CN114107272A - Application of mPGES-2 as drug target for preventing and/or treating aging diseases - Google Patents
Application of mPGES-2 as drug target for preventing and/or treating aging diseases Download PDFInfo
- Publication number
- CN114107272A CN114107272A CN202111538268.7A CN202111538268A CN114107272A CN 114107272 A CN114107272 A CN 114107272A CN 202111538268 A CN202111538268 A CN 202111538268A CN 114107272 A CN114107272 A CN 114107272A
- Authority
- CN
- China
- Prior art keywords
- aging
- mpges
- adriamycin
- induced
- mice
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/90—Isomerases (5.)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y503/00—Intramolecular oxidoreductases (5.3)
- C12Y503/99—Other intramolecular oxidoreductases (5.3.99)
- C12Y503/99003—Prostaglandin-E synthase (5.3.99.3)
Abstract
The invention discloses application of mPGES-2 as a drug target for preventing and/or treating aging diseases. The invention firstly proposes that mPGES-2 is a drug target of adriamycin and hydrogen peroxide induced aging. Experiments show that the mPGES-2 knockout can obviously prolong the service life of the adriamycin-induced aging mice and obviously enhance the movement capacity of the adriamycin-induced aging mice. Meanwhile, mPGES-2 knockout can obviously inhibit the aging of primary mouse fibroblast MEF caused by hydrogen peroxide and promote proliferation. The results show that the knockout of mPGES-2 can improve the aging phenotype induced by adriamycin, delay the natural aging of MEF and accelerate aging caused by hydrogen peroxide, and show that mPGES-2 can be used as a target for preventing and/or treating adriamycin and/or hydrogen peroxide induced aging and aging related diseases thereof, and has very important significance for the development, prevention and/or treatment of the medicines for the diseases in the future.
Description
Technical Field
The invention particularly relates to application of mPGES-2 (microsomal prostaglandin E synthetase-2) as a drug target for treating and/or preventing aging and aging-related diseases, belonging to the technical field of biological medicines.
Background
Aging is a progressive, systemic, multifaceted, very complex process occurring in the later stages of life of an organism
The degradation process of (a). According to the journal report of nature, the population over 60 years old in the world is more than 12 hundred million by 2025, and the population over 60 years old in China is more than 30% by 2050, so that the society enters the deep aging stage. Aging is accompanied by a series of disease problems, and more than 70% of people over 65 have two or more chronic diseases such as arthritis, diabetes, cancer, heart disease, and stroke, and aging has now become a leading risk factor for these chronic diseases.
mPGES-2 is a specific bidirectional enzyme, and mPGES-2 binds glutathione and heme to form a complex, and prostaglandin H2(PGH2) Metabolizing into 12-hydroxyheptadecadienoic acid (12-HHT) and MDA, while mPGES-2 has a synthetic PGE when it is separated from heme2Activity of (2). MDA is a lipid peroxidation product, PGE2Is a well-known inflammatory factor, and oxidative stress and inflammation play an important role in promoting the occurrence and development of aging. However, whether mPGES-2 plays a role in the regulation of aging and its mechanism of action in regulating aging are not clear at present.
Although aging is a necessary rule of life and aging is inevitable, it is possible to delay aging. At present, with the aggravation of aging of population, the aging and the disease problems related to aging are more prominent, and effective anti-aging drug targets are searched out, so that the probability of the occurrence of the senile diseases is necessarily greatly reduced by aiming at developing drugs for preventing or treating aging, the life quality of the elderly is improved, and the service life is prolonged.
Disclosure of Invention
The invention mainly aims to provide application of mPGES-2 as a drug target for preventing and/or treating aging diseases so as to overcome the defects of the prior art.
In order to achieve the purpose, the technical scheme adopted by the invention comprises the following steps:
the embodiment of the invention provides application of mPGES-2 as a target in developing or screening or preparing a medicament for preventing and/or treating aging diseases.
Further, the medicament has at least any one of the following functions: the medicine can promote proliferation of adriamycin-induced senescent cells, promote rejuvenation of adriamycin-induced senescent cells, and delay adriamycin-induced natural senescent cells and/or H2O2The induction accelerates the progression of senescent cells.
Compared with the prior art, the invention has the beneficial effects that: the invention firstly proposes that mPGES-2 is a drug target of aging and aging-related diseases. Experiments show that mPGES-2 knockout obviously improves the movement ability of an aging-accelerating model mouse induced by adriamycin, prolongs the survival time of the model mouse, obviously promotes the proliferation of primary cells of the mouse, delays natural aging and accelerates aging, so that the cells are younger, and the results show that mPGES-2 has obvious effect on aging improvement, can be used as a target point for aging treatment, and has important significance for the development, prevention and treatment of the diseases in the future.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments described in the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a graph of the survival of normal diet mPGES-2 knock-out (KO) mice after doxorubicin administration in combination with control Wild Type (WT) mice in an exemplary embodiment of the invention;
FIG. 2 is a graph showing a comparison of exercise capacity in a rolling bar experiment after administration of doxorubicin to normal diet mPGES-2 Knockout (KO) mice and control Wild Type (WT) mice in an exemplary embodiment of the present invention;
FIG. 3 is a graph showing a comparison of proliferation potency of primary MEF cells of mPGES-2 Knockout (KO) mice with those of control wild-type (WT) mice at different generations in an exemplary embodiment of the present invention;
FIG. 4 is a graph comparing the staining of naturally senescent β -gal cells in mPGES-2 knock-out (KO) mice with control wild-type (WT) mice, passage 5 MEF cells in an exemplary embodiment of the present invention;
FIG. 5 shows mPGES-2 Knockout (KO) mice and control wild-type (WT) mice primary MEF cells administered H in accordance with an exemplary embodiment of the present invention2O2Afterwards, β -gal staining contrast;
FIG. 6 is a comparison of cell cycles of mPGES-2 Knockout (KO) mice and control wild-type (WT) mice at passage 6 MEF in accordance with an exemplary embodiment of the present invention.
Detailed Description
In view of the defects of the prior art, the inventor of the present invention has long studied and largely practiced to propose the technical solution of the present invention, which will be clearly and completely described below, and it is obvious that the described embodiments are a part of the embodiments of the present invention, but not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Specifically, as one aspect of the technical scheme of the invention, the application of mPGES-2 as a target point in developing or screening or preparing a medicament for preventing and/or treating aging diseases is involved.
In some preferred embodiments, the senescence disease is doxorubicin and/or hydrogen peroxide-induced senescence.
Further, the adriamycin is a drug acting on DNA and can cause senescence by inducing DNA damage.
Further, the hydrogen peroxide is capable of causing an imbalance in cellular oxidative stress to induce cellular senescence.
In some preferred embodiments, the inducer used by the aging mouse model when the drug is being tested comprises doxorubicin.
Further, the adriamycin is a drug acting on DNA and can cause mouse aging by inducing DNA damage.
In some preferred embodiments, the model of cellular senescence used in the drug experiments includes a model of natural senescence in primary mouse embryonic fibroblasts (also denoted as MEF) and/or a model of hydrogen peroxide-induced accelerated senescence in primary mouse embryonic fibroblasts.
Further, the drug is at least capable of improving the natural senescence of primary mouse embryonic fibroblasts in a model of natural senescence.
Further, the drug is at least capable of improving aging of primary mouse embryonic fibroblasts in an accelerated aging model.
Further, the hydrogen peroxide is capable of causing an imbalance in cellular oxidative stress to induce cellular senescence.
In some preferred embodiments, the agent is capable of inhibiting at least the activity of mPGES-2.
In some preferred embodiments, the medicament is capable of at least increasing the exercise capacity of doxorubicin-induced aged mice.
In some preferred embodiments, the medicament is capable of at least prolonging the lifespan of an doxorubicin-induced aging mouse.
In some preferred embodiments, the medicament is capable of at least inhibiting Adriamycin-induced aging progression in aging mice.
In some preferred embodiments, the medicament has at least any one of the following functions: the medicine can promote proliferation of adriamycin-induced senescent cells, promote rejuvenation of adriamycin-induced senescent cells, and delay adriamycin-induced natural senescent cells and/or H2O2The induction accelerates the progression of senescent cells.
In some preferred embodiments, the senescence disease is doxorubicin and/or hydrogen peroxide-induced senescence.
The invention firstly proposes that mPGES-2 is a drug target of adriamycin and hydrogen peroxide induced aging. Experiments show that the mPGES-2 knockout can obviously prolong the service life of the adriamycin-induced aging mice and obviously enhance the movement capacity of the adriamycin-induced aging mice. Meanwhile, mPGES-2 knockout can obviously inhibit aging of primary mouse fibroblast MEF caused by hydrogen peroxide, promote proliferation of MEF, prolong G1 phase of cells and enable the cells to be young. The results show that the knockout of mPGES-2 can improve the aging phenotype induced by adriamycin, delay the natural aging of MEF and accelerate aging caused by hydrogen peroxide, and show that mPGES-2 can be used as a target for preventing and/or treating adriamycin and hydrogen peroxide induced aging and aging related diseases thereof, and has very important significance for the development, prevention and/or treatment of the medicines for the diseases in the future.
The technical solutions of the present invention are further described in detail below with reference to several preferred embodiments and the accompanying drawings, which are implemented on the premise of the technical solutions of the present invention, and a detailed implementation manner and a specific operation process are provided, but the scope of the present invention is not limited to the following embodiments.
The experimental materials used in the examples used below were all available from conventional biochemical reagents companies, unless otherwise specified.
Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
The results and analysis of the experiments related to this example are as follows:
firstly, experimental steps
Experimental animals:
the mPGES-2 heterozygous mice used in this example were obtained from Jiangsu Jiejicaokang Biotech, Inc. using CRISPR Cas9 technology, and passed Ptges2 at Xuzhou university of medicine+/-Hybridization results in mPGES-2 wild-type (WT) mice and mPGES-2 Knockout (KO) mice.
Male C57BL/6 mice were purchased from Experimental animals technology, Inc., Vitonuli, Beijing, license number SCXK (Jing) 2007-0001. The mice are placed under the standard conditions of humidity of 50 +/-10% and temperature of 23 +/-2 ℃ for adapting to survival for 12 hours every day and night. Mice had free access to water and food. All animal management and treatment protocols were approved by the animal ethics committee of xu nationality medical university. All experiments were performed as recommended by the ethical guidelines for managing and using animal behavior.
Reagent:
doxorubicin was purchased from seleck, and the Cell senescence β -galactosidase staining kit was purchased from Cell Signaling Technology.
Example 1 Adriamycin-induced aging mouse model
mPGES-2WT and KO mice were selected and divided into cages, and the scoring cage day was D0. A model of aging was constructed by intraperitoneal injection of doxorubicin 10mg/kg body weight at D1 and D7, respectively, and the day's body weight was recorded. D8 is used for adaptation of the rotary rod fatigue tester, and D10 is used for measurement.
Example 2 Rota-Rod:
and evaluating the movement coordination capacity of the mouse by adopting a rotating rod fatigue instrument. The mouse is placed on a roller of a rotating rod type fatigue instrument, and the tail of the mouse is slightly pulled to adapt to the rotating rod so as to keep balanced movement. After three days of acclimation, the test was performed. Setting the speed of the rotating rod: 30r/min, accelerating from 1r/min to 30r/min, accelerating for 150s, and testing for 5 min. Three runs were tested, and the mean was taken, with 10min intervals between runs. Mice drop time was recorded.
Example 3 isolation and culture of MEF cells:
collecting mother mouse pregnant for 13.5 days, killing by breaking neck, sterilizing abdomen with alcohol, aseptically opening abdominal cavity uterus, placing on a flat dish (adding PBS in advance), removing fetal membrane, and taking out fetus (washing with PBS for 3-4 times, removing blood cells)
The mouse embryo was removed from the limbs, head, tail and internal organs with an ophthalmic scissors and washed 2-3 times with PBS. After rinsing, the sections were cut into small tissue pieces of 1mm by ophthalmic scissors.
Adding 4ml of 0.25% trypsin-EDTA, digesting at 37 deg.C for 10-15min, and repeatedly blowing with a gun at 5min intervals until no obvious tissue mass is visible. Digestion was stopped by adding an equal volume of DMEM (10% FBS). The cell suspension was transferred to a centrifuge tube, centrifuged at 1000rpm for 5min, and the supernatant was removed. DMEM (10% FBS)1-2ml suspension cells. 37 ℃ and 5% CO2Culturing under saturated humidity condition. After 24h, the solution was changed and the tissue blocks and non-adherent dead cells were removed. Passage is carried out once in 2-3 days. Starting from the isolation of first generation MEF cells, six well plates were plated, 1 x 106For each well, passages were performed every two days, and the number of cells before passage was recorded for a total of six times.
Example 4H2O2InducedMEF aging model
Taking separated mPGES-2WT and KO MEF cells according to 5 x 105Seeded in 6-well plates. 10 μ M H given by the model group after 24H2O2The control group was given an equal amount of solvent control. Cells were harvested 24h later for senescence-associated analysis.
Example 5 β -galactosidase staining:
cells were as per 5 x 105The density of each well is inoculated on a 6-well plate, the generation cells grow to about 80 percent and are taken out, the culture medium is sucked, 1ml of PBS is added into each well of a six-well plate, and the six-well plate is washed for 3 min. Then fixed with 4% paraformaldehyde for 15min, 1ml per well. PBS wash three times, each for 3 min. PBS was aspirated off, and 1ml of working solution was added (prepared in the dark). The preparation ratio of the working solution is that a ml system is prepared by 10 mul of A solution, 10 mul of B solution, 930 mul of C solution and 50 mul of X-Gal. Adding the working solution, sealing with a sealing film, wrapping with tinfoil (protecting from light), and incubating at 37 deg.C for 24 hr.
Example 6 cell cycle assays
Cells were as per 5 x 105The density per well was plated on 6-well plates, cells were digested with trypsin until about 80% of the cells had grown, collected and washed twice with PBS. Adjustment of cell concentration to 1 x 10 after cell counting6And/ml, 1ml of single cell suspension is taken, centrifuged, supernatant is removed, 500 microliter of cold ethanol with the volume fraction of 70 percent is added into the cells for fixation (2 hours to overnight), the cells are stored at 4 ℃, and the fixation solution is washed by PBS before staining. Adding 500 μ l of PI/RNase A staining working solution prepared in advance, and keeping out of the sun at room temperature for 30-60 min. And (4) operating the machine, and recording red fluorescence at the excitation wavelength 488.
And (3) data analysis:
all values are expressed as mean ± SEM. Statistical analysis was performed using two independent sample T-tests or U-tests. P < 0.05 was considered statistically significant.
Second, experimental results
Effect of mPGES-2 knockout on longevity of Adriamycin-induced aging mice
Taking male mice mPGES-2KO and mPGES-2WT, and administering adriamycin of 10mg/kg to abdominal cavity respectively. The first day of injection was D1, and D7 was given a second dose and the time of death of the mice was recorded. The results are shown in fig. 1, when the mice are injected with adriamycin, the mPGES-2WT mice die quickly, while the death time of the mPGES-2KO mice is obviously lagged behind that of the WT mice, and has obvious statistical difference (P < 0.05), which indicates that the lifetime of the adriamycin mice can be prolonged obviously after the mPGES-2 knockout, and the anti-aging effect is shown.
Effect of mPGES-2 knockout on locomotor Capacity in aging model mice
After doxorubicin-induced mice aged, the mice were tested for locomotor activity by a D10 rotarod fatigue tester, as shown in fig. 2, the residence time of mPGES-2KO mice on the roller wheels was significantly increased compared to WT group with significant difference (. P < 0.05), indicating that mPGES-2 knockout can improve the locomotor activity of mice.
Effect of mPGES-2KO on the proliferative Capacity of mouse Primary MEF cells
The mouse primary cells are undifferentiated cells with strong proliferation capacity, and are helpful for maintaining the normal level of tissue function and resisting the influence of stress such as aging stimulus and the like. As shown in fig. 3, when mPGES-2 was knocked out, the proliferation capacity of MEF cells was significantly increased (. P < 0.01) suggesting that mPGES-2 plays a role in inhibiting senescence of cells.
Effect of mPGES-2KO on Natural senescence of mouse Primary MEF cells
MEF cells are one of the classical models for studying senescence. MEF cells rapidly enter the senescence stage after 4 normal passages, with slower cell proliferation, larger cell morphology and irregular arrangement, with increased senescence markers. According to the invention, the 5 th generation MEF cell is selected for research, the result is shown in figure 4, the beta-Gal positive staining of the normal MEF cell is obviously more than that of mPGES-2 knockout cells, and the cell arrangement is also more disordered. The results show that mPGES-2 knockout can obviously inhibit the natural senescence of MEF cells.
mPGES-2KO vs. H2O2Effect of induced MEF cells on accelerated senescence
Imbalance in oxidative stress is one of the most important factors recognized to cause aging. Hydrogen peroxide can accelerate cellular senescence by oxidation. Administration of 10. mu.M H to Primary MEF cells2O2The staining results after 24h of stimulation are shown in FIG. 5, and mPGES-2 knock-out is clearShow inhibition of H2O2The stimulation to MEF cells effectively reduces the aging degree of cells. The mPGES-2 can be used as a target for treating or preventing the aging and the aging-related diseases.
Effect of mPGES-2KO on the cell cycle of mouse Primary MEF cells
MEF cells rapidly enter senescence after passage 4, and senescent cells often exhibit slowed cell proliferation and cell cycle arrest. The invention selects MEFs of mPGES-2WT and KO of the 5 th generation to explore the influence of mPGES-2 on the cell cycle. As shown in FIG. 6, it was found that mPGES-2 knockout significantly prolonged cellular G1 by flow analysis, suggesting that mPGES-2 knockout may promote cellular proliferation and improve cellular senescence by prolonging cellular G1 phase.
In addition, the inventors of the present invention have also made experiments with other materials, process operations, and process conditions described in the present specification with reference to the above examples, and have obtained preferable results.
It should be understood that the technical solution of the present invention is not limited to the above-mentioned specific embodiments, and all technical modifications made according to the technical solution of the present invention fall within the protection scope of the present invention without departing from the spirit of the present invention and the protection scope of the claims.
Claims (10)
- Application of mPGES-2 as a target point in developing or screening or preparing a medicament for preventing and/or treating aging diseases.
- 2. Use according to claim 1, characterized in that: the senescence disease is doxorubicin and/or hydrogen peroxide-induced senescence.
- 3. Use according to claim 2, characterized in that: the adriamycin is a medicine acting on DNA and can cause senescence by inducing DNA damage.
- 4. Use according to claim 2, characterized in that: the hydrogen peroxide is capable of inducing cellular senescence by causing an imbalance in cellular oxidative stress.
- 5. Use according to claim 1, characterized in that: the drug is capable of inhibiting at least the activity of mPGES-2.
- 6. Use according to claim 1, characterized in that: the drug at least can improve the motor ability of the aged mice induced by the adriamycin.
- 7. Use according to claim 1, characterized in that: the drug is capable of at least prolonging the lifespan of doxorubicin-induced aging mice.
- 8. Use according to claim 1, characterized in that: the drug is at least capable of inhibiting Adriamycin-induced aging progression in aging mice.
- 9. Use according to claim 1, characterized in that: the medicine can promote proliferation of adriamycin-induced senescent cells and promote the rejuvenation of adriamycin-induced senescent cells.
- 10. Use according to claim 1, characterized in that: the medicine can delay natural aging cells and/or H induced by adriamycin2O2The induction accelerates the progression of senescent cells.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111538268.7A CN114107272B (en) | 2021-12-15 | 2021-12-15 | Application of mPGES-2 as target in development or screening or preparation of drugs for preventing and/or treating aging diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111538268.7A CN114107272B (en) | 2021-12-15 | 2021-12-15 | Application of mPGES-2 as target in development or screening or preparation of drugs for preventing and/or treating aging diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114107272A true CN114107272A (en) | 2022-03-01 |
| CN114107272B CN114107272B (en) | 2022-06-24 |
Family
ID=80365678
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111538268.7A Active CN114107272B (en) | 2021-12-15 | 2021-12-15 | Application of mPGES-2 as target in development or screening or preparation of drugs for preventing and/or treating aging diseases |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114107272B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115837022A (en) * | 2023-02-20 | 2023-03-24 | 中山大学附属第八医院（深圳福田） | Application of 1,2,4 triazolo 4,3-B pyridazine derivative in preparation of anti-aging drugs |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150126573A1 (en) * | 2012-05-09 | 2015-05-07 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and pharmaceutical compositions for prevention or treatment of chronic obstructive pulmonary disease |
| US20190167695A1 (en) * | 2017-06-09 | 2019-06-06 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for preventing or treating muscle conditions |
| CN110208532A (en) * | 2019-06-14 | 2019-09-06 | 徐州医科大学 | MPGES-2 is treating or preventing the application in drug induccd acute liver damage as target spot |
| CN111419835A (en) * | 2020-05-18 | 2020-07-17 | 徐州医科大学 | Application of benzenesulfonamide compound as mPGES-2 inhibitor and medicine |
| CN113082209A (en) * | 2021-03-31 | 2021-07-09 | 中国科学技术大学 | CD4+Application of T cell-derived BACE1, EP2 and EP4 as Alzheimer disease treatment target |
| CN113413380A (en) * | 2021-08-10 | 2021-09-21 | 徐州医科大学 | Application of mPGES-2 inhibitor in preparation of medicine for treating and/or preventing nonalcoholic fatty liver disease |
| CN113528572A (en) * | 2021-07-26 | 2021-10-22 | 浙江树人学院（浙江树人大学） | Mouse premature senility model and construction method and application thereof |
| CN113521288A (en) * | 2021-08-10 | 2021-10-22 | 徐州医科大学 | Application of mPGES-2 as drug target for treating and/or preventing fatty liver disease |
| CN114129577A (en) * | 2021-12-15 | 2022-03-04 | 徐州医科大学 | Use of benzenesulfonamide compound in preparation of drugs for preventing and/or treating aging diseases |
-
2021
- 2021-12-15 CN CN202111538268.7A patent/CN114107272B/en active Active
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150126573A1 (en) * | 2012-05-09 | 2015-05-07 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and pharmaceutical compositions for prevention or treatment of chronic obstructive pulmonary disease |
| US20190167695A1 (en) * | 2017-06-09 | 2019-06-06 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for preventing or treating muscle conditions |
| CN111212648A (en) * | 2017-06-09 | 2020-05-29 | 莱兰斯坦福初级大学评议会 | Compositions and methods for preventing or treating muscle disorders |
| CN110208532A (en) * | 2019-06-14 | 2019-09-06 | 徐州医科大学 | MPGES-2 is treating or preventing the application in drug induccd acute liver damage as target spot |
| CN111419835A (en) * | 2020-05-18 | 2020-07-17 | 徐州医科大学 | Application of benzenesulfonamide compound as mPGES-2 inhibitor and medicine |
| CN113082209A (en) * | 2021-03-31 | 2021-07-09 | 中国科学技术大学 | CD4+Application of T cell-derived BACE1, EP2 and EP4 as Alzheimer disease treatment target |
| CN113528572A (en) * | 2021-07-26 | 2021-10-22 | 浙江树人学院（浙江树人大学） | Mouse premature senility model and construction method and application thereof |
| CN113413380A (en) * | 2021-08-10 | 2021-09-21 | 徐州医科大学 | Application of mPGES-2 inhibitor in preparation of medicine for treating and/or preventing nonalcoholic fatty liver disease |
| CN113521288A (en) * | 2021-08-10 | 2021-10-22 | 徐州医科大学 | Application of mPGES-2 as drug target for treating and/or preventing fatty liver disease |
| CN114129577A (en) * | 2021-12-15 | 2022-03-04 | 徐州医科大学 | Use of benzenesulfonamide compound in preparation of drugs for preventing and/or treating aging diseases |
Non-Patent Citations (6)
| Title |
|---|
| DANDAN ZHONG等: "mPGES-2 blockade antagonizes β-cell senescence to ameliorate diabetes by acting on NR4A1", 《NATURE METABOLISM》 * |
| LEIGH A. JANIA等: "Microsomal prostaglandin E synthase-2 is not essential for in vivo prostaglandin E2 biosynthesis", 《PROSTAGLANDINS OTHER LIPID MEDIAT》 * |
| SÉBASTIEN MARTIEN等: "Cellular senescence involves an intracrine prostaglandin E2 pathway in human fibroblasts", 《BIOCHIMICA ET BIOPHYSICA ACTA》 * |
| ZHOU WU等: "Phosphatidylserine-containing liposomes: potential pharmacological interventions against inflammatory and immune diseases through the production of prostaglandin E(2) after uptake by myeloid derived phagocytes", 《ARCH. IMMUNOL. THER. EXP.》 * |
| 王旭光等: "前列腺素E2合成酶研究进展", 《国外医学·生理、病理科学与临床分册》 * |
| 邱梦等: "RNA 干扰mPGES-1 基因对K562/A 细胞增殖及凋亡的影响", 《中山大学学报（医学科学版）》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115837022A (en) * | 2023-02-20 | 2023-03-24 | 中山大学附属第八医院（深圳福田） | Application of 1,2,4 triazolo 4,3-B pyridazine derivative in preparation of anti-aging drugs |
| CN115837022B (en) * | 2023-02-20 | 2023-04-25 | 中山大学附属第八医院（深圳福田） | Application of 1,2, 4-triazolo 4,3-B pyridazine derivative in preparation of anti-aging drugs |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114107272B (en) | 2022-06-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Dickinson et al. | A comparison of some biological characteristics of the mouse-passaged scrapie agents, 22A and ME7 | |
| Heydemann | The super super-healing MRL mouse strain | |
| CN114107272B (en) | Application of mPGES-2 as target in development or screening or preparation of drugs for preventing and/or treating aging diseases | |
| WO2017113649A1 (en) | Siraitia grosvenorii extract and application for pulmonary fibrosis | |
| CN116515747B (en) | Dental pulp mesenchymal stem cell culture method | |
| Zhou et al. | Age-related changes in the global DNA methylation profile of oligodendrocyte progenitor cells derived from rat spinal cords | |
| Liu et al. | Effects of hirudin on high glucose-induced oxidative stress and inflammatory pathway in rat dorsal root ganglion neurons | |
| Zhou et al. | Apoptosis in tracheoesophageal embryogenesis in rat embryos with or without adriamycin treatment | |
| WO2020252845A1 (en) | Anti-aging application of jwa gene and related compound | |
| CN113564103B (en) | Application of 4,4' -dimethoxy chalcone in delaying in-vitro and in-vivo aging of oocyte | |
| WO2023137985A1 (en) | Dietary nutrition supplement for regulating skeletal muscle glucose metabolism and mitochondria generation and use thereof | |
| Ma et al. | The function of Ophiocordyceps sinensis in airway epithelial cell senescence in a rat COPD model | |
| CN111514167B (en) | Application of donkey-hide gelatin in product for relieving oxidative stress injury of cells | |
| CN112972490B (en) | Application of hyaluronic acid in preparing medicine for preventing or treating iron death related diseases | |
| EP3978012A1 (en) | Use of flavin-containing monooxygenase 2 in preparation of drug for treatment of non-alcoholic fatty liver disease | |
| CN104224808B (en) | Minocycline is used for the protective effect for offspring's Cerebral impairment that gestation stress be caused | |
| CN111110830B (en) | Application of bioactive polypeptide PACAP in preparation of medicine for improving fertility of obese men | |
| CN111840278A (en) | Application of combination of compound and vitamin E in preparation of anti-aging drugs or cosmetics | |
| Chen et al. | Protective effect of sulodexide on podocyte injury in adriamycin nephropathy rats | |
| CN115737658B (en) | New application of D-mannose | |
| WO2022114412A1 (en) | Skin-derived fibroblasts exhibiting tendon regeneration effect and use thereof | |
| CN109200289B (en) | FAM134B treats the purposes in pyemic drug in preparation | |
| CN117016484B (en) | Construction method and application of anxiety-like mouse model | |
| CN115400106B (en) | Application of natural compound and composition thereof in removing aging cells | |
| EP3669871B1 (en) | Amd3100 for the treatment and/or prevention of cachexia, and pharmaceutical composition thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |