CN109628461A - A kind of IL-35 recombinant lactic acid bacteria improving colitis - Google Patents
A kind of IL-35 recombinant lactic acid bacteria improving colitis Download PDFInfo
- Publication number
- CN109628461A CN109628461A CN201910094765.9A CN201910094765A CN109628461A CN 109628461 A CN109628461 A CN 109628461A CN 201910094765 A CN201910094765 A CN 201910094765A CN 109628461 A CN109628461 A CN 109628461A
- Authority
- CN
- China
- Prior art keywords
- lactic acid
- acid bacteria
- gene
- ril
- sequence table
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/66—General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligation; Use of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Mycology (AREA)
- Veterinary Medicine (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention discloses recombination rIL-35 genes, its nucleotide sequence is as shown in sequence table SEQ ID NO.1；The lactic acid bacteria expression vectors of rIL-35 gene are carried, it inserts gene shown in sequence table SEQ ID NO.1；Escherichia coli-lactic acid bacteria shuttle expression vector preparation method of rIL-35 gene is carried, it includes: that 1) gene shown in artificial synthesized sequence table SEQ ID NO.1, upstream and downstream joined Sac II and Sma I restriction enzyme site；2) gene and pW425N described in Sac II and Sma I digestion step 1)；Gene shown in sequence table SEQ ID NO.1 is inserted into pW425N；IL-35 recombinant lactic acid bacteria, it has converted the lactic acid bacteria expression vectors of above-mentioned carrying rIL-35 gene；IL-35 recombinant lactic acid bacteria improves or alleviates the application in colitis drug in preparation.
Description
Technical field
The invention belongs to field of biotechnology, and in particular to it is a kind of improve colitis IL-35 recombinant lactic acid bacteria and its preparation
Method.
Background technique
Ulcerative colitis is a kind of colitis disease of idiopathic, it is different from various infectious colonic diseases,
Although lesion sign has similarity, research so far fails to find which kind of pathogenic bacteria is causing a disease for this kind of endo enteritis
It is former.This disease is mainly by the generation of knot, mucous membrane of rectum and submucosa centered on chronic, nonspecific inflammatory lesion, on mucous membrane
Skin and body of gland destroy, hyperplasia or atrophy, inflammatory cell infiltration, crypt abscess are formed, thus mucous hyperemia, erosion, ulcer is presented
And proliferation sexually revises.Clinical manifestation also embodies the characteristics of inflammatory bowel disease, after there is pus and blood stool or mucous bloody stool, inner urgency
Weight, or with abdominal pain, fever etc..The normal burst onset of this disease, state of an illness weight great disparity, most courses of disease are slow, there is recurrent exerbation tendency, few
Number case is broken out at acute, and the state of an illness is dangerous.Ulcerative colitis is one of the disease of gastrointestinal tract most serious, in recent years disease incidence by
Edge up height, and the morbidity of this disease and colon cancer also has certain relationship, therefore is classified as modern difficult treatment by the World Health Organization
One of.
This disease cause of disease and definite pathogenesis are unknown so far at present, it is considered that are related to hereditary, immune, infection, spirit
Equal many factors, therefore treat and still lack specific measure.At present it is generally believed that the treatment mesh of inflammatory bowel disease active stage
Mark is to control inflammation as early as possible, alleviates its clinical symptoms；Disease-free period should then continue its maintenance therapy, while it is multiple to prevent disease
Hair, and prevent and treat inflammatory bowel disease complication.Treatment for the disease, at present still without specific short.Clinical drug therapy master
There are 5-aminosalicylic acid class preparation, glucocorticoid and immunosupress and immunomodulator etc..These therapeutic agents exist
Some side effects, therefore limit its long-time service.Therefore, it develops effectively and the enteral microecological formulation of Small side effects is for prevention
There is important practical usage with treatment colitis.
Studies have shown that proinflammatory Th17 cell ratio in patients of ulcerative colitis or experimental colitis mouse intestinal tissue
Example dramatically increases, and presses down the Treg cell quantity decline of inflammatory.It can by reducing Th17 cell quantity or increase Treg quantity
It is effective to alleviate colitis.Further study show that IL-35 is the suppression inflammatory cytokine of Treg cell secretion, it is able to suppress
The differentiation and proliferation of Th17 cell, while IL-35 can also promote the proliferation of Treg cell.
Lactic acid bacteria is broadly considered the microorganism of safety level as the normal flora in human and animal's enteron aisle.It adopts
With recombinant DNA technology, the lactic acid bacteria expression vectors of foreign gene-carrying are constructed, using lactic acid bacteria as host strain, realize function
Expression of the energy property albumen in lactic acid bacteria, therefore the development and application of recombinant lactic acid bacteria probiotics are widely received.
Summary of the invention
It is an object of the present invention to provide a kind of IL-35 recombinant lactic acid bacterias and preparation method thereof for improving colitis.
RIL-35 gene is recombinated, its nucleotide sequence is as shown in sequence table SEQ ID NO.1.
The lactic acid bacteria expression vectors of rIL-35 gene are carried, it inserts gene shown in sequence table SEQ ID NO.1；
The lactic acid bacteria expression vectors are Escherichia coli-lactic acid bacteria shuttle expression vector；
The Escherichia coli-lactic acid bacteria shuttle expression vector is pW425N.
Escherichia coli-lactic acid bacteria shuttle expression vector preparation method of rIL-35 gene is carried, it includes:
1) gene shown in artificial synthesized sequence table SEQ ID NO.1, upstream and downstream joined Sac II and Sma I restriction enzyme site；
2) gene and pW425N described in Sac II and Sma I digestion step 1)；Gene shown in sequence table SEQ ID NO.1
It is inserted into pW425N.
IL-35 recombinant lactic acid bacteria, it has converted the lactic acid bacteria expression vectors of above-mentioned carrying rIL-35 gene；
The lactic acid bacteria is Lactobacillus acidophilus.
IL-35 recombinant lactic acid bacteria improves or alleviates the application in colitis drug in preparation.
The present invention provides recombination rIL-35 genes, its nucleotide sequence is as shown in sequence table SEQ ID NO.1；It carries
The lactic acid bacteria expression vectors of rIL-35 gene, it inserts gene shown in sequence table SEQ ID NO.1；Carry rIL-35 gene
Escherichia coli-lactic acid bacteria shuttle expression vector preparation method, it includes: 1) artificial synthesized sequence table SEQ ID NO.1 institute
The gene shown, upstream and downstream joined Sac II and Sma I restriction enzyme site；2) described in Sac II and Sma I digestion step 1)
Gene and pW425N；Gene shown in sequence table SEQ ID NO.1 is inserted into pW425N；IL-35 recombinant lactic acid bacteria, on it has been converted
The lactic acid bacteria expression vectors for the carrying rIL-35 gene stated；IL-35 recombinant lactic acid bacteria improves or alleviates colitis drug in preparation
In application.
Detailed description of the invention
The horizontal testing result of Fig. 1 IL-35 recombinant lactic acid bacteria stomach-filling rear intestinal IL-35；
Fig. 2 IL-35 recombinant lactic acid bacteria reduces colitis mice body weight loss rate testing result；
Fig. 3 IL-35 recombinant lactic acid bacteria maintains colitis mice colon lengths testing result；
Fig. 4 IL-35 recombinant lactic acid bacteria alleviates colitis mice intestinal tissue pathological change testing result；
Fig. 5 IL-35 recombinant lactic acid bacteria reduces Th17 cell proportion testing result in colitis mice enteron aisle；
Fig. 6 IL-35 recombinant lactic acid bacteria increases Treg cell proportion testing result in colitis mice enteron aisle.
Specific embodiment
The preparation of 1 IL-35 recombinant lactic acid bacteria of embodiment
IL-35 is the heterodimeric body protein of Ebi3 and IL-12a p35 subunit composition；23 alanine of selection coding Ebi3
To the gene order (Ala23-Pro228,621 bp) of 228 proline peptide fragments, with 23 essences for encoding IL-12a p35 subunit
Propylhomoserin to 215 alanine peptide fragments gene order (Arg23-Ala215,582 bp), with conventional linker protein gene
(45 bp) connects the two；The recombination IL-35 base for using artificial synthesized or round pcr mode to obtain overall length as 1248 bp
Cause is named as rIL-35, and gene order table is as shown in SEQ ID1.
The lactic acid bacteria recombinant expression carrier for carrying rIL-35 gene is constructed using common molecular clone technology；The present embodiment
In, it joined Sac II and Sma I restriction enzyme site in the upstream and downstream of rIL-35 gene, using pW425N lactic acid bacteria expression vectors,
It is finally obtained pW425N/rIL-35；Using but be not limited to Lactobacillus acidophilus (Lactobacillus acidophilus, Lb. acidophilus) it is recipient bacterium, the recombination acidophilus of secretion rIL-35 is obtained by conventional lactic acid bacteria electrotransformation technology
Bacillus acidi lactici is named asLb. acidophilus/rIL-35。
It is horizontal that 2 IL-35 recombinant lactic acid bacteria of embodiment increases mouse intestinal IL-35
The C57BL/6J mouse of 20 6-8 week old is randomly divided into 4 groups, every group 10 (half male and half female).Respectively PBS group,Lb. acidophilus Group (empty bacterium group),Lb. acidophilus/ pW425N group (empty carrier group),Lb. acidophilus/
RIL-35 group and heat-inactivatedLb. acidophilus/ rIL-35 group (Lb. acidophilus/ rIL-35 i).
PBS group is with 0.2 ml PBS stomach-filling, other groups are with 0.2 ml bacterium solution stomach-filling.In addition to PBS group, thalline quantity is each
109cfu/ml.Stomach-filling 3 times weekly after continuous gavage 3 weeks, sample 1 time, are recorded as 7d, 14d and 21d for every 7 days.Sampling sites
For colonic tissue, the level of IL-35 in colonic tissue is detected according to illustrating to operate using IL-35 ELISA kit.As a result
As shown in Figure 1, within the identical sampling time,Lb. acidophilusThe IL-35 level of/rIL-35 group mouse Colon tissue is aobvious
It writes and is higher than other groups, and as the increase in sampling time presentation significantly rises trend, and it is heat-inactivatedLb. acidophilus/
The IL-35 that rIL-35 can not dramatically increase mouse Colon tissue is horizontal.The result shows that IL-35 recombinant lactic acid bacteria increase it is small
The IL-35 of mouse colonic tissue is horizontal.
3 IL-35 recombinant lactic acid bacteria of embodiment alleviates experimental colitis
Mouse experiment colitis is using classical DSS revulsion.Using 3%DSS free water modeling, and by mouse be divided into
Lower experimental group: normal water group (Ctr), 3%DSS group, 3%DSS+ Lb. acidophilus/ pW425N group, 3%DSS+Lb. acidophilus/ rIL-35 group, 3%DSS+ Lb. acidophilus/rIL-35 i group, 3%DSS+IL35 group (tail vein note
Penetrate 3 μ g/ pcs/day of IL-35 albumen).During modeling, mouse weight is weighed daily and calculates body weight loss rate, is tried using stool occult blood
Agent box observes diarrhea of mouse situation according to operation evaluation mouse stool occult blood situation is illustrated daily, and according to described in table 1, calculates small
Mouse disease activity index (Disease active index, DAI) scoring.In experiment the 7th day, mouse is put to death, colon is won,
Each group colon lengths are measured, takes colonic tissue to prepare paraffin section, is dyed by HE, compare each group mouse Colon histopathology
Variation.
The result shows that compared with Ctr group, 3%DSS group, 3%DSS+ Lb. acidophilus/pW425N group and 3%DSS+
Lb. the mouse weight loss late of acidophilus/rIL-35 i group dramatically increases, and 3%DSS+Lb. acidophilus/
The mouse weight loss late of rIL-35 group and 3%DSS+IL35 group is obviously improved, and without significant difference (Fig. 2) between this two groups.
Compared with Ctr group, 3%DSS group, 3%DSS+ Lb. acidophilus/pW425N group and 3%DSS+ Lb. acidophilus/
The colon lengths of the mouse of rIL-35 i group significantly reduce, and 3%DSS+Lb. acidophilus/rIL-35 group and 3%DSS+
The reduction of the mouse Colon length of IL35 group is relieved, and without significant difference (Fig. 3) between this two groups.Compared with Ctr group,
The pathological changes such as the mouse Colon tissue of 3%DSS group shows inflammatory cell infiltration, colonic tissue is destroyed, and 3%DSS+Lb.
The mouse Colon histopathologic change of acidophilus/rIL-35 group is able to be obviously improved (Fig. 4).Illustrate IL-35 recombination lactic acid
Bacterium significantly improves mouse experiment colitis, and effect is consistent with tail vein injection Il-35 albumen.
4 IL-35 recombinant lactic acid bacteria of embodiment increases colonic tissue Treg cell proportion, reduces Th17 cell proportion
The 7th day of mouse modeling experiment as described in Example 3, acquires colonic tissue, and it is thin that cell colonic tissue is obtained after digestion
Born of the same parents' suspension, be respectively adopted anti-CD4-FITC and anti-Foxp3-APC detection Treg cell proportion, anti-CD4-FITC and
Anti-IL17A-PE detects Th17 cell proportion.In the process, it is operated according to antibody operation instructions, first carries out anti-
The padding 30min of CD4-FITC, then the TF Buffer of BD company is used, it operates to specifications and cell is fixed
And permeabilization, and anti-Foxp3-APC or anti-IL17A-PE is respectively adopted and dyes 45 min, it is examined finally by flow cytometry
Survey the ratio of Treg cell and Th17 cell.
The result shows that compared with Ctr group, 3%DSS group, 3%DSS+ Lb. acidophilus/pW425N group and 3%DSS+
Lb. the Th17 cell proportion of proinflammatory dramatically increases in the mouse Colon tissue of acidophilus/rIL-35 i group, and 3%
DSS+Lb. acidophilus/rIL-35 group and 3%DSS+IL35 group then significantly reduce (Fig. 5).Compared with Ctr group, 3%DSS
The mouse knot of group, 3%DSS+ Lb. acidophilus/pW425N group and 3%DSS+ Lb. acidophilus/rIL-35 i group
The Treg cell proportion for pressing down inflammatory in intestinal tissue significantly reduces, and 3%DSS+Lb. acidophilus/rIL-35 group and 3%DSS+
IL35 group then dramatically increases (Fig. 6).Illustrate that IL-35 recombinant lactic acid bacteria increases the suppression inflammatory in experimental colitis mouse intestinal tissue
Treg cell quantity plays and inhibits inflammatory effect.
Sequence table
<110>Hao Fengqi
<120>a kind of IL-35 recombinant lactic acid bacteria for improving colitis
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 1248
<212> DNA
<213> Ebi3 Ala23-Pro228
<400> 1
atggctctcg tggctctaag ccagcccaga gtgcaatgcc atgcttctcg gtatcccgtg 60
gccgtggact gctcctggac tcctctccag gctcccaact ccaccagatc cacgtccttc 120
attgccactt acaggctcgg tgtggccacc cagcagcaga gccagccctg cctacaacgg 180
agcccccagg cctcccgatg caccatcccc gacgtgcacc tgttctccac ggtgccctac 240
atgctaaatg tcactgcagt gcacccaggc ggcgccagca gcagcctcct agcctttgtg 300
gctgagcgaa tcatcaagcc ggaccctccg gaaggcgtgc gcctgcgcac agcgggacag 360
cgcctgcagg tgctctggca tccccctgct tcctggccct tcccggacat cttctctctc 420
aagtaccgac tccgctaccg gcgccgagga gcctctcact tccgccaggt gggacccatt 480
gaagccacga ctttcaccct caggaactcg aaaccccatg ccaagtattg catccaggtg 540
tcagctcagg acctcacaga ttatgggaaa ccaagtgact ggagcctccc tgggcaagta 600
gaaagtgcac cccataagcc cggtggtggt ggttctggtg gtggtggttc tggtggtggt 660
ggttctaggg tcattccagt ctctggacct gccaggtgtc ttagccagtc ccgaaacctg 720
ctgaagacca cagatgacat ggtgaagacg gccagagaaa aactgaaaca ttattcctgc 780
actgctgaag acatcgatca tgaagacatc acacgggacc aaaccagcac attgaagacc 840
tgtttaccac tggaactaca caagaacgag agttgcctgg ctactagaga gacttcttcc 900
acaacaagag ggagctgcct gcccccacag aagacgtctt tgatgatgac cctgtgcctt 960
ggtagcatct atgaggactt gaagatgtac cagacagagt tccaggccat caacgcagca 1020
cttcagaatc acaaccatca gcagatcatt ctagacaagg gcatgctggt ggccatcgat 1080
gagctgatgc agtctctgaa tcataatggc gagactctgc gccagaaacc tcctgtggga 1140
gaagcagacc cttacagagt gaaaatgaag ctctgcatcc tgcttcacgc cttcagcacc 1200
cgcgtcgtga ccatcaacag ggtgatgggc tatctgagct ccgcctga 1248
Claims (8)
1. recombinating rIL-35 gene, its nucleotide sequence is as shown in sequence table SEQ ID NO.1.
2. carrying the lactic acid bacteria expression vectors of rIL-35 gene, it inserts gene shown in sequence table SEQ ID NO.1.
3. the lactic acid bacteria expression vectors according to claim 2 for carrying rIL-35 gene, it is characterised in that: the lactic acid
Bacterium expression vector is Escherichia coli-lactic acid bacteria shuttle expression vector.
4. the lactic acid bacteria expression vectors according to claim 3 for carrying rIL-35 gene, it is characterised in that: the large intestine
Bacillus-lactic acid bacteria shuttle expression vector is pW425N.
5. carrying Escherichia coli-lactic acid bacteria shuttle expression vector preparation method of rIL-35 gene, it includes:
1) gene shown in artificial synthesized sequence table SEQ ID NO.1, upstream and downstream joined Sac II and Sma I restriction enzyme site；
2) gene and pW425N described in Sac II and Sma I digestion step 1)；Gene shown in sequence table SEQ ID NO.1
It is inserted into pW425N.
6. IL-35 recombinant lactic acid bacteria, it has converted the lactic acid bacteria expression vectors as claimed in claim 3 for carrying rIL-35 gene.
7. IL-35 recombinant lactic acid bacteria according to claim 6, it is characterised in that: the lactic acid bacteria is acidophilus lactic acid bar
Bacterium.
8. IL-35 recombinant lactic acid bacteria as claimed in claim 6 improves or alleviates the application in colitis drug in preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910094765.9A CN109628461A (en) | 2019-01-31 | 2019-01-31 | A kind of IL-35 recombinant lactic acid bacteria improving colitis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910094765.9A CN109628461A (en) | 2019-01-31 | 2019-01-31 | A kind of IL-35 recombinant lactic acid bacteria improving colitis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109628461A true CN109628461A (en) | 2019-04-16 |
Family
ID=66064345
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910094765.9A Pending CN109628461A (en) | 2019-01-31 | 2019-01-31 | A kind of IL-35 recombinant lactic acid bacteria improving colitis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109628461A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130164380A1 (en) * | 2010-06-17 | 2013-06-27 | Actogenix Nv | Compositions and methods for treating inflammatory conditions |
| CN104083755A (en) * | 2013-11-21 | 2014-10-08 | 深圳意达凯生物科技有限公司 | Interleukin 37 containing drug, preparation method and application thereof |
| CN107873051A (en) * | 2015-04-15 | 2018-04-03 | 阿雷斯贸易股份有限公司 | Produce TSLP or IL 25 Lactococcus lactis and its as probiotics and the purposes of therapeutic agent |
-
2019
- 2019-01-31 CN CN201910094765.9A patent/CN109628461A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130164380A1 (en) * | 2010-06-17 | 2013-06-27 | Actogenix Nv | Compositions and methods for treating inflammatory conditions |
| CN104083755A (en) * | 2013-11-21 | 2014-10-08 | 深圳意达凯生物科技有限公司 | Interleukin 37 containing drug, preparation method and application thereof |
| CN107873051A (en) * | 2015-04-15 | 2018-04-03 | 阿雷斯贸易股份有限公司 | Produce TSLP or IL 25 Lactococcus lactis and its as probiotics and the purposes of therapeutic agent |
| US20180104285A1 (en) * | 2015-04-15 | 2018-04-19 | Ares Trading S.A. | Lactococcus lactis producing tslp or il-25 and their uses as probiotics and therapeutics |
Non-Patent Citations (2)
| Title |
|---|
| JIANYONG WANG等: "Preventative delivery of IL-35 by Lactococcus lactis ameliorates DSS-induced colitis in mice", 《APPLIED MICROBIOLOGY AND BIOTECHNOLOGY》 * |
| 仝雷等: "重组aFGF乳酸菌的构建、表达及其对小鼠溃疡性结肠炎的药效研究", 《湖北农业科学》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11786567B2 (en) | Compositions and methods for the treatment of type 1 diabetes | |
| Del Carmen et al. | Genetically engineered immunomodulatory Streptococcus thermophilus strains producing antioxidant enzymes exhibit enhanced anti-inflammatory activities | |
| US11896631B2 (en) | Probiotics for use in the treatment of diverticulosis and diverticular disease | |
| Zhang et al. | Probiotic mixture protects dextran sulfate sodium-induced colitis by altering tight junction protein expressions and increasing tregs | |
| CN113430133A (en) | Composite probiotics capable of relieving ulcerative colitis, preparation method and application thereof | |
| Jiang et al. | Lactobacillus acidophilus induces cytokine and chemokine production via NF-κB and p38 mitogen-activated protein kinase signaling pathways in intestinal epithelial cells | |
| US20040106564A1 (en) | Use of slpi for treating chronic inflammatory intestinal diseases | |
| Bhat et al. | Potential probiotic Lactobacillus rhamnosus (MTCC-5897) inhibits Escherichia coli impaired intestinal barrier function by modulating the host tight junction gene response | |
| US20220160794A1 (en) | Use of bacillus amyloliquefaciens and/or bacillus subtilis for the enhancement of active probiotic compositions or for the activation of inactive probiotic compositions, compositions thus obtained, and related method | |
| Lopetuso et al. | Gut microbiota: a key modulator of intestinal healing in inflammatory bowel disease | |
| US11549118B2 (en) | Genetically modified bacteria stably expressing IL-10 and insulin | |
| US20150216932A1 (en) | Probiotic bacteria as carrier for a helminth-derived immunomodulator for the treatment of inflammatory disorders | |
| Chen et al. | Lamina propria interleukin 17 A aggravates natural killer T‐cell activation in autoimmune hepatitis | |
| CN105316252B (en) | A kind of five gene-deleted strain of streptococcus suis 2-type and application | |
| CN109628461A (en) | A kind of IL-35 recombinant lactic acid bacteria improving colitis | |
| Ding et al. | An ROS/DAMP dual-scavenging nanomedicine for normalizing macrophage polarization and microbiome in colitis | |
| CN115364125A (en) | Application of recombinant bifidobacterium longum carrying endostatin protein in preparation of drugs for treating colitis and colorectal cancer of mice | |
| WO2022137644A1 (en) | Bacterium, il10 gene expression enhancer, immune response control enhancer, and preparation | |
| WO2022007741A1 (en) | Genetically engineered live bacteria and methods of constructing the same | |
| Lu et al. | Recent advances in bacteria‐based platforms for inflammatory bowel diseases treatment | |
| He et al. | Wild Cordyceps proteins reinforce intestinal epithelial barrier through MAPK/NF-κB pathway in MRL/lpr mice | |
| Šlemín | Modulation of the immune system by microbiota | |
| Yinhe et al. | Bacteroides thetaiotaomicron and its inactivated bacteria ameliorate colitis by inhibiting macrophage activation | |
| EP4072571A1 (en) | Microbial compositions and methods for treatment and detection of disease | |
| CN115786202A (en) | Probiotic lysate composition and application thereof in preparation of product with anti-enteritis effect |
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: 20190416 |
|
| WD01 | Invention patent application deemed withdrawn after publication |