Carotid Baroreceptor Stimulation Improves Pulmonary Arterial Remodeling and Right Ventricular Dysfunction in Pulmonary Arterial Hypertension.

Autonomic nervous system imbalance is intricately associated with the severity and prognosis of pulmonary arterial hypertension (PAH). Carotid baroreceptor stimulation (CBS) is a nonpharmaceutical intervention for autonomic neuromodulation. The effects of CBS on monocrotaline-induced PAH were investigated in this study, and its underlying mechanisms were elucidated. The results indicated that CBS improved pulmonary hemodynamic status and alleviated right ventricular dysfunction, improving pulmonary arterial remodeling and right ventricular remodeling, thus enhancing the survival rate of monocrotaline-induced PAH rats. The beneficial effects of CBS treatment on PAH might be mediated through the inhibition of sympathetic overactivation and inflammatory immune signaling pathways.

Effects of Astragalus Polysaccharides on CD8+ Tissue-Resident Memory T Cells in Mice with Herpes Simplex.

Objective: This study aimed to explore whether astragalus polysaccharides (APS) could treat herpes simplex by increasing tissue-resident memory CD8+ T cells (CD8+ TRM cells) and analyze its potential mechanism using the network pharmacologic approach. Methods: C57BL/6J male mice aged 6-8 weeks were divided into a model group with HSV-1 infection treated by saline, a control group without HSV-1 infection but treated by saline, and an APS group with HSV-1 infection treated by APS. Clinical signs were observed, and the disease score was recorded every day. The skin lesions on day 9 after infection were taken for flow cytometric analysis to evaluate CD8+ TRM cells. Network pharmacologic analysis was performed to select the potential protein targets of astragalus associated with herpes simplex. Besides, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. The peripheral blood from the retroorbital venous plexus was collected to evaluate the levels of serum interferon-γ (IFN-γ) and interleukin 12 (IL-12). The comparisons of clinical signs, the disease score, CD8+ TRM cells, the serum IFN-γ, and IL-12 levels were performed among the three groups. Results: Compared with the model group, the disease score in the APS group was significantly lower (p < 0.05). On the day 9 after HSV-1 infection, there was no significant difference in the body weight of mice among the three groups. However, compared with the control group or model group, the spleen weight in the APS group increased significantly (p < 0.05). The surface antigens of CD8+ TRM cells had no significant difference between the control group and the model group, while compared with the model group, the surface antigens of CD8 (p < 0.05), CD69 (p < 0.05), and CD103 (p < 0.05) in the APS group increased significantly. Moreover, the serum IL-12 (p < 0.05) and IFN-γ (p < 0.01) levels in the APS group increased significantly compared with the model group. Conclusion: Our study suggested that APS could alleviate the symptoms of the mice infected with HSV-1, and CD8+ TRM cells in the skin lesions and the levels of IL-12 and IFN-γ in the serum of mice with HSV-1 infection increased after the APS treatment, of which the specific underlying mechanism requires further experiments to clarify. In addition, the antiviral effect of APS might be worthy of further development and utilization.

Comparative study of gene expression profiles rooted in acute myocardial infarction and ischemic/reperfusion rat models.

Mining data in depth of genome-wide sequencing data generated from pathological target tissues under disease conditions is necessary for seeking novel functional genes, and developing more biological study directions for the field. Based on our previous published RNA-seq data generated from acute myocardial ischemia and ischemia-reperfusion in rat heart, we re-analysed these two data sets using bioinformatics tools. All these raw fastq files were extracted from Illumina BCL using the Illumina CASAVA program. Four groups were obtained: UD (genes up-regulated in MI but down-regulated in I/R injury), DU (genes down-regulated in MI but up-regulated in I/R injury), UU (genes both up-regulated in MI and I/R injury), and DD (genes both down-regulated in MI and I/R injury) groups. The results showed that 304 common genes in the UD group, 236 common genes in the DU group, 318 common genes in the UU group, and 159 common genes in the DD group detected by comparing data sets of the MI and the I/R injury. We then listed the top 30 DEGs for each group, and carried out GO and KEGG analyses for enrichment and pathway studies for those top expressed genes. Further analysis of INTERPRO Protein Domains and Features enriched by DEGs showed that 20% of the Domains enriched were related to c-type lectin, and 17% of these domains are related to neurotransmitter-gated ion-channel. 15% of PFAM Protein Domains were about Neurotransmitter-gated ion-channel. There were only 8 SMART Protein Domains DEGs enriched and 37.5% of which were concerned about leucine-rich. Collagen involvement in Reactome Pathways accounted for 22.7%. We found that only a few DEGs in these two disease conditions have been reported in the literatures, suggesting that there are many new genes would be considered in the future studies. These analyses would provide some information for seeking more novel targets of these two clinic diseases, acute myocardial ischemia and myocardial ischemia/reperfusion.

Effects of Shengmai injection add-on therapy to chemotherapy in patients with non-small cell lung cancer: a meta-analysis.

PURPOSE: Shengmai injection (SMI) has shown promising outcomes in the management of non-small cell lung cancer (NSCLC). This meta-analysis aimed to investigate the add-on effects of SMI to chemotherapy in NSCLC patients. METHODS: A comprehensive literature search was performed in the Cochrane Library, PubMed, Embase, CNKI, VIP, and Wanfang up to December 2017. Only randomized controlled trials (RCTs) evaluating SMI in combination with chemotherapy versus chemotherapy alone in NSCLC patients were eligible. The outcome measures were quality of life, chemotherapy-induced grade 3/4 myelosuppression or gastrointestinal reactions, and objective tumor response (equals complete response plus partial response). Pooled risk ratio (RR) with 95% confidence interval (CI) was used to evaluate dichotomous and continuous outcome, respectively. RESULTS: A total of 15 RCTs were included and analyzed. Meta-analysis showed that SMI combined with chemotherapy was associated with a significant improvement in Karnofsky Performance Status (RR 2.36; 95% CI 1.50-3.96) compared with the chemotherapy alone. Moreover, adjunctive treatment with SMI significantly reduced grade 3/4 myelosuppression (RR 0.61; 95% CI 0.46-0.81) and gastrointestinal reactions (RR 0.64; 95% CI 0.46-0.90). However, there was no significant difference in objective tumor response (RR 1.17; 95% CI 0.99-1.37) between two groups. CONCLUSIONS: SMI add-on therapy appeared to be more effective in improving quality of life and reducing chemotherapy-induced adverse effects. However, more well-designed RCTs are warranted to confirm the findings of this meta-analysis because of the suboptimal methodological quality of the included trials.

Effects of acupuncture on the levels of serum estradiol and pituitary estrogen receptor beta in a rat model of induced super ovulation.

AIMS: Acupuncture is frequently recommended as a complementary therapy for infertility. However, whether acupuncture can prevent early ovarian hyperstimulation syndrome has not been examined and its potential mechanisms are not well understood. MAIN METHODS: Forty rats were randomized into four groups: Control, Ovarian Stimulation Model, Acupuncture, and Human Chorionic Gonadotropin (HCG). Serum estradiol, progesterone, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were measured by enzyme-linked immunosorbent assay. Pituitary ER mRNA and ERß expression were detected by real-time PCR and western blotting respectively. The pathology of rat ovaries were observed by light microscopy. KEY FINDINGS: We observed significantly lower estradiol levels in the Acupuncture group than in the Model group and increased LH levels in the HCG group than in Model and Acupuncture groups. Testosterone and FSH levels were significantly lower in the Acupuncture group than in the HCG group. Western blotting showed significantly lower pituitary ERß expression in the Model group than in the Control group and higher expression in the Acupuncture group than in the Model group. Real-time PCR showed lower pituitary ER mRNA expression in the Acupuncture group than in the Model group. Hematoxylin and eosin staining showed a lower proportion of atretic follicles in Acupuncture and HCG groups than in Model and Control groups. Instead, Acupuncture and HCG groups showed growing and mature follicles. SIGNIFICANCE: Our results demonstrate a relationship between acupuncture and the hypothalamic-pituitary-gonadal axis, and the potential mechanism underlying the preventative effects of acupuncture on the incidence of early ovarian hyperstimulation syndrome.

circHIPK2-mediated σ-1R promotes endoplasmic reticulum stress in human pulmonary fibroblasts exposed to silica.

Silicosis is characterized by fibroblast accumulation and excessive deposition of extracellular matrix. Although the roles of SiO2-induced chemokines and cytokines released from alveolar macrophages have received significant attention, the direct effects of SiO2 on protein production and functional changes in pulmonary fibroblasts have been less extensively studied. Sigma-1 receptor, which has been associated with cell proliferation and migration in the central nervous system, is expressed in the lung, but its role in silicosis remains unknown. To elucidate the role of sigma-1 receptor in fibrosis induced by silica, both the upstream molecular mechanisms and the functional effects on cell proliferation and migration were investigated. Both molecular biological assays and pharmacological techniques, combined with functional experiments, such as migration and proliferation, were applied in human pulmonary fibroblasts from adults to analyze the molecular and functional changes induced by SiO2. SiO2 induced endoplasmic reticulum stress in association with enhanced expression of sigma-1 receptor. Endoplasmic reticulum stress promoted migration and proliferation of human pulmonary fibroblasts-adult exposed to SiO2, inducing the development of silicosis. Inhibition of sigma-1 receptor ameliorated endoplasmic reticulum stress and fibroblast functional changes induced by SiO2. circHIPK2 is involved in the regulation of sigma-1 receptor in human pulmonary fibroblasts-adult exposed to SiO2. Our study elucidated a link between SiO2-induced fibrosis and sigma-1 receptor signaling, thereby providing novel insight into the potential use of sigma-1 receptor/endoplasmic reticulum stress in the development of novel therapeutic strategies for silicosis treatment.

miR-205 as a biological marker in non-small cell lung cancer.

OBJECTION: The aim of this study is to explain the significance and mechanism of miR-205 in the diagnosis and treatment of non-small cell lung cancer. METHODS: The 70 advanced NSCLC patients, treated in our hospital, were collected from 2011.10 to 2013.9, taking the tissues from cancer and adjacent tissues to measure the miR-205 expression, evaluate the AKT gene and protein expression of cancer and adjacent normal tissues by RT-PCR and Immunohistochemistry (IHC) assays and analyzing the correlation between miR-205 and AKT. Following up the patients for 2 years; Recording patients' survival time. In the cell experiment, Selecting A549 cell as research object, the cells were divided into three groups: Normal control group (NC), Blank control group (BL) and si-miR-205 transfection group (si-miR-205). Cell proliferation rate and apoptosis rate were detected by MTT method and flow cytometry; Measuring invasion and migration of difference groups by transwell and scratch testing, measured the Akt, mTOR,P21, MMP2 and MMP9 gene expression and detected Akt, p-Akt, mTOR, p-mTOR, P21, MMP2 and MMP 9 protein expression levels. RESULTS: Compared with adjacent normal tissue, the miR-205 and AKT gene expression level was significantly increased in NSCLC tissues (P<0.05) and the AKT protein expression was stronger than that of healthy tissues, miR-205 was positive correlation with AKT; In the overall survival, MiR-205 high expression group was significantly higher than low expression group (P<0.05). In the cell experiment, Compared with NC and BL groups, si-miR-205 could significantly reduced the biological activity of A549 cells in proliferation, invasion and migration, and promoted the apoptosis of A549 cells (P<0.05, respectively). Akt, p-Akt, mTOR, p-mTOR, P21, MMP 2 and MMP 9 gene and protein expression of si-miR-205 group were significantly compared with NC and BL groups (P<0.05, respectively). CONCLUSION: miRNA-205 might serve as a potential biomarker for the prognosis of advanced NSCLC, and inhibiting miR-205 expression could decrease A549 cells biological activity by regulating Akt/mTOR/P21 and Akt/MMP 2/MMP 9signaling pathway.

Curcumin suppresses proliferation and invasion in non-small cell lung cancer by modulation of MTA1-mediated Wnt/ß-catenin pathway.

Curcumin, a naturally occurring phenolic compound, has a diversity of antitumor activities. It has been previously demonstrated that curcumin can inhibit the invasion and metastasis of tumors through activation of the tumor suppressor DnaJ-like heat shock protein 40 (HLJ1). However, the specific roles and mechanisms of curcumin in regulating the malignant behaviors of non-small cell lung cancer (NSCLC) cells still remain unclear. In this study, we found that curcumin could inhibit the proliferation and invasion of NSCLC cells and induce G0/G1 phase arrest. Metastasis-associated protein 1 (MTA1) overexpression has been detected in a wide variety of aggressive tumors and plays an important role on cell invasion and metastasis. Our results showed that curcumin could effectively inhibit the MTA1 expression of NSCLC cells. Further research on the subsequent mechanism showed that curcumin inhibited the proliferation and invasion of NSCLC cells through MTA1-mediated inactivation of Wnt/ß-catenin pathway. Wnt/ß-catenin signaling was reported to play a critical cooperative role on promoting lung tumorigenesis. Thus, these investigations provided novel insights into the mechanisms of curcumin on inhibition of NSCLC cell growth and invasion and showed potential therapeutic strategies for NSCLC.

Knocking down the expression of Aurora-A gene inhibits cell proliferation and induces G2/M phase arrest in human small cell lung cancer cells.

A hallmark of small cell lung cancer (SCLC) is frequent relapse characterized by newfound resistance to formerly efficacious chemotherapies. The prognosis for SCLC patients is particularly unfavorable. Aurora kinase A (AURKA), a member of the serine/threonine kinase family, is overexpressed across many types of human tumors. Recent studies have identified AURKA as an important factor in tumorigenesis, but little is known regarding its specific roles in SCLC. The aim of the present study was to establish the roles of AURKA in the molecular pathogenesis of human SCLC. In the present study, we constructed a lentiviral vector to express siRNA against AURKA (LV-AURKA siRNA). As we expected, the viral construct effectively suppressed the expression of the AURKA gene and protein in H446 and H1688 cell lines. Additionally, RNA interference of AURKA inhibited the colony formation and subsequent growth of H446 and H1688 cell lines by increasing the incidence of cell cycle arrest in the G2/M phase. Furthermore, suppression of AURKA by LV-AURKA siRNA also increased apoptosis of SCLC cells. A potential mechanism for the increase of apoptosis is the downregulation of Bcl-2 and upregulation of Bax. AURKA gene suppression may provide a novel, effective therapy for SCLC patients by inhibiting cell division and increasing the rate of apoptosis of SCLC cells.

[The effect of compound macrostem onion capsule on metabolism of arachidonic acid in a rat model of monocrotaline-induced pulmonary artery hypertension].

OBJECTIVE: To study the effect of compound macrostem onion capsule (CMOC) on products of arachidonic acid metabolism in monocrotaline (MCT)-induced pulmonary artery hypertension rats. METHODS: Sixty SD rats were divided into a control group, a model group, and three experimental groups in which the rats were fed with captopril, small dose single dosage, and large dose (double dosage) of CMOC, respectively. The rat model was made by MCT peritoneal injection. The mean pulmonary arterial pressure (mPAP) and the mean right ventricular pressure (mRVP) were measured. Thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin Fia (6-K-PGFia) were determined by RIA method. RESULTS: The mPAP in rats of the model group [(36.9 +/- 4.8) mm Hg, 1 mm Hg = 0.133 kPa] was significantly higher than that of the control group [(16.4 +/- 2.1) mm Hg, all P < 0.01]. The mPAP in rats of the double dosage and single dosage of CMOC groups were (26.2 +/- 2.8) mm Hg and (27.9 +/- 2.8) mm Hg, respectively; both were significantly lower than those of the model group (all P < 0.01). TXB(2) in rats of the model group was significantly higher than that of the control group (P < 0.05), while 6-K-PGFia in the model group was significantly lower than that of the control group (P < 0.01). TXB(2) in rats of the double dosage CMOC group was significantly lower than that of the model group, but 6-K-PGFia in rats of the CMOC groups was significantly higher than that of the model group (P < 0.05, < 0.01). CONCLUSION: CMOC is effective in reducing pulmonary artery hypertension. Inhibition of TXB(2) and augmentation of 6-K-PGFia might be the underlying mechanisms.