Manuka honey's anti-metastatic impact on colon cancer stem-like cells: unveiling its effects on epithelial-mesenchymal transition, angiogenesis and telomere length.

Colorectal cancer often leads to metastasis, with cancer stem cells (CSCs) playing a pivotal role in this process. Two closely linked mechanisms, epithelial-mesenchymal transition and angiogenesis, contribute to metastasis and recent research has also highlighted the impact of telomere replication on this harmful tumor progression. Standard chemotherapy alone can inadvertently promote drug-resistant CSCs, posing a challenge. Combining chemotherapy with other compounds, including natural ones, shows promise in enhancing effectiveness while minimizing side effects. This study investigated the anti-metastatic potential of Manuka honey, both alone and in combination with 5-fluorouracil, using a 3D model of colonospheres enriched with CSC-like cells. In summary, it was observed that the treatment reduced migration ability by downregulating the transcription factors Slug, Snail, and Twist, which are key players in epithelial-mesenchymal transition. Additionally, Manuka honey downregulated pro-angiogenic factors and shortened CSC telomeres by downregulating c-Myc - demonstrating an effective anti-metastatic potential. This study suggests new research opportunities for studying the impact of natural compounds when combined with pharmaceuticals, with the potential to enhance effectiveness and reduce side effects.

Can the phenolic compounds of Manuka honey chemosensitize colon cancer stem cells? A deep insight into the effect on chemoresistance and self-renewal.

Manuka honey, which is rich in pinocembrin, quercetin, naringenin, salicylic, p-coumaric, ferulic, syringic and 3,4-dihydroxybenzoic acids, has been shown to have pleiotropic effects against colon cancer cells. In this study, potential chemosensitizing effects of Manuka honey against 5-Fluorouracil were investigated in colonspheres enriched with cancer stem cells (CSCs), which are responsible for chemoresistance. Results showed that 5-Fluorouracil increased when it was combined with Manuka honey by downregulating the gene expression of both ATP-binding cassette sub-family G member 2, an efflux pump and thymidylate synthase, the main target of 5-Fluorouracil which regulates the ex novo DNA synthesis. Manuka honey was associated with decreased self-renewal ability by CSCs, regulating expression of several genes in Wnt/ß-catenin, Hedgehog and Notch pathways. This preliminary study opens new areas of research into the effects of natural compounds in combination with pharmaceuticals and, potentially, increase efficacy or reduce adverse effects.

The Application of Digital Technologies and Artificial Intelligence in Healthcare: An Overview on Nutrition Assessment.

In the last decade, artificial intelligence (AI) and AI-mediated technologies have undergone rapid evolution in healthcare and medicine, from apps to computer software able to analyze medical images, robotic surgery and advanced data storage system. The main aim of the present commentary is to briefly describe the evolution of AI and its applications in healthcare, particularly in nutrition and clinical biochemistry. Indeed, AI is revealing itself to be an important tool in clinical nutrition by using telematic means to self-monitor various health metrics, including blood glucose levels, body weight, heart rate, fat percentage, blood pressure, activity tracking and calorie intake trackers. In particular, the application of the most common digital technologies used in the field of nutrition as well as the employment of AI in the management of diabetes and obesity, two of the most common nutrition-related pathologies worldwide, will be presented.

Possible role of nutrition in the prevention of inflammatory bowel disease-related colorectal cancer: A focus on human studies.

Patients with inflammatory bowel disease (IBD) are at substantially high risk for colorectal cancer (CRC). IBD-associated CRC accounts for roughly 10% to 15% of the annual mortality in patients with IBD. IBD-related CRC also affects younger patients compared with sporadic CRC, with a 5-y survival rate of 50%. Regardless of medical therapies, the persistent inflammatory state characterizing IBD raises the risk for precancerous changes and CRC, with additional input from several elements, including genetic and environmental risk factors, IBD-associated comorbidities, intestinal barrier dysfunction, and gut microbiota modifications. It is well known that nutritional habits and dietary bioactive compounds can influence IBD-associated inflammation, microbiome abundance and composition, oxidative stress balance, and gut permeability. Additionally, in recent years, results from broad epidemiologic and experimental studies have associated certain foods or nutritional patterns with the risk for colorectal neoplasia. The present study aimed to review the possible role of nutrition in preventing IBD-related CRC, focusing specifically on human studies. It emerges that nutritional interventions based on healthy, nutrient-dense dietary patterns characterized by a high intake of fiber, vegetables, fruit, ω-3 polyunsaturated fatty acids, and a low amount of animal proteins, processed foods, and alcohol, combined with probiotic supplementation have the potential of reducing IBD-activity and preventing the risk of IBD-related CRC through different mechanisms, suggesting that targeted nutritional interventions may represent a novel promising approach for the prevention and management of IBD-associated CRC.

Iron Absorption: Factors, Limitations, and Improvement Methods.

Iron is an essential element for human life since it participates in many functions in the human body, including oxygen transport, immunity, cell division and differentiation, and energy metabolism. Iron homeostasis is mainly controlled by intestinal absorption because iron does not have active excretory mechanisms for humans. Thus, efficient intestinal iron bioavailability is essential to reduce the risk of iron deficiency anemia. There are two forms of iron, heme and nonheme, found in foods. The average daily dietary iron intake is 10 to 15 mg in humans since only 1 to 2 mg is absorbed through the intestinal system. Nutrient-nutrient interactions may play a role in dietary intestinal iron absorption. Dietary inhibitors such as calcium, phytates, polyphenols and enhancers such as ascorbic acid and proteins mainly influence iron bioavailability. Numerous studies have been carried out for years to enhance iron bioavailability and combat iron deficiency. In addition to traditional methods, innovative techniques are being developed day by day to enhance iron bioavailability. This review will provide information about iron bioavailability, factors affecting absorption, iron deficiency, and recent studies on improving iron bioavailability.

Adherence to the Mediterranean-Style Eating Pattern and Macular Degeneration: A Systematic Review of Observational Studies.

Age-related macular degeneration (AMD) is a serious degenerative disease affecting the eyes, and is the main cause of severe vision loss among people >55 years of age in developed countries. Its onset and progression have been associated with several genetic and lifestyle factors, with diet appearing to play a pivotal role in the latter. In particular, dietary eating patterns rich in plant foods have been shown to lower the risk of developing the disease, and to decrease the odds of progressing to more advanced stages in individuals already burdened with early AMD. We systematically reviewed the literature to analyse the relationship between the adherence to a Mediterranean diet, a mainly plant-based dietary pattern, and the onset/progression of AMD. Eight human observational studies were analysed. Despite some differences, they consistently indicate that higher adherence to a Mediterranean eating pattern lowers the odds of developing AMD and decreases the risk of progression to more advanced stages of the disease, establishing the way for preventative measures emphasizing dietary patterns rich in plant-foods.

Organic vs conventional plant-based foods: A review.

Organic farming is characterized by the prohibition of the use of chemical synthetic fertilizers, pesticides, feed additives and genetically modified organisms and by the application of sustainable agricultural technologies based on ecological principles and natural rules. Organic products are believed to be more nutritious and safer foods compared to the conventional alternatives by consumers, with the consequent increase of demand and price of these foodstuffs. However, in academic circles there is much debate on these issues, since there is not a clear scientific evidence of the difference on the environmental impact and on the nutritional quality, safety and health effects between conventional and organic foods. Therefore, this work aims to describe and update the most relevant data on organic foods, by describing the impact of this practice on environment, producers, consumers and society, as well as by comparing the physicochemical, nutritional and phytochemical quality of conventional and organic plant foods.

Bee Products: An Emblematic Example of Underutilized Sources of Bioactive Compounds.

Beside honey, honeybees (Apis mellifera L.) are able to produce many byproducts, including bee pollen, propolis, bee bread, royal jelly, and beeswax. Even if the medicinal properties of these byproducts have been recognized for thousands of years by the ancient civilizations, in the modern era, they have a limited use, essentially as nutritional supplements or health products. However, these natural products are excellent sources of bioactive compounds, macro- and micronutrients, that, in a synergistic way, confer multiple biological activities to these byproducts, such as, for example, antimicrobial, antioxidant, and anti-inflammatory properties. This work aims to update the chemical and phytochemical composition of bee pollen, propolis, bee bread, royal jelly, and beeswax and to summarize the main effects exerted by these byproducts on human health, from the anticancer and immune-modulatory activities to the antidiabetic, hypolipidemic, hypotensive, and anti-allergic properties.

Influence of the extraction method on the recovery of bioactive phenolic compounds from food industry by-products.

Agro-foodindustries generate colossal amounts of non-edible waste and by-products, easily accessible as raw materials for up-cycling active phytochemicals. Phenolic compounds are particularly relevant in this field given their abundance in plant residues and the market interest of their functionalities (e.g. natural antioxidant activity) as part of nutraceutical, cosmetological and biomedical formulations. In "bench-to-bedside" achievements, sample extraction is essential because valorization benefits from matrix desorption and solubilization of targeted phytocompounds. Specifically, the composition and polarity of the extractant, the optimal sample particle size and sample:solvent ratio, as well as pH, pressure and temperature are strategic for the release and stability of mobilized species. On the other hand, current green chemistry environmental rules require extraction approaches that eliminate polluting consumables and reduce energy needs. Thus, the following pages provide an update on advanced technologies for the sustainable and efficient recovery of phenolics from plant matrices.

Manuka honey in combination with 5-Fluorouracil decreases physical parameters of colonspheres enriched with cancer stem-like cells and reduces their resistance to apoptosis.

The aim of the present work was to evaluate the in vitro effect of Manuka honey and its combination with 5-Fu, the most common drug used in the treatment of colon cancer, on the morphological and physical parameters of colonspheres enriched with cancer stem-like cells deriving from HCT-116 colon adenocarcinoma cell line and on the apoptosis rate. Manuka honey, alone and more in combination with 5-Fu, reduced the weight, the diameter and mass density of the spheroids and induced apoptosis through the downregulation of many apoptosis inhibitors, including IAPs (Livin, Survivin, XIAP), IGFs (IGF-I, IGF-II and IGF-IR) and HSPs (HSP-27, HSP-60 and HSP-70). These results led to a reduction in the survival ability of cancer stem-like cells, as well as to a chemosensitizing effect of honey towards 5-Fu, considering that apoptosis resistance is one of the main causes of cancer stem-like cells chemoresistance.

The reciprocal interaction between polyphenols and other dietary compounds: Impact on bioavailability, antioxidant capacity and other physico-chemical and nutritional parameters.

Polyphenols are plant secondary metabolites, whose biological activity has been widely demonstrated. However, the research in this field is a bit reductive, as very frequently the effect of individual compound is investigated in different experimental models, neglecting more complex, but common, relationships that are established in the diet. This review summarizes the data that highlighted the interaction between polyphenols and other food components, especially macro- (lipids, proteins, carbohydrates and fibers) and micronutrients (minerals, vitamins and organic pigments), paying particular attention on their bioavailability, antioxidant capacity and chemical, physical, organoleptic and nutritional characteristics. The topic of food interaction has yet to be extensively studied because a greater knowledge of the food chemistry behind these interactions and the variables that modify their effects, could offer innovations and improvements in various fields ranging from organoleptic, nutritional to health and economic field.

Strawberry (Fragaria × ananassa cv. Romina) methanolic extract attenuates Alzheimer's beta amyloid production and oxidative stress by SKN-1/NRF and DAF-16/FOXO mediated mechanisms in C. elegans.

Bioactive compounds from strawberries have been associated with multiple healthy benefits. The present study aimed to assess chemical characterization of a methanolic extract of the Romina strawberry variety in terms of antioxidant capacity, polyphenols profile and chemical elements content. Additionally, potential toxicity, the effect on amyloid-ß production and oxidative stress of the extract was in vivo evaluated in the experimental model Caenorhabditis elegans. Results revealed an important content in phenolic compounds (mainly ellagic acid and pelargonidin-3-glucoside) and minerals (K, Mg, P and Ca). The treatment with 100, 500 or 1000 µg/mL of strawberry extract did not show toxicity. On the contrary, the extract was able to delay amyloid ß-protein induced paralysis, reduced amyloid-ß aggregation and prevented oxidative stress. The potential molecular mechanisms present behind the observed results explored by RNAi technology revealed that DAF-16/FOXO and SKN-1/NRF2 signaling pathways were, at least partially, involved.

Strawberry tree honey in combination with 5-fluorouracil enhances chemosensitivity in human colon adenocarcinoma cells.

Colorectal cancer remains a challenging health burden worldwide. This study aimed to assess the potentiality of Strawberry tree honey (STH), a polyphenol-enriched food, to increase the effectiveness of 5-Fluorouracil (5-FU) in adenocarcinoma (HCT-116) and metastatic (LoVo) colon cancer cell lines. The combined treatment reduced cell viability and caused oxidative stress, by increasing oxidative biomarkers and decreasing antioxidant defence, in a more potent way compared to 5-FU alone. The expression of endoplasmic reticulum (ATF-6, XBP-1) and MAPK (p-p38 MAPK, p-ERK1/2) markers were also elevated after the combined treatment, enhancing the cell cycle arrest through the modulation of regulatory genes (i.e., cyclins and CDKs). Apoptotic gene (i.e., caspases) expressions were also increased after the combined treatment, while those of proliferation (i.e., EGFR), cell migration, invasion (i.e., matrix metallopeptidase) and epithelial-mesenchymal transition (N-cadherin, ß-catenin) were suppressed. Finally, the combined treatment led cell metabolism towards a quiescent stage, by reducing mitochondrial respiration and glycolysis. In conclusion, this work represents an initial step to highlight the possibility to use STH in combination with 5-FU in the treatment of colon cancer, even if further in vitro an in vivo studies are strongly needed to confirm the possible chemo-sensitizing effects of STH.

The Neuroprotective Effect of L-Carnitine against Glyceraldehyde-Induced Metabolic Impairment: Possible Implications in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive regression and memory loss. Dysfunctions of both glucose metabolism and mitochondrial dynamics have been recognized as the main upstream events of the degenerative processes leading to AD. It has been recently found that correcting cell metabolism by providing alternative substrates can prevent neuronal injury by retaining mitochondrial function and reducing AD marker levels. Here, we induced an AD-like phenotype by using the glycolysis inhibitor glyceraldehyde (GA) and explored whether L-carnitine (4-N-trimethylamino-3-hydroxybutyric acid, LC) could mitigate neuronal damage, both in SH-SY5Y neuroblastoma cells and in rat primary cortical neurons. We have already reported that GA significantly modified AD marker levels; here we demonstrated that GA dramatically compromised cellular bioenergetic status, as revealed by glycolysis and oxygen consumption rate (OCR) evaluation. We found that LC ameliorated cell survival, improved OCR and ATP synthesis, prevented the loss of the mitochondrial membrane potential (Δψm) and reduced the formation of reactive oxygen species (ROS). Of note, the beneficial effect of LC did not rely on the glycolytic pathway rescue. Finally, we noticed that LC significantly reduced the increase in pTau levels induced by GA. Overall, these findings suggest that the use of LC can promote cell survival in the setting of the metabolic impairments commonly observed in AD. Our data suggest that LC may act by maintaining mitochondrial function and by reducing the pTau level.

The Molecular Basis of Different Approaches for the Study of Cancer Stem Cells and the Advantages and Disadvantages of a Three-Dimensional Culture.

Cancer stem cells (CSCs) are a rare tumor subpopulation with high differentiation, proliferative and tumorigenic potential compared to the remaining tumor population. CSCs were first discovered by Bonnet and Dick in 1997 in acute myeloid leukemia. The identification and isolation of these cells in this pioneering study were carried out through the flow cytometry, exploiting the presence of specific cell surface molecular markers (CD34+/CD38-). In the following years, different strategies and projects have been developed for the study of CSCs, which are basically divided into surface markers assays and functional assays; some of these techniques also allow working with a cellular model that better mimics the tumor architecture. The purpose of this mini review is to summarize and briefly describe all the current methods used for the identification, isolation and enrichment of CSCs, describing, where possible, the molecular basis, the advantages and disadvantages of each technique with a particular focus on those that offer a three-dimensional culture.

Nutritional Value and Preventive Role of Nigella sativa L. and Its Main Component Thymoquinone in Cancer: An Evidenced-Based Review of Preclinical and Clinical Studies.

In recent times, scientific attention has been paid to different foods and their bioactive components for the ability to inhibit the onset and progress of different types of cancer. Nigella sativa extract, powder and seed oil and its main components, thymoquinone and α-hederin, have showed potent anticancer and chemosensitizing effects against various types of cancer, such as liver, colon, breast, renal, cervical, lung, ovarian, pancreatic, prostate and skin tumors, through the modulation of various molecular signaling pathways. Herein, the purpose of this review was to highlight the anticancer activity of Nigella sativa and it constitutes, focusing on different in vitro, in vivo and clinical studies and projects, in order to underline their antiproliferative, proapoptotic, cytotoxic and antimetastatic effects. Particular attention has been also given to the synergistic effect of Nigella sativa and it constitutes with chemotherapeutic drugs, and to the synthesized analogs of thymoquinone that seem to enhance the chemo-sensitizing potential. This review could be a useful step towards new research on N. sativa and cancer, to include this plant in the dietary treatments in support to conventional therapies, for the best achievement of therapeutic goals.

Immunoinflammatory effects of dietary bioactive compounds.

Inflammation is a key mechanism of the immune system that can be elicited by several factors, among them several chemical, physical and biological agents. Once stimulated, the inflammatory response activates a series of signaling pathways and a number of immune cells which promote, in a very coordinated manner, the neutralization of the infectious agent. However, if uncontrolled, the inflammatory status may become chronic leading, potentially, to tissue damage and disease onset. Several risk factors are associated with the development of chronic inflammation and, among these factors, diet plays an essential role. In this chapter the effects of some dietary bioactive compounds, including micronutrients, omega-3 fatty acids, nucleotides and polyphenols, on the immunoinflammatory responses in different cellular, animal and human studies have been summarized.

Nutrition and Rheumatoid Arthritis in the 'Omics' Era.

Modern high-throughput 'omics' science tools (including genomics, transcriptomics, proteomics, metabolomics and microbiomics) are currently being applied to nutritional sciences to unravel the fundamental processes of health effects ascribed to particular nutrients in humans and to contribute to more precise nutritional advice. Diet and food components are key environmental factors that interact with the genome, transcriptome, proteome, metabolome and the microbiota, and this life-long interplay defines health and diseases state of the individual. Rheumatoid arthritis (RA) is a chronic autoimmune disease featured by a systemic immune-inflammatory response, in genetically susceptible individuals exposed to environmental triggers, including diet. In recent years increasing evidences suggested that nutritional factors and gut microbiome have a central role in RA risk and progression. The aim of this review is to summarize the main and most recent applications of 'omics' technologies in human nutrition and in RA research, examining the possible influences of some nutrients and nutritional patterns on RA pathogenesis, following a nutrigenomics approach. The opportunities and challenges of novel 'omics technologies' in the exploration of new avenues in RA and nutritional research to prevent and manage RA will be also discussed.

Rosa x hybrida extracts with dual actions: Antiproliferative effects against tumour cells and inhibitor of Alzheimer disease.

Edible flowers are being used as a new ingredient in modern gastronomy. Recently, these products have also gained interest as an important source of phenolic compounds with potential for biomedical applications. The present work studied a methanolic extract of Rosa x hybrida in which 35 individual phenolic compounds were identified. The extract has been evaluated for its antiproliferative properties in ovarian carcinoma cells. Results showed that the antiproliferative effect was associated with the induction of autophagy and apoptosis with the concomitant ROS increase probably related to mitochondria dysfunction. These antiproliferative effects might be associated with some components of the extract such as quercetin. The extract did not induce damage in healthy cells and that it was able to improve the wound healing activity. The present study also evaluated the properties of the mentioned extract in vivo in C. elegans. Tests demonstrated a lack of toxicity in the worm model. Promising results have been obtained in transgenic strains of C. elegans that produce human beta amyloid peptide, suggesting the possible utility of the extract from the point of view of Alzheimer disease. Altogether, results suggest that Rosa x hybrida extracts could be a new tool for the development of functional foods.