64 results about "Disease pathogenesis" patented technology

The methods described herein enable the evaluation of compounds on subjects to assess their therapeutic efficacy or toxic effects. The target of analysis is the underlying biochemical process or processes (i.e., metabolic process) thought to be involved in disease pathogenesis. Molecular flux rates within the one or more biochemical processes serve as biomarkers and are quantitated and compared with the molecular flux rates (i.e., biomarker) from control subjects (i.e., subjects not exposed to the compounds). Any change in the biomarker in the subject relative to the biomarker in the control subject provides the necessary information to evaluate therapeutic efficacy of an administered drug or a toxic effect and to develop the compound further if desired. In one aspect of the invention, stable isotope-labeled substrate molecules are administered to a subject and the label is incorporated into targeted molecules in a manner that reveals molecular flux rates through one or more metabolic pathways of interest. By this method, a comparison between subjects and control subjects reveals the effects of the chemical entity or entities on the biomarkers. This, in turn, allows for the identification of potential therapeutic uses or toxicities of the compound. Combinations of compounds can also be systematically evaluated for complementary, synergistic, or antagonistic actions on the metabolic pathways of interest, using the methods of the present invention as a strategy for identifying and confirming novel therapeutic or toxic combinations of compounds.

The present invention provides methods and systems for conditioning cerebrospinal fluid (CSF). The methods provide for efficiently removing target compounds from CSF. The systems provide for a multilumen flow path and exchange of a majority volume portion of CSF in the CSF space. The removal and / or delivery of specific compounds can be tailored to the pathology of the specific disease. The removal is targeted and specific, for example, through the use of specific size-exclusion thresholds, antibodies against specific toxins, and other chromatographic techniques, as well as delivery and / or removal of targeted therapeutic agents. The invention finds use as a diagnostic, therapeutic and drug delivery platform for a variety of diseases affecting the CNS by accessing the CSF space. Exemplified disease conditions treatable by the present CSF processing systems and methods include, but are not limited to: Cerebral Vasospasm, Guillain Bane Syndrome, illustrating multi-lumen lumbar approach Alzheimer's, Parkinson's, Huntington's, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Spinal Cord Injury, Traumatic Brain Injury, Stroke, Cancer affecting the brain or spinal cord, Prion disease, Encephalitis from various causes, Meningitis from various causes, diseases secondary to enzymatic or metabolic imbalances, Biological Warfare, etc. For the first time, the present invention offers patients a disease-modifying, disruptive technology treatment platform that addresses the known disease pathogenesis of a number of neurologic conditions to which there are presently limited and ineffective treatment options.

The methods described herein enable the evaluation of compounds on subjects to assess their therapeutic efficacy or toxic effects. The target of analysis is the underlying biochemical process or processes (i.e., metabolic process) thought to be involved in disease pathogenesis. Molecular flux rates within the one or more biochemical processes serve as biomarkers and are quantitated and compared with the molecular flux rates (i.e., biomarker) from control subjects (i.e., subjects not exposed to the compounds). Any change in the biomarker in the subject relative to the biomarker in the control subject provides information to evaluate therapeutic efficacy of an administered drug or a toxic effect and to develop the compound further if desired. In one aspect of the invention, stable isotope-labeled substrate molecules are administered to a subject and the label is incorporated into targeted molecules in a manner that reveals molecular flux rates through metabolic pathways of interest.

The invention relates to a kit for auxiliary diagnosis of multiple tumors by taking a micro ribonucleic acid (RNA) combination as a tumor marker, and a detection method of the kit. The invention belongs to the fields of genetic engineering and oncology. The detection method comprises the steps of (1) extracting RNA from serum; (2) carrying out polyadenylation on the 3' end of micro RNA; (3) purifying and recovering a tailing product; (4) carrying out an inverse transcription reaction on the tailing product; (5) testing the relative expression of the micro RNA by means of a fluorescent quantitative PCR (polymerase chain reaction); (6) analyzing the result of the fluorescent quantitative PCR. The kit has the characteristics of high conservative property, space-time specificity, stability, tissue specificity and the like, and plays an important role in the aspects such as disease pathogenesis research, early diagnosis, individualized treatment and prognosis; furthermore, the kit is simple to operate, convenient in material obtaining, safe and noninvasive, and is conveniently used for screening of a great deal of diseases.

The present invention discloses one kind of Chinese medicine preparation for antagonizing bacteria and viruses of pig and improving pork quality and its preparation process, and belongs to the field of medicine technology. The Chinese medicine preparation is prepared with 12 kinds of Chinese medicinal materials, including cablin pochouli herb, elsholtzia, skullcap root, white atractylodes rhizome, honeysuckle stem, etc, and through sorting, mixing, drying, grinding into powder, mixing and packing. It is used to replace antibiotic and can regulate the immunity of pig in different growth stages, prevent and treat diarrhea, pig flu and plague, promote growth of pig and raise pork quality.

The Chinese herbal medicine preparation for puerpera to promote lactation and strengthen physique is oral liquid or granule prepared with astragalus root, angelica, Chuanxiong rhizome, dipsacus root, vegetable sponge and other 11 kinds of Chinese medicinal materials. The present invention is developed based on Chinese medicine theory and disease treating principle and through long term research. The Chinese herbal medicine preparation can regulate the immunity of puerpera comprehensively, dredge milk secreting gland tissues, strengthen hypophysis function, tranquilize, etc. and has obvious curative effect, high safety and low cost.

The invention disclsoes a preparation method of an ALS (Amyotrophic Lateral Sclerosis) patient specific motor neuron. The method comprises the following steps: (1) reprogramming an in-vitro fibroblast carrying ALS related genic mutation from an ALS patient source to obtain induced pluripotent stem cells carrying the ALS related genic mutation (ALS-iPSC); (2) carrying out gene editing on the ALS-iPSC and specifically eliminating the ALS related genic mutation to obtain gene corrected induced pluripotent stem cells (cALS-iPSC); (3) carrying out orient induction and differentiation on the cALS-iPSC and the ALS-iPSC respectively to obtain the ALS patient specific motor neuron carrying the ALS related genic mutation or without the ALS related genic mutation. The specific motor neuron carrying ALS pathogenic gene mutation, obtained by the preparation method, can be used as an effective platform for carrying out efficient and high-throughput individualized drug screening; the ALS patient specific motor neuron without the ALS related genic mutation is hopefully used for treating and preventing ALS. The preparation method of the ALS patient specific motor neuron lays the foundation for ALS disease researches, disease model development, disease pathogenesis researches and disease treatment.

The Chinese medicine fodder additive is prepared with honeysuckle stem, dandelion, teasel root, astragalus root, angelica and other six kinds of Chinese medicinal materials, and through sorting, mixing, drying, grinding, pelletizing and packing. The present invention is developed based on Chinese medicine theory and the physiological features of dairy cow, and has the functions of raising immunity of dairy cow, increasing milk product, reducing disease and raising milk quality.

In one or more embodiments, the present invention provides a novel biomarker which provides a link between a distinct clinical phenotype and a biochemical effect of an autoantibody on an enzyme implicated in disease pathogenesis. In particular, the present invention provides an isolated or purified human autoantibody to PAD3 protein. Methods of diagnosis of subjects for rheumatoid arthritis (RA) using these antibodies as well as diagnosis of the severity of RA in the subject, and methods for monitoring treatment of a subject with RA are also provided. The biomarkers provided herein are also useful in the diagnosis of connective tissue-interstitial lung disease (CT-ILD) in patients having or suspected of having RA.

The invention discloses a traditional Chinese medicinal composition for treating mammary gland tuberculosis. According to the traditional Chinese medicine, the disease pathogenesis are stagnation of liver qi, deficiency of lung and kidney yin, hyperactivity of fire due to yin deficiency, phlegm fire connotation, pus formation due to flesh decay, leakage after burst, prolonged healing, and deficiency of Qi and blood. According to the invention, traditional Chinese medicines scarlet kadsura root, pedunculate acronychia wood or root, villous amomum flower and peduncle, moniliform dendrobium herb, dunn antiotrema root, laxflower embelia root, Hydrangea aspera Don, wintersweet root or stem and nickernut caesalpinia leaf for coursing the liver, rectifying qi, nourishing yin, reducing inner heat, reducing phlegm, resolving masses, moving qi, invigorating blood, relieving swelling and dissipating binds are prepared into an oral decoction, and Japanese mazus herb, variegatedleaf begonia herb, Chinese squill, circaeashape loosestrife herb, emblic leafflower bark and Japanese spiraea leaf are prepared into an external ointment; the composition conducts internal and external therapy on patients and reaches a total effective rate of 93.75% through clinical test, and shows no side effects.

The invention discloses a method for enriching low-abundance protein in serum. The method adopts heparin-agarose as a filler for a purification column; 1.5 mol / L NaCl is used as an eluant; a composition obtained from elution contains abundantly-enriched low-abundance protein; the content of high-abundance protein is very low; the method solves the problem of the interference of the high-abundance protein in the serum, obtains the low-abundance protein of the target class needed in the research and provides the research condition for the further in-depth study of disease diagnosis of a high-efficiency and special low-abundance protein identifier. The method selects the heparin-agarose as a purification material which has low price, simple and feasible chromatography process and good purification effect, can obtain serum protein with more varieties; and the heparin-agarose can be repeatedly utilized. The method can be used for manufacturing a merchandised albumen purification column and has large significance on applying functional proteomics to the search of a disease diagnosis marker, the research of disease pathogenesis and the development and popularization of medicaments.

The invention discloses a method for calculating and identifying protein kinase phosphorylation specific sites, which is characterized in that, the method comprises the following steps: a) establishing a new protein sequence structure characterization method-amino acid three-dimensional character scoring based on the active ingredient analysis method; b) using the amino acid three-dimensional character scoring for characterizing the structure features of the protein kinase phosphorylation specific sites; c) using a Fisher criterion scoring method for selecting parameters which are closely related to the features of the protein kinase phosphorylation specific sites; and d) and establishing a protein kinase phosphorylation specific site identification model by a radial basis kernel support vector machine, carrying out the self-replacement verification respectively, and using the retaining 1 / 10 cross-verification and the external verification for verifying the predictive capability of the method. The method can be used for the identification of the protein kinase phosphorylation specific sites, explore the protein phosphorylation rules under physiological and pathological states, further elaborate the nature of life and the disease pathogenesis and provide the important support for developing new drugs.

The present invention discloses a systematic pharmacological method for personalized medicine. In the present invention, biological networks such as gene dependence networks are employed to reflect relationships between genes in pathogenesis. In combination with the gene expression data of a specific patient, a gene rank algorithm, which is capable of utilizing inter-genetic regulation relationships to mine key genes in the pathogenesis of disease in a specific patient, is used to construct a key genes list. Then, personalized medicine is carried out according to whether the drug targets are significantly targeted to the key genes list in the pathogenesis of disease in the specific patient. The systematic pharmacological method for personalized medicine proposed by the present invention is easy to implement, has low cost and high efficiency, and has wide application prospects in precision medicine and drug discovery.

The present invention relates to means and method for isolating naturally-occurring microorganisms (non-pathogenic bacteria, yeasts or fungi) capable of binding toxins from microorganisms such as bacteria, viruses, fungi, yeasts, or protozoans and / or receptors for these toxins on the surface of mammalian cells, thereby making these receptors inaccessible for said toxins. The naturally-occurring microorganisms that are obtainable by the means and methods of the present invention can be used for adsorbing toxins from pathogenic microorganisms and / or blocking receptors for such toxins on the surface of mammalian cells. These toxin-receptor interactions are known to be critical for disease pathogenesis, making both the toxins and receptors a target for the naturally-occurring microorganisms of the present invention.

The invention provides compositions and methods for visualizing particular tissues and delivering one or more therapeutics to that tissue using single-walled carbon nanotubes (SWNTs), which are taken up and delivered to target tissues by specific monocytes in the body. The delivery of SWNT to target tissues allows the visualization of the affected tissue for diagnostics and therapy in diseases where the specific monocyte is implicated in the disease pathogenesis. These nanotubes can be conjugated to a peptide, such as RGD, which helps direct the SWNT-containing monocytes to the vascular endothelium.

The invention discloses a biological data network processing method based on a similarity network fusion algorithm, and belongs to the technical field of biological information analysis. The method comprises the following steps: firstly, constructing a similarity network by using mRNA, miRNA, lncRNA and the like, fusing similarity matrixes by using an SNF algorithm, creating an available sample network, performing clustering by using spectral clustering, and analyzing the relationship between the networks, so that the method is applied to the fields of discovery, early diagnosis, later treatment and the like of disease pathogenesis. According to the method, a more comprehensive result can be obtained by utilizing the complementarity of different types of data, the method is greatly superior to analysis and establishment of single data, and a basis is established for subsequent comprehensive analysis.

This invention relates to compounds, compositions, and methods useful for modulating the expression and activity of NF-kappa-B by RNA interference (RNAi) using small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA) and double-stranded RNA (dsRNA). Furthermore the invention provides methods for preventing, treating or alleviating NF-kappa-B dependent diseases whereby NF-kappa-B is believed to play a role in the pathogenesis of a disease in a subject, preferably a human, by administration of a therapeutic effective and in a pharmacologically accepted form, the siRNA compounds of the invention.

The invention discloses a microfluidic chip and a design method and application thereof. The microfluidic chip includes a main channel, capture units, and a narrow channel; the main channel is used for transferring cells and cell culture media; the plurality of capture units are arranged on the side wall of the main channel oppositely and at intervals, and the capture units are used for capturingand culturing single cells; the narrow channel is used for communicating two capture units to form an communication path between the single cells after capture and preventing the captured single cellsfrom flowing into the main channel on the opposite side. The microfluidic chip is simple to make and easy to operate, the capture and culture of two kinds of single cells can be realized, researcheson cell-cell interactions are conducted, and the microfluidic chip is suitable for exploring cell heterogeneity and disease pathogenesis. The microfluidic chip can be used for carrying out researcheson the mechanism of tumorigenesis and development and providing a basis and novel research ideas for constructing an effective tumorigenesis model in vitro, and a certain theoretical support is provided for tumorigenesis and development.

Described herein is a microphysiological system for models of disease. Specifically, induced pluripotent stem cells (iPSCs) and iPSC-derived cells, including those obtained from disease patients, are seeded onto microfluidic “chip” devices to study cellular development and disease pathogenesis. Herein, neurodegenerative disease modeling, including Parkinson's Disease (PD) is shown to reproduce key PD pathology in a vascularized human model that contains neurons relating to PD pathology. Such compositions and methods are used for research for PD biomarkers, patient screening for PD risk assessment, and therapeutic discovery and testing. A panel of biomarkers are generated through analysis of living PD-chips by neural activity, whole transcriptomic, proteomic, and metabolomic analysis, and functional enzyme tests of media and tissue. Introducing therapeutics through a vasculature channel, coupled with blood brain barrier penetration studies can be assessed for efficacy in the human neural cells present in the PD-Chip.

The invention is directed to co-culture systems comprising (i) rotating wall vessel (RWV)-cultured epithelial or differentiated tissue attached to microcarrier beads and (ii) the peripheral tissue equivalent (PTE) module of the MIMIC® system, and to methods of using the co-culture systems for assessing chemical or biological (bacterial or viral) insults. The system models mucosal exposure to chemicals, pathogens or antigen at various sites in the human body. The microcarrier and MIMIC® co-culture approach provides an in vitro co-culture model that simultaneously demonstrates mucosa-mediated antigen presentation and immunogenic responses. Models of the present invention can be used, for example, in assessments of disease pathogenesis and in pharmaceutical development, reproductive physiology, and immunological and toxicological evaluations. Models of the present invention can generate patient-specific localized mucosal immunology using primary cells, resembling the human physiological situation.

Induced pluripotent stem cell (iPSC)-based organoid technology has tremendous potential to elucidate the intestinal and colonic epithelium's role in health and disease. Described herein are methods and compositions for generation of intestinal and colonic cells from iPSCs. Derivation of iPSCs from subjected afflicted with early onset and very early onset Inflammatory Bowel Disease (IBD), serves as an excellent model for understanding disease pathogenesis.

The invention provides a multifunctional vector constructed on the basis of a carbon nanomaterial, which belongs to the field of nano-biotechnology. The vector can enter cells, capture protein and carry out fluorescent tracking and positioning of protein in cells and greatly improves efficiency and accuracy of research on the action mechanism of protein. Application of the multifunctional vector in biotechnology will powerfully promote research on functions and interaction of protein, has an academic theoretical value and can produce immense economic benefits and great social influence. The multifunctional vector is mainly used for research on the functions and action mechanism of protein and is applicable to fields like research on pathogenesis of diseases, drug design and gene therapy.

The invention belongs to the technical field of experimental animals, and particularly relates to a preparation method of rat non-alcoholic fatty liver model feed. The method comprises the following steps of accurately weighing basal feed and 2% cholesterol to be mixed; adding grease with the calorie ratio of 40% to be stirred; adding water to be stirred and mixed, and performing granulation through a granulator to obtain soft granulated feed; performing drying at a low temperature to obtain the rat non-alcoholic fatty liver model feed. The invention also provides the rat non-alcoholic fatty liver model feed and an application thereof. Modeling can be completed after a rat is fed with the rat non-alcoholic fatty liver model feed for 8-10 weeks, so that the modeling time is shortened, and an animal model similar to human non-alcoholic fatty liver disease pathogenesis is successfully copied. Besides, the rat is fed with the pure feed, gavage is not needed, animal ethics are met, the ratnon-alcoholic fatty liver model can be obtained, various symptoms of human non-alcoholic fatty liver diseases are simulated, and a theoretical basis is provided for research of human related diseases.

This invention relates to statistically significant methods for metabolomics data analysis that incorporate the structure information of metabolites. Understanding of disease pathogenesis and drug effects, as well as prediction of variation in drug response can be achieved by analyzing quantitative data measuring metabolomics biomarker profiles from biological samples. This invention is to boost the statistical power of analyzing metabolomics data. The comprising methods may include retrieving information of metabolites' chemical structures, converting them into structural data, and integrating the structural data into analysis of metabolite concentration data to improve the evaluation of metabolites and to better identify metabolomics signatures.

The invention provides an application of C188-9, Venetoclax and Bumetanide in drugs for fibrotic diseases from perspective of clinic practice. A RNA recognition sequence (RNA recognition motif, RRM) region of LARP6 protein is taken as a docking target, and subject to computer virtual docking and simulated screening. Finally it is found by cellular and animal experiments that C188-9, Venetoclax andBumetanide (a potent quick-acting diuretic commonly used in clinic practice) combine with the RRM region of LARP6 protein to inhibit stability of collagen mRNA, thereby inhibiting collagen productionand further inhibiting fibrosis-related diseases in the process of occurrence and development of injury-induced fibrosis. The study of the invention enriches basic research on the pathogenesis of fibrosis-related diseases, and provides a new idea for deep exploration of essential causes of the fibrotic diseases. Meanwhile, the C188-9, Venetoclax and Bumetanide can be considered as a new potentialdrug for clinical treatment of the fibrotic diseases.

The present invention relates to monoclonal antibodies that are capable of specifically binding to lectin-like transcript 1 (LLT1), to polynucleotides encoding such antibodies and to cells that express such antibodies. Antibodies of the invention have utility in the treatment of autoimmune diseases and cancer, in which LLT1-and CD161-expressing cells play a role in disease pathogenesis.

The invention discloses a making method of human cockayne syndrome specificity adult stem cells. The method comprises the following steps of (1) performing reprogramming on adult fiber cells from cockayne syndrome patient sources carrying cockayne syndrome specificity ERCC6 gene mutation in an excised manner, so as to obtain induction multipotential stem cells namely CS-iPSC; and (2) performing directional induced differentiation on the CS-iPSC to obtain adult stem cells, so as to obtain the human cockayne syndrome specificity adult stem cells. The prepared mesenchymal stem cells or neural stem cells can be used as an effective platform for high-efficacy high-flux individualized drug screening, and a foundation is established for disease research, disease model development, disease pathogenesis research and disease treatment. The making method has great application prospects in individualized treatment and translational medicine.

The invention discloses a construction method for constructing an Alzheimer's disease animal model and a nucleic acid composition and application thereof, and relates to the technical field of genetic engineering. According to the invention, Thy1-hAPP Sweep, Indiana and Thy1-hPSEN1 M146V and L286V are inserted into a target animal genome and are specifically expressed in a brain region, so that an animal model which can be stably inherited and has a spontaneous classic phenotype of Alzheimer's disease (AD) is obtained. Amyloid protein deposition occurs when the animal model is 1.5 months old, and the amyloid protein deposition increases along with age and is age-dependent. Pathologically along with glial cell hyperplasia, the appearance time is earlier than that of a common AD model. Besides, on the basis that the animal model generates a large amount of A beta deposition, the cognitive and memory ability declines when the animal model is 5 months old, and a convenient and effective way is provided for function analysis of AD related genes, research of disease pathogenesis and drug research and development.

The invention provides compositions and methods for visualizing particular tissues and delivering one or more therapeutics to that tissue using single-walled carbon nanotubes (SWNTs), which are taken up and delivered to target tissues by specific monocytes in the body. The delivery of SWNT to target tissues allows the visualization of the affected tissue for diagnostics and therapy in diseases where the specific monocyte is implicated in the disease pathogenesis. These nanotubes can be conjugated to a peptide, such as RGD, which helps direct the SWNT-containing monocytes to the vascular endothelium.