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Background. Early assessment of infant lung function (ILF) is necessary to improve our understanding of factors that determine long-term respiratory health. Objective. To identify predictors of lung function among infants aged 6 weeks, 6, 12 and 24 months, from low socioeconomic settings, enrolled within the Mother and Child in the Environment (MACE) study. Methods. ILF tests were performed assessing multiple breath washout and tidal breathing during spontaneous sleep. Several risk factors, relating to infant growth, maternal and environmental exposures, were assessed cross-sectionally against the lung function parameters in multivariable models for each age group. Results. Maternal smoking during pregnancy affected the ratio of time to peak expiratory flow, showing a decline across the age groups, while being statistically significant (β (95% confidence interval (CI)) at 6 weeks (-24.6% (-43.92 - -4.59)) and 12 months (-12.68 (-25.25 - -0.11)). Low birthweight was associated with a lower tidal volume at 6 weeks (-5.99 mL (-9.59 - -2.39)), 6 months (-15.02 mL (-22.48 - -7.57)) and 12 months (-23.7 mL (-35.55 - -11.85)), compared with those with normal birthweight. This was further observed for minute ventilation at 6 weeks (-157.78 mL/min (-338.95 - 23.38)), 6 months (-325.57 mL/min (-619.06 - -32.08)) and 12 months (-527.58 mL/min (-947.85 - -107.32)), though less evident at 24 months. Conclusion. Low birthweight was the main predictor for low tidal volumes and minute ventilation at 6 weeks, with smaller differences observed at 12 and 24 months. Lung function development early in life is primarily driven by infant size and postnatal growth factors, consistent with other studies. [ABSTRACT FROM AUTHOR]

A number of genes important for detoxification and antioxidant defense induced by mild stress generated by, for example, physical activity/exercise, caloric restriction, or alcohol may provide health benefits by causing the organism to mount such a defense response. More recently, induction of these defenses has also been attributed to phytochemicals or secondary metabolites from dietary plants. Many polyphenols, which constitute a large fraction of these phytochemicals, increase cellular levels of antioxidants, such as glutathione and other components of the detoxification systems, via the transactivation of genes containing electrophile response elements (EpREs) within their promoters. One such gene, gamma-glutamylcysteine synthetase, has previously been shown to be positively regulated by quercetin, a flavonoid found in high concentrations in onions, apples, and bilberries through EpRE transactivation. As a further step, we have investigated whether bilberries and quercetin have the ability to induce transcription of Fos-related antigen 1 (Fra-1), which contains two EpREs in its promoter. Fra-1 is a member of the activator protein 1 (AP-1) family of transcription factors and, due to the lack of transactivation domain Fra-1, can suppress activation of AP-1. We present results demonstrating that extracts from bilberries, and the flavonoid quercetin, abundant in bilberries, induce the fra-1 promoter and the cellular content of Fra-1 mRNA. We further provide evidence that this induction is mediated through EpREs. [ABSTRACT FROM AUTHOR]

Polyphenols in food plants are a versatile group of phytochemicals with many potentially beneficial activities in terms of disease prevention. In vitro cell culture experiments have shown that polyphenols possess antioxidant properties, and it is thought that these activities account for disease-preventing effects of diets high in polyphenols. However, polyphenols may be regarded as xenobiotics by animal cells and are to some extent treated as such, ie, they interact with phase I and phase II enzyme systems. We recently showed that dietary plant polyphenols, namely, the flavonoids, modulate expression of an important enzyme in both cellular antioxidant defenses and detoxification of xenobiotics, ie, gamma-glutamylcysteine synthetase. This enzyme is rate limiting in the synthesis of the most important endogenous antioxidant in cells, glutathione. We showed in vitro that flavonoids increase expression of gamma-glutamylcysteine synthetase and, by using a unique transgenic reporter mouse strain, we showed increased expression in vivo, with a concomitant increase in the intracellular glutathione concentrations in muscles. Because glutathione is important in redox regulation of transcription factors and enzymes for signal transduction, our results suggest that polyphenol-mediated regulation of glutathione alters cellular processes. Evidently, glutathione is important in many diseases, and regulation of intracellular glutathione concentrations may be one mechanism by which diet influences disease development. The aim of this review is to discuss some of the mechanisms involved in the glutathione-mediated, endogenous, cellular antioxidant defense system, how its possible modulation by dietary polyphenols such as flavonoids may influence disease development, and how it can be studied with in Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Abstract: Dietary components, like β-glucans, can modulate the intestinal immune response. We previously showed that fecal water enriched with oat β-glucan stimulated the cytokine-induced immune response of enterocytes. It is, however, unclear whether β-glucans activate nuclear factor-κB (NF-κB) pathways in the intestine in vivo and if so, whether enterocytes, intestinal leukocytes, or both respond to β-glucans. We evaluated the effects of an oral gavage of 3 mg dietary oat (1→3), (1→4)-β-d-glucans that was administered twice daily during 3.5 days on intestinal NF-κB transactivation and subsequent cytokine production of intestinal leukocytes and enterocytes in 16 NF-κB reporter mice. We hypothesized that oat β-glucan activates the central immune transcription factor NF-κB and increased cytokine secretion, as we previously reported immune stimulating effects by oat β-glucan. We found that mice that were administered oat β-glucans (n = 8) showed an increased intestinal NF-κB transactivation in leukocytes (P = .021) and enterocytes (P = .012), particularly in the proximal part of the small intestine (ileum), as compared to placebo mice (n = 8). Surprisingly, NF-κB was not activated in the colon. Furthermore, the level of interleukin 12 was increased in intestinal lysates from all compartments, whereas the concentration of interferon γ was decreased in the proximal small intestine (P = .046). Finally, tumor necrosis factor α showed a trend toward a reduced production in the colon (P = .057). Because we have earlier shown that human enterocyte cell lines do not express the β-glucan receptor dectin-1 in vitro, we now conclude that after consumption, dietary oat β-glucans most likely firstly activate the intestinal leukocytes, which in turn increases cellular activation of enterocytes. [Copyright &y& Elsevier]

Introduction: Lipopolysaccharides (LPS) present in the intestine are suggested to enter the bloodstream after consumption of high-fat diets and cause systemic inflammation and metabolic dysregulation through a process named "metabolic endotoxemia." This study aimed to determine the role of orally administered LPS to mice in the early stage of chronic low-grade inflammation induced by diet., Methods: We supplemented the drinking water with E. coli derived LPS to mice fed either high-fat Western-style diet (WSD) or standard chow (SC) for 7 weeks ( n  = 16-17). Body weight was recorded weekly. Systemic inflammatory status was assessed by in vivo imaging of NF-κB activity at different time points, and glucose dysregulation was assessed by insulin sensitivity test and glucose tolerance test near the end of the study. Systemic LPS exposure was estimated indirectly via quantification of LPS-binding protein (LBP) and antibodies against LPS in plasma, and directly using an LPS-sensitive cell reporter assay., Results and Discussion: Our results demonstrate that weight development and glucose regulation are not affected by LPS. We observed a transient LPS dependent upregulation of NF-κB activity in the liver region in both diet groups, a response that disappeared within the first week of LPS administration and remained low during the rest of the study. However, WSD fed mice had overall a higher NF-κB activity compared to SC fed mice at all time points independent of LPS administration. Our findings indicate that orally administered LPS has limited to no impact on systemic inflammation and metabolic dysregulation in mice fed a high-fat western diet and we question the capability of intestinally derived LPS to initiate systemic inflammation through a healthy and uncompromised intestine, even when exposed to a high-fat diet., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Harvei, Skogen, Egelandsdal, Birkeland, Paulsen and Carlsen.)

Aims: Enterocins K1 and EJ97 have specific antimicrobial activity against Enterococcus faecium and Enterococcus faecalis, respectively. The aim of this study was to investigate the utility of these enterocins for in vivo treatment of systemic enterococcal infections., Methods and Results: The antimicrobial effect in blood was analysed and compared against the effect in saline. Colony forming unit counts revealed that the enterocins killed all the bacteria within 1 hour. Additionally, the bactericidal effect against E. faecalis was more rapid in blood, indicating a possible synergy between EntEJ97 and blood. Importantly, no enterocin resistant mutants emerged in these experiments. Injecting the enterocins intraperitoneally in an in vivo mouse model and using fluorescence and minimum inhibitory concentration determination to estimate concentrations of the peptides in plasma, indicate that the enterocins exist in circulation in therapeutic concentrations. Alanine aminotransferase detection, and haemolysis analysis indicates that there is no detectable liver damage or haemolytic effect after injection., Conclusions: The study revealed that EntK1 and EntEJ97 are able to kill all bacteria ex vivo in the presence of blood. In vivo experiments determine that the enterocins exist in circulation in therapeutic concentrations without causing liver damage or haemolysis. Future experiments should test these peptides for treatment of infection in a relevant in vivo model., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Specific pathogen-free (SPF) laboratory mice dominate preclinical studies for immunology and vaccinology. Unfortunately, SPF mice often fail to accurately model human responses to vaccination and other immunological perturbations. Several groups have taken different approaches to introduce additional microbial experience to SPF mice to better model human immune experience. How these different models compare is unknown. Here, we directly compare three models: housing SPF mice in a microbe-rich barn-like environment (feralizing), adding wild-caught mice to the barn-like environment (fer-cohoused), or cohousing SPF mice with pet store mice in a barrier facility (pet-cohoused); the two latter representing different murine sources of microbial transmission. Pet-cohousing mice resulted in the greatest microbial exposure. Feralizing alone did not result in the transmission of any pathogens tested, while fer-cohousing resulted in the transmission of several picornaviruses. Murine astrovirus 2, the most common pathogen from pet store mice, was absent from the other two model systems. Previously, we had shown that pet-cohousing reduced the antibody response to vaccination compared with SPF mice. This was not recapitulated in either the feralized or fer-cohoused mice. These data indicate that not all dirty mouse models are equivalent in either microbial experience or immune responses to vaccination. These disparities suggest that more cross model comparisons are needed but also represent opportunities to uncover microbe combination-specific phenotypes and develop more refined experimental models. Given the breadth of microbes encountered by humans across the globe, multiple model systems may be needed to accurately recapitulate heterogenous human immune responses.IMPORTANCEAnimal models are an essential tool for evaluating clinical interventions. Unfortunately, they can often fail to accurately predict outcomes when translated into humans. This failure is due in part to a lack of natural infections experienced by most laboratory animals. To improve the mouse model, we and others have exposed laboratory mice to microbes they would experience in the wild. Although these models have been growing in popularity, these different models have not been specifically compared. Here, we directly compare how three different models of microbial experience impact the immune response to influenza vaccination. We find that these models are not the same and that the degree of microbial exposure affects the magnitude of the response to vaccination. These results provide an opportunity for the field to continue comparing and contrasting these systems to determine which models best recapitulate different aspects of the human condition., Competing Interests: The authors declare no conflict of interest.

Introduction: Avian eggshell membrane (ESM) is a complex extracellular matrix comprising collagens, glycoproteins, proteoglycans, and hyaluronic acid. We have previously demonstrated that ESM possesses anti-inflammatory properties in vitro and regulates wound healing processes in vivo . The present study aimed to investigate if oral intake of micronized ESM could attenuate skeletal muscle aging associated with beneficial alterations in gut microbiota profile and reduced inflammation., Methods: Elderly male C57BL/6 mice were fed an AIN93G diet supplemented with 0, 0.1, 1, or 8% ESM. Young mice were used as reference. The digestibility of ESM was investigated using the static in vitro digestion model INFOGEST for older people and adults, and the gut microbiota profile was analyzed in mice. In addition, we performed a small-scale pre-clinical human study with healthy home-dwelling elderly (>70 years) who received capsules with a placebo or 500 mg ESM every day for 4 weeks and studied the effect on circulating inflammatory markers., Results and Discussion: Intake of ESM in elderly mice impacted and attenuated several well-known hallmarks of aging, such as a reduction in the number of skeletal muscle fibers, the appearance of centronucleated fibers, a decrease in type IIa/IIx fiber type proportion, reduced gene expression of satellite cell markers Sdc3 and Pax7 and increased gene expression of the muscle atrophy marker Fbxo32. Similarly, a transition toward the phenotypic characteristics of young mice was observed for several proteins involved in cellular processes and metabolism. The digestibility of ESM was poor, especially for the elderly condition. Furthermore, our experiments showed that mice fed with 8% ESM had increased gut microbiota diversity and altered microbiota composition compared with the other groups. ESM in the diet also lowered the expression of the inflammation marker TNFA in mice and in vitro in THP-1 macrophages. In the human study, intake of ESM capsules significantly reduced the inflammatory marker CRP. Altogether, our results suggest that ESM, a natural extracellular biomaterial, may be attractive as a nutraceutical candidate with a possible effect on skeletal muscle aging possibly through its immunomodulating effect or gut microbiota., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rønning, Carlsen, Rocha, Rud, Solberg, Høst, Veiseth-Kent, Arnesen, Bergum, Kirkhus, Böcker, Abedali, Rundblad, Bålsrud, Måge, Holven, Ulven and Pedersen.)

In this study, the long-term mortality effects associated with exposure to PM 10 (particles with an aerodynamic diameter smaller than or equal to 10 µm), PM 2.5 (particles with an aerodynamic diameter smaller than or equal to 2.5 µm), BC (black carbon), and NO x (nitrogen oxides) were analyzed in a cohort in southern Sweden during the period from 1991 to 2016. Participants (those residing in Malmö, Sweden, born between 1923 and 1950) were randomly recruited from 1991 to 1996. At enrollment, 30,438 participants underwent a health screening, which consisted of questionnaires about lifestyle and diet, a clinical examination, and blood sampling. Mortality data were retrieved from the Swedish National Cause of Death Register. The modeled concentrations of PM 10 , PM 2.5 , BC, and NO x at the cohort participants' home addresses were used to assess air pollution exposure. Cox proportional hazard models were used to estimate the associations between long-term exposure to PM 10 , PM 2.5 , BC, and NO x and the time until death among the participants during the period from 1991 to 2016. The hazard ratios (HRs) associated with an interquartile range (IQR) increase in each air pollutant were calculated based on the exposure lag windows of the same year (lag0), 1-5 years (lag1-5), and 6-10 years (lag6-10). Three models were used with varying adjustments for possible confounders including both single-pollutant estimates and two-pollutant estimates. With adjustments for all covariates, the HRs for PM 10 , PM 2.5 , BC, and NO x in the single-pollutant models at lag1-5 were 1.06 (95% CI: 1.02-1.11), 1.01 (95% CI: 0.95-1.08), 1.07 (95% CI: 1.04-1.11), and 1.11 (95% CI: 1.07-1.16) per IQR increase, respectively. The HRs, in most cases, decreased with the inclusion of a larger number of covariates in the models. The most robust associations were shown for NO x , with statistically significant positive HRs in all the models. An overall conclusion is that road traffic-related pollutants had a significant association with mortality in the cohort.

Introduction: The aim was to investigate the risk, prevalence, and clinical characteristics of cerebral palsy among children born after assisted reproductive technology (ART) in Norway., Material and Methods: All liveborn children from 2002 to 2015 were included. Information was collected from the Medical Birth Registry of Norway, linked to the Norwegian Quality and Surveillance Registry for Cerebral Palsy as of December 31, 2022. Logistic regression analyses were used to calculate the prevalence of cerebral palsy per 1000 live births after ART and natural conception with birth year as covariate, crude odds ratios (OR) for cerebral palsy among children born after ART using children born after natural conception as reference, and OR adjusted for potential confounders, with 95% confidence intervals (CI). Potential mediators of the association were studied in stratified analyses. Descriptive statistics were used to compare proportions in clinical characteristics among children with cerebral palsy born after ART and natural conception., Results: Among 833 645 livebirths, 23 645 children were born after ART and of the latter 97 were diagnosed with cerebral palsy. The overall prevalence of cerebral palsy after ART was 4.10 per 1000 live births (95% CI 3.36-5.00), decreasing from 7.79 per 1000 in 2002 to 3.55 in 2015. Compared with children born after natural conception, the OR for cerebral palsy was 2.01 (95% CI 1.63-2.47) adjusted for mother's age at birth, parity, and pre-pregnancy health. When restricted to singletons born at term, the adjusted OR for cerebral palsy was 1.13 (95% CI 0.76-1.69). The distribution of cerebral palsy subtypes and the severity of gross and fine motor function and associated impairments did not differ significantly between children with cerebral palsy born after ART and natural conception., Conclusions: Children born after ART had a risk of cerebral palsy that was twice that of children born after natural conception. The increased risk of cerebral palsy after ART is likely attributed to multiple pregnancies and preterm births. The prevalence of cerebral palsy after ART decreased significantly during the study period, despite an increased use of ART in the population. The distribution of clinical characteristics did not differ between children with cerebral palsy born after ART and those born after a natural conception, suggesting that the risk factors for, and causes of cerebral palsy were similar., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: The epidemiological evidence on the interaction between heat and ambient air pollution on mortality is still inconsistent., Objectives: To investigate the interaction between heat and ambient air pollution on daily mortality in a large dataset of 620 cities from 36 countries., Methods: We used daily data on all-cause mortality, air temperature, particulate matter ≤ 10 μm (PM 10 ), PM ≤ 2.5 μm (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) from 620 cities in 36 countries in the period 1995-2020. We restricted the analysis to the six consecutive warmest months in each city. City-specific data were analysed with over-dispersed Poisson regression models, followed by a multilevel random-effects meta-analysis. The joint association between air temperature and air pollutants was modelled with product terms between non-linear functions for air temperature and linear functions for air pollutants., Results: We analyzed 22,630,598 deaths. An increase in mean temperature from the 75 th to the 99 th percentile of city-specific distributions was associated with an average 8.9 % (95 % confidence interval: 7.1 %, 10.7 %) mortality increment, ranging between 5.3 % (3.8 %, 6.9 %) and 12.8 % (8.7 %, 17.0 %), when daily PM 10 was equal to 10 or 90 μg/m 3 , respectively. Corresponding estimates when daily O 3 concentrations were 40 or 160 μg/m 3 were 2.9 % (1.1 %, 4.7 %) and 12.5 % (6.9 %, 18.5 %), respectively. Similarly, a 10 μg/m 3 increment in PM 10 was associated with a 0.54 % (0.10 %, 0.98 %) and 1.21 % (0.69 %, 1.72 %) increase in mortality when daily air temperature was set to the 1 st and 99 th city-specific percentiles, respectively. Corresponding mortality estimate for O 3 across these temperature percentiles were 0.00 % (-0.44 %, 0.44 %) and 0.53 % (0.38 %, 0.68 %). Similar effect modification results, although slightly weaker, were found for PM 2.5 and NO 2 ., Conclusions: Suggestive evidence of effect modification between air temperature and air pollutants on mortality during the warm period was found in a global dataset of 620 cities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Dietary fiber is a term crudely defined as carbohydrates (CHOs) that escape digestion and uptake in the small intestine. Lignin, which is not a CHO, is also a part of the dietary fiber definition. Dietary fibers come in different sizes and forms, with a variety of combinations of monomeric units. Health authorities worldwide have for many years recommended a diet rich in dietary fibers based on consistent findings that dietary fibers are associated with reduced incidences of major non-communicable diseases, including obesity, type 2 diabetes, cardiovascular disease, and colorectal cancer. Most fibers come from common edible foods from the plant kingdom, but fibers are also found in food additives, supplements, and breast milk. The recommended intake in Nordic Nutrition Recommendations 2012 (NNR2012) is 25 g/d for women and 35 g/d for men, whereas the actual intake is significantly lower, ranging from 16 g/d to 22 g/d in women and 18 g/d to 26 g/d in men. New studies since NNR2012 confirm the current view that dietary fiber is beneficial for health, advocating intakes of at least 25 g/day., Competing Interests: The authors have not received any funding or benefits from industry or elsewhere to conduct this study., (© 2023 Harald Carlsen and Anne-Maria Pajari.)

To close the gap between ultra-hygienic research mouse models and the much more environmentally exposed conditions of humans, we have established a system where laboratory mice are raised under a full set of environmental factors present in a naturalistic, farmyard-type habitat-a process we have called feralization. In previous studies we have shown that feralized (Fer) mice were protected against colorectal cancer when compared to conventionally reared laboratory mice (Lab). However, the protective mechanisms remain to be elucidated. Disruption of the protective intestinal barrier is an acknowledged player in colorectal carcinogenesis, and in the current study we assessed colonic mucosal barrier properties in healthy, feralized C57BL/6JRj male mice. While we found no effect of feralization on mucus layer properties, higher expression of genes encoding the mucus components Fcgbp and Clca1 still suggested mucus enforcement due to feralization. Genes encoding other proteins known to be involved in bacterial defense (Itln1, Ang1, Retnlb) and inflammatory mechanisms (Zbp1, Gsdmc2) were also higher expressed in feralized mice, further suggesting that the Fer mice have an altered intestinal mucosal barrier. These findings demonstrate that microbial experience conferred by housing in a farmyard-type environment alters the intestinal barrier properties in mice possibly leading to a more robust protection against disease. Future studies to unravel regulatory roles of feralization on intestinal barrier should aim to conduct proteomic analyses and in vivo performance of the feralized mice intestinal barrier., (© 2023. Springer Nature Limited.)

Cardiovascular disease (CVD) is closely associated with obesity through risk factors such as dyslipidemia and chronic low-grade inflammation, which may be affected by diet. Dietary fats have been extensively studied in relation to CVD risk, however these studies have not always yielded consistent results, most likely due to lack in control of experimental conditions and confounding factors. Here we studied the effects of different plant and animal fats on dyslipidemia, inflammation, and atherosclerosis. Ldlr-/-.Leiden mice were fed isocaloric energy-dense diets with translational macronutrient composition for 28 weeks. The diets were identical apart from the type of fat they contained: either (1) a mixture of olive and rapeseed oil, (2) sunflower oil, (3) pork fat, (4) beef fat, or (5) milk fat. The fatty acid composition of the diets was determined and effects on circulating lipid and inflammatory risk factors and atherosclerosis were examined, complemented by adipose tissue histology and liver transcriptomics. While visceral fat mass, adipocyte size, and adipose tissue inflammation were not differentially affected by the diets, atherosclerotic lesion load and severity was more pronounced with increasing dietary saturated fatty acid content and decreasing monounsaturated and polyunsaturated fatty acid content, and hence most pronounced with beef and milk fat. These differential effects were accompanied by increases in pro-atherogenic plasma lipids/lipoproteins (e.g., triglycerides, apolipoprotein B), activation of pro-atherogenic cytokine/chemokine signaling pathways in liver, and with circulating pro-atherogenic mediators of inflammation altogether providing a rationale for the differential effects of plant and animal fats., (© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: Vitamin A is essential for a wide range of life processes throughout embryogenesis to adult life. With the aim of developing an in vivo model to monitor retinoic acid receptor (RAR) transactivation real-time in intact animals, we generated transgenic mice carrying a luciferase (luc) reporter gene under the control of retinoic acid response elements (RAREs) consisting of three copies of a direct repeat with five spacing nucleotides (DR5). Methods : Transgenic mice carrying a RARE dependent luciferase reporter flanked with insulator sequence were generated by pronuclear injection. RARE dependent luciferase activity was detected by in vivo imaging or in tissue extracts following manipulations with RAR/retinoid X receptor (RXR) agonists, RAR antagonists or in vitamin A deficient mice. Results: We found a strong induction of luciferase activity in a time and dose dependent manner by retinoic acid as well as RAR agonists, but not by the RXR agonist (using n=4-6 per group; 94 mice). In addition, luciferase activity was strongly reduced in vitamin A-deficient mice (n=6-9; 30 mice). These observations confirm that luciferase activity was controlled by RAR activation in the RARE-luc mouse. Luciferase activity was detectable in various organs, with high activity especially in brain and testis, indicating strong retinoid signalling in these tissues. Conclusion: The RARE-luc transgenic mice, which enabled real-time in vivo assessment of RAR activation, will be useful in understanding the normal physiology of vitamin A, the role of retinoid signalling in pathologies as well as to evaluate pharmacological ligands for RARs.

Carotenoids are the most abundant lipophilic secondary plant metabolites and their dietary intake has been related to a large number of potential health benefits relevant for humans, including even reduced total mortality. An important feature is their potential to impact oxidative stress and inflammatory pathways, by interacting with transcription factors. For example, they may act as precursors of bioactive derivatives activating nuclear hormone receptor mediated signalling. These bioactive derivatives, originating e.g. from β-carotene, i.e. retinoids / vitamin A, can activate the nuclear hormone receptors RARs (retinoic acid receptors). Due to new analytical insights, various novel metabolic pathways were recently outlined to be mediated via distinct nuclear hormone receptor activating pathways that were predicted and further confirmed. In this article, we describe old and novel metabolic pathways from various carotenoids towards novel ligands of alternative nuclear hormone receptors. However, to fully elucidate these pathways, a larger array of techniques and tools, starting from organic synthesis, lipidomics, reporter models, classical in vitro and in vivo models and further omics-approaches and their statistical evaluation are needed to comprehensively and conclusively study this topic. Thus, we further describe state-of-the-art techniques from A to Ω elucidating carotenoid biological mediated activities and describe in detail required materials and methods needed - in practical protocol form - for the various steps of carotenoid investigations.

The study aimed to evaluate the antibacterial efficacy of Lugol's solution 5% and Gentian violet 1% against methicillin-resistant Staphylococcus aureus (MRSA) biofilm in vivo. The bactericidal efficacy for treatment of MRSA-biofilm skin wound infection was tested in a murine model. Luciferase-tagged S. aureus Xen31, a MRSA-strain derived from S. aureus ATCC-3359130, was used for infection. Wounds were made in the skin of mice and infected with MRSA. The mice were treated with Lugol's solution and Gentian violet. Application of the antimicrobial agents started 24 hours post infection and was repeated daily for five-days. The antimicrobial effect on the biofilm bacteria was evaluated by measuring bioluminescence from MRSA daily for seven-days. Lugol's solution and Gentian violet showed a significant reduction in luminescent signals from the first assessment day to all subsequent days (P < .001). Lugol's solution and Gentian violet effectively eradicated MRSA in biofilm in vivo and could be alternatives or in addition to topical antibiotics when MRSA-biofilm wound infection is suspected., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

The rise of antibiotic-resistant bacteria is among the biggest challenges in human and veterinary medicine. One of the major factors that contributes to resistance is use of frontline clinical antibiotics in veterinary practices. To avoid this problem, searching for antimicrobials aimed at veterinary applications is becoming especially important. Thiopeptide micrococcin P1 and leaderless peptide EntEJ97s are two different bacteriocins that are very active against many gram-positive bacteria; however, sensitive bacteria can rapidly develop resistance towards those bacteriocins. To overcome this problem, we searched for synergy between those bacteriocins and conventional antibiotics against methicillin-resistant Staphylococcus pseudintermedius (MRSP): a common pathogen in animal skin infections. The two bacteriocins acted synergistically with each other and with penicillin G against MRSP clinical isolates in both planktonic and biofilm assays; they also prevented resistance development. The therapeutic potential was further validated in a murine skin infection model that showed that a combination of micrococcin P1, EntEJ97s and penicillin G reduced cell-forming units of MRSP by 2-log10 CFU/g. Taken together, our data show that a combination of bacteriocins with conventional antibiotics can not only prevent resistance development but also pave the way to revitalize some old, less useful antibiotics, such as penicillin, which by itself has no effect on methicillin-resistant pathogens.

Background: The developing lung is highly susceptible to environmental toxicants, with both short- and long-term exposure to ambient air pollutants linked to early childhood effects. This study assessed the short-term exposure effects of nitrogen dioxide (NO 2 ) and particulate matter (PM 10 ) on lung function in infants aged 6 weeks, 6, 12 and 24 months, the early developmental phase of child growth., Methods: Lung function was determined by multiple breath washout and tidal breathing measurement in non-sedated infants. Individual exposure to NO 2 and PM 10 was determined by hybrid land use regression and dispersion modelling, with two-week average estimates (preceding the test date). Linear mixed models were used to adjust for the repeated measures design and an age*exposure interaction was introduced to obtain effect estimates for each age group., Results: There were 165 infants that had lung function testing, with 82 of them having more than one test occasion. Exposure to PM 10 (μg/m 3 ) resulted in a decline in tidal volume at 6 weeks [-0.4 ml (-0.9; 0.0), p = 0.065], 6 months [-0.5 ml (-1.0; 0.0), p = 0.046] and 12 months [-0.3 ml (-0.7; 0.0), p = 0.045]. PM 10 was related to an increase in respiratory rate and minute ventilation, while a decline was observed for functional residual capacity for the same age groups, though not statistically significant for these outcomes. Such associations were however less evident for exposure to NO 2 , with inconsistent changes observed across measurement parameters and age groups., Conclusion: Our study suggests that PM 10 results in acute lung function impairments among infants from a low-socioeconomic setting, while the association with NO 2 is less convincing., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Rodent studies have shown that legumes can reduce chemical induced colonic inflammation, but the role of faba bean fractions for colon health has not been described. We have investigated the role of protein and fiber fractions of faba beans for colonic health and microbiota composition in a low-grade inflammation mice-model when incorporated in a Western diet (WD). The diet of sixty C57BL/6JRj male mice was standardized to a WD (41% fat, 43% carbohydrates) before were randomly assigned to four groups (n = 12) receiving either 1) WD with 30% of the protein replaced with faba-bean proteins, 2) WD with 7% of the fiber replaced with faba-bean fibers, 3) WD with protein and fiber fractions or 4) plain WD (n = 24). Low-grade inflammation was induced by 1% dextran sodium sulfate (DSS) given to mice for the last six days of the trial. Half (n = 12) in group 4) were given only water (controls). Prior to DSS, body weight, energy intake, glucose and insulin tolerance assays were performed. Inflammatory status in the colon was assessed by biomarkers of inflammation and qRT-PCR analyses of inflammatory related genes. Fecal microbiota composition was assessed by 16S rRNA gene sequencing. 1% DSS treatment increased levels in fecal lipocalin-2 and induced disease activity index score, but the presence of faba bean fractions in WD did not influence these indicators nor the expression level of inflammatory associated genes. However, the mice that had faba-bean proteins had a lower amount of Proteobacteria compared the group on plain WD. The Actinobacteria abundance was also lower in the group that had fiber fraction from faba-beans. Overall, outcomes indicated that in a low-grade inflammation model, replacement of protein and or fiber in a WD with faba bean fractions had marginal effects on inflammatory parameters and colonic microbiota., Competing Interests: The authors have declared that no competing interests exist.