•IL6 is cardio protective during acute insult to the myocardium.•IL6 transitions to a pathogenic factor when it remains elevated chronically.•The transition is associated with specific downstream ...signaling unique to IL6.•Chronic IL6 signaling is associated with heart failure.•In myocarditis chronic IL6 signaling contributes to progression to dilated cardiomyopathy.
IL6 is a pleiotropic cytokine that is made in response to perturbations in homeostasis. IL6 becomes elevated in the acute response to host injury and can activate immune cells, direct immune cell trafficking, signal protective responses in local tissue, initial the acute phase response or initiate wound healing. In the short term this proinflammatory response is protective and limits host damage. It is when this acute response remains chronically activated that IL6 becomes pathogenic to the host. Chronically elevated IL6 levels lead to chronic inflammation and fibrotic disorders. The heart is a tissue where this temporal regulation of IL6 is very apparent. Studies from myocardial infarction show how short-term IL6 signaling can protect and preserve the heart tissue in response to acute damage, where long term IL6 signaling or an over-production of IL6R protein plays a causal role in cardiovascular disease. Thus, IL6 can be both protective and pathogenic, depending on the kinetics of the host response.
Ganoderma lucidum is a mushroom that has been widely used for centuries in Asian countries for its antiaging properties. It is popularly known as “Ling Zhi,” “Reishi,” and “Youngzhi,” and because of ...its benefits, it is known as the “immortality mushroom.” Pharmacological assays have revealed that G. lucidum ameliorates cognitive impairments through inhibition of β‐amyloid and neurofibrillary tangle formation, antioxidant effect, reduction of inflammatory cytokine release and apoptosis, genic expression modulation, among other activities. Chemical investigations on G. lucidum have revealed the presence of metabolites such as triterpenes, which are the most explored in this field, as well as flavonoids, steroids, benzofurans, and alkaloids; in the literature, these have also been reported to have mnemonic activity. These properties of the mushroom make it a potential source of new drugs to prevent or reverse memory disorders, as actual medications are able to only alleviate some symptoms but are unable to stop the progress of cognitive impairments, with no impact on social, familiar, and personal relevance. In this review, we discuss the cognitive findings of G. lucidum reported in the literature, converging the proposed mechanisms through the several pathways that underlie memory and cognition processes. In addition, we highlight the gaps that deserve particular attention to support future studies.
Highlights • Short- and long-term spatial memory deficits are present in prediabetic rats. • Memory deficits are concurrent with increases of GluA1 and GLUN1 hippocampal levels. • Prediabetic rats ...display decreased hippocampal IR-β density. • Memory deficits are concurrent with decreased GR hippocampal levels.
Propolis consists of a honeybee product, with a complex mix of substances that have been widely used in traditional medicine. Among several compounds present in propolis, caffeic acid phenethyl ester ...(CAPE), and pinocembrin emerge as two principal bioactive compounds, with benefits in a variety of body systems. In addition to its well‐explored pharmacological properties, neuropharmacological activities have been poorly discussed. In an unprecedented way, the present review addresses the current finding on the promising therapeutic purposes of propolis, focusing on CAPE and pinocembrin, highlighting its use on neurological disturbance, as cerebral ischemia, neuroinflammation, convulsion, and cognitive impairment, as well as psychiatric disorders, such as anxiety and depression. In addition, we provide a critical analysis, discussion, and systematization of the molecular mechanisms which underlie these central nervous system effects. We hypothesize that the pleiotropic action of CAPE and pinocembrin, per se or associated with other substances present in propolis may result in the therapeutic activities reported. Inhibition of the pro‐inflammatory cascade, antioxidant activity, and positive neurotrophic modulatory effects consist of the main molecular targets attributed to CAPE and pinocembrin in health benefits.
Background
Methamphetamine abuse is a worldwide concern with long‐term health complications. Its impact on neurons has been extensively investigated, and it is currently known that glial cells, ...including astrocytes, are involved in drug‐induced outcomes. Importantly, METH also causes blood‐brain barrier (BBB) disruption and astrocytes are critical for BBB (dys)function. Therefore, we aimed to clarify the involvement of neuroinflammation mediated by astrocytes in BBB permeability and brain oedema induced by METH. Further, we aimed to identify a new approach to counteract METH effects.
Methods
Mice were administered with a METH binge regimen (4 × 10 mg/kg) alone or in combination with parthenolide (PTL; 4 × 1 mg/kg), and hippocampi were analysed. For in vitro studies, mouse primary cultures of astrocytes were exposed to 250 µM METH, alone or co‐treated with 10 µM PTL.
Results
We observed a neuroinflammatory response characterized by astrocytic morphological changes and increased TNF‐α, iNOS and ICAM‐1 protein levels (213.62%, 205.76% and 191.47% of control, respectively). Additionally, brain oedema and BBB disruption were identified by increased water content (81.30% of tissue weight) and albumin (224.40% of control) in the hippocampal tissue, as well as a significant decrease in vessel coverage by astrocytes after METH exposure. Regarding astrocyte cultures, we further identified TNF‐α as a key player in METH‐induced cell swelling. Importantly, PTL (present in feverfew plant) prevented both animal and in vitro effects induced by METH.
Conclusions
We provided important insights on brain dysfunction induced by METH, and we also suggest a new approach to counteract such negative effects.
In the present study, 199 pre-selected Carbohydrate-Active enZymes (CAZymes) and sulfatases were assessed, either alone or in combination, to evaluate their capacity to disrupt Laminaria digitata ...cell wall, with the consequent release of interesting nutritional compounds. A previously characterized individual alginate lyase, belonging to the family 7 of polysaccharide lyases (PL7) and produced by Saccharophagus degradans, was shown to be the most efficient in the in vitro degradation of L. digitata cell wall. The alginate lyase treatment, compared to the control, released up to 7.11 g/L of reducing sugars (p < 0.001) and 8.59 mmol/100 g dried alga of monosaccharides (p < 0.001), and reduced cell wall fluorescence intensity by 39.1% after staining with Calcofluor White (p = 0.001). The hydrolysis of gel-forming polymer alginate by the alginate lyase treatment could prevent the trapping of fatty acids and release beneficial monounsaturated fatty acids, particularly 18:1c9 (p < 0.001), to the extracellular medium. However, no liberation of proteins (p > 0.170) or pigments (p > 0.070) was observed. Overall, these results show the ability of an individual alginate lyase, from PL7 family, to partially degrade L. digitata cell wall under physiological conditions. Therefore, this CAZyme can potentially improve the bioavailability of L. digitata bioactive compounds for monogastric diets, with further application in feed industry.
In nature, the deconstruction of plant carbohydrates is carried out by carbohydrate-active enzymes (CAZymes). A high-throughput (HTP) strategy was used to isolate and clone 1476 genes obtained from a ...diverse library of recombinant CAZymes covering a variety of sequence-based families, enzyme classes, and source organisms. All genes were successfully isolated by either PCR (61%) or gene synthesis (GS) (39%) and were subsequently cloned into Escherichia coli expression vectors. Most proteins (79%) were obtained at a good yield during recombinant expression. A significantly lower number (p < 0.01) of proteins from eukaryotic (57.7%) and archaeal (53.3%) origin were soluble compared to bacteria (79.7%). Genes obtained by GS gave a significantly lower number (p = 0.04) of soluble proteins while the green fluorescent protein tag improved protein solubility (p = 0.05). Finally, a relationship between the amino acid composition and protein solubility was observed. Thus, a lower percentage of non-polar and higher percentage of negatively charged amino acids in a protein may be a good predictor for higher protein solubility in E. coli. The HTP approach presented here is a powerful tool for producing recombinant CAZymes that can be used for future studies of plant cell wall degradation. Successful production and expression of soluble recombinant proteins at a high rate opens new possibilities for the high-throughput production of targets from limitless sources.
The purpose of this study was to evaluate the impact of Chlorella vulgaris (5% in the diet), supplemented or not with two exogenous carbohydrase mixtures on piglets' performance, nutrient ...digestibility and gut morphology, fermentation products and microbiota. Forty-four male piglets weaned at 28 days of age, with 11.2 ± 0.46 kg of live weight, were used and assigned to 1 of 4 dietary treatments: cereal and soybean meal based-diet (control, n = 11), control diet with 5% of C. vulgaris (CH, n = 10), CH diet supplemented with 0.005% of Rovabio
Excel AP (CH + R, n = 10) and CH diet supplemented with 0.01% of a recombinant 4-carbohydrase mixture (CH + M, n = 11). Growth performance was not changed by the of C. vulgaris inclusion during 21 days of trial. However, total tract apparent digestibility of nutritional fractions was negatively impacted by the inclusion. In addition, the viscosity of duodenum plus jejunum contents slightly increased in all groups fed with the microalga. In contrast, dietary microalga increased duodenum villus height and promoted a healthier gut microbiota, with higher abundance of some specific bacterial taxa (Colidextribacter, Oscillospira and Lactobacillus). This study indicates that the dietary inclusion of 5% C. vulgaris improves piglets' gut health without impairing performance. Data also indicate that C. vulgaris reduces nutrient digestibility but promotes compensatory developments of gut mucosa and prebiotic effects. Dietary supplementation with exogenous carbohydrases does not seem to be necessary for this inclusion level. Therefore, the incorporation of CH as a sustainable feed ingredient in piglets' nutrition is a viable alternative approach.
Abstract Psychological stress elicits increases in sympathetic activity accompanied by a marked cardiovascular response. Revealing the relevant central mechanisms involved in this phenomenon could ...contribute significantly to our understanding of the pathogenesis of stress-related cardiovascular diseases, and the key to this understanding is the identification of the nuclei, pathways and neurotransmitters involved in the organization of the cardiovascular response to stress. The present review will focus specifically on the dorsomedial hypothalamus, a brain region now known to play a primary role in the synaptic integration underlying the cardiovascular response to emotional stress.
Food enrichment with minerals has been a method of increasing health benefits. Edible Pleurotus ostreatus mushrooms are a source of dietary elements and antioxidants. In this work, the phenolic ...content, antioxidant activity and metal content of P. ostreatus grown on coffee husk, enriched with iron (Fe), zinc (Zn) and lithium (Li) were investigated. The content of phenolic compounds was found to be different in mushroom enriched with Fe, Zn or Li. In DPPH test, a difference was observed in antioxidant activity; however, no difference in this activity was observed using β-carotene/linoleic acid test. The enrichment with minerals promoted decrease in the content of Fe in three enriched samples. There was no change in the content of Zn in the samples. Observed the accumulation of Li in the sample enriched with LiCl and P. ostreatus enriched with Fe, Zn or Li provided minerals such as K, P, Fe, Zn, Li and Cu. In addition, no heavy metals such as Ni, Cr and Cd were detected, and only low levels of Pb and Al were observed. The study was the first report to demonstrate the understanding of how mineral supplementation reduces antioxidant activity in P. ostreatus enriched with iron, zinc or lithium.
•The Pleurotus ostreatus antioxidant activity was evaluated.•Mineral enrichment reduces antioxidant activity in P. ostreatus.•P. ostreatus are useful sources of antioxidants molecules.•Mycelia of P. ostreatus enriched are dietary sources of bioelements such as K, P, Fe, Zn and Li.
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