifen, conformationally restrained through the incorporation of the benzoxepin ring system. The compounds demonstrate potency at nanomolar concentrations in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity together with low nanomolar binding affinity for the estrogen receptor. The compounds also demonstrate potent antiestrogenic properties in the human uterine Ishikawa cell line. The effect of a number of functional group substitutions on the ER binding properties of the benzoxepin molecular scaffold is examined through a detailed docking and 2D-QSAR computational investigation. The best QSAR model developed for ERalphabeta selectivity yielded R(2) of 0.84 with an RMSE for the training set of 0.30. The predictive quality of the model was Q(2) of 0.72 and RMSE of 0.18 for the test set. One particular compound bearing a 4-fluoro substituent, exhibits 15-fold selectivity for ERbeta and both our docking and QSAR studies converge on the correlation between enhanced lipophilicity and enhanced ERbeta binding for this benzoxepin ring scaffold. 相似文献
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Zijie Chen Zhen Liu Jingjing Liu Xilin Xiao 《Biotechnology and bioengineering》2023,120(12):3501-3517
With the further improvement of food safety requirements, the development of fast, highly sensitive, and portable methods for the determination of foodborne hazardous substances has become a new trend in the food industry. In recent years, biosensors and platforms based on functional nucleic acids, along with a range of signal amplification devices and methods, have been established to enable rapid and sensitive determination of specific substances in samples, opening up a new avenue of analysis and detection. In this paper, functional nucleic acid types including aptamers, deoxyribozymes, and G-quadruplexes which are commonly used in the detection of food source pollutants are introduced. Signal amplification elements include quantum dots, noble metal nanoparticles, magnetic nanoparticles, DNA walkers, and DNA logic gates. Signal amplification technologies including nucleic acid isothermal amplification, hybridization chain reaction, catalytic hairpin assembly, biological barcodes, and microfluidic system are combined with functional nucleic acids sensors and applied to the detection of many foodborne hazardous substances, such as foodborne pathogens, mycotoxins, residual antibiotics, residual pesticides, industrial pollutants, heavy metals, and allergens. Finally, the potential opportunities and broad prospects of functional nucleic acids biosensors in the field of food analysis are discussed. 相似文献
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Nguyen Hoang AT Chen P Juarez J Sachamitr P Billing B Bosnjak L Dahlén B Coles M Svensson M 《American journal of physiology. Lung cellular and molecular physiology》2012,302(2):L226-L237
In lung tissue, dendritic cells (DC) are found in close association with the epithelial cell layer, and there is evidence of DC regulation by the epithelium; that epithelial dysfunction leads to overzealous immune cell activation. However, dissecting basic mechanisms of DC interactions with epithelial cells in human tissue is difficult. Here, we describe a method to generate a three-dimensional organotypic model of the human airway mucosa in which we have implanted human DC. The model recapitulates key anatomical and functional features of lung mucosal tissue, including a stratified epithelial cell layer, deposition of extracellular matrix proteins, and the production of tight junction and adherence junction proteins. Labeling of fixed tissue model sections and imaging of live tissue models also revealed that DC distribute in close association with the epithelial layer. As functional properties of DC may be affected by the local tissue microenvironment, this system provides a tool to study human DC function associated with lung mucosal tissue. As an example, we report that the lung tissue model regulates the capacity of DC to produce the chemokines CCL17, CCL18, and CCL22, leading to enhanced CCL18 expression and reduced CCL17 and CCL22 expression. This novel tissue model thus provides a tool well suited for a wide range of studies, including those on the regulation of DC functional properties within the local tissue microenvironment during homeostasis and inflammatory reactions. 相似文献
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G P Chervonskaia A T Kravchenko V F Runova V M Bedniagin K N Grinberg 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》1988,(12):85-90
The cytotoxic action (CTA) of chemical substances contained as admixtures in medical immunobiological preparations on human diploid cells has been studied. Such chemical substances as rivanol and merthiolate in admissible concentrations show the highest degree of CTA. The results obtained in this investigation indicate that different concentrations of chemical substances may produce equal CTA; thus, thiolate in toxic in a dose of 0.8 microgram/ml; the same CTA is produced by aluminium sulfate in a concentration of 500 micrograms/ml. Small doses of chemical substances, producing no explicit manifestations of the cytotoxic effect, may have latent CTA determined by additional methods of investigation. CTA may be manifested as lethal, sublethal and latent cell lesions. In working out regulations on the test for CTA it is expedient to indicate admissible residual amounts of chemical substances contained in finished medical immunobiological preparations, considering that these amounts must be incapable of producing CTA in cell cultures. The conclusion has been made on the expediency of denoting small amounts of chemical substances capable of producing latent CTA as tentatively tolerable doses. 相似文献
13.
Based on the characterization of the chemical composition of endodermal and
hypodermal cell walls isolated from seven monocotyledonous and three
dicotyledonous plant species, a model of the composition of apoplastic
barriers in roots is proposed. Depending on the species, endodermal and
hypodermal cell walls of roots contained varying amounts of the biopolymers
suberin, lignin, cell wall proteins, and carbohydrates. Although analysis
of the chemical composition of these apoplastic barriers of roots is now
possible, it is pointed out that conclusions from these data concerning the
functional properties of these cell walls can not easily be drawn. However,
in analogy to suberized periderms it is argued that the suberin should play
a role in establishing an apoplastic transport barrier in roots, albeit not
a perfect barrier. Furthermore, due to the combined occurrence of suberin,
lignin and cell wall proteins it is argued that endodermal and hypodermal
cell walls also have an important function as barriers towards pathogens.
Finally, it is pointed out that additional experimental approaches
combining the investigation of transport properties and of the chemical
composition of apoplastic transport barriers in roots are necessary before
the function of endodermal and hypodermal cell walls in roots can be fully
understood. 相似文献
14.
Concepts in nuclear architecture 总被引:14,自引:0,他引:14
Misteli T 《BioEssays : news and reviews in molecular, cellular and developmental biology》2005,27(5):477-487
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Despite considerable investigation, the mechanisms underlying the functional properties of smooth muscle are poorly understood. This can be attributed, at least in part, to a lack of knowledge about the structure and organization of the contractile apparatus inside the muscle cell. Recent observations of the plasticity of smooth muscle and of morphometry of the cell have provided enough information for us to propose a quantitative, although highly simplified, model for the geometric arrangement of contractile units and their collective kinematic functions in smooth muscle, particularly airway smooth muscle. We propose that, to a considerable extent, contractile machinery restructures upon activation of the muscle and adapts to cell geometry at the time of activation. We assume that, under steady-state conditions, the geometric arrangement of contractile units and the filaments within these units determines the kinematic characteristics of the muscle. The model successfully predicts the results of experiments on airway smooth muscle plasticity relating to maximal force generation, maximal velocity of shortening, and the variation of compliance with adapted length. The model is also concordant with morphometric observations that show an increase in myosin filament density when muscle is adapted to a longer length. The model provides a framework for design of experiments to quantitatively test various aspects of smooth muscle plasticity in terms of geometric arrangement of contractile units and the muscle's mechanical properties. 相似文献
16.
N. D. Kreshchenko 《Russian Journal of Developmental Biology》2009,40(1):1-13
The obtained and published data on pharynx regeneration in planarians have been reviewed. Planarians can regenerate from a small body fragment and restore all missing organs including the pharynx. The pharynx is a relatively autonomous organ with a differentiated structure and specialized function. Pharynx regeneration has specific features, and its studies are of considerable theoretical interest. Pharynx regeneration can also be a convenient model to study the molecular mechanisms of regeneration that remain undisclosed. In addition, this model can be used to test biologically active compounds in order to elucidate their effect on morphogenesis. This subject of investigation benefits by a simpler and more adequate analysis as well as a possibility to use large numbers of animals and small quantities of analyzed substances. 相似文献
17.
Bundzikova J Pirnik Z Zelena D Mikkelsen JD Kiss A 《Cellular and molecular neurobiology》2008,28(8):1033-1047
The intention of this review is to emphasize the current knowledge about the extent and importance of the substances co-localized
with magnocellular arginine vasopressin (AVP) and oxytocin (OXY) as potential candidates for the gradual clarification of
their actual role in the regulation of hydromineral homeostasis. Maintenance of the body hydromineral balance depends on the
coordinated action of principal biologically active compounds, AVP and OXY, synthesized in the hypothalamic supraoptic and
paraventricular nuclei. However, on the regulation of water–salt balance, other substances, co-localized with the principal
neuropetides, participate. These can be classified as (1) peptides co-localized with AVP or OXY with unambiguous osmotic function,
including angiotensin II, apelin, corticotropin releasing hormone, and galanin and (2) peptides co-localized with AVP or OXY
with an unknown role in osmotic regulation, including cholecystokinin, chromogranin/secretogranin, dynorphin, endothelin-1,
enkephalin, ferritin protein, interleukin 6, kininogen, neurokinin B, neuropeptide Y, vasoactive intestinal peptide, pituitary
adenylate cyclase-activating polypeptide, TAFA5 protein, thyrotropin releasing hormone, tyrosine hydroxylase, and urocortin.
In this brief review, also the responses of these substances to different hyperosmotic and hypoosmotic challenges are pointed
out. Based on the literature data published recently, the functional implication of the majority of co-localized substances
is still better understood in non-osmotic than osmotic functional circuits. Brattleboro strain of rats that does not express
functional vasopressin was also included in this review. These animals suffer from chronic hypernatremia and hyperosmolality,
accompanied by sustained increase in OXY mRNA in PVN and SON and OXY levels in plasma. They represent an important model of
animals with constantly sustained osmolality, which in the future, will be utilizable for revealing the physiological importance
of biologically active substances co-expressed with AVP and OXY, involved in the regulation of plasma osmolality. 相似文献
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Software-information system Protein Structure Discovery was developed. The system can be used for the wide range of tasks in the field of computer proteomics including prediction of function, structure and immunological properties of proteins. A specially created section of the system allows evaluating the quantitative and qualitative effects of mutations on the structural and functional properties of proteins. There are 19 of different programs integrated into the system, including the database of protein functional sites PDBSite, a PDBSiteScan program for the prediction of functional sites in three-dimensional structures of proteins, and WebProAnalyst program for the quantitative analysis of the structure-activity relationship of proteins. Protein Structure Discovery program has a Web interface and is available for users through the Internet (http://www-bionet.sscc.ru/psd/). For example, binding sites of zinc ion and ADP showed high stability of the method to errors PDBSiteScan reconstruction of spatial structures of proteins in the recognition of functional sites in model structures. 相似文献
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Sahar Melamed Chaim Lalush Tal Elad Sharon Yagur‐Kroll Shimshon Belkin Rami Pedahzur 《Microbial biotechnology》2012,5(4):536-548
The ever‐growing use of pharmaceutical compounds, including antibacterial substances, poses a substantial pollution load on the environment. Such compounds can compromise water quality, contaminate soils, livestock and crops, enhance resistance of microorganisms to antibiotic substances, and hamper human health. We report the construction of a novel panel of genetically engineered Escherichia coli reporter strains for the detection and classification of antibiotic substances. Each of these strains harbours a plasmid that carries a fusion of a selected gene promoter to bioluminescence (luxCDABE) reporter genes and an alternative tryptophan auxotrophy‐based non‐antibiotic selection system. The bioreporter panel was tested for sensitivity and responsiveness to diverse antibiotic substances by monitoring bioluminescence as a function of time and of antibiotic concentrations. All of the tested antibiotics were detected by the panel, which displayed different response patterns for each substance. These unique responses were analysed by several algorithms that enabled clustering the compounds according to their functional properties, and allowed the classification of unknown antibiotic substances with a high degree of accuracy and confidence. 相似文献
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I.G. Minkevich 《Journal of theoretical biology》1982,95(3):569-590
The existing reference system of thermodynamic potentials of substance formation does not outline some important properties inherent to energy transformation and utilization in the cell metabolism. To elicit these properties, a new reference system is suggested. On its basis, a generalized unit of chemical substance reductance, called redoxon, has been developed. The molecules of more reduced substances contain a higher number of redoxons. Energy value of one redoxon is nearly constant in organic compounds but strongly varying in inorganic ones. The stoichiometric and thermodynamic balances of biochemical reactions in the new reference system have been obtained. The suggested approach has been shown to be an adequate tool for the analysis of the mass-energy balance of metabolic processes including heterotrophic and autotrophic growth of intact cells and organisms. 相似文献