Ketogenesis and ketolysis are central metabolic processes activated during the response to fasting. Ketogenesis is regulated in multiple stages, and a nuclear receptor peroxisome proliferator ...activated receptor α (PPARα) is one of the key transcription factors taking part in this regulation. PPARα is an important element in the metabolic network, where it participates in signaling driven by the main nutrient sensors, such as AMP-activated protein kinase (AMPK), PPARγ coactivator 1α (PGC-1α), and mammalian (mechanistic) target of rapamycin (mTOR) and induces hormonal mediators, such as fibroblast growth factor 21 (FGF21). This work describes the regulation of ketogenesis and ketolysis in normal and malignant cells and briefly summarizes the positive effects of ketone bodies in various neuropathologic conditions.
Peroxisome proliferator-activated receptor α is a potent regulator of systemic and cellular metabolism and energy homeostasis, but it also suppresses various inflammatory reactions. In this review, ...we focus on its role in the regulation of innate immunity; in particular, we discuss the PPARα interplay with inflammatory transcription factor signaling, pattern-recognition receptor signaling, and the endocannabinoid system. We also present examples of the PPARα-specific immunomodulatory functions during parasitic, bacterial, and viral infections, as well as approach several issues associated with innate immunity processes, such as the production of reactive nitrogen and oxygen species, phagocytosis, and the effector functions of macrophages, innate lymphoid cells, and mast cells. The described phenomena encourage the application of endogenous and pharmacological PPARα agonists to alleviate the disorders of immunological background and the development of new solutions that engage PPARα activation or suppression.
The biological activity of apple pectin extracted conventionally or enzymatically using endo-xylanase and endo-cellulase, was tested in vitro. The analyses were performerd in tetraplicates and the ...statistical significance of the differences were assessed using ANOVA, Tukey post hoc and LSD (the least significant difference) tests. Multivariate regression analysis was applied to determine the structural components that have a crucial importance for antioxidant and antitumor properties of pectins. The pectins extracted by enzymes contained up to four times more ferulic acid and showed twice as great ability to neutralize free radicals and Fe(III) reduction. The antiradical potential positively correlated with phenols, fucose and rhamnose content. In the assays performed on HT-29 human adenocarcinoma and B16F10 melanoma cell cultures, the "green" pectins, contrary to acid isolated ones, exhibited remarkable anti-neoplastic potential while being nontoxic to nontransformed L929 cell line. The pectins in the dose of 1 mg/mL were capable of inhibiting adhesion (max 23.1%), proliferation (max 40.4%), invasion (max 76.9%) and anchorage-independent growth (max 90%) of HT-29 cells (significance level
< 0.001). These pectin preparations were slightly less active towards B16F10 cells. The enzyme-isolated apple pectins may be useful as a functional food additive and an ingredient of the ointment formulas for post-surgical melanoma treatment.
Mitochondria are crucially important for maintaining not only the energy homeostasis, but the proper cellular functions in a general sense. Impairment of mitochondrial functions is observed in a ...broad variety of pathological states such as neoplastic transformations and cancer, neurodegenerative diseases, metabolic disorders and chronic inflammation. Currently, in parallel to the classical drug design approaches, there is an increasing interest in the screening for natural bioactive substances, mainly phytochemicals, in order to develop new therapeutic solutions for the mentioned pathologies. Dietary phytochemicals such as resveratrol, curcumin and sulforaphane are very well tolerated and can effectively complement classical pharmacological therapeutic regimens. In this paper we disscuss the effect of the chosen phytochemicals (e.g., resveratrol, curcumin, sulforaphane) on various aspects of mitochondrial biology, namely mitochondrial biogenesis, membrane potential and reactive oxygen species production, signaling to and from the nucleus and unfolded protein response.
The application of natural polymer matrices as medical device components or food packaging materials has gained a considerable popularity in recent years, this has occurred in response to the ...increasing plastic pollution hazard. Currently, constant progress is being made in designing two-component or three-component systems that combine natural materials which help to achieve a quality comparable to the purely synthetic counterparts. This study describes a green synthesis preparation of new bionanocomposites consisting of starch/chitosan/graphene oxide (GO), that possess improved biological activities; namely, good tolerability by human cells with concomitant antimicrobial activity. The structural and morphological properties of bionanocomposites were analyzed using the following techniques: dynamic light scattering, scanning and transmission electron microscopy, wettability and free surface energy determination, and Fourier transform infrared spectroscopy. The study confirmed the homogenous distribution of GO layers within the starch/chitosan matrix and their large particle size. The interactions among the components were stronger in thin films. Additionally, differential scanning calorimetry analysis, UV-vis spectroscopy, surface colour measurements, transparency, water content, solubility, and swelling degree of composites were also performed. The mechanical parameters, such as tensile strength and elongation at break (EAB) were measured in order to characterise the functional properties of obtained nanocomposites. The GO additive altered the thermal features of the composites and decreased their brightness. The EAB of composite was improved by the introduction of GO. Importantly, cell-based analyses revealed no toxic effect of the composites on HaCat keratinocytes and HepG2 hepatoma cells, although a pronounced bacteriostatic effect against various strains of pathogenic bacteria was observed. In conclusion, the starch/chitosan/GO nanocomposites reveal numerous useful physicochemical and biological features, which make them a promising alternative for purely synthetic materials.
Peroxisome proliferator-activated receptor alpha (PPARα) is expressed throughout the mammalian gut: in epithelial cells, in the villi of enterocytes and in Paneth cells of intestinal crypts, as well ...as in some immune cells (e.g.,
macrophages, dendritic cells) of the mucosa. This review examines the reciprocal interaction between PPARα activation and intestinal microbiota. We refer to the published data confirming that microbiota products can influence PPARα signaling and, on the other hand, PPARα activation is able to affect microbiota profile, viability, and diversity. PPARα impact on the broad spectrum of events connected to metabolism, signaling (e.g., NO production), immunological tolerance to dietary antigens, immunity and permeability of the gut are also discussed. We believe that the phenomena described here play a prominent role in gut homeostasis. Therefore, in conclusion we propose future directions for research, including the application of synthetic activators and natural endogenous ligands of PPARα (i.e., endocannabinoids) as therapeutics for intestinal pathologies and systemic diseases assumed to be related to gut dysbiosis.
Brussels sprouts provide bioactive compounds with widely acknowledged health-promoting effects observed in various levels: single cells, organs and tissues, or the whole organism. However, the choice ...of the appropriate hydrothermal processing is critical to sustain the nutritional values and cytoprotective activities, as Brussels sprouts are rarely eaten raw. The aim of this study was to evaluate the impact of various culinary methods (boiling, steaming, and sous-vide in comparison to raw plant material) applied to Brussels sprouts on the chosen functions of liver and intestinal cell lines (HepG2 and Caco-2, respectively): the markers of enterocyte differentiation (alkaline phosphatase and sucrase-isomaltase activities and protein level), glutathione store management (total GSH concentration and Glu, Gly, Cys and Met amino acids analysis) and mitochondrial polarization (JC-1 staining analysis). The in vitro digestates from raw Brussels sprouts had a stronger positive effect on the enterocyte marker enzymes in the Caco-2 cultures as compared to the digestates from the hydrothermally processed vegetables (boiled, steamed, and sous-vide). The sous-vide method diminished the intracellular glutathione stores. Hydrothermal processing, particularly steaming and sous-vide had a negative impact on the mitochondrial abundance and polarization as compared to raw vegetables. Our results suggest that shorter processing is more beneficial to retain glutathione and mitochondrial polarization than longer hydrothermal treatment.
Melanins form a diverse group of pigments synthesized in living organisms in the course of hydroxylation and polymerization of organic compounds. Melanin production is observed in all large taxa from ...both Pro- and Eukaryota. The basic functions of melanins are still a matter of controversy and speculation, even though their adaptative importance has been proved. Melanogenesis has probably evolved parallel in various groups of free living organisms to provide protection from environmental stress conditions, but in pathogenic microorganisms it correlates with an increased virulence. The genes responsible for melanization are collected in some cases within operons which find a versatile application in genetic engineering. This review summarizes current views on melanogenesis in Pro- and Eukaryotic microorganisms in terms of their biotechnological and biomedical importance.
Fenofibrate (FF) is a common lipid-lowering drug and a potent agonist of the peroxisome proliferator-activated receptor alpha (PPARα). FF and several other agonists of PPARα have interesting ...anticancer properties, and our recent studies demonstrate that FF is very effective against tumor cells of neuroectodermal origin. In spite of these promising anticancer effects, the molecular mechanism(s) of FF-induced tumor cell toxicity remains to be elucidated. Here we report a novel PPARα-independent mechanism explaining FF's cytotoxicity in vitro and in an intracranial mouse model of glioblastoma. The mechanism involves accumulation of FF in the mitochondrial fraction, followed by immediate impairment of mitochondrial respiration at the level of complex I of the electron transport chain. This mitochondrial action sensitizes tested glioblastoma cells to the PPARα-dependent metabolic switch from glycolysis to fatty acid β-oxidation. As a consequence, prolonged exposure to FF depletes intracellular ATP, activates the AMP-activated protein kinase-mammalian target of rapamycin-autophagy pathway, and results in extensive tumor cell death. Interestingly, autophagy activators attenuate and autophagy inhibitors enhance FF-induced glioblastoma cytotoxicity. Our results explain the molecular basis of FF-induced glioblastoma cytotoxicity and reveal a new supplemental therapeutic approach in which intracranial infusion of FF could selectively trigger metabolic catastrophe in glioblastoma cells.
Hydrogels, based on natural polymers, such as hyaluronic acid, are gaining an increasing popularity because of their biological activity. The antibacterial effect of ozone is widely known and used, ...but the instability the gas causes, severely limits its application. Ozone entrapment in olive oil by its reaction with an unsaturated bond, allows for the formation of stable, therapeutically active ozone derivatives. In this study, we obtained an innovative hydrogel, based on hyaluronic acid containing micro/nanocapsules of ozonated olive oil. By combination of the biocompatible polymer with a high regenerative capacity and biologically active ingredients, we obtained a hydrogel with regenerative properties and a very weak inhibitory effect against both bacterial commensal skin microbiota and pathogenic
-like yeasts. We assessed the stability and rheological properties of the gel, determined the morphology of the composite, using scanning electron microscopy (SEM) and particle size by the dynamic light scattering (DLS) method. We also performed Attenuated total reflectance Fourier transform infrared (FTIR-ATR) spectroscopy. The functional properties, including the antimicrobial potential were assessed by the microbiological analysis and in vitro testing on the HaCat human keratinocyte cell line. The studies proved that the obtained emulsions were rheologically stable, exhibited an antimicrobial effect and did not show cytotoxicity in the HaCat keratinocyte model.
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