Method for screening depleted uranium renal toxicity action target and targeted drug

Abstract

The invention relates to a method for screening depleted uranium renal toxicity action targets and targeted drugs, which comprises the following steps of: 1, searching the action targets related to depleted uranium renal toxicity in a target database, selecting the targets of which the correlation is greater than 10.0, and then performing de-weighting integration to obtain the depleted uranium renal toxicity action targets; the method comprises the following steps: performing protein-protein interaction analysis on uranium-depleted kidney toxicity action targets, hiding free targets, then analyzing unhidden targets to obtain a protein-protein interaction result, obtaining a contribution value of protein according to the protein-protein interaction result, and selecting a core target according to the contribution value; and 3, screening the targeted drug from the drug database based on the core target spot, and classifying and analyzing the screened targeted drug. Through the screening method provided by the invention, the action target of the depleted uranium renal toxicity and the targeted drug for preventing and treating the depleted uranium renal toxicity can be predicted.

Description

Technical Field

[0001] The invention belongs to the technical field of target and drug screening, and in particular relates to a method for screening a depleted uranium nephrotoxicity target and a targeted drug. Background Art

[0002] Depleted uranium (Uranium), especially depleted uranium (DU), is a radioactive material that is widely used in civil and military activities. The nephrotoxicity of depleted uranium is mainly reflected in its chemical toxicity; when the human body ingests or inhales a large amount of depleted uranium particles, the depleted uranium particles will be deposited in the body and may enter the kidneys through the blood circulation, thereby interfering with the normal function of the kidneys, causing kidney damage, and may further cause kidney disease. In addition, the nephrotoxicity of depleted uranium is not only manifested as direct kidney damage, but may also indirectly affect the health of other organs by affecting kidney function. For example, kidney damage may lead to the accumulation of waste and toxins in the body, which in turn causes damage to organs such as the liver and heart. In addition, depleted uranium may further aggravate health problems by interfering with the body's metabolic function and affecting the absorption and utilization of nutrients.

[0003] The nephrotoxicity caused by depleted uranium is clear, but there is currently no effective drug to treat the nephrotoxicity caused by depleted uranium, and the targets and mechanisms of action of depleted uranium nephrotoxicity are also unclear, which limits the research and development of drugs related to depleted uranium nephrotoxicity; therefore, developing a method for screening targets of depleted uranium nephrotoxicity and targeted drugs, and screening out targets of depleted uranium nephrotoxicity and targeted drugs is crucial for the research and development of depleted uranium nephrotoxicity drugs. Summary of the invention

[0004] The purpose of the present invention is to overcome the defects in the prior art and provide a method for screening depleted uranium nephrotoxicity targets and targeted drugs, which can screen out depleted uranium nephrotoxicity targets and targeted drugs, lay a foundation for the research and development of depleted uranium nephrotoxic drugs, shorten the drug research and development cycle, and reduce the cost of drug research and development.

[0005] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0006] A method for screening targets of depleted uranium nephrotoxicity comprises the following steps:

[0007] Targets related to depleted uranium nephrotoxicity were searched in the target database, and targets with correlation greater than 10.0 were selected. Then, deduplication and integration were performed to obtain depleted uranium nephrotoxicity targets.

[0008] As a further technical solution, the target database includes one or both of the Gene Cards database and the OMIM database.

[0009] A method for screening a depleted uranium nephrotoxicity targeted drug comprises the following steps:

[0010] First, protein-protein interaction analysis was performed on the screened depleted uranium nephrotoxicity targets to hide the free targets, and then the unhidden targets were analyzed to obtain protein-protein interaction results. The contribution values ​​of the targets were obtained based on the protein-protein interaction results, and the core targets were selected based on the contribution values.

[0011] Then, based on the core targets, targeted drugs for depleted uranium nephrotoxicity were screened out from the drug database, and the screened targeted drugs for depleted uranium nephrotoxicity were classified and analyzed.

[0012] As a further technical solution, protein-protein interaction analysis was performed on the string12.0 database.

[0013] As a further technical solution, the contribution value of the target was obtained according to the protein-protein interaction results using Cytoscape software.

[0014] As a further technical solution, targets with contribution values ​​greater than 40 are taken as core targets.

[0015] As a further technical solution, the drug database includes the Coremine Medical database.

[0016] The depleted uranium nephrotoxicity targeted drugs screened by the screening method for depleted uranium nephrotoxicity targeted drugs include qi-invigorating and qi-promoting drugs, blood-activating drugs, and heat-clearing and detoxifying drugs;

[0017] Among them, the Qi-tonifying and Qi-promoting drugs include one or more of ginseng, astragalus, and magnolia bark;

[0018] Blood-activating drugs include salvia miltiorrhiza and turmeric;

[0019] Heat-clearing and detoxifying drugs include Scutellaria baicalensis, Rubescens rubescens, and Ricinus bean.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] The present invention collects and processes the target sites of depleted uranium nephrotoxicity, uses protein-protein interaction analysis, obtains the core target sites of depleted uranium nephrotoxicity through Cytoscape, and screens out potential depleted uranium nephrotoxicity targeted drugs through Coremine Medical. The screening method of the present invention can predict the target sites of depleted uranium nephrotoxicity and its targeted drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The present invention is a flow chart for screening targeted drugs for depleted uranium nephrotoxicity.

[0023] Figure 2 The contribution value of the target of depleted uranium nephrotoxicity; DETAILED DESCRIPTION

[0024] The technical solution of the present invention will be described clearly and completely below in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0025] Example 1

[0026] A method for screening targeted drugs for preventing and treating depleted uranium nephrotoxicity comprises the following steps:

[0027] S1. Collect and process the targets of depleted uranium nephrotoxicity

[0028] Enter the keyword "Nephrotoxicity of depleteduranium" in the Gene Cards and OMIM databases, check the targets related to depleted uranium nephrotoxicity, and select the targets with a correlation greater than 10.0. At the same time, through literature retrieval, the retrieved targets are deduplicated and integrated to obtain depleted uranium nephrotoxicity targets. In this embodiment 1, a total of 47 depleted uranium nephrotoxicity targets are obtained, as shown in Table 1;

[0029] Table 1 Targets of depleted uranium nephrotoxicity

[0030]

[0031] S2. Screening of core targets for depleted uranium nephrotoxicity

[0032] The 47 depleted uranium nephrotoxicity targets screened were uploaded to the string12.0 database, and the "Multiple Proteins" project was selected. The Organism was selected as "Homo sapiens". After confirmation, the free targets were hidden, and protein-protein interaction analysis (PPI) was performed to obtain protein-protein interaction results. Then, the protein-protein interaction results were uploaded to Cytoscape 3.9.0 software to obtain the contribution value of the target. The target with a contribution value greater than 40 was regarded as the core target (see Figure 2 );

[0033] The core targets with a target contribution value greater than 40 screened out in this example include ALB, TP53, IL-6

[0034] S3. Screening of potential drugs targeting depleted uranium nephrotoxicity

[0035] According to the screened core targets, the depleted uranium nephrotoxicity core targets were input into the Coremine Medical database, and the screened core targets (ALB, TP53, IL-6) were added. The condition was set to P < 0.05. After selecting the targeted drugs for screening, "Explore" was performed, and the screened depleted uranium nephrotoxicity targeted drugs were summarized, classified and analyzed to obtain potential drug rules for the prevention and treatment of depleted uranium nephrotoxicity. It was found that the screened depleted uranium nephrotoxicity targeted drugs were divided into three categories. The first category was the Qi-invigorating and Qi-promoting category, including ginseng, astragalus, and magnolia bark; the second category was the blood-activating category, including salvia miltiorrhiza and turmeric; the third category was the heat-clearing and detoxifying category, including scutellaria baicalensis, rubescens, and ricinus seeds.

[0036] The above-described embodiments are only preferred embodiments of the present invention, and are not exhaustive of the feasible implementations of the present invention. For those skilled in the art, any obvious changes made thereto without departing from the principles and spirit of the present invention should be considered to be included in the scope of protection of the claims of the present invention.

Claims

1. A method for screening targets of depleted uranium nephrotoxicity, characterized in that: The steps include: Targets related to depleted uranium nephrotoxicity were searched in the target database, and targets with correlation greater than 10.0 were selected. Then, deduplication and integration were performed to obtain depleted uranium nephrotoxicity targets.

2. The method for screening targets of depleted uranium nephrotoxicity according to claim 1, characterized in that: The target database includes one or both of the Gene Cards database and the OMIM database.

3. A method for screening a depleted uranium nephrotoxicity targeted drug, characterized in that: First, a protein-protein interaction analysis is performed on the target of depleted uranium nephrotoxicity described in any one of claims 1-2, free targets are hidden, and then the unhidden targets are analyzed to obtain protein-protein interaction results, and contribution values ​​of the targets are obtained according to the protein-protein interaction results, and core targets are selected according to the contribution values; Then, based on the core targets, targeted drugs for depleted uranium nephrotoxicity were screened out from the drug database, and the screened targeted drugs for depleted uranium nephrotoxicity were classified and analyzed.

4. The method for screening a depleted uranium nephrotoxicity targeted drug according to claim 3, characterized in that: Protein-protein interaction analysis was performed using the string12.0 database.

5. The method for screening a depleted uranium nephrotoxicity targeted drug according to claim 3, characterized in that: The contribution value of the target was obtained according to the protein-protein interaction results using Cytoscape software.

6. The method for screening a depleted uranium nephrotoxicity targeted drug according to claim 3, characterized in that: Targets with contribution values ​​greater than 40 were selected as core targets.

7. The method for screening a depleted uranium nephrotoxicity targeted drug according to claim 3, characterized in that: The drug database includes the Coremine Medical database.

8. A depleted uranium nephrotoxicity targeted drug screened out by the screening method for depleted uranium nephrotoxicity targeted drug according to any one of claims 3 to 7, characterized in that: These include drugs for replenishing qi and promoting qi circulation, drugs for promoting blood circulation, and drugs for clearing away heat and detoxifying; Among them, the Qi-tonifying and Qi-promoting drugs include one or more of ginseng, astragalus, and magnolia bark; Blood-activating drugs include salvia miltiorrhiza and turmeric; Heat-clearing and detoxifying drugs include Scutellaria baicalensis, Rubescens rubescens, and Ricinus bean.

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