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Biomedicine & Pharmacotherapy =... Dec 2023Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of... (Review)
Review
Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of environmental, dietary, and hormonal stimulations or serve as orphan receptors lacking a recognized ligand. They also play an essential role in normal development, metabolism, cell growth, cell division, physiology, reproduction, and homeostasis and function as biological markers for tumor subclassification and as targets for hormone therapy. NRs, including steroid hormone receptors (SHRs), have been studied as tools to examine the fundamentals of transcriptional regulation within the development of mammals and human physiology, in addition to their links to disturbances. In this regard, it is widely recognized that aberrant NR signaling is responsible for the pathological growth of hormone-dependent tumors in response to SHRs dysregulation and consequently represents a potential therapeutic candidate in a range of diseases, as in the case of prostate cancer and breast cancer. On the other hand, phytosterols are a group of plant-derived compounds that act directly as ligands for NRs and have proven their efficacy in the management of diabetes, heart diseases, and cancers. However, these plants are not suggested in cases of hormone-dependent cancer since a certain group of plants contains molecules with a chemical structure similar to that of estrogens, which are known as phytoestrogens or estrogen-like compounds, such as lignans, coumestans, and isoflavones. Therefore, it remains an open and controversial debate regarding whether consuming a phytosterol-rich diet and adopting a vegetarian lifestyle like the Mediterranean diet may increase the risk of developing steroid hormone-dependent cancers by constitutively activating SHRs and thereby leading to tumor transformation. Overall, the purpose of this review is to better understand the relevant mechanistic pathways and explore epidemiological investigations in order to establish that phytosterols may contribute to the activation of NRs as cancer drivers in hormone-dependent cancers.
Topics: Animals; Humans; Male; Breast Neoplasms; Estrogens; Mammals; Phytoestrogens; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; Steroids; Phytosterols
PubMed: 37944439
DOI: 10.1016/j.biopha.2023.115783 -
Redox Biology Aug 2023To identify metabolomic reprogramming in early hyperlipidemia, unbiased metabolome was screened in four tissues from ApoE mice fed with high fat diet (HFD) for 3 weeks....
To identify metabolomic reprogramming in early hyperlipidemia, unbiased metabolome was screened in four tissues from ApoE mice fed with high fat diet (HFD) for 3 weeks. 30, 122, 67, and 97 metabolites in the aorta, heart, liver, and plasma, respectively, were upregulated. 9 upregulated metabolites were uremic toxins, and 13 metabolites, including palmitate, promoted a trained immunity with increased syntheses of acetyl-CoA and cholesterol, increased S-adenosylhomocysteine (SAH) and hypomethylation and decreased glycolysis. The cross-omics analysis found upregulation of 11 metabolite synthetases in ApoE aorta, which promote ROS, cholesterol biosynthesis, and inflammation. Statistical correlation of 12 upregulated metabolites with 37 gene upregulations in ApoE aorta indicated 9 upregulated new metabolites to be proatherogenic. Antioxidant transcription factor NRF2-/- transcriptome analysis indicated that NRF2 suppresses trained immunity-metabolomic reprogramming. Our results have provided novel insights on metabolomic reprogramming in multiple tissues in early hyperlipidemia oriented toward three co-existed new types of trained immunity.
Topics: Mice; Animals; Hyperlipidemias; Acetyl Coenzyme A; S-Adenosylhomocysteine; NF-E2-Related Factor 2; Cholesterol; Diet, High-Fat; Apolipoproteins E; Glycolysis
PubMed: 37364513
DOI: 10.1016/j.redox.2023.102771 -
Frontiers in Endocrinology 2023Fasting morning cortisol (FMC) stress hormone levels, are suggested to reflect increased cardiometabolic risk. Acute response to weight loss diet could elevate FMC.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Fasting morning cortisol (FMC) stress hormone levels, are suggested to reflect increased cardiometabolic risk. Acute response to weight loss diet could elevate FMC. Richer Polyphenols and lower carbohydrates diets could favor FMC levels. We aimed to explore the effect of long-term high polyphenol Mediterranean diet (green-MED) on FMC and its relation to metabolic health.
METHODS
We randomized 294 participants into one of three dietary interventions for 18-months: healthy dietary guidelines (HDG), Mediterranean (MED) diet, and Green-MED diet. Both MED diets were similarly hypocaloric and lower in carbohydrates and included walnuts (28 g/day). The high-polyphenols/low-meat Green-MED group further included green tea (3-4 cups/day) and a Wolffia-globosa Mankai plant 1-cup green shakeFMC was obtained between 07:00-07:30AM at baseline, six, and eighteen-months.
RESULTS
Participants (age=51.1years, 88% men) had a mean BMI of 31.3kg/m, FMC=304.07nmol\L, and glycated-hemoglobin-A1c (HbA1c)=5.5%; 11% had type 2 diabetes and 38% were prediabetes. Baseline FMC was higher among men (308.6 ± 90.05nmol\L) than women (269.6± 83.9nmol\L;p=0.02). Higher baseline FMC was directly associated with age, dysglycemia, MRI-assessed visceral adiposity, fasting plasma glucose (FPG), high-sensitivity C-reactive-protein (hsCRP), testosterone, Progesterone and TSH levels (p ≤ 0.05 for all). The 18-month retention was 89%. After 6 months, there were no significant changes in FMC among all intervention groups. However, after 18-months, both MED groups significantly reduced FMC (MED=-1.6%[-21.45 nmol/L]; Green-MED=-1.8%[-26.67 nmol/L]; p<0.05 vs. baseline), as opposed to HDG dieters (+4%[-12 nmol/L], p=0.28 vs. baseline), whereas Green-MED diet FMC change was significant as compared to HDG diet group (p=0.048 multivariable models). Overall, 18-month decrease in FMC levels was associated with favorable changes in FPG, HbA1c, hsCRP, TSH, testosterone and MRI-assessed hepatosteatosis, and with unfavorable changes of HDLc (p<0.05 for all, weight loss adjusted, multivariable models).
CONCLUSION
Long-term adherence to MED diets, and mainly green-MED/high polyphenols diet, may lower FMC, stress hormone, levels,. Lifestyle-induced FMC decrease may have potential benefits related to cardiometabolic health, irrespective of weight loss.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT03020186.
Topics: Female; Humans; Male; Middle Aged; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet, Mediterranean; Fasting; Glycated Hemoglobin; Hydrocortisone; Testosterone; Thyrotropin; Weight Loss
PubMed: 38034010
DOI: 10.3389/fendo.2023.1243910 -
Nutrients Oct 2023The incidence of type 1 diabetes mellitus in children is considerably increasing in western countries. Thus, identification of the environmental determinants involved... (Review)
Review
AIMS AND HYPOTHESIS
The incidence of type 1 diabetes mellitus in children is considerably increasing in western countries. Thus, identification of the environmental determinants involved could ultimately lead to disease prevention. Here, we aimed to systematically review (PROSPERO ID: CRD42022362522) the current evidence of the association between maternal dietary factors during gestation and the risk of developing type 1 diabetes and/or islet autoimmunity (IA) in murine and human offspring.
METHODS
In accordance with PRISMA guidelines, the present systematic review searched PubMed and Scopus ( = 343) for different combinations of MeSH terms, such as type 1 diabetes, diet, islet autoimmunity, prenatal, nutrient, gluten, gliadin, vitamin, milk, and fibers.
RESULTS
We found that the most investigated dietary factors in the present literature were gluten, dietary advanced glycosylated end products (dAGEs), vitamin D, fatty acids, and iron. The results concerning prenatal exposure to a gluten-free environment showed a consistently protective effect on the development of IA. Prenatal exposures to vitamin D and certain fatty acids appeared to protect against the development of IA, whereas in utero iron and fat exposures correlated with increased risks of IA.
CONCLUSION
We conclude that a definite association is not established for most factors investigated as the literature represents a heterogeneous pool of data, although fetal exposures to some maternal dietary components, such as gluten, show consistent associations with increased risks of IA. We suggest that human prospective dietary intervention studies in both cohort and clinical settings are crucial to better evaluate critical and protective prenatal exposures from the maternal diet during pregnancy.
Topics: Child; Pregnancy; Female; Humans; Animals; Mice; Diabetes Mellitus, Type 1; Autoimmunity; Islets of Langerhans; Vitamin D; Vitamins; Fatty Acids; Glutens; Iron; Autoantibodies; Risk Factors
PubMed: 37892409
DOI: 10.3390/nu15204333 -
Nature Communications Oct 2023Identifying oncological applications for drugs that are already approved for other medical indications is considered a possible solution for the increasing costs of...
Identifying oncological applications for drugs that are already approved for other medical indications is considered a possible solution for the increasing costs of cancer treatment. Under the hypothesis that nutritional stress through fasting might enhance the antitumour properties of at least some non-oncological agents, by screening drug libraries, we find that cholesterol biosynthesis inhibitors (CBIs), including simvastatin, have increased activity against cancers of different histology under fasting conditions. We show fasting's ability to increase CBIs' antitumour effects to depend on the reduction in circulating insulin, insulin-like growth factor-1 and leptin, which blunts the expression of enzymes from the cholesterol biosynthesis pathway and enhances cholesterol efflux from cancer cells. Ultimately, low cholesterol levels through combined fasting and CBIs reduce AKT and STAT3 activity, oxidative phosphorylation and energy stores in the tumour. Our results support further studies of CBIs in combination with fasting-based dietary regimens in cancer treatment and highlight the value of fasting for drug repurposing in oncology.
Topics: Simvastatin; Fasting; Diet; Insulin; Cholesterol
PubMed: 37907500
DOI: 10.1038/s41467-023-42652-1 -
Advances in Nutrition (Bethesda, Md.) Sep 2023The Dietary Guidelines for Americans recommend two-and-a-half cup equivalents of low-fat and fat-free dairy foods per day for children 4-8 y and 3 cup equivalents per... (Review)
Review
The Dietary Guidelines for Americans recommend two-and-a-half cup equivalents of low-fat and fat-free dairy foods per day for children 4-8 y and 3 cup equivalents per day for adolescents aged 9-18 and adults. Currently, the Dietary Guidelines for Americans recognizes 4 nutrients as being of public concern because of suboptimal levels in the diet. These include calcium, dietary fiber, potassium, and vitamin D. In the American diet, dairy foods are leading contributors of calcium, vitamin D, and potassium. Milk, because of its unique nutrient package that provides shortfall nutrients to the diets of children and adolescents, remains an underpinning of dietary recommendations and is included with school meals. Despite this, milk consumption is declining, and >80% of Americans do not meet recommendations for dairy. Data indicate that children and adolescents who consume flavored milk are more likely to consume more dairy and adhere to healthier overall dietary patterns. Flavored milk, however, receives more scrutiny than plain milk because of its contribution of added sugar and calories to the diet and concerns over childhood obesity. Therefore, the purpose of this narrative review is to describe trends in beverage consumption in children and adolescents aged 5-18 y and highlight the science that has examined the impact of including flavored milk in overall healthy dietary patterns within this population.
Topics: Adult; Adolescent; Child; Humans; United States; Animals; Milk; Pediatric Obesity; Diet; Energy Intake; Flavoring Agents; Calcium, Dietary; Vitamins; Diet, Fat-Restricted; Vitamin D
PubMed: 37290718
DOI: 10.1016/j.advnut.2023.06.002 -
International Journal of Molecular... Aug 2023Celiac disease (CD) is a chronic enteropathy caused by the ingestion of gluten in a genetically susceptible individual. Currently, a gluten-free diet (GFD) is the only... (Review)
Review
Celiac disease (CD) is a chronic enteropathy caused by the ingestion of gluten in a genetically susceptible individual. Currently, a gluten-free diet (GFD) is the only recommended treatment. However, unintentional gluten ingestion or a persistent villous atrophy with malabsorption (regardless of a strict GFD) as in the case of Refractory Celiac Disease (RCD) represents a major issue. In this review, we have analysed and discussed data from both randomized controlled trials and observational studies concerning adjunctive therapies as well as novel therapies for the treatment of CD and RCD. The literature search was carried out through Medline and Scopus. In total, 2268 articles have been identified and 49 were included in this review (36 studies resulting from the search strategy and 13 from other sources). Today, GFD remains the only effective treatment, although steroids, mesalamine, and more recently biological therapies have found space in the complex management of RCD. Currently, studies evaluating the effectiveness of novel therapies are still limited and preliminary results have been controversial.
Topics: Humans; Celiac Disease; Dental Care; Glutens; Diet, Gluten-Free; Genetic Predisposition to Disease
PubMed: 37628981
DOI: 10.3390/ijms241612800 -
Journal of Public Health (Oxford,... Nov 2023Previous studies of the UK Biobank have examined intake of single food items and their association with health outcomes. Our aim was to develop a dietary quality score...
BACKGROUND
Previous studies of the UK Biobank have examined intake of single food items and their association with health outcomes. Our aim was to develop a dietary quality score and examine the relationship between this score and markers of cardiometabolic health.
METHODS
Principal component analysis was performed on dietary data from UK Biobank participants. Linear regression was used to analyse the relationship between diet and cardiometabolic health.
RESULTS
The first component explained 14% of the variation in the dietary data. It was characterised by high consumption of meat and low fibre carbohydrates, and a low intake of fruit and vegetables. A higher score, indicative of healthier diet, was associated with lower systolic and diastolic blood pressure (β -0.81, 95% CI -1.0, -0.62; β - .61, 95% CI -0.72, -0.5) and a healthier lipid profile (lower levels of cholesterol β -0.05, 95% CI -0.06, -0.04, triglycerides β -0.05, 95% CI -0.06, -0.03, and higher HDL cholesterol β 0.01, 95% CI 0, 0.01).
CONCLUSIONS
The dietary quality score was a good approximation of overall dietary quality. An unhealthy diet was associated with markers of poorer cardiometabolic health.
Topics: Humans; Biological Specimen Banks; Diet; Cholesterol; Cardiovascular Diseases; United Kingdom
PubMed: 37385972
DOI: 10.1093/pubmed/fdad103 -
The European Respiratory Journal Oct 2023https://bit.ly/3LuzAUJ (Clinical Trial)
Clinical Trial
https://bit.ly/3LuzAUJ
Topics: Humans; Anti-Inflammatory Agents, Non-Steroidal; Diet; Idiopathic Pulmonary Fibrosis; Pyridones; Treatment Outcome; Vital Capacity
PubMed: 37857429
DOI: 10.1183/13993003.00262-2023 -
European Journal of Pharmacology Aug 2023Polycystic ovary syndrome (PCOS) is characterized by reproductive, endocrine, and metabolic disorders. Icariin has been shown to regulate endocrine and metabolic...
Polycystic ovary syndrome (PCOS) is characterized by reproductive, endocrine, and metabolic disorders. Icariin has been shown to regulate endocrine and metabolic imbalances. This study aimed to determine the therapeutic effect and pharmacological mechanism of icariin in PCOS rats. Rats were fed a high-fat diet and gavaged with letrozole to induce PCOS. Thirty-six female rats were randomly divided into four groups: control, model, low-dose, and high-dose icariin. After 30 days of treatment, we evaluated the therapeutic effects on weight and diet, sex hormone levels, ovarian morphology, estrous cycle, inflammatory factors, and indicators of glucolipid metabolism. Combined with the ovarian transcriptome, we verified the key markers of apoptosis and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway by RT-qPCR for mRNA level, western blot, and immunohistochemistry for protein expression. Icariin significantly improved ovarian function and reproductive endocrine disorders by regulating sex hormones, restoring the estrous cycle, and reducing ovarian morphological damage in PCOS rats. Icariin-treated rats had lower weight gain and reduced triglycerides, fasting insulin, HOMA-IR, TNF-α, and interleukin-6 with higher high-density lipoprotein cholesterol levels than PCOS rats. TUNEL staining showed icariin improved apoptosis in the ovaries. This was supported by an increase in Bcl2 and a decrease in Bad and Bax. Icariin decreased the ratios of p-JAK2/JAK2, p-STAT1/STAT1, p-STAT3/STAT3, and p-STAT5a/STAT5a, decreased IL-6, gp130 expression, and increased cytokine-inducible SH2-containing protein (CISH) and suppressor of cytokine signaling 1 (SOCS1) expression. The pharmacological mechanism may be related to the reduction in ovarian apoptosis and inhibition of the IL-6/gp130/JAK2/STATs pathway.
Topics: Humans; Rats; Female; Animals; Polycystic Ovary Syndrome; Letrozole; Interleukin-6; Diet, High-Fat; Cytokine Receptor gp130; Insulin Resistance; Gonadal Steroid Hormones
PubMed: 37269973
DOI: 10.1016/j.ejphar.2023.175825