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Application of up-regulator of hr or nhej pathway in preparation of medicines for treating diabetes and preventing tumor occurrence in diabetic individuals

A technology for diabetes and diabetic retina, applied in the field of biomedicine, can solve the problems of unsatisfactory clinical effects of diabetic complications, achieve the effect of strengthening DNA damage repair and alleviating dysfunction

Active Publication Date: 2022-03-25
SHANGHAI FIRST PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in general, the prevention and treatment of diabetic complications has not yet achieved satisfactory clinical results.
However, there is no report on the role of up-regulators of HR or NHEJ pathways in the prevention and treatment of diabetic vascular complications and tumors.

Method used

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  • Application of up-regulator of hr or nhej pathway in preparation of medicines for treating diabetes and preventing tumor occurrence in diabetic individuals
  • Application of up-regulator of hr or nhej pathway in preparation of medicines for treating diabetes and preventing tumor occurrence in diabetic individuals
  • Application of up-regulator of hr or nhej pathway in preparation of medicines for treating diabetes and preventing tumor occurrence in diabetic individuals

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Experimental program
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Effect test

Embodiment 1

[0090] 1. Method

[0091] 1. Construction of viral vector overexpressing EWS (name: E-OE) or Fbxw7 (name: F-OE) protein

[0092] (1) Amplify the nucleotide sequences of EWS and Fbxw7 by PCR reaction (the EWS sequence is shown in SEQ ID NO: 1, and the Fbxw7 sequence is shown in SEQ ID NO: 2), and the two ends are connected to EcoRI and BamHI restriction sites point;

[0093] (2) Double-enzyme digestion PCR product and purification;

[0094] (3) H201pAdeno-MCMV-EGFP-3FLAG vector plasmid (Shanghai Heyuan Biotechnology Co., Ltd.) was also double-enzyme digested, the large fragment was recovered and purified, and the EWS or Fbxw7 gene fragment in step (2) was inserted by molecular cloning technology instead of EGFP to the EcoRI and BamHI restriction sites of the shuttle plasmid;

[0095] (4) Screening transformants by colony PCR, and the screened positive clones are verified by sequencing;

[0096] (5) Sequencing to verify the correct clone, and perform high-purity plasmid extr...

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Abstract

The invention relates to the application of an up-regulator of HR or NHEJ pathway in the preparation of medicines for treating diabetes and preventing and treating tumors in diabetic individuals. The present invention found that DSB and DSB repair mechanism were damaged in diabetic cells and tissues, and confirmed for the first time that EWS / Fbxw7 repairs damaged DNA by activating HR pathway and NHEJ pathway, and blocks cell cycle in G0 / G1 phase to facilitate DNA repair ; EWS / Fbxw7 can significantly reduce the hyperactivation of PARP in diabetic macrovascular, microvascular endothelium and retinal nerve tissue; the mechanism of inhibiting the hyperactivation of PARP may be related to the activation of HR and NHEJ pathways. It is suggested that the up-regulator of HR or NHEJ pathway can be used to prepare drugs for alleviating the dysfunction of diabetic vascular endothelium, or strengthening DNA damage repair, or treating diabetes, or preventing diabetic complications, or preventing tumor occurrence in diabetic individuals.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of HR or NHEJ pathway up-regulators in the preparation of medicines for treating diabetes and preventing and treating the occurrence of tumors in individuals with diabetes. Background technique [0002] Diabetes mellitus (DM) is a lifelong metabolic disease characterized by chronic hyperglycemia. Diabetic vascular disease is a characteristic pathological change of diabetes, and it is the main cause of disease and disability in patients. Long-term high blood sugar will damage the large blood vessels and micro blood vessels, which will seriously endanger the heart, brain, kidney, peripheral nerves, eyes, feet, etc. [1]. According to the statistics of the American Diabetes Association (ADA), the risk of complications in patients with diabetes for more than 3 years is more than 46%; the probability of complications in patients with diabetes for more than 5 years ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61P3/10A61P35/00A61P25/00A61P9/10A61P13/12A61P17/02A61K49/00C12Q1/6883C12Q1/6886
CPCA61K45/00A61P3/10A61P35/00A61P25/00A61P9/10A61P13/12A61P17/02A61K49/0008C12Q1/6883C12Q1/6886C12Q2600/158
Inventor 韦芳许迅邓骏杰姚谢怡顾青
Owner SHANGHAI FIRST PEOPLES HOSPITAL
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