Application of thyroid hormone and analogue thereof in preparation of drugs for treating sickle-cell disease

A technology for thyroid hormone and sickle cell disease, applied in the field of sickle cell disease, can solve the problems of acute hemolysis, huge economic burden, and high cost of blood transfusion

Inactive Publication Date: 2020-07-17
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
View PDF1 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] 2) Blood transfusion can cause adverse reactions such as fever, chills, and rash, and in severe cases, it can lead to acute hemolysis, tracheal constriction, and blood pressure drop;
[0008] 3) Blood transfusion may face the risk of infectious dise

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Application of thyroid hormone and analogue thereof in preparation of drugs for treating sickle-cell disease
  • Application of thyroid hormone and analogue thereof in preparation of drugs for treating sickle-cell disease
  • Application of thyroid hormone and analogue thereof in preparation of drugs for treating sickle-cell disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] In K562 cells, Triac specifically activates the expression process of ζ-globin gene (HBZ) as follows:

[0036] During the differentiation process of K562 cells, after they were treated with hemin or hemin+Triac for 72 hours, the cells were collected by centrifugation at 2000rpm for 5 minutes, the total RNA was extracted using TRIzol reagent (Invitrogen), and then the reverse transcription kit (ReverTra Ace, TOYOBO) was used Synthesize cDNA, and finally use SYBRGreen Realtime PCR Master Mix (TOYOBO) reagent for quantitative PCR to detect gene expression level.

[0037]The quantitative PCR reaction system is:

[0038]

[0039] The quantitative PCR reaction conditions are:

[0040] Hot start: 95°C, 10 minutes;

[0041] Denaturation: 95°C, 10 seconds;

[0042] Annealing / extension: 60°C, 30 seconds.

[0043] 40 loops.

[0044] Melting curve analysis.

[0045] Such as figure 1 As shown, after K562 was treated with Triac for 72 hours, quantitative PCR results showed ...

Embodiment 2

[0071] During the development of zebrafish embryos, Triac, T3, and T4 were added to zebrafish embryos 96 hours after fertilization. After being treated with Triac, T3, and T4 for 24 hours, the embryos were fixed with 4% paraformaldehyde, and the whole embryo was hybridized in situ. Technique detection ζ-globin gene (hbae5) expression.

[0072] Such as figure 2 As shown, in zebrafish embryos, Triac, T3 and T4 significantly activated the expression of ζ-globin gene (hbae5), that is, significantly upregulated.

Embodiment 3

[0074] During the development of zebrafish embryos, Triac, T3, and T4 were added to zebrafish embryos 96 hours after fertilization. After 24 hours of treatment, the embryos were collected, and total RNA was extracted using TRIzol reagent (Invitrogen), and then reverse transcription kit (ReverTra Ace, TOYOBO) to synthesize cDNA, and finally use SYBRGreen Realtime PCR Master Mix (TOYOBO) reagent for quantitative PCR to detect gene expression level.

[0075] The quantitative PCR reaction system is:

[0076]

[0077] The quantitative PCR reaction conditions are:

[0078] Hot start: 95°C, 10 minutes;

[0079] Denaturation: 95°C, 10 seconds;

[0080] Annealing / extension: 60°C, 30 seconds.

[0081] 40 loops.

[0082] Melting curve analysis.

[0083] Such as image 3 As shown, in zebrafish embryos, Triac, T3 and T4 significantly activated the expression of the ζ-globin gene (hbae5), that is, the quantitative PCR results showed that the expression of the ζ-globin gene (hbae5) ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention provides application of a thyroid hormone and an analogue thereof in preparation of drugs for treating a sickle-cell disease, and particularly relates to application in regulation and control of zeta-globin gene expression. In the K562 cell differentiation process, the thyroid hormone analogue can specifically and remarkably up-regulate the expression of zeta-globin gene (HBZ) by more than 50 times; and after treatment is carried out in a zebra fish embryo of a model animal by the thyroid hormone and the analogue thereof, the expression of the zeta-globin gene (hbae5) can also bespecifically up-regulated by more than 30-70 times. Therefore, the thyroid hormone and the analogue thereof disclosed by the invention can specifically activate the expression of the zeta-globin gene, namely, the silent zeta-globin gene in the body of a sickle-cell disease patient is reactivated to inhibit sickle hemoglobin S polymerization reaction, the thyroid hormone and the analogue become amethod for preparing the drugs for treating the sickle-cell disease, an economical, safe and effective method is provided for treatment of the sickle-cell disease, and the method can be widely appliedand popularized.

Description

technical field [0001] The invention belongs to the technical field of sickle cell disease, and specifically relates to the application of thyroid hormone and analogs thereof in the preparation and treatment of sickle cell disease. Background technique [0002] Sickle-cell disease (SCD) is a hemoglobinopathy with recurrent acute attacks and progressive organ damage. The etiology is due to the mutation of glutamic acid at position 6 of the β-globin chain (β-globin) to valine (β E6V ), resulting in abnormal sickle-shaped hemoglobin S (HbS, α 2 beta S 2 ) formation, replacing normal hemoglobin A (HbA, α 2 beta 2 ). When the partial pressure of oxygen decreases, the solubility of HbS decreases sharply, and tubular polymers are formed through polymerization reaction, which accumulates and precipitates in red blood cells, destroys the structure and deformability of red blood cells, promotes dehydration of red blood cells, and twists red blood cells into stiff sickle cells ( ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K31/198A61K31/192A61P7/06
CPCA61K31/198A61K31/192A61P7/06
Inventor 袁浩朱军
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap