bluuebunny/crossref_metadata_2025_split huggingface dataset:
Daily almond consumption (1.5 oz.) decreases non‐HDL and remnant lipoproteins in mildly hypercholesterolemic individuals
Authors: Berryman Claire E , West Sheila G , Bordi Peter L , Fleming Jennifer A , Kris‐Etherton Penny M 
Published: June 2021

Almonds independently improve total cholesterol, LDL‐C, HDL‐C, apo B, and apo A1, but their effects on emerging lipid risk factors are less well‐known. A randomized, 2‐period (6 wk/period), crossover, controlled‐feeding study was designed to investigate the effects of 1.5 oz./d almonds vs. a calorie‐matched, high CHO snack on CVD risk factors. Differences in nutrient profiles of the control (CON: 59% CHO, 15% PRO, 26% FAT, no almonds/d) and almond (ALD: 51% CHO, 16% PRO, 33% FAT, 1.5 oz. of almonds/d) diets were due to specific nutrients inherent to each snack and did not differ in saturated fat (~7%) or cholesterol (~110 mg/d). Subjects (n=53) were generally healthy adults (BMI 20–35 m/kg2) with elevated LDL‐C (50–95th percentile). Both diets decreased non‐HDL cholesterol (ALD: − 18.7 ± 2.5 and CON: −11.5 ± 2.6 mg/dl; P <0.01 for both); however, there was a greater decrease with ALD vs. CON (P <0.01). The diets had significantly different effects on remnant lipoproteins (ALD: −0.8 ± 1.1 vs. CON: 2.1 ± 1.1 mg/dl; P=0.02), but neither changed from baseline. Both diets reduced LDL1, LDL2, and LDL3 (ALD: −3.3 ± 0.7, −6.4 ± 1.4, −9.4 ± 1.6 and CON: −2.2 ± 0.7, −9.0 ± 1.4, −7.6 ± 1.7 mg/dl, respectively; P <0.01 for all), though there was a greater LDL2 reduction with CON vs. ALD (P=0.03). Almond consumption improves atherogenic lipoprotein subclasses, demonstrating cardiovascular risk reduction beyond established risk factors.Grant Funding Source: Almond Board of California
The interaction of tomato powder and soy germ on prostate carcinogenesis in the TRAMP model
Authors: Zuniga Krystle Erin , Smith Joshua W , Clinton Steven K , Erdman John W 
Published: June 2021

Epidemiological and laboratory studies support the hypotheses that diets rich in soy or tomato products may reduce the risk of prostate cancer (PCa). The objective of this study was to examine the efficacy of dietary tomato and soy germ, alone and in combination, for prevention of PCa in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Four week old, male C57BL/6 × FVB TRAMP mice (n=119) were randomized to consume: AIN‐93G control, 10% tomato powder (TP), 2% soy germ (SG) or 10% tomato powder with 2% soy germ (TP+SG) for 14 weeks. Tomato lycopene and soy germ isoflavones were bioavailable and accumulated in the serum and prostate. 100% of mice fed the control diet had PCa, while incidence was significantly lower in mice consuming TP (61%, p<0.001), SG (66%, p<0.001) and TP+SG (45%, p<0.001). The protection offered by TP+SG was not synergistic, but it was quantitatively the most effective intervention. The ratio of proliferative index to apoptotic index in the prostate was over two times higher in the controls (161 ± 19) than mice consuming TP (75 ± 20, p=0.009), SG (62 ± 19, p=0.001) and TP+SG (70 ± 19, p =0.002), suggesting a greater stimulus for malignant progression in the control group. Maximally effective strategies for PCa prevention may result from optimizing combinations of nutrients and bioactives provided in scientifically designed novel food products targeting high risk populations.Grant Funding Source: NIH (1 F31 CA153804‐01A1 and PHS‐1‐R01 CA125384)
Linking Inflammation to Tumorigenesis in a Mouse Model of High‐Fat‐Diet‐Enhanced Colon Cancer
Authors: Murphy E Angela , Day Stani D , Enos Reilly T , McClellan Jamie L , Steiner Jennifer L , Velazquez Kandy T 
Published: June 2021

We examined the effect of a high‐fat‐diet (HFD) closely mimicking the standard American diet (12% and 40% of total caloric intake from saturated fat and total fat, respectively) on adiposity, polyp characteristics, macrophage markers, and inflammatory mediators in a mouse model of intestinal tumorigenesis. Male ApcMin/+ mice (7–8/group) were fed a control diet (Con) or high‐fat diet (HFD‐12%) from 4 to 12 weeks of age. Body weight and body composition were measured weekly and monthly, respectively. Intestinal tissue was analyzed for polyp burden (number and size). Macrophage markers and inflammatory mediators were examined in the adipose tissue and polyps. The HFD‐12% increased body weight, body fat percent, fat mass and blood glucose (P<0.05), which was associated with an increase in the number of large polyps (P<0.05), but not total polyps. This was linked to an elevation in macrophage markers and inflammatory mediators in the adipose tissue (F4/80, CD11c, TLR‐4 & MCP‐1) and tumor microenvironment (IL‐12, MCP‐1, IL‐6 & TNFa). In summary, a HFD diet similar to the standard American diet increased adiposity and promoted tumorigenesis in concert with alterations in macrophage phenotype and inflammation in adipose tissue and intestinal polyps.This work was supported by an ASPIRE (Advanced Support Programs for Innovative Research Excellence) grant from the University of South Carolina to E.A.M.
Why children use dietary supplements
Authors: Bailey Regan L , Gahche Jaime J , Thomas Paul R , Dwyer Johanna T 
Published: June 2021

BackgroundDietary supplements are used by one‐third of children although the reasons motivating use remain uncertain.ObjectiveTo examine motivations for dietary supplement use, to characterize the types of products used for the most commonly reported motivations, and to relate supplement use to health and demographic factors.DesignMotivations for use of dietary supplements reported for children (< 20; n = 8,245) in NHANES 2007–10, a nationally representative, cross‐sectional population‐based survey.ResultsDietary supplements were used by 31% of children; many different reasons were given: to “improve overall health” (41%), to “maintain health” (37%), for “supplementing the diet” (23%), to “prevent health problems” (20%), and to “boost immunity” (14%). Most children (~90%) who use dietary supplements use a multivitamin‐mineral (MVM) or multi‐vitamin product. Only a small group of supplements used by children (15%) were based on the recommendation of a physician or other healthcare provider.ConclusionsNearly one‐third of children in the US use dietary supplements, most often 1 product and most frequently a MVM. Children most often report using dietary supplements to improve or to maintain overall health. Patterns of use of supplements have been consistent across time in the US: users tend to be non‐Hispanic white, have higher incomes, report more physical activity, and have health insurance.
Benzyl isothiocyanate enhances chemosensitivity and inhibits migration and invasion of head and neck squamous cell carcinoma
Authors: Wolf M. Allison , Bailiff Oksana , Hardman W. Elaine , Claudio Pier Paolo 
Published: June 2021

Approximately 500,000 cases of head and neck squamous cell carcinoma (HNSCC) are reported worldwide each year. Despite recent improvements in cancer treatment, the increase in overall survival of advanced HNSCC has not improved in the past 3 decades. Consequently, our objective is to find new therapeutic options to enhance survival of patients with aggressive HNSCC. Benzyl isothiocyanate (BITC), a natural compound found in cruciferous vegetables, is showing promising results in targeting chemoresistant and metastatic HNSCC cell lines. Our current data suggests that BITC enhances sensitivity of HNSCC cell lines to cisplatin after 24, 48, and 72 hours. A migration assay indicated that the wound healing of metastatic HNSCC cell lines are inhibited by BITC in a dose dependent manner. Additionally, an invasion assay showed that BITC significantly inhibits HNSCC cell invasion towards the chemoattractant EGF after 20 hrs, in a dose dependent manner. Immunofluorescence and Western blot analysis suggest that treatment with BITC inhibits the expression of epithelial‐mesenchymal transition marker, vimentin, in the HN12 cell line. Therefore, the present results suggest that BITC may be able to enhance the effect of chemotherapy, while also reducing migration and invasion of HNSCC cells. Thus suggesting that BITC may be a novel adjuvant therapy for patients with aggressive HNSCC.Grant Funding Source: American Society for Nutrition
Anti‐atherogenic effect of blue‐green algae in male apolipoprotein E knockout mice fed an atherogenic diet
Authors: Ku Chai Siah , Kim Bohkyung , Pham Tho , Wegner Casey J , Yang Yue , Park Youngki , Lee Jiyoung 
Published: June 2021

Development of atherosclerotic plaque in the arteries involves hyperlipidemia and inflammation. We previously reported hypolipidemic and anti‐inflammatory properties of blue‐green algae (BGA) or their organic extracts in vivo and in vitro, respectively. Therefore, BGA may be protective against atherogenesis. To evaluate an anti‐atherogenic effect of Nostoc commune var. sphaeroides Kützing (NO) and Spirulina platensis (SP), 45 male apolipoprotein E knockout mice were fed a high fat/high cholesterol control diet (HF/HC, 15% fat and 0.2% cholesterol by wt) or a HF/HC diet supplemented with 5% of dry, powdered NO or SP by wt for 12 wk. NO supplementation significantly decreased plasma total cholesterol concentrations at 6 and 12 wk than other groups. Plasma triglyceride levels were lower in NO‐fed mice than SP mice. BGA supplementation did not alter liver weight and the expression of hepatic genes for cholesterol synthesis, LDL uptake and lipogenesis compared with control. Plasma tumor necrosis factor α levels were not significantly different between groups. However, when splenocytes isolated from NO and SP‐fed mice were stimulated by lipopolysaccharide ex vivo, interleukin 6 secretion was significantly decreased compared with control splenocytes. In conclusion, different types of BGA may be athero‐protective by exerting hypolipidemic and/or anti‐inflammatory functions. (Funded by NIH R21AT005152)Grant Funding Source: NIH R21AT005152
Central adiposity predicts hippocampal‐dependent relational memory in prepubertal children
Authors: Khan Naiman A , Baym Carol L , Raine Lauren B , Drollette Eric , Scudder Mark , Kramer Arthur F , Cohen Neal J , Hillman Charles H 
Published: June 2021

Central adiposity is a major risk factor for metabolic syndrome and emerging evidence suggests that excess fat mass may negatively affect brain and cognitive health as well. However, the influence of fat distribution on memory has not been examined in children. We investigated the relationship between adiposity and memory in prepubertal children (8–9 years). Participants (N=50) completed tasks assessing working memory and item and relational long‐term memory, which are known to have different brain substrates. Percent fat mass (%FM) and central adiposity (FM‐abd) were measured by DXA. Item and relational memory accuracy were negatively correlated (p<0.05, one‐tailed) with BMI (r=−0.27 and r=−0.36), %FM (r=−0.27 and r=−0.34), and FM‐abd (r=−0.29 and r=−0.40). Working memory was not related to adiposity. Adjusting for demographics (age, sex, SES), IQ, and VO2max, regression analyses showed that FM‐abd (β= −0.37, p=0.02) and BMI (β=−0.33, p=0.03) were negatively associated with relational memory. Neither item nor working memory was related to adiposity, and no memory outcomes were related to %FM. Our findings suggest that distinct forms of memory may be differentially affected by weight status and fat distribution. Given the known dependence of relational memory on the hippocampus, central adiposity may selectively affect hippocampal function in prepubertal children. (Funding source: NIH HD069381)Grant Funding Source: NIH HD069381
Association of food intake with prostate cancer aggressiveness of African and Caucasian Americans in a population‐based study
Authors: Vance Terrence M , Wang Ying , Su L. Joseph , Fontham Elizabeth T. H. , Bensen Jeannette T. , Mohler James L. , Chen Ming‐Hui , Chun Ock K. 
Published: June 2021

This study aimed to determine the association between major food groups that contribute to antioxidant intake and prostate cancer aggressiveness (PCA). Data are from the North Carolina‐Louisiana Prostate Cancer Project, a study of incident prostate cancer in African Americans (AA) (n=925) and Caucasian Americans (CA) (n=1,059). Dietary data were collected by a modified NCI DHQ. Prostate cancer cases were classified as low aggressive (LA) (Gleason score <7, stage ≤T2, PSA <10 ng/ml), high aggressive (HA) (Gleason score ≥8; PSA ≥20 ng/ml; or Gleason score = 7 if stage ≥T3), or intermediate aggressive (IA) (others). AA consuming 1 to 2 cups of fruit drink a week were found to have an odds ratio (OR) for HA vs. LA of 0.43 (95% CI: 0.20, 0.96) and 1 to 2 glasses of wine a week were found to have an OR for IA vs. LA of 0.30 (95% CI: 0.09, 1.00). CA drinking >;2 cups a day of tea were found to have an OR for HA vs. LA of OR 0.44 (95% CI: 0.20, 0.94) and 1 to 2 cups a week of orange juice were found to have an OR for IA vs. LA of OR 0.52 (95% CI: 0.27, 0.98). These results imply that antioxidant rich foods may contribute differently to PCA in CA and AA.Grant Funding Source: NIH Cancer Epidemiology Small Grant #1R03CA159421–01A1.
Higher‐order chromatin folding and gene regulation
Authors: Bickmore Wendy 
Published: June 2021

It is widely appreciated that histone modifications correlate to gene expression states and can, in some cases, directly impact on gene expression and repression. But, our understanding of chromatin states beyond the level of the nucleosome itself is much more rudimentary. Until quite recently there has been little exploration of how these levels of higher‐order chromatin structure might contribute to the regulation of gene expression.Using specific developmentally regulated loci in the mouse, I will discuss how chromatin compaction can act to regulate the spatial and temporal activation of genes during mouse development. I will compare different methods that can probe higher order chromatin structure and will demonstrate their use in both cell culture systems that reflect developmental stages, and in embryos.
Transforming growth factor‐beta‐induced protein ig‐h3 is essential for the formation of human colorectal carcinoma liver metastasis in vivo
Authors: Castronovo Vincent , Blomme Arnaud , Delvaux David , Delvenne Philippe , Detry Olivier , Turtoi Andrei 
Published: June 2021

Transforming growth factor‐beta‐induced protein ig‐h3 (TGFBI) is extracellular matrix component important for cell‐collagen interaction. We and others have reported elevated expression of TGFBI in several human cancers, where its role remains controversial. Current study reports for the first time on the function of TGFBI in colorectal carcinoma liver metastasis (CRC‐LM), a frequently encountered malignancy with no satisfactory treatment to date.We show that TGFBI is highly expressed in human CRC‐LM and in LM originating from breast, lung and pancreatic tumors. From functional perspective, silencing TGFBI in SW1222 human colorectal carcinoma cells lead to a decrease in migration (−70%) and proliferation (−20%). To understand how this effects translate in vivo we have developed a novel animal model of colorectal carcinoma based on chicken chorioallantoic membrane (CAM) that mimics human CRC‐LM. TGFBI silencing resulted in 50% reduction of tumor volume in vivo. Finally, we have demonstrated that TGFBI is systemically reachable target for homing fluorescently‐labeled antibodies injected in tumor bearing animals. Collectively the data show that TGFBI is essential for promoting the development of CRC‐LM and therefore a promising target for designing novel therapeutic approaches.This work is supported by FNRS, Belgium and FP7 EU program.
Effects of subcutaneous daidzein on recovery of function in the rat after ischemic stroke
Authors: Knapp Austen N , Stout Jessica M , Grisley Elizabeth D , Wallace Doug G , Cheatwood Joseph L 
Published: June 2021

Stroke is a leading cause of lasting disability in humans and often results in deficits in sensory and motor functions. There is still a need for a treatment that will enhance recovery and/or reduce behavioral deficits following stroke. In a previous study, our laboratory demonstrated a decrease in post‐stroke behavioral deficits when provided a soy protein‐based diet prior to stroke. Daidzein, a bioactive isoflavone found in soy, is a potential contributor to the observed effects. In the current study, we aimed to examine the effectiveness of daidzein as a post‐stroke treatment by assessing forelimb function to determine post‐stroke behavioral effects and gauge functional recovery. Young adult male Long Evans Hooded rats underwent a middle cerebral artery occlusion (MCAO), which induced a stroke lesion. Following MCAO, rats were treated with vehicle or daidzein by a subcutaneous osmotic minipump. The skilled ladder rung walking task was used to measure forelimb function following stroke. The number of total, slight, and deep slips were compared between groups. No significant differences were found in total slips (slight plus deep) or slight slips(p>;0.05). However, the daidzein group had significantly less deep slips than the vehicle group (p<0.05). These results suggest daidzein mediates neuroprotection and provides enhanced behavioral recovery post‐stroke.Supported by: SIUSOM, SIU REACH, SIU CIRCNSGrant Funding Source: SIU CIRCNS
Single Molecular Analysis of the Encounter of Replication Forks with DNA Interstrand Crosslinks
Authors: Huang Jing , Liu Shuo , Wang Yinsheng , Thazhathveetil Arun Kalliat , Wang Weidong , Seidman Michael M. 
Published: June 2021

DNA interstrand crosslinks (ICLs) are absolute blocks to replication. Progress of ICL repair study, particularly at replication forks, has been limited by the lack of approaches for the direct analysis of replication in the vicinity of ICLs. Additionally, most crosslinking agents generate primarily monoadducts, with only a small fraction of actual ICLs, complicating interpretation of experiments with these compounds.We have developed a novel approach for single‐molecule analysis of replication to study the encounter of individual replication forks with ICLs. We employed antigen tagged psoralen (dig‐pso) which forms a high frequency of ICLs following photoactivation by ultraviolet light (UVA). Cells are treated with dig‐pso/UVA and then pulsed with halogenated thymidine derivatives. The location of replication tracts in the vicinity of ICLs can be determined by immunofluorescent visualization of the thymidine analogues and dig‐pso on DNA fibers. Single fork collisions with the ICLs do occur, but replication on either side of the ICLs is observed more frequently. Similar replication patterns were obtained in both repair proficient and deficient cells, suggesting that replication decisions are made independently of repair competence. Our results argue that cells frequently follow a replication‐replicationrepair model in response to replication blocks.
Argonaute 2‐loaded promoter‐targeted double stranded RNA (Ago2‐ptRNA) mediates gene activation by interacting with the core transcriptional machinery
Authors: Portnoy Victoria , Li Long‐Cheng 
Published: June 2021

Promoter‐targeted double‐stranded RNA (ptRNA) has been shown to mediate potent activation of gene expression in a phenomenon known as RNA activation (RNAa). Previous studies revealed requirement of RNAa on Argonaute 2 (Ago2) protein as well as RNAa association with epigenetic changes at the target promoter. However, its precise molecular nature remains elusive.Using human p21 promoter as a model system, we further characterized RNAa mechanism. ptRNA designed to target p21 promoter is loaded by Ago2 protein, which uses one of the RNA strands to guide it binding to promoter DNA. ptRNA‐Ago2 binding to the promoter target site activate p21 gene expression on transcriptional level. Our biochemical studies revealed the identity of the RNAa effector complex, which contains ptRNA‐loaded Ago2 protein and at least two additional protein components: RNA helicase A (RHA) and RNA polymerase II (RNAP II)‐associated factor CTR9, both capable of recruiting histone modifying enzymes to facilitate transcription initiation and elongation. We show evidence that RNAa effector complex physically associates with RNAPII to facilitate re‐initiation of transcription.Together, our results provide important new insights into RNAa mechanism and allow us to build a working model for RNAa.The research was supported by grants from NIH (1R01GM090293–0109 to L.C.L.) and Department of Defense (W81XWH‐08–1‐0260 to L.C.L.)
The green tea polyphenol EGCG induces Mesenchymal to Epithelial Transition (MET) and tumor regression in Triple Negative Breast Cancer (TNBC) cells and mouse‐xenograft model: Involvement of CCN5
Authors: Das Amlan , Banerjee Snigdha , De Archana , Haque Inamul , Maity Gargi , McEwen Matt , Banerjee Sushanta K 
Published: June 2021

BackgroundEpithelial to Mesenchymal transition (EMT) is an important and coordinated series of events associated with tumor metastasis and invasionRecent studies had shown the importance of CCN5 in the regulation of various carcinomas including the breast cancer. EGCG, the most abundant green tea polyphenol, has been extensively studied as a bioactive dietary component against various types of carcinomas. However, the mechanism of action of EGCG in breast carcinoma is uncertain.ObjectiveThe objective of the present study is to determine whether CCN5 plays any significant role in EGCG‐mediated cytotoxicity in triple negative breast cancer cells.SummaryExposure of triple negative human breast cancer (TNBC) cells, MDA‐MB‐231 and HCC70 to EGCG resulted in a dose‐dependent inhibition of proliferation after 72h and the IC50 was observed around 75μM for MDA‐MB‐231 cells and 50μM for HCC70 respectively. We found EGCG‐treatment effectively induces MET and inhibits the in vitro migration parallel with the induction of CCN5 expression in TNBC cells in a dose‐dependent fashion. Furthermore, consistent with in vitro findings, tumor progression was drastically inhibited in EGCG‐treated MDA‐MB‐ 231‐tumor xenograft in nude mouse model.ConclusionEGCG imparts its anti‐cancer activity via induction of CCN5.(Support: VA Merit Grants, S. Banerjee and S.K. Banerjee)
Investigation of RGS16 mediated inhibition of pancreatic cancer metastasis
Authors: Carper Miranda Bernel , Boskovic Goran , Denvir James , Primerano Donald , Hardman W. Elaine , Claudio Pier Paolo 
Published: June 2021

Pancreatic cancer is ranked as the fourth cause of cancer‐related deaths in the United States with a five‐year survival rate of <5%. This is due in part, to early systemic dissemination. Due to the aggressive nature of this disease, new therapies are needed to inhibit and treat metastatic pancreatic cancer. We have previously performed a microarray analysis to determine proteins regulated by the tumor suppressors p53 and pRb to identify proteins involved in the p53 and pRb cross‐talk pathway. We have found that Regulator of G‐protein signaling (RGS16) is regulated by both p53 and pRb in WI38 normal lung fibroblast cells. RGS16 turns off signaling of several oncogene pathways that are involved in proliferation, chemoresistance, and metastasis. Recently it has also been found that RGS16 is downregulated in metastasized pancreatic cancer. The objective is to investigate the ability of RGS16 to inhibit metastasis by examining pancreatic cancer cell invasion and migration.RGS16 was overexpressed in BxPC‐3 and PANC‐1 pancreatic cancer cell lines. Migration and invasion were investigated using wound‐healing assays and Boyden chambers, respectively. The results suggest that RGS16 is able to inhibit migration and invasion of pancreatic cancer cells.Our data indicates that RGS16 is regulated by both p53 and pRb and overexpression of RGS16 is able to inhibit pancreatic cancer metastasis.