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Application of up-regulating agent of HR or NHEJ pathway in preparation of medicament for treating diabetes mellitus and preventing diabetic individual tumorigenesis

A technology of diabetes and diabetic blood vessels, which is applied in the field of biomedicine and can solve the problems of unsatisfactory clinical effects of diabetic complications

Active Publication Date: 2020-03-10
SHANGHAI FIRST PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This technology can help people with both type I or II diabets by providing ways to stop their blood sugar from getting too much inside them without causing damage themselves. It also helps reduce certain types of cancer that may occur during these conditions.

Problems solved by technology

This patented technical problem addressed in this patents relates to improving the effects of treatments against various metabolism related conditions associated with chronovascular comorbidities including those caused by insurative carbo syndrome, hyperlipemia, obstructive sleep apnea, renal failure, arterial saccumulation, urogenital tract injury, brain deteriorations like stroke, Parkinson disease, amputation, etc., inflammatory bowel adhesions, stomach nerve fibrosity, lung nodules, pulmonarceratitis, heart attacks, abnormal glomerulosferritancies, membrane rupture, bacteria infectious impairment, oxazolidne body accumulations, iron deficiency, copper ion binding proteins, histones, transcription factors, cytochrome family members, ribosircholdimilarsmechanism, ATP dependent chromatin remodeling, autotaxons containing SH3-domain interact domains, calcium regulate signaling cascade systems, and mitochondria act as essential components during these stages. Overall, the goal of developing effective intervention strategies targeting different aspects of these issues will lead to better outcomes for future medical trials.

Method used

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  • Application of up-regulating agent of HR or NHEJ pathway in preparation of medicament for treating diabetes mellitus and preventing diabetic individual tumorigenesis
  • Application of up-regulating agent of HR or NHEJ pathway in preparation of medicament for treating diabetes mellitus and preventing diabetic individual tumorigenesis
  • Application of up-regulating agent of HR or NHEJ pathway in preparation of medicament for treating diabetes mellitus and preventing diabetic individual tumorigenesis

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0090] 1. Method

[0091] 1. Viral vector construction for overexpressing EWS (named: E-OE) or Fbxw7 (named: F-OE) protein

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

[0093] (2) double restriction digestion of PCR products and purification;

[0094] (3) Also double digest the H201pAdeno-MCMV-EGFP-3FLAG vector plasmid (Shanghai Heyuan Biotechnology Co., Ltd.), recover and purify the large fragment, and insert the EWS or Fbxw7 gene fragment in step (2) using molecular cloning technology instead of EGFP to the EcoRI and BamHI restriction sites of the shuttle plasmid;

[0095] (4) Colony PCR screens transformants, and the screened positive clones are sequenced and verified;

[0096] (5) Sequencing verifies the correct clones, and extracts high-purity plasmids;

[00...

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PUM

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Abstract

The invention relates to an application of an up-regulating agent of a homologous recombination repair (HR) or non-homologous end joining (NHEJ) pathway in preparation of a medicament for treating diabetes and preventing diabetic individual tumorigenesis. Inventors find that DSB and DSB repair mechanism damage exist in diabetic human cells and tissue, and confirm that EWS/Fbxw7 repairs damaged DNAby activating the HR pathway and the NHEJ pathway for the first time, and the cell cycle is blocked at G0/G1 phase to facilitate DNA repair; the EWS/Fbxw7 can significantly reduce the excessive activation of PARP in diabetic large blood vessels, microvascular endothelium and retinal nerve tissue; the mechanism that inhibits the excessive activation of the PARP can be related to the activation ofthe HR and NHEJ pathways; and results suggest that the up-regulating agent of the HR or NHEJ pathway can be used to prepare the medicament for alleviating a diabetes mellitus vascular endothelial dysfunction, or strengthening the DNA damage repair, or treating the diabetes mellitus, or preventing diabetic complications, or preventing the diabetic individual tumorigenesis.

Description

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Claims

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Application Information

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Owner SHANGHAI FIRST PEOPLES HOSPITAL
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