Identification and Evaluation of Olive Phenolics in the Context of Amine Oxidase Enzyme Inhibition and Depression: In Silico Modelling and In Vitro Validation.

The Mediterranean diet well known for its beneficial health effects, including mood enhancement, is characterised by the relatively high consumption of extra virgin olive oil (EVOO), which is rich in bioactive phenolic compounds. Over 200 phenolic compounds have been associated with Olea europaea, and of these, only a relatively small fraction have been characterised. Utilising the OliveNetTM library, phenolic compounds were investigated as potential inhibitors of the epigenetic modifier lysine-specific demethylase 1 (LSD1). Furthermore, the compounds were screened for inhibition of the structurally similar monoamine oxidases (MAOs) which are directly implicated in the pathophysiology of depression. Molecular docking highlighted that olive phenolics interact with the active site of LSD1 and MAOs. Protein-peptide docking was also performed to evaluate the interaction of the histone H3 peptide with LSD1, in the presence of ligands bound to the substrate-binding cavity. To validate the in silico studies, the inhibitory activity of phenolic compounds was compared to the clinically approved inhibitor tranylcypromine. Our findings indicate that olive phenolics inhibit LSD1 and the MAOs in vitro. Using a cell culture model system with corticosteroid-stimulated human BJ fibroblast cells, the results demonstrate the attenuation of dexamethasone- and hydrocortisone-induced MAO activity by phenolic compounds. The findings were further corroborated using human embryonic stem cell (hESC)-derived neurons stimulated with all-trans retinoic acid. Overall, the results indicate the inhibition of flavin adenine dinucleotide (FAD)-dependent amine oxidases by olive phenolics. More generally, our findings further support at least a partial mechanism accounting for the antidepressant effects associated with EVOO and the Mediterranean diet.

Selenosugar, selenopolysaccharide, and putative selenoflavonoid in plants.

Selenium (Se) is a naturally occurring essential micronutrient that is required for human health. Selenium supports cellular antioxidant defense and possesses bioeffects such as anti-inflammation, anti-cancer, anti-diabetic, and cardiovascular and liver protective effects arising from Se-enhanced cellular antioxidant activity. Past studies on Se have focused on elucidating Se speciation in foods, biofortification strategies to produce Se-enriched foods to address Se deficiency in the population, and the biochemical activities of Se in health. The bioavailability and toxicity of Se are closely correlated to its chemical forms and may exhibit varying effects on body physiology. Selenium exists in inorganic and organic forms, in which inorganic Se such as sodium selenite and sodium selenate is more widely available. However, it is a challenge for safe and effective supplementation considering inorganic Se low bioavailability and high cytotoxicity. Organic Se, by contrast, exhibits higher bioavailability and lower toxicity and has a more diverse composition and structure. Organic Se exists as selenoamino acids and selenoproteins, but recent research has provided evidence that it also exists as selenosugars, selenopolysaccharides, and possibly as selenoflavonoids. Different food categories contain various Se compounds, and their Se profiles vary significantly. Therefore, it is necessary to delineate Se speciation in foods to understand their impact on health. This comprehensive review documents our knowledge of the recent uncovering of the existence of selenosugars and selenopolysaccharides and the putative evidence for selenoflavonoids. The bioavailability and bioactivities of these food-derived organic Se compounds are highlighted, in addition to their composition, structural features, and structure-activity relationships.

Efficacy of flavonoids on biomarkers of type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

A systematic review and meta-analysis of 28 randomized controlled trials (RCTs) to assess the efficacy of flavonoids intake on key biomarkers related to Type 2 diabetes mellitus was conducted. The mean difference (MD) with 95% confidence intervals (95% CI) was pooled using a random-effects model. Significant reduction in fasting glucose (MD: -0.22, 95% CI: -0.34 to -0.09, p = 0.0013), hemoglobin A1c (HbA1c) (MD: -0.26, 95% CI: -0.46 to -0.05, p = 0.021), homeostasis model assessment of insulin resistance (HOMA-IR) (MD: -0.40, 95% CI: -0.66 to -0.15, p = 0.0039), triglyceride (TG) (MD: -0.13, 95% CI: -0.21 to -0.05, p = 0.002), total cholesterol (TC) (MD: -0.14, 95% CI: -0.21 to -0.08, p = 0.0002), and low density lipoprotein-C (LDL-C) (MD: -0.15; 95% CI: -0.24 to -0.07, p = 0.0009) were observed in intervention group compare to placebo at the end of trial. Moreover, flavonoid intake had negative but non-significant effect on insulin (MD: -0.46), 2 h-postprandial glucose (2 h-PPG) (MD: -0.22), homeostasis model assessment of ß-cell function (HOMA-ß) (MD: -2.81), and insignificantly increased high-density lipoprotein-C (HDL-C) (MD: 0.03). In conclusion, flavonoid intake has modest but statistically significant benefits in glucose metabolism, insulin sensitivity, and lipid metabolism, especially for significantly lowing fasting blood glucose, HOMA-IR, HbA1c, TG, TC, and LDL-C.

Recent development in fabrication and evaluation of phenolic-dietary fiber composites for potential treatment of colonic diseases.

Phenolics have been shown by in vitro and animal studies to have multiple pharmacological effects against various colonic diseases. However, their efficacy against colonic diseases, such as inflammatory bowel diseases, Crohn's disease, and colorectal cancer, is significantly compromised due to their chemical instability and susceptibility to modification along the gastrointestinal tract (GIT) before reaching the colonic site. Dietary fibers are promising candidates that can form phenolic-dietary fiber composites (PDC) to carry phenolics to the colon, as they are natural polysaccharides that are non-digestible in the upper intestinal tract but can be partially or fully degradable by gut microbiota in the colon, triggering the release at this targeted site. In addition, soluble and fermentable dietary fibers confer additional health benefits as prebiotics when used in the PDC fabrication, and the possibility of synergistic relationship between phenolics and fibers in alleviating the disease conditions. The functionalities of PDC need to be characterized in terms of their particle characteristics, molecular interactions, release profiles in simulated digestion and colonic fermentation to fully understand the metabolic fate and health benefits. This review examines recent advancements regarding the approaches for fabrication, characterization, and evaluation of PDC in in vitro conditions.

Unraveling the bioactive interplay: seaweed polysaccharide, polyphenol and their gut modulation effect.

Seaweed is rich in many unique bioactive compounds such as polyphenols and sulfated polysaccharides that are not found in terrestrial plant. The discovery of numerous biological activities from seaweed has made seaweed an attractive functional food source with the potential to be exploited for human health benefits. During food processing and digestion, cell wall polysaccharide and polyphenols commonly interact, and this may influence the nutritional properties of food. Interactions between cell wall polysaccharide and polyphenols in plant-based system has been extensively studied. However, similar interactions in seaweed have received little attention despite the vast disparity between the structural and chemical composition of plant and seaweed cell wall. This poses a challenge in extracting seaweed bioactive compounds with intact biological properties. This review aims to summarize the cell wall polysaccharide and polyphenols present in brown, red and green seaweed, and current knowledge on their potential interactions. Moreover, this review gives an overview of the gut modulation effect of seaweed polysaccharide and polyphenol.

Pediatric Drug-Associated Pancreatitis Reveals Concomitant Risk Factors and Poor Reliability of Causality Scoring: Report From INSPPIRE.

OBJECTIVES: Drug-associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co-risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE-2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children. METHODS: Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non-Medication cases, and ARP-Med vs CP-Med groups. Naranjo score was calculated for each DAP episode. RESULTS: Of 726 children, 392 had ARP and 334 had CP; 51 children (39 ARP and 12 CP) had ≥1 AP associated with a medication; 61% had ≥1 AP without concurrent medication exposure. The Med group had other risk factors present (where tested): 10 of 35 (28.6%) genetic, 1 of 48 (2.1%) autoimmune pancreatitis, 13 of 51 (25.5%) immune-mediated conditions, 11 of 50 (22.0%) obstructive/anatomic, and 28 of 51 (54.9%) systemic risk factors. In Med group, 24 of 51 (47%) had involvement of >1 medication, simultaneously or over different AP episodes. There were 20 ARP and 4 CP cases in "probable" category and 19 ARP and 7 CP in "possible" category by Naranjo scores. CONCLUSIONS: Medications were involved in 51 of 726 (7%) of ARP or CP patients in INSPPIRE-2 cohort; other pancreatitis risk factors were present in most, suggesting a potential additive role of different risks. The Naranjo scoring system failed to identify any cases as "definitive," raising questions about its reliability for DAP.

Fibre fermentation and pig faecal microbiota composition are affected by the interaction between sugarcane fibre and (poly)phenols in vitro.

We investigated the effects of (poly)phenol-rich sugarcane extract (PRSE), sugarcane fibre (SCFiber), and the combination of them (PRSE + SCFiber) on the gut microbiota and short-chain fatty acids (SCFA) production using in vitro digestion and pig faecal fermentation. Measuring total phenolic content and antioxidant activity through the in vitro digestion stages showed that PRSE + SCFiber increased the delivery of (poly)phenols to the in vitro colonic fermentation stage compared to PRSE alone. The PRSE + SCFiber modulated the faecal microbiota profile by enhancing the relative abundances of Prevotella, Lactobacillus, and Blautia, and reducing the relative abundance of Streptococcus. PRSE + SCFiber also mitigated the inhibitory effects of PRSE on SCFA production. These results suggest that the inclusion of sugarcane fibre with PRSE could increase the availability of phenolic compounds in the colon and modulate the gut microbiota towards a more favourable profile.

Selenoproteins in Health.

Selenium (Se) is a naturally occurring essential micronutrient that is required for human health. The existing form of Se includes inorganic and organic. In contrast to the inorganic Se, which has low bioavailability and high cytotoxicity, organic Se exhibits higher bioavailability, lower toxicity, and has a more diverse composition and structure. This review presents the nutritional benefits of Se by listing and linking selenoprotein (SeP) functions to evidence of health benefits. The research status of SeP from foods in recent years is introduced systematically, particularly the sources, biochemical transformation and speciation, and the bioactivities. These aspects are elaborated with references for further research and utilization of organic Se compounds in the field of health.

Application of cellulose- and chitosan-based edible coatings for quality and safety of deep-fried foods.

Excessive oil uptake and formation of carcinogens, such as acrylamide (AA), heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs), during deep-frying are a potential threat for food quality and safety. Cellulose- and chitosan-based edible coatings have been widely applied to deep-fried foods for reduction of oil uptake because of their barrier property to limit oil ingress, and their apparent inhibition of AA formation. Cellulose- and chitosan-based edible coatings have low negative impacts on sensory attributes of fried foods and are low cost, nontoxic, and nonallergenic. They also show great potential for reducing HCAs and PAHs in fried foods. The incorporation of nanoparticles improves mechanical and barrier properties of cellulose and chitosan coatings, which may also contribute to reducing carcinogens derived from deep-frying. Considering the potential for positive health outcomes, cellulose- and chitosan-based edible coatings could be a valuable method for the food industry to improve the quality and safety of deep-fried foods.

Hepatitis E Virus Species C Infection in Humans, Hong Kong.

BACKGROUND: Hepatitis E virus (HEV) variants belonging to Orthohepevirus species A (HEV-A) are the primary cause of human hepatitis E. However, we previously reported that Orthohepevirus species C genotype 1 (HEV-C1), a divergent HEV variant commonly found in rats, also causes hepatitis in humans. Here, we present a clinical-epidemiological investigation of human HEV-C1 infections detected in Hong Kong, with an emphasis on outcomes in immunocompromised individuals. METHODS: A surveillance system for detecting human HEV-C1 infections was established in Hong Kong. Epidemiological and clinical characteristics of HEV-C1 cases identified via this system between 1 August 2019 and 31 December 2020 were retrieved. Phylogenetic analysis of HEV-C1 strain sequences was performed. Infection outcomes of immunocompromised individuals with HEV-A and HEV-C1 infections were analyzed. RESULTS: HEV-C1 accounted for 8 of 53 (15.1%) reverse-transcription polymerase chain reaction (RT-PCR)-confirmed HEV infections in Hong Kong during the study period, raising the total number of HEV-C1 infections detected in the city to 16. Two distinct HEV-C1 strain groups caused human infections. Patients were elderly and/or immunocompromised; half tested negative for HEV immunoglobulin M. Cumulatively, HEV-C1 accounted for 9 of 21 (42.9%) cases of hepatitis E recorded in immunocompromised patients in Hong Kong. Immunocompromised HEV-C1 patients progressed to persistent hepatitis at similar rates (7/9 [77.8%]) as HEV-A patients (10/12 [75%]). HEV-C1 patients responded to oral ribavirin, although response to first course was sometimes poor or delayed. CONCLUSIONS: Dedicated RT-PCR-based surveillance detected human HEV-C1 cases that evade conventional hepatitis E diagnostic testing. Immunosuppressed HEV-C1-infected patients frequently progress to persistent HEV-C1 infection, for which ribavirin is a suitable treatment option.

Analytical sensitivity of the Rapid Antigen Test kits for detection of SARS-CoV-2 Omicron variant BA.2 sublineage.

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) Omicron was classified as a variant of concern in November 2021. The sublineage BA.2 spreads rapidly worldwide. Currently, there is a lack of data for the parallel comparison of Rapid Antigen Test (RAT) Kits to detect SARS-CoV-2 Omicron BA.2. We evaluated the analytical sensitivity of 12 RAT kits to detect Omicron BA.2 in the present study. Analytical sensitivity was determined by means of the limit of detection (LOD). We prepared a dilution set using a respiratory specimen collected from a COVID-19 patient infected by Omicron BA.2. The reverse transcription-polymerase chain reaction was used as a reference method. The LOD results showed that all 12 RAT kits had comparable analytical sensitivity to detect Omicron BA.2. The RAT kits selected in the current study may be used for the first-line screening of the rapid spreading Omicron BA.2.

Revisiting phytate-element interactions: implications for iron, zinc and calcium bioavailability, with emphasis on legumes.

Myo-Inositol hexakisphosphate or phytic acid concentration is a prominent factor known to impede divalent element bioavailability in vegetal foods including legumes. Both in vivo and in vitro studies have suggested that phytic acid and other plant-based constituents may synergistically form insoluble complexes affecting bioavailability of essential elements. This review provides an overview of existing investigations on the role of phytic acid in the binding, solubility and bioavailability of iron, zinc and calcium with a focus on legumes. Given the presence of various interference factors within legume matrices, current findings suggest that the commonly adapted approach of using phytic acid-element molar ratios as a bioavailability predictor may only be valid in limited circumstances. In particular, differences between protein properties and molar concentrations of other interacting ions are likely responsible for the observed poor correlations. The role of phytate degradation in element bioavailability has been previously examined, and in this review we re-emphasize its importance as a tool to enhance mineral bioavailability of mineral fortified legume crops. Food processing strategies to achieve phytate reduction were identified as promising tools to increase mineral bioavailability and included germination and fermentation, particularly when other bioavailability promoters (e.g. NaCl) are simultaneously added.[Formula: see text].

Reduction strategies for polycyclic aromatic hydrocarbons in processed foods.

Polycyclic aromatic hydrocarbons (PAHs) are a large group of carcinogenic compounds. PAHs are ubiquitous in the environment and food, thus human beings may be exposed to PAHs through ingestion (water and food), inhalation (air and smoking), and skin contact in daily life. Dietary intake is the major source of exposure to PAHs in humans. Significant and harmful levels of PAHs can be generated during food processing and cooking. Although the formation of PAHs during processing is almost unavoidable, the levels can be diminished with reduction strategies. This review aims to provide comprehensive insights into the mechanisms underlying the formation of PAHs and factors influencing their formation in processed foods. The strategy for the reduction of PAHs including change in ingredients (i.e., reducing fat content), pretreatment conditions (i.e., reducing the pH), processing methods and parameters (i.e., reducing processing temperature and time), and packaging and storage conditions, are discussed. Potential novel strategies for PAH reduction are also identified and the feasibility is evaluated.

Constraints on Ultralight Scalar Bosons within Black Hole Spin Measurements from the LIGO-Virgo GWTC-2.

Clouds of ultralight bosons-such as axions-can form around a rapidly spinning black hole, if the black hole radius is comparable to the bosons' wavelength. The cloud rapidly extracts angular momentum from the black hole, and reduces it to a characteristic value that depends on the boson's mass as well as on the black hole mass and spin. Therefore, a measurement of a black hole mass and spin can be used to reveal or exclude the existence of such bosons. Using the black holes released by LIGO and Virgo in their GWTC-2, we perform a simultaneous measurement of the black hole spin distribution at formation and the mass of the scalar boson. We find that the data strongly disfavor the existence of scalar bosons in the mass range between 1.3×10^{-13} and 2.7×10^{-13} eV. Our mass constraint is valid for bosons with negligible self-interaction, that is, with a decay constant f_{a}≳10^{14} GeV. The statistical evidence is mostly driven by the two binary black holes systems GW190412 and GW190517, which host rapidly spinning black holes. The region where bosons are excluded narrows down if these two systems merged shortly (∼10^{5} yr) after the black holes formed.

Opportunities for plant-derived enhancers for iron, zinc, and calcium bioavailability: A review.

Understanding of the mechanism of interactions between dietary elements, their salts, and complexing/binding ligands is vital to manage both deficiency and toxicity associated with essential element bioavailability. Numerous mineral ligands are found in both animal and plant foods and are known to exert bioactivity via element chelation resulting in modulation of antioxidant capacity or micobiome metabolism among other physiological outcomes. However, little is explored in the context of dietary mineral ligands and element bioavailability enhancement, particularly with respect to ligands from plant-derived food sources. This review highlights a novel perspective to consider various plant macro/micronutrients as prospective bioavailability enhancing ligands of three essential elements (Fe, Zn, and Ca). We also delineate the molecular mechanisms of the ligand-binding interactions underlying mineral bioaccessibility at the luminal level. We conclude that despite current understandings of some of the structure-activity relationships associated with strong mineral-ligand binding, the physiological links between ligands as element carriers and uptake at targeted sites throughout the gastrointestinal (GI) tract still require more research. The binding behavior of potential ligands in the human diet should be further elucidated and validated using pharmacokinetic approaches and GI models.

Modulation of the human gut microbiota by phenolics and phenolic fiber-rich foods.

The gut microbiota plays a prominent role in human health. Alterations in the gut microbiota are linked to the development of chronic diseases such as obesity, inflammatory bowel disease, metabolic syndrome, and certain cancers. We know that diet plays an important role to initiate, shape, and modulate the gut microbiota. Long-term dietary patterns are shown to be closely related with the gut microbiota enterotypes, specifically long-term consumption of carbohydrates (related to Prevotella abundance) or a diet rich in protein and animal fats (correlated to Bacteroides). Short-term consumption of solely animal- or plant-based diets have rapid and reproducible modulatory effects on the human gut microbiota. These alterations in microbiota profile by dietary alterations can be due to impact of different dietary macronutrients, carbohydrates, protein, and fat, which have diverse modulatory effects on gut microbial composition. Food-derived phenolics, which encompass structural variants of flavonoids, hydroxybenzoic acids, hydroxycinnamic acids, coumarins, stilbenes, ellagitannins, and lignans can modify the gut microbiota. Gut microbes have been shown to act on dietary fibers and phenolics to produce functional metabolites that contribute to gut health. Here, we discuss recent studies on the impacts of phenolics and phenolic fiber-rich foods on the human gut microbiota and provide an insight into potential synergistic roles between their bacterial metabolic products in the regulation of the intestinal microbiota.

Presumed tuberculous uveitis in non-endemic country for tuberculosis: case series from a New Zealand tertiary uveitis clinic.

BACKGROUND: To describe the clinical spectrum of presumed tuberculous (TB) uveitis in a developed, non-endemic country of high immigrant population. DESIGN: Retrospective review of a consecutive case series. PARTICIPANTS: All 39 patients diagnosed with presumed TB uveitis at the tertiary uveitis service in Auckland from 2007 to 2014. METHODS: Clinical chart review. MAIN OUTCOME MEASURES: Patient demographics, risk factors, ophthalmic manifestations, management and outcome. RESULTS: The median age was 37 years (interquartile range [IQR] 31-52) and 56% were female. The majority (97%) were born outside of New Zealand, and 77% had no TB-related history. Radiological abnormalities consistent with TB were evident in seven patients, including three who had culture positive pulmonary disease. Anterior uveitis was diagnosed in ten patients (26%), anterior and intermediate uveitis in eight (21%), posterior uveitis in 13 (33%) and panuveitis in eight (21%). Sixteen (41%) had retinal vasculitis, and five (13%) had multifocal serpiginoid choroiditis. Common complications included cataract (51%), ocular hypertension (36%), broad posterior synechiae (33%) and cystoid macular oedema (28%). Anti-TB treatment was initiated in 30 patients (76%). All but three patients completed the intended course of six to 12 months. Following anti-TB treatment, 67% remained in remission for at least 12 months, and all but two patients successfully stopped systemic steroids. The median initial and final visual acuity was 6/9 (IQR 6/6-6/18) and 6/6 (IQR 6/6-6/9), respectively. CONCLUSIONS: Despite a wide range of ocular presentations and complications, our cohort demonstrated good remission rate and visual prognosis following anti-TB treatment in carefully selected patients.

Optimization of Ultrasonic Extraction Parameters for the Recovery of Phenolic Compounds in Brown Seaweed: Comparison with Conventional Techniques.

Seaweed, in particular, brown seaweed, has gained research interest in the past few years due to its distinctive phenolic profile that has a multitude of bioactive properties. In order to obtain the maximum extraction efficiency of brown seaweed phenolic compounds, Response Surface Methodology was utilized to optimize the ultrasound-assisted extraction (UAE) conditions such as the amplitude, time, solvent:solid ratio, and NaOH concentration. Under optimal conditions, UAE had a higher extraction efficiency of free and bound phenolic compounds compared to conventional extraction (stirred 16 h at 4 °C). This led to higher antioxidant activity in the seaweed extract obtained under UAE conditions. The profiling of phenolic compounds using LC-ESI-QTOF-MS/MS identified a total of 25 phenolics with more phenolics extracted from the free phenolic extraction compared to the bound phenolic extracts. Among them, peonidin 3-O-diglucodise-5-O-glucoside and hesperidin 5,7-O-diglucuronide are unique compounds that were identified in P. comosa, E. radiata and D. potatorum, which are not reported in plants. Overall, our findings provided optimal phenolic extraction from brown seaweed for research into employing brown seaweed as a functional food.