Evaluation of the Effect of Low-dose Aspirin on the Prevention of Preterm Delivery in Women with a History of Spontaneous Preterm Delivery / Avaliação do efeito da aspirina em baixa dose na prevenção do parto prematuro em mulheres com história de parto prematuro espontâneo

Abstract Objective Currently, uteroplacental vascular disorders are considered one of the main mechanisms of spontaneous preterm delivery (PTD). Low-dose aspirin is used to prevent pre-eclampsia, which has a similar mechanism; hence, the present study aimed to investigate the effect of low-dose aspirin on the prevention of PTD in women with a history of spontaneous PTD. Methods The present pilot randomized clinical trial was conducted on 54 pregnant women in the aspirin group (taking 80 mg daily until the 36th week and classic treatment) and 53 patients in the control group (only receiving classic treatment). Results Forty-three patients (40%) presented before 37 weeks due to symptoms of PTL. Preterm delivery (< 37 weeks) occurred in 28 patients (26%), and there was no significant difference between the aspirin and control groups (10 patients [19%] and 18 patients [34%], respectively; p = 0.069). The time of preterm delivery was early (< 34 weeks) in 6 patients (21%), and its cause was spontaneous labor in 23 patients (82%) which was not significantly different between the two groups (p > 0.05). Out of 40 patients with spontaneous labor, 25 patients (63%) had a PTD, which was significantly lower in the aspirin group than in the control group (9 patients [45%] versus 16 patients [80%], respectively; p = 0.022). Conclusion The findings of the present study demonstrated that despite the reduction in the incidence of PTD using low-dose aspirin, the reduction rate was not statistically significant. On the other hand, in patients with spontaneous labor prone to PTD, aspirin was effective in reducing the incidence of PTD.

Resumo Objetivo Atualmente, os distúrbios vasculares uteroplacentários são considerados um dos principais mecanismos de parto prematuro espontâneo (PTD). A aspirina em baixa dose é usada para prevenir a pré-eclâmpsia, que tem um mecanismo semelhante; portanto, o presente estudo teve como objetivo investigar o efeito da aspirina em baixa dosagem na prevenção de PTD em mulheres com história de PTD espontâneo. Métodos O presente ensaio clínico piloto randomizado foi realizado em 54 gestantes do grupo aspirina (tomando 80 mg diários até a 36ª semana e tratamento clássico) e 53 pacientes do grupo controle (somente tratamento clássico). Resultados Quarenta e três pacientes (40%) apresentaram-se antes de 37 semanas devido a sintomas de PTL. O parto prematuro (< 37 semanas) ocorreu em 28 pacientes (26%) e não houve diferença significativa entre os grupos aspirina e controle (10 pacientes [19%] e 18 pacientes [34%], respectivamente; p = 0,069). O tempo de parto prematuro foi precoce (< 34 semanas) em 6 pacientes (21%) e sua causa foi trabalho de parto espontâneo em 23 pacientes (82%) que não foi significativamente diferente entre os dois grupos (p > 0,05). Das 40 pacientes com trabalho de parto espontâneo, 25 pacientes (63%) tiveram PTD, que foi significativamente menor no grupo aspirina do que no grupo controle (9 pacientes [45%] versus 16 pacientes [80%], respectivamente; p = 0,022). Conclusão Os achados do presente estudo demonstraram que, apesar da redução na incidência de DPT com o uso de aspirina em baixa dosagem, a taxa de redução não foi estatisticamente significativa. Por outro lado, em pacientes com trabalho de parto espontâneo propensas a PTD, a aspirina foi eficaz na redução da incidência de PTD.

Penetration ability and biological activity of fusion protein PTD4-Cu, Zn-SOD in human astrocytes in vitro by immunofluorescence test / 西安交通大学学报(医学版)

【Objective】 To observe the penetration and biological activity of PTD4-Cu, Zn-SOD into human astrocytes and whether it can mitigate hypoxia damages. 【Methods】 ①Immunohistochemistry and fluorescence test: We labeled the Cu, Zn-SOD by a monoclonal antibody, combined it with the fluorescent secondary antibody labeled with fluorescein isothiocyanate (FITC) to observe the effect of transduced PTD4-Cu, Zn-SOD on the viability of human astrocytes. ② The experimental group: After hypoxic damage model, the cells were divided into three groups: blank control, group Cu, Zn-SOD, and group PTD4-Cu, Zn-SOD. Group blank was added with DMEM medium (excluding serum) as control; DMEM medium was added to the other two for one hour (excluding serum) with its fusion proteins (Cu, Zn-SOD and PTD4 -Cu, Zn-SOD) with the final concentration of 2 μmoL/L. After the intervention, we used SOD and MDA test kits to observe PTD4-Cu, Zn-SOD and Cu, Zn-SOD in astrocytes after fusion protein intervention. 【Results】 The PTD4-Cu, Zn-SOD fusion protein could have aggregation distribution in the nucleus by FITC fluorescently labeled. After the intervention, it could increase the SOD activity in astrocytes in group PTD4-Cu, Zn-SOD and group Cu, Zn-SOD compared with control group, but the SOD activity was more obvious in the fusion proteins PTD4-Cu, Zn-SOD group. And the dose of MDA was reduced in group PTD4-Cu, Zn-SOD compared with group Cu, Zn-SOD and control group. 【Conclusion】 PTD4-Cu, Zn-SOD fusion protein can transcellular membrane of human astrocytes. The fusion protein PTD4-Cu, Zn-SOD can increase the SOD activity and reduce the content of MDA by human astrocytes from hypoxia injury.

PTD-mFoxp3 fusion protein induces mixed chimerism and reduces the incidence of graft-versus-host disease / 中华器官移植杂志

Objective To establish a stable transplantation tolerance model by combined treatment with PTD-mFoxp3 fusion protein and allogeneic bone marrow transplantation and study its application to reduce the incidence of graft-versus-host disease (GVHD).Method BALB/c mice as recipients were randomly divided into four groups,accepted medical linear accelerator ray 3.0-Gy total body irradiation (TBI) before bone marrow transplantation (BMT),and injected with donor C57BL/6 mice bone marrow cells 3 × 107withinn 4-6 h.The BALB/c mice in group A were given PTD-mFoxp3 fusion protein through tail vein intermittently (day-2,0,1,3,5,7,9,11,13),those in group B given the same dose mFoxp3 protein,those in group C given normal saline,and those in blank control group given no treatment.The symptoms of GVHD were observed after BMT.Chimerisms were determined on the week 1,2,4,8 and12 post-BMT by flow cytometry.Liver and intestinal tissues were collected for pathological examination.Recipient immune response was assessed on the week 4 and 12 by mixed lymphocyte reactions (MLR) after BMT.Results The chimerism level in group A was high [(38.16 ± 3.09) ％] in the first 12 weeks after BMT,and that in group B and group C was reduced [(20.12 ± 4.75) ％ and (15.72 ± 2.36) ％ respectively,P＜0.05].MLR revealed that shown lymphocyte donor-derived lymphocyte proliferation rate at 4th and 12th week in group A was significantly lower than in other groups (P＜0.05).Pathological examination showed infiltration of lymphocytes in the liver and intestine was milder in group A than in other groups.Conclusion PTD-mFoxp3 fusion protein combined with allogeneic bone marrow transplantation can effectively establish a stable transplantation chimeric model and reduce the incidence of GVHD.

Poliovirus-derived CTL-inducing Hepatitis C Vaccine by Modification of RPS-Vax with Protein Transduction Domain

We have reported RPS-Vax system by introducing multiple cloning site (MCS) and 3C-protease cutting site at the N-terminal end of the poliovirus Sabin 1 cDNA. Potential vaccine genes can be easily introduced into recombinant polioviral genome and expressed during the viral replication as a part of virus polyprotein and subsequently processed from the mature viral protein by the poliovirus-specific 3C-protease. However, these poliovirus vector-mediated chimeric viral vaccine was not efficient to induce the cell-mediated immunity because of its rapid cytolytic capacity. In order to make CTL-inducing vaccine vector, we integrated a protein transduction domain (PTD) into the pRPS-Vax vector system right ahead of the MCS, named RPS-Vax/PTD. We have incorporated the HCV core (N-terminal 100aa) antigen into the MCS of pRPSvax-PTD vector, followed by production of chimeric virus, named RPSvax-PTD/HCVc. The chimeric virus was genetically stable during the serial passages. Replication capacity of the RPSvax-PTD/HCVc was 1~2 log lower than that of RPS-Vax control virus. These chimeric virus was very efficient to inducing antigen-specific IgG2a in the immunized mice, implying that the recombinant virus has a capacity to induce HCV-specific Th1 type immunity in the immunized animals or humans.

Poliovirus-derived CTL-inducing Hepatitis C Vaccine by Modification of RPS-Vax with Protein Transduction Domain

We have reported RPS-Vax system by introducing multiple cloning site (MCS) and 3C-protease cutting site at the N-terminal end of the poliovirus Sabin 1 cDNA. Potential vaccine genes can be easily introduced into recombinant polioviral genome and expressed during the viral replication as a part of virus polyprotein and subsequently processed from the mature viral protein by the poliovirus-specific 3C-protease. However, these poliovirus vector-mediated chimeric viral vaccine was not efficient to induce the cell-mediated immunity because of its rapid cytolytic capacity. In order to make CTL-inducing vaccine vector, we integrated a protein transduction domain (PTD) into the pRPS-Vax vector system right ahead of the MCS, named RPS-Vax/PTD. We have incorporated the HCV core (N-terminal 100aa) antigen into the MCS of pRPSvax-PTD vector, followed by production of chimeric virus, named RPSvax-PTD/HCVc. The chimeric virus was genetically stable during the serial passages. Replication capacity of the RPSvax-PTD/HCVc was 1~2 log lower than that of RPS-Vax control virus. These chimeric virus was very efficient to inducing antigen-specific IgG2a in the immunized mice, implying that the recombinant virus has a capacity to induce HCV-specific Th1 type immunity in the immunized animals or humans.