12-o-undecadienoylphorbol-13-acetate and Disease-Models--Animal

The hexanic, ethyl acetate and methanolic extracts from branches of Stenocereus stellatus were tested in both the 12-O-tetradecanoylphorbol-13-acetate (TPA) - induced ear oedema model and antimicrobial activity assay. The % of oedema inhibition, the Minimum Inhibitory Concentration (MIC), as well as the polyphenolic and flavonoid content were determined. Also, extracts were analysed by gas chromatography-mass spectrometry (GC-MS). In TPA model, the three extracts showed moderate oedema inhibition. In the antimicrobial activity assay, methanolic extract shows better MIC against all strains. The lowest MICs were for Candida albicans (31 μg/mL) and Rhizopus sp. (15 μg/mL). Also, 50.78 mg eq. of gallic acid/g extract of polyphenol and 115.12 mg eq. of catequine/g extract of flavonoids content were founded in ethyl acetate extract. In the chromatographic analysis, β-sitosterol, β-amyrine, betulin and some other molecules were identified. The results show that S. stellatus possess antimicrobial activities against some fungus species.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Cactaceae; Candida albicans; Disease Models, Animal; Edema; Flavonoids; Gas Chromatography-Mass Spectrometry; Male; Microbial Sensitivity Tests; Phorbol Esters; Plant Extracts; Polyphenols; Rhizopus; Secondary Metabolism; Sitosterols

The relationship between the brain and the immune system has become increasingly topical as, although it is immune-specialised, the CNS is not free from the influences of the immune system. Recent data indicate that peripheral immune stimulation can significantly affect the CNS. But the mechanisms underpinning this relationship remain unclear. The standard approach to understanding this relationship has relied on systemic immune activation using bacterial components, finding that immune mediators, such as cytokines, can have a significant effect on brain function and behaviour. More rarely have studies used disease models that are representative of human disorders.. Here we use a well-characterised animal model of psoriasis-like skin inflammation-imiquimod-to investigate the effects of tissue-specific peripheral inflammation on the brain. We used full genome array, flow cytometry analysis of immune cell infiltration, doublecortin staining for neural precursor cells and a behavioural read-out exploiting natural burrowing behaviour.. We found that a number of genes are upregulated in the brain following treatment, amongst which is a subset of inflammatory chemokines (CCL3, CCL5, CCL9, CXCL10, CXCL13, CXCL16 and CCR5). Strikingly, this model induced the infiltration of a number of immune cell subsets into the brain parenchyma, including T cells, NK cells and myeloid cells, along with a reduction in neurogenesis and a suppression of burrowing activity.. These findings demonstrate that cutaneous, peripheral immune stimulation is associated with significant leukocyte infiltration into the brain and suggest that chemokines may be amongst the key mediators driving this response.

Topics: Aminoquinolines; Animals; Brain; CD3 Complex; Chemokines; Chemotaxis, Leukocyte; Dermatitis; Disease Models, Animal; Doublecortin Domain Proteins; Female; Flow Cytometry; Gene Expression Profiling; Imiquimod; Interferon Inducers; Leukocytes; Membrane Glycoproteins; Mice; Microtubule-Associated Proteins; Neuropeptides; Oligonucleotide Array Sequence Analysis; Phorbol Esters; RNA, Messenger; Toll-Like Receptor 7

Exercise has been previously reported to lower cancer risk through reducing circulating IGF-1 and IGF-1-dependent signaling in a mouse skin cancer model. This study aims to investigate the underlying mechanisms by which exercise may down-regulate the IGF-1 pathway via p53 and p53-related regulators in the skin epidermis. Female SENCAR mice were pair-fed an AIN-93 diet with or without 10-week treadmill exercise at 20 m/min, 60 min/day and 5 days/week. Animals were topically treated with TPA 2 hours before sacrifice and the target proteins in the epidermis were analyzed by both immunohistochemistry and Western blot. Under TPA or vehicle treatment, MDM2 expression was significantly reduced in exercised mice when compared with sedentary control. Meanwhile, p53 was significantly elevated. In addition, p53-transcriptioned proteins, i.e., p21, IGFBP-3, and PTEN, increased in response to exercise. There was a synergy effect between exercise and TPA on the decreased MDM2 and increased p53, but not p53-transcripted proteins. Taken together, exercise appeared to activate p53, resulting in enhanced expression of p21, IGFBP-3, and PTEN that might induce a negative regulation of IGF-1 pathway and thus contribute to the observed cancer prevention by exercise in this skin cancer model.

Topics: Animals; Cyclin-Dependent Kinase Inhibitor p21; Disease Models, Animal; Epidermis; Female; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Mice, Inbred SENCAR; Phorbol Esters; Physical Conditioning, Animal; Proto-Oncogene Proteins c-mdm2; PTEN Phosphohydrolase; Skin Neoplasms; Tumor Suppressor Protein p53