bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lycopene supplementation inhibited high‐fat diet‐promoted hepatic tumorigenesis in both wild‐type and beta‐carotene‐9’,10’‐oxygenase knockout mice (123.1)
Authors: IP Blanche , Liu Chun , Smith Donald , von Lintig Johannes , Wang Xiang‐Dong 
Published: June 2021

Obesity is associated with increased liver cancer risks, morbidity and mortality. A recent study (Ip et al., 2013) showed that apo‐10’‐lycopenoic acid, a lycopene (LYC) metabolite generated by beta‐carotene‐9’,10’‐oxygenase (BCO2), inhibited carcinogen‐initiated, high‐fat diet (HFD)‐promoted liver inflammation and tumor development. This present investigation examined whether LYC can suppress HFD‐promoted hepatic inflammation and tumorigenesis in BCO2‐knockout (BCO2‐KO) and the respective wild‐type (WT; 129SvJ/SvEvTac) mice. Results showed that 24‐week LYC supplementation (100 mg/kg diet) had similar effects on suppressing HFD‐promoted liver tumor incidence (by 19% vs 20%), number (by 56% vs 55%) and volume (by 96% vs 95%) in WT and BCO2‐KO mice, respectively. LYC chemopreventative effects were associated with reduced pro‐inflammatory signaling (NF‐κB p65, STAT3 phosphorylation; IL‐6 protein), F4/80 gene expression and inflammatory foci (p=0.06) in the livers of WT but not BCO2‐KO mice. On the contrary, protective effects of LYC in BCO2‐KO mice were associated with reduced endoplasmic reticulum stress‐mediated unfolded protein response (IRE1α, PERK signaling pathways) that is linked to increased liver cancer risks. Taken together, this data indicated that LYC can prevent HFD‐promoted hepatic tumorigenesis in mice, but may involve differential mechanisms depending on BCO2 expression.Grant Funding Source: USDA/ARS grant 1950‐51000‐074S
Nutritional modulation of cardiotoxicity and anti‐cancer efficacy related to doxorubicin chemotherapy by glutamine and n‐3 PUFAs (123.8)
Authors: Xue Hongyu , Ren Wenhua , Wischmeyer Paul 
Published: June 2021

Doxorubicin (DOX) has been one of the most effective antitumor agents against a broad spectrum of malignancies. However, DOX‐induced cardiotoxicity forms the major factor limiting the dose escalation of the drug. We here comparatively examined how glutamine and n‐3 PUFAs, when provided individually and in combination, would affect cardiotoxicity and anti‐tumor efficacy related to DOX (cumulative dose 12mg/kg) in a female Fisher rat model bearing mammary adenocarcinoma. Both single glutamine (0.5 g/kg/d) and n‐3 PUFA (EPA+DHA, 0.4g/kg/d) treatments prevented cardiac function deterioration, reducd serum cardiac troponin I levels, attenuated lipid peroxidation and preserved anti‐oxidant enzymatic reserve in the cardiac tissue. Single n‐3 PUFA treatment significantly enhanced anti‐tumor activity of DOX. Intriguingly, providing glutamine and n‐3 PUFAs together did not confer a greater benefit; conversely, individual benefits on cardiotoxicity and anti‐tumor efficacy associated with single treatments were instead partially or completely lost when the nutrients were combined. Both glutamine and n‐3 PUFA have the potential to be developed as novel individual adjuncts for DOX‐based chemotherapy, but may antagonize each other’s effects when combined. This work draws into question the common assumption that there are additive benefits of combinations of nutrients, which are beneficial on an individual basis.Grant Funding Source: American Society of Parenteral and Enteral Nutrition
Mexican children consuming breakfast and ready‐to‐eat cereals had a higher intake and adequacy of micronutrients than breakfast skippers: ENSANUT 2012 (130.4)
Authors: Villalpando Salvador , De la Cruz Gongora Vanessa , Contreras Manzano Alejandra , Beltran‐Velazquez Filiberto , Hervert‐Hernandez Deisy 
Published: June 2021

Mexican children consuming breakfast and ready‐to‐eat cereals had a higher intake and adequacy of micronutrients than breakfast skippers: ENSANUT 2012Salvador Villalpando1, Vanessa De la Cruz Gongora1, Alejandra Contreras Manzano1, Filiberto Beltran‐Velazquez2, Deisy Hervert‐Hernandez21Centro de Investigacion en Nutricion y Salud, Instituto Nacional de Salud Publica, Cuernavaca, México; 2Kellogg Company Mexico, Queretaro, Mexico Studies in children suggest that ready to cereal (RTEC) breakfast eaters are more likely to meet daily nutrient intake guidelines and less likely to be obese. Objective: To examine the nutrient intakes of Mexican children consuming RTEC breakfast, other type of breakfast or breakfast skippers . Methods: Dietary data from children aged 1‐11 years (n=4863) participating in the Mexican National Health and Nutrition Examination Survey (ENSANUT) 2012 were analyzed. Results: Overall, 90% and 86% of children aged 1‐4 and 5‐11 years of age, respectively, ate breakfast. For 1‐4 year old children, energy intakes did not differ among breakfast consumers and breakfast skippers. Children 5‐11 y breakfast consumers, had a higher intake of energy than breakfast skippers (p<0.05). Children who ate breakfast had a higher intake of vitamins A, B2, D, calcium and zinc (p<0.05) than breakfast skippers. Particularly, children who had a breakfast with RTEC had a higher intake of vitamins A, E, B1, B2, B3, B6, folate, iron, calcium and zinc (p<0.05) than children skipping breakfast or consuming other types of breakfast. Conclusion: Children eating breakfast and especially RTEC breakfast had a higher dietary micronutrients intake than breakfast skippers.Grant Funding Source: Supported by a non‐commited grant of Kellogg Company
A combination of Scutellaria baicalensis and Acacia catechu extracts for short‐term symptomatic relief of joint discomfort associated with osteoarthritis of the knee (134.2)
Authors: Elam Marcus , Ormsbee Lauren , Campbell Sara , Rahnama Nader , Payton Mark , Brummel‐Smith Ken , Daggy Bruce , Arjmandi Bahram 
Published: June 2021

The extracts of Scutellaria baicalensis and Acacia catechu have been shown in previous studies to alleviate joint discomfort, reduce stiffness, and improve mobility by reducing the production of proinflammatory molecules over long periods of supplementation. The acute effects of intake of these extracts have not yet been investigated. Thus, we carried out a one week clinical trial for the purpose of examining the extent to which a natural proprietary blend of S. baicalensis and A. catechu (UP446) decreases knee joint pain, mobility, and biomarkers of inflammation in comparison to naproxen. Seventy‐nine men and women (40‐90 years old) diagnosed as having mild to moderate osteoarthritis (OA) consumed either 500 mg/day of the UP446 supplement or 440 mg/day of naproxen for 1 week in a double‐blind randomized control trial. Pain, knee range of motion (ROM), and overall physical activity were evaluated at the start of treatment and at final. Fasting blood was collected for the determination of serum interleukins 1β and 6, tumor necrosis factor‐α, C‐reactive protein and hyaluronic acid with the use of enzyme‐linked immunosorbant assay. The UP446 group experienced a significant decrease in perceived pain (P = .009) time dependently. Stiffness was significantly reduced by both treatments (P = .002, P = .008, UP446 and naproxen, respectively). Significant increases in mean ROM over time (P = .04) were found in the UP446 group. These findings suggest that UP446 is effective in reducing the physical symptoms associated with knee OA.Grant Funding Source: Unigen, Inc.
Neuroinflammation and sickness induced by lipopolysaccharide in adult and aged mice are not mitigated by dietary broccoli (134.4)
Authors: Townsend Brigitte , Chen Yung‐Ju , Jeffery Elisabeth , Johnson Rodney 
Published: June 2021

Aging is associated with chronic neuroinflammation and a heightened neuroinflammatory response during infection resulting in prolonged sickness. Dietary interventions to reduce neuroinflammation are therefore desirable. Broccoli contains glucoraphanin, which is converted to sulforaphane (SFN) during digestion. SFN activates antioxidants including heme oxygenase 1 (HMOX1) and NAD(P)H quinone oxidoreductase (NQO1) and inhibits production of interleukin‐1 (IL‐1β) by lipopolysaccharide (LPS)‐stimulated microglia. Therefore, we hypothesized that dietary broccoli would support an antioxidant response in the brain and inhibit LPS‐induced neuroinflammation and sickness. Adult and aged mice were fed control diet or control diet with 10% broccoli for 4 wk, and then injected i.p. with saline or LPS. After injection social behavior was assessed at 2, 4, 8, and 24 h; and HMOX1, NQO1, and IL‐1β mRNA were quantified in brain at 24 h. LPS reduced social behavior and increased HMOX1, NQO1, and IL‐1β in adult and aged mice (P<0.04); as expected, in aged mice IL‐1β was higher before LPS (P<0.004), tended to be higher after LPS (P=0.11), and restoration of normal behavior took longer (P<0.03). No significant effects of broccoli consumption were evident. Collectively, the results suggest that dietary broccoli does not affect neuroinflammation or sickness in adult or aged mice.Grant Funding Source: Supported by NIH R01AG016710
Dietary α‐mangostin exacerbates colitis and adversely alters the gut microbiota in mice (134.7)
Authors: Gutierrez‐Orozco Fabiola , Thomas‐Ahner Jennifer , Berman‐Booty Lisa , Galley Jeffrey , Chitchumroonchokchai Chureeporn , Mace Thomas , Bailey Michael , Clinton Steven , Lesinski Gregory , Failla Mark 
Published: June 2021

Ulcerative colitis (UC) is characterized by chronic inflammation of the colon partly due to a dysregulated immune response to the gut microbiota. The use of complementary and alternative medicines among UC patients is prevalent. Despite the absence of clinical evidence, nutraceuticals containing mangosteen, a fruit from Southeast Asia, are marketed as beneficial for gut and immune health. We hypothesized that α‐mangostin (α‐MG), the most abundant xanthone in mangosteen, would ameliorate colonic inflammation. The effect of α‐MG on the gut microbiota of healthy mice was also assessed. Dextran sulfate sodium (DSS) was used to induce colitis in C57BL/6J mice fed AIN‐93 (control) diet or AIN‐93 diet with 0.1% α‐MG. Colitis was more severe in mice fed α‐MG than in controls. Mice fed α‐MG also had greater colonic infiltration of immune cells and colonic and systemic inflammation than controls. Interestingly, non‐DSS treated mice fed α‐MG also had increased colonic infiltration of immune cells and inflammation. Moreover, the gut microbiota of these mice had an increased abundance of Proteobacteria and decreased abundance of Firmicutes and Bacteroidetes. This bacterial profile is reminiscent of that seen in human UC. The exacerbating effect of α‐MG on colitis may be associated with its adverse impact on the gut microbiota. The potential for unintended effects of mangosteen products on gut health merits investigation.Grant Funding Source: MCC and FIC at OSU and Conacyt Fellowship (Mexico)
Targeted next‐generation sequencing of the 1‐carbon metabolism pathway: in search for novel genetic modulators of choline deficiency‐mediated organ dysfunction (135.4)
Authors: Corbin Karen , Parker Joel , da Costa Kerry‐Ann , Zeisel Steven 
Published: June 2021

We previously identified three functional single nucleotide polymorphisms (SNPs) that modulate sensitivity to dietary choline deficiency‐mediated organ dysfunction: CHDH rs12676, MTHFD1 rs2236225 and PEMT rs12325817. We aimed to broaden our understanding of the contribution of genetic aberrations in the 1‐carbon pathway to choline deficiency sensitivity. We performed targeted next‐generation sequencing on the following genes: ABCB4, BHMT, CBS, CHDH, CHKA, CHKB, MTHFD1, MTHFR, MTR, PCYT1A, PCYT1B, PEMT, SHMT1, SLC44A1, SLC5A7. The subjects in our study were divided into the following groups based on their response to a choline deficient diet: 1) did not exhibit symptoms of choline deficiency (n = 13); 2) had fatty liver and elevated liver enzymes (n = 15); 3) had elevated skeletal muscle creatine phosphokinase (n = 9). Although our study was underpowered, we identified a set of SNPs that are potential novel genetic modifiers of sensitivity to choline deficiency (primarily in PEMT and MTHFD1) and to organ‐specific deficiency symptoms (primarily in SLC44A1). Importantly, principal components analysis identified a set of SNPs that differentiated those who were sensitive to dietary choline deficiency vs. those that were not (PC1 p‐value = 0.018). Our results delineate candidate SNPs for differentiating individuals that are sensitive to dietary choline deficiency. These SNPs warrant further investigation.Grant Funding Source: NIH U24‐CA143848‐03; P30‐CA016086‐37; P50‐CA058223‐19A1 (JP)
Nutritional factors and non‐Hodgkin’s lymphoma survival in an ethnically diverse population: The Multiethnic Cohort Study (136.1)
Authors: Maskarinec Gertraud , Leo Qi Jie , Ollberding Nicholas , Kolonrl Laurence , Wilkens Lynne , Le Marchand Loic 
Published: June 2021

With an increasing number of non‐Hodgkin’s lymphoma (NHL) survivors, the possible effect of modifiable health behaviors on prognosis has emerged as a topic of interest. For example, obesity appears to be associated with poorer NHL survival. We examined the association of pre‐diagnostic intake of major food groups assessed by food frequency questionnaire at cohort entry with NHL‐specific survival in the five ethnic groups of the Multiethnic Cohort (MEC). MEC participants free of NHL at cohort entry and diagnosed with NHL during follow‐up (N=1348) were followed through linkages to SEER cancer registries and the National Death Index. Cox proportional hazards regression was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for low vs. high intake of meat, fish, vegetables, fruits, dairy, and legumes in relation to NHL‐specific mortality while adjusting for potential confounders including body mass index. The mean age at diagnosis was 70.6 (range 45‐89) years. During 4.3±3.5 years of follow‐up, 679 deaths including 457 NHL‐specific deaths occurred. Consumption of vegetables, fruits, meat, fish, and whole grains was not related to survival, but 蠅1 daily serving of dairy was associated with higher (HR=1.36, 95%CI=1.09‐1.70) and 蠅0.5 daily serving of legumes with lower (HR=0.66, 95%CI=0.49‐0.87) NHL‐specific mortality. Stratification by ethnicity suggested that these associations were limited to Latinos and Whites and not seen in African Americans, Native Hawaiians, and Japanese Americans. Despite the small number of foods associated with survival, the results suggest that diet may influence NHL outcome, possibly through phytanic acids, calcium, or vitamin D in dairy foods and the anti‐inflammatory action of legumes.Grant Funding Source: R37 CA 54281 and P01 CA 33619
Human obesity produces an inflammatory milieu in both the serum and colonic mucosa: implications for carcinogenesis (136.6)
Authors: Pfalzer Anna , Leung Keith , Garcia Paloma , Liu Zhenhua , Mason Joel 
Published: June 2021

Objective‐ Obesity elevates the risk of colon cancer; however, the molecular mechanisms responsible for this association remain speculative. Our lab has previously demonstrated that murine obesity elevates colonic TNFα and IL‐1β, each of which is known to activate important pro‐carcinogenic signaling pathways. We hypothesized that the low‐grade inflammatory state associated with obesity also exists in the human.Methods‐ Whole blood and colonic biopsies were collected from obese (BMI 蠅 30) and lean (BMI 蠄 25) human subjects undergoing routine colonoscopy. Serum and colonic cytokines were measured using chemiluminescence. Gene expression levels were measured using real‐time PCR.Results‐ Serum TNFα was increased 1.5‐fold and IL‐6 was increased approximately 2‐fold in obese subjects compared to lean (p<0.01). Colonic mRNA expression of IL1β was elevated 3.5‐fold in obese subjects compared to lean (p<0.05), whereas expression of TNFα, IL‐6 and IFNγ were not elevated. Protein expression of the cytokines was below the level of detection.Conclusions‐ In addition to confirming that pro‐inflammatory cytokines are elevated systemically in obese humans, we demonstrated that transcript expression for colonic IL‐1β is elevated as well. This increase in colonic expression of IL‐1β appears to be specific since similar elevations do not exist for other pro‐inflammatory cytokines.Grant Funding Source: Supported by: U.S.D.A. Pilot Project grant
Alterations in intestinal morphology, histology and permeability with exogenous glucagon‐like peptide 2 and epidermal growth factor treatment promote intestinal adaptation in neonatal intestinal failure (137.2)
Authors: Lim David , Levesque Crystal , Wales Paul , Vine Donna , Borthwick Faye , Nation Patrick , Wizzard Pamela , Josephson Jessica , Sigalet David , Bigam David , Li Julang , Turner Justine 
Published: June 2021

Background: The peptide factor, glucagon‐like peptide 2 (GLP‐2), augments intestinal adaptation in adults but its efficacy in neonatal short bowel syndrome (nSBS) is not established. GLP‐2 augments the epidermal growth factor (EGF) receptor pathway, suggesting an interactive role in the maintenance of gut health.Objective: To study the efficacy of exogenous GLP‐2 and EGF administration, alone and in combination, on intestinal adaptation and function in a translational piglet model of nSBS.Methods: Neonatal piglets (aged 3‐5 days) received one of 4 treatments (saline (n=3), GLP‐2 (n=3), EGF (n=6) and GLP‐2/EGF (n=3) in combination) for 7 days following a 75% mid‐intestinal resection or no resection (sham control). Structural adaptation was assessed by morphology and histology measures. Jejunal permeability of mannitol and polyethylene glycol (PEG) was assessed using Ussing techniques. A sow‐fed control group (n=6) was also used for comparison.Results: There was no difference in body weight gain or intestinal length between groups. In the resection group, intestinal weight per length increased with EGF treatment compared to saline treatment. Jejunum villus height increased with EGF or GLP‐2 treatment but not in combination, compared to saline treatment (p<0.0001). Combination therapy decreased both jejunum crypt depth compared to saline treatment and ileum crypt depth compared to GLP‐2 or EGF treatment (p<0.001). GLP‐2 alone reduced jejunal permeability of mannitol (p=0.0007) and PEG (p=0.0054) compared to the sham‐saline group. EGF alone increased the permeability of these markers compared to GLP‐2 treatment.Conclusions: Altogether, these findings illustrate a role for GLP‐2 and EGF therapy in intestinal adaption and function but perhaps not in combination. The combination of therapies appears to dampen the adaptive response histologically. The alterations in permeability suggest an improvement in barrier function with GLP‐2 and a promotion in mucosal growth with EGF.Grant Funding Source: Supported by: CIHR, ASPEN
Metabolomic profiling of zebrafish and mouse models of fetal alcohol spectrum disorder: antioxidants and neural‐related lipids (137.5)
Authors: Keller Christine , Sepúlveda Marisol , Jannasch Amber , Keller Jonathan , Roumani Ali , Zhou Feng , Brown Paul 
Published: June 2021

A comprehensive mechanistic profile of metabolite changes occurring in fetal alcohol spectrum disorder (FASD) has yet to be determined. Using zebrafish embryos exposed to 0 ‐ 3 % ethanol from 2 ‐ 24 hours post‐fertiliation, whole‐embryo extracts were examined using a Thermo Fisher LTQ Orbitrap coupled to an Agilent 1100 for liquid chromatography. From this data, we generated a profile of significantly changed metabolites resulting from ethanol treatment. While many of the metabolites have been identified previously, this approach emphasizes the alterations occurring in antioxidant vitamins A, D, and E as well as massive changes in neural‐related lipids such as phosphatidylserines, ceramide, and sphingosine. Additionally, a mouse model comparing 0, 1, or 2 six‐hour 400 mg/dL ethanol exposures were similarly analyzed. Metabolites from the non‐polar extracts of zebrafish and mice were compared, resulting in six significantly changed, commonly‐identified metabolites. These metabolites included short chain fatty acids, phosphatidic acid, and sulfatide. These metabolite profiles provide a more comprehensive understanding of ethanol‐induced changes during development and may lead to better biomarker identification or novel therapies for FASD.Grant Funding Source: Indiana Clinical and Translational Sciences Institute
Transgenerational transmission of bone deficits in growth restricted offspring (137.6)
Authors: Romano Tania , Anevska Kristina , Gallo Linda , Tran Melanie , Wark John , Wlodek Mary 
Published: June 2021

Uteroplacental insufficiency (UPI) reduces uterine blood flow leading to low birth weight offspring with programmed adult bone deficits. We investigated the effects of UPI on F1 maternal bone in pregnancy and if deficits are passed to F2 using embryo‐transfer (ET).UPI was induced by bilateral uterine vessel ligation (Restricted, R; Control, C) in rats. One cohort of pregnant F1 C and F1 R rats was culled on embryonic day (E) 20. ET was performed on E1 in a cohort of F1 females, with F2 embryos gestated in Control (C‐in‐C, R‐in‐C) or Restricted (C‐in‐R, R‐in‐R) mothers. Non‐ET offspring were also generated. Growth and pQCT femur analysis was performed.R F1 females were born 10% lighter than C with shorter femurs, lower bone content, density and strength. These differences were absent in pregnancy. F2 non‐ET offspring were born of normal weight and underwent slowed and accelerated growth without transmission of bone deficits. Day 35 male R‐in‐C and R‐in‐R were heavier with longer femurs, increased bone content and strength compared to C‐in‐C/R. Male R embryo groups had accelerated then slowed growth with increased cortical content at 6 months. Restricted ET females did not develop bone deficits.Deficits observed in non‐pregnant F1 R females were absent during pregnancy, indicating restoration of normal skeletal adaptations. Bone deficits are not passed on from a growth restricted mother to her offspring.
The heat shock protein 70 family members HSC70 and HSP70 play distinct roles in the hepatitis C viral life cycle (144.1)
Authors: Khachatoorian Ronik , Ganapathy Ekambaram , Ahmadieh Yasaman , Wheatley Nicole , Sundberg Christopher , Jung Chun‐Ling , Arumugaswami Vaithilingaraja , Raychaudhuri Santanu , Dasgupta Asim , French Samuel 
Published: June 2021

We have previously identified HSC70 in complex with viral NS5A along with other heat shock proteins. HSC70 has been reported to modulate HCV infectivity. Here, we further analyze the NS5A/HSC70 interaction biochemically and investigate the role of HSC70 in viral life cycle. We demonstrate that HSC70 knockdown significantly affects virus production with no cytotoxicity. We observed that HSC70 knockdown did not affect viral RNA replication and protein production. In fact, we found a slight, but statistically significant increase in viral RNA and protein levels likely caused by compensatory upregulation of HSP70, which we have previously shown to be required for viral protein production. NS5A‐augmented IRES‐mediated translation was also not inhibited by HSC70 knockdown and, rather, slightly increased. In contrast, we discovered that intracellular infectious virion assembly was significantly impaired by HSC70 knockdown. We also discovered that both HSC70 nucleotide binding and substrate binding domains directly bind NS5A. Thus, HSC70 and HSP70 play discrete roles in HCV viral life cycle which is further validated by our finding that knockdown of both HSC70 and HSP70 displays synergistic and dramatic reductions in virus production compared with knockdown of each alone. Investigation of these different functions may facilitate developing of novel strategies that target host proteins to treat HCV infection.Grant Funding Source: NIH R01DK090794, SWF; NIH AI084090, AD