CN113425844A - Drug intervention target of keloid and application thereof - Google Patents
Drug intervention target of keloid and application thereof Download PDFInfo
- Publication number
- CN113425844A CN113425844A CN202110779944.3A CN202110779944A CN113425844A CN 113425844 A CN113425844 A CN 113425844A CN 202110779944 A CN202110779944 A CN 202110779944A CN 113425844 A CN113425844 A CN 113425844A
- Authority
- CN
- China
- Prior art keywords
- keloid
- twist1
- fibrosis
- small molecule
- expression
- 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.)
- Pending
Links
Images
Classifications
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Chemistry (AREA)
Abstract
The invention discloses a drug intervention target for treating keloid skin tissue fibrosis, which is a TWIST1 gene and a coding protein thereof. The gene provided by the invention is highly expressed in the fibroblast derived from keloid. When the TWIST1 is treated by a small molecule inhibitor drug, the fibrosis of fibroblasts from keloid and the expression of related genes of a TGF-beta signal pathway can be obviously reduced, and the pathological fibrosis of keloid skin tissues can be further relieved. Based on the target, the medicine including small molecule inhibitor designed to treat and relieve keloid. The invention provides a new medicine target for treating keloid.
Description
Technical Field
The invention belongs to the field of biological medicine, and particularly relates to a keloid drug intervention target and application thereof in relieving pathological fibrosis of keloid skin tissues.
Background
Keloid (Keloid) is a skin fibrotic disease that occurs after abnormal healing of wounds. Histopathology is manifested by excessive deposition of extracellular matrix. Despite being classified as benign skin growth, keloids can still exhibit tumor-like malignant biological characteristics such as hyperproliferation, resistance to apoptosis, and invasiveness. The growth of the scar exceeds the original damaged area, causing discomfort such as pain and pruritus and bringing serious physical and psychological burden to patients.
Despite some clinical treatments, to date, keloid treatment remains a major challenge, manifested by a high recurrence rate and a lack of effective drug therapy. A core transcription factor gene TWIST1 is found in fibroblasts (Keloid fibroplast) from Keloid sources through large-scale single-cell transcriptomics analysis in the early stage, and in-vitro experiments show that the fibrosis level can be remarkably reduced by using specific inhibitor drug harmine for treatment, so that TWIST1 can be used as a drug treatment target for treating Keloid, and the inhibitor drug harmine can be used as a potential drug for treating Keloid.
Disclosure of Invention
The invention aims to provide a drug intervention target for treating or relieving keloid.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides application of a drug intervention target in treating and relieving keloid fibrosis, wherein the drug intervention target is TWIST1 gene and encoding protein thereof. Preferably, the medicine is an intervention medicine containing a harmine for the target gene TWIST1 or the coding protein thereof.
Wherein, the gene TWIST1 encodes a transcription factor, and the expression is positioned in the nucleus of a fibroblast.
The present invention provides evidence that inhibition of TWIST1 expression in keloid-derived fibroblasts reduces the level of fibrosis in the cells.
The invention relates to four technologies for inhibiting TWIST1 expression, which are respectively a small molecule inhibitor, shRNA, siRNA and a CRISPR/Cas system; the small molecule compound inhibitor performs interference inhibition at the protein level, the shRNA and the siRNA reduce the expression of the protein at the RNA level, and the CRISPR/Cas reduces the expression of the protein at the DNA level; the technique for inhibiting the expression of TWIST1 is preferably a small molecule compound, namely, a harmine.
The invention provides an application of a target gene in a medicament for relieving keloid skin tissue fibrosis, wherein the target gene is TWIST 1. The siRNA drugs, small molecule inhibitors or antibodies designed aiming at the TWIST1 gene and the protein products coded by the same are used for treating keloid and skin fibrosis diseases and are all included in the protection scope of the invention.
The medicament for inhibiting keloid skin tissue fibrosis of the present invention further comprises pharmaceutically acceptable carriers, including but not limited to: liposomes, diluents, buffers, suspensions, emulsions, granules, encapsulating agents, excipients, fillers, adhesives, sprays, transdermal absorbents, humectants, disintegrants, absorption enhancers, surfactants, colorants, flavors, or adsorbent carriers.
The medicament can be prepared into a micro-injection, a dosage form suitable for transfection, an injection, a tablet, a powder, a granule and a capsule. The medicaments in various dosage forms can be prepared according to the conventional method in the pharmaceutical field.
The drugs may be administered alone; or in combination with other agents capable of inhibiting fibrosis.
Further, the invention provides an application of a small molecule inhibitor in a medicament for relieving keloid skin tissue fibrosis, wherein the small molecule inhibitor is a harmine.
Advantageous effects
The invention discloses a drug intervention target for treating keloid skin fibrosis, which is a TWIST1 gene and a protein coded by the same. The gene of the invention is highly expressed in the fibroblast derived from keloid. The small molecular inhibitor harmine of TWIST1 can obviously reduce the fibrosis level of fibroblast from keloid and the expression of TGF-beta signal path related gene, thus effectively relieving the skin tissue fibrosis of the keloid. Based on the target, the medicine including small molecule inhibitor designed to treat and relieve keloid. The invention provides a new medicine target for treating keloid.
Drawings
Figure 1. the TWIST1 inhibitor drug, camine, was able to significantly inhibit the fibrosis of keloid-derived fibroblasts. (a) Schematic diagram of research design. (b) Pictures of the cell status of keloids or fibroblasts of healthy origin after harmine treatment. (c) The volcano plot shows the differentially expressed genes obtained from RNA-seq after the harmine treatment, the left plot shows the scar-derived fibroblasts (keloid fibroplast), and the right plot shows the healthy-derived fibroblasts (normal fibroplast). (d) Functional enrichment analysis showed a pathway down-regulated after harmine treatment in scar-derived fibroblasts. (e) Functional enrichment analysis showed a pathway that was down-regulated after harmine treatment in fibroblasts from healthy sources. (f) Effect of Harmine treatment on mRNA expression of TWIST1 and genes encoding representative fibrotic factors of scar derived fibroblasts. (g) Effect of Harmine treatment on mRNA expression of TWIST1 and genes encoding representative fibrotic factors of fibroblasts of healthy origin. In f and g, q <0.05, q <0.01, q-value was obtained based on RNA-seq differential expression analysis. (h) Western blot analysis after treatment of scar derived fibroblasts by Harmine. (i) Western blot analysis after Harmine treatment of fibroblasts from healthy sources. In h and i, p <0.05, p <0.01, ns: not significant. One-way ANOVA was compared to LSD in multiple.
Detailed Description
The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art.
The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
All materials, reagents and the like in the following examples are commercially available unless otherwise specified.
Example 1
This example demonstrates that the twinst 1 inhibitor drug, camine, can significantly inhibit fibrogenesis (fibrosis) of keloid-derived fibroblasts, while having no or weak effect on fibroblasts of relatively healthy origin (normal fibroblasts).
1. Isolation, culture and treatment of skin fibroblasts
All samples from this study were obtained from Beijing collaborating hospital plastic surgery. All procedures in this study were approved by the Ethics review Committee of Beijing coordination and Hospital, and all subjects in the group had signed informed consent. The invention is combined into 3 cases of keloid patients, and scar skin tissues are taken, and relatively healthy skin tissues around the scar are taken as a control. The dishes were treated for half an hour at 37 ℃ with 0.2% gel coating. The skin tissue is cut into small pieces after the epidermis is removed. These small fragments were then immersed in DMEM (11965-TMUSA) and placed on a gel coated petri dish until completely adhered. Fibroblasts before passage 7 were used for subsequent experiments. When the degree of cell aggregation reached 90% or more, the medium was replaced with a medium supplemented with DMSO or harmine (SH8340, Solarbio, CHINA). Harmine concentrations were 10 or 20. mu.M. After 48 hours of treatment, cells were harvested for subsequent experiments.
2. RNA extraction and RNA-seq
Total RNA extraction was performed using TRIzol reagent (15596026, Invitrogen, USA). Thereafter, RNA-seq Library construction was performed using NEBNext Ultra RNA Library Prep Kit for Illumina (# E7530L, NEB, USA) Kit. Sequencing was done on the Illumina X Ten platform. Adopting fastp software to carry out sequencing data quality control, adopting kallisto software to carry out transcript quantitative analysis, and utilizing slauth software to carry out intergroup difference gene expression analysis. The statistical significance threshold was set at q-value <0.05, while the biological significance threshold was set at ± 2-fold.
3. Protein immunoblot analysis
Whole cell protein extracts were prepared using RIPA buffer (P0013B, Beyotime) supplemented with protease and phosphatase inhibitors (P1046, Beyotime). Protein concentration quantification was performed by BCA assay (23227, Thermo Fisher). The lysate was diluted in 5 XSDS-PAGE loading buffer and cooked for 10 min at 95 ℃. Proteins were separated by 10% SDS-polyacrylamide gel electrophoresis or 4-12% NuPAGE Bis-Tris SDS PAGE gel electrophoresis (NP0322BOX, Invitrogen), and transferred to NC membranes. The membranes were blocked using 1 XTSST (ST673, Beyotime) containing 3% bone serum album (ST023, Beyotime) or 5% skim milk powder (P0216, Beyotime). After blocking for 1 hour at room temperature, the primary antibody was incubated overnight at 4 ℃ and then incubated for 1 hour with an enzyme-labeled secondary antibody (dilution 1: 10000). Finally, detection is carried out by an extra-hypersensitive ECL chemiluminescence kit (P0018A, Beyotime). The primary antibodies used were GAPDH (1:6000, Cell Signaling Technology Cat #2118L), Collagen I (1:4000, Abcam Cat # ab138492), Collagen III (1:2000, Abcam Cat # ab184993), Smad2/Smad3(1:1000, Cell Signaling Technology Cat # 5339S), p-Smad2/Smad3(1:500, Cell Signaling Technology Cat #8828S) and TWIST1(1:100, Abcam Cat # ab 50887). Quantitative analysis of the grey value of the bands was performed using ImageJ software.
4. Results
As shown in figure 1a for an overall schematic of the study design. To demonstrate the role of TWIST1 and its inhibitory drug, camine, in scar fibrogenesis, we isolated scar-derived fibroblasts (keloid fibroblasts) and surrounding relatively healthy skin tissue-derived fibroblasts (normal fibroblasts) and detected changes in gene mRNA expression by RNA-seq and protein expression by immunoblotting after 48 hours of treatment with different concentrations of camine, i.e. 0 (DMSO only), 10 and 20 μ M respectively. The cells were in good condition after the Harmine treatment (fig. 1 b). From the RNA-seq, we found that 10. mu.M of harmine treatment can significantly alter the expression of several hundred genes in the keloid and normal fibrates compared to the DMSO control (FIG. 1 c). Clearly, in keloid fibroplast, 10 μ M harmine treatment can significantly down-regulate extracellular matrix (ECM) -associated pathways (q-value <0.05, log2 fold change < -1, fig. 1 d). In contrast, down-regulated genes in normal fibrates after harmine treatment were not enriched for ECM-associated pathways (fig. 1e), reflecting inhibition of fibrosis. Expression of the TWIST1 gene was significantly inhibited in both keloid and normal fibroplast (q-value <0.05, FIG. 1f and FIG. 1 g). At the same time, fibrosis-associated marker genes such as COL1a1, COL3a1 and FN1 were also significantly inhibited. Important genes in the TGF β signaling pathway, such as TGFBR2 and TGFB1, were also significantly down-regulated. However, the fold change of these downregulated genes was significantly lower in normal fibrablast compared to keloid fibrablast.
Further, Western blot experiments showed that the level of protein expression of TWIST1, Collagen-1, Collagen-3, SMAD2/3 could be significantly reduced by treatment with the harmine in keloid fibroplast (FIG. 1h, p < 0.05). The protein level of phosphorylated SMAD2/3(pSMAD2/3) was also reduced, although not statistically significant. The effect of the harmine treatment on normal fibragast was little or weak at the protein level compared to keloid fibragast, which correlates with relatively low expression of TWIST1 in normal fibragast. In conclusion, the research supports the role of the TWIST1 gene in the scar fibrosis process, and the harmamine can be used as a potential drug for scar treatment.
Although the invention has been described in detail hereinabove with respect to a general description and specific embodiments thereof, it will be apparent to those skilled in the art that modifications or improvements may be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.
Claims (10)
1. The application of a drug intervention target in the drugs for treating and relieving keloid skin tissue fibrosis is disclosed, wherein the drug intervention target is TWIST1 gene and its coding protein.
2. The use of claim 1, wherein said TWIST1 gene is highly expressed in keloid-derived fibroblasts and said TWIST1 gene encodes a transcription factor, the expression of which is localized in the nucleus of fibroblasts.
3. The use of claim 1, wherein said medicament comprises an intervention drug that inhibits said target gene, TWIST1 or the protein encoded thereby.
4. The use of claim 3, wherein there are four techniques for inhibiting expression of the target gene, namely small molecule inhibitors, shRNAs, siRNAs and CRISPR/Cas systems; small molecule inhibitors are interference suppressors at the protein level; both shRNA and siRNA reduce protein expression at the RNA level and CRISPR/Cas reduces protein expression at the DNA level.
5. The use of claim 4, wherein the technology that inhibits expression of the target gene is a small molecule inhibitor and the small molecule inhibitor drug targeting TWIST1 is a harmine.
6. The use of claim 5, wherein the TWIST1 has been harmine-inhibited to significantly down-regulate the expression of fibrosis-associated genes and TGF- β signaling pathway-associated genes, thereby alleviating pathological fibrosis in keloid skin tissue.
7. The use of claim 6, wherein the fibrosis-associated genes comprise COL1A, COL3a1, FN1, and the TGF- β signaling pathway-associated genes comprise TGFB1, TGFBR 2.
8. The use of claim 1, wherein the medicament further comprises pharmaceutically acceptable carriers including, but not limited to: liposomes, diluents, buffers, suspensions, emulsions, granules, encapsulating agents, excipients, fillers, adhesives, sprays, transdermal absorbents, humectants, disintegrants, absorption enhancers, surfactants, colorants, flavors, or adsorbent carriers.
9. The use of claim 8, wherein the medicament is administered alone or in combination with other agents capable of inhibiting fibrosis.
10. The application of a small molecule inhibitor in a medicament for relieving keloid skin tissue fibrosis is disclosed, wherein the small molecule inhibitor is a harmine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110779944.3A CN113425844A (en) | 2021-07-09 | 2021-07-09 | Drug intervention target of keloid and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110779944.3A CN113425844A (en) | 2021-07-09 | 2021-07-09 | Drug intervention target of keloid and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113425844A true CN113425844A (en) | 2021-09-24 |
Family
ID=77759842
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110779944.3A Pending CN113425844A (en) | 2021-07-09 | 2021-07-09 | Drug intervention target of keloid and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113425844A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113209312A (en) * | 2021-05-06 | 2021-08-06 | 吉林大学 | Application of reagent for inhibiting expression of transcription factor MEF2C in preparation of medicine for treating keloid |
| CN115645394A (en) * | 2022-11-01 | 2023-01-31 | 南开大学 | Application of carvedilol hydrochloride in preparation of medicine for treating skin fibrosis diseases |
| CN115851710A (en) * | 2022-08-02 | 2023-03-28 | 中国医学科学院北京协和医院 | siRNA molecule composition and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101450216A (en) * | 2008-11-28 | 2009-06-10 | 北京大学第三医院 | Medicine for preventing hyperplastic scar fibroblast proliferation |
| CN104174032A (en) * | 2014-08-06 | 2014-12-03 | 上海交通大学医学院附属第九人民医院 | siRNA molecular composition and application thereof in treatment on pathological scars |
| CN112485434A (en) * | 2020-11-04 | 2021-03-12 | 中国医学科学院北京协和医院 | Method for obtaining therapeutic target for treating keloid scar on skin |
-
2021
- 2021-07-09 CN CN202110779944.3A patent/CN113425844A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101450216A (en) * | 2008-11-28 | 2009-06-10 | 北京大学第三医院 | Medicine for preventing hyperplastic scar fibroblast proliferation |
| CN104174032A (en) * | 2014-08-06 | 2014-12-03 | 上海交通大学医学院附属第九人民医院 | siRNA molecular composition and application thereof in treatment on pathological scars |
| CN112485434A (en) * | 2020-11-04 | 2021-03-12 | 中国医学科学院北京协和医院 | Method for obtaining therapeutic target for treating keloid scar on skin |
Non-Patent Citations (2)
| Title |
|---|
| X LIU ET AL.: ""Single-cell RNA-seq reveals lineage-specific regulatory changes of fibroblasts and vascular endothelial cells in keloid"", 《BIORXIV》 * |
| X LIU ET AL.: ""Single-Cell RNA-Sequencing Reveals Lineage-Specific Regulatory Changes of Fibroblasts and Vascular Endothelial Cells in Keloids"", 《JOURNAL OF INVESTIGATIVE DERMATOLOGY》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113209312A (en) * | 2021-05-06 | 2021-08-06 | 吉林大学 | Application of reagent for inhibiting expression of transcription factor MEF2C in preparation of medicine for treating keloid |
| CN113209312B (en) * | 2021-05-06 | 2022-06-03 | 吉林大学 | Application of reagent for inhibiting expression of transcription factor MEF2C in preparation of medicine for treating keloid |
| CN115851710A (en) * | 2022-08-02 | 2023-03-28 | 中国医学科学院北京协和医院 | siRNA molecule composition and application thereof |
| CN115645394A (en) * | 2022-11-01 | 2023-01-31 | 南开大学 | Application of carvedilol hydrochloride in preparation of medicine for treating skin fibrosis diseases |
| CN115645394B (en) * | 2022-11-01 | 2024-04-26 | 南开大学 | Application of carvedilol hydrochloride in preparation of medicines for treating skin fibrosis diseases |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113425844A (en) | Drug intervention target of keloid and application thereof | |
| Wen et al. | Bromodomain inhibitor jq1 induces cell cycle arrest and apoptosis of glioma stem cells through the VEGF/PI3K/AKT signaling pathway | |
| Jiang et al. | Noncoding RNAs: new regulatory code in chondrocyte apoptosis and autophagy | |
| Xin et al. | Expansion of CD26 positive fibroblast population promotes keloid progression | |
| JP6514204B2 (en) | Molecular targets for the prevention and / or treatment of fibrosis, hypertrophic scars or keloids | |
| Mou et al. | Macrophage‐targeted delivery of siRNA to silence Mecp2 gene expression attenuates pulmonary fibrosis | |
| Wang et al. | CircRNA RERE promotes the oxidative stress-induced apoptosis and autophagy of nucleus pulposus cells through the miR-299-5p/Galectin-3 axis | |
| Ge et al. | Exosomal USP13 derived from microvascular endothelial cells regulates immune microenvironment and improves functional recovery after spinal cord injury by stabilizing IκBα | |
| Chen et al. | Histone deacetylase inhibitor impairs plasminogen activator inhibitor-1 expression via inhibiting TNF-α-activated MAPK/AP-1 signaling cascade | |
| US20190022097A1 (en) | Molecular targets for the treatment of wounds, in particular chronic wounds | |
| Tian et al. | Exosomes derived from PC‑3 cells suppress osteoclast differentiation by downregulating miR‑148a and blocking the PI3K/AKT/mTOR pathway | |
| KR102026138B1 (en) | Composition for Inhibition or Treatment of Keloids and Hypertrophic Scar Comprising CRIF1 Antagonist | |
| Hu et al. | Keloid patient plasma-derived exosomal hsa_circ_0020792 promotes normal skin fibroblasts proliferation, migration, and fibrogenesis via modulating miR-193a-5p and activating TGF-β1/smad2/3 signaling | |
| Chen et al. | Downregulation of a potential therapeutic target NPAS2, regulated by p53, alleviates pulmonary fibrosis by inhibiting epithelial-mesenchymal transition via suppressing HES1 | |
| CN110904104B (en) | Application of human HIST1H2BK gene and related products | |
| Li et al. | Niao du kang mixture increases the expression of mir-129-5p to relieve renal fibrosis | |
| CN110938691B (en) | Application of human DUS4L gene and related products | |
| Fu et al. | Tanshinone ⅡA inhibits the lipopolysaccharide-induced epithelial-mesenchymal transition and protects bovine endometrial epithelial cells from pyolysin-induced damage by modulating the NF-κB/Snail2 signaling pathway | |
| CN110819631B (en) | Application of human DMBX1 gene and related products | |
| CN111269910B (en) | Application of human DEPDC1 gene and related products | |
| Lian et al. | Genistein Mitigates High Glucose-Induced Podocyte Adhesion Injury by Modulating Autophagy via Mtor Signal | |
| Hao et al. | In vivo CRISPR knockout screen identifies p47 as a suppressor of HER2+ breast cancer metastasis by regulating NEMO trafficking and autophagy flux | |
| Yang et al. | Intrauterine infusion of platelet‐rich plasma improves fibrosis by transforming growth factor beta 1/Smad pathway in a rat intrauterine adhesion model | |
| Cao et al. | Dental Pulp Stem Cell-Derived Exosomes Inhibit Senescence-Induced Chronic Obstructive Pulmonary Disease Through the Nuclear Factor Kappa B Signaling Pathway | |
| Wu et al. | Silibinin attenuates TGF-β2-induced fibrogenic changes in human trabecular meshwork cells by targeting JAK2/STAT3 and PI3K/AKT signaling pathways |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20210924 |
|
| WD01 | Invention patent application deemed withdrawn after publication |