CN113209282B - Application of antibacterial peptide for maintaining abundance of Ackermanella enterica - Google Patents
Application of antibacterial peptide for maintaining abundance of Ackermanella enterica Download PDFInfo
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- CN113209282B CN113209282B CN202110487229.2A CN202110487229A CN113209282B CN 113209282 B CN113209282 B CN 113209282B CN 202110487229 A CN202110487229 A CN 202110487229A CN 113209282 B CN113209282 B CN 113209282B
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Abstract
The invention discloses application of antibacterial peptide in preparing a medicament for regulating intestinal flora, wherein the antibacterial peptide is RNASE 4. The antibacterial peptide enables the proportion of Ackermanella in the intestinal tract to be obviously increased, and the proportion of slime spirulina in the intestinal tract to be obviously reduced. The invention also discloses the application of the antibacterial peptide in preparing the medicament for treating inflammatory bowel diseases, wherein the antibacterial peptide is RNASE 4; inflammatory bowel disease includes ulcerative colitis, Crohn's disease.
Description
Technical Field
The invention relates to an antibacterial peptide for improving intestinal flora, which contains an antibacterial peptide RNASE4 as an effective component, wherein the antibacterial peptide RNASE4 can improve the abundance of the intestinal flora, and particularly relates to the abundance of Ackermansia (Akkermansia mucini philia) in intestinal tracts.
Background
The intestinal flora is the most complex and bulky microecosystem of human body. Recent findings have shown that the human intestinal tract contains about 10 thousands of species14Although the number of the microorganisms is equivalent to that of human cells, the number of the genes encoded by the microorganisms is hundreds of times of that of the human cells. In a normal organism, symbiotic bacteria (intestinal flora living together with organisms) are mainly distributed in the intestinal cavity and the mucous membrane surface and evolve together with a host, so that the integrity of a mucous membrane barrier system can be maintained, and harmful microorganisms such as pathogens and the like can be antagonized; however, adverse environmental factors, adverse lifestyle and self-inherited factors can cause structural and functional disorders of the intestinal symbiotic bacteria, and if the intestinal symbiotic bacteria cannot be effectively recovered in time, the intestinal symbiotic bacteria can causeThe occurrence and development of various chronic intestinal diseases. For example, although the pathogenesis of inflammatory bowel disease is not well defined, the key role of the intestinal flora in the development of the disease is well-recognized, and compared with healthy people, inflammatory bowel disease patients have significantly reduced diversity of intestinal flora, significantly increased harmful flora, and abnormal immune response, damage to mucosal barrier integrity, and finally imbalance of intestinal homeostasis. In conclusion, based on the research of regulating intestinal flora, a new idea is expected to be provided for the prevention and treatment of chronic intestinal diseases such as inflammatory bowel diseases.
The Akkermansia (Akkermansia muciniphila) is a "star probiotic" in the gut flora, the abundance of which is inversely related to a number of diseases. For example, the abundance of akkermansia bacteria in stool samples from patients with inflammatory bowel disease is significantly reduced compared to healthy volunteers; in obese children, the abundance of Ackermansia tabescens is obviously reduced, and the supplemented Ackermansia tabescens can effectively reduce fat and weight; the abundance of akkermansia sp is negatively related to type I diabetes mellitus, and the akkermansia sp plays a protective role in type I diabetes mellitus. Therefore, Ackermansia species play an important role in maintaining the health of the body.
The host can maintain the steady state of intestinal flora by secreting antibacterial peptide molecules, inhibit the growth of harmful bacteria and improve the abundance of beneficial bacteria, thereby participating in the occurrence and development of diseases such as inflammatory bowel diseases and the like. For example, the antibacterial peptide LYPD8 is enriched in intestinal mucus layer, and can be combined with flagellates to limit the mobility of the flagellates as a member of mucosal immunity, while mice with LYPD8 gene deletion can show more serious enteritis symptoms; by administering exogenous recombinant antibacterial peptide LL-37, clostridium difficile can be effectively killed, and intestinal inflammation caused by toxin A is further inhibited; the over-expression of the antimicrobial peptide REG3A can change the intestinal flora structure, increase the content of beneficial bacteria (Ruminococcus and Lachnospiraceae), and effectively alleviate the symptoms of enteritis; the antibacterial peptide RNASE5 can be directly combined on the surface of the cell membrane of alpha proteobacteria and form holes on the membrane, thereby inhibiting the growth of the bacteria. Meanwhile, the antibacterial peptide is taken as a protein secreted by a host, is not easy to generate drug resistance and side effects, and is a clinically ideal drug/preparation for regulating and controlling intestinal flora.
Ribonuclease 4(RNASE 4) is one of the members of the antibacterial peptide family of Ribonuclease a. The mature RNASE4 protein is a secreted single-chain basic protein consisting of 119 amino acid residues and has a relative molecular weight of about 13.8 kDa. The protein retains the structural features common to the families, namely the three enzymatic sites (His-12, Lys-40 and His-116), the functional domain "CKXXNTF" and the 8 cysteine residues that can form intramolecular disulfide bonds. The literature reports that RNASE4 can promote angiogenesis, induce neural development and protect neuron survival under stress conditions to delay the progress of neurodegenerative diseases; meanwhile, RNASE4 can participate in host defense, is highly expressed in the urinary system, and can resist urinary tract pathogenic Escherichia coli (UROPATHOGIC Escherichia coli) infection. However, the role of RNASE4 in gut flora maintenance remains to be addressed.
At present, patents relating to maintaining the abundance of akkermansia enterocolitica are: the invention with application number CN202010831740.5, namely a composition for preventing the reduction of the abundance of Akkermansia mulcinilla bacteria, discloses a composition for regulating the abundance of Ackermansia sp. The invention "composition for improving intestinal flora" having application No. CN201980037944.7 teaches a composition for improving intestinal flora, which contains milbemycin C and/or its glycoside as an effective ingredient and has an effect of improving intestinal flora by proliferating akkermansia sp. The invention with application number of CN201910311683.5 discloses the application of a pharmaceutical composition consisting of berberine hydrochloride and stachyose in adjusting intestinal flora, and can remarkably increase the number of Ackermansonian in animal intestinal tracts.
Disclosure of Invention
The invention aims to provide an antibacterial peptide capable of maintaining the abundance of Ackermanella enterica and provide a new idea for treating intestinal diseases such as clinical inflammatory bowel diseases.
In order to solve the technical problems, the invention provides application of antibacterial peptide in preparing a medicine for regulating intestinal flora, wherein the antibacterial peptide is RNASE4(RNASE4 protein).
As an improvement of the application of the invention: increasing the proportion of the family of the iron bacillaceae (deferribacteriaceae), the genus of the mucospirochetes (mucospirulina), the order of Burkholderiales (Burkholderiales), the class of the gamma-proteobacteria (Gammaproteobacteria), the genus of the coprobacteria (faecalibacterium), the genus of the erythrystrilus (erysipelas), the genus of the tumorous bacterium (ruministrothridium _6), the genus of the lachnospira (Lachnospiraceae _ A2), the genus of the verrucomicrobinia (Verrucomicrobiae), the genus of the Akkermansia (Akkermansia), the family of the Lachnospiraceae (Lachnospiraceae), the family of the psychromyonaceae (psychromyonaceae), the genus of the coccus NK4a214 (ruminococcus _ NK4a214), the genus of the clostridium (lachnococlosporidium) in the gut flora.
As a further improvement of the application of the invention: increasing the proportion of Akkermansia (Akkermansia muciniphila) in the intestinal flora.
Preferably: the antibacterial peptide enables the proportion of Ackermanella in the intestinal tract to be obviously increased, and the proportion of slime spirulina in the intestinal tract to be obviously reduced.
The invention also provides the application of the antibacterial peptide in preparing the medicament for treating the inflammatory bowel disease: the antibacterial peptide is RNASE 4.
As an improvement of the application of the invention: the inflammatory bowel disease comprises ulcerative colitis and Crohn's disease.
The antibacterial peptide RNASE4 may be: a) inhibiting weight loss in an individual with inflammatory bowel disease; b) reducing disease activity in an individual with inflammatory bowel disease; c) reducing the degree of intestinal mucosal damage in an individual with inflammatory bowel disease; and/or d) inhibiting the expression of pro-inflammatory cytokines Ccl2, Ccl3, Cxcl1, Cxcl2, G-CSF, IL-6, IL-1 β, IL-17A, S100A8, Tnf α in the intestinal mucosa of inflammatory bowel disease.
The intestinal flora regulated by the antibacterial peptide RNASE4 can be as follows: a) inhibiting weight loss in an individual with inflammatory bowel disease; b) reducing disease activity in an individual with inflammatory bowel disease; c) reducing the degree of intestinal mucosal damage in an individual with inflammatory bowel disease; and/or d) inhibiting the expression of pro-inflammatory cytokines Ccl2, Ccl3, Cxcl1, Cxcl2, G-CSF, IL-6, IL-1 β, IL-17A, S100A8, Tnf α in the intestinal mucosa of inflammatory bowel disease.
When the antibacterial peptide RNase4 is used as a drug, it can be administered by the conventional method.
The invention has the following technical advantages:
the invention discovers for the first time that the antibacterial peptide RNASE4 can regulate the steady state of intestinal flora and plays an important role in the occurrence and development of inflammatory bowel diseases. Further research shows that the antibacterial peptide RNASE4 can mainly inhibit the growth of spirulina platensis and promote the growth of Ackermansonia, thereby slowing the progress of enteritis and providing a new idea and means for treating inflammatory bowel diseases.
Drawings
The following describes embodiments of the present invention in further detail with reference to the accompanying drawings.
FIG. 1 is a diagram showing the sequencing result of "TG" inserted into mouse RNase4 gene knocked out by RNase 4;
FIG. 2 shows the results of the analysis of the alteration of intestinal flora by RNASE 4;
in fig. 2:
a is the species diversity analysis of the intestinal flora of the wild type and RNase4 gene knockout mice;
b, analyzing PCoA to reflect beta-diversity of the composition of mouse intestinal flora based on the principal coordinates of the non-weighted Unifrac;
c is the difference distance analysis result in the B picture and is shown in a box chart;
d is a group with obvious difference in intestinal flora of mice with wild type and RNase4 gene knockout analyzed by an LEfSe method;
and E is qPCR method for detecting muco spirulina and Ackermansia in intestinal tract.
FIG. 3 shows that RNASE4 has protective effects during enteritis;
in the context of figure 3, it is shown,
a is the daily weight change curve during DSS-treated mice;
b is a change curve of the disease activity index of the mice during DSS induced enteritis;
c is a colorectal representative graph and a colorectal length statistical result of the wild type and the Rnase4 gene knockout mice after DSS treatment is finished;
d is H & E staining representative graph and histological score statistical result of wild type and RNase4 gene knockout mouse distal colon sections;
and E, detecting the expression levels of inflammatory factors and chemokines in colons of wild-type and Rnase4 gene knockout mice by a qPCR method.
Figure 4 shows that gut flora plays a role in RNASE 4-related enteritis;
in the context of figure 4, it is shown,
a is that qPCR method detects the abundance of Ackermanomyces and Spirosoma mucosus after group 1 and group 2 mouse fecal bacteria transplantation;
b is the weight record during the coprophilous fungi transplantation and during the DSS induced enteritis;
c is disease activity index during DSS treatment of coprophilous bacteria transplanted mice;
d is a colon representative graph and a colorectal length statistical result of mice in a group 1 and a group 2 after DSS treatment is finished;
e is H & E staining representative graph and histological score statistical result of the distal colon section of the mice of the group 1 and the group 2;
f is qPCR method to detect the expression levels of inflammatory and chemokine in the colon of group 1 and group 2 mice.
Detailed Description
The invention will be further described with reference to specific examples, but the scope of the invention is not limited thereto:
example 1 RNASE4 altering gut flora composition
1.1 Experimental methods
In this example, 16S rDNA amplicon high-throughput sequencing was used to compare the differences in the flora composition in fecal DNA samples from 6 wild-type mice and 6 RNase4 knockout mice matched for sex, age in week and weight.
The RNase4 gene knockout mouse is constructed by adopting a TALEN technology, and the specific construction process is as follows: forming a dimer by using artificially modified Fok I, performing endonuclease activity under the guidance of a TALEN arm with a DNA recognition structural domain, specifically cutting target gene DNA, inserting a TG (deoxyribose nucleic acid) base into an RNase4 gene on a chromosome 14 of a mouse genome by using a TALEN technology, introducing point mutation to cause frame shift, constructing an RNase4 gene knockout mouse, and successfully inserting the TG base into the genome of the RNase4 gene knockout mouse by sequencing to cause frame shift mutation (figure 1).
First, the bacterial 16S rDNA variable region (V3-V4) was PCR amplified using universal primers 341F and 806R. Then, the PCR product is detected by 2% agarose gel electrophoresis, and the target fragment is recovered by an AxyPrep DNA gel recovery kit, and the quality is detected by a Nanodrop 2000 ultraviolet micro-spectrophotometer and the agarose gel electrophoresis. Next, qualified library was subjected to high throughput sequencing using the Illumina HIseq PE250 platform to obtain raw sequence data of 250bp in length. And then, splicing and filtering the original sequence information, deleting low-quality data, and obtaining a high-quality analysis sequence. And then clustering the obtained sequences according to the standard of 97% similarity to obtain operable classification units (OTU), and performing species abundance and cluster analysis, intra-sample diversity (alpha-diversity) analysis, inter-sample diversity (beta-diversity) analysis and inter-group difference analysis on the samples. Meanwhile, linear discriminant analysis effect size (LEfSe) was used to find significantly different colonies in wild-type mice and Rnase4 knock-out mice. Finally, real-time fluorescent quantitative PCR was used to detect the expression levels of specific slime Spirulina species and Ackermania species, where the Spirulina species used primers were Mucillus-F and Mucillus-R, the Ackermania species used primers were Akkermansia-F and Akkermansia-R, and the internal reference primers were Universal bacterial-F and Universal bacterial-R.
Primer information:
| name of Primary primer | Sequence (5 '-3') |
| 341F | CCTACGGGNGGCWGCAG |
| 806R | GGACTACHVGGGTWTCTAAT |
| Universal bacterial-F | ACTCCTACGGGAGGCAGCAGT |
| Universal bacterial-R | ATTACCGCGGCTGCTGGC |
| Mucispirillum-F | TCTCTTCGGGGATGATTAAAC |
| Mucispirillum-R | AACTTTTCCTATATAAACATGCAC |
| Akkermansia-F | CAGCACGTGAAGGTGGGGAC |
| Akkermansia-R | CCTTGCGGTTGGCTTCAGAT |
1.2 results of the experiment
The intestinal flora analysis result shows that the diversity of the intestinal flora of the RNase4 gene knock-out type mouse is obviously reduced, which indicates that the structure of the intestinal flora is obviously changed by the deletion of the RNase4 (see figure 2. A). Meanwhile, the differences between the flora of the wild type mouse and the flora of the Rnase4 knockout mouse are compared by the analysis of diversity (beta-diversity) among samples. The results of principal coordinate analysis of intestinal flora of two genotype mice based on non-weighted Unifrac show that wild type mice (black dots) are intensively distributed on the right side of the coordinate graph, Rnase4 knockout type mice (hollow dots) are intensively distributed on the left side of the coordinate graph, and no cross overlap exists between the two groups, which indicates that the intestinal flora structure between the wild type mice and the Rnase4 knockout type mice is significantly different (see fig. 2. B). In addition, the results of the differential distance analysis showed that the differential distance between the two groups was significantly greater than the differential distance within each group (see fig. 2.C), further validating the results of the above analysis. Thus, RNASE4 was shown to alter the intestinal flora in mice.
Next, linear discriminant analysis effect size was used to find significantly different populations in wild-type mice and Rnase4 knockout mice. The analysis results showed that the abundance of bacteria such as ferrobacteriaceae (deuteribacter), mucor spirulina (muscspirillum), Burkholderiales (Burkholderiales), gamma proteobacteria (Gammaproteobacteria), coprobacterium (Faecalibaculum), erythrothrix (erysipelastlurium), clostridium tumefaciens (ruminicola _6), and lachnospira (Lachnospiraceae _ a2) was significantly increased in the intestine of Rnase4 knockout mice compared with wild-type mice; whereas bacteria of the phylum Verrucomicrobiae (Verrucomicrobiae), Akkermansia (Akkermansia), Lachnospiraceae (Lachnospiraceae), Psychromonadaceae (Psychromonadaceae), coccus NK4a214 (Ruminococcaceae _ NK4a214), clostridium (lachnoclostrium) and the like were significantly reduced (see fig. 2. D). Among them, the slime spirulina and akkermansia are the most obvious flora to be up-regulated and down-regulated respectively. In order to verify the high-throughput sequencing results, the abundance of the sequences in the intestines of wild mice and Rnase4 knockout mice is quantitatively analyzed by a real-time fluorescent quantitative PCR method. The results show that the abundance of spirulina platensis is remarkably increased and the abundance of akkermansia is remarkably decreased in the intestinal tract of the Rnase4 knockout mouse, which is consistent with the sequencing results (see fig. 2. E).
Example 2 RNase4 protection against enteritis
1.1 Experimental methods
A model of enteritis was induced using Dextran Sulfate Sodium (DSS). First, a DSS drug powder was weighed out to dissolve in sterile water to a final concentration of 2.5% (i.e., 2.5g/100 ml). Then, 8-week-old wild-type and RNase4 gene knockout mice are taken, and drinking water is changed into 2.5% DSS solution in the molding process. Weight change, stool dryness, and hematochezia were recorded on days 1-10 of induced enteritis.
And (3) weight scoring: 0, no weight loss; 1, the reduction is 1-5%; 2, the reduction is 6-10%; 3, the reduction is 11-20%; 4, the reduction is over 20%; and (3) grading the feces: 0, solid stool; 1, solid stool, easy deformation; 2, unformed excrement; 3, liquid stool; stool blood score: 0, negative occult blood detection; 1, occult blood is detected to be positive; 2 blood is visible in the feces; 3, severe hematochezia.
Disease activity index is the average of body weight, stool, and stool blood scores, and is evaluated daily during the course of the experiment. The last day of enteritis induction, mice were sacrificed and colorectal sections of mice were removed and their length measured. Taking a section of about 1cm of a far-end colon tissue to perform formalin fixation, and then performing hematoxylin-eosin staining and histomorphological analysis. Meanwhile, about 1cm of intestinal section is taken to extract tissue RNA, and the inflammatory factor expression condition is detected by a real-time fluorescence quantitative PCR method.
1.2 results of the experiment
The DSS adopted in the embodiment induces the enteritis model, and the DSS can directly destroy colorectal epithelial barriers and increase intestinal permeability so as to induce the enteritis, so that the DSS is the most widely applied IBD disease model at present. In the experiment, after wild-type and Rnase4 knockout mice were treated with 2.5% DSS, the Rnase4 knockout mice had a more significant weight loss (see fig. 3.a) and a higher disease activity index (see fig. 3.B) than the wild-type mice. Mice were sacrificed on the tenth day, dissected and colonic tissue length and permeability thereof were measured, and the results showed that the colonic length was significantly shorter in Rnase4 knockout mice than in wild type mice (see fig. 3. C). The pathological changes of colorectal tissues are evaluated by hematoxylin-eosin staining, and the results show that after DSS induction, the RNase4 gene knockout mouse has more serious colorectal tissue lesions, poorer integrity and higher histopathological score (see figure 3. D). In addition, the expression levels of related inflammatory factors and chemokines in colorectal tissues after DSS treatment are detected by using a real-time fluorescent quantitative PCR (polymerase chain reaction) method, and the expression level of the RNase4 gene knockout mouse is remarkably increased (see FIG. 3. E). The results show that the RNase4 gene knock-out mice are more sensitive to DSS-induced enteritis, namely, the RNase4 has a protective effect in the enteritis occurrence process.
Example 3 intestinal flora plays a role in RNase 4-associated enteritis
1.1 Experimental methods
In this example, intestinal flora of Rnase4 knockout mice was transplanted into mixed antibiotic treated mice by fecal bacteria transplantation, and then the intestinal flora was analyzed for Rnase 4-related enteritis by using DSS induced enteritis model.
The specific process is as follows: firstly, preparing a mixed antibiotic solution (containing 1g/L ampicillin, 1g/L neomycin, 1g/L metronidazole and 0.5g/L vancomycin), and then replacing drinking water of 12 wild-type mice with the mixed antibiotic solution for taking for 4 weeks. After 4 weeks of treatment, feces from each mouse were collected and dissolved in sterile PBS (100 mg feces/1 mL PBS), followed by 4 serial gradient dilutions at a ratio of 1:10, 50. mu.L of each was applied to LB plates, and anaerobic and aerobic culture was performed to detect colony formation. When a sterile colony formed in the LB plate under both culture conditions, it was indicated that the clearance of the mouse intestinal flora was complete. Next, 12 mice were randomly divided into two groups of 6 mice each, and used as recipient mice for fecal bacteria transplantation.
Meanwhile, 6 wild type mice and 6 Rnase4 gene knockout mice matched in sex, week age and weight for about 8 weeks are selected as donor mice for fecal strain transplantation. Approximately 100mg of feces from each donor mouse was collected, dissolved in 2ml of sterile PBS, filtered and the intestinal tract of the different genotype mice was perfused back into the recipient mice by gavage. Transplanting once every 2 days, collecting the receiver mouse excrement after lasting for 2 weeks, extracting excrement DNA, and detecting the planting condition of the target strain by adopting a real-time fluorescent quantitative PCR method. Finally, acute enteritis was induced with 2.5% DSS using the evaluation indices of example 2 including body weight change, disease activity index, colorectal length, pathological tissue morphology and inflammatory factor expression.
1.2 results of the experiment
Removing intestinal flora for four weeks after antibiotic treatment, and then transplanting the feces of wild type and RNase4 gene knockout mice matched in sex, week age and weight into a mouse body treated by mixed antibiotics in a stomach irrigation mode, wherein a feces group of the transferred wild type mouse is marked as a group 1, and a feces group of the transferred RNase4 gene knockout mouse is marked as a group 2; after the continuous coprinus faecalis is transplanted for two weeks, the abundance of the slime spirulina platensis and the alemannia manshurica is detected by a real-time fluorescent quantitative PCR method. The results show that the abundance of slime spirulina platensis is significantly increased and the abundance of akkermansia is significantly decreased in group 2 compared to group 1, suggesting that the fecal bacteria transplantation experiment was successful (see fig. 4. a). The results using the 2.5% DSS induced enteritis model in mice showed a more significant weight loss (see fig. 4.B), a higher disease activity index (see fig. 4.C), a shorter colon length (see fig. 4.D), a more severe intestinal epithelial barrier disruption (see fig. 4.E) and a significant increase in inflammatory factor expression (see fig. 4.F) compared to group 1 in group 2. The above results demonstrate that transferring fecal flora from Rnase4 knockout mice into wild type mice can exacerbate DSS-induced enteritis symptoms.
Finally, it is also noted that the above-mentioned lists merely illustrate a few specific embodiments of the invention. It is obvious that the invention is not limited to the above embodiments, but that many variations are possible. All modifications which can be derived or suggested by a person skilled in the art from the disclosure of the present invention are to be considered within the scope of the invention.
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Claims (5)
1. The application of the antibacterial peptide in preparing the medicine for regulating intestinal flora is characterized in that: the antibacterial peptide is RNASE 4.
2. Use according to claim 1, characterized in that: the proportion of the bacteria in the intestinal flora is reduced, while the proportion of Verrucomicrobiae, Akkeramillarium, Lacciprilium, Erysipellucidium, Ruminostrothridium _6 and Lachnospiraceae _ A2 in the intestinal flora is increased.
3. Use according to claim 2, characterized in that: increasing the ratio of Akkermansia muciniphila in intestinal flora.
4. The application of the antibacterial peptide in preparing the medicine for treating inflammatory bowel diseases is characterized in that: the antibacterial peptide is RNASE 4.
5. Use according to claim 4, characterized in that: the inflammatory bowel disease comprises ulcerative colitis and Crohn's disease.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104031883A (en) * | 2014-05-16 | 2014-09-10 | 浙江大学 | Model for protecting mouse ulcerative colitis by antibacterial peptide C-BF |
| CN104328131A (en) * | 2014-09-04 | 2015-02-04 | 浙江大学 | Recombinant expression, separation and purification method of human ribonuclease 4 protein |
| CN105727311A (en) * | 2016-02-06 | 2016-07-06 | 浙江大学 | Application of RNASE4 serving as drug target to brain glioma inhibition drugs |
| KR20180052178A (en) * | 2016-11-10 | 2018-05-18 | 대한민국(농촌진흥청장) | An anti-microbial peptide, Protaetiamycine 1 isolated from Protaetia brevitarsis seulensis and its synthetic composition |
| CN112646744A (en) * | 2020-12-28 | 2021-04-13 | 江南大学 | Application of lactobacillus reuteri in preventing and relieving ulcerative colitis |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9772334B2 (en) * | 2012-12-10 | 2017-09-26 | The Regents Of The University Of California | Inflammatory bowel disease markers and therapies for colitis-associated intestinal fibrosis |
-
2021
- 2021-05-05 CN CN202110487229.2A patent/CN113209282B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104031883A (en) * | 2014-05-16 | 2014-09-10 | 浙江大学 | Model for protecting mouse ulcerative colitis by antibacterial peptide C-BF |
| CN104328131A (en) * | 2014-09-04 | 2015-02-04 | 浙江大学 | Recombinant expression, separation and purification method of human ribonuclease 4 protein |
| CN105727311A (en) * | 2016-02-06 | 2016-07-06 | 浙江大学 | Application of RNASE4 serving as drug target to brain glioma inhibition drugs |
| KR20180052178A (en) * | 2016-11-10 | 2018-05-18 | 대한민국(농촌진흥청장) | An anti-microbial peptide, Protaetiamycine 1 isolated from Protaetia brevitarsis seulensis and its synthetic composition |
| CN112646744A (en) * | 2020-12-28 | 2021-04-13 | 江南大学 | Application of lactobacillus reuteri in preventing and relieving ulcerative colitis |
Non-Patent Citations (3)
| Title |
|---|
| 动物肠道黏膜抗菌肽维持微生物区系平衡机制研究进展;蔡杰等;《动物营养学报》;20140801;第26卷(第8期);第2071-2076页 * |
| 核糖核酸酶4:一种高保守性多功能的核酸酶;盛静浩;《生物化学与生物物理进展》;20140224;第41卷(第2期);第139-145页 * |
| 血管生成素和核糖核酸酶-4基因表达调控及其生物学功能研究;盛静浩;《中国优秀博硕士学位论文全文数据库（博士） 医药卫生科技辑》;20140415;第E059-23页 * |
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