Function identification of miR394 in tomato resistance to Phytophthora infestans.

MiR394 plays a negative role in tomato resistance to late blight. The lncRNA40787 severing as an eTM for miR394 to regulate LCR and exerting functions in tomato resistance. Tomato (Solanum lycopersicum), which was used as model species for studying the mechanism of plant disease defense, is susceptible to multiple pathogens.

[Inhibitory effect of paeonol on aortic endothelial inflammation in atherosclerotic rats by up-regulation of caveolin-1 expression and suppression of NF-κB pathway].

To explore whether paeonol can play an anti-atherosclerotic role by regulating the expression of aortic caveolin-1 and affecting NF-κB pathway, so as to inhibit the inflammatory response of vascular endothelium in atherosclerotic rats. The atherosclerotic model of rats was induced by high-fat diet and vitamin D_2. The primary culture of vascular endothelial cells(VECs) was carried out by tissue block pre-digestion and adherent method.

Two Trinuclear Cu Complexes: Effect of Phosphonate Ligand on the Magnetic Property and Electrocatalytic Reactivity for Water Oxidation.

Two trinuclear copper phosphonate complexes, [Cu (pda) (tBuPO )]⋅2(Et NH) (1) and [Cu (pda) (PhPO )]⋅2(Et NH) (2), have been synthesized and investigated by a combination of X-ray crystallography, PXRD, magneto- and electrochemistry, EPR, in situ UV-vis spectroelectrochemistry and DLS. The two complexes feature almost identical crystal structures, the anions of which are both supported by pda and tBuPO /PhPO groups, bridging three five-coordinated Cu atoms to form a crown-like structure. This is the first time that trinuclear copper phosphonate complexes have been isolated and characterized.

Alantolactone, a sesquiterpene lactone, inhibits breast cancer growth by antiangiogenic activity via blocking VEGFR2 signaling.

Alantolactone (ALA), a sesquiterpene lactone isolated from several medicinal plants such as Inula helenium, has been identified to have attractive anticancer activity. However, its role in the inhibition of angiogenesis during tumor development remains unclear. In this study, we found ALA can inhibit the proliferation, motility, migration, and tube formation of human umbilical vein endothelial cells.

Tumor priming using metronomic chemotherapy with neovasculature-targeted, nanoparticulate paclitaxel.

Normalization of the tumor microenvironment is a promising approach to render conventional chemotherapy more effective. Although passively targeted drug nanocarriers have been investigated to this end, actively targeted tumor priming remains to be explored. In this work, we demonstrate an effective tumor priming strategy using metronomic application of nanoparticles actively targeted to tumor neovasculature.

IF7-Conjugated Nanoparticles Target Annexin 1 of Tumor Vasculature against P-gp Mediated Multidrug Resistance.

Multidrug resistance is the main cause of clinical chemotherapeutic failure. Antiangiogenic cancer therapy with nanomedicine that allows the targeted delivery of antiangiogenic agents to tumor endothelial cells may contribute to innovative strategies for treating multidrug-resistant cancers. In this study, we developed a new nanodrug delivery system (nano-DDS), with improved antiangiogenic efficacy against multidrug resistant human breast cancer MCF-7/ADR cells.

Raddeanin A, a triterpenoid saponin isolated from Anemone raddeana, suppresses the angiogenesis and growth of human colorectal tumor by inhibiting VEGFR2 signaling.

Raddeanin A (RA) is an active triterpenoid saponin from a traditional Chinese medicinal herb, Anemone raddeana Regel. It was previously reported that RA possessed attractive antitumor activity through inhibiting proliferation and inducing apoptosis of multiple cancer cells. However, whether RA can inhibit angiogenesis, an essential step in cancer development, remains unknown.

Delta-like ligand 4-targeted nanomedicine for antiangiogenic cancer therapy.

Tumor angiogenesis is a multistep process involved with multiple molecular events in cancer microenvironment. Several molecular-targeted agents aiming to suppress tumor angiogenesis have been successfully translated into cancer clinic. However, new strategies are still urgently desired to be excavated to overcome the poor response and resistance in some antiangiogenic therapies.

Platycodin D inhibits tumor growth by antiangiogenic activity via blocking VEGFR2-mediated signaling pathway.

Platycodin D (PD) is an active component mainly isolated from the root of Platycodon grandiflorum. Recent studies proved that PD exhibited inhibitory effect on proliferation, migration, invasion and xenograft growth of diverse cancer cell lines. However, whether PD is suppressive for angiogenesis, an important hallmark in cancer development, remains unknown.

Paeonol protects rat vascular endothelial cells from ox-LDL-induced injury in vitro via downregulating microRNA-21 expression and TNF-α release.

Aim: Paeonol (2'-hydroxy-4'-methoxyacetophenone) from Cortex moutan root is a potential therapeutic agent for atherosclerosis. This study sought to investigate the mechanisms underlying anti-inflammatory effects of paeonol in rat vascular endothelial cells (VECs) in vitro.

Methods: VECs were isolated from rat thoracic aortas.

Selective eradication of tumor vascular pericytes by peptide-conjugated nanoparticles for antiangiogenic therapy of melanoma lung metastasis.

Antiangiogenic cancer therapy based on nanoparticulate drug delivery systems (nano-DDS) is emerging as a promising new approach besides the proved molecular-targeted antiangiogenic agents. The current nano-DDS are restricted to the targeting to tumor vascular endothelial cells, but seldom efforts have been made to target the tumor vascular pericytes which are also actively involved in tumor angiogenesis. In this study, we developed a new nano-DDS, TH10 peptide (TAASGVRSMH) conjugated nanoparticles loading docetaxel (TH10-DTX-NP) that can target the NG2 proteoglycan highly expressed in tumor vascular pericytes, for the investigation of therapeutic efficacy in the mice bearing B16F10-luc-G5 melanoma experimental lung metastasis.

Suppression of colorectal cancer subcutaneous xenograft and experimental lung metastasis using nanoparticle-mediated drug delivery to tumor neovasculature.

Antiangiogenic therapy is a validated approach for colorectal cancer (CRC) treatment. However, diverse adverse effects inevitably appear due to the off-target effect of the approved antiangiogenic inhibitors on the physiological functions and homeostasis. This study was to investigate a new tumor vessel targeting nanoparticulate drug delivery system, F56 peptide conjugated nanoparticles loading vincristine (F56-VCR-NP), for the effective treatment of CRC subcutaneous xenograft and experimental lung metastasis model.

Development and validation of a quantitative liquid chromatography tandem mass spectrometry assay for pristimerin in rat plasma.

A sensitive, rapid and simple LC-MS/MS analysis method was developed and validated for the determination of pristimerin (PR) in rat plasma. Protein precipitation with four volumes of acetonitrile as the precipitation reagent was used as the sample preparation method. The analysis process was performed on a Merck ZIC-HILIC column with the mobile phase of acetonitrile-water (containing 5mM ammonium formate, pH 2.

Nanoparticle-mediated drug delivery to tumor neovasculature to combat P-gp expressing multidrug resistant cancer.

Anticancer drug resistance is a common intractable obstacle in clinical cancer chemotherapy. Here, we hypothesize that antiangiogenic cancer therapy through the targeted delivery of antiangiogenic agents to the tumor endothelial cells (EC), not the resistant cancer cells, may have the potential of combating multidrug resistant cancer. The K237 peptide-conjugated paclitaxel loaded nanoparticles (K237-PTX-NP), which can target KDR receptors highly expressed in the tumor vasculature, were fabricated for this investigation and the human colorectal adenocarcinoma HCT-15 with naturally expressed P-gp on the cell surface was adopted as the resistant tumor model.

The use of nanoparticulate delivery systems in metronomic chemotherapy.

Metronomic chemotherapy aiming at inhibiting tumor angiogenesis with conventional chemotherapeutics is a promising strategy for antiangiogenic cancer therapy. However, current metronomic chemotherapy mainly focuses on free small-molecule drugs, without any effort to achieve tumor-specific biodistribution, which may lead to long-term toxicity concerns. Metronomic chemotherapy using nanoparticulate drug delivery system (DDS) offers significant upside to reduce off-target side effects, decrease accumulated dose, and enhance the efficacy of tumor vessel targeting without compromising antitumor efficacy; but there has been a lack of thorough experimental data describing the targeted metronomic chemotherapy.

K+ channels and the cAMP-PKA pathway modulate TGF-beta1-induced migration of rat vascular myofibroblasts.

Our previous studies have indicated that TGF-beta1 exerts its effect on the expression of A-type potassium channels (I(A)) in rat vascular myofibroblasts by activation of protein kinase C during the phenotypic transformation of vascular fibroblasts to myofibroblasts. In the present study, patch-clamp whole-cell recording and transwell-migration assays were used to examine the effects of TGF-beta1- and phorbol 12-myristate 13-acetate (PMA)-induced expression of I(A) channels on myofibroblast migration and its modulation by the protein kinase A (PKA) pathway. Our results reveal that incubation of fibroblasts with TGF-beta1 or PMA up-regulates the expression of I(A) channels and increases myofibroblast migration.

Mefenamic acid bi-directionally modulates the transient outward K+ current in rat cerebellar granule cells.

The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on ion channels has been widely studied in several cell models, but less is known about their modulatory mechanisms. In this report, the effect of mefenamic acid on voltage-activated transient outward K(+) current (I(A)) in cultured rat cerebellar granule cells was investigated. At a concentration of 5 microM to 100 microM, mefenamic acid reversibly inhibited I(A) in a dose-dependent manner.