High density lipoprotein (HDL) as well as annexin A1 have been reported to be associated with cardiovascular protection. However, the correlation between HDL and annexin A1 was still unknown. In this ...study, HDL increased endothelial annexin A1 and prevented the decrease of annexin A1 in TNF-α-activated endothelial cells in vitro and in vivo, and above effects were attenuated after knockdown of annexin A1. Annexin A1 modulation affected HDL-mediated inhibition of monocyte adhesion to TNF-α-activated endothelium (45.2±13.7% decrease for annexin A1 RNA interference; 78.7±16.3% decrease for anti-Annexin A1 antibody blocking; 11.2±6.9% increase for Ad-ANXA1 transfection). Additionally, HDL up-regulated annexin A1 through scavenger receptor class B type I, involving ERK, p38MAPK, Akt and PKC signaling pathways, and respective inhibitors of these pathways attenuated HDL-induced annexin A1 expression as well as impaired HDL-mediated inhibition of monocyte–endothelial cell adhesion. Apolipoprotein AI also increased annexin A1 and activated similar signaling pathways. Endothelial annexin A1 from apolipoprotein AI knockout mice was decreased in comparison to that from wild type mice. Finally, HDL-induced annexin A1 inhibited cell surface VCAM-1, ICAM-1 and E-selectin, and secretion of MCP-1, IL-8, VCAM-1 and E-selectin, thereby inhibiting monocyte adhesion.
•HDL up-regulated endothelial annexin A1 via SR-BI and activation of ERK, p38MAPK, Akt and PKC signaling pathways.•Endothelial ANXA 1 inhibited monocyte adhesion.•High density lipoprotein-induced annexin A1 not only inhibited cell surface VCAM-1, ICAM-1, and E-selectin but also suppressed secretion of MCP-1, IL-8, VCAM-1 and E-selectin, which alleviated inflammatory response.
To investigate the effect and mechanism of high density lipoprotein (HDL) on type II alveolar epithelial cells during inflammation state.
The original generation of type II alveolar epithelial cells ...were separated in rats and treated with PBS/LPS/HDL/HDL + LPS. To observe the proliferation and migration of type II alveolar epithelial cells with bromodeoxyuridine(BrdU) assay, transwell assay and wound healing experiments. In addition, western blot detected the expression of TP-binding cassette transporter A1 (ABCA1), cystic fibrosis transmembrane conductance regulator (CFTR) and the phosphorylation of AKT/extracellular signal-regulated kinase(ERK)/mitogen-activated protein kinase(MAPK). Enzyme-linked immunosorbent assay (ELISA) tested the secretion of tumor necrosis factor a(TNF-a)/interleukin 1a(IL-1a)/IL-6.
HDL promoted the proliferation (↑17%, p < 0.001 HDL+ LPS vs. LPS) and migration (wounding healing: ↑93%, p < 0.001 HDL+ LPS vs. LPS; transwell migration: ↑154%, p < 0.001 HDL+ LPS vs. LPS) of type II alveolar epithelial cells. Furthermore, HDL increased the phosphorylation of MAPK, but not AKT/ERK. And HDL decreased the secretion of TNF-a (↓46%, p < 0.01 HDL+ LPS vs. LPS) and IL-1a (↓45%, p < 0.001 HDL+ LPS vs. LPS), but not IL-6. In addition, HDL up-regulated the expression of ABCAI (↑99%, p < 0.001 HDL vs. CON) and down-regulated the expression of CFTR (↓25%, p < 0.05 HDL vs. CON) in type II alveolar epithelial cells.
HDL increases the phosphorylation of MAPK, which promotes the proliferation and migration of type II alveolar epithelial cells. And it decreased the secretion of TNF-a/IL-1a and the expression of CFTR. All these suggest that HDL plays an important role in anti-inflammatory effect in inflammation state of lung.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Disruption of endothelial monolayer integrity is the primary instigating factor for many cardiovascular diseases. High density lipoprotein (HDL) oxidized by heme enzyme myeloperoxidase (MPO) is ...dysfunctional in promoting endothelial repair. Apolipoprotein A-1 mimetic 4F with its pleiotropic benefits has been proven effective in many in vivo models. In this study we investigated whether 4F promotes endothelial repair and restores the impaired function of oxidized HDL (Cl/NO2-HDL) in promoting re-endothelialization. We demonstrate that 4F and Cl/NO2-HDL act on scavenger receptor type I (SR-B1) using human aorta endothelial cells (HAEC) and SR-B1 (-/-) mouse aortic endothelial cells. Wound healing, transwell migration, lamellipodia formation and single cell migration assay experiments show that 4F treatment is associated with a recovery of endothelial cell migration and associated with significantly increased endothelial nitric oxide synthase (eNOS) activity, Akt phosphorylation and SR-B1 expression. 4F increases NO generation and diminishes oxidative stress. In vivo, 4F can stimulate cell proliferation and re-endothelialization in the carotid artery after treatment with Cl/NO2-HDL in a carotid artery electric injury model but fails to do so in SR-B1(-/-) mice. These findings demonstrate that 4F promotes endothelial cell migration and has a potential therapeutic benefit against early endothelial injury in cardiovascular diseases.
•4F restores the decreased ability of Cl/NO2-HDL in promoting endothelial repair.•4F increases NO generation and diminishes oxidative stress.•4F increases eNOS activity, Akt phosphorylation and SR-B1 expression.•4F can stimulate re-endothelialization in a carotid artery electric injury model.
Selective alkylation of indazoles is still a highly challenging topic in chemistry and the synthesis of important molecules. Herein, a novel highly selective
-alkylation of indazoles with diazo ...compounds is described in the presence of TfOH. Unlike the traditional metal- and base-catalysed version, this protocol highlights the regioselectivity of alkylation of indazoles and a metal-free catalysis system, affording
-alkylated products in good to excellent yields with high regioselectivity (
/
up to 100/0) and excellent functional group tolerance. Furthermore, a gram scale synthesis was conducted successfully to give rise to the corresponding products. Mechanistic studies through control experiments provide plausible mechanistic proposals.
We have developed a method for highly regioselective S–H bond insertion reactions of various diazo compounds and cyclic thioamide derivatives at room temperature. These reactions provide ...straightforward access to alkylated benzimidazoles, benzothiazoles, and benzoxazoles. This mild method uses readily available TfOH as a catalyst and features a broad substrate scope, good functional group tolerance, good to excellent yields, and high regioselectivities.
Selective alkylation of indazoles is still a highly challenging topic in chemistry and the synthesis of important molecules. Herein, a novel highly selective N2-alkylation of indazoles with diazo ...compounds is described in the presence of TfOH. Unlike the traditional metal- and base-catalysed version, this protocol highlights the regioselectivity of alkylation of indazoles and a metal-free catalysis system, affording N2-alkylated products in good to excellent yields with high regioselectivity (N2/N1 up to 100/0) and excellent functional group tolerance. Furthermore, a gram scale synthesis was conducted successfully to give rise to the corresponding products. Mechanistic studies through control experiments provide plausible mechanistic proposals.
A catalyst- and temperature-controlled selective synthesis of sulfonamide and sulfones from N-tosylhydrazones and MBH carbonates has been developed. The use of palladium catalysts exclusively leads ...to sulfonamide products at room temperature, whereas the selective synthesis of sulfones is dominant for a temperature-controlled coupling reaction without palladium catalysis. Importantly, the catalyst- or temperature-controlled reaction exhibits high nucleophilicity rather than carbene reactivity in these transformations.
Adhesion of disseminating tumor cells to vascular endothelium is a pivotal starting point in the metastasis cascade. We have shown previously that diabetic high-density lipoprotein (HDL) has the ...capability of promoting breast cancer metastasis, and this report summarizes our more recent work studying the role of abnormal HDL in facilitating the adhesion of the circulating tumor cells to the endothelium. This is an initiating step in breast cancer metastasis, and this work assesses the role of ICAM-1 and VCAM-1 in this process. MDA-MB-231, MCF 7, and human umbilical vein endothelial cells (HUVECs) were treated with normal HDL from healthy controls (N-HDL), HDL from breast cancer patients (B-HDL), or HDL from breast cancer patients complicated with type 2 diabetes mellitus (BD-HDL), and the cell adhesion abilities were determined. ICAM-1 and VCAM-1 expression as well as the protein kinase C (PKC) activity were evaluated. The effect of PKC inhibitor and PKC siRNA on adhesion was also studied. The immunohistochemical staining of ICAM-1, VCAM-1, and E-selectin from breast cancer patients and breast cancer patients complicated with type 2 diabetes mellitus (T2DM) were examined. Our results indicate that BD-HDL promoted an increase in breast cancer cell adhesion to HUVECs and stimulated higher ICAM-1 and VCAM-1 expression on the cells surface of both breast cancer and HUVEC cells, along with the activation of PKC. Increased tumor cell (TC)-HUVEC adhesion, as well as ICAM-1 and VCAM-1 expression induced by BD-HDL, could be inhibited by staurosporine and PKC siRNA. In addition, a Db/db type 2 diabetes mouse model has more TC-Vascular Endothelium adhesion compared to a normal model. However, BD patients have a lower expression of ICAM-1, VCAM-1, and E-selectin in their tumor tissues. BD-HDL facilitates the adhesion of tumor cells to vascular endothelium by upregulating the expression of ICAM-1 and VCAM-1, thereby promoting the initial progression of breast cancer metastasis. This work indicates a prospective utilization of HDL-based strategies in the treatment of breast cancer patients with type 2 diabetes.
Selective alkylation of indazoles is still a highly challenging topic in chemistry and the synthesis of important molecules. Herein, a novel highly selective
N
2
-alkylation of indazoles with diazo ...compounds is described in the presence of TfOH. Unlike the traditional metal- and base-catalysed version, this protocol highlights the regioselectivity of alkylation of indazoles and a metal-free catalysis system, affording
N
2
-alkylated products in good to excellent yields with high regioselectivity (
N
2
/
N
1
up to 100/0) and excellent functional group tolerance. Furthermore, a gram scale synthesis was conducted successfully to give rise to the corresponding products. Mechanistic studies through control experiments provide plausible mechanistic proposals.
A novel highly selective
N
2
-alkylation of indazoles with diazo compounds is described in good to excellent yields with high regioselectivity (
N
2
/
N
1
up to 100/0) and excellent functional group tolerance.
Objectives To assess the clinical efficacy and safety of ultrasound-guided stellate ganglion block in the treatment of allergic rhinitis. Methods Sixty patients with allergic rhinitis were selected ...as study subjects and were treated with stellate ganglion blocking. We observed the appearance and time of the patient's Horner syndrome, and compared the patient's clinical symptom scores before and after one month treatment, and calculated the clinical efficacy and overall effective rate. Results After ultrasound-guided stellate ganglion blocking treatment, 97% of patients occurred Horner syndrome within 2 minutes. The scores of sneezing, runny nose, nasal itching, and nasal congestion significantly reduced at one month after treatment compared with those before treatment, in which there was statistically significant difference (P<0.05). The clinical efficacy rate also reached 96.7% after procedures. No serious complications occurred in this study. Conclusions Ultrasound-guided stellate ganglion block can significantly improve the clinical symptoms and the life quality for patients with allergic rhinitis, and it is worthy of extensive clinical application.
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