Carotenoid pattern intake and relation to metabolic status, risk and syndrome, and its components - divergent findings from the ORISCAV-LUX-2 survey.

Carotenoids are generally associated with health-beneficial effects; however, their intake patterns related to the metabolic syndrome (MetS) and its components remain controversial. This cross-sectional study investigated associations between dietary intakes of individual carotenoids, fruits and vegetables, and the MetS and its components. Dietary intakes of 1346 participants of the Observation des Risques et de la Santé Cardio-Vasculaire au Luxembourg (ORISCAV-LUX-2) study were investigated by a 174-item FFQ, and carotenoid intake was determined by linking findings using mainly the USDA food databases. Components of MetS and complementary variables, including anthropometric (BMI, waist circumferences and waist:hip ratio) and biological parameters (TAG, HDL-cholesterol, fasting blood glucose and blood pressure), were measured. Logistic (for MetS) and linear multivariable regression models (including assessing MetS as scores) adjusted for various confounders were created. α-and ß-Carotene, as well as lutein + zeaxanthin, were inversely associated with MetS (also when it was measured on a continuous scale), reducing the odds for MetS by up to 48 %. However, lycopene, phytoene and phytofluene were rather positively associated with MetS scores and its components, though these adverse effects disappeared, at least for lycopene, when controlling for intakes of tomato-based convenience foods, in line with indicating a rather unhealthy/westernised diet. All these associations remained significant when including fruits and vegetables as confounders, suggesting that carotenoids were related to MetS independently from effects within fruits and vegetables. Thus, a high intake of carotenoids was bidirectionally associated with MetS, its severity, risk and its components, depending on the type of carotenoid. Future investigations are warranted to explore the inverse role that tomato-based carotenoids appear to suggest in relation to the MetS.

Increased anti-inflammatory activity and enhanced phytochemical concentrations in superfine powders obtained by controlled differential sieving process from four medicinal plants.

Anti-inflammatory effect of Rosa canina, Salix alba, Scrophularia nodosa and Hedera helix were studied in LPS-stimulated primary peripheral blood mononuclear cells (PBMCs) from mice (n=18) by comparing homogeneous powders of small microparticles (50-100 µm, 100-180 µm and 180-315 µm) obtained from plants via a controlled differential sieving process (CDSp) versus total plant materials obtained via hydroethanolic (HE) extraction. Further, phytochemical composition of the fine powders and HE extracts was determined by LC-PDA-ESI/MS analyses. Results showed that a one-hour pretreatment of PBMCs with fine powders, particularly those with superfine particle sizes (i.e. 50-100 µm and 100-180 µm), significantly inhibited TNFα, IL-1ß, IL-6 and NO production in LPS-stimulated PBMCs, by at least ca. 20% more than HE extracts (all, p<0.05). For each of the plants studied, their superfine powdered fractions were more concentrated in phenolic contents than their HE extracts. Overall, our results further confirm CDSp, as an environmentally friendly method, for improving the concentration of bioactive compounds as well as their biological activities.

Oxidative stress status and vitamin D levels of asymptomatic to mild symptomatic COVID-19 infections during the third trimester of pregnancy: A retrospective study in Metz, France.

It is believed that the subtle equilibrium between tolerance and immunity during the unique biological state of pregnancy, which is characterized by further physiological and hormonal changes, rends pregnant women more vulnerable to coronavirus disease 2019 (COVID-19). In this retrospective study, confirmed COVID-19-positive pregnant women (n = 15) during their third trimester, comprising asymptomatic (n = 7) and mild symptomatic (n = 8), and healthy pregnant controls (n = 20), were enrolled between June 1, 2020 and  June 1, 2021 from the Hospital CHR Metz-Thionville in Metz, France. Vitamin D concentrations, C-reactive protein (CRP), and oxidative stress markers including superoxide dismutase (SOD), catalase (CAT), reduced (GSH) and oxidized (GSSG) glutathione levels, hydrogen peroxide (H2 O2 ), and the total antioxidant capacity, measured the ferric reducing ability of plasma (FRAP), were evaluated in the serum of patients and controls. Results showed that all pregnant women (patients and controls) enrolled in this study were vitamin D deficient (<20 ng/ml). However, mild COVID-19 pregnant women were severely vitamin D deficient (<12 ng/ml), which may suggest a link between vitamin D deficiency and the symptomatology of COVID-19 illness in singleton pregnancy. No differences between the levels of CRP and the majority of the studied oxidative stress markers in COVID-19-positive pregnant women (asymptomatic and/or mildly symptomatic patients) versus COVID-19-negative pregnant women were found, suggesting the absence or a low magnitude of oxidative stress in pregnant women with COVID-19. This may also explain the absence of severe courses of COVID-19 infection. More studies are warranted to investigate the role of vitamin D supplementation and antioxidant-rich diets in the prevention against severe forms of COVID-19 in pregnant women.

Reduction of paw edema and liver oxidative stress in carrageenan-induced acute inflammation by Lobaria pulmonaria and Parmelia caperata, lichen species, in mice.

Paw edema volume reduction is a useful marker in determining the anti-inflammatory effect of drugs and plant extracts in carrageenan-induced acute inflammation. In this study, the anti-inflammatory effect of Lobaria pulmonaria (LP) and Parmelia caperata (PC), two lichen species, was examined in carrageenan-induced mouse paw edema test. Compared to the controls in carrageenan-induced inflammation (n = 5/group), our results showed that pretreatment by single oral doses with PC extract (50-500 mg/kg) gives better results than LP extract (50-500 mg/kg) in terms of anti-edematous activity, as after 4 h of carrageenan subplantar injection, paw edema formation was inhibited at 82-99% by PC while at 35-49% by LP. The higher anti-inflammatory effect of PC, at all doses, was also observed on the time-course of carrageenan-induced paw edema, displaying profile closely similar to that obtained with diclofenac (25 mg/kg), an anti-inflammatory drug reference (all p < 0.001). Both LP and PC, at all doses, significantly ameliorated liver catalase (CAT) activity (all p < 0.05). However, superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity and glutathione (GSH) levels were found increased in liver of PC- compared to LP-carrageenan-injected mice. Our findings demonstrated on one hand higher preventive effects of PC compared to LP in a mouse carrageenan-induced inflammatory model and suggested, on the other hand, that anti-inflammatory effects elicited by the two lichens were closely associated with the amelioration in the endogenous antioxidant status of liver.

Chronic depression-like phenotype in male offspring mice following perinatal exposure to naturally contaminated eels with a mixture of organic and inorganic pollutants.

Previously, we demonstrated that maternal exposure to high, intermediate, or lowly contaminated European eels with a mixture of chemicals, during pregnancy and lactation, resulted in adult despair-like behavior, selectively in male offspring mice. Here, we investigate if depression-like behavior in offspring males was transient or permanent by monitoring immobility behavior, a measure of behavioral despair, at three distinct stages of life, including young adult (post-natal day (PND) 55), mature adult (PND 200) and middle (PNDs 335-336) age, in the forced swimming (FST) and the tail suspension (TST) tests. Oxidative stress markers including malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were evaluated in the hippocampus, prefrontal cortex, and cerebellum of middle-aged animals. Findings showed a significant enhancement of immobility behavior in the TST performed at young adult age (all p < 0.05) in the FST carried out at mature adult age (all p < 0.001) and in both behavioral tests realized at middle age (all p < 0.05, except one p = 0.06) in mice perinatally exposed to eels compared with non-exposed controls. Antioxidant-related enzyme activities, including SOD and CAT, were only elevated in the hippocampus of middle-aged males perinatally exposed to the two more polluted eels (all p < 0.05). Further, lipid peroxidation, assessed by MDA levels, was not found to be differentially regulated in the selected areas of middle-aged brains of exposed mice (all p > 0.05). Collectively, this suggested limited oxidative metabolism disturbances in middle-aged brains exposed to eels. In summary, our results highlighted that offspring males perinatally exposed to naturally contaminated reared and river eels with persistent organic pollutants (POPs) and heavy metals displayed chronic depression-like phenotype. As extrapolation of data to humans should be done with precaution, retrospective and prospective epidemiological studies are needed to clarify this potential relationship, stressed in our animal model, between maternal polluted fish consumption and chronically low mood in offspring.

Behavioral manipulation-key to the successful global spread of the new coronavirus SARS-CoV-2?

Human-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interaction can have an array of various outcomes-it could be mortal, morbid or merely carrying minor health consequences. The very rapid global spread has raised the issue whether there are further multi-dimensional consequences of SARS-CoV-2 infection on human behavior, the key of its transmission. During the coronavirus crisis, odd, abnormal, and irresponsible behavior has been reported in coronavirus disease 2019 (COVID-19) individuals, particularly in super-spreaders, that is, persons with a high viral load, thus constituting also super-emitters. Indeed, cases of infected persons ignoring self-confinement orders, intentionally disregarding physical distancing and multiplying social interactions, or even deliberately sneezing, spitting or coughing were reported. While it is known that some other viruses, such as rabies and even influenza do change human behavior, this remains unclear for SARS-CoV-2. In this perspective, we highlight the possibility that COVID-19 is facilitated by altered human social behavior that benefits SARS-CoV-2 transmission, through showcasing similar virus-induced changed behavior by other pathogens and relating this to reports from the gray literature.

Evidence that hydrogen peroxide, a component of oxidative stress, induces high-anxiety-related behaviour in mice.

The link between oxidative stress and high-anxiety-related behaviour is uncontested; but the cause-effect relationship has yet to be completely elucidated. Here, the behavioural effects of hydrogen peroxide (H2O2), given to mice (n = 10 per group) in drinking water at 1%, were assessed in the light/dark choice test, the open field, the elevated-plus maze and the hole-board test. Compared to controls (drinking only water), subacute exposure (10-15 days) of mice to H2O2, the major component of reactive oxygen species (ROS) and the precursor of potent oxidants (hydroxyl radical and hypochlorous acid), affected emotional responses by inducing an anxious behaviour associated with hyperactivity. Our findings clearly showed that H2O2-treated mice exhibited anxiogenic behaviour in the light/dark choice test and in the hole-board test. Moreover, H2O2-treated mice displayed a hyperactive behaviour, revealed by a significant increase in the number of crossings made in the open field test relative to controls. Although H2O2-exposed mice made significantly less head-dippings in the open arms than controls, H2O2-induced hyperactivity may have blurred anxiogenic-like behaviour in H2O2-treated mice in the elevated-plus maze. Our findings provide the evidence that H2O2, an oxidizing component, caused high-anxiety-related behaviour associated with hyperactivity in mice. Antioxidants may play a role in preventing or attenuating oxidative stress-related anxiety.

Powders with small microparticle size from Hedera helix and Scrophularia nodosa exhibited high preventive antioxidant activity against H2O2-induced oxidative stress in mouse primary spleen cells.

The purpose of this study was to examine the effects of powder particle size on the cytoprotective and antioxidant activity of Hedera helix (HH) and Scrophularia nodosa (SN), two medicinal plants more commonly known as ivy and figwort, against H2O2-induced oxidative stress in mouse primary spleen cells. Thus, the preventive effects of powders of 3 different granulometric classes (50-100 µm, 100-180 µm and 180-315 µm) and those of the hydroethanolic (HE) extract from HH and SN on oxidative stress were compared by monitoring reactive oxygen species (ROS) formation, malondialdehyde (MDA) production, and the activity of enzymatic antioxidants including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Results showed that pretreatment with the 3 fine powders from both plants generally offered to H2O2-exposed spleen cells, a protection against oxidative stress, highlighted by a significant decrease of both ROS formation and the level of MDA (p < 0.001), and a significant increase of GPx activity (p < 0.05). The two superfine powders (i.e. 50-100 µm and 100-180 µm), at 250 µg/mL, were more effective in modulating all oxidative stress markers studied than both HE extracts (p < 0.01), and the powder with the highest particular size (i.e., 180-315 µm) (p < 0.01). Compared to untreated cells, our results suggest that pretreatment with powders, in particular the superfine fractions, has relatively restored the levels of antioxidant-related enzymes including GPx, CAT and SOD. In summary, our results suggest differential effects between the 3 different fine powders studied, with the best cytoprotective and antioxidant activities being in favor of the superfine powders.

Perinatal effects of exposure to PCBs on social preferences in young adult and middle-aged offspring mice.

In social species, social interactions between conspecifics constitute a fundamental component to establish relations, provide best chances to reproduce, and even improve survival rates. In this study, a three-chambered social approach test was used to estimate the level of sociability and level of preference for social novelty in both male and female young adult (postnatal day (PND) 50) and middle-aged (PND 330) offspring mice (n=10 per group) that were perinatally exposed to a mixture of six polychlorinated biphenyls (PCBs), 28, 52, 101, 138, 153, and 180, at environmentally low doses (10 and 1000ng/kg b.w. for dams during gestation and lactation), a profile that closely mimics human exposure to contaminated fish. Our results showed that PCBs bidirectionally modulated social preferences in offspring mice, and the effects were sex and age dependent. However, increased levels of social interactions were rather frequently detected in both assays of the three-chambered test. Reduced social interaction was only induced in 1000ng/kg PCB-exposed middle-aged males, which exhibited similar preferences to social and non-social stimuli when compared to middle-aged controls. Furthermore, results showed that plasma levels of both corticosterone and acetylcholinesterase activity were higher in all PCB-exposed middle-aged males and females than in their control counterparts. In summary, although the effects of PCBs were only of moderate magnitude, our results suggest that a PCB mixture can act as an endocrine disruptor in offspring mice, disturbing the formation of normal social habits.

Hippocampal-dependent memory deficit induced by perinatal exposure to polutted eels in middle-aged offspring mice: Sex differential effects.

The effects of perinatal exposure to low, intermediate, or highly polluted eels on neonatal, postnatal, adult and middle-aged brain inflammation, and on cognitive performances of middle-aged offspring mice were compared to those of offspring controls. Inflammatory markers in microglia were assessed in offspring on the postnatal days-PNDs 1, 21, 100 and 330. Activated p38MAPK, ERK-1/2 and p65, and acetylcholine levels were assessed in the middle-aged hippocampus. Plasma myeloperoxidase and corticosterone levels were evaluated at PND 330. Learning and its retention, and working memory in middle-aged offspring were assessed using the Morris water maze, and Y-maze. Our results showed enhanced microglia production of inflammatory markers across the lifespan of male as well as female exposed offspring. Inflammation and increased p38 MAPK activation were detected in the exposed middle-aged hippocampus of both exposed sexes. Significant levels of MPO, but not corticosterone, were found in middle-aged males and females perinatally exposed to eels. However, decreases in ERK1/2 and p65 activation, and acetylcholine levels were only detected in female hippocampus exposed to either intermediately or highly polluted eels. Sex selective effects were also detected with regard to memory, the only altered cognitive function. Thus, middle-aged females, but not males, perinatally exposed to either intermediately or highly polluted eels take longer to locate the escape platform, spend considerably less time in the platform and perform less visit to the platform in the retention test. Our results suggest perinatal programming of hippocampal-dependent memory deficit by inflammation in middle-aged offspring, in sex and dose dependent manner.

Improvement of cytoprotective and antioxidant activity of Rosa canina L. and Salix alba L. by controlled differential sieving process against H2O2-induced oxidative stress in mouse primary splenocytes.

In this study, cytoprotective and antioxidant activities of Rosa canina (RC) and Salix alba (SA), medicinal plants, were studied on mouse primary splenocytes by comparing Controlled Differential Sieving process (CDSp), which is a novel green solvent-free process, versus a conventional technique, employing hydroethanolic extraction (HEE). Thus, preventive antioxidant activity of three plant powders of homogeneous particle sizes, 50-100 µm, 100-180 µm and 180-315 µm, dissolved directly in the cellular buffer, were compared to those of hydroethanolic (HE) extract, at 2 concentrations (250 and 500 µg/mL) in H2O2-treated spleen cells. Overall, compared to HE extract, the superfine powders, i. e., fractions < 180 µm, at the lowest concentration, resulted in greater reactive oxygen species (ROS) elimination, increased glutathione peroxidase (GPx) activity and lower malondialdehyde (MDA) production. Better antioxidant and preventive effects in pre-treated cells were found with the superfine powders for SA (i. e., 50-100 µm and 100-180 µm, both p < 0.001), and with the intermediate powder for RC (i. e., 100-180 µm, p < 0.05) versus HE extract. The activity levels of catalase (CAT) and superoxide dismutase (SOD) in pretreated splenocytes exposed to H2O2, albeit reduced, were near to those in unexposed cells, suggesting that pretreatment with the fine powders has relatively restored the normal levels of antioxidant-related enzymes. These findings supported that CDSp improved the biological activities of plants, avoiding the use of organic solvents and thus it could be a good alternative to conventional extraction techniques.

Perinatal programming of depressive-like behavior by inflammation in adult offspring mice whose mothers were fed polluted eels: Gender selective effects.

Several lines of evidence indicate that early-life inflammation may predispose to mental illness, including depression, in later-life. We investigated the impact of perinatal exposure to polluted eels on neonatal, postnatal, and adult brain inflammation, and on the resignation behavior of male and female adult offspring mice. The effects of maternal standard diet (laboratory food) were compared to the same diet enriched with low, intermediate, or highly polluted eels. Brain inflammatory markers including cytokines were assessed in offspring mice on the day of birth (i.e., on the postnatal day-PND 1), upon weaning (PND 21) and at adulthood (PND 100). Plasma myeloperoxidase and corticosterone levels were evaluated at PND 100. Immobility behavior of offspring was assessed in adulthood (i.e., at PNDs 95-100), using the tail suspension and forced swimming tests. Chronic brain inflammation was found in male and female offspring mice compared to controls, as assessed at PNDs 1, 21, and 100. The level of myeloperoxidase was found to be significantly higher in both adult males and females vs. control offspring. However, high corticosterone levels were only found in male offspring mice that were perinatally exposed to eels, suggesting a gender-selective dysregulation of the adult hypothalamic-pituitaryadrenal (HPA) axis. Gender-specific differences were also detected in adulthood in regard to offspring resignation behavior. Thus, compared to controls, males, but not females, whose mothers were fed eels during pregnancy and lactation exhibited a depressive-like behavior in adult age in both behavioral models of depression. Depressive symptoms were more pronounced in male mice perinatally exposed to either intermediate or highly polluted eels than those exposed to only lowly polluted eels. Our results indicate that early-life inflammatory insult is a plausible causative factor that induces the depressive phenotype exhibited by male adult offspring mice, most likely through a gender-specific HPA axis enhanced activation.

Chemically Contaminated Eel Fed to Pregnant and Lactating Mouse Dams Causes Hyperactivity in Their Offspring.

This study examined whether perinatal exposure to polluted eels (Anguilla anguilla L.) induces changes in the locomotor activity of offspring mice across lifespan (post-natal days (PNDs) 47 - 329), using the open field and the home cage activity tests. Dams were exposed during gestation and lactation, through diets enriched in eels naturally contaminated with pollutants including PCBs. Analysis of the eel muscle focused on the six non-dioxin-like (NDL) indicator PCBs (Σ6 NDL-PCBs: 28, 52, 101, 138, 153 and 180). Four groups of dams (n = 10 per group) received either a standard diet without eels or eels (0.8 mg/kg/day) containing 85, 216, or 400 ng/kg/day of ϵ6 NDL-PCBs. The open field test showed that early-life exposure to polluted eels increased locomotion in female offspring of exposed dams but not in males, compared to controls. This hyperlocomotion appeared later in life, at PNDs 195 and 329 (up to 32 % increase, p < 0.05). In addition, overactivity was observed in the home cage test at PND 305: exposed offspring females showed a faster overall locomotion speed (3.6 - 4.2 cm/s) than controls (2.9 cm/s, p <0.05); again, males remained unaffected. Covered distances in the home cage test were only elevated significantly in offspring females exposed to highest PCB concentrations (3411 ± 590 cm vs. 1377 ± 114 cm, p < 0.001). These results suggest that early-life exposure to polluted eels containing dietary contaminants including PCBs caused late, persistent and gender-dependent neurobehavioral hyperactive effects in offspring mice. Furthermore, female hyperactivity was associated with a significant inhibition of acetylcholinesterase activity in the hippocampus and the prefrontal cortex.

Dietary early-life exposure to contaminated eels does not impair spatial cognitive performances in adult offspring mice as assessed in the Y-maze and the Morris water maze.

Many environmental contaminants are introduced via the diet and may act as neurotoxins and endocrine disrupters, especially influencing growing organisms in early life. The purpose of this study was to examine whether dietary exposure of dams to fish naturally contaminated with xenobiotics, especially with polychlorinated biphenyls (PCBs) and heavy metals (e.g., mercury and lead), resulted in cognitive function deficits in adult offspring mice. Daily, four groups of dams (n = 10/group) ingested standard diet plus paste with/without eels, during gestation and lactation, from gestational day (GD) six until post natal day (PND) 21 (weaning). Dams orally ingested a standardized amount of eel (0.8 mg kg(-1) d(-1)) containing the six non-dioxin-like (NDL) PCBs (Σ6 NDL-PCBs: 28, 52, 101, 138, 153, and 180) at 0, 85, 216, and 400 ng kg(-1) d(-1). Results showed that early-life exposure to contaminated eels did not (compared to non-exposed controls) impair immediate working memory in the Y-maze in the offspring assessed at PND 38. Furthermore, it did not significantly impact spatial learning and retention memory as measured in the Morris water maze in adult offspring mice (PND 120-123). Our results suggest that perinatal exposure to contaminated eels does not affect spatial cognitive performances, as assessed by the Y-maze and Morris water maze at adult age. Adverse effects of xenobiotics reported earlier might be camouflaged by beneficial eel constituents, such as n-3 fatty acids. However, additional studies are needed to differentiate between potential positive and negative effects following consumption of food items both rich in nutrients and contaminants.