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Uses of hsa-mirna-423-5p and hsa-mirna-423-5p inhibitors

A technology of inhibitors and uses, applied in the field of biomedical engineering, can solve problems such as large side effects and severe liver and kidney damage in patients

Active Publication Date: 2021-05-28
李继承
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The anti-tuberculosis treatment drugs are more serious to the liver and kidney damage of the patient, and the side effects are very serious if taken for a long time

Method used

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  • Uses of hsa-mirna-423-5p and hsa-mirna-423-5p inhibitors
  • Uses of hsa-mirna-423-5p and hsa-mirna-423-5p inhibitors
  • Uses of hsa-mirna-423-5p and hsa-mirna-423-5p inhibitors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Serum hsa-miRNA-423-5p expression level in embodiment 1 pulmonary tuberculosis patients and healthy controls

[0020] 1 material

[0021] 1.1 Case samples

[0022] 1.1.1 Diagnostic criteria for pulmonary tuberculosis

[0023] The clinical diagnosis was based on the diagnostic criteria for pulmonary tuberculosis issued by the Ministry of Health of China and the revised International Tuberculosis Control Regulations.

[0024] All tuberculosis patients who met the following items were included in this embodiment: ① All cases were diagnosed as pulmonary tuberculosis according to the national diagnostic criteria for tuberculosis based on clinical manifestations, bacterial culture and imaging examination; ② HIV tests were negative, no history of tuberculosis, no Chronic obstructive pulmonary disease, asthma, pneumonia, lung cancer, diabetes, hypertension and other complications, normal liver and kidney function, no other congenital diseases, chronic inflammation, autoimmune...

Embodiment 2

[0075] Example 2 hsa-miRNA-423-5p blocks autophagosome maturation

[0076] The hsa-miRNA-423-5p mimic (hsa-miRNA-423-5p mimic for short), which is a nucleic acid fragment 5'-ugaggggcagagagcgagacuuu-3' synthesized in vitro, is stored in vacuum freeze-dried powder at -20°C. The hsa-miRNA-423-5p mimic powder was treated with RNase free ddH 2 O was dissolved at room temperature to 20uM, and stored in aliquots. The hsa-miRNA-423-5p solution was used to transfect human macrophage THP-1 in vitro at a concentration of 100 nM.

[0077] Laser confocal microscopy was used to detect the co-localization of autophagosomes and lysosomes. See the test results figure 2 . exist figure 2 In , compared with the control, the ratio of yellow dots / (yellow dots + green dots) is low, indicating that autophagy maturation is blocked, which is determined by figure 2 It can be seen that hsa-miRNA-423-5p mimic can lead to obvious autophagy maturation inhibition. Further, the expression level of a...

Embodiment 3

[0078] Example 3 hsa-miRNA-423-5p inhibitor relieves the phenomenon of autophagy maturation blockage

[0079] hsa-miRNA-423-5p inhibitor, which is an in vitro synthetic nucleic acid fragment 5'-aaagucutcgcucucugccccuca-3', hsa-miRNA-423-5p inhibitor powder with RNase free ddH 2 O was dissolved at room temperature to 20uM, and stored in aliquots. The hsa-miRNA-423-5p inhibitor solution was used to transfect human macrophage THP-1 in vitro at a concentration of 100 nM.

[0080] Laser confocal microscopy was used to detect the co-localization of autophagosomes and lysosomes. See the test results image 3 . exist image 3 Among them, compared with the hsa-miRNA-423-5p mimic treatment group, the ratio of yellow dots / (yellow dots + green dots) increased, indicating that the blockage of autophagy maturation was released. image 3 It can be seen that hsa-miRNA-423-5p inhibitor can lead to the relief of autophagy maturation blockage. Further, the expression level of a protein VPS...

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Abstract

The invention discloses the use of hsa-miRNA-423-5p in the preparation of an autophagy maturation inhibitor, and the use of the hsa-miRNA-423-5p inhibitor in the preparation of a drug for treating tuberculosis. The expression level of hsa-miRNA-423-5p provided by the present invention in the serum of tuberculosis patients is significantly higher than that of healthy controls, and it is confirmed that when hsa-miRNA-423-5p is highly expressed, it can lead to obvious autophagy maturation blocking phenomenon; hsa When the expression of ‑miRNA‑423‑5p is inhibited, the phenomenon of autophagy maturation inhibition is relieved. Therefore, hsa‑miRNA‑423‑5p can be used as a good target for the treatment of tuberculosis. Moreover, hsa-miRNA-423-5p is a small molecule that exists by itself, so it is superior to chemical drugs in terms of side effects, and will not cause drug-resistant tuberculosis due to repeated medication.

Description

technical field [0001] The invention relates to the technical field of biomedical engineering, in particular to the use of hsa-miRNA-423-5p and hsa-miRNA-423-5p inhibitors. Background technique [0002] Tuberculosis is a lung disease caused by Mycobacterium tuberculosis infection. In the process of anti-Mycobacterium tuberculosis, macrophages play a very important role, including phagocytosis and autophagy and so on. And the literature (Ponpuak M, etal.Delivery of Cytosolic Components by Autophagic Adaptor Protein p62EndowsAutophagosomes with Unique Antimicrobial Properties. Immunity 32,329-341(2010).) showed that the autophagolysosomes in the macrocells that phagocytosed Mycobacterium tuberculosis Phagocytosis is a more efficient way to clear M. tuberculosis than phagocytosis. In the study of macrophages of tuberculosis, ESX-1 has been reported in the literature (Romagnoli A, et al. ESX-1dependent impairment of autophagic flux by Mycobacterium tuberculosis in human dendri...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/6883A61K45/00A61P11/00A61P31/06
CPCA61K45/00A61P11/00A61P31/06C12Q1/6883C12Q2600/106C12Q2600/178
Inventor 李继承屠慧惠
Owner 李继承
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