Background: Stroke is one of the leading causes of death around the world. The sequelae of ischemic stroke cause drastic effects on the quality of life for patients. Sanwujiaowan (SWJW) is a mixture prepared with 5 herbal medicines (Aconiti Lateralis Radix Praeparata, Aconiti Kusnezoffii Radix, Polygoni Multiflori Radix, Aconiti Radix, and Olibanum), with a long history of application in treating the sequelae of stroke. Objectives: To provide evidence and decipher the mechanism of SWJW in alleviating stroke. Materials and methods: In this article, we expanded the indicators of SWJW by an integrated strategy based on signature metabolomics, target proteins, and bioinformatics and probed into the mechanism of SWJW intervention in ischemic stroke in a rat model. Results: The results indicated that SWJW protected rats from nerve damage during the acute phase of ischemic stroke by regulating tau phosphorylation via the PI3K/Akt pathway. Conclusions: This study, for the first time, proved that the reduction of phosphorylated tau was harmful for the neural function in the acute phase of ischemic stroke. Meanwhile, the pathological changes of phosphorylated tau proteins were detected in stroke and recalled by SWJW. This finding may provide a new reference for formulating treatment strategies for the acute phase of ischemic stroke.

Background: Heart failure (HF) is the leading cause of death worldwide. Myocardial infarction (MI) is a major contributor to HF. Shengmai injection (SMI) has exhibited protective efficacy in preventing HF. However, the advantages of SMI in the progression of MI-induced HF remain unclear. Objective: To reveal the advantages of SMI in the progression of MI-induced HF. Methods: The differently expressed proteins in rat models with ischemia at the 7th, 14th, 21st, and 28th days were obtained from PubMed. The “compound-target” network of SMI was constructed via the Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine database. The protein-protein interaction relationship was constructed, and biological function was applied to evaluate the advantage effect of SMI in the progression of MI-induced HF. In addition, the prediction results were validated in rats with left anterior descending coronary artery ligation. The cardiac function and heart performance were observed via echocardiography, hematoxylin-eosin staining, and Masson staining, and the levels of procollagen type I carboxy-terminal propeptide, recombinant versican (VCAN), and collagen 1A1 (COL1A1) weremeasured via enzyme-linked immunosorbent assay in rat plasma. In vitro, H9c2 cells were treated with Angiotensin II (Ang II), and the cell viability, the level of reactive oxygen species (ROS) and Ca , and the expression of ANP and connective tissue growth factor were evaluated. Furthermore, the schizandrin A was identified as one of the possible key compounds. After schizandrin A treatment, the level of ROS and Ca and the expression of COL1A1 and VCAN were evaluated. Results: There were 189 compounds and 1612 targets involved in the “compound-target” network, and an interaction relationship was constructed. According to the top subnetwork, the Gene Ontology annotation revealed that SMI may have an antifibrotic and cardiac protective effect against MI-induced HF. In rats, SMI increased ejection fraction, left ventricular fractional shortening, and cardiac output and decreased fibrosis injury; moreover, SMI decreased the levels of procollagen type I carboxy-terminal propeptide, VCAN, and COL1A1 within 35 days. When compared with the Ang II treatment group, SMI increased cell viability and decreased cellular calcium concentration, ROS generation, and the expression of ANP and connective tissue growth factor in vitro. Furthermore, schizandrin A was discovered to be a possible compound in myocardial protection. Schizandrin A increased cell viability after Ang II treatment while decreasing COL1A1 and VCAN levels. Conclusions: This method demonstrates that SMI has an antifibrotic effect. This study provides a promising perspective on translating omics data to clinical applications, as well as an appealing approach to investigating the precise intervention of a multicomponent drug.

Objective To investigate the effect of bone marrow mesenchymal stem cells(BMSCs)on the inflamma-tory response of lipopolysaccharide(LPS)induced acute lung injury(ALI)in mice.Methods 32 SPF KM mice,aged 4 weeks were randomly divided into four groups,control group,LPS group,dexamethasone treatment group(LPS+DEX)and BMSCs treatment group(LPS+BMSCs).The latter three groups were injected with LPS by tra-cheal puncture to establish mouse ALI model 24 h after modeling,BMSCs isolated from the femur of mice were in-jected into the caudal vein,and DEX were injected into caudal vein at the same time in LPS+DEX group for 3 consecutive days.On the 4th day after cell transplantation or 24 h after DEX injection,the survival quantity of mice was recorded,lung function was detected,and the wet/dry weight ratio(W/D)of lung was measured.Then in-flammatory cells in bronchoalveolar lavage fluid(BALF),lung pathological changes and serum inflammatory cyto-kines were collected.Green fluorescent protein(GFP)staining was used to observe the homing of BMSCs in lung tissues.The mRNA and protein expression of TLR4,MyD88 and NF-κB in lung tissues were detected by RT-PCR and Western blot assay respectively.Results Compared with the control group,LPS model group showed de-creased lung function,significantly increase in the W/D weight ratio of lung,inflammatory cytokines in serum and inflammatory cells in BALF,and severe damage in lung tissue.Compared with LPS group,LPS+DEX group and LPS+BMSCs group showed improved lung function,reduced lung tissue damage,significantly decrease in the W/D weight ratio of lung,inflammatory cytokines in serum and inflammatory cells in BALF.And the expression of TLR4-MyD88-NF-κB signaling pathway-related genes and proteins decreased,the survival quantity increased.Conclusion Homologous BMSCs transplantation can effectively treat LPS-induced acute lung injury,and the mechanism may be related to the regulation of TLR4-MyD88-NF-κB signaling pathway and the reduction of inflam-matory response.These findings provide the experimental basis for BMSCs homologous transplantation for ALI.

Objective:To investigate whether the cyclosporin A (CsA) can improve the blastocyst implantation with mild impaired of trophoblast cells of mice.Methods:1) Totally 30 ICR mice were intraperitoneally injected with 5 mg/kg CsA, then the blood concentrations of CsA in mice were detected at 1 h, 3 h, 4 h, 6 h, 8 h, 10 h, 13 h, 14 h, 16 h and 20 h after administration using chemiluminescence method. 2) A total of 36 mice were randomly divided into control group and experimental group (CsA group); the experimental group was intraperitoneally injected with 5 mg/kg CsA and control group was injected with the equivalent dose olive oil of the same body weight. Embryos were classified into A, B, C types according to the guidelines of Gardner and experimental needs. Embryos were transferred to the uterus in the two groups. The embryo implantation rate was calculated and the leukemia inhibitory factor (LIF) mRNA level was measured by real time fluorescence quantitative PCR in 5.5 d postcoitum (dpc).Results:1) The blood concentration of CsA in mice reached a peak at 6-10 h after administration. 2) The embryo implantation rate of B type [73.9% (34/46)] had significantly improved in experimental group [50.0% (23/46), P=0.018]. 3) The expression of LIF mRNA level was not significantly different between the two groups ( P>0.05). Conclusion:When CsA was administered at a dose of 5 mg/kg, CsA can improve the embryo implantation rate with mild impaired trophoblast cells. CsA might become a potential drug to increase the success rates of the in vitro fertilization.

Objective:To investigate whether the cyclosporin A (CsA) can improve the blastocyst implantation with mild impaired of trophoblast cells of mice.Methods:1) Totally 30 ICR mice were intraperitoneally injected with 5 mg/kg CsA, then the blood concentrations of CsA in mice were detected at 1 h, 3 h, 4 h, 6 h, 8 h, 10 h, 13 h, 14 h, 16 h and 20 h after administration using chemiluminescence method. 2) A total of 36 mice were randomly divided into control group and experimental group (CsA group); the experimental group was intraperitoneally injected with 5 mg/kg CsA and control group was injected with the equivalent dose olive oil of the same body weight. Embryos were classified into A, B, C types according to the guidelines of Gardner and experimental needs. Embryos were transferred to the uterus in the two groups. The embryo implantation rate was calculated and the leukemia inhibitory factor (LIF) mRNA level was measured by real time fluorescence quantitative PCR in 5.5 d postcoitum (dpc).Results:1) The blood concentration of CsA in mice reached a peak at 6-10 h after administration. 2) The embryo implantation rate of B type [73.9% (34/46)] had significantly improved in experimental group [50.0% (23/46), P=0.018]. 3) The expression of LIF mRNA level was not significantly different between the two groups ( P>0.05). Conclusion:When CsA was administered at a dose of 5 mg/kg, CsA can improve the embryo implantation rate with mild impaired trophoblast cells. CsA might become a potential drug to increase the success rates of the in vitro fertilization.