The combined utilization of Chlorhexidine and Voriconazole or Natamycin to combat Fusarium infections.

BACKGROUND: Fusarium species are the fungal pathogens most commonly responsible for the mycotic keratitis, which are resistant to the majority of currently available antifungal agents. The present study was designed to assess the efficacy of a combination of low doses chlorhexidine with two other commonly used drugs (voriconazole and natamycin) to treat Fusarium infections. RESULTS: We utilized combinations of chlorhexidine and natamycin or voriconazole against 20 clinical Fusarium strains in vitro using a checkerboard-based microdilution strategy. In order to more fully understand the synergistic interactions between voriconazole and chlorhexidine, we utilized a Galleria mellonella model to confirm the combined antifungal efficacy of chlorhexidine and voriconazole in vivo. We found that for voriconazole, natamycin, and chlorhexidine as single agents, the minimum inhibitory concentration (MIC) ranges were 2-8, 4-16, and > 16 µg/ml, respectively. In contrast, the MIC values for voriconazole and chlorhexidine were reduced to 0.25-1 and 1-2 µg/ml, respectively, when these agents were administered in combination, with synergy being observed for 90% of tested Fusarium strains. Combined chlorhexidine and natamycin treatment, in contrast, exhibited synergistic activity for only 10% of tested Fusarium strains. We observed no evidence of antagonism. Our in vivo model results further confirmed the synergistic antifungal activity of chlorhexidine and voriconazole. CONCLUSIONS: Our results offer novel evidence that voriconazole and chlorhexidine exhibit synergistic activity when used to suppress the growth of Fusarium spp., and these agents may thus offer value as a combination topical antifungal treatment strategy.

Effect of carboxylation cellulose nanocrystal and grape peel extracts on the physical, mechanical and antioxidant properties of konjac glucomannan films.

Active bionanocomposite films were prepared by incorporating konjac glucomannan (KGM) as a matrix, with carboxylation cellulose nanocrystal (C-CNC) as a reinforcement agent and grape peel extracts (GPE) as a natural antioxidation agent. The effects of C-CNC and/or GPE addition on the structural, morphological, barrier, thermal, mechanical and antioxidant properties of the bionanocomposite films were investigated. The rheological results of film forming solutions revealed that C-CNC and GPE were well dispersed in the KGM matrix. Scanning electron micrographs observed the addition of C-CNC had little effect on the microstructure, while more roughness and unevenness were observed on the film surface and cross-section with the C-CNC and GPE. Furthermore, the water vapor barrier property and transparency of the films improved by the addition of the C-CNC and GPE. Notably, the incorporating of C-CNC or GPE significantly alter the mechanical of the KGM/C-CNC/GPE bionanocomposite films. The highest tensile strength was achieved for the KGM/GPE bionanocomposite film with 10 wt% C-CNC, indicating C-CNC and GPE had synergistic effect on enhancing the TS of KGM film. Moreover, the KGM/C-CNC/GPE films exhibited strong antioxidant activity. These results suggested that KGM/C-CNC/GPE bionanocomposite films can be used as an active food packaging for increasing shelf life of packaged foods.

A novel cyclic dipeptide from deep marine-derived fungus Aspergillus sp. SCSIOW2.

A novel cyclic dipeptide, 14-hydroxy-cyclopeptine (1), was purified from a deep sea derived fungal isolate identified as an Aspergillus sp. The structure was elucidated by detailed spectroscopic analyses using 1D and 2D NMR experiments and high resolution mass spectrometry. The absolute configuration of the amino acid was determined by Marfey's method. Two conformational isomers of 1 were established by ROE analyses. 1 inhibited nitric oxide production with IC50 values at 40.3 µg/mL in a lipopolysaccharide and recombinant mouse interferon-γ -activated macrophage-like cell line, RAW 264.7 and showed no cytotoxic effect in the tested dose range up to 100 µg/mL.

Mulberry fruit prevents LPS-induced NF-κB/pERK/MAPK signals in macrophages and suppresses acute colitis and colorectal tumorigenesis in mice.

Here, we investigated the impact of mulberry fruit (MBF) extracts on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages, and the therapeutic efficacy of MBF diet in mice with dextran sulfate sodium (DSS)-induced acute colitis and MUC2(-/-) mice with colorectal cancer. In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-ß) and IL-6. Particularly, a dose-dependent inhibition on LPS-induced inflammatory responses was observed following treatment with MBF dichloromethane extract (MBF-DE), in which linoleic acid and ethyl linolenate were identified as two active compounds. Moreover, we elucidated that MBF-DE attenuated LPS-induced inflammatory responses by blocking activation of both NF-κB/p65 and pERK/MAPK pathways. In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage. In addition, MBF-fed MUC2(-/-) mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group. Overall, our results demonstrated that MBF suppressed the development of intestinal inflammation and tumorgenesis both in vitro and in vivo, and supports the potential of MBF as a therapeutic functional food for testing in human clinical trials.

Emodin protects against diabetic cardiomyopathy by regulating the AKT/GSK-3ß signaling pathway in the rat model.

Diabetes mellitus (DM) has been recognized as a major health problem. Emodin (Emo) has been reported to exhibit protective effects against diabetic nephropathy. However, little has been known about the effect of Emo on diabetic cardiomyopathy (DCM). A type 2 DM model was induced in rats by low dose streptozotocin (STZ) combined with high energy intake. We found that Emo-treated groups displayed significantly higher body weight (BW) and lower heart weight (HW)/BW. Furthermore, Emo could significantly decrease blood glucose, total cholesterol (TG) levels, and triglyceride (TC) levels in diabetic rats. Moreover, the Emo-treated group showed a marked increase in heart rate (HR) and showed lower left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular posterior wall thickness (LWPWT), and interventricular septal diastolic wall thickness (IVSD). Emo induced a significant increase in phosphorylation of Akt and GSK-3ß in myocardium. These results suggest that Emo may have great therapeutic potential in the treatment of DCM by Akt/GSK-3ß signaling pathway.

Anthocyanin-rich fractions from red raspberries attenuate inflammation in both RAW264.7 macrophages and a mouse model of colitis.

Edible berries have a broad spectrum of biomedical functions, including improving immune responses and reducing risk for chronic diseases. In this study, the anti-inflammatory activities of crude extracts (CEs), anthocyanin-rich fractions (ARFs), and des-anthocyanin fractions (DAFs) from seven berries were evaluated based on their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)/IFN-γ-activated RAW264.7 macrophages. ARFs from red raspberries (RR-ARFs) exhibited the highest efficiency in suppressing NO synthesis. The anti-inflammatory properties were also demonstrated by reducing the expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-1ß) and IL-6 in RAW264.7 cells. The luciferase reporter assay demonstrated that the activities of NF-κB and AP-1 signaling pathways were significantly suppressed by RR-ARFs. Further studies showed that RR-ARFs decreased the phosphorylation of IKK, IκBα, p65 and JNK and the nuclear translocation of p65 in LPS/IFN-γ-stimulated RAW264.7 cells. In a mouse colitis model, dextran sulfate sodium (DSS)-induced weight loss and histological damage were significantly ameliorated by RR-ARFs treatment. Taken together, our results indicate that RR-ARFs attenuate inflammation both in vitro and in vivo primarily by inhibiting the activation of NF-κB and MAPKs. The anti-inflammatory of RR-ARFs could be harnessed and applied in animal agriculture, drug and food industries.

[Effects end mechanisms of curcumol beta-cyclodextrin compound on the proliferation and apoptosls of esophageal carcinoma cell line TE-1].

OBJECTIVE: To investigate the effects and mechanisms of Curcumol beta-cyclodextrin Compound (CbetaC) on the proliferation and apoptosis of esophageal carcinoma cell line TE-1. METHODS: The CbetaC was prepared by saturated solution and confirmed by infrared absorption spectroscopy. The effects of CbetaC (at 25, 50, 100 mg/L) on the proliferation of human esophageal carcinoma cell line TE-1 in vitro was analyzed by MTT assay. The cell cycles and apoptosis were detected by flow cytometer. The relative expression of survivin mRNA was detected by real-time fluorescent quantitative PCR and calculated by the 2(-deltaCt) method. The protein expression of survivin was measured by Western blot. RESULTS: Compared with the control group, results of MTT showed that CbetaC at each dose significantly inhibited the proliferation of TE-1 cells in a dose-dependent manner (P < 0.05). The results of flow cytometry showed that CbetaC resulted in the cell cycle arrest at G0/G1 and G2/M phase, and promoted the cell apoptosis. Besides, when compared with the control group, the protein and mRNA expressions of survivin obviously decreased in each CbetaC group (P < 0.05). CONCLUSIONS: CbetaC could inhibit the proliferation of esophageal carcinoma cell TE-1 and promote the apoptosis. Its inhibition on the survivin expression was correlated with its inhibition on the malignant phenotypes of esophageal carcinoma cells.