163 results about "Cellular metabolism" patented technology

Disclosed are methods for non-destructively measuring in vitro the effect on cellular metabolism of the addition to animal cells in culture of a soluble molecule potentially capable of perturbing the biological state of the cells, such as a drug or drug candidate, a toxin, a ligand known or suspected to bind to a cell surface receptor, a nutrient, a cytokine, a growth factor, a chemokine, a metabolism inhibitor or stimulator. Also disclosed are methods for measuring cell viability, vitality, or quality, e.g., in anticipation of the execution of an experiment on the cells. The measurements are done by observing alteration in the rates of consumption or production of extracellular solutes related to aerobic and anaerobic cellular metabolism, such as oxygen, protons, nutrients, carbon dioxide, lactate, or lactic acid. The methods are particularly useful in drug discovery efforts, such as cancer drug discovery and searches for modulators of cellular metabolism.

The present invention relates to a novel function of lysyl tRNA synthetase (KRS) which enhances tumor cell migration and affects cancer metastasis via KRS's interaction with laminin receptor (67LR) by its translocation to membrane. More particularly, the present invention relates to a method for modulating cancer metastasis or migration, which comprises regulating intracellular levels of KRS; a composition for preventing or treating cancer; use of expression vector for inhibiting the expression of KRS; a method for preventing or treating cancer; use of an agent for inhibiting an activity of KRS; a method for screening an agent which modulates cancer metastasis or migration; and a method for screening an agent which inhibits the interaction of KRS with 67LR, by said novel function. Thus, KRS can modulate cancer metastasis or migration and furthermore, can modulate intra-cellular metabolism related to 67LR. The interaction between KRS and 67LR can be used effectively in treating, preventing and / or diagnosing of various diseases or disorders related to the interaction.

Methods are disclosed for correcting biological information transfer in a patient in need of such therapy which comprise administration to a patient of a composition comprising a therapeutically effective amount of a biocomplex comprising at least one bioactive agent from each of the three informational blocks of biological information transfer, each agent being present in an amount sufficient to correct the biological information transfer of the patient under treatment and resulting in the resumption of normal cell metabolism, said amount being less than the buffering amount of said agent; together with a carrier therefor.

Refractive index of biological specimens is a source of intrinsic contrast that can be explored without any concerns of photobleaching or harmful effects caused by extra contrast agents. This feature also contains rich information that can be related to the metabolism of cells at the cellular and subcellular levels. The present invention relates to systems and methods that can provide, without any moving parts, the 3-D refractive index map of continuously flowing biological samples in a micro-fluidic channel, for example.

The invention provides a computer readable medium or media, having: (a) a first data structure relating a plurality of reactants to a plurality of reactions from a first cell, each of said reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (b) a second data structure relating a plurality of reactants to a plurality of reactions from a second cell, each of said reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (c) a third data structure relating a plurality of intra-system reactants to a plurality of intra-system reactions between said first and second cells, each of said intra-system reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (d) a constraint set for said plurality of reactions for said first, second and third data structures, and (e) commands for determining at least one flux distribution that minimizes or maximizes an objective function when said constraint set is applied to said first and second data structures, wherein said at least one flux distribution is predictive of a physiological function of said first and second cells. The first, second and third data structures also can include a plurality of data structures. Additionally provided is a method for predicting a physiological function of a multicellular organism. The method includes: (a) providing a first data structure relating a plurality of reactants to a plurality of reactions from a first cell, each of said reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (b) providing a second data structure relating a plurality of reactants to a plurality of reactions from a second cell, each of said reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (c) providing a third data structure relating a plurality of intra-system reactants to a plurality of intra-system reactions between said first and second cells, each of said intra-system reactions comprising a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product; (d) providing a constraint set for said plurality of reactions for said first, second and third data structures; (e) providing an objective function, and (f) determining at least one flux distribution that minimizes or maximizes an objective function when said constraint set is applied to said first and second data structures, wherein said at least one flux distribution is predictive of a physiological function of said first and second cells.

A method for determining metabolic flux distribution of a cell, which comprises the steps of: 1) creating a stoichiometric matrix based on formulas of biochemical reactions from a substrate to a product, 2) computing a set of vectors of solutions existing in a solution space which the stoichiometric matrix may have, 3) selecting, from the computed set of vectors of solutions, maximum vectors whose vector elements corresponding to respective substances for which input values can be obtained are maximum, and 4) performing linear combination for the selected vectors in accordance with the following equations to obtain a vector representing metabolic flux distribution: Sflux=∑i=1n⁢ai·pi·S⁡(i)+∑i=1n⁢bi·qi·A⁡(i)(I)∑i=1n⁢ai+∑i=1n⁢bi=1(II)Sflux: Vector representing metabolic flux distribution to be determined, S(i): Vector selected for substance for which inputted value can be obtained, A(i): Adjustment vector, a, b: Coefficients for linear combination (b may be 0), p: Coefficient for obtaining consistency with input value as numerical value, q: Coefficient of adjustment vector.

A drug delivery system detects a cardiac condition indicative of a need for increasing a cardiac metabolic level and, in response, releases a drug into tissue or blood to shift a source of metabolically synthesized energy fueling cardiac contraction from fatty acid to glucose. One example of such a system includes an implantable device detecting an ischemia and a transdermal drug delivery device delivering a drug when an ischemic condition is detected. Another example of such a system includes one or more implantable devices detecting a predefined change in cardiac metabolic level and delivering a drug when the change is detected. Such systems are applied to treat, for example, patients suffering ischemia and / or heart failure and patients having suffered myocardial infarction.

The invention is used as an additive to a culture medium to maintain and grow various cells including stem cells and support their manufactured and secreted products including cytokines, chemokines and growth factors in an environment which provides:a) metabolic enabling or enhancement of measurable parameters within the cellular populationb) availability and usage of nutrients to cellsc) distinct and positive effect on cellular dynamics (i.e. cellular proliferation and secretion of manufactured products by the cells)d) stabilized environment for maintaining conditions for growth and other cellular and metabolic processes including secretion of manufactured products including signaling factorse) enhanced biological cellular function of inherent cellular processesf) non-interference with normal cellular metabolics (i.e. signaling)g) increased protection from toxic effects to the cellh) additional benefits to the cellular population which in absence of the additive would be lacking.

A structured drug system that is useful for delivering a drug payload to a specific tissue or cell type is disclosed. The system is based on purified polymalic acid. This polymer isolated from natural sources is biocompatible, biodegradable and of very low toxicity. The polymer is extremely water soluble and contains a large number of free carboxyl groups which can used to attach a number of different active molecules. In the examples disclosed N-hydroxysuccinimide esters of the carboxyl groups are used to attach such molecules. The active molecules include monoclonal antibodies to promote specific cellular uptake and specific pro-drugs such as antisense nucleic acids designed to modify the cellular metabolism of a target cell. The pro-drugs are advantageously linked by a somewhat labile bond so that they will be released under specific conditions. In addition, the system contains amide-linked valine to encourage membrane disruption under lysosomal conditions. Polyethylene glycol groups are attached to extend the drug system's circulation half-life. In addition, fluorescent reported groups can be readily included to aid in visualizing and confirming drug system targeting. The drug system can deliver treatments for a wide range of diseases and is specially advantageous for treatment of neoplasms.

Nitrosylation of proteins and amino acid groups enables selective regulation of protein function, and also endows the proteins and amino acids with additional smooth muscle relaxant and platelet inhibitory capabilities. Thus, the invention relates to novel compounds achieved by nitrosylation of protein thiols. Such compounds include: S-nitroso-heme proteins, S-nitroso-t-PA, S-nitroso-cathepsin; S-nitroso-lipoproteins; and S-nitroso-immunoglobulins. The invention also relates to therapeutic use if S-nitroso-protein compounds for regulating protein function, cellular metabolism and effecting vasodilation, platelet inhibition, relaxation of non-vascular smooth muscle, and increasing blood oxygen transport by hemoglobin and myoglobin. The compounds are also used to deliver nitric oxide in its most bioactive form in order to achieve the effects described above, or for in vitro nitrosylation of molecules present in the body. The invention also relates to the nitrosylation of oxygen, carbon and nitrogen moieties present on proteins and amino acids, and the use thereof to achieve the above physiological effects.

The invention provides a cosmetic or dermopharmaceutic composition containing an Euglena extract, its use to activate the cellular metabolism and in particular to protect and / or improve the state of the skin and to reduce the signs of ageing in particular and / or cutaneous fatigue.

A biosensor for detecting a bioeffecting substance in a test sample includes a cell network of at least one electrically excitable cell provided on a substrate in a predetermined geometry with a predefined axonal / dendritic polarity. The at least one cell is capable of producing a signal in response to the presence of the bioeffecting substance. At least one signal transducer is provided with the substrate in a predetermined geometry and is capable of detecting the signal produced by the cell. A culture medium capable of supporting metabolism of the cell is also provided.

This invention relates to methods and systems for in silico or bioinformatic modeling of cellular metabolism. The invention includes methods and systems for modeling cellular metabolism of an organism, comprising constructing a flux balance analysis model, and applying constraints to the flux balance analysis model, the constraints selected from the set consisting of: qualitative kinetic information constraints, qualitative regulatory information constraints, and differential DNA microarray experimental data constraints. In addition, the present invention provides for computational procedures for solving metabolic problems.

The present invention relates to novel methods and compositions comprising key metabolic ingredients for treating aged, mature, nutritionally-compromised, or environmentally-damaged skin. These methods and compositions provide improvements in the skin's visual appearance, physiological functions, clinical properties, and biophysical properties.

The invention relates to a preparation method of tissue engineering skin containing appendant organs. In the invention, the preparation method comprises the following steps of: inoculating amniotic mesenchyme stem cells, amniotic mesenchyme stem cells induced to the directions of hair papillae, amniotic epithelial cells and amniotic epithelial cells induced to the directions of the epithelia of the sweat gland into a gel solution, then inoculating the amniotic epithelial cells and the amniotic epithelial cells induced by keratinocyte in a warp direction on the surface of a structure of the hair follicle and the sweat gland after culturing by a dermal layer by induced culture forming the structure of the hair follicle and the sweat gland, and obtaining the tissue engineering skin with the structure of the hair follicle and the sweat gland after culturing. The skin has elasticity, toughness, vigorous cellular metabolism, strong multiplication capacity, sufficient secretion of extracellular matrices, tight linkage of the cuticular layer, the inophragma and the cells of the dermal layer and little possibility of falling off, enhances the success rate of transplantation, can promote the healing of a wound surface, enhances the effects of restoration and replacement and has the function of regulating the immunological rejection of a receptor; by the contained structure of the hair follicle and the sweat gland, the function of the skin is more complete; the adopted amniotic tissues are postpartum wastes and have extensive source, strong cell multiplication capability and multiplepassage frequency; and the invention is beneficial to the mass production of seed cells and lowers the industrialization cost.

A structured drug system that is useful for delivering a drug payload to a specific tissue or cell type is disclosed. The system is based on purified polymalic acid. This polymer isolated from natural sources is biocompatible, biodegradable and of very low toxicity. The polymer is extremely water soluble and contains a large number of free carboxyl groups which can used to attach a number of different active molecules. In the examples disclosed N-hydroxysuccinimide esters of the carboxyl groups are used to attach such molecules. The active molecules include monoclonal antibodies to promote specific cellular uptake and specific pro-drugs such as antisense nucleic acids designed to modify the cellular metabolism of a target cell. The pro-drugs are advantageously linked by a somewhat labile bond so that they will be released under specific conditions. In addition, the system contains amide-linked valine to encourage membrane disruption under lysosomal conditions. Polyethylene glycol groups are attached to extend the drug system's circulation half-life. In addition, fluorescent reported groups can be readily included to aid in visualizing and confirming drug system targeting. The drug system can deliver treatments for a wide range of diseases and is specially advantageous for treatment of neoplasms.

The invention relates to acne treatment emulsion, and belongs to the field of cosmetics. The acne treatment emulsion comprises the following components: component A comprising propylene glycol, xanthan gum and first solvent; component B comprising 2-hydroxyethanesulphonic acid hexyl ether, vitamin B6 and second solvent; component C comprising plant extract, azelaic acid derivatives, dendranthema indica (L.) des moul, salicylic acid, ginseng extract, vitamin E and preservative agent. The acne treatment emulsion has the functions of treating acne, whitening and nourishing skin, moisturizing, reducing oil secretion, and promoting cellular metabolism, the effect is obvious, the action is fast, no acne scar is left after healing, and the acne is not easy to relapse; and the acne treatment emulsion is a cosmetic which is used for preventing and treating acne and whitening skin.

Nitrosylation of proteins and amino acid groups enables selective regulation of protein function, and also endows the proteins and amino acids with additional smooth muscle relaxant and platelet inhibitory capabilities. Thus, the invention relates to novel compounds achieved by nitrosylation of protein thiols. Such compounds include: S-nitroso-t-PA, S-nitroso-cathepsin; S-nitroso-lipoprotein; and S-nitroso-immunoglobulin. The invention also relates to therapeutic use of S-nitroso-protein compounds for regulating protein function, cellular metabolism and effecting vasodilation, platelet inhibition, relaxation of non-vascular smooth muscle, and increasing blood oxygen transport by hemoglobin and myoglobin. The compounds are also used to deliver nitric oxide in its most bioactive form in order to achieve the effects described above, or for in vitro nitrosylation of molecules present in the body. The invention also relates to the nitrosylation of oxygen, carbon and nitrogen moieties present on proteins and amino acids, and the use thereof to achieve the above physiological effects.

This invention uses a receptor molecule such as an antibody etc immobilized to a chip for a solid phase, and a sensor such as a pH electrode or an oxygen electrode or a glucose electrode for a search device. After immobilizing specific living cells by a bio-specific recognition reaction (a special immunity bond reaction) and washing the solid phase chip, one can measure the change of pH or oxygen consumption or glucose consumption from the metabolism of the specific living cells in substrate solution. This makes it possible to measure the activity and quantity of living cells specifically, accurately and quickly.

A rapid and efficient method for novel biological substance screening by surface analysis has been developed using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). This method relies on the surface screening of an array of micro-organisms grown on porous membranes, which had previously been in contact with a solid growth medium. TOF-SIMS analysis differentiates among organisms producing different substances, either directly as molecular product, or indirectly through the use of multivariate statistical data reduction techniques. This method has many advantages over traditional microbial screening methods, which require sample preparation and time for assay development.

The invention discloses a new method for performing data correction by using cell metabolite relative content as cell number index. The new method is characterized by comprising the steps of: realizing the fast quenching of biochemical metabolism in cells by using a simple sample pre-processing method; efficiently extracting small molecule metabolites by an optimized extraction solvent; and roundly and half quantitatively measuring the small molecule compounds in a biological sample by a metabonomics method based on measuring technology like mass spectrum, nuclear magnetic resonance and the like so as to identify a quantitative index of symbolic metabolites in cells to be as the cell number, and regarding the quantitative index as a weight factor to perform data correction. Compared with the quantitative index of the prior cell number, the method is simple, fast and with good repeatability; additional experimental working and the error caused by the additional working are reduced; the accuracy and reliability of experiment result are improved; the difficulty for relatively quantifying the number of in vitro cultured cells is solved; a new displacing method is supplied for cell metabonomics and relevant researches; and the method can be widely used in the relevant researches in the field of cell molecular biology.

A particulate glass for a synthetic bone (including dental) graft includes ZnO, SrO, and may include NaO. The glass promotes cellular metabolism, and upon implantation in living bone tissue induces bone growth at their surface. The ZnO and SrO respectively degrade to provide Zn2+ and Sr2+ ions respectively. The ions released by the glass provide anti-bacterial effects; improved bone formation in place of diseased tissue; inhibition of bone resorption; and radiopacity. There is excellent synergy between the SrO, ZnO, and NaO. The Sr2+ ions have better bone formation effects than the Zn2+ ions, but an anti-bacterial effect which is not as good. Choice of relative proportions of ZnO and SrO combined with the choice of NaO concentration to set the resorption rate allow optimisation. NaO there is control of the degradation rate of the graft; a feature which is advantageous in tailoring the grafts to specific patients and applications. Additionally the sodium (Na) in the glass imparts water solubility, allowing glasses to degrade to their ionic components.

The invention provides a technology for inducing the redifferentiation of calluses of Taxus wallichiana var. mairei to improve or maintain the genetic stability of the cellular metabolism of the Taxus wallichiana var. mairei and improve the content of paclitaxel as a secondary metabolite of the Taxus wallichiana var. mairei. The technology comprises four steps of explant preprocessing, induced culture of calluses, calluses subculture and calluses redifferentiation induction. In the step of induced culture of calluses, subculture is performed four times with 20-35 days for each culture, the calluses with good color and right texture are transferred to an improved MS (Murashige & Skoog) culture medium in which 0.05-0.20mg / L6 of BA, 0.2-2.0mg / L of NAA, 0.1mg / L of KT and 0.5mg / L of CH are added for redifferentiation induction culture, after 45-75 days of the induction culture, tiny sprouts grow from the calluses of the Taxus wallichiana var. mairei, the calluses are harvested at the time, after samples are subjected to drying, weighing and a series of preprocessing, HPLC (High Performance Liquid Chromatography) is adopted to measure the content of the paclitaxel, and a result shows that the content of the paclitaxel is one time higher than that of the calluses which are not subjected to differentiation. In the improved MS culture medium, ammoniacal nitrogen is 2000-2600 mg / L and the nitrate nitrogen is 800-1000mg / L.

The invention discloses a facial mask with functions of skin whitening and spot removing and a preparation method thereof. The facial mask comprises the following spot removing ingredients in percentage by weight: 0.01-0.2 percent of nicotinamide, 0.01-10 percent of scutellaria baicalensis root extract, 0.01-3 percent of tranexamic acid, 0.01-5 percent of yeast extract, 0.01-3 percent of vitamin Cethylether, 0.01-5 percent of boerhavia diffusa root extract and 0.01-2 percent of carnosine. The facial mask is prepared from safe and irritation-free ingredients, and the preparation process is simple and convenient. The facial mask adopts multiple synergized skin whitening and spot removing ingredients and moisturizing ingredients, can be used for effectively inhibiting melanin pigmentation, accelerating cellular metabolism and melanin decomposition, moisturizing skin and enhancing skin moisturizing capacity, thereby achieving multiple functions including skin whitening, spot removing, moisturizing, inflammation resisting, skin repairing and the like and achieving the effects of comprehensive whitening, skin tone brightening and evening and improving skin texture.

The technological process includes inoculation of cell to carrier in fixed bed; continuous perfused culture; detection; regulation and analysis of cell metabolism, growth rate and product synthesis balance; and product recovering and purification. The regulation and analysis of cell metabolism, growth rate and product synthesis balance includes the analysis of glucose, lactic acid, pH and other indexes, adding corresponding amino acid before the cell decline phase, decreasing glucose and blood serum concentration, etc. to realize high density and high yield culture. The product recovering andpurification inclues utilizing Streamline SP medium to recover antibody in supernatant, utilizing DEAE-Sepharose FF anionic exchanger to purify product, freeze drying.

The invention discloses a system and method for simultaneous detection of extracellular environmental toxicants and cell metabolism. In the invention, a Zn<2+> chalcogenide glass sensitive membrane and a Cl<-> polyvinyl chloride sensitive membrane simultaneously deposit and combine on the surface of a light-addressable potentiometric sensor so as to form a Zn<2+> chalcogenide glass sensitive membrane-Cl<-> polyvinyl chloride sensitive membrane-light-addressable potentiometric sensor, which can quickly detect the Zn<2+> concentration of extracellular environmental toxicants and the Cl<-> ion concentration of cell metabolism at the same time, and infer the quantitative relationship between the two. A constructed micro-cavity can improve the sensitivity of ion concentration, and can ensure the consistency of detection conditions simultaneously, thus greatly reducing the part replacement cost and improving the service life of a sensor package unit. The above characteristics can meet the requirements for simultaneous detection of extracellular environmental toxicants and cellular metabolism, so that the system and method of the invention can be widely used in related fields of researchon heavy metal concentration and cell metabolism mechanism.

The invention discloses a preparation method of a water-soluble chitosan-based aggregation-induced emission fluorescent probe with reduction responsiveness, mainly comprising the following steps: modifying chitosan molecules by adopting a hydrochloric acid / methanol mixed solvent system and an EDC / NHS catalytic system, so as to obtain disulfide bond connected carboxylation chitosan CS-ss-COOH; marking tetraphenyl ethylene (TPE) fluorescent molecule to a CS-ss-COOH chain to obtain TPE-CS-ss-COOH with aggregation-induced emission (AIE) characteristic. The fluorescent probe prepared according to the invention not only has good reduction responsiveness and water solubility, but also has aggregation-induced emission characteristic, and compared with conventional fluorescent probes, has the advantages of being high in sensitivity, good in photostability, free from quenching at high concentration, no drifting of fluorescence spectrum, and the like, can also realize further enhancement of the fluorescence intensity in a glutathione solution, is good in imaging effect, and is expected to be applied to the fields of tumor cell specificity tracking, cell metabolism detection, drug metabolism detection, environment monitoring and the like.