bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of Adolescent Caffeine Intake with Blood Pressure in Adolescence and Adulthood
Authors: Estrada Erika , Urbina Elaine M , Daniels Stephen R , Woo Jessica G 
Published: November 2023

ObjectiveHigh blood pressure (HBP) is one of the leading causes of premature death worldwide. Currently, 1 in 3 adults has HBP. Recent studies have shown that caffeine leads to an acute increase in blood pressure after exposure, but the long–term effects of caffeine on blood pressure are unclear. Our study aimed to assess the longer‐term relationships between dietary caffeine intake and blood pressure using data collected in two longitudinal epidemiologic studies: the Princeton Lipid Research Study and the NHLBI Growth Health Study (NGHS).MethodsThe Princeton cohort included 623 subjects who were seen as children/adolescents and again in adulthood. The NGHS cohort included 870 black and white females ages 9 or 10 at enrollment who were followed yearly for up to ten years. Caffeine intake was assessed using a 24‐hour recall for Princeton (childhood only) and 3‐day diet records for NGHS (at 8 of 10 visits). Blood pressure in both studies was assessed using standard mercury sphygmomanometer, and systolic and diastolic z‐scores were calculated for childhood measurements. The relationship between caffeine intake and blood pressure was analyzed for individuals in each visit.ResultsIn the NGHS cohort, caffeine intake increased from a median of 15 mg to 40 mg/day between ages 10 and 19 years, and was significantly higher in white vs. black participants at all ages (p<0.0001). Similar patterns were noted in Princeton. In NGHS, SBP z‐score and DBP z‐scores were higher in black vs. white participants from age 17–19 (p<0.01); in Princeton, BP z‐scores did not differ by race at any childhood age. Cross‐sectionally, neither cohort demonstrated significant correlations between caffeine intake and blood pressure z‐scores during childhood/adolescence, except for a negative correlation seen in NGHS with DBP z‐score at age 16.0 (Spearman correlation=−0.085, p=0.04). Longitudinally, in Princeton, caffeine intake in childhood/adolescence was not associated with systolic or diastolic blood pressure in adult follow up (both p>0.4), adjusting for sex, race, and age and BMI at adult follow up. In NGHS, neither caffeine intake at age 12, nor the change in caffeine intake between ages 12 and 19, were associated with blood pressure z‐scores at participants’ final visits, adjusting for age at final visit and BMI z‐score.DiscussionThe results of these two long‐term studies suggest that caffeine consumption during childhood/adolescence is not associated with blood pressure in either later adolescence or adulthood.Support or Funding InformationEE supported by a grant from the American Heart Association and the CCHMC Schmidlapp Young Women's Scholarship.
Mango (Mangifera Indica L.) in the promotion of intestinal regularity and decreases inflammation in human subjects with constipation
Authors: Mertens‐Talcott Susanne U , Kim Hyemee , Talcott Stephen T , Venancio Vinicius Paula 
Published: November 2023

Chronic constipation is a common gastrointestinal condition associated with intestinal inflammation and a considerably impaired quality of life, affecting approximately 10–20% of the population in the US. Dietary fiber and laxatives have been shown to aid in the treatment of chronic constipation. In this study, the consumption of mango fruit was compared to an equivalent amount of fiber in its effect on abdominal distention and constipation in otherwise healthy human volunteers. The participants were randomly divided into either the experimental mango group or control fiber group. The mango group consumed 300 g of mango daily for 4 weeks, while the fiber group consumed an equivalent fiber amount (1 teaspoon). Questionnaires regarding intestinal evacuation and digestive wellness were collected weekly, and blood and stool samples were collected at the beginning of the study and after four weeks. The results show that the mango group had better improvement of constipation status as compared to the fiber group, based on evacuation categorization (stool frequency, consistency, and shape). Additionally, increase in gastrin and Peptide YY (PYY) were higher in the mango group than the control fiber group. The production of endotoxin and IL‐6 were lower in subjects who received mango treatment. In response to the mango intake, two fecal short chain fatty acids, acetic and valeric acid, were increased. Compared to the consumption of fiber, the consumption of mango in the treatment of chronic constipation had higher subject adherence, improved parameters of intestinal evacuation, reduced the production of endotoxins, reduced inflammation, and increased the concentration of short chain fatty acids, all of which have been established to contribute to intestinal health and wellness.Support or Funding InformationMango National Board
Determination of the in vivo and in vitro protein quality of pulse protein concentrates and isolates.
Authors: Nosworthy Matthew G , Neufeld Jason , House James D 
Published: November 2023

Currently, the use of a rodent bioassay is the officially recognized method for generating data in support of protein content claims for food ingredients. Although there are in vitro methods for calculating protein digestibility, to date no method has been accepted by North American regulatory agencies for use in establishing protein content claims, likely due to a lack of evidence in support of their validity. To this end, we compared the in vivo (%True Fecal Protein Digestibility; %TFPD) and the in vitro protein digestibility (%IVPD) of faba bean, lentil and pea protein concentrates and isolates. Sprague‐Dawley rats (n=70, ~70 g) were randomized to one of seven diets (10% crude protein) based on: casein (reference control), the concentrates of faba bean (FB60), lentil (L55) or pea (P55) or the protein isolates of the same pulses (FB85, L85 and P85 respectively). The %TFPD and protein digestibility corrected amino acid score (PDCAAS) were calculated. The %IVPD was determined via enzymatic digestion with subsequent pH drop, and used to calculate the in vitro PDCAAS (IVPDCAAS). Except for L55, in which the sulfur amino acids were limiting, all experimental diets were limited by tryptophan content. FB60 had a higher AAS than FB85 (0.46 vs 0.58) whereas the AAS of the other diets had the opposite trend (L55‐0.75 vs L85‐ 0.52, P55 – 0.58 vs P85‐ 0.54). Digestibility was greater in the protein isolates than the concentrates, and the in vivo rat bioassay reported higher digestibility than the in vitro method; casein (95 vs 84), FB60 (94 vs 74), FB85 (97 vs 75), L55 (91 vs 75), L85 (96 vs 77), P55 (93 vs 78), P85 (97 vs 78). There was no correlation found between %TPD and %IVPD (R2= 0.027). Interestingly, a strong correlation was found between PDCAAS and IVPDCAAS (R2=0.99, p<0.0001), however the values from the rodent model were greater than the in vitro casein (89 vs 79), FB60 (43 vs 33), FB85 (56 vs 44), L55 (68 vs 56), L85 (50 vs 40), P55 (54 vs 46), P85 (53 vs 43). Excepting faba bean, all pulse concentrates had higher AAS, lower digestibility and greater PDCAAS values than their isolate counterparts. As such, processes used in the isolation of pulse protein sources increased digestibility, but may have led to shifts in protein composition, leading to a lower PDCAAS value. Although the strong correlation found between PDCAAS and IVPDCAAS suggests that in vitro analysis could reduce the requirement of animal experimentation for protein claims, a larger dataset combined with investigation into other potential in vitro methods is required.Support or Funding InformationPulse Canada
Evaluation Of Dietary Assessment Tools: Does ‘Validated’ Mean What We Think It Means?
Authors: Kirkpatrick Sharon I , Subar Amy F , Krebs‐Smith Susan M. , Thompson Frances E , Reedy Jill , Schap TusaRebecca E , Vanderlee Lana , Robson Paula , Csizmadi Ilona , Boucher Beatrice A , Massarelli Isabelle , Rondeau Isabelle 
Published: November 2023

Evaluation of the extent to which self‐report dietary assessment tools accurately capture true intake is critical to informing the collection of dietary intake data that can advance our understanding of diet and health. Such evaluation is challenging due to the lack of unbiased reference measures for dietary intake, forcing reliance on self‐report (and thus error‐prone) measures as comparators. Depending on the type of instrument and its intended use, evaluation is also complicated by the need to test tools in different settings and populations. The objective of this work is to examine challenges in evaluating dietary assessment tools and the ways in which the findings of validation studies are interpreted. We draw upon a scoping review of Canadian studies of free‐living adult populations that included an assessment of dietary intake to illustrate the extent and ways in which validity of tools are addressed. Of 58 studies that used a frequency questionnaire or screener to assess diet, tools were reported to have been validated for the given study sample in a small subgroup. In close to two‐thirds, authors reported that the tool has been validated, in some cases with few details on how it was evaluated and in what population(s). In close to a third, there was little attention to whether tools used have been tested. Given that self‐report instruments cannot be expected to perfectly capture true intake, more nuanced discussions of what it means for a tool to be ‘valid’ as well as the implications of limitations in tools for study results appear warranted. Such discussions are key to improving the quality of self‐reported dietary intake data.Support or Funding InformationThis scoping review was supported by the Canadian Institutes of Health Research (137238) and Canadian Cancer Society Research Institute (702855).
Disease Associated Polymorphisms in MnSOD and GPx‐1 Affect Metabolism, Mitochondrial Membrane Potential and Expression of Signaling Proteins
Authors: Ekoue Dede N , Bera Soumen , Ansong Emmanuel , Hart Peter , Macias Virgilia , Kajdacsy‐Balla Andre , Bonini Marcelo , Diamond Alan M 
Published: November 2023

MnSOD detoxifies superoxide and impacts tumor biology by generating H2O2 which can diffuse through the mitochondrial membrane and affect metabolism and apoptosis. The selenium‐dependent enzyme GPx‐1 localizes to both the cytoplasm and the mitochondria and reduces H2O2 to water and may therefore modulate the impact of MnSOD on carcinogenesis. A val to ala polymorphism in codon 16 of the MnSOD gene has been shown to be associated with increased prostate cancer risk in men with the lowest level of dietary antioxidant intake and individuals who consumed less dietary antioxidants, including selenium, had the greatest risk of prostate cancer. A polymorphism in the GPx‐1 gene resulting in a leucine (L) instead of a proline (P) at position 198 has been reported to be associated with elevated cancer risk. To examine the molecular mechanism behind the epidemiological observation that genotypes in GPx‐1 gene modify elevated risk of cancer associated with MnSOD genotypes, MCF‐7 human breast cancer cells null for GPx‐1 and having negligible levels of endogenous MnSOD were transfected with GPx‐1 and MnSOD allele‐specific expression constructs to determine outcomes related to cellular signaling and metabolism. MnSOD and GPx‐1 alleles differentially interacted to modulate the expression of the anti‐oxidant stress response regulator Nrf2, the cell adhesion protein E‐Cadherin, the cell signaling protein pAkt, the anti‐apoptotic protein Bcl‐2 and the mitochondria located deacetylase Sirt3. Also, co‐expression of the GPx‐1A7L and either MnSODval or MnSODala increased oxidative phosphorylation as measured by O2 uptake using the Seahorse XF24 XF analyzer, which simultaneously determines relative mitochondrial respiration and glycolysis. In order to assess whether GPx‐1 and MnSOD allelic variants modulate mitochondrial membrane potential, CMX‐ROS fluorescence was measured. Independent and irrespective of which allele was evaluated, MnSOD and GPx‐1 individually decreased mitochondrial potential as compared to that seen using MCF‐7 control cells. In addition, co‐expression of GPx‐1A7L with either MnSODval or MnSODala further decreased membrane potential above that observed for either MnSOD and GPx‐1 alone. In order to determine if MnSOD and GPx‐1 levels are associated with a higher risk for biochemical recurrence of prostate cancer after radical prostatectomy, immunohistochemistry of human prostate tissue cores will be performed. Preliminary results indicate that a high MnSOD/GPx‐1 ratio was observed in prostate cancer tissue compared to adjacent normal tissue.Support or Funding InformationThis research was supported by the National Cancer Institute of the National Institutes of Health under Award Number R21CA182103 awarded to AMD and DNE.
Overexpression of Ghrelin Is Associated with Poor Prognosis of Renal Cell Carcinoma and Promotes Metastasis through GHSR‐mediated Activation of AKT‐Snail Pathway
Authors: Lin Tsung‐Chieh , Hsu Shih‐Lan , Hsiao Michael 
Published: November 2023

Loss of cell‐cell adhesion, increased cell motility, and extracellular matrix (ECM) degradation are critical factors in cancer cell metastasis. In this study, we identified ghrelin as a pro‐metastasis molecule in renal cell carcinoma. Ghrelin is an appetite‐regulating molecule that promotes growth hormone (GH) release and food intake through growth hormone secretagogue receptor (GHS‐R). Ghrelin expression is observed in proximal and distal renal tubules, where renal cell carcinoma (RCC) arises. However, whether ghrelin is up‐regulated and promotes renal cell carcinogenesis remains unclear. In this study, we found ghrelin was highly expressed in renal tumours, especially in metastatic RCC. In addition, high ghrelin levels correlated with poor outcome, lymph node and distant metastasis. Our results also showed the addition of ghrelin promoted the migration ability of RCC cell lines 786–0, ACHN and A‐498. Furthermore, knockdown of ghrelin expression reduced in vitro migration and in vivo metastasis, suggesting a requirement for ghrelin accumulation in the microenvironment for RCC metastasis. Analysis of microarray signatures using Ingenuity Pathway Analysis (IPA) and MetaCore pointed to the potential regulation by ghrelin of Snail, a transcriptional repressor of E‐cadherin. We further observed that Ghrelin increased the expression, nuclear translocation and promoter‐binding activity of Snail. Snail silencing blocked the ghrelin‐mediated effects on E‐cadherin repression and cell migration. Snail–E‐cadherin regulation was mediated by GHS‐R‐triggered Akt phosphorylation at Ser473 and Thr308. Pretreatment with PI3K inhibitors, LY294002 and wortmannin, as well as Akt siRNA, decreased ghrelin‐induced Akt phosphorylation, Snail promoter binding activity and migration. Taken together, our findings indicate that ghrelin can activate Snail function via the GHS‐R–PI3K–Akt axis, which may contribute to RCC metastasis.(This study was supported by Academia Sinica to Dr. Michael Hsiao.)
Ischemia/reperfusion‐induced myocardial injury in mice with diabetes mellitus: role of silent information regulator 1
Authors: Tao Aibin , Mele Tina , Kao Raymond , Martin Claudio , Rui Tao 
Published: November 2023

The aims of this study is to determine whether silent information regulator 1 (Sirt1) is involved in the increased susceptibility of the diabetic myocardium to ischemia/reperfusion‐induced (I/R) injury.MethodsIn vivo: mouse model of diabetes was induced by streptozotocin and myocardial levels of Sirt1 assessed (Western). In vitro: isolated cardiomyocytes were conditioned with high glucose (HG) followed by anoxia/reoxygenation (A/R) challenge. Myocyte Sirt1, Dynamin‐related protein 1 (Drp1) expression (Western) and myocyte apoptosis (Caspase 3 activity and cell death ELISA) were assessed.ResultsMyocardial levels of Sirt1 were decreased in mice with diabetes. Sirt1 expression in myocytes with HG was down‐regulated. Myocytes with HG incurred reduced Drp1 S637 phosphorylation and increased apoptosis as compared to naive myocytes challenged with A/R. The effects were prevented by pretreatment of the myocytes with Sirt1 activator or over‐expression of Sirt1 in cardiomyocytes with HG.ConclusionIncreased vulnerability of diabetic myocardium to I/R injury may be attributed to decreased Sirt1 and subsequent Drp1 activation. (*Corresponding author)Support or Funding InformationIRF of Lawson Health Research Institute (IRF 2014‐25); National Natural Science Foundation of China (81370333); Natural Science Foundation of Jiangsu Province, China (BK2015‐1332)
Different Duration of Diet Transitions from a High‐fat Diet to a Normal‐fat Diet before Pregnancy Deferentially Affect the Phenotypes of Offspring Obesity with a Sex‐dependent Manner
Authors: Fu Qiang , Zhou Yi , Xu Huiting , Olson Patrick , Xie Linglin 
Published: November 2023

It is now well established that in utero and in early life exposure to under‐nutrition or over‐nutrition can disrupt normal growth and development and thus results in a higher risk for offspring obesity in adult life. Therefore, important information/evidence is urgently needed regarding if and how a pre‐pregnancy healthy diet strategy would be beneficial to obese women or women who have been on long‐term unhealthy western‐style diet on pregnancy outcomes. Unfortunately, no evidence‐based strategy regarding the optimal duration of the diet intervention for the women at childbearing age is currently available. We used a murine model to study whether switching from a high‐fat diet to a normal‐fat diet (H1N group) 1 week, 5 weeks (H5N group) or 9 weeks (H9N group) before pregnancy could lead to in utero reprogramming of female offspring obesity; comparator groups were offspring given a consistent maternal high‐fat diet (HF group) or normal‐fat diet (NF group) until weaning. Another group of offspring (the REF group), which were fed the control diet and were born to breeding pairs given the control diet, served as the reference group to show the normal ranges for a given characteristic. After weaning, all offspring were given the high‐fat diet for either 9 or 12 weeks before killed humanely. The female offspring of H1N dam were obese and the female offspring of HF and H5N dams were overweight, while the NF and H9N female offspring slowly gained body weight during experimental period and were only lightly but significantly higher than REF female offspring at week 12. However, only male offspring from H1N group, but not other groups, were obese; and the HF male offspring slowly gained body weight and was heavier than H5N, H9N NF or REF at week 12. There were significantly enlarged subcutaneous fat and gonadal fat pads in H1N male offspring versus male from any other dams. For female, only H1N offspring, but not other groups, enlarged gonadal fat pads, but not subcutaneous fat pad. We performed IPGTTs of the offspring at the end of week 9 and week 12 of the postweaning HF diet. At both time points, female HF, H1N and H5N, but not NF and H9N offspring were glucose intolerant. However for male, only H1N and H5N, but not NF, HF or H9N offspring were glucose intolerant. In addition, the glucose level of H5N male offspring was unable to return to basal level, suggesting a high risk for diabetes. In summary, our data suggested that a short term transition (H1N and H5N) were not beneficial to reduce offspring obesity, however a longer tern transition (H9N) reduced the risk for offspring obesity and the phenotypes of obesity were gender dependent.Support or Funding InformationThis study is supported by grants from the National Institutes of Health (NIH‐1R15HL117238 to LX and the American Heart Association (Scientist Development Grant13SDG14650009 to LX).
Regulation And Function Of Fatty Acid Desaturases
Authors: Ntambi James , Burhans Maggie S. , Guo Chang‐An , Bond Laura M. 
Published: November 2023

Stearoyl‐CoA desaturase is a central lipogenic enzyme catalyzing the synthesis of monounsaturated fatty acids mainly oleate (C18:1) and palmitoleate (C16:1) which are the major monounsaturated fatty acids of membrane phospholipids, triglycerides, wax esters and cholesterol esters. Several SCD gene isoforms (SCD1‐4) exist in the mouse. While SCD1, 2 and 4 desaturate both 16:0 and 18:0 to 16:1n7 and 18:1n9 respectively, the SCD3 isoform has a substrate specificity and prefers desaturation of 16:0 to 16:1n7. 16:1n7 has been labeled as a lipokine that represses hepatic de novo lipogenesis and improves insulin signaling in muscle. We found that mice with a targeted disruption of the SCD3 isoform (SCD3−/−) exhibit dramatic brown adipose tissue (BAT) expansion and whitening with paradoxical increase in monounsaturated fatty acids and triglyceride accumulation. The alteration in fatty acid composition and lipid metanbolism causes reduced abundance of electron transport chain components and near ablation of UCP1 in BAT. Interestingly, this decreased protein abundance is not driven by repressed gene transcription and likely stems from protein instability and degradation. Consequently, the SCD3−/− mice have impaired cold tolerance and cannot maintain core body temperature during a 4ºC cold challenge past 6 hours. Meanwhile, the subcutaneous WAT of the KO mice shows increased expression of genes associated with fatty acid oxidation and thermogenesis. These observations suggest that SCD3 expression plays distinct roles in BAT and subcuteneous fat depots and help to elucidate how changes in monounsaturated fatty acids modulate metabolic activities in adipocytes.Support or Funding InformationSupported by NIH grants RO1DK62388 and T32 GM07215.
How Different Are We? Performing Formalin Fixed Paraffin Embedded Tissue Immunohistochemistry Across Species.
Authors: Gibson‐Corley Katherine N. , Ofori‐Amanfo Georgina , Leidinger Mariah R. , Lambertz Allyn M. 
Published: November 2023

The Comparative Pathology Laboratory (CPL) at the University of Iowa is affiliated with both a teaching hospital and a research university, which provides the opportunity to work with tissues from humans and a variety of research animals, including mice, rats, ferrets, rabbits, sheep and pigs. The CPL has developed procedures for immunohistochemical (IHC) antibodies on organisms for which the antibody has not previously been validated. In many instances, non‐standard research organisms are not referenced on antibody datasheets. Peer‐reviewed journal articles are referenced, but infrequently mention the organism and tissue we seek to study. The CPL utilizes Basic Local Alignment Search Tool (BLAST) software to compare antibodies against the organism of interest. BLAST comparisons between the two genetic sequences guide us to the antibody with the greatest probability of success. From years of experience, education, and experimentation, the CPL has developed guidelines for each animal of interest including the most successful blocking reagents and antigen retrieval methods. Since each antibody is unique, the CPL has also developed troubleshooting guidelines based on the IHC output which will be outlined. If a genetically similar antibody can be located, the CPL can create an IHC protocol using a limited number of variables to create a quality product: appropriate positive control tissue, antigen retrieval method, protein block, and primary dilution.Support or Funding InformationInternal funding; Department of Pathology, University of Iowa