Assessment of dietary intake of bioactive food compounds according to income level in the Brazilian population.

There is an inverse association between bioactive compounds intake and disease risk. The knowledge of its consumption according to socio-economic strata is important, which allows identification of potential intervention targets. Thus, we aimed to investigate bioactive compounds intake according to income level in Brazilian population. Data were obtained from the Brazilian Household Budget Survey, a cross-sectional survey which included data on individual food intake of 34,003 subjects aged 10 years and over collected using two 24-h dietary records. Polyphenol and carotenoid content of foods was identified using published databases. Total polyphenol and carotenoid intake were determined according to per capita income, as well as main food sources. Total polyphenols and flavonoids intake increased with income level, and subjects with lower income showed higher phenolic acids intake than individuals in highest income (p = 0.0001). Total carotenoids and classes intake (with exception to ß-cryptoxanthin and zeaxanthin) were higher among subjects in highest income quartile, compared to the lowest quartile (p = 0.0001). Coffee was major source to total polyphenols and phenolic acids intake, and orange juice was main flavonoid provider in individuals from all income levels. In the upper income quartile, total carotenoid was supplied mainly by tomato and kale, and fruits had important contribution to carotenoid intake in the lowest income quartile. There is important influence of income level on diet quality regarding intake of foods with bioactive compounds, and individuals with lower income may experience lower quality diets due to less availability of foods with bioactive compounds.

Identification of Food Compounds as inhibitors of SARS-CoV-2 main protease using molecular docking and molecular dynamics simulations.

SARS-CoV-2 has rapidly emerged as a global pandemic with high infection rate. At present, there is no drug available for this deadly disease. Recently, Mpro (Main Protease) enzyme has been identified as essential proteins for the survival of this virus. In the present work, Lipinski's rules and molecular docking have been performed to identify plausible inhibitors of Mpro using food compounds. For virtual screening, a database of food compounds was downloaded and then filtered using Lipinski's rule of five. Then, molecular docking was accomplished to identify hits using Mpro protein as the target enzyme. This led to identification of a Spermidine derivative as a hit. In the next step, Spermidine derivatives were collected from PubMed and screened for their binding with Mpro protein. In addition, molecular dynamic simulations (200 ns) were executed to get additional information. Some of the compounds are found to have strong affinity for Mpro, therefore these hits could be used to develop a therapeutic agent for SARS-CoV-2.

miRNAs and Novel Food Compounds Related to the Browning Process.

Obesity prevalence is rapidly increasing worldwide. With the discovery of brown adipose tissue (BAT) in adult humans, BAT activation has emerged as a potential strategy for increasing energy expenditure. Recently, the presence of a third type of fat, referred to as beige or brite (brown in white), has been recognized to be present in certain kinds of white adipose tissue (WAT) depots. It has been suggested that WAT can undergo the process of browning in response to stimuli that induce and enhance the expression of thermogenesis: a metabolic feature typically associated with BAT. MicroRNAs (miRNAs) are small transcriptional regulators that control gene expression in a variety of tissues, including WAT and BAT. Likewise, it was shown that several food compounds could influence miRNAs associated with browning, thus, potentially contributing to the management of excessive adipose tissue accumulation (obesity) through specific nutritional and dietetic approaches. Therefore, this has created significant excitement towards the development of a promising dietary strategy to promote browning/beiging in WAT to potentially contribute to combat the growing epidemic of obesity. For this reason, we summarize the current knowledge about miRNAs and food compounds that could be applied in promoting adipose browning, as well as the cellular mechanisms involved.

Analysis of Fatty Acid Esters of Hydroxyl Fatty Acid in Selected Plant Food.

Metabolic syndrome, characterized by obesity, low-grade inflammation, insulin resistance, hyperglycemia, dyslipidemia and hypertension, is a major risk factor for cardiovascular mortality. Preclinical studies on recently discovered classes of lipids - fatty acid esters of hydroxy fatty acids (FAHFA) have revealed their anti-inflammatory and insulin-sensitizing potential. The FAHFA levels are significantly decreased in insulin-resistant individuals, their application exhibited anti-inflammatory effects and restoring the glucose-insulin homeostasis. The aim of our research was to analyze the overall FAHFA composition in a common diet, as only a partial FAHFA composition has been revealed so far (only the PAHSA subclass was analyzed in a few foods). A new approach to the FAHFAs analysis includes nano-LC and post-column modifier followed by negative ion mass spectrometry, in order to obtain maximum sensitivity. Analysis of different foods - oat (whole grain, coarse flakes and fine flakes), apple, clementine, lemon, strawberry, blueberry, mango, kiwi, avocado, pineapple, banana, onion, garlic, cherry tomato, carrot, parsley root, pepper and radish - exhibited wide inter-food variation in the FAHFA profiles. Sixteen analyzed FAHFAs (palmitic, oleic, palmitoleic and stearic hydroxy-esters) showed microgram to low nanogram levels (0.165 ng/g - 32 µg/g FW), with the highest abundancy in oat, clementine, garlic and pineapple. Stearic acid hydroxy stearic acid (SAHSA) was the most abundant FAHFA, especially in the food with antioxidative, anti-inflammatory and beneficial metabolic effects. In contrary, the PAHSA - previously proven to have the strongest antihyperglycemic and insulin-sensitizing effects, was not present in some foods (radish, avocado, mango, lemon, cherry tomato, kiwi). Our study proves the importance of overall FAHFA analysis in food (especially in a functional food), because of their potential metabolic benefits and possible future incorporation in special diets.

[Microbial production of food compounds with carbon dioxide and derived low-carbon molecules as substrates].

The construction and optimization of microbial cell factories are crucial steps and key technologies in achieving green biomanufacturing. As concern has been aroused regarding the excessive carbon dioxide (CO2) emissions and food security, a new and promising research field, microbial conversion of CO2 into food compounds, has emerged. The research in this field not only holds significant implications for achieving the carbon peaking and carbon neutrality goals but also plays a role in maintaining food security. This paper provides a comprehensive review and outlook of the research on utilizing CO2 and its derived low-carbon chemicals for the production of food compounds, focusing on the production of glucose, sugar derivatives, and single-cell proteins and the development of artificial CO2 fixation pathways.

A Shared Perspective on in Vitro and in Vivo Models to Assay Intestinal Transepithelial Transport of Food Compounds.

Assessing nutrient bioavailability is complex, as the process involves multiple digestion steps, several cellular environments, and regulatory-metabolic mechanisms. Several in vitro models of different physiological relevance are used to study nutrient absorption, providing significant challenges in data evaluation. However, such in vitro models are needed for mechanistic studies as well as to screen for biological functionality of the food structures designed. This collaborative work aims to put into perspective the wide-range of models to assay the permeability of food compounds considering the particular nature of the different molecules, and, where possible, in vivo data are provided for comparison.

Detoxification activity of bioactive food compounds against ethanol-induced injuries and hangover symptoms: A review.

Alcohol drinking is a popular activity among adolescents in many countries, largely due to its pleasant, relaxing effects. As a major concern, ethanol consumption put the drinkers at risk of nutrients' deficiency due to the disordered eating, anorexia, and malabsorption of nutrients. Moreover, alcohol drinking may lead to the development of hangover symptoms including diarrhea, thirsty, fatigue, and oxidative stress. A broad range of functional food components with antioxidant and/or anti-inflammatory properties including pectin, aloe vera polysaccharides, chito-oligosaccharides, and other herbal components have been explored due to their detoxification effects against ethanol. The underlying anti-hangover mechanisms include reducing the intestinal absorption of ethanol or its metabolites, increasing the activity of ethanol metabolizing enzymes, development of fatty acid ß-oxidation in mitochondria, inhibition of inflammatory response, blocking the target receptors of ethanol in the body, and possession of antioxidant activity under the oxidative stress developed by ethanol consumption. Therefore, the development of bioactive food-based therapeutic formula can assist clinicians and also drinkers in the alleviation of alcohol side effects.

The Preventive Mechanisms of Bioactive Food Compounds against Obesity-Induced Inflammation.

Dietary patterns are promising strategies for preventing and treating obesity and its coexisting inflammatory processes. Bioactive food compounds have received considerable attention due to their actions against obesity-induced inflammation, with limited harmful side effects. They are perceived as food ingredients or dietary supplements other than those necessary to meet basic human nutritional needs and are responsible for positive changes in the state of health. These include polyphenols, unsaturated fatty acids, and probiotics. Although the exact mechanisms of bioactive food compounds' action are still poorly understood, studies have indicated that they involve the modulation of the secretion of proinflammatory cytokines, adipokines, and hormones; regulate gene expression in adipose tissue; and modify the signaling pathways responsible for the inflammatory response. Targeting the consumption and/or supplementation of foods with anti-inflammatory potential may represent a new approach to obesity-induced inflammation treatment. Nevertheless, more studies are needed to evaluate strategies for bioactive food compound intake, especially times and doses. Moreover, worldwide education about the advantages of bioactive food compound consumption is warranted to limit the consequences of unhealthy dietary patterns. This work presents a review and synthesis of recent data on the preventive mechanisms of bioactive food compounds in the context of obesity-induced inflammation.

Highlights on the Role of Galectin-3 in Colorectal Cancer and the Preventive/Therapeutic Potential of Food-Derived Inhibitors.

Colorectal cancer (CRC) is a leading cause of death worldwide. Despite advances in surgical and therapeutic management, tumor metastases and resistance to therapy still represent major hurdles. CRC risk is highly modifiable by lifestyle factors, including diet, which strongly influences both cancer incidence and related mortality. Galectin-3 (Gal-3) is a multifaceted protein involved in multiple pathophysiological pathways underlying chronic inflammation and cancer. Its versatility is given by the ability to participate in a wide range of tumor-promoting processes, including cell-cell/cell-matrix interactions, cell growth regulation and apoptosis, and the immunosuppressive tumor microenvironment. This review provides an updated summary of preclinical and observational human studies investigating the pathogenetic role of Gal-3 in intestinal inflammation and CRC, as well as the potential of Gal-3 activity inhibition by plant-source food-derived bioactive compounds to control CRC onset/growth. These studies highlight both direct and immuno-mediated effects of Gal-3 on tumor growth and invasiveness and its potential role as a CRC prognostic biomarker. Substantial evidence indicates natural food-derived Gal-3 inhibitors as promising candidates for CRC prevention and therapy. However, critical issues, such as their bioavailability and efficacy, in controlled human studies need to be addressed to translate research progress into clinical applications.

Identification of bio-active food compounds as potential SARS-CoV-2 PLpro inhibitors-modulators via negative image-based screening and computational simulations.

Despite significant studies on the COVID-19 pandemic, scientists around the world are still battling to find a definitive therapy against the ongoing severe global health crisis. In this study, advanced computational approaches have been employed to identify bioactive food constituents as potential SARS-CoV-2 PLpro inhibitors-modulators. As a validated antiviral drug target, PLpro has gained tremendous attention for therapeutics developments. Therefore, targeting the multifunctional SARS-CoV-2 PLpro protein, ∼1039 bioactive dietary compounds have been screened extensively through novel techniques like negative image-based (NIB) screening and molecular docking approaches. In particular, the three different models of NIB screening have been generated and used to re-score the dietary compounds based on the negative image which is created by reversing the shape and electrostatics features of PLpro protein's ligand-binding cavity. Further, 100 ns molecular dynamics simulation has been performed and MM-GBSA based binding free energies have been estimated for the final proposed four dietary compounds (PC000550, PC000361, PC000558, and PC000573) as potential inhibitors/modulators of SARS-CoV-2 PLpro protein. Employed computational study outcome also has been compared with respect to the earlier experimentally investigated compound GRL0617 against SARS-CoV-2 PLpro protein, which suggests much greater interaction potential in terms of binding affinity and other energetic contributions for the proposed dietary compounds. Hence, the present study suggests that proposed dietary compounds can be suitable chemical entities for modulating the activity of PLpro protein or can be further utilized for optimizing or screening of novel chemical surrogates, however also needs experimental evaluation for entry in clinical studies for better assessment.

Identification of potent food constituents as SARS-CoV-2 papain-like protease modulators through advanced pharmacoinformatics approaches.

The current ongoing pandemic of COVID-19 urges immediate treatment measures for controlling the highly contagious SARS-CoV-2 infections. The papain-like protease (PLpro), which is released from nsp3, is presently being evaluated as a significant anti-viral drug target for COVID-19 therapy development. Particularly, PLpro is implicated in the cleavage of viral polyproteins and antagonizes the host innate immune response through its deubiquitinating and deISGylating actions, thus making it a high-profile antiviral therapeutic target. The present study reports a few specific food compounds that can bind tightly with the SARS-CoV-2 PLpro protein identified through extensive computational screening techniques. Precisely, extensive advanced computational approaches combining target-based virtual screening, particularly employing sub-structure based similarity search, molecular docking, molecular dynamics (MD) simulations, and MM-GBSA based binding free energy calculations have been employed for the identification of the most promising food compounds with substantial functional implications as SARS-CoV-2 PLpro protein inhibitors/modulators. Observations from the present research investigation also provide a deeper understanding of the binding modes of the proposed four food compounds with SARS-CoV-2 PLpro protein. In docking analyses, all compounds have established essential inter-molecular interaction profiles at the active site cavity of the SARS-CoV-2 PLpro protein. Similarly, the long-range 100 ns conventional MD simulation studies also provided an in-depth understanding of probable interactions and dynamic behaviour of the SARS-CoV-2 PLpro protein-food compound complexes. Binding free energies of all molecular systems revealed a strong interaction affinity of food compounds towards the SARS-CoV-2 PLpro protein. Moreover, clear-cut comparative analyses against the known standard inhibitor also suggest that proposed food compounds may act as potential active chemical entities for modulating the action of the SARS-CoV-2 PLpro protein.

An In Vitro Protocol to Study the Modulatory Effects of a Food or Biocompound on Human Gut Microbiome and Metabolome.

The gut microbiota plays a key role in gastrointestinal immune and metabolic functions and is influenced by dietary composition. An in vitro protocol simulating the physiological conditions of the digestive system helps to study the effects of foods/biocompounds on gut microbiome and metabolome. The Dynamic-Colonic Gastrointestinal Digester consists of five interconnected compartments, double jacket vessels that simulate the physiological conditions of the stomach, the small intestine and the three colonic sections, which are the ascending colon, transverse colon and descending colon. Human faeces are required to reproduce the conditions and culture medium of the human colon, allowing the growth of the intestinal microbiota. After a stabilization period of 12 days, a food/biocompound can be introduced to study its modulatory effects during the next 14 days (treatment period). At the end of the stabilization and treatment period, samples taken from the colon compartments are analysed. The 16S rRNA gene analysis reveals the microbiota composition. The untargeted metabolomics analysis gives more than 10,000 features (metabolites/compounds). The present protocol allows in vitro testing of the modulatory effects of foods or biocompounds on gut microbiota composition and metabolic activity.

Direct Contact Ultrasound in Food Processing: Impact on Food Quality.

Consumers' demand for "minimally processed" products that maintain the "fresh-like" characteristics has increased in recent years. Ultrasound (US) is a non-thermal technology that enhances mass and energy transfer processes resulting in improved food quality. A new method of applying US to food without using a liquid or gaseous medium for the propagation of acoustic waves has recently been under research. It is known as direct contact US, since the food is directly placed on a plate where the transducers are located. In this type of systems, the main effect is not cavitation but acoustic vibration, which encourages mass and energy transfer processes due to the "sponge effect." Furthermore, as the product is not immersed in a liquid medium, the loss of hydrophilic nutritional compounds is reduced; systems such as these can thus be more easily implemented on an industrial level. Nevertheless, the very few studies that have been published about these systems mainly focus on dehydration and freezing. This article summarizes published research on the impact of direct contact US in nutritional and organoleptic quality of food in order to assess their potential to meet new market trends.

Updated Prediction of Aggregators and Assay-Interfering Substructures in Food Compounds.

Positive outcomes in biochemical and biological assays of food compounds may appear due to the well-described capacity of some compounds to form colloidal aggregates that adsorb proteins, resulting in their denaturation and loss of function. This phenomenon can lead to wrongly ascribing mechanisms of biological action for these compounds (false positives) as the effect is nonspecific and promiscuous. Similar false positives can show up due to chemical (photo)reactivity, redox cycling, metal chelation, interferences with the assay technology, membrane disruption, etc., which are more frequently observed when the tested molecule has some definite interfering substructures. Although discarding false positives can be achieved experimentally, it would be very useful to have in advance a prognostic value for possible aggregation and/or interference based only in the chemical structure of the compound tested in order to be aware of possible issues, help in prioritization of compounds to test, design of appropriate assays, etc. Previously, we applied cheminformatic tools derived from the drug discovery field to identify putative aggregators and interfering substructures in a database of food compounds, the FooDB, comprising 26,457 molecules at that time. Here, we provide an updated account of that analysis based on a current, much-expanded version of the FooDB, comprising a total of 70,855 compounds. In addition, we also apply a novel machine learning model (SCAM Detective) to predict aggregators with 46-53% increased accuracies over previous models. In this way, we expect to provide the researchers in the mode of action of food compounds with a much improved, robust, and widened set of putative aggregators and interfering substructures of food compounds.

Bioactive Peptides and Hydrolysates from Egg Proteins as a New Tool for Protection Against Cardiovascular Problems.

The aim of the present work is to review the potential beneficial effects of dietary supplementation with bioactive egg protein hydrolysates or peptides on cardiometabolic changes associated with oxidative stress. The development of nutritionally improved food products designed to address specific health concerns is of particular interest because many bioactive food compounds can be potentially useful in various physiological functions such as for reducing oxidative stress. The results presented suggest that egg hydrolysates or derived peptides could be included in the diet to prevent and/or reduce some cardiometabolic complications associated with oxidative stress-related diseases.

Analysis of Nuisance Substructures and Aggregators in a Comprehensive Database of Food Chemical Compounds.

The mechanistic understanding of the biological effects of foods involves the testing of food compounds in biochemical and biological assays. Positive results in these assays can be artifactual due to some properties of the compound: namely chemical reactivity, membrane disruption, redox cycling, etc., or through the formation of colloidal aggregates. Within the drug discovery field, a wide set of so-called "nuisance" filters have been developed to identify substructures prone to assay artifacts and/or promiscuity, e.g., the pan-assay interference compounds (PAINS) and others. In the subarea of natural products, a similar concept is the so-called invalid metabolic panaceas (IMPs). Finally, tools to identify putative aggregators have also been developed. Here, we analyzed the presence of nuisance substructures, IMPs, and aggregators in a large database of food compounds (the FooDB), which should be useful to the researchers working in the field, in order to be aware of possible artifact/promiscuity issues in their assays.

Anti-trichomonad activities of different compounds from foods, marine products, and medicinal plants: a review.

Human trichomoniasis, caused by the pathogenic parasitic protozoan Trichomonas vaginalis, is the most common non-viral sexually transmitted disease that contributes to reproductive morbidity in affected women and possibly to prostate cancer in men. Tritrichomonas foetus strains cause the disease trichomoniasis in farm animals (cattle, bulls, pigs) and diarrhea in domestic animals (cats and dogs). Because some T. vaginalis strains have become resistant to the widely used drug metronidazole, there is a need to develop alternative treatments, based on safe natural products that have the potential to replace and/or enhance the activity of lower doses of metronidazole. To help meet this need, this overview collates and interprets worldwide reported studies on the efficacy of structurally different classes of food, marine, and medicinal plant extracts and some of their bioactive pure compounds against T. vaginalis and T. foetus in vitro and in infected mice and women. Active food extracts include potato peels and their glycoalkaloids α-chaconine and α-solanine, caffeic and chlorogenic acids, and quercetin; the tomato glycoalkaloid α-tomatine; theaflavin-rich black tea extracts and bioactive theaflavins; plant essential oils and their compounds (+)-α-bisabolol and eugenol; the grape skin compound resveratrol; the kidney bean lectin, marine extracts from algae, seaweeds, and fungi and compounds that are derived from fungi; medicinal extracts and about 30 isolated pure compounds. Also covered are the inactivation of drug-resistant T. vaginalis and T. foetus strains by sensitized light; anti-trichomonad effects in mice and women; beneficial effects of probiotics in women; and mechanisms that govern cell death. The summarized findings will hopefully stimulate additional research, including molecular-mechanism-guided inactivations and human clinical studies, that will help ameliorate adverse effects of pathogenic protozoa.

Bioactive food compounds, epigenetics and chronic disease prevention: Focus on early-life interventions with polyphenols.

Consumption of bioactive compounds such as polyphenols, isothiocyanates, sulfur-containing compounds and terpenoids, found in fruits and vegetables, is associated with prevention of chronic disease. These bioactive food compounds elicit their protective effects through complex mechanisms at the cellular and molecular, including epigenetic levels. According to the Developmental Origins of Health and Disease (DOHaD) paradigm, in utero exposure to stressors such as malnutrition through maternal diet would impair fetal development and epigenetically program increased risk of metabolic diseases and some cancers in adult life. In addition, a role for fathers´ diet during preconception on their offspring health and chronic disease susceptibility has also emerged. This highlights early life as a promising window of opportunity for starting dietary interventions focusing on preventing chronic diseases. However, knowledge on the potential beneficial impact of early life exposure to bioactive food compounds is limited. Among the studies that have investigated bioactive food compounds in the context of DOHaD, most have focused on the impact of dietary polyphenols. Thus, in this review we discuss experimental evidence supporting a role for the dietary polyphenols resveratrol, genistein, epigallocatechin-3-gallate and anthocyanins in chronic disease prevention considering a perspective from early-life interventions through maternal and paternal diets and focusing on epigenetics as a potential underlying mechanism.

Induction of Synthetic Lethality by Natural Compounds Targeting Cancer Signaling.

Despite the breakthroughs that have been achieved, significant unmet needs relating to the inadequate efficacy and toxicity of currently-available cancer therapies remain. Kinase inhibitors are a class of agents that target signaling factors responsible for the survival of malignant cells, and may address at least some of these issues. The concept of synthetic lethality provides a potential solution to counteract pathway redundancies, and refers to situations in which a mutation in one of two particular genes alone permits cell survival, while simultaneous mutation in both results in cell death. When exploited in the context of cancer therapy, pathways that are uniquely upregulated in cancer cells become selective targets, with reduced off-target toxicity toward their healthy counterparts. Natural compounds represent a large and readily-accessible library of bioactive structures that can be screened for synthetically lethal interactions by testing for the inhibition of kinases relevant to cancer cell survival. In this review, we discuss the concept of synthetic lethality and focus on scenarios in which natural compounds that target kinases may be applied to tip the balance in favor of cancer cell death during therapeutic challenge.

Low-density lipoprotein oxidation biomarkers in human health and disease and effects of bioactive compounds.

Based on the significance of oxidized low-density lipoprotein (LDL) in health and disease, this review focuses on human studies addressing oxidation of LDL, including three lines of biomarkers, (i) ex vivo LDL resistance to oxidation, a "challenge test" model, (ii) circulating oxidized LDL, indicating the "current in vivo status", and (iii) autoantibodies against oxidized LDL as fingerprints of an immune response to oxidized LDL, along with circulating oxysterols and 4-hydroxynonenal as biomarkers of lipid peroxidation. Lipid peroxidation and oxidized LDL are hallmarks in the development of various metabolic, cardiovascular and other diseases. Changes further occur across life stages from infancy to older age as well as in athletes and smokers. Given their responsiveness to targeted nutritional interventions, markers of LDL oxidation have been employed in a rapidly growing number of human studies for more than 2 decades. There is growing interest in foods, which, besides providing energy and nutrients, exert beneficial effects on human health, such as protection of DNA, proteins and lipids from oxidative damage. Any health claim, however, needs to be substantiated by supportive evidence derived from human studies, using reliable biomarkers to demonstrate such beneficial effects. A large body of evidence has accumulated, demonstrating protection of LDL from oxidation by bioactive food compounds, including vitamins, other micronutrients and secondary plant ingredients, which will facilitate the selection of oxidation biomarkers for future human intervention studies and health claim support.