33 results about "Pharmacodynamic Study" patented technology

The invention relates to the field of medicinal chemistry, and discloses application of cyclobutene amide compounds in antiviral drugs. The structural characteristics of the compounds are as shown in a general formula (I), wherein EWG is an electron withdrawing group and is selected from aryl-substituted sulfonyl; r1 is selected from alkyl or aryl; r2 is selected from alkyl or aryl; and n represents the number of carbon atoms and may be 1 or 2. In-vitro pharmacodynamic studies show that the series of compounds have a remarkable inhibition effect on influenza A virus (H1N1 subtype), and the antiviral efficacy of the compounds is obviously superior to that of a clinical common antiviral drug ribavirin. In addition, toxicological evaluation proves that the compounds have ideal safety characteristics. The cyclobuteneamide derivative can be used as an effective component for developing an anti-influenza A virus drug, and a new candidate drug molecule is provided for clinical treatment of influenza virus infection. # imgabs0 #

The present invention discloses a method and a kit for determining the concentration of olverembatinib in human plasma or cerebrospinal fluid based on LC-MS / MS. First, working solutions of olverembatinib standard curves with different concentrations and working solutions of olverembatinib quality controls with different concentrations are prepared. Then, an internal standard working solution is configured. Finally, the internal standard working solution is added to the sample to be tested, vortexed and mixed, and then pretreated to obtain a supernatant. The supernatant is taken and injected into an LC-MS / MS instrument for detection and analysis. The present invention not only has simple pretreatment, low cost, short analysis time, and good specificity, but also has high sensitivity of the detection method, and the lower limit of quantification can reach the picogram level, which is rare in other LC-MS / MS detection methods. This method can be used for the pharmacokinetic-pharmacodynamic study of olverembatinib and the determination of the concentration of olverembatinib in the plasma and cerebrospinal fluid of conventional clinical patients.

The invention belongs to the technical field of medicines. The invention relates to a plaster, in particular to a plaster containing anilinoprofen and a composition. The invention provides an externally applied medicine containing anilinoprofen or a composition containing anilinoprofen and iguratimod. Pharmacodynamic studies show that the aniline-ibuprofen single-prescription plaster can treat osteoarthritis (OA) and rheumatoid arthritis (RA), can effectively inhibit arthrocele and volume increase, remarkably reduces the level of proinflammatory factors, and improves the pathological score of joint tissue. After the anilinoprofen and the iguratimod are combined for use, the curative effect is further enhanced, multiple indexes are obviously superior to those of a single drug group, and an obvious synergistic interaction effect is shown. The iguratimod and anilinoprofen compound preparation disclosed by the invention is developed in an external form such as a gel plaster for the first time, an external compound system of anilinoprofen and iguratimod is innovatively constructed, a safe, effective and convenient novel local treatment choice is provided for OA / RA patients, especially people with oral taboo or needing long-term treatment, and the iguratimod and anilinoprofen compound preparation has good clinical transformation potential and application value.

The invention discloses an mRNA medicine of acetaldehyde dehydrogenase and application of the mRNA medicine, and belongs to the technical field of biological medicine. An mRNA coding optimization design is carried out based on an ALDH2 amino acid sequence, and a candidate molecule YQTQ-01 with high expression performance is obtained through in-vitro expression screening. Wild type mouse in-vivo experiments prove that the molecule can significantly improve the expression level of ALDH2 protein, and subsequent mouse pharmacodynamic studies show that the molecule has a definite aldehyde metabolism regulation function. Experimental data reveals that the YQTQ-01 can effectively promote removal of toxic aldehyde substances by enhancing the activity of acetaldehyde dehydrogenase, and a novel intervention scheme is provided for treatment of alcoholic liver injury, aldehyde metabolic disturbance and other diseases.

The invention discloses an application of ligularia virgaurea alcohol extract in preparation of a medicine for preventing or treating drug-induced liver injury, relates to the technical field of biological medicines, and proves that the ligularia virgaurea alcohol extract has an obvious effect of improving acute drug-induced liver injury for the first time. The traditional Chinese medicine composition can obviously improve serum biochemical indexes, inflammatory factor levels and hepatic tissue pathological states of mice with acute drug-induced liver injury, improve the activity of superoxide dismutase (SOD) and glutathione (GSH) in hepatic tissues, and reduce the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). Pharmacodynamic tests prove that the ligularia nobilis alcohol extract has a remarkable liver injury protection effect, and is low in effective dose and free of toxic and side effects. Therefore, the invention may become an alternative drug for preventing and treating drug-induced liver injury.

The scheme discloses an alkaloid compound with 14, 21 oxygen bridge structures and a preparation method and application thereof in the field of traditional Chinese medicine extraction and separation. The ethyl acetate extraction part of ethanol extracts of toad skin is repeatedly separated and purified by combining various chromatography technologies; 1D and 2D nuclear magnetic and high resolution mass spectrometry are used to identify the structures of two new compounds, and the molecular formula and structure formula of the two new compounds are deduced. In vitro pharmacodynamic studies show that the two alkaloid compounds with 14, 21 oxygen bridge structures have good inhibition on colon cancer cells (HCT-116), and IC 50 The two alkaloid compounds with 14, 21 oxygen bridge structures have good inhibition on colon cancer cells (HCT-116), and IC 50 values are 0.92 μM and 10.91 μM respectively. The present application is helpful for the development and utilization of natural compounds from toad.

The invention discloses an effective part for chemoradiotherapy-induced oral mucositis in traditional Chinese medicinal material white flower and a preparation process of the effective part. The effective part is identified as a flavonoid component through standard substance spectrogram comparison. Tests prove that the production process of the effective part is practical and feasible, and the total flavonoids in the finally obtained extracting solution are greater than or equal to 50%. Besides, pharmacodynamic studies show that the effective part has a remarkable bacteriostasis effect on staphylococcus aureus, escherichia coli and candida albicans, the bacteriostasis rate is larger than or equal to 80%, the effective part has a remarkable treatment effect on rat oral mucosa acute inflammation caused by chemoradiotherapy, and the application prospect of the effective part in the adaptation disease is shown.

This invention relates to the field of medicinal chemistry, specifically disclosing 4-(2-fluoro-4-iodophenoxy)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazoline, its preparation method, and its applications. A novel N-[4-(quinazoline-4-yl)oxyphenyl]biarylsulfonamide compound prepared from this intermediate is a dual inhibitor targeting EGFR and c-Met. The quinazoline core and sulfonamide biaryl side chain in its molecular structure can specifically recognize and bind to mutant EGFR and abnormally activated c-Met, significantly enhancing its selective killing effect on tumor cells. Pharmacodynamic studies show that it exhibits excellent inhibitory activity against the human lung cancer cell line (NCI-H1975) at the cellular level, with an IC50 of [missing information - likely an IC50 value] against p-EGFR. 50 A value of 1.56 nM for p-Met IC 50 The value is 1.8nM.

This invention discloses a macroporous resin purification method for Compound Muniziqi Formula. The method includes the following steps: (1) macroporous resin pretreatment; (2) column packing; (3) sample loading; and (4) obtaining the total alkaloid fraction and / or the total saponin fraction; optionally, (5) obtaining the total flavonoid fraction. This invention utilizes the macroporous resin method to establish a process for simultaneously enriching alkaloids, flavonoids, and saponins in Compound Muniziqi Formula, and simultaneously preliminarily separating the total extract, total alkaloids, total flavonoids, and / or total saponin fraction; on the other hand, in pharmacodynamic studies, the anti-inflammatory and antioxidant activities of Compound Muniziqi Formula and its different fractions in vivo and in vitro are studied using cell models, thereby elucidating the pharmacodynamic material basis of Compound Muniziqi Formula and its alkaloids, flavonoids, and saponins, laying the foundation for the further development and expansion of the indications of Compound Muniziqi Formula.

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to application of a ginseng and astragalus hypoglycemic preparation in preparation of medicines for preventing or treating pulmonary fibrosis. Pharmacodynamics shows that the ginseng and astragalus hypoglycemic granules can remarkably reduce expression of TGF-beta1, p-Smad3, p-P38MAPK and CollagenIII protein of diabetic pulmonary fibrosis model rat lung tissue, can effectively improve the pulmonary function and pulmonary fibrosis of diabetic mice, and have a remarkable protection effect on the diabetic mice lung tissue. The ginseng and astragalus hypoglycemic preparation can obviously reduce the expression of inflammatory factors TNF-alpha, IL-1beta and IL-6 of pulmonary fibrosis model mice, improve the SOD activity of mouse lung tissues and the T-AOC level of serum, and reduce the MDA level of the mouse lung tissues; the medicine can be used for treating pulmonary fibrosis. Meanwhile, the ginseng and astragalus hypoglycemic preparation is high in safety and small in toxic and side effects, and the clinical medication selection of patients is enriched.

The invention relates to a composition for strengthening brain, developing intelligence and improving memory and application thereof, and belongs to the technical field of traditional Chinese medicines. The technical problems that an existing Wang tonifying heart pill is relatively backward in process and large in dosage are solved. The composition consists of the following traditional Chinese medicine extracts in parts by mass: 2-8 parts of a traditional Chinese medicine extract A, 3-7 parts of a traditional Chinese medicine extract B, 4-8 parts of a traditional Chinese medicine extract C and 2-6 parts of a traditional Chinese medicine extract D. According to the traditional Chinese medicine composition, the Tianwang heart-tonifying classic prescription is applied, effective components are extracted and separated through modern science and technology, effective extracts are obtained, the curative effect is exerted through the corresponding proportion, and pharmacodynamic research shows that the traditional Chinese medicine composition can achieve the effects of strengthening the brain, improving intelligence and improving the memory through the effects of nourishing yin and blood, clearing away the heart fire and soothing the nerves. And the related process is advanced, and the dose is not large.

The invention provides a preparation method of a pharmaceutical composition for treating adenomyosis. The preparation method comprises the following steps: a, weighing the following raw material medicines in parts by weight: 25-35 parts of sculellaria barbata, 25-35 parts of oldenlandia diffusa, 5-15 parts of spina gleditsiae, 10-20 parts of curcuma zedoary, 5-15 parts of ground beeltle, 10-20 parts of rhizoma curculiginis, 10-20 parts of epimedium and 15-25 parts of polyporus umbellatus; b, extracting spina gleditsiae, curcuma zedoary, oldenlandia diffusa and sculellaria barbata by C, extracting rhizoma curculiginis, herba epimedii, ground beetles and polyporus umbellatus with water; and d, combining the extracts in the steps b and c, concentrating, and adding pharmaceutically acceptable auxiliary materials or auxiliary components to prepare a pharmaceutically common preparation. Pharmacodynamic studies prove that the pharmaceutical composition can obviously improve uterine injury of experimental adenomyosis rats, and the pharmaceutical effect of the pharmaceutical composition is better than that of a traditional Chinese medicine clinical conventional water decoction preparation under the condition of equal dosage or 1 / 2 dosage, so that the pharmaceutical composition prepared by the innovative preparation method has better pharmaceutical effect than that of clinical water decoction, and the pharmaceutical composition is suitable for clinical application. The compound has remarkable application potential in preparation of drugs or hospital preparations.

Provided herein are methods and compositions related to in vivo testing of therapeutic agents comprising a human Fc in genetically modified rodents (e.g., testing the pharmacokinetic and / or pharmacodynamic properties of such therapeutic agents in genetically modified rodents). In some embodiments, the genetically modified rodents express antibodies comprising a human Fc (e.g., human IgG1 Fc, human IgG4 Fc). In some embodiments, the rodents express fully human antibodies (i.e., antibodies having human heavy chains and human light (γ or κ) chains). In certain embodiments, the genetically modified rodent comprises one or more Fc receptors with human extracellular domains (e.g., neonatal Fc receptor (FcRn), β-2-microglobulin polypeptide (β2M), Fcε receptor 1α (FcεR1α), Fcγ receptor 1α (FcγR1a), Fcγ receptor 2a (FcγR2a), Fcγ receptor 2b (FcγR2b), Fcγ receptor 3a (FcγR3a), Fcγ receptor 3b (FcγR3b), Fcγ receptor 2c (FcγR2c)). The transmembrane and cytoplasmic domains of the receptor can be human or non-human (e.g., rodent).

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to dexamethasone single-phase zero-order release sustained-release microspheres as well as a preparation method and application thereof. The dexamethasone sustained-release microspheres are prepared by an emulsification-solvent evaporation method, the release platform phase of the microspheres is improved by adding a release accelerator, and finally the dexamethasone sustained-release microspheres with a single-phase zero-order release behavior are obtained. Experimental results show that various representations of the sustained-release microspheres meet the requirements of preparations, and in-vivo pharmacodynamic studies of rats also show that the sustained-release microspheres can protect articular cartilage and maintain a normal cartilage structure, and have the same curative effect as commercially available dexamethasone acetate injection. Therefore, the dexamethasone sustained-release microsphere which is used for articular cavity injection and has a good release behavior is successfully developed, the advantages of articular cavity injection drugs can be fully played, the drugs can be continuously and stably released, long-acting treatment of arthritis is achieved, and the dexamethasone sustained-release microsphere has important clinical application value and wide market prospects.

The present invention discloses an anticoagulant peptide, its preparation method and application. The present invention optimizes the extraction and separation method of anticoagulant activity of Eupolyphaga sinensis, thereby detecting ultra-trace anticoagulant peptide RF7 from complex crude peptide extracts, and using the NanoLC-Q-Orbitrap-MS / MS method to perform high-throughput analysis and identification of the peptide sequences of the screened active anticoagulant peptides. Through the search and comparison of the intelligent data processing system and the polypeptide database, the biological information and pharmaceutical components of the anticoagulant peptide are comprehensively analyzed. Finally, by constructing molecular level, cell and animal models, pharmacokinetic and pharmacodynamic studies are carried out on the anticoagulant peptides with obvious activity to evaluate the safety and effectiveness of the drug, laying a research foundation for the development and drug-likeness evaluation of new anticoagulant drugs.

The invention discloses a traditional Chinese medicine composition which comprises the following medicinal materials in terms of 50 preparation units: 60-100 parts of pseudo-ginseng, 60-100 parts of vinegar-processed rhizoma corydalis, 20-60 parts of starfish, 20-60 parts of ground beeltle, 5-15 parts of processed semen strychni, 10-30 parts of safflower, 1-20 parts of vinegar-processed frankincense, 1-20 parts of vinegar-processed myrrh, 1-10 parts of borneol and 0.1-1 part of artificial musk. The invention further discloses a preparation method of a tincture of the traditional Chinese medicine composition and application of the traditional Chinese medicine composition in preparation of medicines for treating acute and chronic falling trauma, neck, shoulder, waist and knee pain or arthralgia. The traditional Chinese medicine composition disclosed by the invention has the effects of relaxing muscles and tendons, promoting blood circulation, dredging collaterals, dissipating blood stasis, diminishing swelling and relieving pain. Pharmacodynamic studies show that the traditional Chinese medicine composition disclosed by the invention takes effect quickly and has a good curative effect when being used for treating symptoms such as traumatic injuries, blood stasis swelling and swelling and red and swollen injuries. The traditional Chinese medicine composition disclosed by the invention effectively relieves the injury condition of a tested animal, and is free of irritation and sensitization to the tested animal in a skin medication toxicity test.

This invention relates to a CDK12 / PARP dual-target inhibitor, its preparation method, and its application. The inhibitor has the general structural formula (I). Specifically, it relates to a CDK12 / PARP dual-target inhibitor, its preparation method, and its application. Pharmacodynamic studies have demonstrated that the CDK12 / PARP dual-target inhibitor of this invention has significant anti-tumor efficacy. The CDK12 / PARP dual-target inhibitor comprises substituted compounds having the general formula (I), or their stereoisomers, hydrates, or pharmaceutically acceptable salts. Compared with the prior art, the compound structure of this invention is novel, and experiments show that it has good CDK12 and PARP enzyme inhibitory activity, and can be used to prepare drugs with CDK12 / PARP dual-target anti-tumor activity.

The invention relates to the technical field of pharmacological research, in particular to a drug target of tribulus terrestris extract for treating pulmonary fibrosis as well as a screening method and application of the drug target. According to the invention, the effective treatment effect of TED on PF is determined through pharmacodynamic research. The SCD2 protein is preliminarily screened as the target protein by using a 4D-SmartDIA quantitative proteomics technology, the protein expression level proves that the SCD2 expression and phosphorylation level in the mouse lung tissue after TED treatment are obviously increased, and the interaction between SCD2 and phosphorylation is investigated and determined. Therefore, the SCD2 can be used as a drug target for predicting the treatment of the TED on the PF. And a basis is provided for development of PF treatment drugs.

This invention relates to thyroxine receptor β-selective agonist compounds represented by general formula I, pharmaceutical compositions thereof, and uses. These compounds maintain good THR-β agonist activity while improving selectivity for THR-α and druggability, and exhibit certain activity in in vivo pharmacodynamic studies.

The application is a colon-targeting lipid nanoparticle based on ginsenoside Rg3, a calcium alginate microsphere thereof and application thereof in treating ulcerative colitis, and belongs to the technical field of new excipients and new dosage forms of pharmaceutical preparations, and particularly relates to an oral colon-targeting delivery system for treating ulcerative colitis. The system replaces cholesterol in traditional lipid nanoparticles with ginsenoside Rg3, constructs lipid nanoparticles capable of efficiently loading TNF-alpha siRNA, and effectively improves the targeting property and lysosome escape ability of the lipid nanoparticles on inflammatory macrophages. In order to further realize colon-specific delivery, the above-mentioned lipid nanoparticles are loaded in a pH-responsive calcium alginate microsphere, so that the drug is kept stable in the upper gastrointestinal tract and is released in a responsive manner in the colon. Pharmacodynamic studies show that the drug delivery system can significantly relieve the symptoms of colitis, effectively silence the expression of TNF-alpha, repair the intestinal barrier, and regulate the intestinal microbiota. The application provides a safe and efficient new strategy for solving the problems of poor gastrointestinal stability and low targeting efficiency of oral delivery of nucleic acid drugs.

The invention belongs to the technical field of organoid culture, and discloses a hydrogel-based bionic brain micro-tissue as well as a construction method and application thereof. The hydrogel-based bionic brain micro-tissue is prepared by controlling the proportion of methylacryloylated gelatin to methylacryloylated hyaluronic acid, the proportion of a photoinitiator, the proportion of graphene oxide and key parameters of photocuring treatment. The hydrogel-based bionic brain micro-tissue has the advantages of definite components, controllable structure and form, low cost, easiness in standardization and the like, and meanwhile, the hydrogel-based bionic brain micro-tissue shows the biological properties of high cell activity, excellent biocompatibility, good safety and outstanding physiological-like functions. The method can be applied to the fields of brain-like tissue construction, nervous system disease modeling and mechanism research, neurodrug pharmacodynamics research, drug neurotoxicity evaluation or developmental biology research and the like.

The invention belongs to the technical field of traditional Chinese medicine, and discloses a preparation method and application of a Tibetan medicine Sibiraea angustata extract, and the specific preparation process is as follows: performing heat reflux extraction on Sibiraea angustata with ethanol, and performing reduced pressure concentration to obtain a Sibiraea angustata ethanol crude extract; adding ultrapure water into the ethanol crude extract of the sibiraea angustata to prepare a suspension; degreasing the suspension with petroleum ether, extracting with ethyl acetate, and recovering the solvent under reduced pressure to obtain an ethyl acetate extract (SA-EAE); according to the invention, an HPLC-Q-TOF-MS / MS (High Performance Liquid Chromatography-Quantitative Time of Flight-Mass Spectrometry-Mass Spectrometry) method is adopted to qualitatively analyze the extract, and the result shows that the extract contains 32 compounds of 8 classes, including flavonoids (45%), phenolic acids (20%), triterpenoids (15%) and the like. A high fat diet-induced metabolism-related fatty liver disease (MAFLD) mouse model is adopted, pharmacodynamic research on the metabolism-related fatty liver disease finds that the extract disclosed by the invention can be used for remarkably improving the fatty metabolic disorder, so that the extract disclosed by the invention has a prospect of being developed into the medicine for improving the glycolipid metabolic disorder and the inflammatory response.

The application discloses a uniform Fructus aurantii polysaccharide and a preparation method and application thereof, and comprises the following steps: after defatting Fructus aurantii powder by petroleum ether, the Fructus aurantii powder is sequentially subjected to hot water extraction, primary alcohol precipitation, secondary alcohol precipitation, precipitation redissolution, protein removal by a Sevag method and decolorization to obtain Fructus aurantii crude polysaccharide; the Fructus aurantii crude polysaccharide is separated by anion exchange chromatography and dextran exclusion gel chromatography in series to obtain the uniform Fructus aurantii polysaccharide. The uniform Fructus aurantii polysaccharide is obtained by extraction and separation from Fructus aurantii for the first time, and the pharmacodynamic study shows that the uniform Fructus aurantii polysaccharide has the action of inhibiting hepatoma cell activity, thereby providing a new thought for developing and preparing an anti-human hepatoma cell drug; the preparation process is simple, the uniform polysaccharide can be quickly obtained, and the application is suitable for large-scale production.

Provided are an interleukin receptor antagonist and an application thereof, and specifically provided is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof. The provided compound exhibits potent biological activity and good pharmacokinetic properties, or demonstrates good efficacy in animal pharmacodynamic studies. c[X4-X5-X6-X7-X8-X9]-X10-X11-X12-X13-X14-X15-X16 (I)

This invention discloses the pharmaceutical use of schisandrin B in the preparation of analgesic drugs, wherein the analgesia is for the treatment or prevention of chemotherapy-induced neuropathic pain, and the analgesic drug can reduce mechanical and cold hyperalgesia in a chemotherapy-induced neuropathic pain model. Pharmacodynamic studies of this invention demonstrate that oral administration of schisandrin B can reduce chemotherapy-induced neuropathic pain, thereby effectively exerting an analgesic effect, and can be used as a therapeutic or preventative analgesic drug.

This invention belongs to the field of biomedical technology and provides a mussel adhesive protein and azelastine hydrochloride nasal thermosensitive gel, its preparation and application. The mussel adhesive protein and azelastine hydrochloride nasal thermosensitive gel includes an active ingredient and pharmaceutically acceptable excipients. The active ingredient is recombinant mussel adhesive protein mefp-5 subtype and azelastine hydrochloride. The excipients include a thermosensitive polymer, which is mixed with the active ingredient to form a thermosensitive gel system. This invention solves the technical problem that existing single-drug formulations cannot simultaneously provide rapid symptom relief and long-term mucosal barrier repair for allergic rhinitis by combining recombinant mussel adhesive protein mefp-5 subtype with mucosal repair function with azelastine hydrochloride, which has rapid anti-allergic effects. Pharmacodynamic studies have confirmed that the two active ingredients exhibit a significant synergistic effect (CDI < 0.7) in improving allergy symptoms, inhibiting inflammatory responses, and repairing the mucosal barrier.

The invention discloses a preparation method and application of a traditional Chinese medicine spray for treating asthma, and belongs to the technical field of traditional Chinese medicine preparations. The stability problem of the traditional Chinese medicine spray is systematically solved through the synergistic effect of alcohol precipitation impurity removal, volatile oil clathration, pH regulation and control and the ternary stabilizer. Pharmacodynamic studies show that the spray can remarkably reduce the inflammatory factor level of asthma model mice and prolong the incubation period of asthma inducing of guinea pigs, has the effect better than that of oral granules, takes effect quickly and is suitable for quick relief in the acute attack period of asthma.

The application belongs to the field of traditional Chinese medicines, and particularly discloses application of a leech dredging collaterals preparation in preparation of an anti-tumor medicine. The leech dredging collaterals preparation is prepared from four raw medicinal materials of astragalus, ligusticum wallichii, leech and salvia miltiorrhiza, and has the effects of tonifying qi and activating blood and dredging qi and collaterals. Pharmacodynamic studies show that the leech dredging collaterals preparation has the effects of inhibiting growth of liver tumors and lung tumors, is safe and has a good effect, expands the clinical application range of the leech dredging collaterals preparation, and has a good popularization and application prospect.

This application proposes the use of ACSL4 and / or TfR1 genes as targets in the preparation of drugs for the prevention or treatment of non-alcoholic fatty liver disease (NAFLD) under hypoxic conditions. The drugs include resveratrol, which inhibits hypoxia-induced ferroptosis by downregulating the expression of key ferroptosis genes ACSL4 and TfR1. Compared with existing technologies, this application has the following advantages: This application reveals the antioxidant, anti-inflammatory, liver-damage-alleviating, and lipid metabolism-regulating effects of resveratrol using a hypoxic NAFLD model. Pharmacodynamic studies targeting resveratrol demonstrate that ACSL4 and TfR1 have a significant ability to regulate ferroptosis and may affect the progression of NAFLD, which is of great significance for the development of subsequent related drugs and the rational use of medications at high altitudes.

Provided herein are methods and compositions related to in vivo testing of therapeutic agents comprising human Fc in genetically modified rodents (e.g., testing pharmacokinetic and / or pharmacokinetic properties of such therapeutic agents in genetically modified rodents). In some embodiments, the genetically modified rodent expresses an antibody comprising a human Fc (e.g., human IgG1 Fc, human IgG4 Fc). In some embodiments, the rodent expresses a fully human antibody (i.e., an antibody having a human heavy chain and a human light (gamma or kappa) chain). In certain embodiments, the genetically modified rodents comprise one or more Fc receptors having a human extracellular domain (e.g., neonatal Fc receptor (FcRn), beta-2-microglobulin polypeptide (beta2M), Fc epsilon receptor 1 alpha (Fc epsilon R1 alpha), Fc gamma receptor 1 alpha (Fc gamma R1a), Fc gamma receptor 2a (Fc gamma R2a), Fc gamma receptor 2b (Fc gamma R2b), Fc gamma receptor 3a (Fc gamma R3a), Fc gamma receptor 3b (Fc gamma R3b), Fc gamma receptor 2c (Fc gamma R2c)). The transmembrane and cytoplasmic domains of the receptors can be human or non-human (e.g., rodents).