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International Journal of Molecular... May 2024The diterpene cafestol represents the most potent cholesterol-elevating compound known in the human diet, being responsible for more than 80% of the effect of coffee on...
The diterpene cafestol represents the most potent cholesterol-elevating compound known in the human diet, being responsible for more than 80% of the effect of coffee on serum lipids, with a mechanism still not fully clarified. In the present study, the interaction of cafestol and 16--methylcafestol with the stabilized ligand-binding domain (LBD) of the Farnesoid X Receptor was evaluated by fluorescence and circular dichroism. Fluorescence quenching was observed with both cafestol and 16--methylcafestol due to an interaction occurring in the close environment of the tryptophan W454 residue of the protein, as confirmed by docking and molecular dynamics. A conformational change of the protein was also observed by circular dichroism, particularly for cafestol. These results provide evidence at the molecular level of the interactions of FXR with the coffee diterpenes, confirming that cafestol can act as an agonist of FXR, causing an enhancement of the cholesterol level in blood serum.
Topics: Diterpenes; Receptors, Cytoplasmic and Nuclear; Cholesterol; Humans; Coffee; Molecular Docking Simulation; Protein Binding; Molecular Dynamics Simulation; Circular Dichroism
PubMed: 38892285
DOI: 10.3390/ijms25116096 -
International Journal of Molecular... May 2024Anxiety is a common comorbidity of obesity, resulting from prescribing long-term caloric restriction diets (CRDs); patients with a reduced food intake lose weight but...
Anxiety is a common comorbidity of obesity, resulting from prescribing long-term caloric restriction diets (CRDs); patients with a reduced food intake lose weight but present anxious behaviors, poor treatment adherence, and weight regain in the subsequent 5 years. Intermittent fasting (IF) restricts feeding time to 8 h during the activity phase, reducing patients' weight even with no caloric restriction; it is unknown whether an IF regime with ad libitum feeding avoids stress and anxiety development. We compared the corticosterone blood concentration between male Wistar rats fed ad libitum or calorie-restricted with all-day or IF food access after 4 weeks, along with their anxiety parameters when performing the elevated plus maze (EPM). As the amygdalar thyrotropin-releasing hormone (TRH) is believed to have anxiolytic properties, we evaluated its expression changes in association with anxiety levels. The groups formed were the following: a control which was offered food ad libitum (C-adlib) or 30% of C-adlib's energy requirements (C-CRD) all day, and IF groups provided food ad libitum (IF-adlib) or 30% of C-adlib's requirements (IF-CRD) with access from 9:00 to 17:00 h. On day 28, the rats performed the EPM and, after 30 min, were decapitated to analyze their amygdalar TRH mRNA expression by in situ hybridization and corticosterone serum levels. Interestingly, circadian feeding synchronization reduced the body weight, food intake, and animal anxiety levels in both IF groups, with ad libitum (IF-adlib) or restricted (IF-CRD) food access. The anxiety levels of the experimental groups resulted to be negatively associated with TRH expression, which supported its anxiolytic role. Therefore, the low anxiety levels induced by synchronizing feeding with the activity phase would help patients who are dieting to improve their diet therapy adherence.
Topics: Animals; Anxiety; Rats; Male; Amygdala; Thyrotropin-Releasing Hormone; Rats, Wistar; Caloric Restriction; Circadian Rhythm; Corticosterone; Down-Regulation; Feeding Behavior; Fasting; Eating; Body Weight
PubMed: 38892044
DOI: 10.3390/ijms25115857 -
BMC Pregnancy and Childbirth Jun 2024The current study sought to investigate the correlation between vitamin D supplementation in pregnant women with vitamin D deficiency in early pregnancy and the...
BACKGROUND
The current study sought to investigate the correlation between vitamin D supplementation in pregnant women with vitamin D deficiency in early pregnancy and the incidence of prenatal depression prior to delivery.
METHODS
This is a retrospective, single-center study that was conducted at a tertiary hospital in Chengdu, China. We conducted an analysis on pregnant women who were initially diagnosed with vitamin D deficiency at 12-14 weeks of gestation. After starting vitamin D supplementation at a dose of 800 IU daily from 14 weeks onwards, we measured both their vitamin D concentration and depression scores again during median gestational week 39 prior to delivery.
RESULTS
The study cohort comprised 1365 women who had been diagnosed with vitamin D deficiency at 12-14 weeks of gestation between November 1st, 2021 to November 1st, 2022. 537 pairs were matched based on a propensity score to control for other confounding factors. After propensity score matching, the baseline vitamin D levels were made consistent between the groups (P = 0.512). The incidence of depression in patients in vitamin D deficiency group following vitamin D supplementation was significantly higher than insufficiency group and reached statistical significance (P < 0.001). Additionally, we observed that serum 25-(OH) D concentration achieving insufficiency status after supplementation was 59.12%.
CONCLUSION
Our study indicates that daily supplementation of 800IU of vitamin D can improve the depressive symptoms of individuals who are vitamin D deficiency during early pregnancy but achieve vitamin D insufficiency after supplementation during prenatal period.
Topics: Humans; Female; Pregnancy; Vitamin D Deficiency; Retrospective Studies; Vitamin D; Dietary Supplements; Adult; Depression; Pregnancy Complications; China; Incidence; Vitamins; Prenatal Care
PubMed: 38890581
DOI: 10.1186/s12884-024-06631-8 -
Journal of Animal Physiology and Animal... Jun 2024Aquafeed additive quality and quantity remain pivotal factors that constrain the sustainability and progress of aquaculture feed development. This study investigates the...
Effects of dietary supplementation with benthic diatom Amphora coffeaeformis on blood biochemistry, steroid hormone levels and seed production efficiency of Nile tilapia Oreochromis niloticus broodstock.
Aquafeed additive quality and quantity remain pivotal factors that constrain the sustainability and progress of aquaculture feed development. This study investigates the impact of incorporating the benthic diatom Amphora coffeaeformis into the diet of Nile tilapia (Oreochromis niloticus) broodstock, on the blood biochemistry, steroid hormone (SH) levels and seed production efficiency. Broodstock females displaying mature ovary indications were initially combined with males at a ratio of three females to one male. A total of 384 adult Nile tilapia (288 females and 96 males) were used, with 32 fish (24 females and eight males) assigned to each of 12 concrete tanks (8 m³; 2 m × 4 m × 1 m), with three replicate tanks for each dietary treatment, throughout a 14-day spawning cycle until egg harvest. Fish were fed one of four different dietary treatments: AM (control diet), and AM, AM and AM enriched with the diatom A. coffeaeformis at levels of 20, 40 and 60 g/kg of diet respectively. At the trial's conclusion, total protein, albumin, triglyceride and creatinine), SHs (follicle-stimulating hormone, luteinizing hormone, free testosterone, total testosterone, progesterone and prolactin) and seeds production efficiency of Nile tilapia improved significantly (p < 0.05) in alignment with the increment of A. coffeaeformis supplementation. The findings propose that including A. coffeaeformis at levels ranging from 4% to 6% could be effectively employed as a feed additive during the Nile tilapia broodstock's spawning season.
PubMed: 38879794
DOI: 10.1111/jpn.14004 -
Progress in Neuro-psychopharmacology &... Jun 2024The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic... (Review)
Review
BACKGROUND
The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD.
METHODS
PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected.
RESULTS
Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1β, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients.
CONCLUSION
Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.
PubMed: 38879067
DOI: 10.1016/j.pnpbp.2024.111056 -
International Journal of Hygiene and... Jul 2024Zearalenone (ZEN) is a fungal-derived toxin found in global food supplies including cereal grains and processed foods, impacting populations worldwide through diet....
Zearalenone (ZEN) is a fungal-derived toxin found in global food supplies including cereal grains and processed foods, impacting populations worldwide through diet. Because the chemical structure of ZEN and metabolites closely resembles 17β-estradiol (E2), they interact with estrogen receptors α/β earning their designation as 'mycoestrogens'. In animal models, gestational exposure to mycoestrogens disrupts estrogen activity and impairs fetal growth. Here, our objective was to evaluate relationships between mycoestrogen exposure and sex steroid hormone concentrations in maternal circulation and cord blood for the first time in humans. In each trimester, pregnant participants in the UPSIDE study (n = 297) provided urine for mycoestrogen analysis and serum for hormone analysis. At birth, placental mycoestrogens and cord steroids were measured. We fitted longitudinal models examining log-transformed mycoestrogen concentrations in relation to log-transformed hormones, adjusting for covariates. Secondarily, multivariable linear models examined associations at each time point (1st, 2nd, 3rd trimesters, delivery). We additionally considered effect modification by fetal sex. ZEN and its metabolite, α-zearalenol (α-ZOL), were detected in >93% and >75% of urine samples; >80% of placentas had detectable mycoestrogens. Longitudinal models from the full cohort exhibited few significant associations. In sex-stratified analyses, in pregnancies with male fetuses, estrone (E1) and free testosterone (fT) were inversely associated with ZEN (E1 %Δ: -6.68 95%CI: -12.34, -0.65; fT %Δ: -3.22 95%CI: -5.68, -0.70); while α-ZOL was positively associated with E2 (%Δ: 5.61 95%CI: -1.54, 9.85) in pregnancies with female fetuses. In analysis with cord hormones, urinary mycoestrogens were inversely associated with androstenedione (%Δ: 9.15 95%CI: 14.64, -3.30) in both sexes, and placental mycoestrogens were positively associated with cord fT (%Δ: 37.13, 95%CI: 4.86, 79.34) amongst male offspring. Findings support the hypothesis that mycoestrogens act as endocrine disruptors in humans, as in animal models and livestock. Additional work is needed to understand impacts on maternal and child health.
Topics: Humans; Female; Fetal Blood; Pregnancy; Zearalenone; Adult; Male; Gonadal Steroid Hormones; Maternal Exposure; Cohort Studies; Zeranol; Estradiol; Young Adult; Placenta
PubMed: 38878407
DOI: 10.1016/j.ijheh.2024.114405 -
Food and Chemical Toxicology : An... Jun 2024Diclofenac, a traditional non-steroidal anti-inflammatory drug, is commonly used for treating chronic pain and inflammation. Recently, a number of articles have...
Diclofenac, a traditional non-steroidal anti-inflammatory drug, is commonly used for treating chronic pain and inflammation. Recently, a number of articles have highlighted the toxicities associated with diclofenac. The current study explores the molecular mechanism of diclofenac induced cardiac toxicity following oxidative stress. Diclofenac inhibits catalase, disrupts the redox balance in cardiac tissue, accelerates the monoamine oxidase induced hydroperoxide generation and eventually inhibits crucial mitochondrial enzyme, viz., aldehyde dehydrogenase, thereby causing myocardial injury. Melatonin, the pineal indoleamine with high antioxidative efficacy, is well known for its cardio-protective properties and its dietary consumption has profound impact on cardiac health. The present study demonstrates perhaps for the first time, that apart from ameliorating oxidative load in the cardiac tissue, melatonin also attenuates the inhibition of catalase and aldehyde dehydrogenase, and prevents stress mediated stimulation of monoamine oxidase. Moreover, favourable binding of diclofenac with melatonin may protect the myocardium from the deleterious effects of this drug. The results indicate toward a novel mechanism of protection by melatonin, having future therapeutic relevance.
PubMed: 38876380
DOI: 10.1016/j.fct.2024.114813 -
Journal of Zoo and Wildlife Medicine :... Jun 2024An understanding of species-specific vitamin D metabolism and its role in calcium homeostasis is essential for correct diet formulation and development of husbandry...
An understanding of species-specific vitamin D metabolism and its role in calcium homeostasis is essential for correct diet formulation and development of husbandry protocols for managed nondomestic species. This study documented serum vitamin D metabolites and other analytes involved in calcium homeostasis in Asian elephants () managed at a latitude similar to their wild natural habitat. Serum values for 33 elephants managed at a low latitude were measured in the peak of summer, revealing low vitamin D (25(OH)D 2.3 ± 0.6 ng/ ml and 24,25(OH)D 2.17 ± 0.52 ng/ml) and nondetectable vitamin D. Serum minerals (calcium, phosphorus, magnesium), ionized calcium, and parathyroid hormone were within normal reported ranges. In comparison with previously reported values in elephants managed at a high latitude, 25(OH)D ( < 0.001), 24,25(OH)D ( = 0.001), and magnesium ( = 0.013) were significantly lower, and parathyroid hormone was significantly higher ( < 0.001). The lack of D production during ample sun exposure at a low latitude suggests that Asian elephants are incapable of cutaneous photobiosynthesis of vitamin D, and that low serum D is normal for this species.
Topics: Animals; Elephants; Calcium; Vitamin D; Biomarkers; Female; Male; Homeostasis; Animals, Zoo
PubMed: 38875199
DOI: 10.1638/2023-0082 -
Paediatric Drugs Jul 2024Alirocumab (Praluent), a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor that has been co-developed by Regeneron Pharmaceuticals, Inc. and Sanofi... (Review)
Review
Alirocumab (Praluent), a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor that has been co-developed by Regeneron Pharmaceuticals, Inc. and Sanofi (formerly sanofi-aventis), is approved globally for use in adults with established cardiovascular disease, primary hyperlipidemia [including heterozygous familial hypercholesterolemia (HeFH) or homozygous familial hypercholesterolemia (HoFH)]. In November 2023, based on clinical data in patients aged 8-17 years, alirocumab received its first pediatric approval in the EU as an adjunct to diet alone, or in combination with a statin and/or other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, in pediatric patients aged ≥ 8 years with HeFH. Alirocumab was approved a few months later in the US for use as an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged ≥ 8 years with HeFH to reduce LDL-C. This article summarizes the milestones in the development of alirocumab leading to this first pediatric approval for HeFH.
Topics: Humans; Antibodies, Monoclonal, Humanized; Child; Adolescent; Drug Approval; Hyperlipoproteinemia Type II; Anticholesteremic Agents; PCSK9 Inhibitors; Cholesterol, LDL
PubMed: 38874895
DOI: 10.1007/s40272-024-00637-7 -
Molecular Biology Reports Jun 2024Background this study was conducted to assess the effects of vitamin D on differentiation of bone marrow- derived mesenchymal stem cells (BM-MSCs) into insulin producing...
Background this study was conducted to assess the effects of vitamin D on differentiation of bone marrow- derived mesenchymal stem cells (BM-MSCs) into insulin producing cells (IPCs). Method BM-MSCs were isolated from femur and tibia of rats and incubated in low (LG) or high glucose (HG) (5mM or 25mM), or high glucose DMEM media supplemented with vitamin D (0.2nM) (HGD) for 14 days. Cells viability was analysis by MTT assay. Differentiation of SCs was confirmed using measuring genes expression level of pdx and insulin, and insulin secretion, glucose stimulated insulin secretion, and insulin content by ELISA method. Results Cell viability was significantly higher in HGD than LG (p < 0.05) in day 3, also, in HG and HGD than LG (p < 0.001), and HGD vs. HG (p < 0.001) in day 7. Pdx1 and insulin level was markedly higher in HGD than LG (p < 0.05 and p < 0.01). pdx1 expression was markedly higher in HGD (p < 0.05) than LG, also insulin expression the HG (p < 0.05), and HGD (p < 0.01) groups compared to the LG group. Insulin release at 5mM glucose was notably higher in the HGD group compared to LG (p < 0.05), and at 25mM glucose, both HG and HGD showed significant increases vs. LG (p < 0.05 and p < 0.01, respectively). Insulin content was significantly higher in both 5mM and 25mM glucose for HG and HGD vs. LG (p < 0.01 and p < 0.001, respectively). In conclusion, treatment BM-MSCs with vitamin D could increase their differentiation into IPCs and it can be considered as a potential supplementary agent in enhancing differentiation SCs into insulin generating cells.
Topics: Mesenchymal Stem Cells; Animals; Cell Differentiation; Vitamin D; Rats; Insulin; Insulin-Secreting Cells; Bone Marrow Cells; Glucose; Homeodomain Proteins; Cells, Cultured; Cell Survival; Male; Trans-Activators; Dietary Supplements; Insulin Secretion
PubMed: 38874843
DOI: 10.1007/s11033-024-09681-5