19 results about "CCL4" patented technology

Provided herein are methods and immune biomarkers that identify progression and treatment options for multiple sclerosis (MS). Also provided are materials and methods for the prognosis, staging, and monitoring of MS in a sample and include methods of determining a subject as being at risk of developing MS. The methods include detecting at least one biomarker, such as CXCL13, CXCL10, CD27, NEFL, CCL4, and / or CCL3 in cerebrospinal fluid (CSF) in the subject; and administering a pharmaceutically effective amount of a treatment (e.g., tolebrutinib and potentially one or more additional therapies, such as an anti-CD20 therapy) to the subject.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a small molecule compound P7C3 in preparation of a pharmaceutical preparation for inhibiting hepatic fibrosis. According to the invention, a CCl4-induced hepatic fibrosis mouse model is used for verifying the treatment effect of P7C3 on hepatic fibrosis. Meanwhile, the influence of P7C3 on HSC activation and proliferation is verified, eIF4A1 is a direct target of P7C3 for inhibiting HSC activation, and P7C3 is a promising anti-hepatic fibrosis therapeutic drug and an effective eIF4A1 inhibitor.

Provided are a CAR-T cell having good blood-brain barrier permeability, a product, and a use. On the basis of the research on CAR-T cell therapy for central nervous system diseases, provided are a CAR-T cell having good blood-brain barrier permeability and a corresponding drug, for use in treating or relieving central nervous system diseases. Such a CAR-T cell uses a B cell maturation antigen as a target, and highly expresses a CXCR3 chemokine receptor and CCL1, CCL3 and CCL4 chemokines. Also provided is a product for testing and determining the blood-brain barrier permeability of the CAR-T cell, e.g., a probe, a reagent, and a kit, thereby accurately testing and determining the blood-brain barrier permeability of a certain CAR-T cell.

The application discloses a construction method and application of engineering escherichia coli for producing humulone, and the pTrcHis2B-IDI plasmid and pACYDuet-1-CCL4-VPS-PT1-linker-PT2 plasmid are transferred into engineering escherichia coli Trc-low competent cells to obtain the engineering escherichia coli for producing humulone. The engineering humulone bacteria are constructed based on the Trc-low competent cell host, the pACYDuet-1-CCL4-VPS-PT1-linker-PT2 is combined with the pTrcHis2B-IDI, the side chain precursor activation function of CCL4 is matched with the IDI / DMAPP donor module, the VPS-mediated skeleton construction and the PT1 / PT2-mediated continuous isoprenylation process are further connected, the humulone target path can be more completely operated in the same host, and therefore the specificity, continuity and directional guiding ability of the product biosynthesis are improved.

The invention discloses rhizoma acori graminei polysaccharide as well as a preparation method and application thereof. According to the method disclosed by the invention, the acorus tatarinowii polysaccharide is obtained from the root tuber of the acorus tatarinowii Schott by adopting the methods of water extraction, alcohol precipitation and column separation and purification. Cell experiment results show that the rhizoma acori graminei polysaccharide can significantly inhibit activation of TGF-beta induced hepatic stellate cells (LX-2), and carbon tetrachloride (CCl4) induced hepatic fibrosis mouse model experiments show that the rhizoma acori graminei polysaccharide can significantly reduce CCl4 induced collagen deposition and expression of liver tissue alpha-smooth muscle actin (alpha-SMA), and can significantly inhibit TGF-beta induced hepatic stellate cells (LX-2) activation. The content of asparaginic acid aminotransferase (AST), alanine aminotransferase (ALT) and the like in serum of a hepatic fibrosis model mouse is reduced, and the compound can be used for preparing candidate carbohydrate drugs or liver protection health care products for treating and / or treating hepatic fibrosis.

The invention belongs to the technical field of fungal polysaccharide application, and particularly relates to a yellow-rose yellow-meat boletus polysaccharide as well as a preparation method and application thereof. The preparation method comprises the following steps: extracting crude polysaccharide from boletus rosea sporocarp through a water extraction and alcohol precipitation method, and then carrying out deproteinization, decoloration and DEAE-52 cellulose column chromatography separation and purification to obtain the purified polysaccharide BPP-1 of the boletus rosea water component. CCl4 is selected as an inducer of oxidative stress injury of the MIHA cells to construct a hepatic cell oxidative injury model, and the model is utilized to evaluate the protective effect of BPP-1 on CCl4-induced MIHA cell hepatic injury. The result shows that the BPP-1 reduces the release of ALT and AST, improves the GSH level and the SOD enzyme activity at the same time, inhibits the generation of a lipid peroxidation product MDA, and effectively reduces the damage of CCl4 to liver cells. The results show that BPP-1 has a certain protection effect on CCl4-induced hepatocyte injury, and BPP-1 may be a potential antioxidant and can alleviate oxidative injury of liver.

The application belongs to the technical field of biology, and specifically discloses a method for rapidly constructing a liver fibrosis animal model, which establishes a mouse liver fibrosis model by jointly using CCl4 and a MEK1 / 2 kinase inhibitor, i.e., trametinib. The trametinib can inhibit the MEK1 / 2 kinase and the ERK1 / 2 pathway. Compared with a traditional CCl4 modeling method, the modeling method provided by the application has the advantages of rapid modeling speed, obvious liver fibrosis phenotype after two weeks of administration, and the like. After four weeks of administration, the liver fibrosis degree of the "CCl4+trametinib" group is significantly higher than that of the CCl4 group, and meanwhile, the liver damage of the mouse is also significantly aggravated, but the trametinib has no obvious influence on the kidney function. In general, the liver fibrosis model provided by the application has the advantages of high specificity, rapid modeling speed, obvious phenotype, simple and safe operation, and the like, and is a modeling method superior to the traditional CCl4 modeling method.

The invention relates to a T cell intracellular factor composition and application thereof, the T cell intracellular factor composition is selected from multiple of CCL3, CCL4, IFN gamma and TNFa, and the expression levels of the CCL3, the CCL4, the IFN gamma and the TNFa in peripheral blood of active tuberculosis patients are obviously different. As the expression levels in the peripheral blood of the active tuberculosis patient are obviously different, different stages and health states of tuberculosis can be accurately distinguished, the accuracy and specificity of diagnosis are obviously improved, and a reliable basis is provided for clinical diagnosis.

The invention relates to a marker and a prediction model for predicting the shunt operation curative effect of an idiopathic normal pressure hydrocephalus patient and application of the marker and the prediction model, and belongs to the technical field of biological detection. The marker combination disclosed by the invention comprises genes IFN gamma, IL-1beta, IL-6, TNF-alpha, CCL3, CCL4, CCL5, CXCL16, GZMB and TGF beta. The marker combination provided by the invention is closely related to the prognosis effect of the iNPH, and a prediction model for the shunt operation curative effect of the patient with the idiopathic normal pressure hydrocephalus can be further constructed through the marker combination. The embodiment verifies that when the marker combination is used for predicting the shunt operation curative effect of the idiopathic normal pressure hydrocephalus patient, the sensitivity can reach 100.0%, and the specificity can reach 96.0%.

The invention relates to the technical field of animal model construction and evaluation, in particular to an evaluation method of a CCl4-induced cirrhosis model and application of the evaluation method. Comprising the following steps: S1, establishing a rat liver cirrhosis model by adopting a CCl4 induction mode; s2, performing ultrasonic imaging on the liver cirrhosis model rat to obtain a gray value of the liver of the liver cirrhosis model rat; s3, evaluating the liver injury degree of the liver cirrhosis model rat according to the gray value of the liver of the liver cirrhosis model rat. The invention provides a method for accurately and comprehensively evaluating the liver injury degree without preparing pathological tissue slices or detecting liver functions or additionally adding experimental animals, and the method has important significance on screening of animal models and development of related animal experiments.

Provided herein are methods and immune biomarkers for identifying multiple sclerosis (MS) progression and treatment options. Materials and methods for prognosing, staging, and monitoring MS in a sample are also provided, including methods for determining a subject as at risk for developing MS. The methods include detecting at least one biomarker, such as CXCL13, CXCL10, CD27, NEFL, CCL4, and / or CCL3, in the cerebrospinal fluid (CSF) of a subject, and administering a pharmaceutically effective amount of a therapy (e.g., trebrutinib and potentially one or more additional therapies, e.g., an anti-CD20 therapy) to the subject.

Provided herein are methods and immune biomarkers for identifying progression and therapeutic selection of multiple sclerosis (MS). Also provided are materials and methods for prognosis, staging, and monitoring of MS in a sample, and including methods of determining that a subject is at risk of developing MS. The method comprises detecting at least one biomarker, such as CXCL13, CXCL10, CD27, NEFL, CCL4, and / or CCL3, in the cerebrospinal fluid (CSF) of the subject; and administering to the subject a pharmaceutically effective amount of a treatment (e.g., tobutinib and potentially one or more additional therapies, such as an anti-CD20 therapy).

The invention relates to hepatic fibrosis intervention, and provides a pharmaceutical composition for treating and / or preventing hepatic fibrosis related to TET2 function deficiency type myeloid cells and application of the pharmaceutical composition. The composition comprises: (a) an inhibitor or antagonist for inhibiting chemotactic signals mediated by CCL2 and / or CCL8 and CCR2 and / or CCR3; and (b) an IL-6 pathway inhibitor. Preferably, (a) is Bindarit or a pharmaceutically acceptable salt thereof, and (b) is an IL-6 neutralizing antibody or an IL-6 receptor antibody. According to the composition, by reducing mononuclear cell recruitment / proinflammatory mononuclear cell source macrophage infiltration and blocking IL-6 mediated hepatic stellate cell activation, collagen deposition is relieved, and fibrosis indexes such as alpha-SMA and Col1a1 are reduced. Animal experiments show that in a CCl4-induced myeloid Tet2 deletion mouse model and an old-age chimeric model, combined administration is superior to single administration.

Embodiments disclosed herein provide compositions for increasing CCL3 and / or CCL4 interactions with CCR5 and / or CCR1 to enhance an immune response. Applicants identified specific interactions between CD8+ T cells and inflammatory monocytes / macrophages that change during tumor progression from small to medium to large tumors. The ligands CCL3 and CCL4 are expressed in a specific subset of T cells (CD8+ PD-1+ TIM3+ T cells). The receptors CCR5 and CCR1 are expressed in inflammatory monocytes / macrophages. Modulation or maintenance of these interactions can allow enhanced immune responses for treating cancer, as well as for vaccination.

Disclosed is a CAR-T cell with good blood-brain barrier permeability, a product, and use thereof, relating to the technical field of treatment of central nervous system diseases. Based on the study on CAR-T cell immunotherapy for central nervous system diseases, this disclosure provides a CAR-T cell with good blood-brain barrier permeability and a corresponding drug for treating or improving the central nervous system diseases. The CAR-T cell targets B-cell maturation antigens and highly expresses a chemokine receptor CXCR3 and chemokines CCL1, CCL3, and CCL4. This disclosure further provides a product for detecting and judging the blood-brain barrier permeability of the CAR-T cell, such as probes, reagents, and kits, which can accurately detect and judge the blood-brain barrier permeability of a specific CAR-T cell.

The invention relates to a macrophage-targeted C5aR1 knock-down AAV virus and an application thereof. By adopting an adeno-associated virus vector system driven by an F4 / 80 promoter, macrophage specific C5aR1 gene knock-down is successfully realized through caudal vein injection, and the expression quantity of the macrophage specific C5aR1 gene knock-down is obviously reduced by more than 90% (AAV.shC5aR1 vs AAV.null, Plt, 0.01). The key regulation effect of the C5aR1 gene in the CCl4-induced hepatic fibrosis process is clarified for the first time, it is proved that targeted knock-down macrophage C5aR1 can remarkably improve liver function indexes, relieve inflammatory response and reverse the fibrosis process, an ideal preclinical research model is provided for developing C5aR1-targeted hepatic fibrosis treatment drugs, and the C5aR1-targeted hepatic fibrosis treatment drugs have important clinical application value.

The invention belongs to the technical field of biology, and particularly relates to a group of markers for predicting the immunotherapy effect of EGFR gene mutation NSCLC patients and application of the markers. The biomarker disclosed by the invention is simple and convenient to sample and quick in result reporting. The biomarker disclosed by the invention is high in accuracy: the AUC of CCL4 is equal to 0.771, the sensitivity is 0.64, the specificity is 0.67 ([95% CI: 0.62-0.93]); plt; 0.05) of the substrate (1); the AUC of the PD-L1 is equal to 0.720, the sensitivity is 0.60, the specificity is 0.82 ([95% CI: 0.55-0.89]); plt; 0.05) of the method. In a screening queue, a combined diagnosis ROC curve of CCL4 and PD-L1 is as follows: AUC is equal to 0.907, the sensitivity is 0.667, and the specificity is 1.000 ([95% CI: 0.696-1.000]); plt; 0.05) of the substrate (1); in the verification queue, the AUC of the combined diagnosis of CCL4 and PD-L1 is equal to 0.833, the sensitivity is 0.69, the specificity is 0.91, and the AUC is less than [95% CI: 0.70-0.96]; plt; 0.05) of the substrate (1); therefore, the efficiency of combined diagnosis of the CCL4 and the PD-L1 is higher than that of diagnosis by independently using the CCL4 or the PD-L1; the marker is high in diagnosis efficiency, the immunotherapy curative effect of the NSCLC patient with EGFR gene mutation is predicted, and clinical guidance is provided.

The present invention relates to a method of identifying a T-cell reactive to cells presenting a T-cell activating antigen (cancer-reactive T-cell), comprising (a) determining expression of at least one of CCL4. CCL4L2. CCL3. CCL3L1, and CXCL13 in T-cells from a sample of a subject: and (b) identifying a cancer-reactive T-cell based on the determination of step (a). The present invention also relates to a method of identifying a TCR binding to a cancer cell of a subject. said method comprising (A) identifying a cancer reactive T-cell according to the afore-said method (B) providing the amino acid sequences of at least the complementarity determining regions (CDRs) of the TCR of the cancer-reactive T-cell identified in step (A): and. hereby. (C) identifying a TCR binding to a cancer cell. The present invention further relates to further methods and cancer-reactive T-cells related thereto.