The Hallmarks of Flavonoids in Cancer

Flavonoids represent an important group of bioactive compounds derived from plant-based foods and beverages with known biological activity in cells. From the modulation of inflammation to the inhibition of cell proliferation, flavonoids have been described as important therapeutic adjuvants against several diseases, including diabetes, arteriosclerosis, neurological disorders, and cancer. Cancer is a complex and multifactor disease that has been studied for years however, its prevention is still one of the best known and efficient factors impacting the epidemiology of the disease. In the molecular and cellular context, some of the mechanisms underlying the oncogenesis and the progression of the disease are understood, known as the hallmarks of cancer. In this text, we review important molecular signaling pathways, including inflammation, immunity, redox metabolism, cell growth, autophagy, apoptosis, and cell cycle, and analyze the known mechanisms of action of flavonoids in cancer. The current literature provides enough evidence supporting that flavonoids may be important adjuvants in cancer therapy, highlighting the importance of healthy and balanced diets to prevent the onset and progression of the disease.     

Polyphenols and Fish Oils for Improving Metabolic Health: A Revision of the Recent Evidence for Their Combined Nutraceutical Effects

Polyphenols and omega-3 polyunsaturated fatty acids from fish oils, i.e., eicosapentaenoic and docosahexaenoic acids, are well-recognized nutraceuticals, and their single antioxidant and anti-inflammatory properties have been demonstrated in several studies found in the literature. It has been reported that the combination of these nutraceuticals can lead to three-fold increases in glutathione peroxidase activity, two-fold increases in plasma antioxidant capacity, decreases of 50–100% in lipid peroxidation, protein carbonylation, and urinary 8-isoprotanes, as well as 50–200% attenuation of common inflammation biomarkers, among other effects, as compared to their individual capacities. Therefore, the adequate combination of those bioactive food compounds and their single properties should offer a powerful tool for the design of successfully nutritional interventions for the prevention and palliation of a plethora of human metabolic diseases, frequently diet-induced, whose etiology and progression are characterized by redox homeostasis disturbances and a low-grade of chronic inflammation. However, the certain mechanisms behind their biological activities, in vivo interaction (both between them and other food compounds), and their optimal doses and consumption are not well-known yet. Therefore, we review here the recent evidence accumulated during the last decade about the cooperative action between polyphenols and fish oils against diet-related metabolic alterations, focusing on the mechanisms and pathways described and the effects reported. The final objective is to provide useful information for strategies for personalized nutrition based on these nutraceuticals.     

Overview of the Polyphenols in Salicornia: From Recovery to Health-Promoting Effect

Nowadays, there has been considerable attention paid toward the recovery of waste plant matrices as possible sources of functional compounds with healthy properties. In this regard, we focus our attention on Salicornia, a halophyte plant that grows abundantly on the coasts of the Mediterranean area. Salicornia is used not only as a seasoned vegetable but also in traditional medicine for its beneficial effects in protecting against diseases such as obesity, diabetes, and cancer. In numerous research studies, Salicornia consumption has been highly suggested due to its high level of bioactive molecules, among which, polyphenols are prevalent. The antioxidant and antiradical activity of polyphenols makes Salicornia a functional food candidate with potential beneficial activities for human health. Therefore, this review provides specific and compiled information for optimizing and developing new extraction processes for the recovery of bioactive compounds from Salicornia; focusing particular attention on polyphenols and their health benefits.     

Small Molecule Soluble Epoxide Hydrolase Inhibitors in Multitarget and Combination Therapies for Inflammation and Cancer

The enzyme soluble epoxide hydrolase (sEH) plays a central role in metabolism of bioactive lipid signaling molecules. The substrate-specific hydrolase activity of sEH converts epoxyeicosatrienoic acids (EETs) to less bioactive dihydroxyeicosatrienoic acids. EETs exhibit anti-inflammatory, analgesic, antihypertensive, cardio-protective and organ-protective properties. Accordingly, sEH inhibition is a promising therapeutic strategy for addressing a variety of diseases. In this review, we describe small molecule architectures that have been commonly deployed as sEH inhibitors with respect to angiogenesis, inflammation and cancer. We juxtapose commonly used synthetic scaffolds and natural products within the paradigm of a multitarget approach for addressing inflammation and inflammation induced carcinogenesis. Structural insights from the inhibitor complexes and novel strategies for development of sEH-based multitarget inhibitors are also presented. While sEH inhibition is likely to suppress inflammation-induced carcinogenesis, it can also lead to enhanced angiogenesis via increased EET concentrations. In this regard, sEH inhibitors in combination chemotherapy are described. Urea and amide-based architectures feature prominently across multitarget inhibition and combination chemotherapy applications of sEH inhibitors.     

Therapeutic Potential of Targeting the HMGB1/RAGE Axis in Inflammatory Diseases

High mobility group box 1 (HMGB1) is a nuclear protein that can interact with a receptor for advanced glycation end-products (RAGE; a multi-ligand immunoglobulin receptor) and mediates the inflammatory pathways that lead to various pathological conditions, such as cancer, diabetes, neurodegenerative disorders, and cardiovascular diseases. Blocking the HMGB1/RAGE axis could be an effective therapeutic approach to treat these inflammatory conditions, which has been successfully employed by various research groups recently. In this article, we critically review the structural insights and functional mechanism of HMGB1 and RAGE to mediate inflammatory processes. More importantly, current perspectives of recent therapeutic approaches utilized to inhibit the communication between HMGB1 and RAGE using small molecules are also summarized along with their clinical progression to treat various inflammatory disorders. Encouraging results are reported by investigators focusing on HMGB1/RAGE signaling leading to the identification of compounds that could be useful in further clinical studies. We highlight the current gaps in our knowledge and future directions for the therapeutic potential of targeting key molecules in HMGB1/RAGE signaling in the pathophysiology of inflammatory diseases.     

Recent Advances in the Antiproliferative and Proapoptotic Activity of Various Plant Extracts and Constituents against Murine Malignant Melanoma

Although conventional medicine, chemical drug synthesis and pharmaceutical research are advancing at a rapid pace, nature remains a major supplier of biological molecules. Natural bioactive compounds are studied closely especially as an alternative to the limitations of conventional therapy in many diseases, melanoma being one of them. Malignant melanoma is a highly aggressive type of cancer, and the current methods of treatment used are cryotherapy, external surgery, radiation therapy, chemotherapy, photodynamic therapy, biological therapy, and targeted drug therapy. Unfortunately, these treatment methods are often inefficient, extremely expensive and cause many side effects, which is why focusing on melanoma chemoprevention and adjuvant therapy with natural herbal phytoconstituents is an emerging strategy to prevent, cure or treat melanoma. This review aims to examine the latest discoveries in terms of potential natural bioactive compounds that possess important activity against the development and spread of murine melanoma cancer. In particular, the use of different phytochemicals such as phenolic acids, flavonoids, anthocyanins, terpenoids, essential oils and carotenoids in vitro and in vivo models will be discussed. These data are helpful in guiding researchers in the direction of studying phytonutrients with important effects in the prevention and treatment of melanoma.     

Inhibition of 2-oxoglutarate dependent oxygenases

2-Oxoglutarate (2OG) dependent oxygenases are ubiquitous iron enzymes that couple substrate oxidation to the conversion of 2OG to succinate and carbon dioxide. In humans their roles include collagen biosynthesis, fatty acid metabolism, DNA repair, RNA and chromatin modifications, and hypoxic sensing. Commercial applications of 2OG oxygenase inhibitors began with plant growth retardants, and now extend to a clinically used pharmaceutical compound for cardioprotection. Several 2OG oxygenases are now being targeted for therapeutic intervention for diseases including anaemia, inflammation and cancer. In this critical review, we describe studies on the inhibition of 2OG oxygenases, focusing on small molecules, and discuss the potential of 2OG oxygenases as therapeutic targets (295 references).     

外泌体生物分析及其临床应用研究进展

外泌体是具有各种关键生物活性分子(如脂质、 蛋白质和核酸)的细胞外囊泡. 它们可以由所有类型的细胞分泌, 并分布在所有生物流体中, 如血液、 唾液、 汗水和尿液等. 更重要的是, 外泌体可以参与多种生理活动, 包括细胞间通讯、 哺乳动物的繁殖和免疫反应, 并在新陈代谢以及心血管疾病、 神经变性和癌症等疾病的病理进展中起重要作用, 这使其成为备受关注的天然非侵入性生物标记物, 并且被认为是可用于临床诊断和治疗的潜在工具。本文综述了用于检测外泌体的生物传感器的最新发展, 包括荧光、 电化学、 电化学发光、 表面增强拉曼光谱、 比色法和微流控技术等分析方法; 总结了在临床诊断和疾病治疗中外泌体的临床应用; 还讨论了外泌体检测所面临的挑战以及外泌体在临床诊断和疾病治疗等方面的应用潜力.     

Flavonoids: A Myth or a Reality for Cancer Therapy?

Nutraceuticals are biologically active molecules present in foods; they can have beneficial effects on health, but they are not available in large enough quantities to perform this function. Plant metabolites, such as polyphenols, are widely diffused in the plant kingdom, where they play fundamental roles in plant development and interactions with the environment. Among these, flavonoids are of particular interest as they have significant effects on human health. In vitro and/or in vivo studies described flavonoids as essential nutrients for preventing several diseases. They display broad and promising bioactivities to fight cancer, inflammation, bacterial infections, as well as to reduce the severity of neurodegenerative and cardiovascular diseases or diabetes. Therefore, it is not surprising that interest in flavonoids has sharply increased in recent years. More than 23,000 scientific publications on flavonoids have described the potential anticancer activity of these natural molecules in the last decade. Studies, in vitro and in vivo, show that flavonoids exhibit anticancer properties, and many epidemiological studies confirm that dietary intake of flavonoids leads to a reduced risk of cancer. This review provides a glimpse of the mechanisms of action of flavonoids on cancer cells.     

Prospects of Curcumin Nanoformulations in Cancer Management

There is increasing interest in the use of natural compounds with beneficial pharmacological effects for managing diseases. Curcumin (CUR) is a phytochemical that is reportedly effective against some cancers through its ability to regulate signaling pathways and protein expression in cancer development and progression. Unfortunately, its use is limited due to its hydrophobicity, low bioavailability, chemical instability, photodegradation, and fast metabolism. Nanoparticles (NPs) are drug delivery systems that can increase the bioavailability of hydrophobic drugs and improve drug targeting to cancer cells via different mechanisms and formulation techniques. In this review, we have discussed various CUR-NPs that have been evaluated for their potential use in treating cancers. Formulations reviewed include lipid, gold, zinc oxide, magnetic, polymeric, and silica NPs, as well as micelles, dendrimers, nanogels, cyclodextrin complexes, and liposomes, with an emphasis on their formulation and characteristics. CUR incorporation into the NPs enhanced its pharmaceutical and therapeutic significance with respect to solubility, absorption, bioavailability, stability, plasma half-life, targeted delivery, and anticancer effect. Our review shows that several CUR-NPs have promising anticancer activity; however, clinical reports on them are limited. We believe that clinical trials must be conducted on CUR-NPs to ensure their effective translation into clinical applications.     

Mechanisms,Anti-Quorum-Sensing Actions,and Clinical Trials of Medicinal Plant Bioactive Compounds against Bacteria: A Comprehensive Review

Bacterial strains have developed an ability to resist antibiotics via numerous mechanisms. Recently, researchers conducted several studies to identify natural bioactive compounds, particularly secondary metabolites of medicinal plants, such as terpenoids, flavonoids, and phenolic acids, as antibacterial agents. These molecules exert several mechanisms of action at different structural, cellular, and molecular levels, which could make them candidates or lead compounds for developing natural antibiotics. Research findings revealed that these bioactive compounds can inhibit the synthesis of DNA and proteins, block oxidative respiration, increase membrane permeability, and decrease membrane integrity. Furthermore, recent investigations showed that some bacterial strains resist these different mechanisms of antibacterial agents. Researchers demonstrated that this resistance to antibiotics is linked to a microbial cell-to-cell communication system called quorum sensing (QS). Consequently, inhibition of QS or quorum quenching is a promising strategy to not only overcome the resistance problems but also to treat infections. In this respect, various bioactive molecules, including terpenoids, flavonoids, and phenolic acids, exhibit numerous anti-QS mechanisms via the inhibition of auto-inducer releases, sequestration of QS-mediated molecules, and deregulation of QS gene expression. However, clinical applications of these molecules have not been fully covered, which limits their use against infectious diseases. Accordingly, the aim of the present work was to discuss the role of the QS system in bacteria and its involvement in virulence and resistance to antibiotics. In addition, the present review summarizes the most recent and relevant literature pertaining to the anti-quorum sensing of secondary metabolites and its relationship to antibacterial activity.     

The Roles and Associated Mechanisms of Adipokines in Development of Metabolic Syndrome

Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered adipose tissue, adipokines, play critical roles in the development of metabolic syndrome. Although the adipokines leptin and adiponectin improve insulin sensitivity, others contribute to the development of glucose intolerance, including visfatin, fetuin-A, resistin, and plasminogen activator inhibitor-1 (PAI-1). Leptin and adiponectin increase fatty acid oxidation, prevent foam cell formation, and improve lipid metabolism, while visfatin, fetuin-A, PAI-1, and resistin have pro-atherogenic properties. In this review, we briefly summarize the role of various adipokines in the development of metabolic syndrome, focusing on glucose homeostasis and lipid metabolism.     

Bioactive Structure of Membrane Lipids and Natural Products Elucidated by a Chemistry‐Based Approach

Determining the bioactive structure of membrane lipids is a new concept, which aims to examine the functions of lipids with respect to their three‐dimensional structures. As lipids are dynamic by nature, their “structure” does not refer solely to a static picture but also to the local and global motions of the lipid molecules. We consider that interactions with lipids, which are completely defined by their structures, are controlled by the chemical, functional, and conformational matching between lipids and between lipid and protein. In this review, we describe recent advances in understanding the bioactive structures of membrane lipids bound to proteins and related molecules, including some of our recent results. By examining recent works on lipid‐raft‐related molecules, lipid–protein interactions, and membrane‐active natural products, we discuss current perspectives on membrane structural biology.     

Phenylethyl Isothiocyanate: A Bioactive Agent for Gastrointestinal Health

The incidence of gastrointestinal pathologies (cancer in particular) has increased progressively, with considerable morbidity and mortality, and a high economic impact on the healthcare system. The dietary intake of natural phytochemicals with certain bioactive properties has shown therapeutic and preventive effects on these pathologies. This includes the cruciferous vegetable derivative phenylethyl isothiocyanate (PEITC), a bioactive compound present in some vegetables, such as watercress. Notably, PEITC has antioxidant, anti-inflammatory, bactericidal, and anticarcinogenic properties. This review summarized the current knowledge on the role of PEITC as a potential natural nutraceutical or an adjuvant against oxidative/inflammatory-related disorders in the gastrointestinal tract. We also discussed the safe and recommended dose of PEITC. In addition, we established a framework to guide the research and development of sustainable methodologies for obtaining and stabilizing this natural molecule for industrial use. With PEITC, there is great potential to develop a viable strategy for preventing cancer and other associated diseases of the gastrointestinal tract. However, this topic still needs more scientific studies to help develop new PEITC products for the nutraceutical, pharmaceutical, or food industries.     

High throughput screening technology and the small molecules modulating aging related signals

Aging and its related diseases are severe issues in modern society. Many efforts have been made to understand the mechanisms of aging and to find the ways to prevent age-related diseases. Identifying the compounds targeting aging-related signals is a challenging work because there are so many proteins and signals involved. Recently, alone with the progresses in high throughput screening (HTS) technology, increasing numbers of small molecules targeting aging-related pathologic processes have been identified. In this review, we introduce the basic workflow, classification and assay strategies of HTS technology, and sort out known small molecules identified via HTS technology by their roles in aging related diseases, such as neural degenerative diseases, diabetes and tumors. Given the fact that application of HTS on aging research is still at an early stage, we also summarize the cellular mechanisms about aging process, paralleled with the compounds which can modulate the functions of proteins important for aging signals. Finally, we briefly discuss some advanced HTS technologies for their potent applications on the discovery of anti-aging compounds. The main purpose of this review is to provide updated and useful information to those who are interested in pharmacology and HTS technology, but not familiar with aging biology, or vice versa.     

Lupin (Lupinus albus L.) Seeds: Balancing the Good and the Bad and Addressing Future Challenges

Lupinus albus L. (lupine) is a legume whose grain/seed has gained increasing interest. Its recognized nutritional properties, namely a high content of protein, dietary fiber and its low fat content, make lupine a suitable alternative not only for animal protein, but also as a substitute for more processed and less balanced flours from a nutritional point of view, used in the preparation of bread, cakes and cookies, among others. In addition, its nutritional and bioactive compounds have potential benefits for human health in the prevention and treatment of some diseases. However, the existence of some anti-nutritional compounds and contaminants reveal some concern, requiring effective methods for their detection and eventual removal. This review intends to address the potential of lupine (L. albus) in food and human health and to balance the pros and cons. Nutritional and anti-nutritional components of L. albus seeds and possible contaminants of lupine seeds are examined. The potential health benefits of lupine (seeds), including energy metabolism, cardiovascular diseases, hypertension, glucose and insulin metabolism, bower function and anticonvulsant action, are discussed based on scientific evidence (both clinical trials and studies performed with animal models).     

Dietary Polyphenols: Extraction,Identification, Bioavailability,and Role for Prevention and Treatment of Colorectal and Prostate Cancers

Fruits, vegetables, and other edible plants in our diet have numerous health benefits, due to the bioactive compounds in these food items, including polyphenols. These plants are a rich and promising source of natural products and phytochemicals that can be used to treat and prevent numerous diseases and prevent the progression of cancer. Dietary polyphenols exhibit chemo-preventive and therapeutic effects against various ailments, including several types of cancer. The current study focuses on polyphenol’s traditional and advanced extraction methods, with supercritical extraction as a novel approach. It also deals with their identification, bioavailability, and role in preventing and treating colorectal and prostate cancers. Additionally, the article covers the literature that deals with the anticancer activities of polyphenols, as well as their potential use as anticancer agents.     

Measurement of lipid flux to advance translational research: evolution of classic methods to the future of precision health

Over the past 70 years, the study of lipid metabolism has led to important discoveries in identifying the underlying mechanisms of chronic diseases. Advances in the use of stable isotopes and mass spectrometry in humans have expanded our knowledge of target molecules that contribute to pathologies and lipid metabolic pathways. These advances have been leveraged within two research paths, leading to the ability (1) to quantitate lipid flux to understand the fundamentals of human physiology and pathology and (2) to perform untargeted analyses of human blood and tissues derived from a single timepoint to identify lipidomic patterns that predict disease. This review describes the physiological and analytical parameters that influence these measurements and how these issues will propel the coming together of the two fields of metabolic tracing and lipidomics. The potential of data science to advance these fields is also discussed. Future developments are needed to increase the precision of lipid measurements in human samples, leading to discoveries in how individuals vary in their production, storage, and use of lipids. New techniques are critical to support clinical strategies to prevent disease and to identify mechanisms by which treatments confer health benefits with the overall goal of reducing the burden of human disease.Subject terms: Metabolomics, Translational research, Machine learning     

Particles and microfluidics merged: perspectives of highly sensitive diagnostic detection

There is a growing need for diagnostic technologies that provide laboratories with solutions that improve quality, enhance laboratory system productivity, and provide accurate detection of a broad range of infectious diseases and cancers. Recent advances in micro- and nanoscience and engineering, in particular in the areas of particles and microfluidic technologies, have advanced the “lab-on-a-chip” concept towards the development of a new generation of point-of-care diagnostic devices that could significantly enhance test sensitivity and speed. In this review, we will discuss many of the recent advances in microfluidics and particle technologies with an eye towards merging these two technologies for application in medical diagnostics. Although the potential diagnostic applications are virtually unlimited, the most important applications are foreseen in the areas of biomarker research, cancer diagnosis, and detection of infectious microorganisms.