23 results about "Translocator protein" patented technology

Disclosed herein are methods of assessing changes of expression in patients' nervous systems of molecules responsive to treatments modulating nuclear receptors for retinoid X (RXR alpha, beta, or gamma), Nurr1(NR4A2) nuclear receptors, Nur77 (NR4A1) nuclear receptors, dopamine active transporter (DAT), or dopa decarboxylase (DDC), for nervous system disorders or conditions related to these molecules.

Provided are a fluorine-18-labeled positron emission tomography (PET) radiotracer for diagnosing neuroinflammation, stroke or cerebral infarction and a method for diagnosing cancer in a subject including administering a fluorine-18-labeled PET radiotracer a subject, obtaining in vivo PET images of the uptake of the fluorine-18-labeled positron emission tomography (PET) radiotracer in a lesion in the subject, and evaluating the uptake of the fluorine-18-labeled radiotracer in the lesion.

Disclosed are genetically engineered Schizosaccharomyces pombe strains capable of fermenting glucose to produce malic acid. The S. pombe strains produce an exogenous malate dehydrogenase (MDH) enzyme and optionally produce an exogenous pyruvate carboxylase (PYC) enzyme or an exogenous phosphoenolpyruvate carboxylase (PPC) enzyme. Additionally, the S. pombe strains may be further engineered to produce a fumarase selectively located in mitochondria and / or have an inactivated mitochondrial citrate transporter, so that the resulting S. pombe strains are capable of producing malic acid as the predominant C4 dicarboxylic acid. Also disclosed are methods of producing malic acid with the S. pombe strains.

The invention belongs to the technical field of medicines, and discloses a KRT6A gene expression inhibitor and application thereof in preparation of a medicine for treating gemcitabine drug-resistant pancreatic cancer. Researches find that KRT6A is abnormally highly expressed in pancreatic cancer and is closely related to poor curative effect of gemcitabine. According to the inhibitor, KRT6A gene expression is specifically silenced in a tumor targeted delivery mode, expression and functions of nucleoside transporter ENT1 are recovered, and cellular uptake of gemcitabine is enhanced; the compound can inhibit MIF-CD44 / CD74 signal axis mediated tumor-associated macrophage M2 type polarization, reduce exogenous pyrimidine nucleoside supply and weaken competitive inhibition of the compound and gemcitabine in nucleoside transport and metabolic pathways, so that effective uptake and efficacy of gemcitabine in pancreatic cancer cells are synergistically improved, and gemcitabine drug resistance is reversed or relieved. The invention provides a new and effective technical scheme for clinical treatment of gemcitabine drug-resistant pancreatic cancer.

The application discloses a ricin toxin detection sensor based on competitive binding of ricin to mitochondrial adenine nucleotide translocator (ANT) and a detection method, which comprises ANT protein, hollow dialysis fiber, chemical cross-linking agent and fluorescently labeled ATP. When in use, the ANT is first fixed on the inner wall of the hollow fiber dialysis membrane and the fluorescently labeled ATP (cy5-12-ATP or cy3-12-ATP or DEPC-12-ATP) is added; then, it is placed in the to-be-detected solution for 30-60 seconds, and then is placed under a fluorescence detection instrument (such as a fluorescence microscope) for observation, so that the presence or absence of the ricin toxin and the approximate concentration of the toxin are determined; then, the relative intensity of the fluorescence of the to-be-detected solution is determined; a standard curve of the corresponding relationship between the concentration of the fluorescent group and the concentration of the toxin is established; and the concentration of the ricin toxin in the to-be-detected solution is obtained by substituting the concentration of the fluorescent group of the to-be-detected solution into the above standard curve and performing calculation. The application can effectively improve the detection efficiency, simplify the detection method and be widely applied in the society.

A fluorine-18-labeled positron emission tomography (PET) radiotracer for diagnosing neuroinflammation, stroke or cerebral infarction and a method for using the radiotracer are provided.

Methods for diagnosing a peripheral nervous system (PNS) neuropathy comprising administering to a subject in need of treatment thereof, at least one of a translocator protein (TSPO)-targeting compound or a PSMA-targeting compound and taking an image, are disclosed.

The present disclosure provides a therapeutic method of treating cancer metastasis by inducing clearance of EVs using a binding agent specific to an EV protein. The method utilizes one or more binding agents specific to EV proteins, where the EV proteins are selected from prostaglandin F2 receptor negative regulator (PTGFRN); basigin (BSG); immunoglobulin superfamily member 2 (IGSF2); immunoglobulin superfamily member 3 (IGSF3); immunoglobulin superfamily member 8 (IGSF8); integrin beta-1 (ITGB1); integrin alpha-4 (ITGA4); 4F2 cell-surface antigen heavy chain (SLC3A2); a class of ATP transporter proteins (ATP1A1, ATP1A2, ATP1A3, ATP1A4, ATP1B3, ATP2B1, ATP2B2, ATP2B3, ATP2B4); CD13 (aminopeptidase N); MME (neprilysin), ENPP1 (ectonucleotide pyrophosphatase / phosphodiesterase family member 1); and NRP1 (neuropilin-1). Further provided herein includes a pharmaceutical composition for the treatment of cancer metastasis.

The invention provides an SLC16A3 inhibitor based on ferroptosis regulation and application of the SLC16A3 inhibitor in lung adenocarcinoma, and relates to the technical field of biological treatment drugs. The SLC16A3 inhibitor is a drug MSC-4381, the drug MSC-4381 is an effective SLC16A3 inhibitor, the SLC16A3 inhibitor can be used for inhibiting lactic acid transporter SLC16A3, breaking the redox steady state of tumor cells, inducing ferroptosis and remarkably enhancing the curative effect of the drug gefitinib, and in an in-vivo and in-vitro model, cell proliferation, migration and invasion can be inhibited through SLC16A3 knock-down or pharmacological inhibition, so that the SLC16A3 inhibitor can be used for preventing and treating the tumor cells. The MSC-4381 and the gefitinib are combined to promote lipid peroxidation and iron ion accumulation, the tumor growth can be obviously delayed through drug combination of the MSC-4381 and the gefitinib, the effect can be partially reversed through the Ferrostatin-1, the ferroptosis-dependent mechanism of the MSC-4381 and the gefitinib is verified, and transcriptional regulation and control of the SLC16A3 by the HIF1A and influence on ferroptosis resistance are clear. The invention provides a feasible combined medication strategy, verifies the significant tumor inhibition effect of the HIF1A-SLC16A3 axis in cell and animal models, reveals the key effect of the HIF1A-SLC16A3 axis in lung adenocarcinoma drug resistance formation, and provides a new combined treatment strategy and a new molecular target.

The invention generally relates to products for use in the treatment and / or prevention of Pulmonary Arterial Hypertension (PAH). More specifically, the invention relates to translocator protein (TSPO) binding members which treat or prevent pulmonary endothelial cell dysfunction, and the use of such TSPO binding members for use in the treatment and / or prevention of PAH.

Hepcidin is an hyposideremic hormone made primarily by the liver. To address the role of hepcidin made specifically by the intestine in lowering serum iron, the inventors generated transgenic mice overexpressing the peptide specifically in this tissue. These mice exhibit, at one month of age, a severe hyposideremia, along with decreased haematological indices and hair loss. Mechanistically, they showed that intestinal hepcidin made by the transgenic mice had no effect on intestinal ferroportin, but, in contrast, induced a striking down-regulation of Divalent Metal Transporter 1 (DMT1) protein at the apical side of the enterocyte. Intestinal hepcidin can be produced in the apical side suggesting the direct role of apical hepcidin on DMT1. To confirm the therapeutic capacity of hepcidin on regulation of DMT1, the inventors developed probiotics (engineered recombinant lactic acid bacteria), capable of delivering hepcidin directly into the lumen of the intestine. They orally administrated daily these probiotics in hemochromatosis mice model, after 28 days of treatments they observe a decrease of iron overload. Thus, the present invention relates to a method for preventing or treating an iron overload associated disease in a subject in need thereof, comprising administering locally in the gut of the subject hepcidin.

Described herein are equilibrative nucleoside transporter inhibitors and methods of making and using same. In some embodiments, the inhibitors are used for the prevention and / or treatment of pain.

The present disclosure relates to the field of diseases caused by reduced synaptic inhibition, preferably those caused by reduced activity of potassium (K) / chlorine (Cl) cotransporter (KCC2). The present disclosure relates to oligonucleotides and their use in RNA editing methods that target the target adenosine in the SLC12A5 precursor mRNA encoding KCC2 or in the codon encoding the phosphorylation site in the mRNA, preferably the adenosine in the codon encoding threonine at position 1007 of the KCC2b isoform. Through editing, threonine is replaced by alanine, so that phosphorylation sites are removed, and the activity of KCC2 protein in the process of recovering GABA (gamma-aminobutyric acid) capable of inhibiting tension is increased. The disclosure further relates to oligonucleotides for the treatment of chronic pain and epilepsy.

The double-stranded oligonucleotide, the double-stranded oligonucleotide conjugate and the pharmaceutical composition provided by the invention can inhibit the expression of urate transporter 1, reduce the content of URAT1 protein and obviously reduce blood uric acid. The oligonucleotide conjugate and the pharmaceutical composition thereof provided by the disclosure are helpful for treating and / or preventing pathological conditions or diseases related to URAT1 expression, including hyperuricemia or gout.

Provided herein are ibogaine compounds which can be useful for methods of treating a neuropsychiatric disease or neurological disorder, for increasing neural plasticity, or for modulating the function of a serotonin transporter.

This disclosure relates to the field of diseases caused by reduced synaptic inhibition, preferably diseases caused by reduced activity of the potassium (K) / chloride (Cl) cotransporter (KCC2). This disclosure relates to oligonucleotides in RNA editing methods and their use in targeting adenosine in a codon encoding a phosphorylation site in the SLC12A5 mRNA precursor or mRNA encoding KCC2, preferably adenosine in a codon encoding threonine at position 1007 of the KCC2b isoform. Through editing, threonine is replaced by alanine, thereby removing the phosphorylation site and thereby increasing the activity of the KCC2 protein in a process that restores its GABAergic inhibitory tendency. This disclosure further relates to oligonucleotides for use in the treatment of chronic pain and epilepsy.

The invention belongs to the field of biotechnology and immunotherapy, and particularly relates to an NK92 cell for expressing a CD276 chimeric antigen receptor and an SLC1A5 transporter and application of the NK92 cell. The invention provides a novel genetically engineered NK92 cell, the cell not only can efficiently target CD276 positive tumor cells, but also can enhance the adaptability of the cell to glutamine deficiency in a tumor microenvironment through metabolic engineering modification, so that the in-vivo and in-vitro durability, the multiplication capacity and the anti-tumor curative effect of the cell are remarkably improved. The preparation method of the NK92 cell comprises the steps of (1) construction of a recombinant lentivirus expression vector, (2) lentivirus packaging, (3) cell infection, (4) cell amplification and the like. Experiments prove that compared with an NK92 cell which only expresses the CD276-CAR, the CD276-CAR-SLC1A5-NK92 cell has the advantage that the killing ability and the multiplication ability of the CD276 positive tumor cell under the glutamine limiting condition are remarkably improved. Compared with an NK92 cell which only expresses the CD276-CAR, the CD276-CAR-SLC1A5-NK92 cell disclosed by the invention has the advantage that the CD276-CAR-SLC1A5-NK92 cell has a stronger tumor inhibition capability in a tumor-bearing mouse model.

The present invention relates to pharmaceutical composition(s) comprising particles comprising one or more compounds which are inhibitors of microsomal triglyceride transfer protein and / or apolipoprotein B (Apo B) secretion, wherein at least 50% of the particles are characterized by a volume particle fraction less than 10 μm, more preferably less than 5 μm, more preferably less than 2.5 μm. The pharmaceutical composition can be useful for the prevention and treatment of various diseases, particularly atherosclerosis and its clinical sequelae, for lowering serum lipids, and related ailments. The invention further relates to methods of treating diseases, such as hypertriglyceridemia, hyperchylomicronemia, atherosclerosis, obesity, and related conditions using the compounds. A method for decreasing apolipoprotein B (apo B) secretion is also provided.

The disclosure relates to the field of diseases caused by a lowered synaptic inhibition, preferably those that are caused by a diminished activity of the potassium (K) / chloride (Cl) Cotransporter 2 (KCC2). The disclosure involves oligonucleotides and the use thereof in RNA editing methods in targeting a variety of target adenosines in the human SLC12A5 transcript molecule that encodes KCC2. The transcript molecule is edited such that the resulting KCC2 protein has a gain-of-function and / or different function, for example reduced autoinhibition. The disclosure relates to oligonucleotides and their use in the treatment of neurodevelopment disorders, neuropsychiatric disorders, chronic pain disorders, and / or epilepsy.

Methods for treating or reducing inflammation, in is in a site or an organ excluding the central nervous system of a subject in need thereof, by administering a pharmaceutical composition comprising the translocator protein ligand 2-Cl-MGV-1, are provided.

The present invention relates to a Matriptase-2 (MT2) inhibitor, a TMPRSS6 inhibitor, an iron transporter blocking agent, or a hepcidin enhancer. In particular, the present invention relates to the use of compounds capable of reducing at least one of systemic iron levels, transferrin saturation (Tsat), non-transferrin binding iron (NTBI), and labile plasma iron (LPI). This can be accomplished by inhibiting the expression of a target gene, wherein the target gene can be transmembrane protease serine 6 (TMPRSS6). Further, the invention relates to compositions comprising said compounds and to methods of using such compounds and / or compositions. Uses may include therapeutic uses, such as for reducing iron overload and preventing iron-related toxicity before, during or after chemotherapy pretreatment, stem cell transplantation and colonization.

The invention discloses a targeted mitochondria lactic acid nano-drug compound as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The nano-drug compound comprises a lipidosome delivery carrier, a lactic acid transporter MCT1 inhibitor AZD3965 loaded in lipidosome, and mitochondrial targeting cationic group triphenyl phosphate TPP and heart targeting peptide CTP which are coupled to the surface of the lipidosome. The nano-drug provided by the invention can effectively and quickly deliver an effective drug lactic acid transporter MCT1 inhibitor AZD3965 to mitochondria in the heart, effectively reduce lactic acid entering the mitochondria, reduce abundance of heart mitochondria protein lactylation modification, improve the cardiac function index of a myocarditis group, relieve the degree of cardiac fibrosis, and improve the cardiac function index of a myocardial infarction group. The myocardial mitochondrial injury is improved, the inflammatory factor level is reduced, and the effect of improving myocarditis is further achieved. And moreover, the nano-drug shows good in-vivo safety and biocompatibility in vivo. The invention provides a new scheme for treating myocarditis.