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Medicine for treating doxorubicin-induced cardiotoxic injury and application

A technology of cardiotoxicity and doxorubicin, applied in the field of biomedicine, can solve the problems of increasing the four-year cumulative incidence of the second malignant tumor, side effects, thrombocytopenia, etc., and achieve the effect of improving cardiomyocyte apoptosis

Active Publication Date: 2022-05-17
SHANGHAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patented technology prevents certain substances from affecting cellular functions when used on cancer patients who have been treated with chemotherapy (doxycycline). It suggests injecting this gene into cells infected with adenovirus type 35 which causes death if administered without permission.

Problems solved by technology

This patents discusses how chemotherapy agents like Doxycyline (DOX) or Daunosupressin help reduce symptoms associated with cancer but they still result in severe complications due to their harmful effect upon other tissues called the heart's blood vessels. There needs to be a way to specifically attack these chemical therapies without causing any negative health consequences.

Method used

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  • Medicine for treating doxorubicin-induced cardiotoxic injury and application
  • Medicine for treating doxorubicin-induced cardiotoxic injury and application
  • Medicine for treating doxorubicin-induced cardiotoxic injury and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] 1. Construction of circ-ZNF609 shRNA:

[0031] Firstly, the sequence of circZNF609 was obtained from the circBase database (species human source: hsa_circ_0000615 and mouse source: mmu_circ_0001797). Design siRNA sequences across the back-splicing site of the circular RNA:

[0032] siRNA#1 (SEQ ID NO.5): 5'-AGTCAAGTCTGAAAAGCAATGAT-3'

[0033] siRNA#2 (SEQ ID NO.4): 5'-AGTCAAGTCTGAAAAGCAATG-3'

[0034] After designing the siRNA, insert the shRNA structure template:

[0035] For shRNA#1:

[0036] Forward primer (SEQ ID NO.6): 5'-GATCAGTCAAGTCTGAAAAGCAATGATCTCGAGATCATTGCTTTTCAGACTTGACT TTTTTG-3'

[0037] Reverse primer (SEQ ID NO.7): 5'-AATT CAAAAAGTCAAGTCTGAAAAGCAATGATCTCGAGATCATTGCTTTTCAGACTTGACT-3'

[0038] For shRNA#2:

[0039] Forward primer (SEQ ID NO.2): 5'-GATCAGTCAAGTCTGAAAAGCAATGCTCGAGCATTGCTTTTCAGACTTGACT TTTTTG-3'

[0040] Reverse primer (SEQ ID NO.3): 5'-AATT CAAAAAAGTCAAGTCTGAAAAGCAATGCTCGAGCATTGCTTTTCAGACTTGACT-3';

[0041] The resulting shRNA sequen...

Embodiment 2

[0060] 1. Establishment of doxorubicin-induced cardiotoxic injury model in mice

[0061] Take C57BL / 6J wild-type male mice aged 8-10 weeks, and give the mice intraperitoneal injection of doxorubicin at a dose of 5 mg / kg to induce cardiotoxic injury to the mice, once a week for 4 weeks, and the corresponding model The control model, that is, the control group mice, were replaced by intraperitoneal injection of an equal volume of normal saline once a week for 4 weeks. The mice were sacrificed 7 days after the last administration was completed.

[0062] 2. AAV9-sh-circ-ZNF609 injection

[0063] will be 10 11 A dose of vg / mouse was injected into the mice through tail vein injection, and a cardiotoxic injury model was constructed 1 week later. Where vg represents vector genome. The specific experimental process is as follows:

[0064] First, divide the experimental mice into 4 groups, namely control virus + normal saline group, control virus + doxorubicin group, AAV9-shRNA-cir...

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Abstract

The invention provides a medicine for treating doxorubicin-induced cardiotoxic injury and application, and relates to the technical field of biological medicine. The invention provides application of a reagent for interfering expression of circular RNAcirc-ZNF609 in myocardial tissue in preparation of a medicine for preventing and/or treating doxorubicin-induced cardiotoxic injury, the reagent or the medicine can deliver a gene sequence of circ-ZNF609shRNA which is artificially designed into the myocardial tissue based on AAV virus, and the reagent or the medicine can be used for preparing a medicine for preventing and/or treating doxorubicin-induced cardiotoxic injury. The application has the effects of inhibiting apoptosis of myocardial cells, improving the systolic function of the heart and resisting doxorubicin-induced cardiac toxic injury by inhibiting apoptosis of the circular RNAcirc-ZNF609 in myocardial tissues and interfering expression of the circular RNAcirc-ZNF609 in the myocardial tissues.

Description

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Claims

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Application Information

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Owner SHANGHAI UNIV
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