RESUMO
Anopheles gambiae s.s. is a key vector of Plasmodium parasites. Repellents, which may be a promising alternative to pesticides used to control malaria mosquitoes. Although citronellal is a known mosquito repellent, its repellency characteristics are largely unknown. Determining the specific odorant-binding proteins (OBPs) and odorant receptors (ORs) that detect and transfer the citronellal molecule in A. gambiae s.s. will help to define the mode of action of this compound. In this research, we assessed the repellent activity of citronellal in A. gambiae s.s. using a Y-tube olfactory meter, screened candidate citronellal-binding OBPs and ORs using reverse molecular docking, clarified the binding properties of predicted proteins for citronellal using fluorescence competition binding assay. Results showed that citronellal had a dosage effect on repelling A. gambiae s.s.. The 50% repellent rate was determined to be 4.02 nmol. Results of simulated molecular docking showed that the only proteins that bound tightly with citronellal were AgamOBP4 and AgamORC7. Fluorescence competitive binding assays confirmed the simulations. This research determined that citronellal was captured by AgamOBP4 and transmitted to AgamORC7 in A. gambiae s.s.. Our study will be beneficial in the further understanding the repellent mechanism of citronellal against A. gambiae s.s..
Assuntos
Monoterpenos Acíclicos/farmacologia , Aldeídos/farmacologia , Anopheles/efeitos dos fármacos , Animais , Anopheles/metabolismo , Feminino , Proteínas de Insetos/metabolismo , Repelentes de Insetos/farmacologia , Malária/prevenção & controle , Simulação de Acoplamento Molecular , Mosquitos Vetores/efeitos dos fármacos , Receptores Odorantes/metabolismoRESUMO
Automatic delineation and segmentation of airway structures from endoscopic optical coherence tomography (OCT) images improve image analysis efficiency and thus has been of particular interest. Conventional two-dimensional automatic segmentation methods, such as the dynamic programming approach, ensures the edge-continuity in the xz-direction (intra-B-scan), but fails to preserve the surface-continuity when concerning the y-direction (inter-B-scan). To solve this, we present a novel automatic three-dimensional (3D) airway segmentation strategy. Our segmentation scheme includes an artifact-oriented pre-processing pipeline and a modified 3D optimal graph search algorithm incorporating adaptive tissue-curvature adjustment. The proposed algorithm is tested on endoscopic airway OCT image data sets acquired by different swept-source OCT platforms, and on different animal and human models. With our method, the results show continuous surface segmentation performance, which is both robust and accurate.
RESUMO
The World Cancer Research Fund International has released 32 anticancer effects (ACEs) that targeted every stage of cancer processes. Thus, we designed two formulas of natural food combination Diet I and Diet II, mainly produced by elite crop varieties rich in ACEs with different mixture ratios, and evaluated their cancer preventive effects on N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. After 20 weeks of dietary intervention, Diet I and Diet II reduced incidence, size, and number of hepatic nodules (p < 0.01) and prevented hepatic tumor formation in NDEA-induced hepatocarcinogenesis rats. Low-grade hepatic dysplasia incidence was 20% for Diet II and 40% for Diet I, and apparent hepatocellular carcinomas (HCC) rates were both 0, while 90% HCC in control diet treatment group (p < 0.01). Diet I and Diet II ameliorated abnormal liver function enzymes, reduced serum alpha fetal protein, tumor-specific growth factor, dickkopf-related protein 1, tumor necrosis factor-alpha and interleukin-6 levels, regulated hepatic phase I and II xenobiotic-metabolizing enzymes, enhanced antioxidant capacity, suppressed NDEA-initiated oxidative DNA damage, and induced apoptosis coupled to down-regulation of proinflammatory, invasion, and angiogenesis markers. Daily intake of combination diet produced from ACEs-rich elite crop varieties can effectively prevent or delay occurrence and development of NDEA-induced hepatocarcinogenesis in rats.
RESUMO
The hierarchical microtextured/nanotextured topographies have been recognized to have better tissue integration properties, but the underlying mechanisms are only partially understood. Hedgehog signaling plays a pivotal role in developmental and homeostatic angiogenesis. We suppose that the Hedgehog-Gli1 signaling may play a significant role in the response of endothelial cells to microtextured/nanotextured topographies (MNTs). To confirm this hypothesis, we produced the MNTs decorated with TiO2 nanotubes of two different diameters (25 and 70 nm), and the proliferation, apoptosis, angiogenesis-related genes expression and Hedgehog signaling activity of human umbilical vein endothelial cells (HUVECs) grown onto these MNTs were measured. Our results showed that the MNTs induced significantly high expression of Sonic Hedgehog (SHH), Smoothened (SMO) and GLI1 in the HUVECs as well as high activation of Hedgehog-Gli1 signaling, compared to the smooth surface. The HUVECs grown on the MNTs showed significantly high levels of adhesion, proliferation and expression of angiogenesis-related genes, including angiopoietin-1 (ANG-1), vascular endothelial growth factor (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2) and endothelial nitric oxide synthase (ENOS); these enhancements were attenuated by siRNA-mediated depletion of SMO, which indicated a significant role of Hedgehog-Gli1 signaling in mediating the enhanced effect of the MNTs on the angiogenic potential of HUVECs. This study may contribute to the modification of biomaterial surfaces for better tissue integration and clinical performance.
Assuntos
Proliferação de Células/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Nanotubos/química , Neovascularização Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Titânio , Proteína GLI1 em Dedos de Zinco/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Propriedades de Superfície , Titânio/química , Titânio/farmacologiaRESUMO
PURPOSE: To analyze the effects of different processes during bonding on endogenous cysteine cathepsin activity in dentin. MATERIALS AND METHODS: Dentin powder, prepared from extracted human third molars, was divided into 10 groups. Two lots of dentin powder were used to detect the effects of the procedure of protein extraction on endogenous cathepsin activity. The others were used to study effects of different acid-etching or adhesive treatments on enzyme activity. Concentrations of 37% phosphoric acid or 10% phosphoric acid, two etch-and-rinse adhesive systems, and two self-etching adhesive systems were used as dentin powder treatments. The untreated mineralized dentin powder was set as the control. After treatment, the proteins of each group were extracted. The total cathepsin activity in the extracts of each group was monitored with a fluorescence reader. RESULTS: In the control group, there were no significant differences in cathepsin activity between the protein extract before EDTA treatment and the protein extract after EDTA treatment (p > 0.05). The cathepsin activities of the three different extracts in the 37% phosphoric acid-treated group were different from each other (p < 0.05). The two acid-etching groups and two etch-and-rinse groups showed significant enzyme activity reduction vs the control group (p < 0.05). There were no significant differences between those four groups (p > 0.05). Treating the dentin powder with any of the two self-etching adhesives resulted in an increase in cathepsin activity (p < 0.05). CONCLUSIONS: The activity of cysteine cathepsins can be detected in dentin powder. Treatment with EDTA during protein extraction exerted an influence on cathepsin activity. Acid etching or etch-and-rinse adhesive systems may reduce the activity of endogenous cathepsins in dentin. Self-etching adhesive systems may increase the enzyme activity.
Assuntos
Condicionamento Ácido do Dente/métodos , Catepsinas/análise , Colagem Dentária/métodos , Dentina/enzimologia , Catepsinas/antagonistas & inibidores , Catepsinas/efeitos dos fármacos , Compostos Cromogênicos , Cisteína Proteases/análise , Cisteína Proteases/efeitos dos fármacos , Inibidores de Cisteína Proteinase/farmacologia , Cimentos Dentários/farmacologia , Dentina/efeitos dos fármacos , Adesivos Dentinários/farmacologia , Ácido Edético/farmacologia , Corantes Fluorescentes , Humanos , Leucina/análogos & derivados , Leucina/farmacologia , Ácidos Fosfóricos/farmacologia , Ácidos Polimetacrílicos/farmacologia , Cimentos de Resina/farmacologiaRESUMO
OBJECTIVE: To investigate the effect of baicalein and quercetin on the enzymatic resistance of dentin matrix collagen. METHODS: Baicalein, quercetin and proanthocyanidin were dissolved in 20% dimethyl sulfoxide (DMSO) ethanol and prepared into pretreatment agents with a concentration of 50 g/L. Demineralized dentin specimens were prepared and immersed in pretreatment agents at 37 °C for 24 h, then they were digested in solution containing type?collagenase. The pretreatment agents of blank control group and negative control group were 20% DMSO ethanol, blank control group were digested in solution without collagenase. The ultimate tensile strength (UTS) and the hydroxyproline content of enzymolysis liquid in each group were measured respectively after collagenase digestion for 24 h, the dentin collagen morphology were observed under a field emission scanning electron microscopic (FE-SEM) after collagenase digestion for 12 h. RESULTS: After collagenase digestion for 24 h, the baicalein group had the highest UTS [(16.00±1.31) MPa], followed by proanthocyanidin group [(12.64±0.91) MPa], blank control group [(7.84±1.18) MPa], quercetin group [(3.20±1.07) MPa], and negative control group (0 MPa). Significant differences were detected among the UTS in each two group (P < 0.01). The hydroxyproline content in blank control group was the lowest [(0.40 ± 0.16) mg/L], followed by baicalein group[(2.95 ± 0.18) mg/L], proanthocyanidin group [(4.78±0.38) mg/L], quercetin group[(28.22±1.53) mg/L], and negative control group [(34.39±0.39) mg/L]. There were significant differences among the hydroxyproline contents in each group (P < 0.01). After collagenase digestion for 12 h, intact collagen network could be seen in blank control group under a FE-SEM. Collagen network in negative control group suffered nearly complete destruction and collapsed. In quercetin group, most of collagen collapsed. In proanthocyanidin group, a small portion of collagen destruction and collapse could be seen. In baicalein group, collagen network remained intact. CONCLUSIONS: The use of baicalein and quercetin could improve enzymatic resistance of dentin matrix collagen at a concentration of 50 g/L. The effect of baicalein was better than that of proanthocyanidin while the effect of quercetin was weaker than that of proanthocyanidin.