43 results about "Inflammatory pathways" patented technology

The present invention is concerned with new compounds, and particularly those having a fused bicyclic ring substituted with an amidine moiety. These compounds are each potent inhibitors of Factor D of the alternate pathway of complement, C1s of the classical pathway of complement, Factors Xa, XIIa, VIIa and thrombin of the coagulation pathway, plasmin in the fibrinolytic pathway, and kallikrein and high molecular weight kininogen in the inflammatory pathways. These proteases, which have serine in their active site, are called serine proteases and they are pivotal to most of the processes of inflammation and coagulation. In fact, these various systems are interactive with one another and it is difficult to activate one pathway without it influencing the others.

Described herein are systems and methods for applying extremely low duty-cycle stimulation sufficient to treat chronic inflammation with progressively longer delays (off periods) from an initial stimulation. In particular, described herein are supra-threshold pulses of electrical stimulation sufficient to result in a long-lasting (e.g., >48 hours) inhibition of pro-inflammatory cytokines and / or effects of chronic inflammation; the delay between initial doses (which may be single-pulse doses) may be extended for subsequent doses, potentially dramatically enhancing battery and device longevity.

This document provides methods and materials related to regulating inflammatory pathways. For example, compositions and kits containing two or more of an anticholinesterase compound, a choline compound, and a carnitine compound and methods for using the compositions and kits described herein to support acetylcholine function to regulate one or more inflammatory pathways are provided.

Activation of 5-HT2A receptors using agonists at surprisingly low concentrations was shown to potently inhibit TNF-α-induced inflammation in multiple cell types. Significantly, proinflammatory markers were also inhibited by the agonist, (R)-DOI, even many hours after treatment with TNF-α. With the exception of a few natural toxins, no current drugs or small molecule therapeutics demonstrate a comparable potency for any physiological effect. TNF-α and TNF-α receptor mediated inflammatory pathways have been strongly implicated in a number of diseases, including atherosclerosis, asthma, rheumatoid arthritis, psoriasis, type II diabetes, depression, schizophrenia, and Alzheimer's disease. Importantly, because (R)-DOI can significantly inhibit the effects of TNF-α many hours after the administration of TNF-α, potential therapies could be aimed not only at preventing inflammation, but also treating inflammatory injury that has already occurred or is ongoing.

The invention discloses an application of Cornulin as a target in preparation of a drug for preventing and treating psoriasis. Cornulin is taken as the drug target on the gene level and / or the protein level for the drug. Cornulin is positively correlated with development of psoriasis, when a Cornulin antibody with proper concentration is used for treating an imiquimod mouse model of psoriasis, scales and skin lesion thickness can be improved, and AKT signals can be inhibited to inhibit development of psoriasis and inhibit skin lesion for returning to normal; compared with other psoriasis treating drugs, and the Cornulin antibody has the advantages that the intervention target is clearer, that is, AKT signal related molecular pathways in inflammatory pathways for psoriasis incidence are targeted.

The present invention relates to peptidomimetic macrocycles comprising at least one macrocycle-forming linker and an amino acid sequence chosen from the group consisting of : i) an amino acid sequence with at least about 50%, 60%, 70%, 80%, 90%, or 95% sequence identity to a human sequence IRAK2 54-71 (SEQ ID No.1) and 100% identity with the amino acids in the positions 5-6, 9-11, 14-15 or ii) an amino acid sequence with at least about 50%, 60%, 70, 80%, 90%, or 95% sequence identity to a human sequence IRAKM 66-83 (SEQ ID No.2) and 100% identity with the amino acids in the positions 5-6, 9-11, 13-14, wherein the peptidomimetic macrocycle comprises an a-helix and at least two natural or two non-natural amino acids crosslinked by a macrocycle-forming linker. It also concerns method of preparation of said peptidomimetic macrocycles and uses thereof, pharmaceutical composition and uses thereof, in particular as inhibitors of inflammatory pathways.

Methods and compositions are disclosed to treat neuropsychiatric disorders based upon a new framework of diagnosis. Axis I biomarkers include genes related to prefrontal dopamine synthesis and / or dopamine degradation. Axis II includes genes related to re uptake of dopamine, norepinephrine and serotonin and autonomic hyperactivity. Axis III includes genes relates to impairments in inflammatory pathways, glutamate neurotransmission and / or neurotrophic factors. Axis IV includes genes related to glutamate reuptake and predisposition to addictive behavior, and obsessive compulsions.

The instant invention relates to a transgenic, non-human animal that carries a mutation in the gene encoding C-reactive protein (CRP). Preferably, the invention relates to an animal comprising a homozygous CRP-deficient mouse and techniques for producing such animals. The invention also relates to organs, tissues, cells, cell lines and sub-cellular fractions derived from such animals. Techniques for generating total or tissue-specific CRP knockout animals are also described. The invention further relates to the use of such knockout animals for the study of the role of CRP proteins in vivo or ex vivo, particularly in relation to its role in inflammatory pathway and in the etiology human diseases.

The subject invention pertains to methods of identifying miRNAs that are differentially expressed in a lymphatic vessel cell under a proinflammatory stimulus. The invention also pertains to profiles of miRNAs that are differentially expressed in a lymphatic vessel cell under a proinflammatory stimulus and their use as biomarkers for diagnosis of inflammation mediated diseases. The current invention also provides therapeutic agents for the treatment of inflammation mediated lymphatic diseases wherein the therapeutic agents are capable of modulating the activity of the miRNAs differentially expressed in a lymphatic vessel cell under a proinflammatory stimulus.

The invention discloses an application of pyrroloquinoline quinone to medicines resistant to asthma and allergic reaction. Pyrroloquinoline quinone can relieve allergic airway inflammation through antioxidant and anti-inflammatory effects, and is a potential novel medicine for the treating asthma. Pyrroloquinoline quinone has high antioxidant and anti-inflammatory effects. The in-vivo and in-vitrostudies carried out by the invention show that pyrroloquinoline quinone can reduce allergic airway inflammation by improving the immune microenvironment and regulating a JAK-STAT signaling pathway, and research shows that pyrroloquinoline quinone is safe for oral administration, so that pyrroloquinoline quinone is a potential novel medicine for treating asthma. Pyrroloquinoline quinone exists naturally in nature and can be supplemented by diet, the safety is good, the side effects are low, and the accessibility is high. Pyrroloquinoline quinone is a non-glucocorticoid immunomodulator that targets an asthma inflammatory pathway, the mechanism of medicine action is different from that of current medicines for treating asthma, and mutual complementing can be carried out.

The invention relates to the technical field of natural drugs, and particularly relates to a preparation method and application of a herba chloranthi serrati extract. The invention provides the application of the herba chloranthi serrati extract. A CCK8 cell proliferation detection experiment shows that the herba chloranthi serrati extract has no cytotoxicity effect on HepG2.2.15, has an obvious inhibiting effect on HBsAg and HBeAg antigen secretion, and shows a better anti-hepatitis B virus application prospect. The content of AST in HepG2.2.15 cell supernatant can be reduced, and a better anti-liver injury effect is shown. Huvec cell model transcriptome data analysis shows that the gene expression level of inflammatory pathways such as a TNF signal pathway and an IL-17 signal pathway can be effectively regulated, and a better liver inflammation regulating function is achieved.

Compounds and methods for multi-targeted protein kinase modulation for angiogenesis, cancer treatment or the inflammatory pathways associated with those conditions are disclosed. The compounds and methods disclosed are based on substituted 1,3-cyclopentadione compounds.

The present invention describes a multifunctional system in which a nanostructure (size range of about 10-1000 nm) degrades on exposure to an infection and its associated inflammatory milieu. The degraded nanostructures release the encapsulated drug during the process of degradation, where the kinetics of drug release is determined by the severity of the infection and inflammation. This degradation is triggered by proteases secreted by the pathogen, host polymorphonuclear leucocytes and other host cells. The nanostructures are conjugated to anti-TLR (Toll-like receptor) ligands for targeting the corneal epithelium and blocking the inflammatory pathway.

The invention relates to the field of traditional Chinese medicines, in particular to an application of eight-treasure pills in preparation of a medicine for preventing and treating the liver cancer.The invention discloses prevention and treatment effects of the eight-treasure pills on solid tumor and advanced ascites tumor of the liver cancer. The mechanism of action is that anti-tumor cell proliferation is generated by inhibiting activation of a JAK / STAT signaling pathway. It is further defined that the effect is to inhibit a tumor promotion inflammatory pathway by inhibiting phosphorylation of STAT3. Lymphocytes in ascites can be activated to secrete and express IFN-gamma, the survival time of tumor-bearing mice is remarkably prolonged, and the application prospect of tumor drugs is great.

The invention provides a polypeptide that attenuates the activation of Fas, TNFR1, or both. The polypeptide can be used to treat conditions associated with dysregulation of the cell death or inflammatory pathway and can be formulated into pharmaceutical compositions for medical or veterinary use.

The invention provides a method for regulating the polarization state of macrophages. The method comprises the step of activating cholinergic anti-inflammatory pathways of the macrophages by adoptingcholinergic anti-inflammatory pathway agonists and / or vagus nerve electrical stimulation signals. According to the method in the invention, the cholinergic anti-inflammatory pathway agonists are adopted to stimulate the macrophages in vitro; or the electrical stimulation signals are adopted to stimulate vagus nerves in vivo; therefore, the cholinergic anti-inflammatory pathways are activated; polarization of M1 type macrophages is inhibited; polarization of M2 type macrophages is promoted; a regulating effect on macrophage polarization types is achieved; and the method has the important significance in the aspects of specifically regulating the functions of the polarized macrophages and diseases caused by the polarized macrophages.

Described herein are methods for treating a subject suffering from or at risk for a condition mediated by an inflammatory cytokine cascade, by electrically or mechanically stimulating vagus nerve activity in an amount sufficient to inhibit the inflammatory cytokine cascade.

A recombinant construct arranged for expression of a specific hairpin microRNA which disrupts crosstalk between the two inflammatory pathways is described for intervening in early cancer progression events. Accordingly, the construct can be used as a molecular therapeutic approach to prevent cancer of epithelial origin in mammals, which include but are by no means limited to cancers of the head and neck, lung, breast, ovarian, and prostate tissues.

Use of dietary fibre material extracted from grasses of the Poaceae family such as sugarcane, sweet sorghum and bamboo for the alleviation of chronic inflammation through improvement in intestinal flora and reduction of pro-inflammatory pathways.

A multifunctional system in which a nanostructure (size range of about 10-1000 nm) degrades on exposure to an infection and its associated inflammatory milieu. The degraded nanostructures release the encapsulated drug during the process of degradation, where the kinetics of drug release is determined by the severity of the infection and inflammation. This degradation is triggered by proteases secreted by the pathogen, host polymorphonuclear leucocytes and other host cells. The nanostructures are conjugated to anti-TLR (Toll-like receptor) ligands for targeting the corneal epithelium and blocking the inflammatory pathway.

There is provided a method of modifying vasoactivity by regulating a soluble Aβ pro-inflammatory pathway. Also provided is a method of modifying inflammatory reactions in microglia and neurons by regulating a soluble Aβ pro-inflammatory pathway. A method of treating patients with vascular disease by modifying an intracellular soluble Aβ pro-inflammatory pathway is also provided. A pharmaceutical composition consisting essentially of an effective amount of a soluble Aβ pro-inflammatory pathway regulator in a pharmaceutically effective carrier is also provided.

The invention discloses an anti-glioma polypeptide molecule which consists of a leader peptide TAT and PICK1. The invention also discloses an application of the anti-glioma polypeptide molecule in preparing anti-glioma medicaments and an application of the anti-glioma polypeptide molecule in a nude mouse subcutaneous glioma model. The polypeptide molecule disclosed by the invention penetrates through cell membranes to be combined with the intracellular TLR4 so as to cause endocytosis, so that the inflammatory pathway of the polypeptide molecule is blocked, and generation and development of gliomas are realized. Therefore, the invention provides guidance for the fields related to drug guidance and treatment methods, and provides theoretical basis for target diagnosis of gliomas and preparation of treatment drugs.

Clostridium difficile infection is the leading cause of hospital acquired antibiotic-associated diarrhea in the US (Bartlett, in 2006). The increased prevalence of circulating C. difficile strains poses a significant health threat to US health care facilities. Strains expressing the toxin C. difficile Transferase (CDT), in addition to Toxins A and B (TcdA and TcdB), are more virulent and are associated with higher mortality rates (Bacci et al., 2011). We recently identified a protective role for eosinophils against C. difficile pathogenesis (Buonomo et al., 2016). We have also defined CDT's ability to increase host inflammation and suppress protective eosinophils through a TLR2 dependent mechanism (Cowardin et al., 2016). How CDT promotes virulence and eosinophil suppression via TLR2 is still under investigation. We employed a genome-wide microarray approach to reveal divergent transcriptional profiles between protected (TLR2− / −) and unprotected (WT) mice infected with either CDT expressing or CDT mutant strains of C. difficile. This work revealed novel host mediated TLR2-dependent inflammatory pathways to CDT. We provide an unbiased framework for understanding the host immune response to the binary toxin CDT produced by C. difficile and how TLR2 signaling enhances virulence.

The invention discloses a composition for treating severe depression, which is characterized in that it comprises buprenorphine active ingredients and dextromethorphan active ingredients; the weight ratio of the buprenorphine active ingredients and dextromethorphan active ingredients is 1:7.5‑300. Through the synergistic compounding of buprenorphine and dextromethorphan, the present invention stimulates mu opioid receptors, antagonizes kappa opioid receptors, antagonizes NMDA receptors, stimulates sigma-1 receptors, antagonizes 5-HT receptors and NE The combination of multiple targets and multiple mechanisms, such as receptors and blocking inflammatory pathways, can greatly improve the therapeutic effect on patients with major depressive disorder (MDD), especially treatment-resistant depression (TRD), while dextromethorphan reduces The dosage and addictiveness of buprenorphine have been improved, and it has the advantages of multi-target, quick onset and low addictiveness.

The invention discloses a composition for treating major depressive disorder. The composition is characterized by comprising buprenorphine active ingredients and dextromethorphan active ingredients, wherein the weight ratio of the buprenorphine active ingredients to the dextromethorphan active ingredients is 1: (7.5-300). Through synergistic compounding of buprenorphine and dextromethorphan, underthe combined action of multiple targets and multiple mechanisms such as activation of mu opioid receptors, antagonism of kappa opioid receptors, antagonism of NMDA receptors, activation of sigma-1 receptors, antagonism of 5-HT receptors and NE receptors, blocking of inflammatory pathways and the like, the composition can greatly improve the treatment effect on patients with major depressive disorder (MDD), and especially with treatment refractory depression (TRD); and meanwhile, the dosage and addiction of the buprenorphine are reduced through the dextromethorphan, and the composition has theadvantages of being multi-target, rapid in effect taking and low in addiction.

The present invention relates to peptidomimetic macrocycles comprising at least one macrocycle-forming linker and an amino acid sequence chosen from the group consisting of: i) an amino acid sequence with at least about 50%, 60%, 70%, 80%, 90%, or 95% sequence identity to a human sequence IRAK2 54-71 (SEQ ID No 1) and 100% identity with the amino acids in the positions 5-6, 9-11, 14-15 or ii) an amino acid sequence with at least about 50%, 60%, 70, 80%, 90%, or 95% sequence identity to a human sequence IRAKM 66-83 (SEQ ID No2) and 100% identity with the amino acids in the positions 5-6, 9-11, 13-14, wherein the peptidomimetic macrocycle comprises an α-helix and at least two natural or two non-natural amino acids crosslinked by a macrocycle-forming linker. It also concerns method of preparation of said peptidomimetic macrocycles and uses thereof, pharmaceutical composition and uses thereof, in particular as inhibitors of inflammatory pathways.

Adrenergic receptor modulating compounds and methods of using the same are provided. Also provided are methods of treating a subject for a disease or condition associated with an adrenergic receptor including administering a therapeutically effective amount of the subject compound. Aspects of the disclosure include a method of modulating an inflammatory pathway in a cell, such as the production ofTNF-[alpha] in the cell. The method can include contacting a cell with a [beta]1-selective adrenergic receptor modulating compound to selectively activate a cAMP pathway over a [beta]-arrestin pathway in the cell. Pharmaceutical compositions and kits which include the subject compounds are provided.

Adrenergic receptor modulating compounds and methods of using the same are provided. Also provided are methods of treating a subject for a disease or condition associated with an adrenergic receptor including administering a therapeutically effective amount of the subject compound. Aspects of the disclosure include a method of modulating an inflammatory pathway in a cell, such as the production of TNF-alpha in the cell. The method can include contacting a cell with β1-selective adrenergic receptor modulating compound to selectively activate a cAMP pathway over a beta-arrestin pathway in the cell. Pharmaceutical compositions and kits which include the subject compounds are provided.

The present disclosure is directed to methods of treating fibrotic conditions by administration of TR[beta] agonists. The disclosure provides methods wherein the abnormal deposition of extracellular matrix components, such as collagen, keratin, or elastin, is reduced, either through interaction of TR[beta] agonists with TGF-beta-dependent inflammatory pathways, or by other mechanisms, thereby ameliorating fibrotic symptoms.