bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing the Impacts of Early Interventional Ketogenic Diet on Brain Vasculature, Energy Metabolism, and Cognition
Authors: Ma David , Wang Amy , Hoffmann Jared , Bakshi Vikas , Parikh Ishita , Guo Janet , Armstrong Rachel , Hartz Anika , Bauer Bjoern , Lin Ailing 
Published: November 2023

The ketogenic diet (KD), or the low‐carbohydrate and high‐fat diet, has served as a therapeutic for medically intractable epilepsy for the past ninety years. Recent studies have shown the neurological benefits derived from ketone bodies. However, KD's impact on overall in vivo brain function remains largely unexplored. The aim of this study was to characterize the interaction between specialized nutrition and in vivo brain function. Subjects were age‐matched and gender‐matched young wild type mice models, divided into two groups based on diet: Western (control) diet or KD. We employed multimodal, non‐invasive neuroimaging (MRI/MRS) to determine in vivo brain cerebral blood flow and energy metabolites. We also assessed the animal's memory and learning ability with the Radial Arm Water Maze and the Novel Object Recognition Test. In addition, we performed western blots and BBB function analysis. Blood glucose, blood ketone bodies, and body weight were also measured. We found distinct patterns between Western and Ketogenic diet – the KD group exhibited significantly higher cerebral blood flow in the dorsal thalamus and the hypothalamus compared to the control. We observed significant modulation of the metabolites alanine and lactate, and identified a potential interaction with astrocytes. When examining the behavioral test results, there is indication that KD fortifies various memory and sensory functions, consist with our CBF data. Furthermore, KD mice exhibited significantly higher brain endothelial NOS and brain capillary P‐glycoprotein, as well as a significantly lower expression of the mechanistic target of Rapamycin. Our novel findings demonstrate KD produces noticeable shifts in brain vascular and metabolic function, while maintaining cognition in a young mice model. These results provide rationale for KD as a viable early interventional dietary measure.Support or Funding InformationThis research was supported by NIH grant K01AG040164.
Dairy Product Intake is Associated with Cognition but not Cognitive Decline in the NuAge Community‐Dwelling Older Adult Cohort
Authors: Tessier Anne‐Julie , Farsijani Samaneh , Payette Hélène , Morais José A. , Gaudreau Pierrette , Shatenstein Bryna , Chevalier Stéphanie 
Published: November 2023

BackgroundDairy products (DP) may exert a role in cognition, possibly through their content in bioactive peptides, vitamin B12, calcium and fermented products. Sparse evidence from cohort studies has related total DP intake to cognitive status, but its impact on age‐related cognitive decline remains unknown.ObjectiveTo study associations between total daily intake of DP, high‐fat (HF) and low‐fat (LF) DP, DP categories, and cognition at baseline (T1) and as a 3 y‐change in community‐dwelling older adults.MethodsAnalyses were conducted on 702 men and 797 women of the Quebec longitudinal study on nutrition and aging (NuAge) aged 67–84 y at T1. Yearly average total dairy intake was calculated from averaging 3 non‐consecutive 24‐h food recalls collected at T1 and 3 at T3. Number of DP servings was calculated as per Canadian Food Guide portion sizes. Cognitive function was assessed yearly by the Modified Mini‐Mental Examination State (3MS). Baseline cross‐sectional associations were estimated using multivariate regression models adjusted for sex, age, education, symptoms of depression (GDS) and global diet quality (Canadian‐Healthy Eating Index, C‐HEI). Longitudinal associations were investigated using linear mixed models over 3 years.ResultsBaseline 3MS score was 93.2 ± 4.6 in men and 94.6 ± 4.1 in women (p<0.001), and total dairy intake 1.43± 0.84 and 1.38 ± 0.76 servings/d (p=NS). Over 3 years, the 3MS score decreased by 2.2 ± 5.5% (p<0.001) with a greater decline in men (2.6 ± 5.5%) than women (1.9 ± 5.4%; p<0.001). At baseline, total dairy intake was associated with 3MS score (std β=0.181, p<0.001) in the whole cohort. Though the level of education was the main determinant of 3MS, the association with dairy remained significant in a multivariate model including all predictors (R2=0.241). The relationship was also observed in both men and women separately. Among DPs, milk, yogurt, cheese as well as HF and LF dairy intake were associated with baseline 3MS score but only cheese or HF dairy intake remained significant predictors after adjustments (std β=0.055, p=0.018, R2=0.240). Usual total dairy intake was not associated with the rate of cognitive decline over 3 years.ConclusionsTotal dairy, especially HF dairy, were independently and cross‐sectionally associated with cognition, providing further evidence in this novel area. Since full fat cheese largely contributed to HF dairy intake, cheese‐specific nutrients including fatty acids point to potential unique mechanisms in cognitive function. The absence of an association between dairy intake and cognitive decline may be explained by the modest 3‐year decline in this healthy cohort. Longer follow‐up investigation of distinct cognitive domains, and in cognitively impaired older adults, is warranted.Support or Funding InformationDairy Farmers of Canada
The Combinatory Effects of Diet and Exercise on BDNF Gene Expression
Authors: Zeeni Nadine , Haidar Edwina Abou , Azar Adriana , Ghanem Anthony , Bassil Katherine , Bassil Maya , Sleiman Sama 
Published: November 2023

Brain Derived Neurotrophic Factor (BDNF) plays a critical role in the synaptic activity and plasticity of mature neurons and regulates the formation and maintenance of memory. Furthermore, human and mouse BDNF levels were found to be altered in psychiatric diseases. Actually, BDNF signaling not only contributes to the pathophysiology of depression, but also is important for the therapeutic effects of antidepressants. On the other hand, exercise induces beneficial responses in the brain, many of which are mediated through induction of BDNF expression. Moreover, BDNF expression was shown to be enhanced under select dietary conditions. However the exact mechanisms for these inductions have been elusive. The aim of the present work was to explore the effect of combining different diets with exercise on BDNF expression in the brain.First, C57BL/6 mice were divided into 6 groups based on the diet they received (standard versus high protein versus high fat) and whether they were provided with a running wheel to exercise during 28 days or not. Results showed that high protein diets induced BDNF expression and that combining this diet with voluntary exercise had an additive effect on BDNF expression. In contrast, a high fat diet attenuated the positive effects of exercise on BDNF expression.In a second experiment, the effect of dietary leucine (1.5% or 3%) was tested in mice exposed to the same 28‐day voluntary exercise paradigm as the first experiment. Results showed that supplementation with 1.5% leucine significantly induced BDNF in the brain, and this effect was additive with exercise as well. Future work will investigate whether the effect found is restricted to leucine or may be extended to other branched chain amino acids such as isoleucine or valine.The present results enrich our understanding of how exercise and different diets coordinate to induce BDNF gene expression and may be used in identifying novel therapeutic targets for depression.
Low Serum Retinol Concentration Explain Higher Hepcidin Levels In Mexican Older Adults
Authors: De la Cruz‐Góngora Vanessa , Salinas‐Rodríguez Aarón , Villalpando Salvador 
Published: November 2023

BackgroundElevated hepcidin levels have been linked to anemia of inflammation (AI). Retinol deficiency has shown to modulate hepcidin expression in animals; however, no studies have explored low serum retinol (LSR) concentration in older adults (OA) and their possible association with hepcidin concentrations. Anemia affect 27% of Mexican OA and inflammation may play a role in the production of anemia in this population. Understanding the mechanisms that play a role in the control hepcidin secretion is an important goal in the prevention of AI.AimTo explore if low serum retinol is associated with higher serum hepcidin concentrations in Mexican older adults (≥60years).MethodsMexican OA were participants in a crossectional study to identify the main causes of anemia. They were recruited in August 2015. Fasting serum samples were collected in 535 OA. Serum retinol (SR) was measured by HPLC and LSR was defined if SR<20μg/dL. Hepcidin (ng/mL) was measured using a commercial ELISA kit. Due to skewed distribution of hepcidin, a quantil regression model was used to associate the LSR and hepcidin, adjusting by sex, age, BMI, ferritin, transferrin receptor, vitamin B12 status, IL‐6, C reactive protein, Alpha‐1‐acid glycoprotein, diabetes, hypertension, tertil of socioeconomic status, sarcopenia and functional disability.ResultsMean age was 71.5y for male and 70.7y for female. LSR was present in 3.2% of OA. Mexican OA with low serum retinol had 12.2 ng/mL higher hepcidin levels than OA with normal serum retinol levels (p=0.03). Hepcidin adjusted median (by confounders) were (median±EE): 19.4± 1.0 ng/mL in OA with normal serum retinol and 31.9±5.7 ng/mL in OA with LSR. Sarcopenic OA had higher hepcidin levels (coef: 7.5 ng/mL, p=0.03) than OA non‐sarcopenic.ConclusionsLSR levels in OA explain their higher hepcidin concentrations. Retinol concentrations affects iron homeostasis but the mechanism is unclear. This data document for the first time that in humans, low serum retinol concentration is inversely associated with hepcidin concentrations. Further longitudinal studies are needed to understand the role of serum hepcidin and Retinol in the development of AI in OA.Support or Funding InformationCONACYT‐FONSEC SSA/IMSS/ISSSTE SALUD 2014‐1, S0008‐2014‐1‐000000000234157
Brain Plasticity: Measuring Protein Synthesis Rates in the Human Brain
Authors: Smeets Joey S.J. , Horstman Astrid M.H. , Schijns Olaf E.M.G. , Dings Jim T.A. , Hoogland Govert , Gijsen Annemie P. , Goessens Joy P.B. , van Loon Luc J.C. 
Published: November 2023

IntroductionBrain plasticity is a term typically used to refer to the ability of the brain to reorganize itself throughout life. Though the term is often applied in neuroscience to express synaptic or non‐synaptic plasticity, information on whether neuroplasticity is also accompanied by a high brain tissue protein turnover rate is scarce. Because of obvious limitations with regard to brain tissue sampling no study has ever directly measured brain protein synthesis rates in vivo in humans. In this study, we applied contemporary stable isotope methodology to assess protein synthesis rates in vivo in human brain tissue of patients operated for drug‐resistant epilepsy.MethodsSix otherwise healthy patients (47±6 y), scheduled to undergo resective surgery for treatment of drug‐resistant temporomesial epilepsy, were included in this study. Primed continuous intravenous infusions with L‐[ring‐13C6]‐Phenylalanine and L‐[3,5‐2H2]‐Tyrosine were initiated 2.5 h prior to surgery and continued during surgery. Throughout the surgical procedure the following tissue samples were obtained: temporal neocortex, hippocampus, temporalis muscle, and vastus lateralis muscle. Tissue‐specific fractional protein synthesis rates (%/h) were assessed by measuring the incorporation of labelled L‐[ring‐13C6]‐Phenylalanine in tissue protein and were compared between the different tissues using a paired t test.ResultsSerum L‐[ring‐13C6]‐Phenylalanine enrichments averaged 8.1±0.7 MPE throughout the surgical procedure. Protein synthesis rates of temporal neocortex and hippocampus tissue averaged 0.17±0.01 and 0.13±0.01 %/h, respectively, with a significant difference between both tissues (P<0.05). Brain tissue protein synthesis rates were 3–4 fold higher compared to skeletal muscle protein synthesis rates (0.05±0.01 %/h; P<0.001).ConclusionThis is the first study to present protein synthesis rates in vivo in the human brain. With brain protein synthesis rates being several‐fold higher compared to skeletal muscle protein synthesis rates, the human brain displays a degree of tissue plasticity much higher than generally assumed.
Effect of Gastric By‐pass on Dietary Protein Bioavailability and Protein Anabolism in Rats
Authors: Gaudichon Claire , Tessier Romain , Ribeiro‐Parenti Lara , Bruneau Ouafa , Cavin Jean‐Baptiste , Khodorova Nadezda , Bado André , Tomé Daniel , Le Gall Maude 
Published: November 2023

IntroductionBariatric surgery is an efficient treatment of massive obesity but it can trigger nutritional deficiencies, especially regarding vitamins and proteins. Protein wasting may be observed although there are large prevalence variations in the literature. Additionally to a low protein intake, protein malabsorption logically appears as a risk factor of protein wasting. However, there is little data on protein digestion after bariatric surgery. Our study aimed to assess the effect of gastric‐bypass (RYGB) on dietary protein bioavailability and protein status in rats.MethodsRats were fed for 3 months an obesogenic diet. Eighteen rats underwent RYGB surgery (survival: n=9) and 10 Sham (survival: n=10) served as control that were pair‐fed. For 15 d post‐surgery, dietary intake, weight and body composition were measured. After 15 d, rats were given a test meal containing 15N labeled proteins. They were sacrificed 6 h after the meal and dietary proteins were quantified in gastrointestinal segments (stomach, duodenum, jejunum, ileum, caecum and colon) by elemental analyzer coupled to isotope ratio mass spectrometer. Small intestine morphology was studied by histology. The protein Fractional Synthesis Rate (FSR) was measured in the liver, kidney, muscle and skin using a 13C valine flooding dose before sacrifice. Results (means ± SEM) were analyzed using a t test (P<0.05).ResultsCompared to baseline, RYGB decreased dietary intake by 49%. Despite pair‐feeding, weight loss was higher in RYGB than in Sham (14±2 % vs 7±0.8 %, P= 0.002), as well as fat mass loss (33±5 % vs 20±1 %, P=0.03). Lean mass loss was 7±1.5 %. in both groups. Six hours after the meal test, there was more dietary nitrogen in the caecum of Sham than RYGB but no difference was detected in other intestinal segments. Real protein digestibility was lower in Sham than RYGB (93.1±0.6 % vs 95.2±0.7%, P=0.03). Histology revealed a hypertrophy of jejunum mucosa in RYGB. The FSR of kidney protein was strongly decreased (P<0.001) in RYGB (72.2±3.2 %/j) compared to sham (98.4±3.3 %/j). Protein anabolism was similar between groups in other tissues.ConclusionWe showed that dietary protein bioavailability was paradoxically improved in RYGB, an effect that can be attributed to the jejunum mucosa hypertrophy. We also revealed that RYGB markedly lowered protein anabolism in the kidney. It will be interesting to identify which protein are involved in this effect.
Aloe‐emodin attenuates inflammatory signaling cascade in Pam3CSK4‐stimulated macrophages
Authors: Park Mi‐Young , Kim Soon‐Kyung 
Published: November 2023

Aloe‐emodin (AE) is an ingredient of aloe and is known to exhibit anti‐inflammatory activities. However, little is known about underlying molecular mechanisms of inflammatory modulation in vitro. In the present study, we investigated the anti‐inflammatory potential of AE using Pam3CSK4‐stimulated macrophages. RAW 264.7 macrophages was treated with AE (0–20 mM) for 1 h followed by Pam3CSK4 for 1 h, and then the mRNA expression levels of cytokines were measured. The effect of AE on the TLR2‐related molecules was also investigated in Pam3CSK4‐stimulated RAW264.7 macrophages. AE attenuated Pam3CSK4‐stimulated expression of proinflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and interleukin‐1β (IL‐1β) in both RAW264.7 macrophages and DMEMs. AE showed reduction on mRNA levels of toll‐like receptor 2 (TLR2) and on activation of the nuclear factor‐kappa B (NF‐κB) and mitogen‐activated protein kinase (MAPK) phosphorylation. Our data suggest that AE exerts its anti‐inflammatory effect by suppressing the TLR2‐mediated of NF‐κB and MAPK signaling pathways in macrophages.Support or Funding InformationThis study was supported by Soonchunhyang University Research Fund.
Dietary Patterns and Lung Function: Assessment of the Alternative Health Eating Index‐2010 (AHEI‐2010) and Rate of Change in Forced Expiratory Volume in the First Second (FEV1)
Authors: Rettig Samantha A. , Xu Jiayi , Karr Alexandra R. , Tang Wenbo , Guertin Kristin A. , Goodman Phyllis J. , Minasian Lori M. , Lippman Scott M. , Klein Eric A. , Cassano Patricia A. 
Published: November 2023

ObjectivePrior studies of diet and lung function focus on individual nutrients or foods, whereas US Dietary Guidelines focus on dietary patterns. We investigated the association of the Alternative Healthy Eating Index‐2010 (AHEI‐2010), a measure of overall dietary quality and compliance to the US dietary guidelines, and lung function, quantified by the rate of change in forced expiratory volume in the first second (FEV1).MethodsThe Respiratory Ancillary Study (RAS; N=2,920), which was nested within SELECT (Selenium and Vitamin E Cancer Prevention Trial), studied the effect of supplementation with vitamin E and selenium on the longitudinal trajectory in lung function. RAS also assessed usual dietary intake with a food frequency questionnaire (FFQ) at study baseline; the current analysis investigated the AHEI‐2010 score (higher score indicates greater compliance to dietary guidelines), derived from the FFQ, in relation to rate of change in FEV1. Linear mixed‐effects models estimated the AHEI‐2010—rate of change in FEV1 association, with AHEI‐2010 as a continuous variable (null hypothesis β=0). Models were adjusted for race, age, height, weight, smoking status and pack‐years, education, marital status, residence status, treatment arm, multivitamin use, and energy intake, and extended to test the AHEI‐2010 score × smoking interaction.ResultsA higher AHEI‐2010 score was associated with a slower rate of decline in FEV1 across the full cohort such that an increase of 10 (~1SD) in AHEI‐2010 was associated with a 7.0 mL/year attenuation in the rate of decline (P=0.0009). Models confirmed a statistically significant interaction of AHEI‐2010 and smoking status (P=0.0278), which indicated a stronger association of AHEI‐2010—rate of decline in FEV1 in current smokers compared to never/former smokers. In current smokers, an increase of 10 (~1SD) in AHEI‐2010 was associated with a 17 mL/year attenuation in the annual decline in FEV1 (95% CI: 7, 26); in never/former smokers the same increase in AHEI‐2010 was associated with a 5mL/year (95% CI: 0.4, 9) attenuation in rate of decline.ConclusionsIn a population of North American men, a higher AHEI‐2010 score was associated with a slower decline in lung function, and the association was 3‐fold stronger in current smokers compared to never/former smokers. Translating this to dietary intake, in smoking men consuming one additional serving of vegetables or fruit/day (i.e., increase of 2 in AHEI‐2010), the annual rate of decline in FEV1 was attenuated by 3.3 mL/year.Support or Funding InformationFunding: NHLBI R01HL071022 (PAC), and, in part, by NCI U10CA37429 and 5UM1CA182883
Feasibility and Reliability of The Monell Forced Choice Test to Measure Sweet Taste Preference in Ghanaian Children Aged 4–6 y
Authors: Okronipa Harriet , Arimond Mary , Arnold Charles D. , Adu‐Afarwuah Seth , Tamakloe Solace M. , Young Rebecca Tree , Dewey Kathryn 
Published: November 2023

Introduction and objectiveLittle or no research involving the measurement of sweet taste preference in children has been done in a developing country setting. In a randomized controlled trial to examine the efficacy of small‐quantity lipid‐based nutrient supplements (LNS) for supporting healthy growth and development, infants received 0 g or 20 g daily SQ‐LNS from 6–18 months of age. The SQ‐LNS was moderately sweet, with 4 g of total sugars per daily dose, including lactose (in milk) and sucrose. As part of a follow‐up aiming to assess impact on subsequent sweet taste preference, we tested the feasibility and reliability of the Monell forced choice taste test to measure sweet taste preference among Ghanaian children aged 4–6 y.MethodsA total of 598 children were recruited and taken through the 2‐series taste test. Each series included a number of forced choices between two concentrations of sucrose in water, one lower and one higher, across a range of 3 – 36% w/v concentrations. Each child tasted two solutions and was asked to point to the one they preferred. Choices continued at varying concentrations until a single preferred concentration was identified. In the first series the less sweet solution was always tasted first, and in the second the sweeter solution was tasted first. Reliability was assessed by calculating the percent agreement between the first and second series.ResultsThe test required an average of 3.8 and 3.7 presentations of sucrose solution pairs for series 1 and 2, respectively. About 47% chose the same or next closest sucrose concentration in series 1 and 2, and 38% chose > 2 concentrations higher/lower. Child age (P<0.001) but not level of schooling (P=0.4601) was associated with the percent agreement between series 1 and 2. Compared to children who were 6 y old at the time of testing, children aged 4 y [OR (95% CI): 5.96 (2.04, 17.45)] and 5 y [3.05 (1.03, 9.00)] were more likely to prefer > 2 concentrations higher/lower in series 1 versus 2.ConclusionIn our setting and possibly other low income settings similar to our study area, the Monell forced choice test is feasible but may be acceptably reliable only among children aged 6 y and above.Support or Funding InformationThis study was funded by a grant from the Bill & Melinda Gates Foundation to the University of California, Davis, USA.
Lycopene protects kidney against atrazine‐induced oxidative stress and autophagy via activating the AMPK pathway
Authors: Lin Jia , Xia Jun , Li Xue‐Nan , Zhang Cong , Li Wei , Li Jin‐Long 
Published: November 2023

The environmental persistence and bioaccumulation of herbicide atrazine (ATR) may pose a significant threat to human health, especially causing nephritic dysfunction. Lycopene (LYC) has been shown to exhibit nephritic disease preventive effects. However, chemopreventive potential of LYC against ATR‐induced nephrotoxicity remains unclear. To determine the effects of ATR and/or LYC on kidney, mice were treated with ATR (50 mg/kg or 200 mg/kg) and/or LYC (5 mg/kg) by intragastric administration for 21 days. The results revealed that ATR led to increased serum creatinine content and significantly histological alterations. Notably, supplementary LYC significantly decreased ATR and its main metabolites (DACT) contents. LYC administration reverted ATR‐induced dysregulation of oxidative stress markers including pancreatic malondialdehyde, hydrogen peroxide and redox enzymes superoxide dismutase, glutathione peroxidase and catalase. LYC treatment downregulated ATR‐induced increase of nuclear factor erythroid 2‐related factor 2 (Nrf2) expression and Nrf2‐regulated redox genes including quinoneoxidoreductase‐1, heme oxidase‐1. In addition, LYC suppressed ATR‐induced activation of autophagy containing LC3II/LC3I, ATGs, Belin1, p62, in parallel with increased AMPK activation. Together, our findings demonstrate that LYC suppresses the expression of antioxidant enzymes and p62 by activating Nrf2 signaling pathway, then stimulating AMPK pathway to resist ATR‐induced renal oxidative stress and autophagy.Support or Funding InformationChina New Century Excellent Talents in University (No. NECT‐1207‐02), National Natural Science Foundation of China (No. 31572586) and Academic Backbone Project of Northeast Agricultural University (No. 15XG16).