The bark of Cinnamomum cassia (C. cassia) has been used for the management of coronary heart disease (CHD) and diabetes mellitus. C. cassia may target the vasculature, as it stimulates angiogenesis, promotes blood circulation and wound healing. However, the active components and working mechanisms of C. cassia are not fully elucidated. The Shexiang Baoxin pill (SBP), which consists of seven medicinal materials, including C. cassia etc., is widely used as a traditional Chinese patent medicine for the treatment of CHD. Here, 22 single effective components of SBP were evaluated against the human umbilical vein endothelial cells (HUVECs). We demonstrated that in HUVECs, cinnamaldehyde (CA) stimulated proliferation, migration, and tube formation. CA also activated the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Furthermore, the secretion of vascular endothelial growth factor (VEGF) from HUVECs was increased by CA. In vivo, CA partially restored intersegmental vessels in zebrafish pretreated with PTK787, which is a selective inhibitor for vascular endothelial growth factor receptor (VEGFR). CA also showed pro-angiogenic efficacy in the Matrigel plug assay. Additionally, CA attenuated wound sizes in a cutaneous wound model, and elevated VEGF protein and CD31-positive vascular density at the margin of these wounds. These results illustrate that CA accelerates wound healing by inducing angiogenesis in the wound area. The potential mechanism involves activation of the PI3K/AKT and MAPK signaling pathways. Such a small non-peptide molecule may have clinical applications for promoting therapeutic angiogenesis in chronic diabetic wounds and myocardial infarction.
BackgroundWe observed the effects of nuclear factor E2-related factor 2 (Nrf2) downregulation via intrahippocampal injection of a lentiviral vector on cognition in senescence-accelerated mouse prone 8 (SAMP8) to investigate the role of the (Nrf2)/antioxidant response element (ARE) pathway in age-related changes.Material/MethodsControl lentivirus and Nrf2-shRNA-lentivirus were separately injected into the hippocampus of 4-month-old SAMR1 and SAMP8 mice and then successfully downregulated Nrf2 expression in this brain region. Five months later, cognitive function tests, including the novel object test, the Morris water maze test, and the passive avoidance task were conducted. Glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba1) immunohistochemistry was performed to observe an inflammatory response. Presynaptic synapsin (SYN) were observed by immunofluorescence. We then determined the Nrf2-regulated, heme oxygenase-1 (HO-1), P65, postsynaptic density protein (PSD), and SYN protein levels. The ultrastructure of neurons and synapses in the hippocampal CA1 region was observed by transmission electron microscopy.ResultsAging led to a decline in cognitive function compared with SAMR1 mice and the Nrf2-shRNA-lentivirus further exacerbated the cognitive impairment in SAMP8 mice. Nrf2, HO-1, PSD, and SYN levels were significantly reduced (all P<0.05) but high levels of inflammation were detected in SAMP8 mice with low expression of Nrf2. Furthermore, neurons were vacuolated, the number of organelles decreased, and the number of synapses decreased.ConclusionsDownregulation of Nrf2 suppressed the Nrf2/ARE pathway, activated oxidative stress and neuroinflammation, and accelerated cognitive impairment in SAMP8 mice. Downregulation of Nrf2 accelerates the aging process through neuroinflammation and synaptic plasticity.
Hypopharyngeal carcinoma has one of the highest mortality rates of head and neck cancer, therefore, the identification of markers associated with the pathogenesis and development of hypopharyngeal cancer is critical. Down syndrome critical region 1 (DSCR1) is associated with carcinogenesis and tumor growth in several types of malignancy. Activation of the vascular endothelial growth factor (VEGF) signaling pathway upregulates DSCR1. The aims of the present study were to determine the expression levels of DSCR1 and VEGF‑C in hypopharyngeal cancer, and investigate the association between DSCR1 and angiogenesis in the disease. Tissue samples from 94 cases of pathologically confirmed hypopharyngeal squamous cell carcinoma were collected. The mRNA levels of DSCR1 and VEGF‑C in cancerous and paracancerous tissues were examined using semi‑quantitative reverse transcription‑polymerase chain reaction. Microvessel density (MVD) was counted, according to the number of cluster of differentiation 34‑positive cells. Spearman's correlation analysis was utilized to analyze the association between DSCR1 and angiogenesis. The relative mRNA expression levels of DSCR1 and VEGF‑C, and the MVD were significantly increased in the cancerous tissue samples from the patients with hypopharyngeal cancer, compared with the paracancerous tissue samples from these patients. Higher levels of DSCR1 and increased MVD were associated with poorly differentiated tumors and lymph node metastasis. The mRNA expression levels of DSCR1 were positively correlated with the mRNA levels of VEGF‑C in the cancerous tissues. The protein expression levels of DSCR1 were also positively correlated with MVD in the cancerous tissues. The results indicated that DSCR1 is involved in tumor angiogenesis in patients with hypopharyngeal cancer, and is closely associated with the progression of the disease.
Data on the association between -1607 1G > 2G polymorphism in the promoter region of matrix metalloproteinase-1 (MMP1) and nasopharyngeal carcinoma (NPC) are conflicting. The aim of this study was to confirm whether this polymorphism was a causative factor of NPC. We searched PubMed, Embase, and China National Knowledge Infrastructure (CNKI) for studies on the present topic. A total of four publications (1,044 NPC patients and 1,284 healthy control subjects) were included and meta-analysis was performed to assess the association between -1607 1G > 2G polymorphism and NPC risk. Odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated for 1G1G versus 2G2G, 1G1G + 1G2G versus 2G2G, 1G1G versus 1G2G + 2G2G, 1G versus 2G, and 1G2G versus 2G2G contrast models. Meta-analysis results showed significantly reduced risk of NPC associated with the 1G1G versus 2G2G, 1G versus 2G and 1G2G versus 2G2G contrast models (OR = 0.61, 95 % CI 0.49-0.77; OR = 0.78, 95 % CI 0.65-0.92; OR = 0.86, 95 % CI 0.74-0.99, respectively). When we continued to perform subgroup analysis by ethnicity, the significant association persisted in Asian population and was most pronounced under the 1G2G versus 2G2G model (OR = 0.85, 95 % CI 0.73-0.99). These data suggested that MMP1 -1607 1G > 2G polymorphism was associated with reduced risk of NPC, particularly in the population of Asian descent.
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