Urolithins are intestinal microbial metabolites produced from ellagitannin- and ellagic acid-containing foods such as walnuts, strawberries, and pomegranates. These metabolites, better absorbed than ...their precursors, can contribute significantly to the beneficial properties attributed to the polyphenols ellagitannins and ellagic acid (EA). However, both the ability of producing the final metabolites in this catabolism (urolithins A, B and isourolithin A) and the health benefits associated with ellagitannin consumption differ considerably among individuals depending on their gut microbiota composition. Three human urolithin metabotypes have been previously described, i.e., metabotype 0 (urolithin non-producers), metabotype A (production of urolithin A as unique final urolithin) and metabotype B (urolithin B and/or isourolithin A are produced besides urolithin A). Although production of some intermediary urolithins has been recently attributed to intestinal species from
family named
and
, the identification of the microorganisms responsible for the complete transformation of EA into the final urolithins, especially those related to metabotype B, are still unknown. In the present research we illustrate the isolation of urolithin-producing strains from human feces of a healthy adult and their ability to transform EA into different urolithin metabolites, including isourolithin A. The isolates belong to a new genus from
family. EA transformation and urolithin production arisen during the stationary phase of the growth of the bacteria under anaerobic conditions. The HPLC-DAD-MS analyses demonstrated the sequential appearance of 3,8,9,10-tetrahydroxy-urolithin (urolithin M6), 3,8,9-trihydroxy-urolithin (urolithin C) and 3,9-dihydroxy-urolithin (isourolithin A) while 3,8-dihydroxy-urolithin (urolithin A) and 3-hydroxy-urolithin (urolithin B) were not detected. For the first time isourolithin A production capacity of pure strains has been described. The biological activity attributed to urolithins A and B and isourolithin A (anti-inflammatory, anti-carcinogenic, cardioprotective, and neuroprotective properties) explains the relevance of identifying these urolithin-producing bacteria as potential novel probiotics with applications in the development of functional foods and nutraceuticals. Their human administration could improve the health benefits upon ellagitannin consumption, especially in metabotype 0 individuals. However, further research is necessary to probe well-established beneficial effects on the host and safety requirements before being considered among the next-generation probiotics.
Angiopoietin 1 (angpt1) is essential for angiogenesis. However, its role in neurogenesis is largely undiscovered. This study aimed to identify the role of angpt1 in brain development, the mode of ...action of angpt1, and its prime targets in the zebrafish brain.
We investigated the effects of embryonic brain angiogenesis and neural development using qPCR,
hybridization, microangiography, retrograde labeling, and immunostaining in the
,
,
mutant fish and transgenic overexpression of
in the zebrafish larval brains.
We showed the co-localization of angpt1 with
,
, and
in the proliferation zone in the larval brain. Additionally, lack of
was associated with downregulation of
(
), and several neurogenic factors despite upregulation of
(
),
,
(
), and glial markers. We further demonstrated that the targeted
and
mutant fish showed severely irregular cerebrovascular development, aberrant hindbrain patterning, expansion of the radial glial progenitors, downregulation of cell proliferation, deficiencies of dopaminergic, histaminergic, and GABAergic populations in the caudal hypothalamus. In contrast to
and
mutants, the
mutant fish regularly grew with no apparent phenotypes. Notably, the neural-specific
overexpression driven by the
promoter significantly increased cell proliferation and neuronal progenitor cells but decreased GABAergic neurons, and this neurogenic activity was independent of its typical receptor
.
Our results prove that
and
, besides regulating vascular development, act as a neurogenic factor via notch and wnt signaling pathways in the neural proliferation zone in the developing brain, indicating a novel role of dual regulation of
in embryonic neurogenesis that supports the concept of angiopoietin-based therapeutics in neurological disorders.
Leaf‐cutter ants are a prominent feature in Neotropical ecosystems, but a comprehensive assessment of their effects on ecosystem functions is lacking. We reviewed the literature and used our own ...recent findings to identify knowledge gaps and develop a framework to quantify the effects of leaf‐cutter ants on ecosystem processes.
Leaf‐cutter ants disturb the soil structure during nest excavation changing soil aeration and temperature. They mix relatively nutrient‐poor soil from deeper layers with the upper organic‐rich layers increasing the heterogeneity of carbon and nutrients within nest soils.
Leaf‐cutter ants account for about 25% of all herbivory in Neotropical forest ecosystems, moving 10%–15% of leaves in their foraging range to their nests. Fungal symbionts transform the fresh, nutrient‐rich vegetative material to produce hyphal nodules to feed the ants. Organic material from roots and arbuscular mycorrhizal fungi enhances carbon and nutrient turnover in nest soils and creates biogeochemical hot spots. Breakdown of organic matter, microbial and ant respiration, and nest waste material decomposition result in increased CO2, CH4, and N2O production, but the build‐up of gases and heat within the nest is mitigated by the tunnel network ventilation system. Nest ventilation dynamics are challenging to measure without bias, and improved sensor systems would likely solve this problem.
Canopy gaps above leaf‐cutter ant nests change the light, wind and temperature regimes, which affects ecosystem processes. Nests differ in density and size depending on colony age, forest type and disturbance level and change over time resulting in spatial and temporal changes of ecosystem processes. These characteristics remain a challenge to evaluate rapidly and non‐destructively.
Addressing the knowledge gaps identified in this synthesis will bring insights into physical and biological processes driving biogeochemical cycles at the nest and ecosystem scale and will improve our understanding of ecosystem biogeochemical heterogeneity and larger scale ecological phenomena.
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Plain Language Summary
Scope
Ellagitannins, ellagic acid, and the colonic metabolites urolithins (Uros) exhibit anticancer effects against colon cells, but a comprehensive molecular analysis has not been done. Herein, we ...used a panel of cell lines to first time evaluate the antiproliferative properties and accompanying molecular responses of two ellagitannin metabolites mixtures mimicking the situation in vivo and of each individual metabolite.
Methods and results
We examined cell growth, cell cycle, apoptosis, and the expression of related genes and microRNAs (miRs) in a panel of nonmalignant and malignant colon cell lines. Regardless of the composition, the mixed metabolites similarly inhibited proliferation, induced cycle arrest, and apoptosis. All the metabolites contributed to these effects, but Uro‐A, isourolithin A, Uro‐C, and Uro‐D were more potent than Uro‐B and ellagic acid. Despite molecular differences between the cell lines, we discerned relevant changes in key cancer markers and corroborated the induction of CDKN1A (cyclin‐dependent kinase inhibitor 1A gene (p21, Cip1); encoding p21) as a common step underlying the anticancer properties of Uros. Interestingly, cell‐unique downregulation of miR‐224 or upregulation of miR‐215 was found associated with CDKN1A induction.
Conclusion
Physiologically relevant mixtures of Uros exert anticancer effects against colon cancer cells via a common CDKN1A upregulatory mechanism. Other associated molecular responses are however heterogeneous and mostly cell‐specific.
Physiologically relevant (qualitatively and quantitatively) mixtures of ellagitannin metabolites, mimicking human urolithin metabotypes, as well as the individual compounds (Uro‐A ∼ IsoUro‐A ∼ Uro‐C ∼ Uro‐D > Uro‐B ∼ EA) exert cell‐specific anticancer effects (cell proliferation inhibition and cell‐cycle arrest) against colon cancer cells via a common induction of CDKN1A with the involvement of specific microRNAs.
The search for complementary treatments in primary prevention of cardiovascular disease (CVD) is a high-priority challenge. Grape and wine polyphenol resveratrol confers CV benefits, in part by ...exerting anti-inflammatory effects. However, the evidence in human long-term clinical trials has yet to be established. We aimed to investigate the effects of a dietary resveratrol-rich grape supplement on the inflammatory and fibrinolytic status of subjects at high risk of CVD and treated according to current guidelines for primary prevention of CVD. Seventy-five patients undergoing primary prevention of CVD participated in this triple-blinded, randomized, parallel, dose–response, placebo-controlled, 1-year follow-up trial. Patients, allocated in 3 groups, consumed placebo (maltodextrin), a resveratrol-rich grape supplement (resveratrol 8 mg), or a conventional grape supplement lacking resveratrol, for the first 6 months and a double dose for the next 6 months. In contrast to placebo and conventional grape supplement, the resveratrol-rich grape supplement significantly decreased high-sensitivity C-reactive protein (−26%, p = 0.03), tumor necrosis factor-α (−19.8%, p = 0.01), plasminogen activator inhibitor type 1 (−16.8%, p = 0.03), and interleukin-6/interleukin-10 ratio (−24%, p = 0.04) and increased anti-inflammatory interleukin-10 (19.8%, p = 0.00). Adiponectin (6.5%, p = 0.07) and soluble intercellular adhesion molecule-1 (−5.7%, p = 0.06) tended to increase and decrease, respectively. No adverse effects were observed in any patient. In conclusion, 1-year consumption of a resveratrol-rich grape supplement improved the inflammatory and fibrinolytic status in patients who were on statins for primary prevention of CVD and at high CVD risk (i.e., with diabetes or hypercholesterolemia plus ≥1 other CV risk factor). Our results show for the first time that a dietary intervention with grape resveratrol could complement the gold standard therapy in the primary prevention of CVD.
Invasive species have come to the forefront of conservation biology as a major threat to native biodiversity. Habitats dominated by shrub honeysuckles (Lonicera spp.) in the United States have been ...characterized as "ecological traps" by ecologists. Here we tested this hypothesis by investigating the effects of shrub honeysuckles on the nesting ecology of native birds in seven study sites in central Pennsylvania, USA. We examined how the abundance of shrub honeysuckles influenced the selection of nesting substrates and habitat for a community of common songbirds, and the parental-care behavior and nestling development of gray catbirds (Dumetella carolinensis). We found that birds had a strong bias towards nesting in honeysuckle shrubs, but not necessarily for nesting in honeysuckle-dominated habitats. Nest predation rates were affected by the density of nests in a habitat, but not by the overall abundance of honeysuckles in such habitats. Honeysuckle abundance in the habitat did show significant effects on some parental-care behavioral parameters: catbirds had higher nest visitation rates and shorter visit lengths in areas of high honeysuckle density. On average, Gray catbirds fed fruit 12%±0.31 s.e. of their nestling-feeding bouts, mostly fruits of shrub honeysuckles. Nestlings in sites with high honeysuckle density also showed higher mass:tarsus ratios, suggesting a good (possibly better) physiological condition of catbird nestlings at the time of fledging. Our study shows that honeysuckle-dominated habitats could have equivocal effects on nesting parameters of common species of native birds. We advise more caution in the widespread denomination of novel plant communities with high densities of honeysuckle as "ecological traps" as effects can be null or positive on native birds in certain localities.
This study assessed 16 different honey samples in order to select the best one for therapeutic purposes. First, a study of honey’s main bioactive compounds was carried out. Then phenolic profiles ...were determined and specific compounds quantified using a HPLC system coupled to a mass spectrometer. Then, antioxidant activity, by three in vitro methods, and antibacterial activity against reference strains and clinical isolates were evaluated. Great variability among samples was observed regarding ascorbic acid (between 0.34 ± 0.00 and 75.8 ± 0.41 mg/100 g honey; p < 0.001), total phenolic compounds (between 23.1 ± 0.83 and 158 ± 5.37 mg/100 g honey; p < 0.001), and total flavonoid contents (between 1.65 ± 0.11 and 5.93 ± 0.21 mg/100 g honey; p < 0.001). Forty-nine different phenolic compounds were detected, but only 46 of them were quantified by HPLC. The concentration of phenolic compounds and the phenolic profiles varied widely among samples (between 1.06 ± 0.04 and 18.6 ± 0.73 mg/100 g honey; p < 0.001). Antioxidant activity also varied significantly among the samples. All honey varieties exhibited antibacterial activity against both reference and clinical strains (effective concentrations ranged between 0.05 and 0.40 g/mL depending on the honey sample and bacteria tested). Overall, samples with better combinations of bioactive properties were avocado and chestnut honeys.
In this work, polymer blend nanocomposites based on carbon fillers were produced via melt‐compounding in a twin‐screw extruder. A combination of several matrices (LLDPE, EMA, and LLDPE/EMA) and ...fillers (FLG, FWCNT, and FLG/FWCNT) was used. Thermal enhancement as the consequence of few‐walled carbon nanotube addition, led to significant improvements in the initial degradation temperatures of LLDPE (383.2 > 441.2°C), EMA (371.2 > 417.3°C), and LLDPE/EMA (390.55 > 430.62°C) matrixes, respectively. The evaluation of the dynamic‐mechanical behavior of the compositions showed an increase of 80% in the storage module for LLDPE‐based nanocomposites, a reduction of 30% for blend‐based nanocomposites, and a non‐change for EMA nanocomposites. Tenacity property was considerably improved, achieving a value 78% higher to the LLDPE/EMA blend, mainly due to the possible migration of the nanoparticles from EMA phase to the LLDPE phase, creating a more efficient physical network with well‐developed percolating structure, which facilitates the dissipation of energy during mechanical loading. In summary, it can be observed that the morphology control as well as the nanofillers location, proved to be extremely relevant factors to produce a polymer film with enormous gains in the thermal and mechanical properties.
Thermal‐stability and toughening behavior with adding of carbonaceous fillers.
The bacteria harbored by fungus-growing ants produce a variety of small molecules that help maintain a complex multilateral symbiosis. In a survey of antifungal compounds from these bacteria, we ...discovered selvamicin, an unusual antifungal polyene macrolide, in bacterial isolates from two neighboring ant nests. Selvamicin resembles the clinically important antifungals nystatin A₁ and amphotericin B, but it has several distinctive structural features: a noncationic 6-deoxymannose sugar at the canonical glycosylation site and a second sugar, an unusual 4-O-methyldigitoxose, at the opposite end of selvamicin’s shortened polyene macrolide. It also lacks some of the pharmacokinetic liabilities of the clinical agents and appears to have a different target. Whole genome sequencing revealed the putative type I polyketide gene cluster responsible for selvamicin’s biosynthesis including a subcluster of genes consistent with selvamicin’s 4-O-methyldigitoxose sugar. Although the selvamicin biosynthetic cluster is virtually identical in both bacterial producers, in one it is on the chromosome, in the other it is on a plasmid. These alternative genomic contexts illustrate the biosynthetic gene cluster mobility that underlies the diversity and distribution of chemical defenses by the specialized bacteria in this multilateral symbiosis.
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