139 results about "Cytokine storm" patented technology

The embodiment of the invention is to conformationally constrain neutralizing B cell epitopes of CoV-2, CoV-n B cell epitopes of the open reading frame proteins, including the membrane S protein, constrained by protein scaffolds, including camelid VHH nanobody in order to elicit neutralizing and blocking antibodies against viral infection. B cell epitopes are molecularly evolved by ribosome display to preempt emerging viral B cell epitopes. Moreover, CTL epitopes are designed from the open reading frame protein for eliciting cell mediated viral protection. Furthermore, mRNA vaccines are prepared for eliciting protective immunity and prevent cytokine storms.

The invention relates to the technical field of biological medicine, in particular to an antibody aiming at staphylococcus aureus enterotoxin B and application thereof. A heavy chain variable region of the antibody provided by the invention comprises CDR sequences as shown in SEQ ID NO.1-3, and a light chain variable region of the antibody comprises CDR sequences as shown in SEQ ID NO.9-11. The antibody has high affinity, can specifically bind to staphylococcus aureus SEB, can block binding of SEB and MHC II / TCR, significantly inhibits cytokine storm, shows a dose-dependent protection effect in an MRSA systemic infection model, and can be used for preparing an MRSA systemic infection model. The monoclonal antibody can be used for treating, preventing or diagnosing the infection of the staphylococcus aureus, provides a solution of non-antibiotic therapy for SEB poisoning and drug-resistant staphylococcus aureus infection, and has important clinical and public health values.

The invention provides an application of a compound Aldometanib in preparation of a medicine for preventing and treating immune-related adverse reactions and diseases. Based on the first discovered prevention and treatment effects of Aldometanib on fatal immune hepatitis, immune myocarditis, pneumonia and enteritis, the invention specifically discloses application of Aldometanib in preparation of drugs for prevention and treatment of immune-related adverse reactions and diseases, and the main mechanism is that Aldometanib activates immune cells AMPK, enhances catabolism of immune cells, promotes immune cell apoptosis, promotes immune cell apoptosis, and improves immune cell apoptosis. The anabolism of the immune cells is inhibited, so that the expression of effector factors of the immune cells is controlled, and inflammatory factor storm is inhibited. Aldometanib has the effects of preventing the occurrence of immune-related adverse reactions and diseases, and inhibiting the attack levels of the immune-related adverse reactions and diseases, so that non-lethal and lethal injuries caused by an immune system to body organs are reduced.

The invention belongs to the technical field of medicines, and discloses application of baicalein in drugs related to the treatment effect of S protein and LPS induced acute lung injury. Specifically, the invention discloses an application of baicalein in preparation of drugs playing a protective role in treating pulmonary edema, inflammatory cell infiltration and cytokine storm caused by acute lung injury induced by S protein combined with LPS. Pharmacological experiments prove that baicalein has an anti-inflammatory effect in treatment of acute lung injury induced by S protein combined with LPS, and can improve pulmonary edema and promote lesion lung tissue repair.

The invention provides a quadruple plasma blood purification device and purification method. The quadruple plasma blood purification device comprises a primary plasma separator, a secondary plasma separator, a perfusion device and a dialyzer, the inlet of the primary plasma separator is connected with the artery of a patient; an inlet of the secondary plasma separator is connected with the primary plasma separator; an inlet of the perfusion device is connected with the secondary plasma separator; and the dialyzer is respectively connected with the perfusion device and the primary plasma separator. According to the technology, only one-time operation is needed for treatment for 6-12 hours, multiple operations are not needed, meanwhile, the core pathogenesis of hypertriglyceridemia, cytokine storm sepsis, internal environment disorder and renal insufficiency which cause pancreatitis is solved, the treatment time is saved to a great extent, the risk that the illness state develops to death is reduced, and the treatment cost is reduced. The clinical effective treatment rate is improved; in addition, only one set of equipment is needed, and the device has the advantages of low cost, simplicity and convenience in operation, low time, manpower and financial resource consumption, high treatment efficiency and the like.

To provide novel strategies to control cytokine release syndromes, and especially cytokine storms.SOLUTION: Embodiments of the disclosure include methods and compositions related to treatment and prevention of an excess of cytokines in an individual using fibroblasts or fibroblast-derived microvesicles. In particular embodiments, there are methods and compositions for treating and preventing toxicities in an individual that may be the result of cytokine release syndrome. In specific cases, an individual is treated for cytokine release syndrome with fibroblasts having one or more specific markers.SELECTED DRAWING: Figure 1

The invention discloses a minimally invasive flexible piezoelectric-triboelectric hybrid nanometer nerve stimulation device and application thereof.The middle layer of the nerve stimulation device is a PVDF / TMCM-MnCl3 composite nanofiber membrane, Au electrodes are evaporated on the two faces of the PVDF / TMCM-MnCl3 composite nanofiber membrane, two gold wire or copper wire electrodes are connected with the Au electrodes respectively, and the two gold wire or copper wire electrodes are connected with the Au electrodes respectively. The surface of the Au electrode is subjected to primary packaging by adopting a PU waterproof film, and the surface of the PU waterproof film is subjected to secondary packaging by adopting PDMS. The nerve stimulation device is used for conventional treatment of SIRS. The vagus nerve stimulator can generate an adjustable current up to 0.85 mA under programmable ultrasonic driving, and can be directly used for VNS. The PTNG is ultrasonically driven in vitro to assist the VNS in treating lipopolysaccharide-induced SIRS rats, release of inflammatory factors such as TNF-alpha, IFN-gamma and IL-1beta can be effectively reduced, cytokine storm is relieved, and multi-organ tissue damage and dysfunction are relieved, so that the survival hope is improved.

The invention provides a phenylacrylamide compound and a preparation method and application thereof, the phenylacrylamide compound has a structure as shown in a formula I. The phenylacrylamide compound provided by the invention can be well combined with a plurality of target proteins, especially has good inhibitory activity on ACAT1 and 3-KAT targets, and can be used for preparing a medicine for treating cancer. Moreover, the compound has better bioavailability, and can be used for preparing drugs for preventing or treating tumors, cancer pain, radiotherapy and chemotherapy injury, autoimmune diseases, infection and drug-induced myocarditis, cytokine storm, ischemic heart disease, inflammatory diseases and neurodegenerative diseases or anti-aging drugs.

The invention provides a dynamic regulation and control method for optimizing CAR-T cell amplification conditions, which comprises the following steps: acquiring high-frequency cell activity monitoring data from a cell culture system, and extracting metabolic marker fluctuation and proliferation rate mutation from the high-frequency cell activity monitoring data to obtain real-time cell state parameters; comparing the real-time cell state parameters with a T cell subset proportion and a cell factor release mode in historical immune data of the patient to obtain a cell state deviation value, and determining an abnormal fluctuation condition of proliferation rate mutation according to the cell state deviation value; if the abnormal fluctuation of the proliferation rate mutation exceeds a preset fluctuation threshold value, capturing proliferation signal abnormity by analyzing metabolic marker fluctuation and metabolic waste accumulation according to the cell state deviation value; according to the targeted culture parameter set, adjusting the oxygen supply quantity and the culture solution microenvironment of an oxygen concentration control system to obtain a culture environment for inhibiting cytokine storm and proliferation signal abnormity.

The present Invention relates to a newly designed product, i.e. substance (B+C) that combines two different mechanisms of action that allow the control of aldosterone synthesis and secretion without compromising the metabolism of cortisol (corticosterone In rats) in the.tone glomerulosa of the adrenal gland. The innovative design of the described molecule enables ths individual use of substance (B+C) in the treatment of diseases such as hyper and hypo aldosteronism, Conn's syndrome and cytokine storm caused by Covid infection or as co-therapy with corticosteroids in the treatment of a whole range of immunological diseases. The innovative design of Substance (8+C) has an additional practical and economic advantage because the patient receives both components of substance (B+C) simultaneously with just one application, regardless of the medicine formulation. This not only simplifies the medicine synthesis, dosing and clinical research, but also the application of the medicine in clinical practice. For successful and selective control of aldosterone synthesis, which in nature also means selective control of blood pressure, it was necessary to combine the two substances described in order to ensure action in patients with elevated and / or towered blood pressure with one application of Substance (B+C). This feature of Substance (B+C) is important, especially in the treatment of patients with permanently impaired aldosterone synthesis, such as Conn's disease and similar autoimmune diseases, or in combmatton with corticosteroids where prolonged or repeated corticosteroid therapy is indicated. Finally, this invention is extremely important because It enables the safe treatment of a large group of patients with hypertension who also have secondary diseases of the immune system, various inflammations or viral Infections such as Covid where corticosteroid therapy is indicated, but difficult to implement in practice due to the negative effect of corticosteroids on blood pressure.

The current invention provides novel approaches to the treatment of various disease states that lead to altered cytokine release or cytokine storms. These diseases include viral infections immunological and other non-immunological diseases. Specifically, the invention provides methods targeting ZHX2 including methods of inhibition, blocking or depletion of ZHX2 in order to treat various disease states.

The invention relates to the technical field of biological medicines, and particularly discloses application of betaine in preparation of a medicine for preventing or treating sepsis myocardial injury. Betaine (BET) provided by the invention can be used for effectively relieving cytokine storm caused by sepsis injury and inhibiting reduction of core body temperature of a mouse; the abnormal blood routine and blood biochemical indexes are improved. In addition, betaine can reduce generation of active oxygen in myocardial cells of the HL-1 mouse and improve mitochondrial membrane potential imbalance of the myocardial cells of the HL-1 mouse. The chemical structural formula of the betaine is shown in the specification.

The invention relates to the technical field of drugs, in particular to multifunctional polymyxin B nanoparticles and preparation and application thereof.The multifunctional nanospheres (HPK) of polymyxin B (PMB) are synthesized by connecting hyaluronic acid and polymyxin B through Schiff base bonds and combining KAFAK, and the multifunctional nanospheres (HPK) serve as candidate drugs for refractory infectious diseases and can release PMB in response to the infected microenvironment, so that the effect of treating the refractory infectious diseases is achieved. The targeted infection site removes bacteria and various inflammatory mediators to reduce cytokine storm, including removal of LPS and active oxygen, and inhibition of macrophage activation. Hyaluronic acid (HA) serves as a carrier of PMB, the HA and the PMB are tightly connected through a pH sensitive bond Schiff base bond, the hyaluronic acid can change the biological distribution condition of the PMB, and a targeted CD44 receptor, hyaluronidase and the Schiff base bond can achieve PMB acidic microenvironment targeted delivery and meanwhile cooperate with PMB to resist bacteria and KAFAK to resist inflammation. The design and preparation of HPK effectively achieve the effects of reducing toxicity and enhancing efficacy on PMB.

Provided are compositions that include compositions of galactosyl -conjugated lipid nanoparticles (LNPs) encapsulating one or more active agents. In some embodiments, the galactosyl- conjugated LNPs have a lipid component having D-Lin~MC3-DMA, ALC-0315 and. SM-102, cholesterol, DSPC and DOPE, and DMG-2000-PEG. In some embodiments, the GalNAc-conjugated LNP has one or more galactosyl moieties bioconjugated to cholesterol present with a lipid component of the GalNAc -conjugated LNP. Also provided are methods for treating and / or preventing diseases, disorders, and / or conditions associated, with undesirable PCSK9 gene expression, optionally a cardiovascular disease, disorder, or condition, including but not limited, to atherosclerosis and / or thrombosis, and sepsis, septic shock, cytokine storm, or sequelae thereof.

The invention relates to the field of animal models, in particular to a cytokine storm mouse model and a preparation method thereof. The method comprises the following step: injecting one or more of IL-1beta, IL-6, TNF-alpha, IL-2 and IFN-gamma into a mouse to obtain the cytokine storm mouse model. According to the method, the original microenvironment of the mouse can be changed after five cytokines are inoculated into the body of the mouse, and the multi-cytokine storm mouse model established by the method has the advantages of short disease occurrence time, long and stable model maintenance time and better clinical manifestation effect of simulating related diseases of the cytokine release syndrome.

Provided are compounds, compositions, and methods for re-polarizing tumor-associated macrophages (TAMs), reducing macrophage-mediated inflammation, and treating diseases. The compound or pharmaceutical composition can be administered to a subject in need thereof, the compound comprising a polymeric carbohydrate backbone and one or more mannose-binding C-type lectin receptor targeting moieties, and the therapeutic agent comprising one or more reactive hydroxyl groups and being attached to the polymeric carbohydrate backbone via a cleavable linker. The cleavable linker can comprise one or more carbonate and / or disulfide moieties. Diseases to be treated can include cancer, autoimmune diseases, inflammatory disorders, non-alcoholic steatohepatitis (NASH), acute respiratory distress syndrome (ARDS), sepsis, coronavirus infection, influenza infection, cytokine storm, and other macrophage-related diseases.

The present invention discloses a recombinant nucleic acid molecule encoded by at least ORF (100, 100a) to reduce cytokine storm during immunotherapy. The recombinant nucleic acid molecule comprises at least one first hairpin ring structure, at least one second hairpin ring structure and a first promoter (120). The first hairpin loop structure is formed from one or more first short hairpin RNA (130a) sequences. The first hairpin ring structure modulates the amount of interleukin 6 (IL6) cytokine during immunotherapy. The second hairpin loop structure is formed from one or more second short hairpin RNA (130b) sequences. The second hairpin ring structure modulates the amount of granulocyte monocyte colony stimulating factor (GMCSF) cytokine during immunotherapy and is disposed upstream or downstream of the first hairpin ring structure. The first promoter (120) is disposed upstream of the first hairpin ring structure and the second hairpin ring structure.

The present disclosure provides use of a promyelocytic leukemia 1 (PML-1) protein in preparation of a drug for inhibiting a cytokine storm, and belongs to the technical field of biomedicine. The present disclosure further provides use of a PML-1 protein and / or a product expressing the PML-1 protein in preparation of a drug for inhibiting a cytokine storm. In the present disclosure, the PML-1 protein and / or the product expressing the PML-1 protein can significantly inhibit the expression of proteins TAB1, TAK1, and p-TAK1 and inhibit inflammatory cytokines TNF-α, IL-1β, MIP-1α, IL-6, IL-8, and MCP-1 in an inflammatory signaling pathway, thereby inhibiting the cytokine storm. The PML-1 protein can be directly used for the treatment of inflammations and related diseases. Compared with traditional chemical anti-inflammatory drugs, the protein shows more significant curative effect, stronger specificity, lower toxicity, smaller side effects, and clearer biological functions, exhibiting broad application prospects.

The present invention belongs to the field of biomedicine and materials, and specifically relates to a protein-coupled imidazoquinoline compound and a synthesis method and application thereof. The present invention aims at the problem that imidazoquinoline agonists have large toxic side effects and are prone to cause cytokine storms when used in vivo. By coupling the active amino group of the imidazoquinoline agonist with albumin, which has low human immunogenicity, good biosafety and accumulation advantage at tumor sites, through a reduced glutathione-responsive linker, the targeting and responsive release at the tumor site are achieved, thereby reducing systemic nonspecific toxicity, reducing the possibility of causing cytokine storms, improving the immunosuppressive microenvironment of the tumor, activating anti-tumor immunity, and achieving better therapeutic effects and biosafety.

The invention discloses a chimeric antigen receptor targeting ALPPL2 and HER2 proteins, T lymphocytes modified by the chimeric antigen receptor and application of the chimeric antigen receptor and the T lymphocytes in preparation of products for killing or assisting in killing tumor cells. The receptor comprises a first antibody and a second antibody, wherein the first antibody is formed by connecting an ALPPL2 single-chain antibody and an SNIPRs signal molecule, and the second antibody is formed by connecting an HER2 single-chain antibody and an IL10 cell factor. According to the CAR-T cell disclosed by the invention, the off-target activity faced by conventional CAR-T is effectively reduced, the possibility of occurrence of cytokine storm is reduced, and the safety is higher; meanwhile, the autosecreted IL10 cell factor promotes CAR-T cell proliferation and effect functions, and the activity and durability of the CAR-T in killing tumor cells are obviously improved.

An embodiment provides a method for treating a body fluid of a patient with an inflammatory cytokine storm, including: removing the body fluid from a patient; applying a treatment to the body fluid, wherein the treatment comprises an antibody that joins with an antigen in the body fluid to form an antibody-antigen complex; removing the antibody-antigen complex from the body fluid; and returning the body fluid to the patient. Other aspects are described and claimed.

To provide methods for providing information on the specific types of bacteria among the bacteria contained in the intestinal flora to use them as materials for judging treatment policies and the like; and to provide methods for predicting COVID-19 exacerbation and methods for predicting cytokine storm exacerbation using the information.SOLUTION: Provided is a method for providing information on the genus Collinsella in the intestinal flora, comprising: an analysis step of analyzing the type and amount of the bacteria contained in a stool sample, and an information provision step of providing information on the ratio of the genus Collinsella in the intestinal flora, COVID-19 exacerbation being predicted based on the information provided.SELECTED DRAWING: None

The present Invention relates to a newly designed product, i.e. substance (B+C) that combines two different mechanisms of action that allow the control of aldosterone synthesis and secretion without compromising the metabolism of cortisol (corticosterone In rats) in the.tone glomerulosa of the adrenal gland. The innovative design of the described molecule enables ths individual use of substance (B+C) in the treatment of diseases such as hyper and hypo aldosteronism, Conn's syndrome and cytokine storm caused by Covid infection or as co-therapy with corticosteroids in the treatment of a whole range of immunological diseases. The innovative design of Substance (8+C) has an additional practical and economic advantage because the patient receives both components of substance (B+C) simultaneously with just one application, regardless of the medicine formulation. This not only simplifies the medicine synthesis, dosing and clinical research, but also the application of the medicine in clinical practice. For successful and selective control of aldosterone synthesis, which in nature also means selective control of blood pressure, it was necessary to combine the two substances described in order to ensure action in patients with elevated and / or towered blood pressure with one application of Substance (B+C). This feature of Substance (B+C) is important, especially in the treatment of patients with permanently impaired aldosterone synthesis, such as Conn's disease and similar autoimmune diseases, or in combmatton with corticosteroids where prolonged or repeated corticosteroid therapy is indicated. Finally, this invention is extremely important because It enables the safe treatment of a large group of patients with hypertension who also have secondary diseases of the immune system, various inflammations or viral Infections such as Covid where corticosteroid therapy is indicated, but difficult to implement in practice due to the negative effect of corticosteroids on blood pressure.

We describe peptides and their uses for the treatment of, e.g. acute myocardial infarction and other cytokine storm-associated conditions.

The invention relates to a bispecific antibody targeting B7H7 and CD3 and application of the bispecific antibody. Wherein the bispecific antibody comprises: a first antigen binding region, the first antigen binding region having CD3 binding activity; and a second antigen binding region, the second antigen binding region having B7H7 binding activity; wherein the first antigen binding region comprises an anti-CD3 antibody, the anti-CD3 antibody comprises a heavy chain complementarity determining region HCDR, and the HCDR comprises an amino acid sequence selected from at least one of SEQ ID NO: 4-6 and 66; the second antigen binding region comprises an anti-B7H7 antibody, the anti-B7H7 antibody comprises a heavy chain complementarity determining region HCDR, and the HCDR of the anti-B7H7 antibody comprises an amino acid sequence selected from at least one of SEQ ID NO: 26-28. The bispecific antibody with the sequence can be combined with human and monkey B7H7 with high specificity and high affinity, can be combined with human and monkey CD3 with low affinity and high specificity, can promote PBMC to kill tumor cells, and has good anti-cancer activity and higher treatment safety; the occurrence risk of cytokine storm caused by the CD3 bispecific antibody is effectively reduced.

The application provides a Brucella virus-influenza virus A co-infection mouse model and a construction method and application thereof, and belongs to the technical field of mouse model construction.The construction method of the Brucella virus-influenza virus A co-infection mouse model provided by the application is that after the mouse is anesthetized, the mouse is infected with the influenza virus A by using a lung delivery method, and 10-14 hours later, the mouse is infected with the Brucella by using the lung delivery method.The Brucella virus-influenza virus A co-infection mouse model is constructed, which is used for exploring the synergistic pathogenic mechanism of Brucella and influenza virus co-infection leading to acute lung injury and cytokine storm, screening characteristic indexes of co-infection acute lung injury and cytokine storm, and providing candidate targets for early diagnosis, prevention and clinical intervention treatment.

The invention provides a chimeric autoantibody receptor of a targeted acetylcholine receptor antibody, a CAAR-T cell and application of the chimeric autoantibody receptor in a medicine for preventing and treating myasthenia gravis, and belongs to the technical field of biological medicines. The invention provides a chimeric autoantibody receptor (CAAR) targeting an acetylcholine receptor antibody, which is characterized in that three extracellular domains of an AChR alpha subunit are connected in series through L1 and L2 connecting peptides or G4S connecting peptides to form an extracellular domain, and meanwhile, CD3 gamma only containing an ITAM motif is used as a signal transduction domain. The CAAR is expressed on the surface of a T cell, and the obtained CAAR-T not only has relatively strong binding capacity with an anti-AChR antibody, shows a relatively strong killing effect on pathogenic B cells expressing the anti-AChR antibody, can effectively relieve the symptom of myasthenia gravis, but also has relatively low risk of inducing cytokine storm, and has good drug safety.

The invention belongs to the field of medicine, and particularly relates to a nanoparticle HA-ADH-GL for inhibiting influenza virus as well as a preparation method and application of the nanoparticle HA-ADH-GL. The nanoparticle is a HA-ADH-GL conjugate synthesized by connecting glycyrrhizic acid (GL) with hyaluronic acid (HA) and a linker adipic dihydrazide (ADH), wherein the hyaluronic acid (HA) and the linker are good in biocompatibility and hydrophilicity. The nanoparticles can inhibit influenza virus replication and cytokine storm. The preparation method of the nanoparticles is simple, the cost is low, the water solubility of glycyrrhizic acid is improved, no biological safety risk and other problems exist, and reference is provided for research and development of antiviral drugs in the future.

The present invention discloses a recombinant nucleic acid molecule encoded by at least ORFs (100, 100a, 100b) for reducing cytokine storm during immunotherapy. The recombinant nucleic acid molecule comprises at least one hairpin loop structure and a first promoter (120). The hairpin loop structure regulates the amount of granulocyte-monocyte colony-stimulating factor (GMCSF) cytokine during immunotherapy. The hairpin loop structure is formed by one or more short hairpin RNA (130) sequences. The first promoter (120) is located upstream of the at least one hairpin loop structure.

The invention provides a chip model for detecting whether candidate drugs can cause cytokine storm, and belongs to the technical field of biomedicine. The chip model comprises a culture plate, the culture plate comprises a plurality of culture units, and each culture unit comprises a culture solution channel and a plurality of cell growth holes communicated with the culture solution channel; the bottom of the cell growth hole is lower than the bottom of the culture solution channel to form a growth hole concave part. According to the chip model, medicine combined immune cell killing can be carried out while 3D cell culture is realized, and whether side reaction is generated or not is detected in subsequent experiments. According to the application, higher-throughput culture and detection can be carried out, the experimental purpose of detecting and evaluating a plurality of anti-tumor drugs on the same chip is achieved, and drug safety evaluation can be carried out through components of a culture solution while drug effect evaluation is carried out.