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Cells Oct 2023Estrogens have been implicated in the pathogenesis of various cancers, with increasing concern regarding the overall rising incidence of disease and exposure to... (Review)
Review
Estrogens have been implicated in the pathogenesis of various cancers, with increasing concern regarding the overall rising incidence of disease and exposure to environmental estrogens. Estrogens, both endogenous and environmental, manifest their actions through intracellular and plasma membrane receptors, named ERα, ERβ, and GPER. Collectively, they act to promote a broad transcriptional response that is mediated through multiple regulatory enhancers, including estrogen response elements (EREs), serum response elements (SREs), and cyclic AMP response elements (CREs). Yet, the design and rational assignment of antiestrogen therapy for breast cancer has strictly relied upon an endogenous estrogen-ER binary rubric that does not account for environmental estrogens or GPER. New endocrine therapies have focused on the development of drugs that degrade ER via ER complex destabilization or direct enzymatic ubiquitination. However, these new approaches do not broadly treat all cancer-involved receptors, including GPER. The latter is concerning since GPER is directly associated with tumor size, distant metastases, cancer stem cell activity, and endocrine resistance, indicating the importance of targeting this receptor to achieve a more complete therapeutic response. This review focuses on the critical importance and value of GPER-targeted therapeutics as part of a more holistic approach to the treatment of estrogen-driven malignancies.
Topics: Humans; Female; Receptors, Estrogen; Estrogens; Receptors, G-Protein-Coupled; Breast Neoplasms; GTP-Binding Proteins
PubMed: 37887304
DOI: 10.3390/cells12202460 -
The Veterinary Clinics of North... Sep 2023Infertility in the dog is a common reason for presentation of stud dogs for assessment with veterinarians. This article aims to discuss and outline some of the tests... (Review)
Review
Infertility in the dog is a common reason for presentation of stud dogs for assessment with veterinarians. This article aims to discuss and outline some of the tests that can be done to try to ascertain the underlying cause of abnormalities found in a semen assessment. Topics discussed are semen alkaline phosphatase measurement, retrograde ejaculation assessment, ultrasound of the male reproductive tract, semen culture, human chorionic gonadotropin response testing, dietary assessment for phytoestrogens, environmental impacts on spermatogenesis, testicular biopsy, supplements to improve semen quality and quantity, and when to expect an improvement in semen quality after starting treatment.
Topics: Dogs; Male; Humans; Animals; Semen Analysis; Infertility, Male; Semen; Spermatogenesis; Chorionic Gonadotropin; Dog Diseases
PubMed: 37221101
DOI: 10.1016/j.cvsm.2023.04.006 -
Molecules (Basel, Switzerland) Nov 2023Genistein is a natural compound belonging to flavonoids, having antioxidant, anti-inflammatory, and anti-neoplastic properties. Genistein is considered a phytoestrogen.... (Review)
Review
Genistein is a natural compound belonging to flavonoids, having antioxidant, anti-inflammatory, and anti-neoplastic properties. Genistein is considered a phytoestrogen. As such, genistein can bind estrogen receptors (ERα and ERβ), although with a lower affinity than that of estradiol. Despite considerable work, the effects of genistein are not well established yet. This review aims to clarify the role of genistein on female and male reproductive functions in mammals. In females, at a high dose, genistein diminishes the ovarian activity regulating several pathway molecules, such as topoisomerase isoform I and II, protein tyrosine kinases (v-src, Mek-4, ABL, PKC, Syk, EGFR, FGFR), ABC, CFTR, Glut1, Glut4, 5α-reductase, PPAR-γ, mitogen-activated protein kinase A, protein histidine kinase, and recently circulating RNA-miRNA. The effect of genistein on pregnancy is still controversial. In males, genistein exerts an estrogenic effect by inducing testosterone biosynthesis. The interaction of genistein with both natural and synthetic endocrine disruptors has a negative effect on testis function. The positive effect of genistein on sperm quality is still in debate. In conclusion, genistein has a potentially beneficial effect on the mechanisms regulating the reproduction of females and males. However, this is dependent on the dose, the species, the route, and the time of administration.
Topics: Pregnancy; Animals; Male; Female; Genistein; Semen; Phytoestrogens; Receptors, Estrogen; Estrogen Receptor alpha; Reproduction; Mammals
PubMed: 37959856
DOI: 10.3390/molecules28217436 -
Phytomedicine : International Journal... Feb 2024Non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), carries a high risk of cirrhosis and hepatocellular carcinoma....
BACKGROUND
Non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), carries a high risk of cirrhosis and hepatocellular carcinoma. With the increasing incidence of NASH, the accompanying medical burden is also increasing rapidly, so the development of safe and reliable drugs is urgent. Formononetin (FMNT) has a variety of pharmacological effects such as antioxidant and anti-inflammation, and plays a major role in regulating lipid metabolism, reducing hepatic steatosis and so on, but the mechanism for alleviating NASH is unclear.
MATERIALS AND METHODS
We firstly established a mouse model on NASH through methionine-choline deficient (MCD) diet to investigate the improvement of FMNT as well as the effects of fatty acid β oxidation and SIRT1/PGC-1α/PPARα pathway. Then, we explored the mechanisms of FMNT regulation in SIRT1/PGC-1α/PPARα pathway and fatty acid β oxidation based on genes silencing of SIRT1 and PGC1A. In addition, SIRT1 agonist (SRT1720) and inhibitor (EX527) were used to verify the mechanism of FMNT on improvement of NASH.
RESULTS
Our study found that after FMNT intervention, activities of ALT and AST and TG level were improved, and liver function and hepatocellular steatosis on NASH mice were significantly improved. The detection of β oxidation related indicators showed that FMNT intervention up-regulated FAO capacity, level of carnitine, and the levels of ACADM and CPT1A. The detection of factors related to the SIRT1/PGC-1α/PPARα pathway showed that FMNT activated and promoted the expression of SIRT1/PGC-1α/PPARα pathway, including up-regulating the expression level of SIRT1, improving the activity of SIRT1, promoting the deacetylation of PGC-1α, and promoting the transcriptional activity of PPARα. Furthermore, after genes silencing of SIRT1 and PGC1A, we found that FMNT intervention could not alleviate NASH, including improvement of hepatocellular steatosis, enhancement of β oxidation, and regulation of SIRT1/PGC-1α/PPARα pathway. Afterwards, we used SRT1720 as a positive control, and the results indicated that FMNT and SRT1720 intervention had no significant difference on improving hepatocellular steatosis and promoting fatty acid β oxidation. Besides, we found that when EX527 intervention inhibited expression of SIRT1, the improvement of FMNT on NASH was weakened or even disappeared.
CONCLUSION
In summary, our results demonstrated that FMNT intervention activated SIRT1/PGC-1α/PPARα pathway to promote fatty acid β oxidation and regulate lipid metabolism in liver, ultimately improved hepatocellular steatosis on NASH mice.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; PPAR alpha; Sirtuin 1; Liver; Liver Neoplasms; Fatty Acids; Mice, Inbred C57BL; Isoflavones
PubMed: 38185065
DOI: 10.1016/j.phymed.2023.155285 -
Clinical Therapeutics Aug 2023Hyperlipoproteinemia (a) is a prevalent complication in dialysis patients, with no valid treatment strategy. The aim of this narrative review was to investigate the... (Review)
Review
PURPOSE
Hyperlipoproteinemia (a) is a prevalent complication in dialysis patients, with no valid treatment strategy. The aim of this narrative review was to investigate the clinical significance of hyperlipoproteinemia (a) and phytoestrogen therapy in dialysis patients.
METHODS
A comprehensive literature search of the published data was performed regarding the effects of phytoestrogen therapy on hyperlipoproteinemia (a) in dialysis patients.
FINDINGS
Hyperlipoproteinemia (a) occurs in dialysis patients due to decreased catabolism and increased synthesis of lipoprotein (a) [Lp(a)]. A few clinical trials have studied the effects of phytoestrogens on serum Lp(a). All studies of dialysis patients or nonuremic individuals with hyperlipoproteinemia (a), except one, showed that phytoestrogens could significantly reduce serum Lp(a) levels. However, all investigations of phytoestrogen therapy in individuals with normal serum Lp(a) levels showed that it had no effect on serum Lp(a). Phytoestrogens seem to have effects similar to those of estrogen in lowering Lp(a) concentrations.
IMPLICATIONS
Considering the high prevalence of hyperlipoproteinemia (a) in dialysis patients, phytoestrogen therapy is a reasonable approach for reducing serum Lp(a) levels and its complications in these patients.
Topics: Humans; Phytoestrogens; Renal Dialysis; Lipoprotein(a); Hyperlipoproteinemias
PubMed: 37442657
DOI: 10.1016/j.clinthera.2023.06.017 -
Nutrition (Burbank, Los Angeles County,... Mar 2024The skin protects humans from pathogens, ultraviolet light, chemicals, mechanical, thermal, and physical injuries as well as hazardous substances. Other important roles... (Review)
Review
The skin protects humans from pathogens, ultraviolet light, chemicals, mechanical, thermal, and physical injuries as well as hazardous substances. Other important roles of the skin include the regulation of several important physiological processes of the body, sensing stimuli, synthesis of vitamin D, and immune surveillance. However, aging, diseases and environmental conditions significantly change the skin's behavior and functioning. The treatment and prevention strategies for various skin diseases especially photoaging usually include topical treatment with medical cosmetology, active ingredients and other physical means of photoprotection. In recent times, however, there is an increasing consciousness about the role of diet and nutrition in skin health with certain dietary components emerging as an adequate alternative approach to alleviate and prevent both endogenous and exogenous aging symptoms. Therefore, this narrative review uniquely discusses the basic structure of the skin and also addresses common dermatological signs of damaged skin, the impacts of unhealthy diet habits on the skin, and the beneficial effects of some healthy diet habits on skin health. The information and data were collated from various literature databases and resources such as Science Direct, PubMed, Wiley, Springer, Taylor and Francis, Inflibnet, Scopus, Google, and Google Scholar using relevant keywords Medical Subject Headings (MeSH). In conclusion, diet and nutrition play essential roles in the optimum functioning of the human body, including the skin. Thus, certain diet habits such as less water intake, high-fat diet, refined sugar, and certain food additives are unhealthy and harmful to the skin while alternative healthy diet habits such as adequate water intake; consumption of antioxidants and polyphenolic-rich fruits, vegetables, nuts, and legumes; a low glycemic index diet; probiotics; and phytoestrogens should be adopted to enhance skin health.
Topics: Humans; Diet; Nutritional Status; Vegetables; Fruit; Feeding Behavior
PubMed: 38232577
DOI: 10.1016/j.nut.2023.112350 -
International Journal of Molecular... Aug 2023Phytoestrogens are plant-derived bioactive compounds with estrogen-like properties. Their potential health benefits, especially in cancer prevention and treatment, have... (Review)
Review
Phytoestrogens are plant-derived bioactive compounds with estrogen-like properties. Their potential health benefits, especially in cancer prevention and treatment, have been a subject of considerable research in the past decade. Phytoestrogens exert their effects, at least in part, through interactions with estrogen receptors (ERs), mimicking or inhibiting the actions of natural estrogens. Recently, there has been growing interest in exploring the impact of phytoestrogens on osteosarcoma (OS), a type of bone malignancy that primarily affects children and young adults and is currently presenting limited treatment options. Considering the critical role of the estrogen/ERs axis in bone development and growth, the modulation of ERs has emerged as a highly promising approach in the treatment of OS. This review provides an extensive overview of current literature on the effects of phytoestrogens on human OS models. It delves into the multiple mechanisms through which these molecules regulate the cell cycle, apoptosis, and key pathways implicated in the growth and progression of OS, including ER signaling. Moreover, potential interactions between phytoestrogens and conventional chemotherapy agents commonly used in OS treatment will be examined. Understanding the impact of these compounds in OS holds great promise for developing novel therapeutic approaches that can augment current OS treatment modalities.
Topics: Child; Young Adult; Humans; Phytoestrogens; Osteosarcoma; Apoptosis; Estrogens; Bone Neoplasms
PubMed: 37686148
DOI: 10.3390/ijms241713344 -
Annali Di Igiene : Medicina Preventiva... 2023Aging is a complex and gradual biological process that represents the major risk factor with respect to the development of chronic degenerative diseases, often...
BACKGROUND
Aging is a complex and gradual biological process that represents the major risk factor with respect to the development of chronic degenerative diseases, often associated with disability. Diet and nu-trition, coupled with proper physical activity have a significant impact on the health status of the elderly with a decreased risk of disease being indicative of successful aging. Musculoskeletal conditions such as osteoporosis and sarcopenia are the most frequently reported disorders among the elderly community.
METHODS
This study presents a systematic review of the literature on the potential benefits of several nutra-ceuticals in promoting healthy aging and in reducing the risk of chronic diseases in elderly individuals.
RESULTS
Dietary components including vitamins (vitamin C, B vitamin and vitamin K) flavonoids (e.g., quercetin, anthocyanins, and isoflavones), minerals (e.g., magnesium, zinc and potassium) and other nutrients such phytoestrogens, amino acids, and omega-3 fatty acids help in slowing the aging process, which ultimately results in increased lifespan and longevity.
CONCLUSIONS
This paper highlights the key nutrients and phytochemicals of nutraceutical importance for the healthy aging of the elderly population. Although the scientific literature provides evidences of therapeutic effectiveness of nutraceuticals, more in-depth clinical investigations are needed.
Topics: Aged; Humans; Healthy Aging; Anthocyanins; Dietary Supplements; Vitamins; Diet; Vitamin K
PubMed: 36515582
DOI: 10.7416/ai.2022.2552 -
European Journal of Immunology Nov 2023Multiple sclerosis (MS) is a chronic and progressive autoimmune disease of the central nervous system (CNS), with both genetic and environmental factors contributing to... (Review)
Review
Multiple sclerosis (MS) is a chronic and progressive autoimmune disease of the central nervous system (CNS), with both genetic and environmental factors contributing to the pathobiology of the disease. Although HLA genes have emerged as the strongest genetic factor linked to MS, consensus on the environmental risk factors is lacking. Recently, the gut microbiota has garnered increasing attention as a potential environmental factor in MS, as mounting evidence suggests that individuals with MS exhibit microbial dysbiosis (changes in the gut microbiome). Thus, there has been a strong emphasis on understanding the role of the gut microbiome in the pathobiology of MS, specifically, factors regulating the gut microbiota and the mechanism(s) through which gut microbes may contribute to MS. Among all factors, diet has emerged to have the strongest influence on the composition and function of gut microbiota. As MS patients lack gut bacteria capable of metabolizing dietary phytoestrogen, we will specifically discuss the role of a phytoestrogen diet and phytoestrogen metabolizing gut bacteria in the pathobiology of MS. A better understanding of these mechanisms will help to harness the enormous potential of the gut microbiota as potential therapeutics to treat MS and other autoimmune diseases.
Topics: Humans; Multiple Sclerosis; Phytoestrogens; Microbiota; Autoimmune Diseases; Bacteria; Diet; Dysbiosis
PubMed: 37673213
DOI: 10.1002/eji.202250236 -
The Journal of Nutritional Biochemistry Aug 2023The human gut is a host for trillions of microorganisms, divided into more than 3,000 heterogeneous species that is called the gut microbiota. The gut microbiota... (Review)
Review
The human gut is a host for trillions of microorganisms, divided into more than 3,000 heterogeneous species that is called the gut microbiota. The gut microbiota composition can be altered by many different endogenous and exogenous factors, especially diet and nutrition. A diet rich in phytoestrogens, a variable group of chemical compounds similar to 17-β-estradiol (E2), the essential female steroid sex hormone is potent to change the composition of gut microbiota. However, the metabolism of phytoestrogens also highly depends on the action of enzymes produced by gut microbiota. Novel studies have shown that phytoestrogens could play an important role in the treatment of different types of cancers, such as breast cancer in women, due to their potential to decrease estrogen levels. This review aims to summarize recent findings about the lively dialogue between phytoestrogens and gut microbiota and to address their possible future application, especially in treating patients with diagnosed breast cancer. A potential therapeutic approach for the prevention and improving outcomes in breast cancer patients could be based on targeted probiotic supplementation with the use of soy phytoestrogens. A positive effect of probiotics on the outcome and survival of patients with breast cancer has been established. However, more in vivo scientific studies are needed to pave the way for the use of probiotics and phytoestrogens in the clinical practice of breast cancer treatment.
Topics: Female; Humans; Phytoestrogens; Gastrointestinal Microbiome; Estrogens; Breast Neoplasms; Biotransformation; Isoflavones
PubMed: 37100304
DOI: 10.1016/j.jnutbio.2023.109368