Insulin in Central Nervous System: More than Just a Peripheral Hormone

Insulin signaling in central nervous system (CNS) has emerged as a novel field of research since decreased brain insulin levels and/or signaling were associated to impaired learning, memory, and age-related neurodegenerative diseases. Thus, besides its well-known role in longevity, insulin may constitute a promising therapy against diabetes- and age-related neurodegenerative disorders. More interestingly, insulin has been also faced as the potential missing link between diabetes and aging in CNS, with Alzheimer's disease (AD) considered as the “brain-type diabetes.” In fact, brain insulin has been shown to regulate both peripheral and central glucose metabolism, neurotransmission, learning, and memory and to be neuroprotective. And a future challenge will be to unravel the complex interactions between aging and diabetes, which, we believe, will allow the development of efficient preventive and therapeutic strategies to overcome age-related diseases and to prolong human “healthy” longevity. Herewith, we aim to integrate the metabolic, neuromodulatory, and neuroprotective roles of insulin in two age-related pathologies: diabetes and AD, both in terms of intracellular signaling and potential therapeutic approach

Vital imaging of H9c2 myoblasts exposed to tert-butylhydroperoxide – characterization of morphological features of cell death

BACKGROUND: When exposed to oxidative conditions, cells suffer not only biochemical alterations, but also morphologic changes. Oxidative stress is a condition induced by some pro-oxidant compounds, such as by tert-butylhydroperoxide (tBHP) and can also be induced in vivo by ischemia/reperfusion conditions, which is very common in cardiac tissue. The cell line H9c2 has been used as an in vitro cellular model for both skeletal and cardiac muscle. Understanding how these cells respond to oxidative agents may furnish novel insights into how cardiac and skeletal tissues respond to oxidative stress conditions. The objective of this work was to characterize, through vital imaging, morphological alterations and the appearance of apoptotic hallmarks, with a special focus on mitochondrial changes, upon exposure of H9c2 cells to tBHP. RESULTS: When exposed to tBHP, an increase in intracellular oxidative stress was detected in H9c2 cells by epifluorescence microscopy, which was accompanied by an increase in cell death that was prevented by the antioxidants Trolox and N-acetylcysteine. Several morphological alterations characteristic of apoptosis were noted, including changes in nuclear morphology, translocation of phosphatidylserine to the outer leaflet of the cell membrane, and cell blebbing. An increase in the exposure period or in tBHP concentration resulted in a clear loss of membrane integrity, which is characteristic of necrosis. Changes in mitochondrial morphology, consisting of a transition from long filaments to small and round fragments, were also detected in H9c2 cells after treatment with tBHP. Bax aggregates near mitochondrial networks were formed after short periods of incubation. CONCLUSION: Vital imaging of alterations in cell morphology is a useful method to characterize cellular responses to oxidative stress. In the present work, we report two distinct patterns of morphological alterations in H9c2 cells exposed to tBHP, a pro-oxidant agent frequently used as model to induce oxidative stress. In particular, dynamic changes in mitochondrial networks could be visualized, which appear to be centrally involved in how these cells respond to oxidative stress. The data also indicate that the cause of H9c2 cell death following tBHP exposure is increased intracellular oxidative stress

Valorization of coffee agro-industry residues for prebiotic production by one-pot fermentation

Prebiotics are interesting compounds able to modulate the gut microbiota by inducing the growth or activity of beneficial bacteria in the gastrointestinal tract, while the pathogenic ones are inhibited. Several carbohydrates have been considered prebiotics including xylooligosaccarides (XOS). XOS are the only nutraceuticals that can be produced from lignocellulosic biomass. Indeed, XOS can be produced from agro-residues, which is encouraging to the food ingredient industries, as these raw materials are inexpensive, abundant and renewable in nature. In particular, the coffee agro-industry generates million tonnes of solid residues yearly worldwide, including coffee sliver skin (CSS). The use of coffee agro-industry residues for XOS production through a sustainable process is undoubtably aligned with the concept of circular economy. In this work, the production potential of XOS was evaluated for CSS and CSS pellets (CP), using one-pot fermentation by recombinant Bacillus subtills. In previous work, this strain was genetically modified to express the xylanase gene (xyn2) from Trichoderma reesei. CP presented the highest potential for XOS production. After process optimization, the highest reducing sugars yield (63 ± 3 mg.gCP-1) was achieved at 8 h, 45 °C, pH 7.0 and 10 g.L-1 of CP. One-pot fermentation proved to be a promising strategy for XOS production from CP, presenting advantages over the use of commercial enzymes. This study provides important insights for novel bioprocess integration approaches using agro-residues towards production cost reduction.info:eu-repo/semantics/publishedVersio

FK506 prevents mitochondrial-dependent apoptotic cell death induced by 3-nitropropionic acid in rat primary cortical cultures

The mitochondrial toxin 3-nitropropionic acid (3-NP) has been largely used to study neurodegenerative disorders in which bioenergetic defects are implicated. In the present study, we analyzed the molecular pathways involved in FK506 neuroprotection against cell death induced by 3-NP, using cultured cortical neurons. 3-NP induced cytochrome c release and increased caspases -2, -3, -8, and -9-like activities, although, calpain activity was not significantly affected. FK506 decreased cytochrome c release and caspase-3-like activity induced by 3-NP, without changing the activities of other caspases. FK-506 also decreased the number of apoptotic neurons, determined by Hoechst. Under these conditions, FK506 alone significantly reduced calcineurin activity by about 50%. Our results also showed a decrease in mitochondrial Bax and an increase in mitochondrial Bcl-2 levels upon exposure to FK506 and 3-NP. However, no significant changes occurred in total Bcl-2 and Bax levels. Altogether, the results suggest that FK506 neuroprotection against 3-NP-induced apoptosis is associated with the redistribution of Bcl-2 and Bax in the mitochondrial membrane.http://www.sciencedirect.com/science/article/B6WNK-4DFBTRN-1/1/437ab5ac7896585944bdb87bca46a53

Cognitive appraisal in fish: stressor predictability modulates the physiological and neurobehavioural stress response in sea bass

The role of cognitive factors in triggering the stress response is well established in humans and mammals (aka cognitive appraisal theory) but very seldom studied in other vertebrate taxa. Predictability is a key factor of the cognitive evaluation of stimuli. In this study, we tested the effects of stressor predictability on behavioral, physiological and neuromolecular responses in the European sea bass (Dicentrarchus labrax). Groups of four fish were exposed to a predictable (signalled) or unpredictable (unsignalled) stressor. Stressor predictability elicited a lower behavioural response and reduced cortisol levels. Using the expression of immediate early genes (c-fos, egr-1, bdnf and npas4) as markers of neuronal activity, we monitored the activity of three sea bass brain regions known to be implicated in stressor appraisal: the dorsomedian telencephalon, Dm (putative homologue of the pallial amygdala); and the dorsal (Dld) and ventral (Dlv) subareas of the dorsolateral telencephalon (putative homologue of the hippocampus). The activity of both the Dm and Dlv significantly responded to stressor predictability, suggesting an evolutionarily conserved role of these two brain regions in information processing related to stressor appraisal. These results indicate that stressor predictability plays a key role in the activation of the stress response in a teleost fish, hence highlighting the role of cognitive processes in fish stress.info:eu-repo/semantics/publishedVersio

Tamoxifen and estradiol interact with the flavin mononucleotide site of complex I leading to mitochondrial failure

This study evaluated the action of tamoxifen and estradiol on the function of isolated liver mitochondria. We observed that although tamoxifen and estradiol per se did not affect mitochondrial complexes II, III, or IV, complex I is affected, this effect being more drastic (except for state 4 of respiration) when mitochondria were coincubated with both drugs. Furthermore, using two respiratory chain inhibitors, rotenone and diphenyliodonium chloride, we identified the flavin mononucleotide site of complex I as the target of tamoxifen and/or estradiol action(s). Tamoxifen (25 microm) per se induced a significant increase in hydrogen peroxide production and state 4 of respiration. Additionally, a significant decrease in respiratory control ratio, transmembrane, and depolarization potentials were observed. Estradiol per se decreased carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP)-stimulated respiration, state 3 of respiration, and respiratory control ratio and increased lag phase of repolarization. With the exception of state 4 of respiration whose increase induced by tamoxifen was reversed by the presence of estradiol, the effects of tamoxifen were highly exacerbated when estradiol was present. We observed that 10 microm tamoxifen in the presence of estradiol affected mitochondria significantly by decreasing FCCP-stimulated respiration, state 3 of respiration, respiratory control ratio, and ADP depolarization and increasing the lag phase of repolarization. All of the deleterious effects induced by 25 microm tamoxifen were highly exacerbated in the presence of estradiol. Furthermore, we observed that the effects of both compounds were independent of estrogen receptors because the pure estrogen antagonist ICI 182,780 did not interfere with tamoxifen and/or estradiol detrimental effects. Altogether, our data provide a mechanistic explanation for the multiple cytotoxic effects of tamoxifen including its capacity to destroy tamoxifen-resistant breast cancer cells in the presence of estradiol. This new piece of information provides a basis for the development of new and promising anticancer therapeutic strategie

Oxidative Stress and Drugs of Abuse: An Update

Drug addiction is a public health and social burden. Presently, the most abused illicit substance is cannabis, followed by amphetamines, cocaine and opioids, with different prevalence in different countries. Several evidences support a role for oxidative stress in the toxicity induced by many drugs of abuse in different organs, such as the brain, heart, liver or kidneys. This leads to oxidation of important cellular macromolecules, and may culminate in cell dysfunction and death. In this review we describe the evidences for oxidative damage and depletion of antioxidants upon exposure to drugs of abuse, especially amphetamines, cocaine and opiates. We also discuss the sources of oxidative stress induced by drugs of abuse, including oxidative metabolism of drugs, oxidative metabolism of monoamines by monoamine oxidases or by auto-oxidation, mitochondrial dysfunction, excitotoxicity, microglial activation, inflammation, hyperthermia and the effects of drug interactions. These consolidate oxidative stress as a relevant mechanism contributing for the cytotoxicity of drugs of abuse and for behavioral changes associated with drug addiction

How managerial coaching promotes employees' affective commitment and individual performance

Abstract Purpose: This study sought to provide a more comprehensive understanding of how managers’ coaching skills can affect individual performance through the mediating role of affective commitment. Design/methodology/approach: The sample included 198 employees from diverse organizations. Based on an online survey, respondents assessed their managers’ coaching skills and reported their own individual performance and affective commitment to their organization. Findings: The findings show that managers’ coaching skills have a positive impact on individual performance and affective commitment, with the latter mediating the relationship between the first two variables. Research limitations/implications: Additional studies with larger samples are needed to understand more fully not only the impact of managers’ coaching skills on individual performance but also other psychosocial variables affecting that relationship. Practical implications: Organizations can increase employees’ affective commitment and individual performance by encouraging managers to integrate more coaching skills into their leadership styles. Originality/value: This study is the first to integrate managers’ coaching skills, affective commitment, and individual performance into a single research model, thereby extending previous research on this topic.info:eu-repo/semantics/publishedVersio

Marine-inspired drugs and biomaterials in the perspective of pancreatic cancer therapies

Despite its low prevalence, pancreatic cancer (PC) is one of the deadliest, typically characterised as silent in early stages and with a dramatically poor prognosis when in its advanced stages, commonly associated with a high degree of metastasis. Many efforts have been made in pursuing innovative therapeutical approaches, from the search for new cytotoxic drugs and other bioactive compounds, to the development of more targeted approaches, including improved drug delivery devices. Marine biotechnology has been contributing to this quest by providing new chemical leads and materials originating from different organisms. In this review, marine biodiscovery for PC is addressed, particularly regarding marine invertebrates (namely sponges, molluscs, and bryozoans), seaweeds, fungi, and bacteria. In addition, the development of biomaterials based on marine-originating compounds, particularly chitosan, fucoidan, and alginate, for the production of advanced cancer therapies, is also discussed. The key role that drug delivery can play in new cancer treatments is highlighted, as therapeutical outcomes need to be improved to give further hope to patients.The authors would like to acknowledge the funding from the European Union Framework Program for Research and Innovation Horizon 2020 through project SponGES (H2020-BG-01-2015-679849) and from the European Regional Development Fund, through INTERREG España-Portugal 2014-2020 under BLUEBIOLAB (0474_BLUEBIOLAB_1_E) project and through NORTE2020/PT2020 Programme under ATLANTIDA (Norte-01-0145-FEDER-000040) project