bluuebunny/crossref_metadata_2025_split huggingface dataset:
All trans‐Retinoic Acid Mediates Wnt/β‐catenin Signaling through MED28 in Human Colon Cancer Cells
Authors: Hsieh Nien‐Tsu , Huang Chun‐Yin , Li Chun‐I , Lee Ming‐Fen 
Published: June 2021

MED28 exhibits several cellular roles, including a Mediator subunit for transcription and an interactor with Grb2, Src kinases, actin cytoskeleton, and merlin. MED28 is also found highly expressed in breast, prostate, and colorectal cancers. All trans‐retinoic acid (ATRA), a family member of the essential nutrient vitamin A, has been used in the patients of acute promyelocytic leukemia and explored in the prevention and treatment of other types of cancer. Our laboratory previously showed that MED28 mediates Wnt/β‐catenin signaling in human colon cancer; the current study is to further investigate the effect of ATRA on MED28 in colorectal cancer. ATRA reduced the expression of MED28 in HCT116, HT29, SW480, and SW620 colon cancer cells. The transcriptional activity of the TOPflash reporter construct decreased upon ATRA treatment. Moreover, ATRA reduced the expression levels of cyclin D1 and c‐Myc. Our data indicate that ATRA exhibits a repressive effect on Wnt/β‐catenin signaling through MED28 in colorectal cancer.(This work was supported by the grant NSC102‐2320‐B‐309‐001‐MY3 to M‐F Lee.)
Global DNA Methylation and Hydroxymethylation Differ in Hepatocellular‐ and Cholangio‐Carcinoma and Relate to Survival Rate
Authors: Udali Silvia , Guarini Patrizia , Moruzzi Sara , Ruzzenente Andrea , Tammen Stephanie , Guglielmi Alfredo , Conci Simone , Pattini Patrizia , Choi Sang‐Woon , Friso Simonetta 
Published: June 2021

DNA hydroxymethylation has been recently recognized as a novel epigenetic mark. Primary liver cancers, hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), are highly prevalent but epigenetically poorly characterized. Aims were to determine by a LC/MS/MS method methylcytosine (mCyt) and hydroxymethylcytosine (hmCyt) content in HCC and CC tissues as compared with homologous non‐neoplastic tissues and to analyze the survival rate according to mCyt and hmCyt levels in peripheral blood mononuclear cells (PBMCs) DNA. Thirty‐one HCC and 16 CC patients participated to the study; mCyt content was significantly lower in HCC than CC tissues (3.97% vs 5.26% respectively, p<0.0001). HCC tissues showed a lower mCyt compared to non‐neoplastic tissues (3.97% vs 4.82% mCyt, respectively, p<0.0001). No such difference was instead detected for the comparison of CC and non‐neoplastic tissues. HmCyt was similar in HCC and CC tissues, while it was reduced in HCC and CC as compared to homologous non‐neoplastic tissues (0.044 vs 0.128, p<0.0001 for HCC and 0.030 vs 0.124, p=0.026 for CC).The survival rate at 48 months in liver cancer patients with PBMCs mCyt>5.59% was higher than in those with lower mCyt levels (p=0.034).DNA hypomethylation distinguishes HCC from CC while DNA hypo‐hydroxymethylation characterizes both HCC and CC. PBMCs DNA mCyt content >5.59% relates to a favorable outcome in primary liver cancers.
Prostate Specific Antigen Ratio is Negatively Associated with Blood Cadmium Concentration and Smoking Status
Authors: Vance Terrence , Chun Ock 
Published: June 2021

Smoking is a risk factor for several diseases, notably cardiovascular disease and lung cancer. There is evidence that smoking is associated with an increased risk of prostate cancer, though the mechanisms by and the extent to which smoking may affect prostate cancer risk are unknown. Tobacco smoke contains myriad carcinogens, including cadmium. Cadmium is a toxic transition metal and environmental pollutant found in tobacco, and environmental exposure to cadmium has been associated with greater risk of prostate cancer. We hypothesized that blood cadmium (BCd) would be associated with PSA ratio and that this association would depend on smoking status. We examined the level of prostate specific antigen (PSA), free PSA (fPSA), and fPSA ratio, which better predicts risk of advanced prostate cancer, BCd, and smoking status of 6,007 men in the National Health and Nutrition Examination Survey (NHANES) 2003‐2010. Multiple linear regression was used to predict PSA ratio from BCd, smoking status, age, and ethnicity. Current smokers (CS) were found to have significantly (P < 0.05) lower fPSA and fPSA ratio, and greater BCd compared with non‐smokers (NS) and former smokers (FS) (CS vs. NS: fPSA, 0.31 vs. 0.38 ng/mL; fPSA ratio, 29.1% vs. 31.8%; BCd, 1.30 vs. 0.27 μg/L). Based on the final regression model, BCd was associated with a lower fPSA ratio among CS compared with NS and FS. Compared with NS and FS, for CS a 10% increase in BCd corresponded to a predicted decrease in fPSA ratio of 37% for White and Black men, 54% for Hispanic men, and 217% for other men. These results suggest that smoking is associated with a lower fPSA ratio – and thus potentially greater risk of prostate cancer – and that this effect may be partly attributable to cadmium exposure.Funding: NIH #1R03CA159421‐01A1
Blueberries Attenuate DNA Damage in Postmenopausal Women
Authors: Johnson Sarah , Feresin Rafaela , Navaei Negin , Elam Marcus , Hooshmand Shirin , Payton Mark , Levenson Cathy , Arjmandi Bahram 
Published: June 2021

Preclinical research findings suggest a role for blueberries in cancer prevention. The objective of this study was to indirectly evaluate the cancer‐preventive effects of blueberries in humans. Forty postmenopausal women with pre‐ and stage 1‐hypertension were randomly assigned to receive either 22 g freeze‐dried highbush blueberry powder or 22 g control powder per day for 8 weeks. Plasma 8‐hydroxy‐2'‐deoxyguanosine (8‐OHdG) was measured at baseline, 4 and 8 weeks. There was a significant (P < 0.01) difference between groups at 4 weeks of treatment such that levels were lower in the blueberry group. Although not statistically significant, mean 8‐OHdG values were 12.5% lower than baseline at 4 weeks in the blueberry‐treated group (0.32 ± 0.01 ng/mL at baseline, 0.28 ± 0.01 ng/mL at 4 weeks) whereas there was a 12.9% increase in the control group (0.31 ± 0.01 ng/mL at baseline, 0.35 ± 0.02 ng/mL at 4 weeks). Mean 8‐OHdG values increased to that of baseline at 8 weeks in the blueberry‐treated group while there were no changes in the control group. These findings provide indirect evidence that blueberry consumption may exert cancer‐protective effects. Future studies are needed to determine the longer‐term outcomes with respect to cancer.Support: US Highbush Blueberry Council
Dysfunctional Cardiac Fatty Acid Metabolism in Cystathionine‐beta‐Synthase +/‐ Mice with Obesity
Authors: Glier Melissa , Wambolt Rich , da Silva Robin , Gerrard Sarah , Aleliunas Rika , Jacobs Rene , Allard Michael , Devlin Angela 
Published: June 2021

Obesity‐related cardiac lipid accumulation is associated with toxicity and dysfunction. Cysteine is required for the synthesis of the antioxidant glutathione, supplied by the transsulfuration of homocysteine by cystathionine‐beta‐synthase (Cbs). Cbs+/‐ mice with diet‐induced obesity have reduced cardiac glutathione, and greater glucose intolerance and cardiac lipotoxicity. Our objective was to determine the functional effects and mechanisms of cardiac lipotoxicity in Cbs+/‐ mice with diet‐induced obesity. Cbs+/‐ and Cbs+/+ mice were fed a control‐diet (CD) or a high‐fat diet (HFD) from weaning for 20 weeks. Cbs+/‐ mice fed CD had less visceral adiposity compared to Cbs+/+ mice. Ex vivo working heart assessments revealed greater palmitate oxidation in mice fed the HFD than CD. Independent of diet, Cbs+/‐ mice had reduced palmitate oxidation compared to Cbs+/+ mice. Cbs+/‐ mice had larger hearts and more arachidonic acid (AA) and docosahexaenoic acid (DHA) concentrations in the heart than Cbs+/+ mice. Mice fed the HFD had higher AA, but lower DHA concentrations in the heart than mice fed the CD; effects greatest in Cbs+/‐ mice. A lower ratio of phosphorylated‐AMPKα/AMPKα expression was observed in Cbs+/‐ than Cbs+/+ mice, and this occurred to a greater extent in those fed the HFD. Cbs+/‐ mice with diet‐induced obesity have altered cardiac fatty acid metabolism and larger hearts, further supporting a role for Cbs in obesity‐related cardiac lipotoxicity.Supported by NSERC and CIHR
Stable iron isotopic techniques and plasma hepcidin profiles to optimize iron supplementation regimens
Authors: Moretti Diego , Goede Jeroen , Christophe Zeder , Swinkels Dorine , Tjalsma Harold , Melse Alida , Zimmermann Michael 
Published: June 2021

BackgroundOral iron supplementation is used to treat iron deficiency, but absorption is often low and correction is variable.ObjectiveDetermine the duration and magnitude of the plasma hepcidin (pHep) response induced by oral iron (Fe) supplements and concomitantly measure bioavailability in healthy iron depleted young women.MethodspHep (measured by C‐ELISA), iron status and inflammation were monitored at regular intervals. On day 1, no supplements were given (control day). On days 2 and 3, subjects received iron supplements containing 40, 60, 80, 160 or 240 mg Fe as FeSO4 as either single or two consecutive daily doses extrinsically labeled with stable iron isotopes. Iron bioavailability was measured by the isotopic enrichment of erythrocytic iron 14 days after administration.ResultsBoth Fe dose (P<0.05) and time of day (P<0.05) were associated with increase in pHep. Compared to control days, pHep was significantly higher at 8h and 24h after administration for 60, 80, 160 and 240 mg (P<0.05) but not for 40 mg Fe. Total Fe absorption from the Fe dose on the second day of administration compared to a single Fe dose on the first day was decreased for all dosages above 40 mg( P<0.01). With twice per day dosing (60 mg Fe) the afternoon dose was less bioavailable (P<0.05).ConclusionIn Fe‐depleted women, consecutive day doses of supplemental Fe at 60 mg or above increase pHep and decrease fractional Fe bioavailability. These new data will help guide optimal dosing regimens.
Dietary Strawberries Increase Glutathione in Obese Participants with Above Optimal Serum Lipids
Authors: MORRIS STACY , BETTS NANCY , LYONS TIMOTHY , BASU Arpita 
Published: June 2021

BackgroundDietary flavonoid intake, especially berry flavonoids, has been associated with antioxidant functions and metal chelation in mechanistic studies. Purpose: We examined the hypothesis that freeze‐dried strawberries (FDS) improve antioxidant biomarkers in adults with abdominal adiposity and elevated serum lipids. Methods: In a randomized dose‐response controlled trial, 60 volunteers [5 men and 55 women; age: 49 ± 10 years; BMI: 36 ± 5 kg/m2 (mean±SD)] were assigned to one of the following arms: low dose FDS (LD‐FDS) (25g/d), low dose control (LD‐C), high dose FDS (HD‐FDS) (50g/d), and high dose control (HD‐C) beverages for 12 weeks. Control beverages were matched for calories and total fiber. Serum levels of trace elements (copper, iron, selenium, zinc) and whole blood glutathione (GSH), and catalase activity were examined at screening (0 week) and after 12 weeks intervention. Results: At 12 weeks, glutathione levels were higher in HD‐FDS vs. LD‐FDS, as well as vs. HD‐C, and catalase activity was lower in HD‐FDS vs. baseline (all P<0.05). No differences were noted in serum trace elements following FDS intervention.ConclusionsDietary strawberries, especially at high doses may selectively modulate antioxidant biomarkers that influence risk factors of chronic diseases. These results need further confirmation in larger trials.
Effect of Grape Consumption on Biomarkers of Endothelial and Cardiovascular Health
Authors: Hu Qian , Randolph Jody , Giebler Kathryn , Stevens Allison , Steinberg Francene 
Published: June 2021

Polyphenols have been associated with cardio‐protective benefits, however causal mechanisms remain elusive. This randomized, double‐blind, crossover study examines acute and longer‐term effects of grape consumption on biomarkers of endothelial and cardiovascular health. It was hypothesized that polyphenol‐rich grape consumption would protect against diet‐induced elevations and long‐term impairment in biomarkers of endothelial dysfunction during the acute postprandial period and after 4 weeks respectively. Twenty obese (BMI 37.0±9.9) but otherwise healthy adults were provided with isocaloric sachets of freeze‐dried whole grape powder (grape) (1 60g sachet/day=297mg polyphenol) and placebo (1 60g sachet/day=0mg polyphenol) for daily consumption, each treatment for 4 weeks separated by 2 week washout. To examine acute effects, postprandial blood samples were collected at 0, 1, 3 and 5 hours following a high fat high carbohydrate (HFHC) meal challenge and grape or placebo consumption. Longer‐term effects were examined by fasted blood samples collected on the last day of each 4‐week intervention. HDL increased (p<0.05) after 4 week grape consumption, but no other significant changes in lipids or blood glucose were noted between groups. Data analyzed by repeated measures, 2‐way ANOVA, showed that PAI‐1 and MCP‐1 were significantly elevated in plasma after HFHC challenge (p<0.05). However, no significant differences in plasma sICAM, sVCAM, ET‐1, PAI‐1 or MCP‐1 were detected between grape and placebo treatments after HFHC challenge or 4‐week intervention. Grape consumption has some beneficial effects on markers of cardiovascular health.Supported by California Table Grape Commission and USDA CRIS CA‐S*‐NTR‐6316‐H
Phenol Loss in Heating of Extra Virgin Olive Oil is Dependent on Temperature, Time, and Cooking Conditions
Authors: Flynn Mary , Wang Selina 
Published: June 2021

ObjectiveThe currently available studies that assess the effect of heat on extra virgin olive oil utilize cooking temperatures and times that would exceed normal home‐cooking conditions. We tested the effect of temperatures and cooking conditions reflective of home‐cooking on the content of total phenols, and individual phenols (e.g. oleocanthal, α‐tocopherol and hydroxytyrosol) in olive oils with a range of total phenol content.Methods: olive oil with low (140 mg/kg), medium (300 mg/kg), and high (450 mg/kg) total phenol content was heated to 121°C and 180 °C on a stovetop for 10 minutes and baked in an oven for 30 minutes at 204 °C. After cooling, the oils were analyzed and some of the results are summarized in the table below.

10 mins @121°C (stove top)
10 mins @180°C (stove top)
30 mins @ 204°C (oven)

Phenol content (mg/kg)
Total phenol loss (%)
Oleocanthal loss (%)
Total phenol loss (%)
Oleocanthal loss (%)
Total phenol loss (%)
Oleocanthal loss (%)

Low (140)
2
21
58
53
27
38

Med. (300)
11
3
71
14
44
9

High (450)
41
18
79
35
44
32

ConclusionsLoss of total phenol content in extra virgin olive oil is lower for stove top cooking at common home cooking temperatures (121°C) and for baking (204°C) compared to frying temperature (180°C). Air exposure during the frying process may be responsible for the higher losses when compared with baking. Oleocanthal, an anti‐inflammatory compound, is relatively heat resistant. Future experiments should test the effects of heating the oils with food.
A traditional Mexican diet decreased oxidative stress, improves carbohydrate and lipid metabolism and modifies the microbiota in a diet‐induced obesity
Authors: Avila‐Nava Azalia , Noriega Lilia , Tovar Armando , Torres Nimbe 
Published: June 2021

Corn, beans, chia and pumpkin seeds, nopal and tomato were part of the ancient Mexican diet with high antioxidant activity. Nowadays in Mexico there is decrease in the consumption of these traditional foods and an increase in obesity.The aim of this work was to study the effect of the consumption of a traditional Mexican diet (TMD) in a model of diet‐induced obesity (DIO). To induce obesity, Sprague Dawley rats were fed a high‐fat diet+5 % of sucrose (HFD+S) in the water during 6 months. After that, rats were divided in 3 groups (n=6 per group): 1) obese rats fed HFD+S, 2) obese rats fed control diet, and 3) obese rats fed TMD during 3 months. Animals fed TMD decreased body weight, improved glucose tolerance and decrease serum and liver cholesterol triglycerides. These results could be explained by an increase in liver antioxidant enzymes, decrease in liver and brain MDA, increase in liver P‐AKT associated with insulin signaling, increase in energy expenditure and UCP‐1 protein in white adipose tissue, decrease in the expression of proteins involved in lipogenesis such as SREBP1c and FAS in liver, and by modifying the microbiota. These results indicate that the consumption of vegetable protein, functional foods, omega 3 fatty acids and bioactive compounds present in the TMD decreased significantly obesity induced by a high fat diet.
ADIPOSE TISSUE EXTRACELLULAR MATRIX REMODELLING IN CANCER CACHEXIA
Authors: Alves Michele , Matos Neto Emidio , Maximiliano Linda , Alcantara Paulo , Otoch Jose , Batista Miguel , Seelaender Marilia 
Published: June 2021

Cachexia is a paraneoplastic syndrome in which white adipose tissue (WAT) suffers profound wasting. WAT alterations that may lead to extracellular matrix (ECM) rearrangement. AIM: to assess the effects of cachexia upon ECM of subcutaneous adipose tissue (SAT) by examining the expression of collagens IIIα1 (COL3A1), VIα1 (COL6A1) and fibronectin (FN1). MethodsPatients of the University Hospital were enrolled in 2 groups: Cachectic cancer (CACS,n=14)(gastrointestinal tumours) and Control (C, n=8) (hernia). One gram of SAT was collected in surgery and fixed in 4% formaldehyde and paraffin embedded. The sections (5µm) were stained by Picro Sirius red (PS) for polarized light microscopy, or employed for immunostaining, when slides were incubated with the antibodies overnight (4ºC). Gene expression analysis was performed by RTqPCR and normalised to reference gene 18s. ResultsPS stain demonstrated a strong presence of collagen in the SAT of CACS, and preserved ECM architecture was observed in C. Increased amounts of COL3A1 were found in CACS, despite no changes in gene expression. Immunostaining for COL6A1 was modified in CACS, with collagen aggregates in fibrotic areas and increased mRNA levels of COL6A1 (p<0.05). FN1 labelling was most evident in concomitance to augmented mRNA levels in CACS, comparing with C. ConclusionsCancer cachexia deeply affects SAT organization, causing accumulation of ECM components in the adipose pad leading to remodelling during cachexia. The increase of COL3A1, COL6A1 and FN1 may be directly related with the emergence of tissue fibrosis. Ethics: ICB/USP(788);HU/USP(752/07). Funding: FAPESP (012/50079‐0).
CTBP‐BRCA1 modulates Epithelial Cell Fate in Breast Cancer
Authors: byun Jung , Gardner Kevin 
Published: June 2021

Epithelial cells retain incredible plasticity. They can differentiate and self‐renew during embryonic development. The epithelial cells can lose their typical epithelial features and change to a mesenchymal state by activating epithelial mesenchymal transition (EMT), whose process is critical for breast cancer metastasis. BRCA1 is tumor suppressor gene that represses malignant transformation by safeguarding the fidelity of DNA replication chromosomal segregation and has been demonstrated to play a possible role in mammary differentiation. C‐terminal binding protein (CTBP) is a dimeric nuclear protein and an epigenetic regulator that is activated in the presence of NADH to recruit and target a variety of histone modifying complexes and transcriptional regulators to chromatin, thus providing a defined mechanism through which carbohydrate metabolism can drive epigenetic regulatory events. We have recently shown that CTBP drives epithelial mesenchymal transition (EMT), genome instability, and the acquisition of stem cell tumor‐initiating cell‐like pathways in breast cancer.Here we demonstrate that CTBP and BRCA1 competitively regulate epithelial features including epithelial polarity and lumen development in MCF10A 3D gland formation assays. Loss of BRCA1 appears to perturb mammary epithelial differentiation whereas CTBP depletion enhances epithelial differentiation. These findings define dynamic yet antagonist roles for CtBP and BRCA1 in mammary gland growth and development.
Diabetic Ketoacidosis Alters Plasma Levels of Matrix Metalloproteinases and PMN‐Specific Elastase in Children
Authors: Woo Martin , Cepinskas Gediminas , Clarson Cheril , Fraser Douglas 
Published: June 2021

IntroductionDiabetic ketoacidosis (DKA) is associated with cerebrovascular complications in children such as vasogenic edema. Circulating matrix metalloproteinases (MMPs), their endogenous inhibitors (TIMPs), and other proteases may contribute to loss of cerebrovascular endothelial cell junctional integrity. Our aim was to determine the effects of acute DKA on systemic MMP/TIMP levels, as well as polymorphonuclear neutrophil(PMN)‐specific elastase.MethodsPlasma was obtained from children ages 4‐17 years old, with type‐1 diabetes, either in an acute DKA state or insulin‐controlled (CON). DKA and CON samples were age‐ and sex‐matched for all experiments. Gelatin zymography was used to assess gelatinolytic activity. ELISA‐based methods were used to assess plasma concentration of proteins.ResultsDKA plasma showed significantly increased MMP‐9 activity(P<0.01) and decreased MMP‐2 activity(P<0.001), compared to CON plasma. MMP‐9 activity in DKA plasma was inversely correlated with pH(P<0.05). DKA plasma had increased circulating levels of MMP‐3(P<0.05), MMP‐8(P<0.001) and TIMP‐4(P<0.01). In addition, a significant increase in circulating levels of PMN elastase(P<0.001) was detected in DKA plasma.SummaryDKA is associated with dynamic changes in plasma levels of MMP‐2, MMP‐3, MMP‐8, MMP‐9 and TIMP‐4, as well as PMN elastase, which may contribute to loss of blood‐brain barrier integrity.
What Do Academic Investigators Want and Get from Preclinical Collaboration with the Pharmaceutical Industry?
Authors: Amiri Marjan , Michel Martin 
Published: June 2021

ObjectiveAs research collaboration between academia and the pharmaceutical industry is important, we explored expectations and experience of investigators with preclinical collaborations.MethodsAcademic investigators from Western Europe, North America and Japan with preclinical publications in the obstructed airways or diabetes field were invited to anonymously participate in a web‐based survey.ResultsResults were similar in the obstructed airways and diabetes field (134 investigators total, 28% of invitees). Obtaining funding, freedom to publish and obtaining compounds were the most important goals, cultivating professional relationships, getting external scientific input, direct relationship to disease treatment and involvement with drug development were less important. Among eight characteristics of the primary contact person in the company, trustworthiness ranked highest, followed by collaborative spirit and transparent information sharing; supportiveness, scientific qualification, accessibility and timeliness of responses ranked lower, and friendliness lowest. Overall satisfaction in their latest collaborations was typically rated as very good. However, the process of reaching a contract was often considered too long and difficult, for which both university and company legal departments were reported as culprits.ConclusionsWhile generally satisfied in their preclinical collaboration with the pharmaceutical industry, academic investigators look for improved contracting procedures.