bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic Reviews of Current Literature Fail to Establish Dietary Benzo[a]pyrene, Heterocyclic Aromatic Amines, or Heme Iron as Mechanisms Linking Red and Processed Meat Consumption with Cancer Risk
Authors: Kuratko Connye , Dunaif George E , Coughlin James R , Weatherford Charli A , Van Elswyk Mary E , McNeill Shalene 
Published: November 2023

Dietary exposure to potentially high‐risk compounds such as heterocyclic aromatic amines (HAAs) or the polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP), formed in meat during cooking, or from exposure to hemeiron naturally occurring in meat, have all been proposed as possible mechanisms responsible for the reported weak association between red and processed meat consumption and increased cancer risk in observational studies. In this study, a systematic review of the mechanistic literature was used to examine the available evidence‐base to determine if sufficient evidence exists to link heme iron, BaP, or HAAs from red and processed meat to increased cancer risk. Inclusion criteria required that study designs accommodate exposure from a whole food or in the context of a well‐described diet and that outcomes adequately represent normal physiology of the tissue of interest. Results regarding dietary Ba Prevealed, of 51 studies published since 2000, only 4 met the full criteria for inclusion. The primary reasons for study exclusion were a failure to evaluate effects of BaP administered orally or as part of a diet and a failure to adequately represent non‐cancerous tissue physiology. Regarding dietary HAAs, of 294studies published since 2000, 29 publications met the full criteria for inclusion. Only 3 of the included studies utilized an animal model to investigate HAA intake from foods or as part of a well‐described diet and only one type of HAA was evaluated in the included animal studies. In the human studies there was near‐exclusive use of a single, non‐comprehensive database, rather than actual and/or direct analytical measurement of dietary HAAs. And regarding dietary heme iron, of 210 search results since 2000, only 13publications met the full criteria for inclusion. The type of heme iron supplemented in animal diets, as surrogates for naturally occurring heme iron, were found to independently affect the outcomes in some studies. The use of hemeiron surrogates has not been systematically validated against naturally occurring heme iron. For all compounds, the exclusive use of carcinogen‐treated animals was questioned as well as the use of in vitro cytotoxicity assays as surrogates for normal colon physiology. In each case, evidence was found to be weak and inadequate in both humans and animals concerning the mechanistic relationship between the dietary exposures of BaP, HAAs, or heme iron and human cancer.Support or Funding InformationSupport from the Beef Checkoff
Excess dietary iron modulates intestinal tumorigenesis
Authors: Glosser Logan , Swain James 
Published: November 2023

Research on dietary iron in humans has primarily focused on prevention of anemia and common diseases associated with iron deficiency. However, due to the prevalence of iron‐fortified and high iron content foods, especially within the United States, research increasingly is concerned with possible deleterious health effects of excess iron intake. One such effect may be altered cancer risk and/or progression. To determine the effect that excess dietary iron may have on tumor growth, we used weanling Apcmin+/− mice – a model of human familial adenomatous polyposis coli ‐ to study the effect of feeding mice for 10‐weeks one of three diets, modified based on iron content: as 1) normal (45 mg/kg), 2) moderately high (225 mg/kg), and 3) high iron (450mg/kg). Intestinal tissue sections from the jejunum, duodenum, and the ilium were collected. Morphological analysis included measurements of total tumor number and tumor surface area (i.e. tumor burden). Histological evaluation for Ki‐67‐ a proliferative marker protein – was conducted to visualize pertinent cells within full‐height, well‐oriented, villi were analyzed. Data show that when mice consumed the high iron diet (Group 3) total tumor number and surface area ‐ combined from all three intestinal sections ‐ increased approximately 2‐fold (p<0.05) in comparison to the moderate and low iron diets (Groups 1 and 2). Immunohistochemical analyses using Ki‐67 illustrated that the percentage of stained cells increased approximately five‐fold when comparing the high iron diet (group 3) vs. the normal (or adequate) iron diet (group 1). Overall, findings suggest that excess dietary iron may adversely affect health by promoting intestinal tumorigenesis.Support or Funding InformationSupported in part via CWRU CTSA Grant Number UL1 RR024989 NCRR/NIH (JS) and SAGES Capstone Resource Grant (CWRU; LG)
Metabolic Responses to a Traditional Mexican versus commonly consumed U.S. Diet among Women of Mexican Descent: A Randomized Crossover Feeding Trial
Authors: Santiago‐Torres Margarita , Kratz Mario , Lampe Johanna W , De Dieu Tapsoba Jean , Breymeyer Kara L , Levy Lisa , Villaseñor Adriana , Wang Ching‐Yun , Song Xiaoling , Neuhouser Marian L 
Published: November 2023

BackgroundMexican immigrants are disproportionally affected by diet‐related risk of metabolic dysfunction. Whether adhering to a traditional Mexican diet or adopting a U.S. diet contributes to metabolic changes associated with future risk of type 2 diabetes (T2D) and other chronic diseases has not been investigated.ObjectiveTo test in a randomized crossover feeding trial the metabolic responses to a Mexican versus a commonly consumed U.S. diet.DesignFirst and second generation, healthy women of Mexican descent (n=53) were randomized in a crossover design to consume a Mexican or U.S. diet for 24 days each, separated by a 28‐day washout period. Diets were eucaloric and similar in macronutrient composition. The metabolic responses to diets were assessed by measuring fasting serum concentrations of glucose, insulin, IGF‐1, IGFBP‐3, adiponectin, CRP and IL‐6 as well as the homeostasis model assessment insulin resistance (HOMAIR) at the beginning and end of each period. Linear mixed models tested the intervention effect on the biomarkers, while adjusting for diet sequence, feeding period, baseline and washout biomarker concentrations, age, acculturation and BMI.ResultsCompared to the U.S. diet, the Mexican diet reduced insulin by 14% [geometric means (95% CI), 9.3 (8.3, 10.3) vs. 8.0 (7.2, 8.9) μU/mL; P = 0.02], HOMAIR by 15% [2.0 (1.8, 2.3) vs. 1.7 (1.6, 2.0); P = 0.02], and IGFBP‐3 by 6% (mean ± SEM, 2,420 ± 29 vs. 2,292 ± 29 ng/mL; P < 0.01), and tended to reduce circulating concentrations of IGF‐1 by 4% (149 ± 2.6 vs. 144 ± 2.5 ng/mL; P = 0.06). There was no significant intervention effect on serum concentrations of glucose, adiponectin, CRP or IL‐6 in the U.S. versus Mexican diet.ConclusionsCompared to the U.S. diet, the traditional Mexican diet modestly improved insulin sensitivity under conditions of weight stability, while having no impact on biomarkers of inflammation among healthy women of Mexican descent.Support or Funding InformationThis work was supported by the National Cancer Institute (NCI) grant P50 CA148143 and the Cancer Center Support Grant P30CA 015704. M. Santiago‐Torres is currently supported by grant R25 CA094880 from the NCI.The trial was registered at clinicaltrials.gov (identifier: NCT01369173)
Sulforaphane Bioavailability and Chemopreventive Activity in Women Scheduled for Breast Biopsy
Authors: Atwell Lauren L , Zhang Zhenzhen , Mori Motomi , Farris Paige E , Vetto John T , Naik Arpana M , Oh Karen Y , Thuillier Philippe , Ho Emily , Shannon Jackilen 
Published: November 2023

Epidemiological studies suggest a protective effect of cruciferous vegetables on breast cancer. Sulforaphane (SFN), an active food component derived from crucifers, has been shown to be effective in breast cancer chemoprevention. This study evaluated the chemopreventive effect of SFN on selective biomarkers from blood and breast tissues. In a 2–8‐week double‐blinded, randomized controlled trial, 54 women with abnormal mammograms and scheduled for breast biopsy were randomized to consume a placebo or a glucoraphanin (GFN) supplement providing SFN or placebo (n = 27). Plasma and urinary SFN metabolites, peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity, and tissue biomarkers (H3K18ac, H3K9ac, HDAC3, HDAC6, Ki‐67, p21) were measured before and after the intervention in benign, ductal carcinoma in situ (DCIS), or invasive ductal carcinoma (IDC) breast tissues. Within the supplement group, Ki‐67 (p = 0.003) and HDAC3 (p = 0.044) levels significantly decreased in benign tissue. Pre‐to‐post‐intervention changes in these biomarkers were not significantly different between treatment groups after multiple comparison adjustment. GFN supplementation was associated with a significant decrease in PBMC HDAC activity (p = 0.04). No significant associations were observed between SFN and examined tissue biomarkers when comparing treatment groups. This study provides evidence that GFN supplementation for a few weeks is safe but may not be sufficient for producing changes in breast tissue tumor biomarkers. Future studies employing larger sample sizes should evaluate alternative dosing and duration regimens to inform dietary SFN strategies in breast cancer chemoprevention.Support or Funding InformationNCI: R21 CA132236‐01A2, P01 CA090890, P30 CA069533NCATS: UL1TR000128NIEHS: P30 ES000210
The Long‐Term Influence of Nutrition Intervention on Nutritional Status and Survival in Digestive Cancer Patients
Authors: Li Pei‐Rong , Wen Cheng‐Fan , Chi I‐Chen , Chen Tsung‐Ming 
Published: November 2023

BackgroundThe previous study showed cancer patients were the highest incidence of malnutrition. Nutritional statuses of 75% cancer patients were worse during hospitalization. The digestive cancers which were higher prevalence of malnutrition included stomach cancer (65–58%), colorectal cancer (57%), esophageal cancer (80–83%). Head and neck cancer pa tients with dysphagia or/and odynophagia since the side effects of treatment and tumor location were poor intake. Approximately 30–50% of head and neck cancer patients had a problem of weight loss. It was difficult to evaluate the improved nutritional status after nutrition intervention in a short period of hospitalization. The purpose of study was to investigate whether nutritional intervention could improve long‐term nutritional status for digestive and head and neck cancer patients.MethodsThis was a retrospectively observational study. The medical records of digestive and head‐neck cancer patients receiving nutritional intervention during hospitalization were reviewed (n=133). Patients’ anthropometric measurements and blood biochemical parameters were recorded before and after nutritional intervention for one year later (data were between 180 to 400 days after nutritional intervention, the closest 365 days). The patients were further tracked three‐year survival.ResultPatients’ BMI (Body Mass Index) was significantly reduced one year later after nutritional intervention (23.9±5.4 vs. 22.9±4.9 kg/m2, p=0.002), but it was still within the standard range (18.5≦BMI<24). There were no significant differences in blood biochemical parameters related nutrition. Patients were further allocated into two groups, albumin≦3.0 group or albumin>3.0 group based on albumin level before nutritional intention. It was showed patients’ albumin significantly enhanced in albumin≦3.0 group (p=0.035) and significantly reduced in albumin>3.0 group (p=0.003). It is positively correlation between improving patient albumin percentage with patients’ survival.ConclusionsThe long‐term nutritional status of digestive and head‐neck cancer patients with albumin≦3.0 could be improved by nutritional intervention, perhaps resulting in improved survival. Albumin≦3.0 could further be used as an indicators of nutritional intervention.
Health Behaviors of Breast Cancer Survivors Compared to the General Population: A Cross‐sectional Analysis of a diverse population
Authors: Kim Hyunju , Caulfield Laura 
Published: November 2023

A breast cancer diagnosis can be a potential ‘teachable’ moment as individuals may be particularly motivated to make positive behavior changes. However, it remains unclear whether breast cancer survivors’ smoking, diet, physical activity and weight status differ from those of the general population. There is also a lack of research on racially and ethnically diverse groups. The objective of this study was to compare health behaviors of breast cancer survivors to the general female population using a diverse state‐wide survey. We assessed four health behaviors (current smoker, ≤5 servings of fruits and vegetable intake per day, physical inactivity and overweight/obesity) of 1,028 breast cancer survivors and 23,869 females without a history of breast cancer in the 2005California Health Interview Survey (CHIS). We conducted multivariate logistic regression analyses adjusting for race/ethnicity, age, education, income, nativity, current insurance status and marital status. All models included sampling weights. Breast cancer survivors had significantly lower odds of smoking (OR= 0.39, 95% CI: 0.21, 0.74), but higher odds of physical inactivity (OR= 1.27, 95% CI: 1.01, 1.60) compared to those without a history of breast cancer. Non‐Hispanic White and Other race (Pacific Islander, American Indian, other single/multiple race) cancer survivors had significantly higher odds of inactivity (ORwhite=1.36, 95% CI: 1.05, 1.74; ORother=6.32, 95% CI: 1.38, 28.90). No significant associations were observed for dietary intake or weight status. In a large diverse sample, breast cancer survivors were less likely to smoke or exercise than non‐cancer controls. Some groups were particularly vulnerable to physical inactivity. Culturally sensitive health promotion interventions which focus on improving physical activity levels of breast cancer survivors are needed.Support or Funding InformationNone
Delta‐Tocotrienol Dose‐Dependently Decreased Adiposity and Inflammation and Increased Markers of Lipid Oxidation in High Fat Fed Mice
Authors: Allen London Tashae , Ramalingam Latha , Shen Chwan‐Li , Tomison Michael D , Kaur Gurvinder , Dufour Jannette , Chung Eunhee , Moustaid‐Moussa Naima 
Published: November 2023

Obesity is a disease that affects one in three American adults. Inflammation has been established as a major underlying basis for obesity and related chronic disorders. Several plant bioactive compounds with anti‐inflammatory properties have been used to reduce obesity and associated metabolic complications. Hence we are investigating the effect of delta‐tocotrienol (δT3), a member of the vitamin E family as an anti‐obesity agent. We hypothesize that δT3 will reduce obesity and insulin resistance through its anti‐inflammatory and anti‐oxidant properties. To test our hypothesis, we used C57BL/6J male mice that were fed a high fat diet (HF) with and without supplementation of increasing levels of delta‐tocotrienol (HF+δT3) up to 1,600mg/kg for 14 weeks. Glucose and insulin tolerance tests were administered two weeks prior to the end of treatments. Serum and tissues including adipose tissue were collected at the end of the study. Our results show significant improvements in glucose clearance in the δT3‐supplemented groups compared to the HF group. Fat pad weights were reduced dose‐dependently by δT3. These changes were also associated with smaller fat cell size and reduced crown like structures macrophages in adipose tissue histology sections from HF+δT3 compared to HF‐ fed mice. We also performed mechanistic analyses that revealed reduction of mRNA and protein expression of pro‐inflammatory adipokines (e.g. resistin, leptin, and MCP‐1) and increased expression of anti‐inflammatory adipokines (e.g. adiponectin and IL‐10 in HF+δT3 compared to HF‐fed mice. Moreover, δT3 dose‐dependently increase fatty acid oxidizing gene. In summary, dietary delta‐tocotrienol exerted promising anti‐obesity and anti‐inflammatory effects that may be mediated in part by adipose tissue.Support or Funding InformationSupported by a research grant from American River Nutrition, Inc.
Digital Gene Expression (DGE) Analysis of Nutritional Pancreatic Atrophy of Chicks Induced by the Se/Vitamin E Deficiencies
Authors: Huang Jia‐Qiang , Wang Yun‐Yun , Wang Qing‐Yu , Xiao Cheng , Ren Fa‐Zheng , Lei Xin Gen 
Published: November 2023

Nutritional pancreatic atrophy (NPA) is a classical Se/vitamin E deficiency disease of chicks. We previously determined responses of mRNA abundances of 25 selenoprotein genes in various tissues of chicks to the deficiencies of these two nutrients. The present DGE analysis was performed to reveal effects of dietary Se/vitamin E deficiencies on the pancreatic transcriptome of chicks and to identify global gene association with the NPA. We fed 4 groups of day‐old broiler chicks (n = 40/group) with a corn‐soy basal diet (BD: 10 μg Se/kg, no vitamin E added), the BD plus all‐rac‐a‐tocopheryl acetate at 50 mg/kg, Se (as sodium selenite) at 0.3 mg/kg, or both of these nutrients for 6 wk. High incidences of NPA (70%) and mortality (35%) of chicks were induced by BD, starting at wk 3. Both NPA incidences and mortality were prevented by dietary Se supplementation. On day 18, chicks were killed to collect pancreases for the DGE analysis. Pancreatic RNA samples were pooled from five individual chicks into each of the four dietary groups, respectively. Dietary Se deficiency altered expression of 884 unigenes, with 360 unigenes up‐regulated and 524 unigenes down‐regulated. Of the differentially expressed genes, 530 unigenes were annotated and 65 were classified into metabolism pathways. Real‐time PCR analyses of selected four unigenes related to selenocompound metabolic and apoptotic pathways showed consistent results with those obtained from the DGE analysis, which confirms the quality of the sequencing data for further gene expression characterization. In conclusion, our pancreatic transcriptiom data of the chicks fed the four experimental diets will facilliate mechanistic investigation on the pathogenesis of NPA induced by the dietary Se/vitamin E deficiencies.Support or Funding Information(This research is supported in part by a NSFC grant #31320103920).
Potential Role of the 15kDa Selenoprotein in Colorectal Inflammation
Authors: Peters Kristin M , Carlson Bradley A , Garrett Katie N , Canter Jessica A , Tobe Ryuta , Seifried Harold E , Yu Yunkai , Cao Liang , Gladyshev Vadim N , Davis Cindy D , Hatfield Dolph L , Tsuji Petra A 
Published: November 2023

The micronutrient selenium (Se) exerts its mechanistic effects largely through incorporation into selenoproteins. The 15kDa selenoprotein (Sep15) is thought to be involved in regulation of protein folding, as well as in cell homeostasis as an oxidoreductase. Previous results suggest that Sep15 deficiency is protective against formation of pre‐neoplastic lesions in colon epithelia, possibly due to increased interferon‐γ‐regulated gene expression, suggesting a role for Sep15 in inflammation. Currently, we are examining Sep15 knockout (KO) mice and littermate controls that were maintained on Se‐deficient (0.02 ppm) or Se‐adequate (0.1 ppm) diets, as Se‐deficiency itself results in upregulation of inflammation‐associated gene expression. Treatment with 2% dextran sulfate sodium (DSS) in drinking water for one week was used to induce colitis. To examine the role of Sep15 and dietary Se in inflammation, serum and spleens were collected, and mRNA and protein were isolated from colon epithelial tissues and spleens. Gene expression is being analyzed by microarray analyses, quantitative RT‐PCR, ELISA and Western blotting. Preliminary results show that serum interleukin‐6 levels were increased in Sep15 KO mice compared to controls, independent of Se and DSS treatment. In contrast, serum interferon‐γ was significantly higher in Sep15 KO mice compared to littermate controls under Se‐deficient conditions, but decreased under Se‐adequate conditions. The contribution of other cytokines is currently being assessed. Microarray analyses of colon epithelia showed that mRNA expression of the seven top up‐regulated genes in Sep15 KO mice were changed regardless of DSS treatment. These genes are known to be involved in immune and pro‐inflammatory responses. Inflammation‐related gene expression in spleens is currently being assessed; however, spleen mass as percent of body weight did not change significantly between control and Sep15 KO mice, dietary Se, or DSS treatment. Thus, our preliminary analyses indicate that Sep15 may influence the expression of and changes in pro‐inflammatory genes, and that Sep15 may be involved in the regulation of inflammatory responses.Support or Funding InformationNCI Intramural support; NIH CA080946 (VNG); Office of Dietary Supplements; Towson University Jess & Mildred Fisher Endowed Chair (PAT)
Formate: A New Frontier in Fetal One‐Carbon Metabolism
Authors: MacMillan Luke , Harnett Brian J , Quilty Rebecca , Tingley Garrett , Brosnan Margaret E. , Brosnan John T. 
Published: November 2023

For years the significance of formate in one‐carbon metabolism has been underappreciated. It is known that formate can be produced by the mitochondria and incorporated into the cytosolic tetrahydrofolate pool where its carbon is used for three canonical processes i) purine synthesis ii) thymidylate synthesis and iii) transmethylation reactions. Our lab has recently reported on elevated levels of formate in the plasma of fetal and neonatal sheep which decline after birth (Washburn et al. 2015, AJP). We now report a similar phenomenon in rats where fetal rat pups at 19 ± 1 days gestational age have high levels of plasma formate (225 ± 42.1 μM) which decline after birth to normal adult levels by 4–5 weeks of age (60.8 ± 19.8 μM). In parallel with our sheep data, we find elevated formate concentration in the amniotic fluid taken from the fetal pups at day 19 of gestation.Infusion of 13C‐formate into pregnant rats showed that very little formate crosses the placenta suggesting that fetal formate is either produced by the placenta or synthesized in the fetus. We isolated placental mitochondria to determine their capacity for producing formate. Our results show that placental mitochondria are just as effective as liver mitochondria from both pregnant and non‐pregnant rats at producing formate from serine (Table 1).These data suggest a critical role for formate in fetal one‐carbon metabolism.Support or Funding InformationFunded by the Research and Development Corporation of Newfoundland and Labrador (RDC) and the Canadian Institutes of Health Research (CIHR).

Source of Mitochondria
Formate production (nmol formate/mg protein/10 mins)

Placenta
3.13 ± 2.11

Liver (Pregnant rat)
3.02 ± 3.77

Liver (Non‐Pregnant rat)
3.18 ± 0.84

Formate production from isolated mitochondria using serine as one‐carbon donor.