Co-culture Model Using Two Types of Adherent Cell Lines

Embryo implantation is affected by the interactions among different cell types in the mother-embryo interface. The direct and indirect communications ...

Southern Medical University

Epidermal growth factor receptor (EGFR) has gained significant attention as a therapeutic target. Several EGFR targeting drugs (Gefitinib and Erlotinib) have been approved by US Food and Drug Administration (FDA) and have received high approval in clinical treatment. Nevertheless, the curative effect of these medicines varied in many solid tumors because of the different levels of expression and mutations of EGFR. Therefore, several PET radiotracers have been developed for the selective treatment of responsive patients who undergo PET/CT imaging for tyrosine kinase inhibitor (TKI) therapy. In this study, a novel fluorine-18 labeled 4-anilinoquinazoline based PET tracer, 1N-(3-(1-(2-F-fluoroethyl)-1H-1,2,3-triazol-4-yl)phenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine (F-FEA-Erlotinib), was synthesized and biological evaluation was performed in vitro and in vivo. F-FEA-Erlotinib was achieved within 50min with over 88% radiochemical yield (decay corrected RCY), an average specific activity over 50GBq/μmol, and over 99% radiochemical purity. In vitro stability study showed no decomposition of F-FEA-Erlotinib after incubated in PBS and FBS for 2h. Cellular uptake and efflux experiment results indicated the specific binding of F-FEA-Erlotinib to HCC827 cell line with EGFR exon 19 deletions. In vivo, Biodistribution studies revealed that F-FEA-Erlotinib exhibited rapid blood clearance both through hepatobiliary and renal excretion. The tumor uptake of F-FEA-Erlotinib in HepG2, HCC827, and A431 tumor xenografts, with different EGFR expression and mutations, was visualized in PET images. Our results demonstrate the feasibility of using F-FEA-Erlotinib as a PET tracer for screening EGFR TKIs sensitive patients.

Radiosynthesis and biological evaluation of F-labeled 4-anilinoquinazoline derivative (F-FEA-Erlotinib) as a potential EGFR PET agent.

Glycyrrhizinic acid (GA), a principal component derived from licorice which is used extensively as a natural sweetener and traditional folk herbal medicine, is attracting considerable attention because of its broad range of bioactivities. However, the anti-inflammatory mechanism of GA on 12--tetradecanoylphorbol-13-acetate (TPA)-mediated skin inflammation has not been elucidated. Herein, we investigated the anti-inflammatory activity of GA by using a TPA-induced mouse ear model. It was indicated that GA, applied topically onto mouse ears, effectively inhibited the TPA-mediated expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner, respectively. Mechanistic investigations demonstrated that GA down-regulated the expressions of IκBα and p65 and blocked the phosphorylation of IκBα and p65 in TPA-induced mouse skin. Moreover, GA significantly inhibited the TPA-mediated activation of extracellular signal-regulated kinase (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K)/Akt, which are upstream of nuclear factor-kB (NF-κB). Taken together, these results indicated that GA, being of natural origin, may be a potential agent for preventing inflammatory diseases.

Glycyrrhizic acid from licorice down-regulates inflammatory responses  blocking MAPK and PI3K/Akt-dependent NF-κB signalling pathways in TPA-induced skin inflammation.

Glycyrrhizinic acid (GA), a major active ingredient enriched in the roots of licorice, possesses well-confirmed anti-inflammatory effects.

Suppressive effect of glycyrrhizic acid against lipopolysaccharide-induced neuroinflammation and cognitive impairment in C57 mice via toll-like receptor 4 signaling pathway.

Tolfenamic acid (TA) and glycyrrhizic acid (GA) are well-known components with anti-inflammatory properties. However, their combined effects on inflammation have not been well studied. The present study aimed to investigate the  anti-inflammatory effects of TA combined with GA using a 12--tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model, as well as the underlying mechanisms thereof. The results indicated that TA combined with GA led to a stronger inhibition on TPA-induced mouse ear edema compared to the singular treatments. In addition, the combined treatment significantly alleviated subcutaneous tissue inflammation caused by TPA. Further mechanistic investigations demonstrated that TA combined with GA decreased the levels of TPA-induced interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Furthermore, the combined treatment effectively inhibited nuclear factor-κB (NF-κB), extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), phosphor-ERK1/2 and phosphor-JNK, which was accompanied by blocking of the activation and the phosphorylation in mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt signaling pathways. Collectively, our findings revealed that different anti-inflammatory components used in combination lead to enhanced inhibitory effects against inflammation.

Synergistic effect of tolfenamic acid and glycyrrhizic acid on TPA-induced skin inflammation in mice.

Early diagnosis is critical to improve outcomes in rheumatoid arthritis (RA), but current diagnostic tools have limited sensitivity. Here we report a large-scale multicenter study involving training and validation cohorts of 3,262 participants. We show that serum levels of soluble scavenger receptor-A (sSR-A) are increased in patients with RA and correlate positively with clinical and immunological features of the disease. This discriminatory capacity of sSR-A is clinically valuable and complements the diagnosis for early stage and seronegative RA. sSR-A also has 15.97% prevalence in undifferentiated arthritis patients. Furthermore, administration of SR-A accelerates the onset of experimental arthritis in mice, whereas inhibition of SR-A ameliorates the disease pathogenesis. Together, these data identify sSR-A as a potential biomarker in diagnosis of RA, and targeting SR-A might be a therapeutic strategy.

Scavenger receptor-A is a biomarker and effector of rheumatoid arthritis: A large-scale multicenter study.

Neuroinflammatory cytokines are promising therapeutic targets for the treatment of Alzheimer's disease. Herein, we described our efforts toward the investigation of cinnamic acid derivatives as antineuroinflammatory agents. Intensive structural modifications led to the identification of compound  as the most effective antineuroinflammatory agent . The oral administration of compound  could reverse lipopolysaccharide (LPS)-induced memory disturbance and normalize glucose uptake and metabolism in the brains of mice. Further biological studies  revealed that compound  was directly bound to the mitogen-activated protein kinase (MAPK) signaling pathway, resulting in suppression of its downstream signaling pathway by blocking neuroinflammatory progression. Docking studies showed that compound  could be inserted into the active pocket of interleukin-1β (IL-1β). Furthermore, it was confirmed that compound  formed hydrogen bonds with SER84 to enhance the binding affinity. Taken together, these results are of great importance in the development of cinnamic acid derivatives for the treatment of Alzheimer's disease.

Xi Zheng

The First Clinical Medicine College

Southern Medical University

Co-culture Model Using Two Types of Adherent Cell Lines

Xi Zheng

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}The First Clinical Medicine College

Southern Medical University

Co-culture Model Using Two Types of Adherent Cell Lines

The First Clinical Medicine College