Effect of Liuweibuqi capsule, a Chinese patent medicine, on the JAK1/STAT3 pathway and MMP9/TIMP1 in a chronic obstructive pulmonary disease rat model

AbstractObjectiveTo observe effect of Liuweibuqi Capsule, a Traditional Chinese Medicine (TCM), on the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and matrix metalloproteinases (MMPs) in a chronic obstructive pulmonary disease (COPD) rat model with lung deficiency in terms of TCM's pattern differentiation.MethodsRats were randomly divided into a normal group, model group, Liuweibuqi group, Jinshuibao group, and spleen aminopeptidase group (n= 10). Aside from the normal group, all rats were exposed to smoke plus lipopolysaccharide tracheal instillation to establish the COPD model with lung deficiency. Models were established after 28 days and then the normal and model groups were given normal saline (0.09 g/kg), Liuweibuqi group was given Liuweibuqi capsule (0.35 g/kg), Jinshuibao group was given Jinshuibao capsules (0.495 g/kg), and the spleen group was given spleen aminopeptidase (0.33 mg/kg), once a day for 30 days. Changes in symptoms, signs, and lung histology were observed. Lung function was measured with a spirometer. Serum cytokines were detected using enzyme-linked immunosorbent assay, and changes in the JAK/STAT pathway, MMP-9, and MMPs inhibitor 1 (TIMP1) were detected by immunohistochemistry, RT-PCR, and western blotting, respectively.ResultsCompared with the normal group, lung tissue was damaged, and lung function was reduced in the model control group. Additionally, the levels of interleukin (IL)-1β, γ interferon (IFN-γ), and IL-6 were higher, while IL-4 and IL-10 were lower in the model control group than those in the normal group. The expressions of JAK1, STAT3, p-STAT3, and MMP-9 mRNA and protein in lung tissue were higher, and TIMP1 mRNA and protein was lower in the model group compared with the normal group. After treatment, compared with the model group, the expression of inflammatory cytokines was lower in each treatment group, and expressions of JAK/STAT pathway, MMPs were lower. Compared with the positive control groups, the Jinshuibao and spleen aminopeptidase groups, lung function was better, and JAK1, STAT3, and p-STAT3 protein were lower and TIMP1 was higher in the Liuweibuqi group.ConclusionLiuweibuqi capsules can improve the symptoms of COPD possibly by regulating the expression of the JAK1/STAT3 pathway and MMP9/TIMP1

Transplantation of human villous trophoblasts preserves cardiac function in mice with acute myocardial infarction

Over the past decade, cell therapies have provided promising strategies for the treatment of ischaemic cardiomyopathy. Particularly, the beneficial effects of stem cells, including bone marrow stem cells (BMSCs), endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), have been demonstrated by substantial preclinical and clinical studies. Nevertheless stem cell therapy is not always safe and effective. Hence, there is an urgent need for alternative sources of cells to promote cardiac regeneration. Human villous trophoblasts (HVTs) play key roles in embryonic implantation and placentation. In this study, we show that HVTs can promote tube formation of human umbilical vein endothelial cells (HUVECs) on Matrigel and enhance the resistance of neonatal rat cardiomyocytes (NRCMs) to oxidative stress in vitro. Delivery of HVTs to ischaemic area of heart preserved cardiac function and reduced fibrosis in a mouse model of acute myocardial infarction (AMI). Histological analysis revealed that transplantation of HVTs promoted angiogenesis in AMI mouse hearts. In addition, our data indicate that HVTs exert their therapeutic benefit through paracrine mechanisms. Meanwhile, injection of HVTs to mouse hearts did not elicit severe immune response. Taken together, our study demonstrates HVT may be used as a source for cell therapy or a tool to study cell-derived soluble factors for AMI treatment

A Regenerative Cardiac Patch Formed by Spray Painting of Biomaterials onto the Heart

Layering a regenerative polymer scaffold on the surface of the heart, termed as a cardiac patch, has been proven to be effective in preserving cardiac function after myocardial infarction (MI). However, the placement of such a patch on the heart usually needs open-chest surgery, which is traumatic, therefore prevents the translation of this strategy into the clinic. We sought to device a way to apply a cardiac patch by spray painting in situ polymerizable biomaterials onto the heart with a minimally invasive procedure. To prove the concept, we used platelet fibrin gel as the “paint” material in a mouse model of MI. The use of the spraying system allowed for placement of a uniform cardiac patch on the heart in a mini-invasive manner without the need for sutures or glue. The spray treatment promoted cardiac repair and attenuated cardiac dysfunction after MI

Therapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome

Stem cell therapy represents a promising strategy in regenerative medicine. However, cells need to be carefully preserved and processed before usage. In addition, cell transplantation carries immunogenicity and/or tumourigenicity risks. Mounting lines of evidence indicate that stem cells exert their beneficial effects mainly through secretion (of regenerative factors) and membrane-based cell–cell interaction with the injured cells. Here, we fabricate a synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. In conclusion, CMMPs act as ‘synthetic stem cells’ which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration

Cardiac regenerative potential of cardiosphere-derived cells from adult dog hearts

The regenerative potential of cardiosphere-derived cells (CDCs) for ischaemic heart disease has been demonstrated in mice, rats, pigs and a recently completed clinical trial. The regenerative potential of CDCs from dog hearts has yet to be tested. Here, we show that canine CDCs can be produced from adult dog hearts. These cells display similar phenotypes in comparison to previously studied CDCs derived from rodents and human beings. Canine CDCs can differentiate into cardiomyocytes, smooth muscle cells and endothelial cells in vitro. In addition, conditioned media from canine CDCs promote angiogenesis but inhibit cardiomyocyte death. In a doxorubicin-induced mouse model of dilated cardiomyopathy (DCM), intravenous infusion of canine CDCs improves cardiac function and decreases cardiac fibrosis. Histology revealed that injected canine CDCs engraft in the mouse heart and increase capillary density. Out study demonstrates the regenerative potential of canine CDCs in a mouse model of DCM

Cardiac regenerative potential of cardiosphere-derived cells from adult dog hearts

The regenerative potential of cardiosphere-derived cells (CDCs) for ischaemic heart disease has been demonstrated in mice, rats, pigs and a recently completed clinical trial. The regenerative potential of CDCs from dog hearts has yet to be tested. Here, we show that canine CDCs can be produced from adult dog hearts. These cells display similar phenotypes in comparison to previously studied CDCs derived from rodents and human beings. Canine CDCs can differentiate into cardiomyocytes, smooth muscle cells and endothelial cells in vitro. In addition, conditioned media from canine CDCs promote angiogenesis but inhibit cardiomyocyte death. In a doxorubicin-induced mouse model of dilated cardiomyopathy (DCM), intravenous infusion of canine CDCs improves cardiac function and decreases cardiac fibrosis. Histology revealed that injected canine CDCs engraft in the mouse heart and increase capillary density. Out study demonstrates the regenerative potential of canine CDCs in a mouse model of DCM

Rapid and Efficient Production of Coronary Artery Ligation and Myocardial Infarction in Mice Using Surgical Clips

AimsThe coronary artery ligation model in rodents mimics human myocardial infarction (MI). Normally mechanical ventilation and prolonged anesthesia period are needed. Recently, a method has been developed to create MI by popping-out the heart (without ventilation) followed by immediate suture ligation. Mortality is high due to the time-consuming suture ligation process while the heart is exposed. We sought to improve this method and reduce mortality by rapid coronary ligation using a surgical clip instead of a suture.Methods and ResultsMice were randomized into 3 groups: clip MI (CMI), suture MI (SMI), or sham (SHAM). In all groups, heart was manually exposed without intubation through a small incision on the chest wall. Unlike the conventional SMI method, mice in the CMI group received a metal clip on left anterior descending artery (LAD), quickly dispensed by an AutoSuture Surgiclip™. The CMI method took only 1/3 of ligation time of the standard SMI method and improved post-MI survival rate. TTC staining and Masson’s trichrome staining revealed a similar degree of infarct size in the SMI and CMI groups. Echocardiograph confirmed that both SMI and CMI groups had a similar reduction of ejection fraction and fraction shortening over the time. Histological analysis showed that the numbers of CD68+ macrophages and apoptotic cells (TUNEL-positive) are indistinguishable between the two groups.ConclusionThis new method, taking only less than 3 minutes to complete, represents an efficient myocardial infarction model in rodents

The joint inversion of regional water reserve changes in the Qinghai-Tibet Plateau based on GRACE RL06 and TRMM data

In the past decade, independent component analysis (ICA) has been gradually introduced into the component extraction of Earth's time-varying gravity field. Because of the independence of the extracted components, ICA solves the key problem that the extracted components are only irrelevant when using principal component analysis (PCA). The FastICA algorithm based on negative entropy is a common ICA method. The algorithm converges faster than the gradient algorithm, and the robustness of negative entropy is better. In this paper, the above algorithm is used to explore the relationship between the water storage components and precipitation components of the Qinghai-Tibet Plateau. The research indicates that there is a 7-month delay effect on the changes in water reserves on the Plateau compared to precipitation. It shows that in addition to seasonal frozen soils and glaciers, and the precipitation from the monsoon climate, there are also objective delays caused by regional water exchange. In view of the characteristic signals, the changes in annual average water reserves between central Qinghai, western Tibet, and central and eastern Tibet have reversed. It is pointed out that in the context of accelerated melting of frozen soil and glaciers caused by global warming, the regional water reserve changes due to different climate and flow regions. In addition, the changes of water reserves in the above areas are also different due to the north and south plate tectonics of the Qinghai-Tibet Plateau. Therefore, through the above studies, the feasibility of using the FastICA algorithm to analyze changes in regional water reserve components and their related factors on a large scale has been proven

Error Factor and Mathematical Model of Positioning with Odometer Wheel

High positioning accuracy with odometer wheel is of great importance for internal pipeline defect detection. In current research, the qualitative analysis is focused on and the accumulation characteristics of positioning errors are not shown. Based on this, the models and the accumulation characteristics of positioning errors are investigated in this paper. The errors are classified into systematic errors and random errors. Systematic errors consist of difference between actual and nominal diameters, diameter difference among wheels, and terminal error. Random errors consist of initial point error, weld error, and oversized clearance. The mathematical models of the errors are obtained by the methods of quantitative analysis and contrastive analysis. Through calculation examples, the results show the relationship of the errors and the effect of each error on total error. Diameter calibration and detection in sections are proposed to improve the positioning accuracy

Coseismic Deformation and Fault Inversion of the 2017 Jiuzhaigou Ms 7.0 Earthquake: Constraints from Steerable Pyramid and InSAR Observations

The 8 August 2017 Ms 7.0 Jiuzhaigou earthquake was generated in the transition zone between the Tazang fault, Huya fault, and Minjiang fault, all being part of the East Kunlun fault system. In this study, two pairs of SAR (synthetic aperture radar) data from Sentinel-1 satellite were used to derive the surface displacement observations along the satellite line-of-sight (LOS) directions using the differential interferometric SAR (D-InSAR) method. A steerable pyramid filtering method (i.e., a method for a linear multiscale, multidirectional decomposition and filtering technology) was proposed to optimize and enhance the geological features from interferometric image and coseismic deformation field. The 3D deformation was derived under the constraint of the combined D-InSAR and MAI method. The small baseline subset InSAR (SBAS-InSAR) time series method was used to obtain the cumulative deformation across the fault system. Fault slip inversion results from interferogram of InSAR indicate that the 2017 Jiuzhaigou earthquake was dominated by left-lateral slip, the surface movement was dominated by horizontal deformation, the vertical deformation was small, and the coseismic deformation variable in the east–west direction was the largest, with a maximum deformation of 0.2 m to the east and 0.14 m to the west. The maximum slip is about 77 cm, which is located at a depth of 9 km. The moment magnitude obtained by inversion is Mw 6.6, and the seismic fault is the Huya fault