Advances in wound treatment depend on the availability of animal models that reflect key aspects of human wound healing physiology. To this date, the accepted mouse models do not reflect defects in ...the healing process for chronic wounds that are associated with type two diabetic skin ulcers. The long term, systemic physiologic stress that occurs in middle aged or older Type 2 diabetes patients is difficult to simulate in preclinical animal model. We have strived to incorporate the essential elements of this stress in a manageable mouse model: long term metabolic stress from obesity to include the effects of middle age and thereafter onset of diabetes. At six-weeks age, male C57BL/6 mice were separated into groups fed a chow and High-Fat Diet for 0.5, 3, and 6 months. Treatment groups included long term, obesity stressed mice with induction of diabetes by streptozotocin at 5 months, and further physiologic evaluation at 8 months old. We show that this model results in a severe metabolic phenotype with insulin resistance and glucose intolerance associated with obesity and, more importantly, skin changes. The phenotype of this older age mouse model included a transcriptional signature of gene expression in skin that overlapped that observed with elderly patients who develop diabetic foot ulcers. We believe this unique old age phenotype contrasts with current mice models with induced diabetes.
Under high-fat feeding, the hypothalamus atypically undergoes pro-inflammatory signaling activation. Recent data from transcriptomic analysis of microglia from rodents and humans has allowed the ...identification of several microglial subpopulations throughout the brain. Numerous studies have clarified the roles of these cells in hypothalamic inflammation, but how each microglial subset plays its functions upon inflammatory stimuli remains unexplored. Fortunately, these data unveiling microglial heterogeneity have triggered the development of novel experimental models for studying the roles and characteristics of each microglial subtype. In this review, we explore microglial heterogeneity in the hypothalamus and their crosstalk with astrocytes under high fat diet-induced inflammation. We present novel currently available ex vivo and in vivo experimental models that can be useful when designing a new research project in this field of study. Last, we examine the transcriptomic data already published to identify how the hypothalamic microglial signature changes upon short-term and prolonged high-fat feeding.
Modifications in the microbiota caused by environmental and genetic reasons can unbalance the intestinal homeostasis, deregulating the host’s metabolism and immune system, intensifying the risk ...factors for the development and aggravation of non-alcoholic fat liver disease (NAFLD). The use of probiotics, prebiotics and synbiotics have been considered a potential and promising strategy to regulate the gut microbiota and produce beneficial effects in patients with liver conditions. For this reason, this review aimed to evaluate the effectiveness of probiotics, prebiotics, and symbiotics in patients with NAFLD and NASH. Pubmed, Embase, and Cochrane databases were consulted, and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines were followed. The clinical trials used in this study demonstrated that gut microbiota interventions could improve a wide range of markers of inflammation, glycemia, insulin resistance, dyslipidemia, obesity, liver injury (decrease of hepatic enzymes and steatosis and fibrosis). Although microbiota modulators do not play a healing role, they can work as an important adjunct therapy in pathological processes involving NAFLD and its spectrums, either by improving the intestinal barrier or by preventing the formation of toxic metabolites for the liver or by acting on the immune system.
Glutamic acid promotes hair growth in mice Jara, Carlos Poblete; de Andrade Berti, Beatriz; Mendes, Natália Ferreira ...
Scientific reports,
07/2021, Letnik:
11, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Glutamic acid is the main excitatory neurotransmitter acting both in the brain and in peripheral tissues. Abnormal distribution of glutamic acid receptors occurs in skin hyperproliferative conditions ...such as psoriasis and skin regeneration; however, the biological function of glutamic acid in the skin remains unclear. Using ex vivo, in vivo and in silico approaches, we showed that exogenous glutamic acid promotes hair growth and keratinocyte proliferation. Topical application of glutamic acid decreased the expression of genes related to apoptosis in the skin, whereas glutamic acid increased cell viability and proliferation in human keratinocyte cultures. In addition, we identified the keratinocyte glutamic acid excitotoxic concentration, providing evidence for the existence of a novel skin signalling pathway mediated by a neurotransmitter that controls keratinocyte and hair follicle proliferation. Thus, glutamic acid emerges as a component of the peripheral nervous system that acts to control cell growth in the skin. These results raise the perspective of the pharmacological and nutritional use of glutamic acid to treat skin diseases.
The bioactive properties (antioxidant and antitumour activities, and hepatotoxicity) of the infusion and methanolic extracts of Chenopodium ambrosioides L., a plant commonly used in Portuguese folk ...medicine, were compared. The chemical composition in hydrophilic (sugars, organic acids and phenolic compounds) and lipophilic (fatty acids and tocopherols) fractions were determined. In general, the infusion revealed higher antioxidant activity, while the methanolic extract was the only one showing antitumour effects against colon, cervical and hepatocellular carcinoma cell lines. No toxicity in non-tumour cells was observed either for the infusion or the extract. The studied plant proved to be a good source of natural antioxidants and other bioactive compounds, which may have industrial use. As far as we know, this is the first detailed chemical characterization and bioactivity evaluation of C. ambrosioides methanolic extract and infusion.
► A chemical and nutritional inventory of Portuguese wild mushrooms was performed. ► Wild mushrooms from different habitats are nutritionally well-balanced foods. ► Mushrooms have micronutrients and ...non-nutrients with antioxidant properties. ► Wild mushrooms can be used in diet as nutraceuticals and/or functional foods.
Mushrooms have been valued as highly tasty/nutritional foods and as a source of compounds with medicinal properties. The huge mushrooms reservoir of Northeast Portugal must be chemically and nutritionally characterized for the benefit of the local populations and for the genetic conservation of wild macrofungi. Herein, a chemical, nutritional and bioactive inventory of potentially interesting species (and not yet characterized in the literature) from different habitats (
Castanea sativa,
Pinus sp.,
Quercus sp., fields and mixed stands) was performed. Besides macronutrients with a well-balanced proportion, the studied wild mushrooms also have important micronutrients (vitamins) and non-nutrients (phenolics) with bioactive properties such as antioxidant potential. Furthermore, being a source of important antioxidants the wild species, mainly
Suillus variegatus (
Pinus sp. habitat),
Boletus armeniacus (
C. sativa habitat),
Clavariadelphus pistillaris (
Quercus sp. habitat),
Agaricus lutosus (fields) and
Bovista aestivalis (mixed stands), can be used in human diet as nutraceuticals and/or functional foods maintaining and promoting health, longevity and life quality.
Epidermal growth factor (EGF) promotes cell growth, proliferation, and survival in numerous tissues. Piperonylic acid, a metabolite present in peppers (Piper nigrum L. and Piper longum L.), can bind ...to the epidermal growth factor receptor (EGFR) and induce an intracellular signaling cascade leading to the transcription of genes responsible for these actions, especially in keratinocytes. These cells are fundamental in maintaining cutaneous homeostasis and are the first to be damaged in the case of a wound. Thus, we hypothesized that piperonylic acid improves wound healing. C57BL6/J male mice were submitted to dorsal skin wounds caused by a 6 mm punch and treated topically with piperonylic acid or vehicle. The wounds were evaluated macro- and microscopically, and tissue samples were collected for immunofluorescence and real-time PCR analyses on days 6, 9 and 19 post-injury. Topical piperonylic acid improved wound healing from day 6 post-injury until closure. This phenomenon apparently occurred through EGFR activation. In addition, piperonylic acid modulated the gene expression of interleukin (Il)-6, il-1β, tumor necrosis factor (Tnf)-α, il-10, monocyte chemoattractant protein (Mcp)-1 and insulin-like growth factor (Igf)-1, which are important for the healing process. By day 19 post-injury, the new tissue showed greater deposition of type I collagen and a morphology closer to intact skin, with more dermal papillae and hair follicles. We conclude that piperonylic acid may be a viable option for the treatment of skin wounds.
Photobiomodulation (PBM) has been applied as a non-invasive technique for treating temporomandibular joint symptoms, especially on painful condition's relief, however the anti-inflammatory mechanism ...underlying the effect of PBM remains uncertain. This study aims to evaluate the mechanisms of action of PBM (808 nm) in a carrageenan-induced inflammation on temporomandibular joint (TMJ) of rats. In this study male Wistar rats were pre-treated with irradiation of a low-power diode laser for 15 s on TMJ (infra-red 808 nm, 100 mW, 50 J/cm2 and 1.5 J) 15 min prior an injection in the temporomandibular joint of carrageenan (100 μg/TMJ). 1 h after the TMJ treatments, the rats were terminally anesthetized for joint cavity wash and periarticular tissues collect. Samples analysis demonstrated that PBM inhibit leukocytes chemotaxis in the TMJ and significantly reduces amounts of TNF-α, IL-1β and CINC-1. In addition, Western blotting analysis demonstrated that PBM significantly decreased the protein levels of P2X3 and P2X7 receptors in the periarticular tissues. On the other hand, PBM was able to increase protein level of IL-10 (anti-inflammatory cytokine). In summary, it is possible to suggest that PBM inhibit inflammatory chemotaxis, modulation the balance of the pro- and anti-inflammatory characteristics of inflammatory cells.
•PBM prevents inflammatory chemotaxis in a carrageenan-induced inflammation on TMJ.•Levels of pro-inflammatory cytokines (TNF-α, IL-1β and CINC-1) are reduced with PBM.•Levels of IL-10 (anti-inflammatory cytokine) are increased with PBM.•PBM decreased protein levels of purinergic receptors (P2X3 and P2X7) on TMJ.
Several scientific studies have been proving the bioactive effects of many aromatic and medicinal plants associated with the presence of a high number of bioactive compounds, namely phenolic ...compounds. The antioxidant, anti-inflammatory, and antimicrobial capacities of these molecules have aroused high interest in some industrial sectors, including food, pharmaceuticals, and cosmetics. This work aimed to determine the phenolic profiles of the infusions and hydroethanolic extracts of five plants (Carpobrotus edulis, Genista tridentata, Verbascum sinuatum, Cytisus multiflorus, and Calluna vulgaris) that have been employed in many traditional preparations. In addition, the antioxidant, antimicrobial, anti-inflammatory, and anti-tumoral activity of each different preparation was evaluated using in vitro assays. The HPLC-DAD-ESI/MS profile revealed the presence of eighty phenolic compounds, belonging to seven different families of compounds. Regarding antioxidant properties, the hydroethanolic extract of C. edulis showed a potent effect in the TBARS assay (IC50 = 1.20 µg/mL), while G. tridentata hydroethanolic extract achieved better results in the OxHLIA test (IC50 = 76 µg/mL). For cytotoxic and anti-inflammatory results, V. sinuatum infusions stood out significantly, with GI50 = 59.1–92.1 µg/mL and IC50 = 121.1 µg/mL, respectively. Finally, C. edulis hydroethanolic extract displayed the most relevant antibacterial activity, showing MBC values of 0.25–1 mg/mL, while G. tridentata hydroethanolic extract exerted the greatest antifungal effects (MFC of 0.5–1 mg/mL). The results of this study deepen the knowledge of the phenolic profiles and also provide evidence on the bioactive properties of the species selected, which could be considered highly valuable options for research and application in several sectors, namely food, cosmetics, and pharmaceuticals.
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