CN104906104A - Applications of a TGF-beta1 receptor blocker in preparation of medicines treating Hydatid disease - Google Patents
Applications of a TGF-beta1 receptor blocker in preparation of medicines treating Hydatid disease Download PDFInfo
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- CN104906104A CN104906104A CN201510245580.5A CN201510245580A CN104906104A CN 104906104 A CN104906104 A CN 104906104A CN 201510245580 A CN201510245580 A CN 201510245580A CN 104906104 A CN104906104 A CN 104906104A
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Abstract
The invention provides applications of a TGF-beta1 receptor blocker in preparation of medicines treating the Hydatid disease. Concretely, through immune escape of TGF-beta1 receptor blockers for inhibition of infection of intermediate hosts by echinococcosis granulosis cysts, increase of the number of CD<4+>T cells, decrease of the number of CD<8+> T cells, raising of the CD<4+>/CD<8+>T cell ratio, decrease of the number of CD<4+>CD<25+> T cells, increase of expression of active receptors NKG2D of NK cells and raising of the cracking rate of target cells Yac-1 by NK cells in host cells are caused. Researches show that NK cell viability is in positive correlation with active receptor NKG2D number. Results show that the provided method can enhance inhibition of hosts to echinococcosis granulosis cyst infection effectively. The method can be used for treating the Hydatid disease effectively, and has good clinic application prospects.
Description
Technical field
The present invention relates to a kind of method for the treatment of echinococcosis, be specifically related to TGF-β1receptor blocker and apply in the medicine of preparation treatment echinococcosis, belong to biomedicine field.
Background technology
Echinococcosis (Hydatid disease), also known as echinococcosis, is a kind of parasitic disease having a strong impact on human and livestock health that echinococcus parasitizes intermediate host and causes.Echinococcosis is in surgical procedure or in normal patient body, and due to encapsulation cracking, part protoscolex may enter in tissue, causes subinfection again, brings very large difficulty also to the treatment of echinococcosis.
For the treatment of echinococcosis, this area has developed multiple therapeutic scheme, and mainly based on surgical operation, medical chemotherapy is auxiliary method.But the method has many drawbacks, as operative treatment is comparatively large to injury of human, and easily recur.At present, main anti-treating echinococcosis has praziquantel and the large class of benzimidazoles residues two, but because this two classes medicine still exists many weak points, as: toxic and side effects is comparatively large, and individual difference is large, some patients can not tolerate, or generation drug resistance, have bibliographical information, its chemotherapy only has the patient of 30% to be cured following up a case by regular visits in 1 year, the patient of 30% ~ 50% improves, and curative effect is unstable.
In addition, echinococcosis is the same with other parasitic disease, it is a chronic infection process, it is also chronic and lasting process to the effect of host, interaction between the two and pathogenic immunologic mechanism very complicated, in addition this sick incidence of occult, most of patients is all carry out hospital admission because of the complication of echinococcosis.
In order to improve therapeutic effect further, in recent years, Chinese scholars has carried out large quantifier elimination and clinical position in fields such as Echinococcus hydatid cyst pathogenesis, novel anti-hydatid drugs.
Transforming growth factor-β (transforming growth factor-β, TGF-β) is the TGF-beta superfamily belonging to one group of adjustment Growth of Cells recently found and differentiation.TGF-β 1 belongs to the secreted polypeptide factor, is distributed in Various Tissues cell, and TGF-β 1 is kind of a multi-functional somatomedin.TGF-β has adjustment cell proliferation, Growth Control, differentiation, the formation of irritation cell epimatrix, multiple biological function such as increase adhesion molecule expression and Immunosuppression response etc.
CD4
+cD25
+regulatory T cells (regulatory T cells, Tregs) be naturally occurring in body, that there is unique regulatory function T cell subgroup, it is different from Th1 and Th2, by secretion SC factor TGF-β 1 and IL-10 membrane molecule or with other cells directly contact etc., mode plays immunosuppressive action widely for it, suppresses propagation and the activation of the panimmunity cell such as T lymphocyte and NK cell in body.Find in patients with hydatidosis serum, IL-10 and TGF-β is significantly higher than normal healthy controls group in the expression of echinococcosis group; External mouse experiment finds, protoscolex/capsule liquid and mouse lymphocyte Dual culture group TGF-β 1 are significantly higher than matched group; Prompting under this special Infection Status, may can strengthen the response of immunosuppressant associated immune and stimulate Treg cell, thus strengthen the immunosuppressive action to host.
Research finds, polypide why can in host long term survival, depend on the immune evasion function to host.At present about the issuable immune evasion of drift of the research mainly Th1/Th2 of polypide immunologic escape.Treg cell is a kind of novel T cell subgroup, be different from Th1 and Th2 effector T cell, atopen and correlation factor TGF-β, IL-10 high expressed of Treg cell is found near echinococcosis focus, applicant is found by research before, and Echinococcus Granulosus Cysts/capsule liquid inductance dye can make mice Treg cell quantity, atopen and correlation factor TGF-β increase.Therefore, theoretically, utilize TGF-β1receptor blocker can be used for prevention Echinococcus hydatid cyst palindromia, but how to utilize TGF-β1receptor blocker for the preparation for the treatment of echinococcosis, particularly for the host in Echinococcus granulosus, there is no report.
From current clinical practice, although the clinical diagnosis of echinococcosis and study on prevention work have been made significant headway, but, research and develop that a kind of toxic and side effects is little, efficacy stability, effectively can treat Echinococcus granulosus and the medicine preventing it to recur and application thereof, remain the difficult problem that this area is urgently to be resolved hurrily.
Summary of the invention
The object of the invention is to explore by further investigation a kind of method that the TGF-of utilization β1receptor blocker effectively treats Echinococcus granulosus and recurrence thereof.
Applicant have extensively studied Biological Mechanism and the initial infection host immune response mechanism of echinococcosis morbidity.Applicant is by setting up Echinococcus granulosus mouse model, and research finds that Echinococcus Granulosus Cysts impels CD4 by promoting splenocyte secretion inhibition molecule TGF-β 1
+cD25
+t cell is broken up, thus lowers the expression of NK cytoactive receptor NKG2D, final suppression NK cell killing and wounding Echinococcus Granulosus Cysts protoscolex, and forms the immune evasion to host., say in theory for this reason, if the immunologic escape of Echinococcus hydatid cyst polypide in host effectively can be suppressed, reactivate the immunoreation of host body, just can effectively treat Echinococcus granulosus and relapse thereof.
Specifically, the present invention is achieved through the following technical solutions:
TGF-β1receptor blocker is applied in the medicine of preparation treatment echinococcosis, and this application process comprises applies a certain amount of TGF-β1receptor blocker to the host in Echinococcus granulosus.
SB-431542, SB-505124 and SB-525334 are effective TGF-β1receptor blockeres, the Smad2/3 phosphorylation that can effectively suppress TGF-β 1 to induce and nuclear translocation, applicant is found by research, and SB-525334 is best to the inhibition of host cell TGF-β I receptor.
Applicant adopts following test procedure: prepare Echinococcus Granulosus Cysts protoscolex; Separating mouse spleen cell; After external TGF-β1receptor blocks, Echinococcus Granulosus Cysts and mouse lymphocyte divide into groups Dual culture; LDH method detects the killing activity of NK; Fluidic cell dyeing and detection lymphocyte quantity; Interpretation of result.
Wherein, applicants studied the combination of TGF-β1receptor blocking-up between concentration, protoscolex concentration and both variable concentrations, each test is all provided with negative control, positive control, blank and technology and repeats, result shows, when protoscolex concentration is 1000/mL-2000/about mL, the best effort concentration of SB-525334 is: 10-20 μm of ol/mL.
Working concentration is adopted to be after the SB-525334 extracorporeal blocking TGF-β1receptor of 10-20 μm of ol/mL, Echinococcus Granulosus Cysts and mouse lymphocyte 37 DEG C, 5%CO
2dual culture 48 h before harvest cell, analyzes group experiment result.Result shows, in TGF-β1receptor blocking-up group, the active acceptor NKG2D of NK cells in mice and the killing activity of NK cell are significantly higher than negative control and blank group, and namely TGF-β1receptor can make the killing activity of the active acceptor NKG2D of mice NK and NK cell recover even to exceed levels found in normal controls after blocking.
In addition, the CD4 of echinococcus group
+t cell reduces, and CD8
+t cell then increases, thus makes CD4
+/ CD8
+the ratio of T reduces, consistent with the result that clinical packages parasitosis patient lymphocytes subgroup is analyzed.But TGF-β1receptor blocking-up group, CD4
+t cell increases, and CD8
+t cell then reduces, thus makes CD4
+/ CD8
+the ratio of T cell is increased to close to normal host CD4
+/ CD8
+the ratio level of T cell.
Finally, CD4
+/ CD25
+the Echinococcus Granulosus Cysts that T cell ratio blocks at TGF-β1receptor and mouse lymphocyte Dual culture group are significantly lower than not blocking TGF-β1receptor group (P < 0.001), and a little higher than blank group, but no significant difference.Namely external echinococcus and mouse lymphocyte Dual culture can make CD4
+cD25
+t cell ratio increases, and after selecting the TGF-β1receptor blocker of aforementioned optimization concentration, host cell CD4
+/ CD25
+t cell ratio drops to normal level.
In sum, the TGF-β1receptor blocker of employing appropriate amount can make the host cell CD4 in Echinococcus granulosus
+cD25
+t cell quantity reduces, CD4
+/ CD8
+t cell ratio raises, the expression of NK cytoactive receptor NKG2D is increased, and make because infecting Echinococcus Granulosus Cysts and downtrod NK cell killing activity is restored, therefore, TGF-β1receptor blocker can be used as preparation treatment echinococcosis and the active drug preventing it to recur clinically, has good potential applicability in clinical practice.
Accompanying drawing explanation
After Fig. 1 shows the external TGF-β1receptor blocking-up of Flow cytometry, Echinococcus Granulosus Cysts is to mice CD4
+cD25
+the impact of T cell.
A: after the external TGF-β1receptor of flow cytomery blocks, Echinococcus Granulosus Cysts is to mice CD4
+cD25
+the streaming result figure of T cell; B:CD4
+cD25
+t cell streaming result statistical analysis figure, PSC+SB group mice CD4
+cD25
+t cell quantity is significantly lower than PSC+PBS group; Note: PSC: protoscolex; SB:TGF-β1receptor blocker (SB-525334); 1640:RPMI-1640 culture medium; *: P < 0.05, * *: P < 0.001.
Fig. 2 is that after the external TGF-β1receptor of Flow cytometry blocks, Echinococcus Granulosus Cysts is on the impact of mouse T cell subgroup.
A: flow cytomery respectively organizes CD4
+/ CD8
+1 streaming result figure of T cell; B: flow cytometer detection respectively organizes CD4
+t cell ratiometric result statistical analysis figure, PSC+SB group is all higher than PBS+PSC group; C: flow cytometer detection respectively organizes CD8
+t cell ratiometric result statistical analysis figure, PSC+SB group is all lower than PSC+PBS group; D respectively organizes CD4
+/ CD8
+t cell ratio result statistical analysis figure, comparatively PBS+PSC group is high for PSC+SB group; Note: PSC: protoscolex; SB:TGF-β1receptor blocker (SB-525334); *: P < 0.05, * *: P < 0.001.
Fig. 3 is that after the external TGF-β1receptor of Flow cytometry blocks, Echinococcus Granulosus Cysts is on the impact of NK cells in mice.
The result figure of A Flow cytometry NK cytoactive receptor NKG2D; B flow cytometer detection respectively organizes NKG2D result statistical analysis figure, and the expression of PSC+SB group is significantly higher than other group; C LDH method detects the statistical analysis figure of each group of NK cells in mice killing activity, and PSC+SB group NK cells in mice killing activity is apparently higher than other group; The correlation analysis of D NK cells in mice killing activity and its active acceptor NKG2D, R2=0.904; Note: PSC: protoscolex; SB:TGF-β1receptor blocker (SB-525334); *: P < 0.05, * *: P < 0.001.
Detailed description of the invention
1. the preparation of Echinococcus Granulosus Cysts protoscolex:
From the Hepar Caprae seu ovis infecting echinococcosis granulosa, aseptic aspiration is without calcification, without infecting, entirely whole single bladder type Echinococcus Granulosus Cysts encapsulation content, be placed in sterile centrifugation tube, protoscolex (Protoscole, PSC) natural sedimentation, again with containing rinsing in 100IU/mL penicillin and the dual anti-aseptic PBS (pH 7.3) of streptomycin 3 times, removing brood capsule fragment makes its natural sedimentation, through 0.5% eosin stains 5min, identify the activated polypide number of tool (> 90%) under the microscope, the protoscolex suspension made containing protoscolex 10000/mL is diluted with containing dual anti-aseptic PBS, for subsequent use.
2 Mouse spleen cells are separated:
De-neck puts to death mice, asepticly wins mouse spleen, scrapes splenocyte with 1 5mL and 1 1mL syringe in containing the little plate of a little PBS.The splenocyte scraped with 1mL syringe pump 3-5 time, makes splenocyte dispersion as far as possible.Add the mouse lymphocyte separating medium of 3mL to 1 new centrifuge tube, then the splenocyte suspension of about 1.5mL is slowly added (V separating medium: V splenocyte suspension=2: 1), 2000r/min, centrifugalize in 20 minutes.Cloud batt layer (buffy coat) in the middle of taking out uses 3mL PBS, 1000r/min, washing in 5 minutes 2-3 time.Finally sedimentation cell is suspended in 1mL1640 liquid.Cell counting, is made into 2-3 × 10
6individual/mL, for subsequent use.
3., after external TGF-β1receptor blocks, Echinococcus Granulosus Cysts and mouse lymphocyte Dual culture divide into groups:
Often group establishes 3 multiple holes, 37 DEG C, 5%CO
2cultivate 48 h before harvest cells, PBS washs 2 times, for the change of flow cytomery T cell subgroup, CD4
+cD25
+the change of T cell, NK cell and active acceptor NKG2D thereof; NK cell killing activity is detected with lactic dehydrogenase enzyme process.
Table 1 Echinococcus Granulosus Cysts and mouse lymphocyte Dual culture divide into groups
4.LDH method detects the killing activity of NK:
Get effector lymphocyte's lymphocyte 1 × 10
7individual/mL and target cell Yac-1 cells 1 × 10
5the each 0.1mL of individual/mL (E: T=100: 1) adds in Tissue Culture Plate, if 3 multiple holes, establish target cell Spontaneous release hole (0.1mL target cell+0.1mL 10%FCS-RPMI-1640 culture fluid) and maximum release aperture (0.1mL target cell+0.1mL1%NP40 liquid) simultaneously, 1000r/min, low-speed centrifugal 2 minutes.Put 37 DEG C, 5%CO
2hatch 2 hours.1000r/min, centrifugal 5 minutes.Drawing each hole supernatant 0.1mL adds in new 96 orifice plates, 37 DEG C, 10 minutes.Every hole adds the LDH substrate solution that 0.1mL newly prepares again, room temperature lucifuge reaction 10 ~ 15 minutes.Add 30 μ l 1m
ol/L citric acid stop buffer stops enzymatic reflection.Enzyme connection monitor reads each hole A value under 570nm wavelength.
Calculate: according to following formulae discovery NK cytoactive:
5. fluidic cell dyeing and detection:
Get 1 × 10
6individual splenocyte, adds mice serum and hatches 15min in each pipe, then adds Anti-Mouse CD49b-FITC (DX-5) respectively, Anti-Mouse CD314-PE (NKG2D) antibody, and at 4 DEG C, lucifuge hatches 30min, carries out padding; PBS washs 1 time, adds 0.5mL PBS re-suspended cell, detects with FACS AriaIII flow cytometer.
6. data analysis:
All data SPSS17.0 software carries out statistical analysis, measurement data employing x ±
srepresent.Compare the t parameter inspection of employing two sample average between two groups, between many groups, compare employing variance analysis.
7. result of the test:
(1), after external TGF-β1receptor blocks, Echinococcus Granulosus Cysts is to Dual culture mouse lymphocyte CD4
+cD25
+the impact of T cell change
Flow cytometry respectively organizes CD4
+cD25
+the change (Fig. 1-A) of T cell, grain echinococcus infected group CD4
+cD25
+t cell quantity comparatively TGF-β1receptor blocker and Echinococcus Granulosus Cysts effect group altogether high; CD4
+cD25
+t cell quantity is in a little higher than PBS+PSC500 group of PBS+PSC1000 group, but no difference of science of statistics; Through q inspection, PBS+PSC group CD4
+cD25
+t cell quantity is significantly higher than PSC+SB group (Fig. 1-B, P < 0.001), namely after to TGF-β1receptor specific inhibition, and CD4
+cD25
+t cell quantity significantly declines and close to the quantity of normal group.
After being blocked by external TGF-β1receptor, Echinococcus Granulosus Cysts and mouse lymphocyte Dual culture, flow cytomery CD4
+cD25
+the ratio change of T cell.Result is pointed out, CD4
+cD25
+the Echinococcus Granulosus Cysts that T cell ratio blocks at TGF-β1receptor and mouse lymphocyte Dual culture group are significantly lower than not blocking TGF-β1receptor group (P < 0.001), and a little higher than blank group (1640 groups), but no significant difference.Namely external echinococcus and mouse lymphocyte Dual culture can make CD4
+cD25
+t cell ratio increases, and after the blocking-up of TGF-β1receptor, can make CD4
+cD25
+t cell ratio drops to normal level.
(2), after external TGF-β1receptor blocks, Echinococcus Granulosus Cysts is on the impact of T lymphocyte subsets in spleen of mice immunized
I. after extracorporeal blocking TGF-β1receptor, the mice CD4 of Echinococcus Granulosus Cysts mediation
+t cell quantity raises
CD4 after the external TGF-β1receptor of Flow cytometry blocks
+the change (Fig. 2-A) of T cell ratio.Streaming result shows each group of CD4
+t cell ratio, TGF-β1receptor blocker processed group (SB+PSC group) is higher than echinococcus group (PBS+PSC group), finds that SB+PSC group is all significantly higher than PBS+PSC group (P < 0.05) through statistical analysis.SB+PSC1000 group CD4
+t cell ratio is the highest, is significantly higher than other groups.
II. after extracorporeal blocking TGF-β1receptor, the mice CD8 of Echinococcus Granulosus Cysts mediation
+t cell quantity reduces
CD8 after the external TGF-β1receptor of Flow cytometry blocks
+the change (Fig. 2-B) of T cell ratio.Result shows, in TGF-β1receptor blocker processed group (SB+PSC group) lower than echinococcus group (PBS+PSC), and SB+PSC1000 group CD8
+t cell ratio is minimum; Through statistical analysis, SB+PSC1000 group CD8+T cell proportion significantly lower than PBS+PSC group, SB+PSC500 group and other organize difference significantly (Fig. 2-C, P < 0.05).
III., after external TGF-β1receptor blocks, Echinococcus Granulosus Cysts is to mice CD4
+/ CD8
+the ratio of T cell increases
Flow cytometry respectively organizes mice CD4
+/ CD8
+the change (Fig. 2-A) of T cell ratio, CD4
+/ CD8
+t cell ratio, the highest in SB+PSC1000 group, PBS+PSC500 group is minimum, through statistical analysis, SB+PSC group CD4
+/ CD8
+t cell ratio is significantly higher than PBS+PSC group (Fig. 2-D, P < 0.05).
This experiment utilizes flow cytomery respectively to organize the change of T cell subgroup, the CD4 of echinococcus group
+t cell reduces, and CD8
+t cell is then once many, thus makes CD4
+/ CD8
+the ratio of T reduces, consistent with the result that clinical packages parasitosis patient lymphocytes subgroup is analyzed.But TGF-β1receptor blocking-up group, CD4
+t cell is once many, and CD8
+t cell then reduces, thus makes CD4
+/ CD8
+the ratio of T increases, and contributes to stoping or control Echinococcus Granulosus Cysts at machine tumor growth.
(3), after external TGF-β1receptor blocks, Echinococcus Granulosus Cysts is on the impact of NK cells in mice
I., after extracorporeal blocking TGF-β1receptor, the expression of the Dual culture NK cells in mice active acceptor NKG2D of Echinococcus Granulosus Cysts mediation increases
Flow cytometry respectively organizes the expression (Fig. 3-A) of NK cells in mice active acceptor NKG2D.The expression of NK cells in mice active acceptor NKG2D is expressed higher than Echinococcus Granulosus Cysts group at TGF-β1receptor blocker and Echinococcus Granulosus Cysts effect group altogether; The expression of the active acceptor NKG2D of NK cell is significantly higher than PBS+SB group in PBS+PSC group, and PBS+PSC1000 group is the highest, is significantly higher than other groups (Fig. 3-B, P < 0.05); Namely, after to TGF-β1receptor specific inhibition, the expression of the active acceptor NKG2D of NK cell significantly increases.
II., after extracorporeal blocking TGF-β1receptor, the cleavage rate of the target cell Yac-1 of Echinococcus Granulosus Cysts mediation increases
The cleavage rate (NK cell killing activity) of each group of NK cell to target cell Yac-1 cell is detected with lactic dehydrogenase enzyme process (LDH), from the visible NK cells in mice of Fig. 3 C to the cleavage rate of target cell, PBS+PSC group and 1640 groups lower, and the NK cell killing activity of (SB+PSC group) increases after TGF-β1receptor is by specific inhibition; Find that the NK cell killing activity of TGF-β1receptor blocking-up group (SB+PSC) is significantly higher than other groups (Fig. 3-C) respectively through statistical analysis, the a little higher than SB+PSC500 group of NK cell killing activity of SB+PSC1000 group, but no difference of science of statistics.
III. after extracorporeal blocking TGF-β1receptor, the correlation analysis of Echinococcus Granulosus Cysts and active acceptor NKG2D active to Dual culture NK cells in mice
Correlation analysis is carried out to the activity of each group of NK cells in mice and the expression of results of active acceptor NKG2D thereof, result shows, the killing activity of each group of NK cells in mice and the expression of its active acceptor NKG2D are proportionate, coefficient R 2=0.904 (Fig. 3-D).
This experiment shows, echinococcus group, and the active acceptor NKG2D of NK cells in mice is consistent with normal level with the killing activity of NK cell, then NK cells in mice killing activity may not be activated or receptor suppression; And in TGF-β1receptor blocking-up group, the active acceptor NKG2D of NK cells in mice and the killing activity of NK cell are significantly higher than echinococcus group and 1640 groups, and namely TGF-β1receptor can make the active acceptor NKG2D of mice NK and the killing activity of NK cell recover after blocking.
In sum, suppress Echinococcus Granulosus Cysts to the immune evasion of host in infection by TGF-β1receptor blocker, cause CD4
+cD25
+t cell quantity reduces and CD4
+/ CD8
+t cell ratio raises, and the expression of NK cytoactive receptor NKG2D is increased, and the NK cell killing activity be suppressed is restored.Above-mentioned result of the test shows, TGF-β1receptor blocker is adopted to suppress Echinococcus Granulosus Cysts to the immune evasion of host in infection, effectively can strengthen the inhibitory action of host to Echinococcus granulosus, the method can be effective to treat echinococcosis, has good potential applicability in clinical practice.
Claims (4)
1.TGF-β1receptor blocker is applied in the medicine of preparation treatment echinococcosis, it is characterized in that, comprises and apply TGF-β1receptor blocker to the host in Echinococcus granulosus.
2. the method for claim 1, is characterized in that, described TGF-β1receptor blocker is SB-431542, SB-505124 or SB-525334.
3. method as claimed in claim 2, it is characterized in that, described TGF-β1receptor blocker is SB525334, and its working concentration is 10-20 μm of ol/mL.
4. method as claimed in claim 3, it is characterized in that, described host cell concentration is: 5 × 10
5-5 × 10
6individual/mL, Echinococcus Granulosus Cysts protoscolex concentration is: 1000-4000/ml.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105902526A (en) * | 2016-05-06 | 2016-08-31 | 兰州大学 | Application of Masoprocol in preparing drug for treating echinococcosis |
| CN106074564A (en) * | 2016-07-04 | 2016-11-09 | 中国疾病预防控制中心寄生虫病预防控制所 | Ursolic acid application in preparing anti-hydatid drugs |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101475938A (en) * | 2009-01-07 | 2009-07-08 | 新疆医科大学 | Echinococcosis antigen gene (egG1Y162 antigen gene), and recombinant protein and use thereof |
| CN103038343A (en) * | 2010-03-23 | 2013-04-10 | 英特瑞克斯顿股份有限公司 | Vectors conditionally expressing therapeutic proteins, host cells comprising the vectors, and uses thereof. |
| CN102309757B (en) * | 2010-07-09 | 2014-09-17 | 中国科学院上海巴斯德研究所 | Novel regulatory factor of FOXP3 and regulatory T cells, and use thereof |
| CN104490886A (en) * | 2014-10-23 | 2015-04-08 | 陈雪玲 | Use of TGF-beta 1 receptor blocker in preparation of drugs for preventing echinococcosis recurrence |
-
2015
- 2015-05-15 CN CN201510245580.5A patent/CN104906104A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101475938A (en) * | 2009-01-07 | 2009-07-08 | 新疆医科大学 | Echinococcosis antigen gene (egG1Y162 antigen gene), and recombinant protein and use thereof |
| CN103038343A (en) * | 2010-03-23 | 2013-04-10 | 英特瑞克斯顿股份有限公司 | Vectors conditionally expressing therapeutic proteins, host cells comprising the vectors, and uses thereof. |
| CN102309757B (en) * | 2010-07-09 | 2014-09-17 | 中国科学院上海巴斯德研究所 | Novel regulatory factor of FOXP3 and regulatory T cells, and use thereof |
| CN104490886A (en) * | 2014-10-23 | 2015-04-08 | 陈雪玲 | Use of TGF-beta 1 receptor blocker in preparation of drugs for preventing echinococcosis recurrence |
Non-Patent Citations (4)
| Title |
|---|
| 印双红等: "小鼠细粒棘球蚴感染早期对NK细胞影响的初步研究", 《中国免疫学杂志》 * |
| 吴向未等: "TGF-β、TNF-α mRNA在肝包虫囊肿周围人体纤维囊壁中的特异性分层表达", 《中国地方病学杂志》 * |
| 陈小林等: "原头蚴及囊液促体外培养小鼠脾细胞TGF-β表达的研究", 《中国病原生物学杂志》 * |
| 陈小林等: "细粒棘球蚴囊对体外培养小鼠T淋巴细胞影响的初步研究", 《中国免疫学杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105902526A (en) * | 2016-05-06 | 2016-08-31 | 兰州大学 | Application of Masoprocol in preparing drug for treating echinococcosis |
| CN106074564A (en) * | 2016-07-04 | 2016-11-09 | 中国疾病预防控制中心寄生虫病预防控制所 | Ursolic acid application in preparing anti-hydatid drugs |
| CN106074564B (en) * | 2016-07-04 | 2019-04-09 | 中国疾病预防控制中心寄生虫病预防控制所 | Ursolic acid is preparing the application in anti-hydatid drugs |
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