51 results about "Cell selectivity" patented technology

The invention discloses a full D-type antibacterial peptide with high enzymolysis stability and broad-spectrum antibacterial activity and application thereof. The antibacterial peptide is obtained by sequentially and repeatedly arranging D-type tryptophan, D-type arginine and D-type lysine for four times and carrying out C-terminal amidation; the amino acid sequence of the gene is (D-Trp)-(D-Arg)-(D-Lys)-(D-Trp)-(D-Arg)-(D-Lys)-(D-Trp)-(D-Arg)-(D-Lys)-(D-Trp)-(D-Arg)-(D-Lys)-(D-Trp)-(D-Arg)-(D-Lys)-NH2, and is marked as DWRK-12. The antibacterial peptide shows broad-spectrum antibacterial activity and excellent stability, can effectively resist clinically separated multidrug resistant strains, and keeps high cell selectivity at the same time. Due to the characteristics, the antibacterial peptide has important application value in the aspect of developing novel antibacterial drugs, especially in the field of treatment of infection of multiple drug-resistant bacteria.

The invention provides a duodenal mucosa adjusting system and method based on pulsed electric field ablation and application of the duodenal mucosa adjusting system and method in diabetes treatment, the duodenal mucosa adjusting system comprises an intelligent control host capable of achieving bidirectional data transmission and an adjustable catheter, and the intelligent control host initializes parameters and adjusts pulse parameters by monitoring impedance data in real time until pulses are interrupted or terminated; periodic ablation is carried out, periodic intervals are used for measuring impedance data, the ablation depth is evaluated according to the impedance change rate, and whether next section ablation is carried out or not is judged till full-area ablation is completed. The far-end ablation adopts a structure of combining fusiform flexible support and annular electrode spiral arrangement to ensure that an ablation field uniformly covers mucous membrane plica of a duodenum bulb part and a descending part; a cell selective ablation mechanism is adopted, the critical electric field intensity is set, K cell electroporation is selectively induced, and meanwhile goblet cells are protected.

Disclosed are compositions and methods useful for targeting and internalizing molecules into cells of interest and for penetration by molecules of tissues of interest. The compositions and methods are based on peptide sequences that are selectively internalized by a cell, penetrate tissue, or both. The disclosed internalization and tissue penetration is useful for delivering therapeutic and detectable agents to cells and tissues of interest.

The invention belongs to the technical field of medicines, and particularly relates to application of a xanthohumol substance in preparation of a microglial cell selective polarization preparation, the xanthohumol substance is xanthohumol or a xanthohumol derivative, and microglial cells are selectively polarized to M2 type. Experiments prove that when PolyI: C induces activation of microglial cells, expression of M2 type microglial cell surface markers YM is reduced, while after the microglial cells are subjected to xanthohumol pretreatment and then subjected to PolyI: C stimulation, activation of the microglial cells induced by PolyI: C is reduced, expression of the M2 type microglial cell surface markers YM is increased, activation of the microglial cells induced by PolyI: C is reduced, and activation of the microglial cells induced by PolyI: C is reduced. Therefore, Xn can inhibit inflammatory response by adjusting activated microglial cells to be polarized to M2.

The invention relates to a selective cell killing device based on surface and interface pH regulation and application thereof. The method comprises the following steps: depositing a noble metal material capable of regulating and controlling extracellular proton concentration on one side of a substrate to form a regulation and control layer, and connecting the regulation and control layer to an external preset dynamic voltage control unit through a wire; the regulation and control layer is attached to the surface of the tissue; a dynamic voltage is periodically applied to the regulation and control layer through an external preset dynamic voltage control unit, so that the pH value of the interface microenvironment of the regulation and control layer and tissue cells is alternately changed between 5 and 8, and accurate selective killing of the cells is realized. A preset dynamic voltage control scheme based on a cancer cell glycolysis oscillation period is adopted, so that the pH value of a local surface interface can be regulated and controlled according to a set period, the excretion of lactic acid and protons of cancer cells is continuously and effectively interfered, and the cancer cells are prevented from generating adaptive reaction.

The invention relates to the technical field of nerve cell marking and regulation and control, in particular to a nerve cell living body selective protein modification probe capable of penetrating a blood brain barrier and application of the nerve cell living body selective protein modification probe. The protein body part specifically targets a living glutamic acid energetic neuron cell membrane, the protein body part and / or a modified part thereof can regulate and control the function of the glutamic acid energetic neuron, and a coding sequence of the protein body part comprises a sequence as shown in SEQ ID NO: 1 or a sequence having at least 85% identity with the SEQ ID NO: 1. The protein modified probe provided by the invention provides a new feasible thought for developing in-vivo nerve cell selective markers and regulation tools which are non-gene transfection of blood brain barrier penetration, are high in biological safety, are more stable and are easy to obtain and have nerve cell specific type selectivity.

The invention relates to the combination of a cell-selective promoter to drive the N-terminal part of the transgene and a compact ubiquitous promoter with similar expression levels to drive the C-terminal part of the transgene (or vice versa) for dual AAV intein-mediated delivery to obtain cell-selective, efficient transgene expression.

The present invention relates to a method for the genome editing of cells at a target locus by homology directed repair (HDR) within a cell population and concurrently enriching within said cell population the HDR-genome edited cells. The present invention also relates to a method for the selective depletion of cells comprising a target locus within a cell population.

Programmable guide RNAs (gRNAs) play a central role in the CRISPR revolution sweeping biology and medicine by directing the function of a Cas protein effector to a target gene of choice. To achieve programmable control over regulatory scope, the activity of a conditional guide RNA (cgRNA) depends on the presence or absence of an RNA trigger, allowing for cell-selective regulation of CRISPR / Cas function. Unlike a standard gRNA, a cgRNA is programmable at multiple levels, with the target-binding sequence controlling the target of Cas activity (edit, silence, induce, or bind a gene of choice) and the triggerbinding sequence controlling the scope of Cas activity. cgRNA mechanisms that are allosteric allow for independent design of the target and trigger sequences, providing the flexibility to select the regulatory target and scope independently. Disclosed herein are allosteric cgRNA mechanisms for both ON→OFF logic (conditional inactivation by an RNA trigger) and OFF→ON logic (conditional activation by an RNA trigger). Allosteric cgRNAs enable restriction of CRISPR / Cas function to a desired cell type, tissue, organ, or disease state. Allosteric cgRNAs provide a versatile platform for cell-selective and tissue-selective research tools, biotechnologies, diagnostics, and therapeutics.

The present invention discloses an application of an oxamide compound in the preparation of an anti-liver cancer drug. The oxamide compound is N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxamide, and the molecular formula is C 22 H 22 N4O3, with a molecular weight of 390.44 and a structural formula as shown in Formula (I), investigated the effect of N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxalamide on the proliferation of liver cancer cells. The results showed that N-(4,5,6,7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl)phenyl)oxalamide exhibited significant anti-proliferation activity against human liver cancer cells (Hep G2, Hep 3B, PLC / PRF / 5, and Huh7), while exhibiting low toxicity against normal human liver cells (LX-2). This suggests that it possesses strong anti-liver cancer activity and excellent cell selectivity. Therefore, it is expected to be used in the preparation of anti-liver cancer drugs.

The invention discloses a cell-penetrating peptide CPP137 as well as a compound, a composition and application thereof, and belongs to the technical field of polypeptides. According to the application, a cell-penetrating peptide CPP137 with immune cell selectivity is screened out from a plague bacillus sORF library. The polypeptide not only can be efficiently internalized by THP-1 (M0 type) mononuclear cells, but also can specifically target two key antigen presenting cells, namely primary macrophages and dendritic cells (DC), in a complex human whole blood physiological environment, but is not obviously combined with other blood cell types. Therefore, the cell-penetrating peptide CPP137 is a targeted delivery carrier with great potential, can be used for specifically delivering a therapeutic load to myeloid immune cells, and is used for treating intracellular infection and immune-related diseases or used as a vaccine development platform. Meanwhile, CPP137 can also be used as a specific diagnostic marker or an imaging probe for detecting or tracing pathological states related to macrophages / DC.

This invention discloses a type of click-type covalent drug, its regionally selective delivery system, and its applications. The invention comprises two parts: a click-type covalent drug and a tumor regionally selective delivery system. The click-type covalent drug consists of three parts: an azacyclic alkyne (DBCO), a small molecule drug, and a linker, having the structure of Formula 1. Optionally, the small molecule drug is a membrane protein inhibitor, an immunomodulator, or a chemotherapeutic drug. The click-type covalent drug reacts with azide-labeled target cells via a click reaction, forming a covalent bond that binds to the cell membrane, increasing the local drug concentration and prolonging the drug retention time, thereby enhancing selective inhibition of the target cells. The regionally selective delivery system is co-assembled from an amphiphilic block polymer and the click-type covalent drug for regionally selective delivery. This invention achieves covalent binding to azide-labeled tumor cells through the click-type covalent drug, while having no effect on unlabeled normal cells, reducing toxic side effects on normal tissues.

The disclosure features compositions or systems and uses thereof, comprising a first polynucleotide encoding a target molecule, optionally a second polynucleotide encoding an effector, repressor, or endonuclease molecule; optionally a recognition or cleavage site in the first or second polynucleotide, and optionally a repressor / effector binding site in the first polynucleotide. The disclosure also features compositions or systems and uses thereof, comprising a messenger RNA (mRNA) comprising (i) an open reading frame encoding a polypeptide, and (ii) at least six miR142 target sites.

This invention belongs to the field of guided bone regeneration materials technology, specifically relating to an arginine carbon dot photoinitiated hydrogel prepolymer, its preparation method, and its application. The arginine carbon dot photoinitiated hydrogel prepolymer of this invention, when used for alveolar bone regeneration, inhibits the proliferation / migration of gingival fibroblasts (hGFs) while simultaneously inducing and promoting the proliferation / migration and osteogenic differentiation of bone marrow mesenchymal stem cells (hBMSCs), thus creating a "reverse-response" cell-selective regulatory effect.

The invention discloses an asymmetric antibacterial peptide taking PG as a center as well as a preparation method and application thereof, and belongs to the technical field of bioengineering. The amino acid sequence of the antibacterial peptide is as shown in SEQ ID No.1, and the C end of the antibacterial peptide is amidated by adopting-NH2; detection on antibacterial activity, hemolytic activity, cytotoxicity and salt ion stability of the antibacterial peptide shows that the antibacterial peptide has optimal cell selectivity (SI = 72.60), does not show obvious cytotoxicity when the test concentration is 32 mu M or below, and can keep ideal stability in salt ions with different physiological concentrations. In conclusion, the antibacterial peptide has the potential to become a broad-spectrum antibacterial drug for treating gram-positive bacterium and gram-negative bacterium infection.

The present invention belongs to the technical field of chemical medicine, and particularly relates to a mitochondrion-targeted honokiol derivative, a preparation method thereof and an application thereof. It is a compound represented by Formula I or Formula II, or a pharmaceutically acceptable salt of the compound represented by Formula I or Formula II, or a pharmaceutically acceptable ester of the compound represented by Formula I or Formula II, or a pharmaceutically acceptable solvate of the compound represented by Formula I or Formula II; #imgabs0# wherein, R1 is a straight-chain or branched-chain saturated alkyl group with 1 to 5 carbon atoms, R2 is a straight-chain or branched-chain saturated alkyl group with 1 to 5 carbon atoms, and n is an integer from 1 to 10. The mitochondrion-targeted honokiol derivative provided by the present invention not only has higher anti-tumor activity and cell selectivity, but also can improve the in vivo toxicity to the Caenorhabditis elegans model.

The present invention discloses a preparation method and application of a branched antibacterial peptide KW, belonging to the field of biotechnology. The antibacterial peptide KW includes a Lys and two heptapeptide groups with two α-helix structures. The amino acid sequence of the heptapeptide group is shown in SEQ ID No.1. The C-terminus of Arg at the 7th position of the first heptapeptide group is connected to the ε-N terminus of Lys, and the N-terminus of Leu at the 1st position of the second heptapeptide group is connected to the C-terminus of Lys. Moreover, the C-terminus of the antibacterial peptide KW is amidated with an amino group. The branched antibacterial peptide can significantly improve the problem of high toxicity caused by linear polypeptides and further enhance cell selectivity on the basis of ensuring a certain antibacterial activity. In addition, the branched antibacterial peptide KW has the potential to become a broad-spectrum antibacterial drug for treating Gram-positive and Gram-negative bacterial infections and has high application value.

The invention discloses an application of an oxamide compound in preparation of an anti-liver cancer drug, the oxamide compound is N-(4, 5, 6, 7-tetrahydro-1H-indazole-5-)-N '-(4-(p-tolyl) phenyl) oxamide, the molecular formula is C22H22N4O3, the molecular weight is 390.44, and the structural formula is as shown in formula (I). By investigating the influence of N-(4, 5, 6, 7-tetrahydro-1H-indazole-5-)-N '-(4-(p-tolyl) phenyl) oxamide on hepatoma cell proliferation, the obtained experimental result shows that N-(4, 5, 6, 7-tetrahydro-1H-indazole-5-)-N'-(4-(p-tolyl) phenyl) oxamide shows remarkable proliferation inhibition activity on human hepatoma cells (Hep G2, Hep 3B, PLC / PRF / 5 and Huh7), and the N-(4, 5, 6, 7-tetrahydro-1H-indazole-5-)-N '-(4-(p-tolyl) phenyl) oxamide can be used for preparing the liver cancer cell proliferation inhibitor. Meanwhile, the toxicity to human normal liver cells LX-2 is relatively low, which indicates that the compound has relatively strong anti-hepatoma activity and good cell selectivity. Therefore, the compound is expected to be applied to preparation of anti-hepatoma drugs.

The invention provides a D-pi-A type organic antibacterial photosensitizer as well as a synthesis method and application thereof, and belongs to the field of photodynamic therapy application of photosensitizers and antibiosis. The AIE type photosensitizer with bacterial cell selectivity is synthesized by taking methoxy-substituted triphenylamine as an electron donor, pyridinium as an electron acceptor and thiophene as an electron pi bridge through a series of simple organic reactions, and can be applied to antibacterial photodynamic therapy; the photosensitizer can realize bacterial imaging and selectively exert a photodynamic effect on bacteria by being connected with a hydrophilic group, has a good treatment effect and biological safety, and has a relatively strong application prospect in antibacterial photodynamic therapy.

The present invention discloses an asymmetric antimicrobial peptide centered on PG, a preparation method thereof, and an application thereof, belonging to the field of bioengineering technology. The amino acid sequence of the antimicrobial peptide is shown in SEQ ID No. 1, and its C-terminus is amidated with ‑NH2; the antimicrobial peptide of the present invention is tested for antimicrobial activity, hemolytic activity, cytotoxicity, and salt ion stability, and it is found that it has the best cell selectivity (SI=72.60), and does not show obvious cytotoxicity below the test concentration of 32 μM, and can maintain relatively ideal stability in salt ions of different physiological concentrations. In summary, the antimicrobial peptide of the present invention has the potential to become a broad-spectrum antimicrobial drug for the treatment of Gram-positive and Gram-negative bacterial infections.

The present disclosure provides compositions and methods for the selective transduction and genome editing of human cells (e.g., hematopoietic stem and progenitors cells, HSPCs) using engineered viral like particles (eVLPs). Aspects of the disclosure provide eVLP compositions comprising fusion proteins comprising a targeting moiety. In some embodiments, the fusion proteins comprise a cytokine conjugated to a transmembrane protein and / or an envelope glycoprotein. In other embodiments, the fusion proteins comprise a targeting moiety domain, a stalk protein domain, a transmembrane and / or envelope glycoprotein domain. Targeted-eVLP architectures comprising various targeting domains, stalk domains, transmembrane domains, and envelope glycoproteins are also provided herein. Other aspects of the disclosure provide eVLP compositions comprising envelope glycoproteins comprising non-natural sugars and methods of conjugating said eVLPs to various targeting moieties using bio-orthogonal click chemistry. Polynucleotides, vectors, cells, and kits useful for producing the articles, and performing the methods, described herein are also provided.

Programmable guide RNAs (gRNAs) play a central role in the CRISPR revolution sweeping biology and medicine by directing the function of a Cas protein effector to a target gene of choice. To achieve programmable control over regulatory scope, the activity of a conditional guide RNA (cgRNA) depends on the presence or absence of an RNA trigger, allowing for cell-selective regulation of CRISPR / Cas function. Unlike a standard gRNA, a cgRNA is programmable at multiple levels, with the target-binding sequence controlling the target of Cas activity (edit, silence, induce, or bind a gene of choice) and the trigger-binding sequence controlling the scope of Cas activity. cgRNA mechanisms that are allosteric allow for independent design of the target and trigger sequences, providing the flexibility to select the regulatory target and scope independently. Disclosed herein are allosteric cgRNA mechanisms for both ON→OFF logic (conditional inactivation by an RNA trigger) and OFF→ON logic (conditional activation by an RNA trigger). Allosteric cgRNAs enable restriction of CRISPR / Cas function to a desired cell type, tissue, organ, or disease state. Allosteric cgRNAs provide a versatile platform for cell-selective and tissue-selective research tools, biotechnologies, diagnostics, and therapeutics.

The invention discloses a lipidosome drug delivery system, a preparation method thereof, a lipidosome preparation, application, and a fat-reducing drug or a medical beauty product containing the lipidosome drug delivery system. The liposome drug delivery system comprises deoxycholic acid and phospholipid; the phospholipids comprise a first phospholipid and optionally comprise a second phospholipid; the mass ratio of deoxycholic acid to phospholipid is (1: 2.5)-(1: 35). The drug delivery system can be further prepared into a liposome preparation which is used for fat-reducing drugs or medical beauty supplies. The lipidosome drug delivery system, the lipidosome preparation drug or the medical beauty product has excellent adipocyte selectivity, realizes a good adipose tissue dissolving effect, has small side effects and high safety, and has a good market application prospect.

The invention provides a preparation method and application of a tumor targeting peptide / cell penetrating peptide-SN38 conjugate, and belongs to the technical field of polypeptide preparation and biological medicine. The invention provides a series of novel tumor targeting peptide / cell penetrating peptide-SN38 conjugates, and provides an efficient synthesis method of polypeptide solid phase coupling SN38. The novel tumor targeting peptide / cell penetrating peptide-SN38 conjugate prepared by the invention can effectively solve a series of defects of poor cell selectivity, poor water solubility, poor uptake and the like of SN38, shows a relatively strong effect of inhibiting tumor cell proliferation, further improves the anti-tumor application potential of SN38, and realizes a safer and more effective cancer treatment function.

The application discloses a deer-derived antibacterial peptide against gram-negative bacteria and a preparation method and application thereof, belongs to the technical field of biology, and the amino acid sequence is shown as SEQ ID No. 1. It is tested that the antibacterial peptide S6 has obvious inhibiting effect on most of tested gram-negative bacteria, the average antibacterial activity reaches 8.00 muM, the hemolytic activity and cytotoxicity are relatively low, the cell selectivity index is 32, and the antibacterial peptide S6 has relatively strong anti-enzymatic ability. The antibacterial mechanism of the antibacterial peptide S6 is determined, it is judged that the antibacterial peptide S6 has recognition and damage effects on the cell membrane of gram-negative bacteria, and finally leads to the death of bacteria. Therefore, the antibacterial peptide S6 is an antibacterial peptide against gram-negative bacteria with high clinical application value.

The invention discloses a method for in-vitro study of tumor cell epithelial-mesenchymal transition / interstitial-epithelial transition cell molecular biological characteristics, which comprises the following steps: in a specific flowing suspension culture environment simulating a blood flow environment, using an epithelial marker and an interstitial marker which include but are not limited to the epithelial marker and the interstitial marker, and carrying out in-vitro study on tumor cell epithelial-mesenchymal transition / interstitial-epithelial transition cell molecular biological characteristics. The cell survival rate and the change of molecular biological characteristics of the cells in the adherent culture process before flowing, after flowing and after flowing are observed, and a simple and effective circulating tumor cell transformation in-vitro research method is provided. According to the method, epithelial / mesenchymal transformation and mesenchymal / epithelial transformation characteristics of target cells are observed in in-vitro culture cells for the first time, so that the characteristics of transformation from epithelial type to mesenchymal type in an in-vitro flowing suspension culture environment are reproduced for the first time; the method is used for analyzing the selective survival of target cells in a blood flowing environment and researching the survival and diffusion mechanism and diffusion capacity of different types of tumor cells in blood, and an effective research method is provided for clinical cancer diffusion prevention.

The invention provides a microbial production cell for the synthesis of a product, further comprising a charge-dependent genetic circuit whose expression confers a selective growth and / or survival advantage to those cells that synthesize the product, while limiting the proliferation of unproductive or non-productive escape cells.

The present application relates to the technical field of submicron preparation of organic active ingredients, and discloses a nerve immunoregulator targeting microglia cells and a preparation method thereof, which comprises the following steps: mixing a parasite kinase inhibitor and a lipid carrier material in anhydrous ethanol to configure a clear and uniform phase mixed mother liquor, dropping the mixed mother liquor into deionized water, and dispersing and wrapping the mixed mother liquor in a continuous ultrasonic field to form a preparation suspension containing drug lipid microparticles; centrifugally separating the preparation suspension containing drug lipid microparticles to collect precipitates; resuspending the precipitates in a mannitol aqueous solution; and removing water by vacuum freeze-drying. The present application regulates the crystallization kinetics path, inhibits spontaneous aggregation of the raw drug to guarantee the spatial stability of the preparation, improves the selective enrichment degree of central target cells, crosses the barrier along the pathological leakage channel, and releases the active ingredients in situ to calm the neuroimmunological storm.

The invention discloses an autophagy regulator and a preparation method and application thereof, relates to a dual-targeting fluorescent organic small molecule autophagy activation and autophagy inhibitor and application thereof, and aims to solve the problems of single autophagy regulation targeting, no cell selectivity and poor cancer cell killing effect in the prior art.