20 results about "Hypoxia response" patented technology

The invention discloses a universal mononuclear / macrophage delivery system for enhancing fibrosis part drug accumulation and application, and the universal mononuclear / macrophage delivery system comprises the following steps: (1) preparation of a carrier: adding a low-oxygen response element HRE fused MMP14 plasmid into an aqueous phase solution, then preparing an RMR-LNP suspension from the aqueous phase solution and an oil phase solution by adopting a microfluidic technology, and purifying to obtain the carrier; then, DSPE-PEG2000-TriArg is added into the purified system, incubation is carried out, and RMR-L-TriArg is obtained; and (2) transfecting the mononuclear / macrophage: co-incubating the RMR-L-TriArg and the mononuclear / macrophage, and then transfecting to obtain the mononuclear / macrophage delivery system for enhancing the drug accumulation at the fibrosis part. By constructing MMP14 high-expression macrophages, delivery to the hepatic fibrosis site can be increased, accumulation of drugs is increased, and the treatment effect is enhanced.

The present disclosure provides engineered mesenchymal stem cells (MSCs), a pharmaceutical composition containing the same, and use thereof in the manufacture of a medicament for treating cancer. The mesenchymal stem cells (MSCs) comprise an introduced NQO1 protein-coding sequence and / or an introduced hypoxia response element (HRE), and a nucleic acid encoding one or more immunostimulatory cytokines.

This invention discloses a method for assessing hypoxia response based on dynamic evaluation of heart rate deceleration force and HRV, belonging to the field of biomedical signal processing. The method simultaneously acquires electrocardiogram (ECG) signals and environmental and blood oxygen parameters to dynamically correct the risk baseline; extracts frequency domain, time domain, and heart rate deceleration force features from the ECG signals and establishes a dual-channel cross-judgment logic; inputs the judgment results with the current blood oxygen saturation into a lightweight neural network inference output risk stratification; controls a wearable actuator to initiate multi-target stratified sequential stimulation including heat and vibration based on the stratification results, and adaptively updates the individualized hyperthermia prescription based on the intervention efficacy index, ultimately achieving dual-channel synergistic control of oxygen therapy and hyperthermia. This invention effectively solves the shortcomings of traditional methods, such as delayed early warning and inability to dynamically correct in non-networked environments, constructing a closed loop from precise monitoring to multi-target synergistic intervention, significantly improving the body's adaptability and resilience to hypoxia.

The invention relates to hypoxia response therapeutic VEGFA (vascular endothelial growth factor A) mRNA (messenger Ribonucleic Acid) and application thereof. The mRNA comprises a 5'end cap, a 5 'UTR (Untranslated Region) containing a Kozak sequence, VEGFA ORF (Open Region Fragment), a 3' UTR containing an RNA (Ribonucleic Acid) binding protein HuR binding site, a RhoBAST fluorescent aptamer at the tail end of the 3 'UTR and a PolyA tail. According to the design, through a HuR hypoxia-dependent nuclear plasma transport mechanism, the stability of mRNA in hypoxic cells is improved by 2.5 times, the protein expression quantity is improved by 2 times, and proliferation of endothelial cells is remarkably promoted. Further disclosed is a VEGFA mRNA delivery system based on engineered extracellular vesicles (EVs): EVs surface modified kidney targeting peptide LTH. The system is efficiently accumulated in ischemic kidneys, VEGFA expression is remarkably enhanced, and abnormal vascular hyperplasia of external renal organs is avoided. Animal experiments prove that the survival rate of a renal ischemia-reperfusion injury model can be increased to 100% by intravenous injection of drug-loaded EVs, and the capillary density is remarkably increased 7 days after treatment. The invention is suitable for treating ischemic diseases, organ ischemia reperfusion injury or chronic wounds and the like, and has the advantages of accurate targeting, hypoxia response, high stability and safety.

The invention relates to a hypoxia targeting hyaluronic acid nano delivery system and a construction method and application thereof, the construction method comprises the following preparation method: S1, dissolving 2-nitroimidazole and K2CO3 in dimethylformamide, carrying out high temperature alkali treatment, adding N-Boc-bromoethylamine, and carrying out high temperature reaction to obtain Boc-NIH; s2, dissolving the Boc-2-NIH in dichloromethane, adding trifluoroacetic acid for deprotection, and adjusting the pH value to be neutral, so as to obtain 2-NIH; s3, dissolving HA in deionized water, sequentially adding EDC and NHS to activate carboxyl, then adding 2-NIH, reacting at room temperature, and dialyzing to obtain a hypoxic targeting hyaluronic acid nano delivery carrier HA-NIH; s4, HA-NIH loads a drug, and the hypoxia targeted hyaluronic acid nano delivery system is formed. According to the invention, a bifunctional nano system with CD44 active targeting and hypoxia response release is successfully constructed, a dynamic regulation and control mechanism of HA molecular weight on a targeting-permeation-retention effect is provided, and a synergistic effect of tumor stem cell microenvironment specific response and drug space-time release is realized.

This invention belongs to the field of nanomedicine technology, specifically relating to a pH / hypoxia dual-responsive polymer, nanomicelles, their preparation method, and applications. The pH / hypoxia dual-responsive polymer is a hydroxyethyl deacetylated chitosan modified with p-nitrobenzyl chloroformate and cinnamaldehyde. Ropivacaine is loaded onto it and prepared into nanomicelles for use as a drug delivery system after tumor surgery. Due to its acid sensitivity and hypoxia response, it can intelligently identify the tumor microenvironment, achieving precise drug delivery.

The invention relates to an application of a multifunctional supramolecular nano-platform drug, in particular to an application of a multifunctional supramolecular nano-platform in preparation of a drug for treating liver ischemia reperfusion injury. The multifunctional supramolecular nano platform is a GalAC4A supramolecular carrier loaded with naringenin NAR. The multifunctional supramolecular nano platform is prepared from naringenin NAR, galactose Gal and CAC4A in azo calixarene. The multifunctional supramolecular nano platform is a nano compound of NAR (at) GalAC4A. The multifunctional supramolecular nano platform realizes specific targeting of hepatocytes through endocytosis mediated by an asialoglycoprotein receptor. The invention provides a novel'receptor recognition-hypoxia response-collaborative treatment ', a three-party design strategy is provided, a GalAC4A supermolecular carrier loaded with naringenin (NAR) is successfully constructed, and the NAR-coated GalAC4A nano-composite is formed.

The invention relates to a biomarker of periapical cells and application of the biomarker, and belongs to the technical field of biological detection. The objective of the invention is to solve the problem that a conventional periodontal cell marker has expression overlap with other interstitial cells under an anoxic condition, cannot accurately distinguish tip periodontal cell subgroups, and hinders functional research and targeted therapy development thereof. The method comprises the following steps: screening 15 specific genes (including Adamts9, Cd93, Ctla2a, Fkbp1a, Angpt2 and the like) as periapical cell biomarkers by adopting machine learning according to brain single cell sequencing data of a high-altitude hypoxia mouse; and constructing a logistic regression prediction model to realize cell identification. According to the biomarker combination and the biomarker model, the false detection rate (lt; 5%). A new molecular marker for accurately identifying periapical cells is developed through a machine learning method based on a big data set, and a brand new breakthrough is provided for developing hypoxia response type periapical cell specific markers and functional targets.

The invention provides cyclic peptides that are able to disrupt the typical response to hypoxia and which have particular utility in the treatment of cancers and von Hippel-Lindau disease.

The invention provides an SNP (Single Nucleotide Polymorphism) genetic marker for predicting hypoxia reaction risk and a detection kit thereof. The kit is based on a Rea l-t time PCR (Polymerase Chain Reaction) technology, performs targeted detection on three core SNP (Single Nucleotide Polymorphism) sites (such as chr1.40149875T and chr6.89858851A) related to hypoxia sensitivity, and evaluates the hypoxia tolerance of an individual in combination with a genetic risk scoring model. The kit disclosed by the invention is suitable for low-oxygen reaction risk layering in scenes such as plateau operation, exercise training, clinical anesthesia and the like, and has relatively high sensitivity and practicability.

The application discloses a urine detection method based on platinum ultra-nanoparticles responding to hypoxia and application thereof. The platinum ultra-nanoparticles PNCA are formed by covalently connecting the ultra-small platinum nanoclusters after amination with 4,4'-dicarboxylic azobenzene azo responding to hypoxia through EDC / NHS reaction, and after wrapping the nanoparticles with a layer of hyaluronic acid HA, the nanoparticles can specifically target tumor sites. Then, under the action of the hypoxia environment reductase in the tumor site, the PNCA nanoparticles can be reduced and degraded into many small PtNCs, re-entering the blood circulation, and since the particle size is less than the critical value 5.5 nm that can be removed by the kidney, the nanoparticles can be excreted from the kidney to the urine for disease state detection. Due to the excellent hypoxia response effect of the PNCA nanoparticles and the high kidney removal effect of the PtNCs, the application has obvious advantages in in vivo application.

The application discloses a kind of group and individualized respiratory process modeling method based on sensitivity optimization, belong to biomedical engineering and physiology technical field, including the following steps: S1, data preparation;S2, model construction and parameter optimization;S3, model verification.The application adopts the above-mentioned group and individualized respiratory process modeling method based on sensitivity optimization, which realizes the accurate simulation of blood oxygen saturation, respiratory rate and tidal volume, captures the hypoxic response characteristics, avoids the influence of low-quality signals, and makes the daily difference simulation have higher fitting accuracy.

The application belongs to the technical field of biological medicine, and particularly relates to a beta-carboline quinoline azo oxonium based on hypoxia response and a preparation method and application thereof. The application constructs a brain ischemia activated beta-carboline quinoline azo oxonium shown in the following formula. The beta-carboline quinoline azo oxonium realizes focal specific release of NO through reduction and fracture of an azo bond, and can integrate near-infrared fluorescence imaging function to provide real-time visual monitoring for treatment response.

The present application relates to a kind of expression secretory IL-2 fusion protein of engineered TIL cell and its application.It is specifically, the present application provides the fusion protein of IL-2 and CD25, and is designed using the double hypoxia response element (HRE) and oxygen-dependent degradation domain (ODD) element group hypoxia sensing safety switch, control fusion protein only expresses in hypoxic environment, on the one hand, realizes the specific concentration expression of IL-2 in tumor microenvironment, enhances tumor local concentration, can effectively maintain the anti-tumor activity of TIL in tumor tissue;On the other hand, the security risk brought by IL-2 system exposure is minimized.Meanwhile, the endogenous TIM-3 expression of TIL cell is silenced, so as to effectively reduce TIL exhaustion, further enhance the anti-tumor activity of TIL cell.

Application of a multifunctional supramolecular nanoplatform drug: The application of a multifunctional supramolecular nanoplatform in the preparation of drugs for liver ischemia-reperfusion injury. The multifunctional supramolecular nanoplatform is a GalAC4A supramolecular carrier loaded with naringenin (NAR). The multifunctional supramolecular nanoplatform is prepared from naringenin (NAR), galactose (Gal), and CAC4A from azocalixarene. The multifunctional supramolecular nanoplatform is a NAR@GalAC4A nanocomposite. The multifunctional supramolecular nanoplatform achieves hepatocyte-specific targeting through desialyl glycoprotein receptor-mediated endocytosis. This invention proposes a novel "receptor recognition-hypoxia response-synergistic therapy" three-pronged design strategy, successfully constructing a GalAC4A supramolecular carrier loaded with naringenin (NAR) to form a NAR@GalAC4A nanocomposite.

A system includes an enclosed tent or chamber or a breathing apparatus, a hypoxia induction system and a device for measuring arterial oxygen saturation in a subject breathing air within the enclosed tent or chamber or from the breathing apparatus. The hypoxia induction system delivers oxygen-depleted air having between 5 to 20% O2 to the enclosed tent or chamber or breathing apparatus. The system adjusts the oxygen content of the oxygen-depleted air being delivered to the enclosed tent or chamber or the breathing apparatus based upon the arterial oxygen saturation measured by the device such that oxygen saturation in the subject is maintained within a range of 50% to 90%.

The invention relates to the field of biological medicine, and discloses application of urine-derived stem cells in ED treatment. According to the scheme, a 9-copy hypoxia response element, a minimum promoter, a vascular endothelial growth factor and a nerve growth factor gene are introduced into urine-derived stem cells by utilizing a lentiviral vector, and a hypoxia response type gene modified cell system is constructed. Through local injection of the cavernous body, the cells accurately start factor expression in an anoxic microenvironment. According to the invention, deep coupling of vascular regeneration and neural restoration can be realized, expression can be automatically reduced along with rising of tissue oxygen content, excessive hyperplasia complications can be avoided, and closed-loop intelligent treatment of pathological induction-precise intervention can be realized.

The invention provides a low-oxygen-response norcantharidin prodrug and a preparation method and application thereof, and belongs to the technical field of medical prodrugs, the preparation method comprises the following steps: dispersing NCTD and hydrochloric acid in pure water, and carrying out a ring-opening reaction to obtain a first product; dispersing the first product in dichloromethane, sequentially dropwise adding oxalyl chloride and a catalyst DMF, and carrying out acylating chlorination reaction to obtain a second product; and dispersing the second product and 4, 4-bis (hydroxymethyl) azobenzene in DMF (Dimethyl Formamide), and adding a catalyst 4-dimethylaminopyridine to carry out polymerization reaction to obtain the norcantharidin prodrug NCTD-NN with low oxygen response. The structure of the NCTD-NN contains an azo bond with a hypoxia response function, and the experimental result of in-vitro simulation of a tumor hypoxia environment shows that the azo bond of the NCTD-NN can respond to fracture and release NCTD in a free state, the effect of chemotherapy is fully played, and the NCTD-NN has a controllable drug release function.

The application provides a bionic nanodrug for improving the effect of radiotherapy and chemotherapy, a preparation method and application thereof. The bionic nanodrug comprises a shell, a drug carrier, a first active component and a second active component. The drug carrier is wrapped in the shell, and the drug carrier is loaded with the first active component and the second active component. The shell comprises tumor cell membranes. The first active component is an antitumor chemical drug. The second active component is a targeted interference gene. The structural formula of the drug carrier is shown as formula I, wherein n=4-8 and m=5-10. The aforementioned bionic nanodrug can be used as a tumor targeted therapy drug, realizes efficient crossing of a blood-brain barrier by a nanocarrier and precise targeting of brain glioma cells, realizes intratumoral hypoxia response / degradability of a nanosensitizer, reduces neurotoxicity caused by accumulation of the nanosensitizer in normal tissues, has good biocompatibility, realizes radiotherapy and chemotherapy sensitization effect of brain glioma and other tumors for multiple targets, and improves the treatment effect.

The invention relates to an H2O2 / hypoxia dual-response sectional drug delivery system based on a microneedle structure, which is used for treating burn wounds. The system comprises a soluble microneedle matrix containing sodium percarbonate, H2O2 response microspheres embedded in microneedles and functional components encapsulated in the microspheres. The H2O2 response microspheres are formed by crosslinking polyvinyl alcohol and 1, 4-phenylenediboronic acid through boric acid ester bonds, and a MnO2 nano material with catalase-like activity and hypoxia response drug-loaded micelles formed by self-assembly of nitroimidazole modified hyaluronic acid are encapsulated in the microspheres. After the micro-needle is applied to a burn wound, hydrogen peroxide generated in situ by sodium percarbonate triggers the microspheres to break and release functional components, and MnO2 catalyzes oxygen generation to promote diffusion of drugs to deep tissues; then, under the hypoxic microenvironment formed in the inflammation process, the micelles are discombined to release the medicine, and segmented and sequential medicine delivery is achieved. The invention can break through the physical barrier of the burn wound, improve the deep drug delivery efficiency and reduce the times of dressing change, and is suitable for continuous treatment of the burn wound.