OBJECTIVE: To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid (BDSF) and fluconazole (FLU) or itraconazole (ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo. METHODS: Minimum inhibitory concentrations (MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). RESULTS: BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ⪕ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 μg/mL. The qRT-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mRNA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis. CONCLUSION The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.
Antifungal Agents ; pharmacology ; Burkholderia cenocepacia ; chemistry ; Candida albicans ; drug effects ; physiology ; Candidiasis ; drug therapy ; Drug Resistance, Fungal ; Fatty Acids, Monounsaturated ; adverse effects ; Fluconazole ; pharmacology ; Humans ; Microbial Sensitivity Tests ; Triazoles ; metabolism

OBJECTIVE: To evaluate the efficacy of cis-2-dodecenoic acid (BDSF) in the treatment and prevention of vaginal candidiasis in vivo. METHODS: The activities of different concentrations of BDSF against the virulence factors of Candida albicans (C. albicans) were determined in vitro. An experimental mouse model of Candida vaginitis was treated with 250 μmol/L BDSF. Treatment efficiency was evaluated in accordance with vaginal fungal burden and inflammation symptoms. RESULTS: In vitro experiments indicated that BDSF attenuated the adhesion and damage of C. albicans to epithelial cells by decreasing phospholipase secretion and blocking filament formation. Treatment with 30 μmol/L BDSF reduced the adhesion and damage of C. albicans to epithelial cells by 36.9% and 42.3%, respectively. Treatment with 200 μmol/L BDSF completely inhibited phospholipase activity. In vivo mouse experiments demonstrated that BDSF could effectively eliminate vaginal infection and relieve inflammatory symptoms. Four days of treatment with 250 μmol/L BDSF reduced vaginal fungal loads by 6-fold and depressed inflammation. Moreover, BDSF treatment decreased the expression levels of the inflammatory chemokine-associated genes MCP-1 and IGFBP3 by 2.5- and 2-fold, respectively. CONCLUSION BDSF is a novel alternative drug that can efficiently control vaginal candidiasis by inhibiting the virulence factors of C. albicans.
Animals ; Candida albicans ; drug effects ; metabolism ; pathogenicity ; physiology ; Candidiasis, Vulvovaginal ; drug therapy ; genetics ; immunology ; microbiology ; Chemokine CCL2 ; genetics ; immunology ; Disease Models, Animal ; Fatty Acids, Monounsaturated ; administration & dosage ; Female ; Fungal Proteins ; genetics ; metabolism ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; genetics ; immunology ; Mice ; Virulence ; drug effects ; Virulence Factors ; genetics ; metabolism

Animals ; Body Weight ; physiology ; Computational Biology ; methods ; Disease Models, Animal ; Doxorubicin ; toxicity ; Fatty Acids, Monounsaturated ; blood ; metabolism ; Glomerulosclerosis, Focal Segmental ; blood ; chemically induced ; metabolism ; Male ; Methoxyhydroxyphenylglycol ; analogs & derivatives ; blood ; metabolism ; Mice ; Mice, Inbred BALB C ; Pyridoxine ; blood ; metabolism ; Valine ; analogs & derivatives ; blood ; metabolism ; Vanillic Acid ; blood ; metabolism

Forest musk deer is one of the large-scale farming musk deer animals with the largest population at the same time. The male musk deer can secrete valuable medicines, which has high medicinal and economic value. Due to the loss of habitat and indiscriminate hunting, the numbers of wild population specie and the distribution have been drastically reduced. Therefore, in-depth understanding of the molecular genetics progress of forest musk deer will pave a way for musk deer protection and breeding. In this review, the progress associated with the molecular marker, genetic classification, artificial breeding, musk secretion and disease in past decades were reviewed, in order to provide a theoretical basis for subsequent molecular genetic researches in forest musk deer.
Animals ; Breeding ; Deer ; classification ; genetics ; growth & development ; metabolism ; Ecosystem ; Fatty Acids, Monounsaturated ; chemistry ; metabolism ; Female ; Male

OBJECTIVETo study the effects of drug plasma of musk and olibanum (DP-M&O) on the release of inflammatory cytokines from monocytes and the expressions of the proteins associated with inflammation of prostatic or endothelial cells induced by prostate antigen (PAg) stimulation.

METHODSWe prepared DP-M&O using SD rats and monocytes and PAgs using BALB/c mice. We pre-treated the monocytes with DP-M&O at the gradient concentrations of 0, 2.5, 5, 10, and 20% for 1 hour, activated them with PAgs, and then cultured them for 96 hours, followed by detection of the release of inflammatory cytokines. We co-cultured the prostate RWPE-1 cells with the endothelial EA. hy926 cells, pre-treated them with the same gradient concentrations of DP-M&O as above for 1 hour, activated with PAgs, and cultured for 96 hours. Then we determined the expression levels of the proteins associated with inflammation of RWPE-1 and EA. hy926 cells by Western blot.

RESULTSDP-M&O decreased the levels of TNF-alpha, IL-1beta, IL-6, and IL-8 and increased that of IL-10 in a concentration-dependent manner. Significant differences were found between the 20% P-M&O and PAg groups in the release of the inflammatory cytokines TNF-alpha (70.8 +/- 22.3 vs. 277.1 +/- 65.5, P < 0.01) , IL-113 (277.5 +/- 22.6 vs. 630.4 +/- 89.7, P <0.01), IL-6 (232.7 +/- 62.7 vs. 994.2 vs. 182.3, P < 0.01), IL-8 (227.3 +/- 79.2 vs. 769.3 +/- 284.1, P < 0.01), and IL-10 (640.2 +/- 201.2 vs. 271.1 +/- 55.8, P < 0.01). Compared with the PAg group, the 10 and 20% P-M&O groups showed remarkable decreases in the protein expression of MCP-1/CCL2 in the RWPE-1 cells (1.12 +/- 0.34 vs. 0.56 +/- 0.11 and 0.34 +/- 0.08) and that of VCAM-1 in the EA. hy926 cells (0.94 +/- 0.22 vs. 0.52 +/- 0.17 and 0.38 +/- 0.12) (P < 0.05 or 0.01).

CONCLUSIONThe compatibility of musk and olibanum can decrease the expression of MCP-1/CCL2 in prostate cells and VCAM-1 in vascular endothelial cells, blocking the adhesion of leucocytes and suppressing inflammatory response.

Animals ; Blotting, Western ; Cytokines ; metabolism ; Endothelial Cells ; drug effects ; metabolism ; Fatty Acids, Monounsaturated ; pharmacology ; Frankincense ; pharmacology ; Inflammation ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; Male ; Mice ; Mice, Inbred BALB C ; Monocytes ; drug effects ; metabolism ; Prostate ; cytology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism ; Vascular Cell Adhesion Molecule-1 ; metabolism

OBJECTIVETo investigate the effects of the combination of musk and olibanum on the tight junction protein expressions in prostatic epithelial cells of normal and chronic prostatitis (CP) rats.

METHODSEighty male SD rats were randomly divided into 8 groups of equal number: normal control, normal musk, normal olibanum, normal musk + olibanum, CP model control, CP model musk, CP model olibanum, and CP model musk + olibanum. At 60 days after modeling, the rats in the control, musk, olibanum, and musk + olibanum groups were treated intragastrically with normal saline, musk (0.021 g per kg body weight per day), olibanum (1.05 g per kg body weight per day), or musk + olibanum respectively, all for 3 days. Then, all the rats were sacrificed and their prostate tissues harvested for detection of the expressions of the tight junction proteins Claudin-1, Claudin-3, Occludin, and ZO-1 in the prostatic epithelial cells by immunohistochemical staining.

RESULTSIn the CP models, only the expression of Claudin-1 was significantly increased. In the normal rats, the expression of Claudin-1 was remarkably upregulated after treated with musk (824.6 ± 393.3, P < 0.05), olibanum (982.0 ± 334.0, P < 0.05), and musk + olibanum (1088.1 ± 640.2, P < 0.01); that of Claudin-3 was elevated markedly by olibanum (1 009.5 ± 243.6, P < 0.05) and insignificantly by musk (597.5 ± 80.7), but the increasing effect of olibanum was reduced by musk + olibanum (678.4 ± 255.1). No statistically significant differences were found in the expression of Occludin among the rats treated with musk (693.0 ± 424.8), olibanum (732.1 ± 302.0), and musk + olibanum (560.2 ± 202.3), or in that of ZO-1 in the animals treated with musk (290.0 ± 166.8) and olibanum (419.7 ± 108.1), but the latter was markedly decreased in the musk + olibanum group (197.7 ± 98.2, P < 0.05). In the CP rat models, both the expressions of Claudin-1 (823.0 ± 100.1, P < 0.01) and Occludin (1160.0 ± 32.2, P < 0.05) were significantly increased. The expression of Claudin-1 was remarkably down-regulated by musk (764.9 ± 179.0), olibanum (468.4 ± 220.4), and musk + olibanum (335.1 ± 204.0) (all P < 0.05), but that of Claudin-3 up-regulated by musk (744.6 ± 94.5) and olibanum (700.1 ± 223.7) (both P < 0.05). The expression of Occludin was reduced by musk (615.0 ± 221.0), olibanum (749.6 ± 321.7), and musk + olibanum (505.8 ± 523.7), while that of ZO-1 increased by olibaum (443.2 ± 44.9) and decreased by musk + olibanum (213.5 ± 24.9, P < 0.05).

CONCLUSIONIn physiological and pathological conditions, the combination of musk and olibanum acts on the expressions of tight junction proteins in prostate epithelial cells in a selective and dual-targeting manner, promoting their permeability by down-regulating the expression of ZO-1 and maintaining their structural stability by regulating the expressions of Claudin-1, Claudin-3, and Occludin.

Animals ; Claudins ; metabolism ; Down-Regulation ; Epithelial Cells ; drug effects ; Fatty Acids, Monounsaturated ; chemistry ; Frankincense ; chemistry ; Male ; Occludin ; metabolism ; Prostate ; cytology ; Prostatitis ; Rats ; Rats, Sprague-Dawley ; Tight Junction Proteins ; metabolism ; Up-Regulation

Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.
Animals ; Biological Products ; CHO Cells ; Cricetulus ; Drug Interactions ; Fatty Acids, Monounsaturated ; pharmacology ; Flavonoids ; pharmacology ; Indoles ; pharmacology ; Inhibitory Concentration 50 ; Organic Anion Transporters ; genetics ; metabolism ; Rosuvastatin Calcium ; pharmacology ; Structure-Activity Relationship

OBJECTIVETo summarize the importance of Mediterranean diet in the prevention and management of type 2 diabetes.

DATA SOURCESWe searched electronic database on PubMed up to 14 April 2014, we identified these articles with following key words: "Mediterranean diet" and "diabetes". The initial search resulted in 451 entries. The search strategy had no language and publication date restrictions. The relevance of the studies was assessed based only on the title and abstract. The studies included in our review had to match the following inclusion criteria: (1) randomized clinical trials and meta-analysis or systematic review, and (2) provided strong evidence for the diet as a way to prevent type 2 diabetes, and improve glycemic control and cardiovascular risk factors in diabetic patients. We reviewed 49 manuscripts and only 22 met our inclusion criteria.

STUDY SELECTIONRelevant literatures including randomized control trials, meta-analysis or systematic review.

RESULTSBased on several studies, Mediterranean diet is inversely related to type 2 diabetes and plays important roles in the management of type 2 diabetes. Based on the evidence gathered and evaluated from various studies, we concluded combination and interaction of Mediterranean diet components, such as fruits, vegetables, nuts, legumes, whole grains, fish and moderate intakes of red wine, which contain essential nutrients and health promoting properties, including high fibers, high magnesium, high anti-oxidant and high monounsaturatal fatty acids (MUFA). Interaction and combination of these essential nutrients and health promoting properties found to lower body weight, hemoglobin A1C (HbA1c), low density lipoprotein (LDL), oxidative-stress and improve high density lipoprotein (HDL) level; which are beneficial for prevention and prognosis improvement of type 2 diabetes.

CONCLUSIONSIn the modern society, poor dietary habits accompanied by inadequate physical activity are associated with the risk of having obesity and type 2 diabetes. Promoting healthy lifestyle and diet are not only beneficial in the prevention and treatment of various diseases but also important in maintaining the overall health. Switching from unhealthy diet to health-friendly diet such as Mediterranean diet represents healthy lifestyle choice.

Antioxidants ; metabolism ; Diabetes Mellitus, Type 2 ; metabolism ; prevention & control ; Diet, Mediterranean ; Fatty Acids, Monounsaturated ; metabolism ; Humans ; Magnesium ; metabolism

OBJECTIVETo identify the anti-inflammatory effects of artificial musk aqueous extract(AME)on lipopolysaccharide-stimulated cytokines secreted or released by RAW264.7 cells.

METHODSCytokines including interleukin(IL)-6,IL-10,and tumor necrosis factor Α were determined using cytokine enzyme-linked immunosorbent assay kits.

RESULTCompared with model group,the levels of major cytokines such as tumor necrosis factor Α,IL-6,and IL-10 significantly decreased in different AME groups in a dose-dependent manner.

CONCLUSIONIn lipopolysaccharide-stimulated RAW264.7 macrophages,AME can remarkably inhibit the release of inflammatory cytokines and thus exerts its anti-inflammatory effects.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Cell Line, Tumor ; Cytokines ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Fatty Acids, Monounsaturated ; pharmacology ; Inflammation Mediators ; metabolism ; Interleukin-6 ; metabolism ; Lipopolysaccharides ; Macrophages ; Tumor Necrosis Factor-alpha ; metabolism

Forest musk deer (Moschus berezovskii), a rare wild medicinal animal, is listed under the category of the state key protected wildlife list of China. Musk, secreted by the musk glands, is with high economic and medicinal value and used as precious traditional medicine in China. In order to meet the needs of musk in Chinese traditional medicine, forest musk deer farming was conducted in 1950s, but the research progress on musk secretion mechanism was slow. Therefore, by reviewing the histological and anatomical structure of forest musk deer musk gland, the relationship between sex hormones and the musk secretion process, and the molecular mechanism of the musk secretion, the existing problems in investigating the musk secretion mechanism were analyzed and the development trends in this field were also discussed, in order to provide a reference for further studies on the musk secretion mechanism and improve musk production of forest musk deer.
Animals ; Deer ; metabolism ; Exocrine Glands ; anatomy & histology ; chemistry ; secretion ; Fatty Acids, Monounsaturated ; chemistry ; metabolism ; Male