30 results about "Active tuberculosis" patented technology

The invention discloses an active tuberculosis diagnostic marker, a kit and application thereof. In particular to application of a reagent for detecting a diagnostic marker in preparation of a kit for diagnosing active tuberculosis, the diagnostic marker is a biomarker TRIM22 in a blood sample, and the sequence of the TRIM22 is as shown in SEQ ID NO: 1. According to the invention, TRIM22 in a blood sample is used as a biomarker for detecting active tuberculosis for the first time. Results of ROC curve analysis show that the expression level of TRIM22 in whole blood has good sensitivity and specificity for active tuberculosis diagnosis. Therefore, the invention overcomes the defects of low detection rate, long time consumption and the like of the existing active tuberculosis diagnosis, has the characteristics of good specificity and high sensitivity, and has good clinical application value for the auxiliary diagnosis of the active tuberculosis.

Disclosed are an mRNA pharmaceutical composition for preventing and treating tuberculosis and use thereof. The mRNA pharmaceutical composition comprises: an mRNA molecule encoding a Mycobacterium tuberculosis antigen, and a pharmaceutically acceptable excipient. The Mycobacterium tuberculosis antigen comprises the following antigen components: at least one early-secreted antigen of Mycobacterium tuberculosis or an immunologically active fragment thereof; PE / PPE family antigen WAG22 of Mycobacterium tuberculosis or an immunologically active fragment thereof; and at least one latent-related antigen of Mycobacterium tuberculosis or an immunologically active fragment thereof. The mRNA pharmaceutical composition does not comprise or further comprises an mRNA molecule encoding a cytokine. The pharmaceutical composition is used for preparing a tuberculosis vaccine, which may serve as a prophylactic vaccine for preventing latent activation or as a therapeutic drug for treating active tuberculosis, exhibiting a significant inhibitory effect on Mycobacterium tuberculosis.

The invention provides an mRNA (messenger ribonucleic acid) pharmaceutical composition for preventing and treating tuberculosis and application of the mRNA pharmaceutical composition. The mRNA pharmaceutical composition for preventing and treating tuberculosis comprises mRNA molecules for coding mycobacterium tuberculosis antigens and pharmaceutically acceptable auxiliary materials, the mycobacterium tuberculosis antigen comprises the following antigen components: at least one mycobacterium tuberculosis early secretion antigen or an immunocompetence fragment thereof; a mycobacterium tuberculosis PE / PPE family antigen Rv3872 or an immunocompetence fragment thereof; and at least one mycobacterium tuberculosis latent associated antigen or an immunocompetent fragment thereof; the mRNA pharmaceutical composition does not include or further includes an mRNA molecule encoding a cytokine. The pharmaceutical composition provided by the invention is used for preparing tuberculosis vaccines, can be used as a prophylactic vaccine for preventing latent activation, can also be used as a therapeutic drug for treating active tuberculosis, and has a remarkable inhibition effect on mycobacterium tuberculosis.

The present application relates to the technical field of diagnostic markers, in particular to a marker combination and its application in diagnosing active tuberculosis and distinguishing between latent tuberculosis infection and active tuberculosis. The lectin combination provided by the present application can be used as a marker for ATB diagnosis and distinguishing between LTBI and ATB, and has high specificity and sensitivity. The lectin combination provided by the present application in combination with detection of specific antibodies of mycobacterium tuberculosis antigens can further improve the diagnostic effect. The marker and its detection products provided by the present application have good application potential in ATB diagnosis and distinguishing between LTBI and ATB, and are expected to overcome the limitations of existing diagnostic techniques, improve the diagnostic accuracy and sensitivity of tuberculosis, and provide new ideas and technical means for early detection, precise treatment and effective prevention and control of tuberculosis.

The present invention relates to the use of a therapeutic agent based on cell wall fragments of a virulent strain of Mycobacterium tuberculosis-complex for the preparation of a drug for the treatment of patients with active tuberculosis.

The invention belongs to the technical field of tuberculosis detection, and provides a microRNA combination for bimodal differentiation of tuberculosis infection, a kit and a detection system. Nine specific microRNAs and one specific internal reference microRNA are taken as markers, the microRNAs in plasma are rapidly released by adopting a direct splitting method, the relative expression quantity of the markers is synchronously detected in combination with a tailing method reverse transcription technology, a four-group primer grouping amplification technology and a fluorescent PCR technology, a comprehensive risk value is calculated through a built-in algorithm, and latent tuberculosis infection, active infection and a negative state are synchronously distinguished. According to the invention, sputum samples are not needed, the detection is rapid and efficient, the detection sensitivity and specificity of active tuberculosis infection reach 92%, the detection sensitivity and specificity of latent tuberculosis infection reach 93%, the detection specificity reaches 90%, the operation is convenient, and the application range is wide.

The application relates to an active pulmonary tuberculosis marker and application thereof, the active pulmonary tuberculosis marker is PCBP1, the expression of the PCBP1 in peripheral blood mononuclear cells of an active pulmonary tuberculosis patient is obviously down-regulated, the down-regulated PCBP1 has certain significance for diagnosis of the active pulmonary tuberculosis patient. Moreover, the expression amount of the PCBP1 in the APTB patient is detected by using an RT-qPCR and western blot method, the disease can be diagnosed, and then the active pulmonary tuberculosis diagnosis reagent can be prepared. The application discloses that the PCBP1 can be used as the active pulmonary tuberculosis marker for the first time, and provides a new direction for clinical diagnosis of the active pulmonary tuberculosis.

The invention discloses a three-gene combination, a primer probe set and a system for qPCR (quantitative polymerase chain reaction) rapid screening of tuberculosis progression risk and application of the three-gene combination, the primer probe set and the system. The method comprises the following steps: firstly, screening out candidate genes APOL1, C1QC and SOCS1 which are stable across time windows and have high prediction performance; then a three-gene combination scoring you model (PRI3) composed of APOL1, C1QC and SOCS1 is constructed and used for predicting the risk that a latent tuberculosis infected individual progresses into active tuberculosis within a set time window; the method comprises the following steps of: firstly, selecting a reference model (RISK6, Sweeney3, Gliddon4 and BATF2), then performing performance verification in an independent verification queue, and comparing with the existing reference model (RISK6, Sweeney3, Gliddon4 and BATF2), and the result shows that the scoring model disclosed by the invention can keep stable performance in adult population and multiple time windows (such as 0-6 months, 0-12 months and 0-24 months). The scheme of the invention is suitable for crowd screening, disease early warning and individualized intervention decision.

An mRNA pharmaceutical composition for preventing and treating tuberculosis and use thereof. The mRNA pharmaceutical composition comprises: an mRNA molecule encoding a Mycobacterium tuberculosis antigen, and a pharmaceutically acceptable excipient. The Mycobacterium tuberculosis antigen comprises the following antigen components: at least one Mycobacterium tuberculosis early-secreted antigen or an immunologically active fragment thereof; Mycobacterium tuberculosis PE / PPE family antigen Rv3872 or an immunologically active fragment thereof; and at least one Mycobacterium tuberculosis latency-associated antigen or an immunologically active fragment thereof. The mRNA pharmaceutical composition does not comprise or further comprises an mRNA molecule encoding a cytokine. The pharmaceutical composition is used for preparing a tuberculosis vaccine, which can be used not only as a prophylactic vaccine for preventing latency activation, but also as a therapeutic drug for treating active tuberculosis, and has a significant inhibitory effect on Mycobacterium tuberculosis.

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 tuberculosis antigen specific host biomarker for detecting tuberculosis infection and a kit, and belongs to the field of biological medicines. The biomarker comprises IFN gamma, CXCL10, IL-2, IL-3, GBP6, ULBP2, CXCL11, ATP13A3, RHOV, ATP2B1, IL-22 and MMP1 (Metallocin Protein Protein 1). According to the present invention, the specific RD1 region antigen or peptide pool from mycobacterium tuberculosis and the specific RD2 region antigen or peptide pool from mycobacterium tuberculosis are jointly used as the antigen irritants to stimulate peripheral whole blood or peripheral blood mononuclear cells (PBMCs) of an individual to be detected, and then the expression quantity change of the host biomarker before and after the stimulation is detected; the kit can effectively distinguish tuberculosis infected patients from non-tuberculosis infected individuals, can identify and diagnose active tuberculosis and latent tuberculosis infected patients, solves the defects of insufficient sensitivity and limited specificity of the existing diagnostic technology, and has high diagnostic efficiency.

The invention provides an mRNA (messenger ribonucleic acid) pharmaceutical composition for preventing and treating tuberculosis and application of the mRNA pharmaceutical composition. The mRNA pharmaceutical composition for preventing and treating tuberculosis comprises mRNA molecules for coding mycobacterium tuberculosis antigens and pharmaceutically acceptable auxiliary materials, the mycobacterium tuberculosis antigen comprises the following antigen components: at least one mycobacterium tuberculosis early secretion antigen or an immunocompetence fragment thereof; at least one Mycobacterium tuberculosis PE / PPE family antigen or an immunologically active fragment thereof; and at least one mycobacterium tuberculosis latent associated antigen or an immunocompetent fragment thereof; the mRNA pharmaceutical composition does not include or further includes an mRNA molecule encoding a cytokine. The pharmaceutical composition provided by the invention is used for preparing tuberculosis vaccines, can be used as a prophylactic vaccine for preventing latent activation, can also be used as a therapeutic drug for treating active tuberculosis, and has a remarkable inhibition effect on mycobacterium tuberculosis.

The invention discloses application of a reagent for detecting the content or expression level of TIPE2 in a sample in preparation of a reagent for diagnosing and / or predicting active tuberculosis. In the application, the sample comprises a blood sample. According to the application, the TIPE2 in a blood sample is used as the biomarker for detecting the active tuberculosis for the first time. Results of ROC curve analysis show that the expression level of the TIPE2 in whole blood has good sensitivity and specificity on active tuberculosis diagnosis.

The present application provides siRNA delivery nanomaterials targeting M2 macrophages, which are mannosylated bovine serum albumin nanoparticles encapsulating siRNA interfering with KLK12. The mannose coating of the materials of the present application can provide targeting effect on M2 macrophages, and the siRNA released after endocytosis of the materials can silence the expression of KLK12 and its downstream MMPs genes, reduce the degradation of collagen fibers in lung tissues, thereby controlling the number and volume of pulmonary tuberculosis granulomas, preventing the occurrence of active tuberculosis, and providing a new option for the treatment of tuberculosis.

An mRNA pharmaceutical composition for preventing and treating tuberculosis and use thereof. The mRNA pharmaceutical composition comprises: an mRNA molecule encoding a Mycobacterium tuberculosis antigen, and a pharmaceutically acceptable excipient. The Mycobacterium tuberculosis antigen comprises the following antigen components: at least one Mycobacterium tuberculosis early-secreted antigen or an immunologically active fragment thereof; at least one Mycobacterium tuberculosis PE / PPE family antigen or an immunologically active fragment thereof; and at least one Mycobacterium tuberculosis latency-associated antigen or an immunologically active fragment thereof. The mRNA pharmaceutical composition does not comprise or further comprises an mRNA molecule encoding a cytokine. The pharmaceutical composition is used for preparing a tuberculosis vaccine, which can be used not only as a prophylactic vaccine for preventing latency activation, but also as a therapeutic drug for treating active tuberculosis, and has a significant inhibitory effect on Mycobacterium tuberculosis.

The invention discloses a tuberculosis auxiliary diagnosis system fusing chest radiography and breath sound characteristics. The tuberculosis auxiliary diagnosis system comprises a breath sound acquisition module, a breath sound dynamic analysis module, a chest radiography acquisition module, a chest radiography detection module, an activity discrimination fusion module and a result output module. Breathing sound signals are collected at a plurality of standard point positions on the body surface of a patient, dynamic abnormal indexes are extracted, meanwhile, chest radiography images are obtained, focus attribute information is recognized, an activity judgment fusion module conducts consistency analysis on the chest radiography images and the dynamic abnormal indexes, standardized risk scores are generated, and high-risk, low-risk or uncertain grading results are output. According to the method, the misdiagnosis and missed diagnosis risks can be effectively reduced under the complex conditions of old focus combined activities, early hidden cases, combined chronic obstructive pulmonary disease and the like, and a visual diagnosis report containing a chest radiograph thermodynamic diagram and a breath sound frequency spectrum is provided. Compared with single chest radiography or single breath sound analysis, the sensitivity and specificity of active tuberculosis diagnosis are improved, and the method has high clinical application value.

The present invention relates to a method for detecting Mycobacterium tuberculosis, which can replace the conventional culture method that takes a long time of four to eight weeks to detect active tuberculosis, and which is a method for detecting active Mycobacterium tuberculosis by using isotopes on a sample of a patient's sputum or bronchoalveolar lavage fluid.

This invention provides a biomarker for the differential diagnosis of active pulmonary tuberculosis. The biomarker is TRANCE protein. The AUC value of this biomarker for the differential diagnosis of patients with active pulmonary tuberculosis is >0.8, indicating that the biomarker screened by this invention has high diagnostic efficacy for active pulmonary tuberculosis.

The invention discloses a combined marker for risk assessment of active tuberculosis and application of the combined marker. The combined marker comprises interleukin 6, a chemotactic factor ligand 9, a chemotactic factor ligand 10 and a vascular endothelial growth factor. According to the disclosure, the combined marker for evaluating the risk of active tuberculosis of the subject and the application thereof can be provided.

Provided in the present invention is a biomarker for the differential diagnosis of active pulmonary tuberculosis, wherein the biomarker is a TRANCE protein, and has an AUC value of >0.8 for the differential diagnosis of patients with active pulmonary tuberculosis, indicating that the biomarker screened in the present invention has a relatively high diagnostic efficacy on active pulmonary tuberculosis.

The invention relates to an active tuberculosis diagnostic marker CCND1 and application thereof, in particular to application of a reagent for detecting the diagnostic marker in preparation of a kit for diagnosing active tuberculosis, the diagnostic marker is a biomarker CCND1 in a blood sample, and the sequence of the CCND1 is as shown in SEQ ID NO: 1. The CCND1 in a blood sample is adopted as the biomarker for detecting the active tuberculosis for the first time, ROC curve analysis is adopted, the area under the curve (AUC) reaches up to 0.8263, and it is prompted that the mRNA expression level of the CCND1 can be used as an efficient biomarker for distinguishing active TB patients and non-tuberculosis people.

The application discloses a fusion protein PP13138R and application thereof in tuberculosis prevention. Specifically disclosed is a fusion protein comprising HTL, CTL and B cell epitopes in series, PorB, PADRE and RS-09. The application screens 34 epitopes for Mycobacterium tuberculosis, which have good immunogenicity and antigenicity and no toxicity and no sensitization, and have the characteristics of high population coverage and the like. The auxiliary peptide PADRE is further added to improve the immunogenicity of the vaccine, and the PorB and RS-09 are added to endow the vaccine with a targeted delivery function. In-vitro experiments prove that the PP13138R can stimulate human peripheral blood mononuclear cells to produce an immune response, and is an advantage protective antigen. The PP13138R has the advantages of simple preparation method, low cost, high yield and higher safety as a vaccine. The application has great value for the prevention and treatment of active tuberculosis and latent tuberculosis infection.

The application discloses a tuberculosis diagnosis circRNA marker, primers and application thereof. The application screens two circRNAs which are significantly highly expressed in PBMC of active pulmonary tuberculosis patients, namely, hsa_circ_0002371, a transcription region of which is located on chromosome 10 and formed by reverse splicing of exons 20 and 21 of a CCAR1 gene, and hsa_circ_0007460, a transcription region of which is located on chromosome 1 and formed by reverse splicing of exons 6-9 of a GOSR1 gene. The application further discloses primers in a tuberculosis diagnosis kit based on the circRNA marker. The circRNA marker can effectively distinguish uninfected people from active pulmonary tuberculosis patients, provides a new thought for studying the pathogenesis of active pulmonary tuberculosis, and provides a new target for early diagnosis of active pulmonary tuberculosis.

The invention relates to a novel coding gene Rv3864c (-4341113-4341511) of mycobacterium tuberculosis H37Rv and a coding protein of the novel coding gene Rv3864c (-4341113-4341511). The Rv3864c gene has high specificity, secretory property and antigenicity, and can be independently or jointly used for clinical rapid screening of latent tuberculosis infected persons and active tuberculosis patients and protecting human bodies from being infected by mycobacterium tuberculosis.

The application can diagnose the infection of a tuberculosis patient by detecting the expression amount of the LLGL2 gene, and the detection method is simple, fast, and has high detection quality and accuracy, and the sensitivity and specificity are all greater than 80%. When the expression amount of the biomarker LLGL2 gene is greater than 1.476, the subject is judged as a latent tuberculosis infection patient; when the expression amount of the biomarker LLGL2 gene is less than or equal to 1.476, the subject is judged as not suspected to be a latent tuberculosis infection patient, and needs further diagnosis. When the expression amount of the biomarker LLGL2 gene is less than 0.8653, the subject is judged as an active tuberculosis patient; when the expression amount of the biomarker LLGL2 gene is greater than or equal to 0.8653, the subject is judged as not suspected to be an active tuberculosis patient, and needs further diagnosis.

The application discloses a fusion protein HP13138PB and application thereof in tuberculosis prevention. Specifically disclosed is a fusion protein comprising HTL, CTL and B cell epitopes in series, HBD-3, PSM alpha 4 and PADRE. The application screens 34 epitopes for mycobacterium tuberculosis, which have good immunogenicity and antigenicity and no toxicity and sensitization, and have the characteristics of high population coverage and the like. The immunogenicity of the vaccine is improved by further adding antibacterial peptide HBD-3 and auxiliary peptide PADRE, and PSM alpha 4 is added to endow the vaccine with targeted delivery function. In-vitro experiments prove that HP13138PB can stimulate human peripheral blood mononuclear cells to produce an immune response, and is an advantage protective antigen. The HP13138PB as a vaccine has the advantages of simple preparation method, low cost, high yield and higher safety and the like. The application has great value for the prevention and treatment of active tuberculosis and latent tuberculosis infection.

This invention discloses the polypeptide fusion protein CP13138P and its application in tuberculosis prevention. Specifically, it discloses a fusion protein comprising tandem HTL, CTL, and B-cell epitopes, CTB, Pam2Cys, and PADRE. This invention screened 34 epitopes targeting Mycobacterium tuberculosis, which exhibit excellent immunogenicity and antigenicity, are non-toxic and non-sensitizing, and have high population coverage. In vitro experiments demonstrate that CP13138P can stimulate an immune response in human peripheral blood mononuclear cells (PBMCs), increasing IFN-γ in PBMCs. + The number of T lymphocytes is significantly increased, and they secrete significantly high levels of more than a dozen cytokines, including G-CSF, making them a dominant protective antigen. CP13138P, as a vaccine, has advantages such as simple preparation method, low cost, high yield, and enhanced safety. This invention has significant value for the prevention and treatment of active tuberculosis and latent tuberculosis infection.

The invention discloses a marker for differential diagnosis of tuberculosis and nontuberculous mycobacterium infection and curative effect monitoring of active tuberculosis and application of the marker, and belongs to the technical field of biological detection. The markers are one or more of GPX3, FGB and ATRN in plasma, and substances for detecting the markers can be used for preparing products for differential diagnosis and / or curative effect monitoring of tuberculosis. According to the invention, markers capable of identifying mycobacterium tuberculosis infection and non-mycobacterium tuberculosis infection as well as distinguishing active tuberculosis and curative tuberculosis are screened out, and the markers have excellent diagnostic performance. The invention lays a foundation for accurate typing of tuberculosis.

The application belongs to the technical field of biology and specifically relates to screening and application of a small-molecule compound for resisting mycobacterium tuberculosis infection. The application is based on the special structure of HDAC6, confirms that HDAC6 specificity is maintained in the expression of macrophages of tuberculosis resistors, and proves that the ability of macrophages from the tuberculosis resistor population to efficiently remove Mtb infection depends on HDAC6. Protein targets for inhibiting HDAC6 degradation are explored, and corresponding inhibitors are screened, so that a small-molecule compound for inhibiting HDAC6 is found in the ubiquitination region of HDAC6, a new idea is provided for treating tuberculosis, and a theoretical basis is laid for an immunotherapy scheme for active tuberculosis patients.

This invention discloses the fusion protein PP19128R and its application in the prevention or treatment of Mycobacterium tuberculosis infection. Specifically, it discloses a fusion protein comprising tandem HTL, CTL, and B-cell epitopes, PorB, RS-09, and PADRE. This invention screened 39 epitopes targeting Mycobacterium tuberculosis, which exhibit excellent immunogenicity and antigenicity, are non-toxic and non-sensitizing, and have high population coverage. The helper peptide PADRE is further added to enhance the immunogenicity of the vaccine, and PorB and RS-09 are added to endow the vaccine with targeted delivery function. In vitro experiments demonstrate that PP19128R can stimulate an immune response in human peripheral blood mononuclear cells, making it a superior protective antigen. PP19128R as a vaccine has advantages such as simple preparation method, low cost, high yield, and enhanced safety. This invention has significant value for the prevention and treatment of active tuberculosis and latent tuberculosis infection.