Palladium-Catalyzed Three-Component Cascade Carbonylation Reaction to Construct Benzofuran Derivatives.

A novel three-component cyclization carbonylation reaction of iodoarene-tethered propargyl ethers with amine and CO is reported. This palladium-catalyzed cascade reaction undergoes a sequence of oxidative addition, unsaturated bond migration, carbonyl insertion, and nucleophilic attack to deliver the benzofuran skeleton. Both aromatic amines and aliphatic amines could proceed smoothly in this transformation under one atm of CO.

Quercetin pretreatment enhances the radiosensitivity of colon cancer cells by targeting Notch-1 pathway.

Cancer stem-like cells are rare immortal cells within tumor, which are thought to play important roles in ionizing radiation (IR) therapy-resistance. Quercetin is a natural flavonoid with potential anti-cancer properties without significant cytotoxicity in normal tissues. In this study, we demonstrated that quercetin-IR combination treatment exhibited more dramatic anti-cancer effect than either quercetin or IR treatment alone via targeting colon cancer stem cells (CSCs) and inhibiting the Notch-1 signaling. These effects were further verified by in vivo studies which showed remarkable decrease of the CSCs markers and the expression of Notch-1 signaling proteins in human colon cancer xenografts in nude mice. Co-treatment with quercetin and low dose of radiation significantly reduced the expressions of all five proteins of γ-secretase complex in HT-29 and DLD-1 cells. In addition, ectopic expression of the Notch intracellular domain (NICD) partly reversed the inhibition effects by the combination therapy. In conclusion, our results indicated that the combination of quercetin (20 µM) and IR (5Gy) might be a promising therapeutic strategy for colon cancer treatment by targeting colon cancer stem-like cells and inhibiting the Notch-1 signaling. In future studies, we intend to further explore the potential therapeutic efficacy of the quercetin-radiation combination treatment in clinical trials.

Berberine Attenuates Cholesterol Accumulation in Macrophage Foam Cells by Suppressing AP-1 Activity and Activation of the Nrf2/HO-1 Pathway.

Atherosclerosis is a chronic inflammation condition resulting from the interaction between lipoproteins, monocyte-derived macrophages, T lymphocytes, and other cellular elements in the arterial wall. Macrophage-derived foam cells play a key role in both early and advanced stage of atherosclerosis. Previous studies have shown that berberine could inhibit foam cell formation and prevent experimental atherosclerosis. However, its underlying molecular mechanisms have not been fully clarified. In this study, we explored the cholesterol-lowering effects of berberine in macrophage-derived foam cells and investigated its possible mechanisms in prevention and treatment of atherosclerosis. Here, we demonstrated that berberine could inhibit atherosclerosis in apolipoprotein E-deficient mice and induce cholesterol reduction as well as decrease the content of macrophages. Berberine can regulate oxLDL uptake and cholesterol efflux, thus suppresses foam cell formation. Mechanisms study showed that berberine can suppress scavenger receptor expression via inhibiting the activity of AP-1 and upregulate ATP-binding cassette transporter via activating Nrf2/HO-1 signaling in human macrophage. In summary, berberine significantly inhibits atherosclerotic disease development by regulating lipid homeostasis and suppressing macrophage foam cell formation.

Spatio-temporal localization of HIF-1alpha and COX-2 during irradiation-induced oral mucositis in a rat model system.

PURPOSE: Oral mucositis is a common side effect of radiotherapy for head and neck cancer. The purpose of this study was to examine the significance of and the relationship between hypoxia inducible factor-1alpha (HIF-1alpha) and cyclooxygenase-2 (COX-2) gene expression and the corresponding protein levels in irradiated rat mucosa. MATERIAL AND METHODS: A Sprague-Dawley rat model of irradiation-induced oral mucositis was generated. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the HIF-1alpha and COX-2 mRNA level in rat buccal mucosa exposed to a fractionated irradiation regime. The Streptavidin-Biotin-Complex method was applied to delineate the in situ localization, intensity, and distribution of both proteins. The right buccal mucosa was not irradiated and used as control tissue. RESULTS: The RT-PCR analyses demonstrated that, upon irradiation, HIF-1alpha and COX-2 expression was significantly induced in the left buccal mucosa in contrast to control buccal mucosa. Based on immunohistochemical analyses, the HIF-1alpha and COX-2 level, in situ localization, and the type of cells exhibiting the highest HIF-1alpha and COX-2 amounts appear to correlate. CONCLUSIONS: The expression and protein levels of HIF-1alpha and COX-2 are substantially enhanced in irradiated rat mucosa and correlate with each other and with the severity of irradiation-induced oral mucositis.

Lnc-NTF3-5 promotes osteogenic differentiation of maxillary sinus membrane stem cells via sponging miR-93-3p.

BACKGROUND: The function and the mechanism of long non-coding RNAs (lncRNAs) on the osteogenic differentiation of maxillary sinus membrane stem cells (MSMSCs) remain largely unknown. MATERIALS AND METHODS: The expression of lnc-NTF3-5 and Runt-related transcription factor 2 (RUNX2), Osterix (OSX), and Alkaline Phosphatase (ALP) was examined by quantitative real-time PCR (qRT-PCR) in MSMSCs during the process osteogenic differentiation. Then the function of lnc-NTF3-5 was evaluated by loss- and gain-of-function techniques, as well as qRT-PCR, western blot, and Alizarin Red staining. In addition, the microRNAs (miRNAs) sponge potential of lnc-NTF3-5 was assessed through RNA immunoprecipitation, dual luciferase reporter assay, and in vivo ectopic bone formation. RESULTS: Lnc-NTF3-5, RUNX2, OSX, and ALP increased alone with the differentiation. Inhibition of lnc-NTF3-5 decreased the expression of RUNX2, OSX, and ALP both at mRNA and protein levels. Alizarin red staining showed similar trend. In contrast, overexpression of lnc-NTF3-5 presented totally opposite effects. Besides, overexpression of lnc-NTF3-5 could decrease the expression of microRNA-93-3p (miR-93-3p). Enhance miR-93-3p could also inhibit the expression level of lnc-NTF3-5. RNA immunoprecipitation demonstrated that lnc-NTF3-5 is directly bound to miR-93-3p and dual luciferase reporter assay proved that miR-93-3p targets 3' UTR of RUNX2 to regulate its expression. Ultimately, in vivo bone formation study showed that lnc-NTF3-5 and miR-93-3p inhibitor co-transfection group displayed the strongest bone formation. CONCLUSIONS: The novel pathway lnc-NTF3-5/miR-93-3p/RUNX2 could regulate osteogenic differentiation of MSMSCs and might serve as a therapeutic target for bone regeneration in the posterior maxilla.

Guided bone regeneration using collagen membranes for sinus augmentation.

We investigated the effect of guided bony regeneration using collagen membranes for sinus augmentation in the first maxillary molars of 18 adult female beagle dogs. The teeth were extracted bilaterally and the sinus floors were lifted with simultaneous implantation. The grafted material composed of a combination of autografts and Bio-oss in a 2:1 ratio. On the experimental side in each dog, collagen membrane was folded at the lateral osteotomy window, at the apex of the implants, and at a certain part of the palatal bone. On the opposite (control) side, the collagen membrane covered the osteotomy window. Six animals were killed at each of 4, 12, and 24 weeks postoperatively. Gross observation, biomechanical testing, and histological examinations were made. On the experimental side, grafted materials showed no obvious resorption or subsidence, and a new bone had formed at the apex of the implants. On the control side, the grafted materials had been shifted and absorbed. Histological examination showed increased formation of a new bone in the experimental group, which matured over time. At 4 weeks, inflammatory cells were present in the control group, which showed less maturation of the new bone. The pull-out force increased with time and, at week 24, there was a significant difference in pull-out force between the two groups (p<0.01). Guided bony regeneration with the enfolded coverage of membrane can effectively reduce resorption of grafted bone on the apical surface of implants and stimulate formation of the new bone in sinus augmentation.

[Maxillary sinus augmentation with simultaneous implantation using guided bone regeneration].

OBJECTIVE: To investigate the effect of new bone formation in sinus augmentation with guided bone regeneration (GBR) using collagen membranes. METHODS: The first maxillary molars of 18 adult female Beagle dogs were extracted and the sinus floors of both sides were lifted with simultaneous implantation. A combination of autografts and Bio-Oss in a 2:1 ratio was placed in the space under the membrane. On the experimental side in each dog, the collagen membrane was folded at the lateral osteotomy window, the apex of the implants and a certain part of palatal bone. On the contralateral control side, the collagen membrane only covered the osteotomy window. Six animals were sacrificed at 4, 12, and 24 weeks respectively after surgery. Gross observation, biomechanical testing and histological examinations were performed. RESULTS: The translocation of grafted materials and bone absorption were found on the top of implants in the control side, and the grafted materials kept original shape at the experimental side at 4th week. The granule of Bio-oss absorbed obviously at 12th and 24th week. The pull-out force increased with time. At 24th week, the force of pull out was 558.1 ± 37.4 N at the study side, and 471.4 ± 31.5 N at the control side. There was a significant difference in the pull-out force was noted between the two groups (P < 0.01). Histological examination showed new bone formation on the sinus floor, and the grafted materials gradually reduced with time CONCLUSIONS: GBR with the enfolded-coverage of the membrane can effectively decrease absorption of the grafted materialon the apical surface of implants and stimulate new bone formation in the sinus augmentation.