37 results about "Glucose deprivation" patented technology

A method of post-stroke treatment at delayed timepoints with sigma receptor agonists. Sigma receptors are promising targets for neuroprotection following ischemia. One of the key components in the demise of neurons following ischemic injury is the disruption of intracellular calcium homeostasis. The sigma receptor agonist, DTG, was shown to depress [Ca2+]i elevations observed in response to ischemia induced by sodium azide and glucose deprivation. Two sigma receptor antagonists, metaphit and BD-1047, were shown to blunt the ability of DTG to inhibit ischemia-evoked increases in [Ca2+]i. DTG inhibition of ischemia-induced increases in [Ca2+]i was mimicked by the sigma-1 receptor-selective agonists, carbetapentane, (+)-pentazocine and PRE-084, but not by the sigma-2 selective agonist, ibogaine, showing that activation of sigma-1 receptors is responsible for the effects. Activation of sigma receptors can ameliorate [Ca2+]i dysregulation associated with ischemia in cortical neurons, providing neuroprotective properties. The effects of 1,3-di-o-tolyguanidine (DTG), a high affinity sigma receptor agonist, as a potential treatment for decreasing infarct area at delayed time points was further examined in rats. DTG treatment significantly reduced infarct area in both cortical / striatal and cortical / hippocampal regions by >80%, relative to control rats. These findings were confirmed by immunohistochemical experiments using the neuronal marker, mouse anti-neuronal nuclei monoclonal antibody (NeuN), which showed that application of DTG significantly increased the number of viable neurons in these regions. Furthermore, DTG blocked the inflammatory response evoked by MCAO, as indicated by decreases in the number of reactive astrocytes and activated microglia / macrophages detected by immunostaining for glial fibrillary acidic protein (GFAP) and binding of isolectin IB4, respectively. Thus, the sigma receptor-selective agonist, DTG, can enhance neuronal survival when administered 24 hr after an ischemic stroke. In addition, the efficacy of sigma receptors for stroke treatment at delayed time points is likely the result of combined neuroprotective and anti-inflammatory properties of these receptors.

Glucose deprivation is an attractive strategy in cancer research and treatment. Cancer cells upregulate glucose uptake and metabolism for maintaining accelerated growth and proliferation rates. Specifically blocking these processes is likely to provide new insights to the role of glucose transport and metabolism in tumorigenesis, as well as in apoptosis. As solid tumors outgrow the surrounding vasculature, they encounter microenvironments with a limited supply of nutrients leading to a glucose deprived environment in some regions of the tumor. Cancer cells living in the glucose deprived environment undergo changes to prevent glucose deprivation-induced apoptosis. Knowing how cancer cells evade apoptosis induction is also likely to yield valuable information and knowledge of how to overcome the resistance to apoptosis induction in cancer cells. Disclosed herein are novel anticancer compounds that inhibit basal glucose transport, resulting in tumor suppression and new methods for the study of glucose deprivation in animal cancer research.

The invention relates to a chip for simulating a cerebral ischemia re-filled pathologic model and belongs to the technical field of microfluidics. The chip mainly comprises four layers, wherein a first layer serves as a culture solution and inoculated cell inlet, a second layer and a porous membrane between a second-layer chip and a third-layer chip jointly simulate a blood-brain barrier system, achip of each layer is provided with a liquid inflow or outflow channel, the third-layer chip and a porous membrane between the third-layer chip and a fourth-layer chip jointly simulate a brain tissuefunctional unit, the chips are similarly provided with liquid inflow or outflow channels, the fourth-layer chip serves as a culture solution outlet, and moreover, microchannels are arranged between the second-layer chip and the third-layer chip and between the third-layer chip and the fourth-layer chip. The chip has multicell co-culture capability; and through designing the porous membranes and culture holes, contactless information exchange among cells, which flow through a culture solution, among multiple cells can be achieved, then, an oxygen-glucose deprivation process of a human brain issimulated, and then, a cerebral ischemia process and cerebral ischemia re-filling of human are simulated.

The invention provides new uses, compositions and methods of administration for specific binding agents to von Wiliebrand Factor (vWF) in patients with thromboembolic disorders and in particular new combined uses with thrombolytic agents such as tissue plasminogen activator in patients with thromboembolic disorders such as e.g. ischemic stroke. Furthermore, a new group of vWF binding agents and an improved Middle Cerebral Artery Thrombosis Model in guinea pigs to study the effects of stroke such as ischemia (oxygen and glucose depriviation) and hemorrhage (bleeding), in particular hemorrhage, are provided.

The invention belongs to the technical field of biological medicines and in particular relates to an acute brain and spinal ischemia / reperfusion injury cellular network model as well as a construction method and application thereof. The cellular network model comprises primary isogenous central nervous system capillary endothelial cells, astrocytes and neurons, wherein the endothelial cells, astrocytes and neurons are three-dimensionally co-cultured according to the relative spatial position and quantity relations of the endothelial cells, astrocytes and neurons in vivo; the environment of oxygen and glucose deprivation / reoxygenation and recovery of glucose in a central nervous system during acute brain / spinal ischemia / reperfusion injury in vivo is simulated by utilizing a low oxygen regulation system / ordinary cell culture system and glucose-free cell culture fluid / normal cell culture fluid. The cellular network model has the beneficial effects that a medicine research mode of adopting the central nervous system capillary endothelial cell culture fluid in lumens of inserts for administration is put forward for the first time, so that the cellular network model further conforms to the organism pharmacokinetics; the cellular network model is used for further research of acute brain / spinal ischemia / reperfusion injury emergence and development mechanisms; the new cellular network model is provided for research and evaluation of clinical diagnostic markers and medicines.

The invention discloses a method for constructing a blood-spinal cord barrier (BSCB) oxygen-glucose deprivation / reoxygenation (OGD / R) injury model and an application thereof. Spinal cord derived microvascular endothelial cells were cultured in the upper chamber and mixed glial cells were cultured in the bottom chamber of the transwell culture system to construct the in vitro BSCB model. Microvascular endothelial cells in the upper chamber of transwell and mixed glial cells in the lower chamber of transwell interact with each other by secreting cytokines to form molecular membranes with good barrier function. OGD / R can effectively simulate the injury of BSCB induced by ischemia / reperfusion in vivo, and can more directly and accurately understand the changes of structure and function of BSCBafter ischemia / reperfusion injury. The results of the study have a high reference value, thus providing an effective basis for clinical study of BSCB.

The invention discloses an optical-activity neoclausenamidone derivative and application thereof. The structural formula of a compound is shown in the description (I), wherein R is C1-C4 paraffin, C2-C4 alkylene and C2-C4 alkyne or -COR1; R1 is selected from C1-C4 substituted or non-substituted paraffin, C1-C4 substituted or non-substituted alkylene and substituted or non-substituted phenyl or heterocyclic-ring aromatic rings; the substituent groups in R1 comprise phenyl, halogenated phenyl, C1-C4 alkyl-substituted phenyl, C1-C4 alkyl-halide-group-substituted phenyl, naphthoxy and pyridine orthiophene. The compound is novel in structure, has a great protection function on epencephalon particle nerve cell injuries induced by glutamic acid and nerve cell or tissue injuries caused by brain ischemia and can be used as a nerve cell protective agent, the injury of glutamic acid or oxygen and glucose deprivation to nerve cells is reduced, and accordingly neurodegenerative diseases, such as cerebral apoplexy, traumatic brain damage and senile dementia, caused by the injury are prevented and / or treated. The compound is shown in the description.

The invention discloses a preparation method of human adult neural stem cells and application thereof in prevention and treatment of cerebral apoplexy. Specifically, a cell line established by the method highly expresses neural stem cell markers including Nestin, Musashi, Sox2, CD133 and the like, still keeps high dryness when being passed to a P20 generation, and is high in stability. A culture supernatant of the cell line has a remarkable improvement effect on nerve cell damage caused by hydrogen peroxide and oxygen-glucose deprivation, has a remarkable improvement effect on animal models inan acute stage and a sequelae stage of the cerebral apoplexy, and can be used as a drug for preventing and treating the cerebral apoplexy.

The present invention provides a train-like pharmaceutical composition (configuration, or dosage form) comprising segments linearly arranged in series like cars of a train. When the pharmaceutical composition is administrated into a patient's body, some of the segments are “visible” to an instrument, but others are not. However, “invisible” segments can be estimated, deduced, calculated, or inferred from “visible” segments. The “invisible” segments can be used for neutralizing intratumoral lactic acidosis combined with glucose deprivation to control tumor, among other applications.

The invention discloses application of medioresinol in preparation of a drug for preventing or treating the cerebral injury and a pharmaceutical composition thereof. The invention provides applicationof medioresinol in preparation of a drug for preventing or treating the cerebral injury for the first time; the medioresinol has an obvious effect on prevention or treatment of the cerebral injury, especially the cerebral injury caused by the cerebral arterial thrombosis; and the cerebral injury caused by the cerebral arterial thrombosis can be obviously reduced. The experiment discovers that themedioresinol has an effect of inhibiting brain microvascular endothelial cell damage caused by oxygen-glucose deprivation and is capable of obviously reducing the permeability of a blood brain barrier under oxygen-glucose deprivation. The medioresinol can reduce the volume of cerebral infarction under middle cerebral artery occlusion remarkably. The pharmaceutical composition containing the medioresinol can become a novel drug for preventing and / or treating the cerebral injury and is used for treating various cerebrovascular diseases including cerebral arterial thrombosis.

The invention discloses application of axitinib and analogues in preparing an anti-ischemic cerebral stroke medicine. According to the invention, the treatment effect of axitinib on ischemic cerebral stroke is evaluated, and it is found that axitinib can reduce the cerebral ischemia infarction volume of middle cerebral artery occlusion and reperfusion model rats, relieve cerebral edema and improve dyskinesia; and axitinib can also slow down the apoptosis state of bEnd.3 cerebrovascular cells under the oxygen-glucose deprivation condition. Therefore, the axitinib and the analogue thereof can be used for preparing the anti-ischemic cerebral stroke medicine.

The invention relates to the field of medicinal chemistry, in particular to an organic nitrite donor ketal type prodrug containing a 1-nitromethyl-2-phenylethylene skeleton, a preparation method of the prodrug and medical application of a medicinal composition of a compound I in prevention or treatment of cerebral ischemia, myocardial ischemia and pulmonary arterial hypertension. Compared with a previously designed and synthesized organic nitrite donor compound VI, the ketal type prodrug I of the organic nitrite donor has better plasma stability, and the strategy of the ketal type prodrug I can further improve the played ischemia protection effect and improve the survival rate of oxygen-glucose deprivation / reperfusion (OGD / R) primary neuronal cells. Meanwhile, the pharmacokinetic study shows that the ketal prodrug type donor has a better pharmacokinetic behavior. In addition, the prodrug strategy can significantly reduce MCAO rat cerebral infarction volume and cerebral water content, accelerate rat ischemic brain tissue endothelial cell proliferation, and promote angiogenesis.

The invention relates to the technical field of novel medicinal application, and particularly relates to novel medicinal application of a CB2 receptor stimulant. An endocannabinoid signal system can be used for maintaining the energy balance and glucose homeostasis in a body; when fat and skeletal muscle cells are subjected to glucose deprivation, the messenger-ribonucleic acid (RNA) expression profile of the signal system changes, and ECS has the effects of mediating insulin resistance and regulating diabetes mellitus, obesity and other metabolic diseases. Animal tests of SER 601 in the CB2 receptor stimulant prove that the CB2 receptor stimulant has a remarkable effect for improving pancreas islet function, improving insulin sensitivity and improving accumulation of whole body fat, especially abdominal fat. The CB2 receptor stimulant can be used for reducing the content of fat in a body while improving the insulin sensitivity, preventing / treating diabetes mellitus patients, especially patients with type 2 diabetes mellitus, and preventing / treating obesity, lipodystrophy, weight and fat reduction and other diseases.

The invention relates to the technical field of biomedicine, in particular to application of circUTRN in preparation of a medicine for treating heart failure, a recombinant vector and the medicine for treating heart failure. Experiments prove that the medicine for treating heart failure prepared from circUTRN can treat or improve heart failure, and especially has a good treatment effect on heart failure caused by ischemia reperfusion injury; specifically, the circUTRN has the effect of improving cardiac systolic insufficiency caused by myocardial ischemia reperfusion injury for 3 weeks; in addition, the circUTRN can also reduce the infarction area of the acute myocardial ischemia reperfusion injury; overexpression of the circUTRN can inhibit myocardial cell apoptosis induced by oxygen-glucose deprivation / recovery.

The invention relates to the field of biological medicines, in particular to building of an extracorporal ischemia model for oxygen-glucose deprivation on a hippocampal section. Cell deaths and ischemia caused by cerebral injury mainly result from dysregulation of Ca2+ ions. Depolarization of neuron cytomembrane results in activation of voltage gate Ca2+ control aisle and internal flow of Ca2+. In experiments, two kinds of Cav2.1 aisle alpha 1 subunit mutant mice (rolling Nagoya and leaner mice) are utilized to study the physiological effect of CaV2.1 (P-Q type) in ischemic neuron injury. As partial ischemia experiments show, the brain tissue embolism areas of the two kinds of mutant models of rolling Nagoya and leaner mice are obviously reduced compared with those of wild type mice. In the study of extracorporal Ca2+ imaging, the growth rate of Ca2+ concentration in the two kinds of Cav2.1 aisle mutant mice is very low compared with that of the wild type mice. These study results show that it is necessary to build the extracorporal ischemia model for oxygen-glucose deprivation on the hippocampal section.

According to the construction method for constructing the myocardial ischemia-reperfusion insulin resistance model by using the primary myocardial cells, the primary myocardial cells are obtained from an SD newborn suckling mouse, and an in-vivo myocardial ischemia-reperfusion experimental model is simulated through an experimental method of oxygen-glucose deprivation and reoxygenation. The model is low in economic cost, short in experimental period and few in interference factors, directly reflects pathophysiological changes of organ tissues, and has better stability compared with an animal model.

The invention discloses application of branched aminotransferase 1 and / or branched aminotransferase 2. The invention for the first time finds that expression of branched aminotransferase 1 (BCAT1) andbranched aminotransferase 2 (BCAT2) in the cardiac tissue of an acute myocardial ischemia model mouse is abnormally reduced, and the phenomenon of abnormal reduction of expression also occurs in an oxygen-glucose deprivation induced myocardial injury cell model. Cardiac in-situ BCAT1 and BCAT2 protein overexpression is carried out on the mouse respectively, thus finding that myocardial ischemia injury can be effectively relieved. Therefore, the BCAT1 and the BCAT2 are proved to be able to serve as novel treatment targets for screening drugs for preventing, relieving and / or treating myocardialischemia injury.

The invention discloses application of silymarin in preparation of a medicine for preventing and / or treating Parkinson's disease, and relates to the field of the medicine for preventing and / or treating Parkinson's disease. Experiments prove that silymarin can inhibit the killing effect of rotenone on human SH-SY5Y cells. The silymarin can inhibit DNA double-chain damage caused by rotenone, can inhibit endoplasmic reticulum stress reaction caused by rotenone, and can inhibit protein aggregation caused by rotenone. Further, the experiments prove that silymarin can inhibit the injury effect of oxygen-glucose deprivation (OGD) on neurons, and has the effect of preventing and / or treating neuronal injury and death after cerebral ischemia. The invention develops a new application of silymarin, and provides a new prevention and treatment way and a new prevention and treatment method for preventing and treating the Parkinson's disease, which is a common nervous system disease affecting the life quality of old people.

The invention provides the application of silymarin in preparation of drugs for preventing and / or treating neuronal injury after cerebral ischemia and relates to the technical field of prevention and treatment of cerebral ischemia, experiments prove that silymarin can inhibit human SH-SY5Y cell injury and death induced by oxygen-glucose deprivation, and silymarin can significantly inhibit AIF nuclear translocation induced by oxygen-glucose deprivation, so that silymarin can be used for preparing drugs for preventing and / or treating neuronal injury after cerebral ischemia. Silymarin inhibits expression up-regulation of gamma-H2AX induced by oxygen-glucose deprivation in a concentration-dependent manner, can inhibit DNA double-chain damage of human SH-SY5Y cells caused by oxygen-glucose deprivation, and inhibits quantity up-regulation of proteins labeled by oxygen-glucose deprivation induced Ubiquitin in a concentration-dependent manner. Silymarin can inhibit protein aggregation caused by oxygen-glucose deprivation. The invention develops a new application of silymarin, and provides a new prevention and treatment way and a new prevention and treatment method for preventing and treating common nervous system diseases which are cerebral ischemia and influence the life quality of old people.

Using high-throughput screening, in an oxygen-glucose deprivation (OGD) model, isoxsuprine hydrochloride was identified as a potent neuroprotective compound. In an animal middle artery occlusion (MCAO) model of transient focal ischemia, isoxsuprine significantly reduced infarct volume compared to vehicle. The invention, therefore, provides methods of treatment and pharmaceutical compositions that are useful in the treatment and prevention of a wide-variety of ischemia-related injuries, including stroke.

The invention discloses the use of swertiamain (Swertiamain) in the preparation of drugs for the treatment of ischemic stroke, and the protection of swertiamain on PC-12 cells after oxygen-glucose deprivation is explored by establishing an oxygen-glucose deprivation model Effect and possible mechanism of action, the experimental results of the present invention show that after oxygen-glucose deprivation reperfusion, it reduces intracellular active oxygen, malondialdehyde content, improves superoxide dismutase, catalase, glutathione In addition, swertiamarin can reduce the apoptosis rate of PC-12 cells and the expression of apoptosis-related proteins, and reduce the apoptosis of PC12 cells caused by oxygen-glucose deprivation-reperfusion, It shows that the protective effect of swertiamarin may be related to anti-oxidation and anti-apoptosis. These results prove that swertiamarin has a protective effect on ischemic injury.

The present invention provides a train-like pharmaceutical composition (configuration, or dosage form) comprising segments linearly arranged in series like cars of a train. When the pharmaceutical composition is administrated into a patient's body, some of the segments are “visible” to an instrument, but others are not. However, “invisible” segments can be estimated, deduced, calculated, or inferred from “visible” segments. The “invisible” segments can be used for neutralizing intratumoral lactic acidosis combined with glucose deprivation to control tumor, among other applications.

The invention discloses application of aloperine (ALO) as a medicine used for treating cerebral arterial thrombosis. An oxygen and glucose deprivation model is built, and a protective effect of ALO to neonatal rat brain ischemia after oxygen and glucose deprivation and a possible mechanism are studied; results show that active oxygen and malonaldehyde contents in cells are reduced after oxygen and glucose deprivation and reperfusion, the contents of three antioxidant enzymes, namely catalase, superoxide dismutase and glutathion peroxidase, are increased, and the total antioxidant capacity is improved; besides, ALO can be used for stabilizing the mitochondrial membrane potential and reducing the apoptosis rate of a hippocampal neuron and calcium ion concentration, so that the protective effect of ALO can be related to oxidation resistance. Therefore, ALO has a protective effect on ischemic injury.

The invention belongs to the field of medicines, in particular relates to a compound 3, 7, 11-cembratriene-2, 6-diol as well as a preparation method and application thereof. The novel tobacco compound3, 7, 11-cembratriene-2, 6-diol has an obvious effect of preventing and treating neurodegenerative diseases, firstly, the novel tobacco compound 3, 7, 11-cembratriene-2, 6-diol has an obvious protective effect on SH-SY5Y cell oxygen sugar deprivation injury; and 2, an obvious protection effect is achieved on glutamic acid induced damage of SH-SY5Y cells. Pharmacological tests prove that the compound can effectively inhibit oxygen-glucose deprivation and glutamic acid induced neuron damage, and have the potential of being further developed into drugs for preventing and / or treating stroke and other neurodegenerative diseases.