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      Current Perspectives on the Beneficial Effects of Soybean Isoflavones and Their Metabolites for Humans

      review-article
      Antioxidants
      MDPI
      soybean-derived isoflavones, physiological effect, gene regulation, health benefit mechanism

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          Abstract

          Soybeans are rich in proteins and lipids and have become a staple part of the human diet. Besides their nutritional excellence, they have also been shown to contain various functional components, including isoflavones, and have consequently received increasing attention as a functional food item. Isoflavones are structurally similar to 17-β-estradiol and bind to estrogen receptors (ERα and ERβ). The estrogenic activity of isoflavones ranges from a hundredth to a thousandth of that of estrogen itself. Isoflavones play a role in regulating the effects of estrogen in the human body, depending on the situation. Thus, when estrogen is insufficient, isoflavones perform the functions of estrogen, and when estrogen is excessive, isoflavones block the estrogen receptors to which estrogen binds, thus acting as an estrogen antagonist. In particular, estrogen antagonistic activity is important in the breast, endometrium, and prostate, and such antagonistic activity suppresses cancer occurrence. Genistein, an isoflavone, has cancer-suppressing effects on estrogen receptor-positive (ER+) cancers, including breast cancer. It suppresses the function of enzymes such as tyrosine protein kinase, mitogen-activated kinase, and DNA polymerase II, thus inhibiting cell proliferation and inducing apoptosis. Genistein is the most biologically active and potent isoflavone candidate for cancer prevention. Furthermore, among the various physiological functions of isoflavones, they are best known for their antioxidant activities. S-Equol, a metabolite of genistein and daidzein, has strong antioxidative effects; however, the ability to metabolize daidzein into S-equol varies based on racial and individual differences. The antioxidant activity of isoflavones may be effective in preventing dementia by inhibiting the phosphorylation of Alzheimer’s-related tau proteins. Genistein also reduces allergic responses by limiting the expression of mast cell IgE receptors, which are involved in allergic responses. In addition, they have been known to prevent and treat various diseases, including cardiovascular diseases, metabolic syndromes, osteoporosis, diabetes, brain-related diseases, high blood pressure, hyperlipidemia, obesity, and inflammation. Further, it also has positive effects on menstrual irregularity in non-menopausal women and relieving menopausal symptoms in middle-aged women. Recently, soybean consumption has shown steep increasing trend in Western countries where the intake was previously only 1/20–1/50 of that in Asian countries. In this review, Ihave dealt with the latest research trends that have shown substantial interest in the biological efficacy of isoflavones in humans and plants, and their related mechanisms.

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          Flavonoids: an overview

          Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. These natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients so called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD. Information on the working mechanisms of flavonoids is still not understood properly. However, it has widely been known for centuries that derivatives of plant origin possess a broad spectrum of biological activity. Current trends of research and development activities on flavonoids relate to isolation, identification, characterisation and functions of flavonoids and finally their applications on health benefits. Molecular docking and knowledge of bioinformatics are also being used to predict potential applications and manufacturing by industry. In the present review, attempts have been made to discuss the current trends of research and development on flavonoids, working mechanisms of flavonoids, flavonoid functions and applications, prediction of flavonoids as potential drugs in preventing chronic diseases and future research directions.
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            The Epidemiology of Obesity: A Big Picture.

            The epidemic of overweight and obesity presents a major challenge to chronic disease prevention and health across the life course around the world. Fueled by economic growth, industrialization, mechanized transport, urbanization, an increasingly sedentary lifestyle, and a nutritional transition to processed foods and high-calorie diets over the last 30 years, many countries have witnessed the prevalence of obesity in its citizens double and even quadruple. A rising prevalence of childhood obesity, in particular, forebodes a staggering burden of disease in individuals and healthcare systems in the decades to come. A complex, multifactorial disease, with genetic, behavioral, socioeconomic, and environmental origins, obesity raises the risk of debilitating morbidity and mortality. Relying primarily on epidemiologic evidence published within the last decade, this non-exhaustive review discusses the extent of the obesity epidemic, its risk factors-known and novel-, sequelae, and economic impact across the globe.
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              Targeting cancer stem cell pathways for cancer therapy

              Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Antioxidants (Basel)
                Antioxidants (Basel)
                antioxidants
                Antioxidants
                MDPI
                2076-3921
                30 June 2021
                July 2021
                : 10
                : 7
                : 1064
                Affiliations
                Advanced Bio-Resource Research Center, Kyungpook National University, Daegu 41566, Korea; 92kis@ 123456hanmail.net
                Author information
                https://orcid.org/0000-0003-2579-2027
                Article
                antioxidants-10-01064
                10.3390/antiox10071064
                8301030
                34209224
                ad843b37-c571-4b2c-8206-aa0c5685f95b
                © 2021 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 10 June 2021
                : 28 June 2021
                Categories
                Review

                soybean-derived isoflavones,physiological effect,gene regulation,health benefit mechanism

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