The Effects of Encapsulation on the In Vitro Anti-Clostridial Activity of Olive Mill Wastewater Polyphenolic Extracts: A Promising Strategy to Limit Microbial Growth in Food Systems.

Despite the technologies applied to food production, microbial contamination and chemical deterioration are still matters of great concern. In order to limit these phenomena, new natural approaches should be applied. In this context, the present study aimed to assess the antioxidant and anti-Clostridial effects of two different polyphenolic extracts derived from olive mill vegetation water, one liquid (LE) and one encapsulated (EE). The extracts have been preliminary characterized using Liquid Chromatography Quadrupole Time-Of Flight spectrometry. The Oxygen Radical Absorbance Capacity method was used to determine the antioxidant capacity, registering a higher value for EE compared to that for LE (3256 ± 85 and 2446 ± 13 µgTE/g, respectively). The antibacterial activity against C. perfringens, C. botulinum and C. difficile was studied by the agar well diffusion method, MIC and MBC determination and a time-kill test. The results confirm that EE and LE are able to limit microbial growth, albeit with minor effects when the phenolic compounds are encapsulated. Further studies are needed to evaluate the possible application of these extracts in food systems.

Aryl Hydrocarbon Receptor Agonism Antagonizes the Hypoxia-driven Inflammation in Cystic Fibrosis.

Hypoxia contributes to the exaggerated yet ineffective airway inflammation that fails to oppose infections in cystic fibrosis (CF). However, the potential for impairment of essential immune functions by HIF-1α (hypoxia-inducible factor 1α) inhibition demands a better comprehension of downstream hypoxia-dependent pathways that are amenable for manipulation. We assessed here whether hypoxia may interfere with the activity of AhR (aryl hydrocarbon receptor), a versatile environmental sensor highly expressed in the lungs, where it plays a homeostatic role. We used murine models of Aspergillus fumigatus infection in vivo and human cells in vitro to define the functional role of AhR in CF, evaluate the impact of hypoxia on AhR expression and activity, and assess whether AhR agonism may antagonize hypoxia-driven inflammation. We demonstrated that there is an important interferential cross-talk between the AhR and HIF-1α signaling pathways in murine and human CF, in that HIF-1α induction squelched the normal AhR response through an impaired formation of the AhR:ARNT (aryl hydrocarbon receptor nuclear translocator)/HIF-1ß heterodimer. However, functional studies and analysis of the AhR genetic variability in patients with CF proved that AhR agonism could prevent hypoxia-driven inflammation, restore immune homeostasis, and improve lung function. This study emphasizes the contribution of environmental factors, such as infections, in CF disease progression and suggests the exploitation of hypoxia:xenobiotic receptor cross-talk for antiinflammatory therapy in CF.

Occurrence of Hydroxytyrosol, Tyrosol and Their Metabolites in Italian Cheese.

Tyrosol (T) and hydroxytyrosol (HT) are phenyl alcohol polyphenols with well-recognized health-promoting properties. They are widely diffused in several vegetables, especially in olive products (leaves, fruits and oil). Therefore, they could be present in food produced from herbivorous animals such as in milk and cheese. In this study, an analytical method to determine T, HT and some of their phase II metabolites (sulphates and glucuronides) in cheese was developed and validated. Samples were extracted with an acidic mixture of MeOH/water 80/20 (v/v) and, after a low temperature clean-up, the extracts were evaporated and injected in a liquid-chromatography coupled with high resolution mass spectrometry (LC-Q-Orbitrap). A validation study demonstrated satisfactory method performance characteristics (selectivity, linearity, precision, recovery factors, detection and quantification limits). The developed protocol was then applied to analyze 36 Italian cheeses made from ewe, goat and cow milk. The sum of detected compounds (T, tyrosol sulfate, hydroxytyrosol-3-O-sulfate and hydroxytyrosol-4-O-sulfate) reached as high as 2300 µg kg-1 on a dry weight basis, although in about 45% of cow cheeses it did not exceed 50 µg kg-1. Ewe cheeses were significantly richer of polyphenols (sum) as well as HT sulfate metabolites than cow cheeses. In conclusion, results shows that cheese cannot be considered an important dietary source of these valuable compounds.

Transfer of a Multiclass Method for over 60 Antibiotics in Food from High Resolution to Low Resolution Mass Spectrometry.

A multiclass method has been developed to screen and confirm a wide range of anti-microbial residues in muscle and milk, and validated using liquid-chromatography coupled to (low-resolution, LR) tandem mass spectrometry (LC-QqQ). Over sixty antibiotics, belonging to ten distinct families, were included in the method scope. The development process was rapidly concluded as a result of two previously implemented methods. This consisted of identical sample treatments, followed by liquid chromatography, and coupled with high-resolution (HR) mass spectrometry (LC-Q-Orbitrap). The validation study was performed in the range between 10-1500 µg·kg-1 for muscles and 2-333 µg·kg-1 for milk. The main performance characteristics were estimated and, then, compared to those previously obtained with HR technique. The validity of the method transfer was ascertained also through inter-laboratory studies.

Chloroperfluoropolyether carboxylate compounds: A review.

Several new per- and polyfluoroalkyl substances (PFASs) have been synthesized to replace traditional (legacy) PFASs frequently without clear information on their structure, use and potential toxicity. Among them, chloroperfluoropolyether carboxylates (ClPFPECAs) are an emerging group used as processing aids in the production of fluoropolymers to replace the ammonium salt of perfluorononanoic acid (PFNA). The Solvay Company has produced ClPFPECAs as a mixture of six congeners (oligomers) since the mid-1990s, but other possible manufacturers and annual quantities synthesized and used worldwide are unknown. Initial studies to monitor their presence were conducted because of public authority concerns about suspect environmental contamination near fluoropolymer plants. As of 2015, these chemicals have been found in soil, water, vegetative tissues and wildlife, as well as in biological fluids of exposed workers and people, in research carried out mainly in the United States (New Jersey) and Italy. Analysis of wildlife collected even in non-industrialized areas demonstrated widespread occurrence of ClPFPECAs. From the analytical point of view, the (presumptive) evidence of their presence was obtained through the application of non-targeted approaches performed by liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Available toxicological data show that ClPFPECAs have similar adverse effects than the compounds which they have replaced, whereas their carcinogenic potential and reproductive damage are currently unknown. All these observations once again cast doubt on whether many alternatives to traditional PFAS are actually safer for the environment and health.

Assessment of the combined inputs of antimicrobials from top soil improvers and irrigation waters on green leafy vegetable fields.

Sustainable food systems involve the recycling of biowaste and water. This study characterizes thirty-one top soil improvers of anthropogenic, animal, and green waste origin, along with eleven irrigation waters from rivers, channels, and civil wastewater treatment plants (cWWTPs) for the presence of antimicrobials. Liquid chromatography coupled with hybrid High-Resolution Mass Spectrometry (LC-HRMS/MS) was employed to identify forty-eight drugs belonging to the classes of sulfonamides (11), tetracyclines (7), fluoroquinolones (10), macrolides (12), amphenicols (3), pleuromutilins (2), diaminopyrimidines (1), rifamycins (1) and licosamides (1). Sludge from cWWTPs, animal manure, slurry, and poultry litter exhibited the highest loads for sulfonamides, tetracyclines, fluoroquinolones and macrolides (80, 470, 885, and 4,487 ng g-1 wet weight, respectively) with nor- and ciprofloxacin serving as markers for anthropogenic sources. In compost and digestate, antimicrobials were found to be almost always below the limits of quantification. Reused water from cWWTPs for irrigation in open-field lettuce production were contaminated in the range of 12-221 ng L-1 with sulfonamides, tetracyclines, and fluoroquinolones, compared to very few detected in channels and surface waters. The Antimicrobials Hazard Index (HI), based on the Predicted No Effect Concentration for Antimicrobial Resistance (PNECAMR), was significantly >100 in contaminated topsoil improvers from urban and animal sources. Accounting for worst-case inputs from topsoil improvers and irrigation water, as well as dilution factors in amended soil, fluoroquinolones only exhibited an HI around 1 in open fields for lettuce production. The origin of topsoil improvers plays a pivotal role in ensuring safe and sustainable leafy vegetable production, thereby mitigating the risk of Antimicrobial Resistance (AMR) onset in food-borne diseases and the transfer of AMR elements to the human gut flora.

Olive Mill Waste-Water Extract Enriched in Hydroxytyrosol and Tyrosol Modulates Host-Pathogen Interaction in IPEC-J2 Cells.

The dietary supplementation of olive oil by-products, including olive mill waste-water (OMWW) in animal diets, is a novel application that allows for their re-utilization and recycling and could potentially decrease the use of antibiotics, antimicrobial resistance risk in livestock species, and the occurrence of intestinal diseases. Salmonella serovar typhimurium is one of the most widespread intestinal pathogens in the world, causing enterocolitis in pigs. The aim of this study was to investigate the effect of an OMWW extract enriched in polyphenols (hydroxytyrosol and tyrosol) in the immune response of an intestinal porcine epithelial cell line (IPEC-J2) following S. typhimurium infection. Cells were pre-treated with OMWW-extract polyphenols (OMWW-EP, 0.35 and 1.4 µg) for 24 h and then infected with S. typhimurium for 1 h. We evaluated bacterial invasiveness and assayed IPEC-J2 gene expression with RT-qPCR and cytokine release with an ELISA test. The obtained results showed that OMWW-EP (1.4 µg) significantly reduced S. typhimurium invasiveness; 0.35 µg decreased the IPEC-J2 gene expression of IL1B, MYD88, DEFB1 and DEFB4A, while 1.4 µg down-regulated IL1B and DEFB4A and increased TGFB1. The cytokine content was unchanged in infected cells. This is the first study demonstrating the in vitro immunomodulatory and antimicrobial activity of OMWW extracts enriched in polyphenols, suggesting a protective role of OMWW polyphenols on the pig intestine and their potential application as feed supplements in farm animals such as pigs.

Impact of Soil Fertilization with Pig Slurry on Antibiotic Residues and Resistance Genes: A Longitudinal Study.

The impact of soil fertilization with animal manure on the spread and persistence of antibiotic resistance in the environment is far from being fully understood. To add knowledge about persistence and correlations between antibiotic residues and antibiotic resistance genes (ARGs) in fertilized soil, a longitudinal soil mesocosm study was conducted. Soil samples were collected from the mesocosms immediately before spreading and then afterward at fifteen time points during a 320-day observation period. Eight ARGs (ermB, sul1, tetA, tetG, tetM, cfr, fexA, and optrA) and the class 1 integron-integrase gene, intI1, were determined in both pig slurry and soil, as well as residues of 36 antibiotics. Soil chemical and biochemical parameters were also measured. Twelve antibiotics were detected in the slurry in the range of 3 µg kg-1-3605 µg kg-1, with doxycycline, lincomycin, and tiamulin being the most abundant, whereas ermB, sul1, and tetM were the predominant ARGs. Before spreading, neither antibiotic residues nor ARGs were detectable in the soil; afterwards, their concentrations mirrored those in the slurry, with a gradual decline over the duration of the experiment. After about three months, the effect of the amendment was almost over, and no further evolution was observed.

Occurrence and pattern of legacy and emerging per- and Poly-FluoroAlkyl substances (PFAS) in eggs of loggerhead turtle Caretta caretta from western Mediterranean.

Per-and Poly-FluoroAlkyl Substances (PFAS) are a class of persistent, toxic, and mobile and chemicals both from industrial sources and from the use and disposal of Consumers products containing PFAS, whose concentration in marine food webs could pose a toxicological risk for biota and humans. In 2021, unhatched eggs were sampled from 41 loggerhead turtle Caretta caretta nests from the Italian shores of the Campania Region (Southern Italy). Whole eggs were analysed for the presence of 66 legacy and emerging PFAS with Liquid Chromatography coupled to Hybrid High Resolution Mass Spectrometry. A median Σ66 Per- and Poly-FluoroAlkyl Substances value of 3.34 ng/g egg fresh weight was found; perfluoroctane sulfonate (PFOS) represented the most contributing congener (47%), followed by perfluoro-n-undecanoic acid, perfluoro-n-tridecanoic acid, perfluoro-n-decanoic acid, perfluoro-n-decanoic acid, and perfluoro-n-tetradecanoic acid, respectively. Such compounds showed a log-norm distribution, suggesting found concentrations could represent the baseline levels in the considered sampling area. Emerging ChloroPolyFluoroPolyEthers Carboxylic Acids (ClPFECAs) were found in 20 out of 41 samples in the range 0.01-1.59 ng/g. Four samples had 20-100 fold higher concentration compared to that of other samples, suggesting the presence of hot spot areas possibly related to presence of fluoropolymer-based marine litter turtles may ingest. The analysis of two paired eggs/liver samples recovered from stranded animals revealed PFAS concentration in the same order of magnitude, supporting the role of vitellogenin in their selective transfer to yolk. Significant (P = 0.0155) Kendall negative correlation coefficient of -0.2705 among PFOS content in eggs and the recorded hatching success prompts for further investigation on associated exposure assessment and related eco-toxicity risk. This work reports for the first time PFAS presence in georeferenced loggerhead turtle eggs of the Mediterranean Sea and results represent a starting point to study PFAS time-trends in this vulnerable species.

Development and validation of a multiresidue liquid chromatography/tandem mass spectrometry method for 11 coccidiostats in feed.

A confirmatory method for the determination of 11 regulated coccidiostats including the ionophore antibiotics lasalocid, maduramicin, monensin, narasin, salinomycin, and semduramicin and the chemical coccidiostats decoquinate, diclazuril, halofuginone, nicarbazin, and robenidine in animal feed was developed and validated. The procedure was intended for the identification and quantification of the coccidiostats at concentrations relating both to the unintentional carryover as stated in Regulation 574/2011 and to the authorized levels in target feed. The analytes were determined by LC/MS/MS in the positive or negative electrospray ionization mode. The method performance characteristics were estimated in the relevant application field from 0.003 to 200 mg/kg. Validation criteria of linearity, specificity, trueness, precision, LOD, and LOQ along with measurement uncertainty were estimated for all analytes. Absolute and relative matrix effects were also studied. The results proved that the method performance was satisfactory, and it was successfully applied to carryover control by analyzing 165 feed samples collected within regulatory monitoring plans. Finally, since the carryover phenomenon in feed may result in the presence of residues in food products of animal origin, a survey has been carried out on the occurrence of coccidiostats in 167 eggs and animal muscles.

Optimization of Ultrasound-Assisted Extraction of Chlorogenic Acid from Potato Sprout Waste and Enhancement of the In Vitro Total Antioxidant Capacity.

Potato sprouts, an underutilized by-product of potato processing, could be exploited for the recovery of caffeoyl-quinic acids (CQAs), a family of polyphenols with well-recognized biological activities. In this work, the predominant compound of this class, 5-CQA, was extracted by Ultrasound-Assisted Extraction (UAE) under conditions optimized by an Experimental Design. The investigated variables solid/solvent ratio (1:10-1:50 g/mL), water content in ethanol (30-100% v/v) and UAE time (5-20 min) highlighted a critical influence of the last two factors on the extraction efficiency: extracts richer in 5-CQA were obtained with lower water content (30%) and time (5 min). The addition of ascorbic acid (1.7 mM) as anti-browning agent to the extraction solvent improved the extraction efficiency of 5-CQA compared to acetic and citric acids (3158.71 µg/mL, 1766.71 µg/mL, 1468.20 µg/mL, respectively). A parallel trend for the three acids and an increase in 5-CQA recovery was obtained with the use of freeze-dried sprouts (4980.05 µg/mL, 4795.62, 4211.25 µg/mL, respectively). Total antioxidant capacity (TAC) in vitro demonstrated UAE being a more valuable technique than conventional maceration. Furthermore, three-times-higher values of TPC (7.89 mg GAE/g) and TAC (FRAP: 24.01 mg TE/g; DPPH: 26.20 mg TE/g; ABTS 26.72 mg TE/g) were measured for the optimized extract compared to the initial one. An HPLC-DAD method was applied to monitor 5-CQA recovery, while an LC-HRMS/MS investigation allowed us to perform analyte identity confirmation along with detection of the glycoalkaloids α-solanine and α-chaconine. This evidence underlines the necessity to develop purification strategies in order to maximize the potential of potato sprout waste as a source of 5-CQA.

Concentrations and co-occurrence of 101 emerging and legacy organic pollutants in the ultrafine, fine and coarse fractions of airborne particulates associated with treatment of waste from electrical and electronic equipment.

Occupational exposure to airborne particles can increase the development of morbidity, also because of the chemical composition of particulate matter (PM). In workplace, where manual and mechanical disassembly of electric and electronic equipment (EEE) take place, there are evident risks of respiratory exposure to a great number of different toxic organic compounds present in the electrical and plastic materials of which the equipment is made. Airborne particles are numerous, cover a wide range of sizes and are rich in toxic organic compounds. In the present work, a sampling program was conducted and ultrafine, fine and coarse airborne particles were collected in three EEE waste treatment plants. Afterwards, the extraction and analysis of polycyclic aromatic hydrocarbons (PAHs), their nitro and oxygenated derivatives (nitroPAHs, oxyPAHs), organophosphorus compounds (OPEs), Brominated Flame Retardants (BFRs), polychlorinated biphenyls (PCBs), Polybrominated Diphenyl Ethers (PBDEs), and polyfluoralkyl substances (PFASs) was performed. The percentage ratio of the mass of organic compounds and the mass of the ultrafine fraction of PM (PM0.1) was higher than those of the fine and coarse fractions. Even with low concentrations, the co-occurrence of numerous potentially toxic compounds capable of easily reaching other organs passing by the lung vasculature, through the lymph makes the working environment unhealthy.

Bridging of host-microbiota tryptophan partitioning by the serotonin pathway in fungal pneumonia.

The aromatic amino acid L-tryptophan (Trp) is essentially metabolized along the host and microbial pathways. While much is known about the role played by downstream metabolites of each pathways in intestinal homeostasis, their role in lung immune homeostasis is underappreciated. Here we have examined the role played by the Trp hydroxylase/5-hydroxytryptamine (5-HT) pathway in calibrating host and microbial Trp metabolism during Aspergillus fumigatus pneumonia. We found that 5-HT produced by mast cells essentially contributed to pathogen clearance and immune homeostasis in infection by promoting the host protective indoleamine-2,3-dioxygenase 1/kynurenine pathway and limiting the microbial activation of the indole/aryl hydrocarbon receptor pathway. This occurred via regulation of lung and intestinal microbiota and signaling pathways. 5-HT was deficient in the sputa of patients with Cystic fibrosis, while 5-HT supplementation restored the dysregulated Trp partitioning in murine disease. These findings suggest that 5-HT, by bridging host-microbiota Trp partitioning, may have clinical effects beyond its mood regulatory function in respiratory pathologies with an inflammatory component.

Dual species sphingosine-1-phosphate lyase inhibitors to combine antifungal and anti-inflammatory activities in cystic fibrosis: a feasibility study.

Cystic fibrosis (CF) is an autosomal recessive disorder characterized by respiratory failure due to a vicious cycle of defective Cystic Fibrosis Transmembrane conductance Regulator (CFTR) function, chronic inflammation and recurrent bacterial and fungal infections. Although the recent introduction of CFTR correctors/potentiators has revolutionized the clinical management of CF patients, resurgence of inflammation and persistence of pathogens still posit a major concern and should be targeted contextually. On the background of a network-based selectivity that allows to target the same enzyme in the host and microbes with different outcomes, we focused on sphingosine-1-phosphate (S1P) lyase (SPL) of the sphingolipid metabolism as a potential candidate to uniquely induce anti-inflammatory and antifungal activities in CF. As a feasibility study, herein we show that interfering with S1P metabolism improved the immune response in a murine model of CF with aspergillosis while preventing germination of Aspergillus fumigatus conidia. In addition, in an early drug discovery process, we purified human and A. fumigatus SPL, characterized their biochemical and structural properties, and performed an in silico screening to identify potential dual species SPL inhibitors. We identified two hits behaving as competitive inhibitors of pathogen and host SPL, thus paving the way for hit-to-lead and translational studies for the development of drug candidates capable of restraining fungal growth and increasing antifungal resistance.

Investigation on chlorogenic acid stability in aqueous solution after microwave treatment.

Recently, several health benefits associated with the consumption of foods rich in chlorogenic acid (5-CQA) have been reported. However, an important issue is its low stability during extraction and food processing, resulting in isomerization to neochlorogenic and cryptochlorogenic acids and the formation of further degradation products. This work describes the evaluation of 5-CQA reactivity in commercial waters after microwave treatment. An optimized HPLC-UV method was used to monitor 5-CQA conversion to its main isomers, while LC-HRMS/MS was performed for the elucidation of transformation products. Results revealed different degrees of isomerization in 5-CQA depending on the water sample, and the formation of oxidation derivatives of CQA isomers. This study highlights the importance of analytical monitoring of food compounds, during microwave treatment for example. In the case of 5-CQA, understanding of the degradation process would allow better preservation of bioactive constituent in foods and beverages and health promoting effects.

In-depth characterization of phenolic profiling of Moraiolo extra-virgin olive oil extract and initial investigation of the inhibitory effect on Indoleamine-2,3-Dioxygenase (IDO1) enzyme.

In this research, the phenolic extract from Moraiolo extra-virgin olive oil (EVOO) was thoroughly characterized. A reversed-phase HPLC method with a photodiode detector allowed to measure a total phenol content higher than 500 mg/kg EVOO, with elevated amounts of oleocanthal, oleacein, and oleouropein aglycone (131.2, 213.5, and 158.4 mg/kg EVOO, respectively). Appreciable amounts of (+)-pinoresinol and (+)- 1-acetoxy-pinoresinol, 3.2 and 12.5 mg/kg EVOO respectively, were measured. High-resolution mass spectrometry with Orbitrap mass analyzer technology was used to confirm the identity of the analytes. Afterwards, the extract was tested, for the first time, for its activity on Indoleamine-2,3-Dioxygenase (IDO1). This enzyme appears as a promising target for the modulation of the neuroinflammatory-oxidative processes relying on the pathogenesis of several neurodegenerative diseases. The extract showed an inhibitory effect on the catalytic activity of both human and murine IDO1, with a good safety at the concentrations of 15 and 30 µg/mL.

Pharmacokinetics of cannabidiol following single oral and oral transmucosal administration in dogs.

Introduction: In the last few years, different formulations containing cannabidiol (CBD) were tested with regard to its efficacy on chronic pain, refractory epilepsy, anxiety, aggressive behavior and atopic dermatitis in dogs. CBD is generally administered orally, but its low bioavailability, probably due to a first-pass metabolism, represents a great limitation. The aim of this study was to evaluate if CBD bioavailability increases after oral transmucosal administration (OTM) compared to oral treatment. Methods: Twelve dogs diagnosed with mild chronic pain were enrolled in the study and treated once orally or OTM (6 dogs/group) with a pure CBD in oil formulation at a dosing rate of 1 mg/kg b.w. At prefixed time points, blood samples were collected to define CBD plasma concentrations vs. time profiles, and the main pharmacokinetics parameters were obtained by non-compartmental model. Results: CBD Cmax, Tmax, terminal half-life and AUC0 - t were 206.77 ± 167 and 200.33 ± 158.33 ng/mL, 2.17 ± 0.98 and 1.92 ± 1.11 h, 2.67 ± 0.53 and 2.62 ± 0.64 h, 647.51 ± 453.17, and 536.05 ± 370.21 h*ng/mL, following oral and OTM administration, respectively. No significant difference in pharmacokinetic parameters were observed between treatments. Discussion: The OTM administration did not increase cannabidiol bioavailability compared to oral treatment. The almost perfectly superimposable mean plasma concentrations of cannabidiol following the two treatments suggests that CBD is not able to be adsorbed by the oral mucosa or that its absorption is very scarce, and that CBD is swallowed and absorbed in the gastrointestinal tract.

Anakinra restores cellular proteostasis by coupling mitochondrial redox balance to autophagy.

Autophagy selectively degrades aggregation-prone misfolded proteins caused by defective cellular proteostasis. However, the complexity of autophagy may prevent the full appreciation of how its modulation could be used as a therapeutic strategy in disease management. Here, we define a molecular pathway through which recombinant IL-1 receptor antagonist (IL-1Ra, anakinra) affects cellular proteostasis independently from the IL-1 receptor (IL-1R1). Anakinra promoted H2O2-driven autophagy through a xenobiotic sensing pathway involving the aryl hydrocarbon receptor that, activated through the indoleamine 2,3-dioxygenase 1-kynurenine pathway, transcriptionally activated NADPH oxidase 4 independent of the IL-1R1. By coupling the mitochondrial redox balance to autophagy, anakinra improved the dysregulated proteostasis network in murine and human cystic fibrosis. We anticipate that anakinra may represent a therapeutic option in addition to its IL-1R1-dependent antiinflammatory properties by acting at the intersection of mitochondrial oxidative stress and autophagy with the capacity to restore conditions in which defective proteostasis leads to human disease.

Enteric formulated indole-3-carboxaldehyde targets the aryl hydrocarbon receptor for protection in a murine model of metabolic syndrome.

The metabolic syndrome (MetSyn) is a disorder characterized by a cluster of diseases where the regulation of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor endowed with ligand- and context-dependent activities, can have a major therapeutic relevance. We have recently discovered a tryptophan metabolite of microbial origin, indole-3-carboxaldehyde (3-IAld), able to regulate intestinal mucosal homeostasis by acting as a ligand of AhR. This makes 3-IAld a potential candidate to treat MetSyn related ailments. Herein, we provide a proof of concept on the efficacy and safety of 3-IAld encapsulated in enteric microparticles (MP) in vivo in a MetSyn murine model. In particular, we showed that 3-IAld: i) is released from MPs in the intestine and potentially metabolized; ii) is able to activate AhR locally; iii) prevents the metabolic complications and the intestinal epithelial barrier dysfunction; iv) is not associated with toxic events. This study does not only extend the biological activity of 3-IAld in vivo, but also provides hints on the therapeutic potential of 3-IAld delivered by enteric MP in MetSyn related diseases.

Effects of Dietary Polyphenols from Olive Mill Waste Waters on Inflammatory and Apoptotic Effectors in Rabbit Ovary.

The aim of this study was to evaluate the effect of dietary polyphenols on the expression of the effectors involved in inflammation and apoptosis in rabbit ovary. New Zealand White female rabbits were fed a basal control diet (CTR), or the same diet supplemented with a polyphenolic concentrate (POL, 282.4 mg/kg) obtained from olive mill waste waters. The follicle counts and the relative mRNA (RT-qPCR) and protein (immunohistochemistry) expression of the effectors involved in inflammation (cyclooxygenase-2; interleukin-1beta; tumor necrosis factor-alpha, TNFA) and apoptosis (BCL2-associated X protein, BAX), detected in the ovaries of both groups, were examined. The POL diet increased the primary and total follicles number. Cyclooxygenase-2 gene expression was higher (p < 0.05) in the POL group than in the CTR group, whereas BAX was lower (p < 0.05) in POL than CTR. Immunohistochemistry revealed the presence of all the proteins examined, with weaker (p < 0.05) COX2 and BAX signals in POL. No differences between the CTR and POL groups were observed for IL1B and TNFA gene and protein expression. These preliminary findings show that dietary polyphenols modulate inflammatory and apoptotic activities in rabbit ovary, regulating cyclooxygenase-2 and BAX expression, thus suggesting a functional involvement of these dietary compounds in mammalian reproduction.