bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing Six Commercially‐Available Teas for Polyphenol Content and Antioxidative Capacity in Relation to Steep Time
Authors: McAlpine Michael D. , Ward Wendy E. 
Published: November 2023

Globally, tea is the most commonly consumed beverage after water and is associated with many health benefits. These health benefits are often attributed to the unique profile and abundance of polyphenols in tea. In vivo, polyphenols have been shown to exhibit antioxidant activity and are thus capable of inhibiting free radical production. The purpose of this study was to characterize six popular and commercially available teas in terms of total polyphenolic content (TPC) and relative antioxidant capacity after varying the steep times. Dragonwell (DW), Japanese Sencha (JS), English Breakfast (EB), Golden Monkey (GM), Green Rooibos (GR), and Red Rooibos (RR) loose leaf teas were individually steeped in water for 5 or 10 minutes at the manufacturer's recommended temperature (79°C for DW, JS; 96°C for EB, GM, GR, RR) to extract polyphenols. TPC was determined using Folin‐Ciocalteau's reagent with Gallic acid as a standard; and antioxidative capacity was determined by the ability of a normalized amount of polyphenols (1μg/ml) from each tea to scavenge the free radical 2, 2‐diphenyl‐1‐picrylhydrazyl (DPPH). TPC was observed to be significantly greater (p<0.05) after 10 minutes of steeping than it was after 5 minutes for each of the teas. However, 66–73% of polyphenols measured at 10 minutes were extracted in the first 5 minutes (% of total TPC extracted: DW=66.08±6.36, JS=73.37±3.08, EB=71.74±4.74, GM=65.40±2.69, GR=68.31±3.17, RR=71.14±5.95) regardless of tea type. After 5 minutes of steeping, significant differences (p<0.05) in TPC were observed among different teas (JS~EB>DW>GM~GR~RR). Different teas with their respective polyphenol profiles also varied (p<0.05) in their ability to inhibit the free radical DPPH (% inhibition: DW>JS~EB~GM>GR>RR). In summary, TPC varies greatly among types of tea, but the majority of polyphenols are extracted after 5 minutes of steeping regardless of tea type. The wide range in the ability of the different teas to scavenge free radicals, even after normalizing for TPC, indicates an important role for the specific polyphenol profile and potential different health benefits among teas.Support or Funding InformationNSERC
“Genetic Haplotypes and Family History of Alzheimer's Disease Modify Homocysteine and Influence Neurovascular Pathology”
Authors: Webb Joe L , Willette Auriel A 
Published: November 2023

ObjectiveTo delineate novel relationships between Alzheimer disease (AD) factors, such as Translocase of the Outer Mitochondrial Membrane ‐ kD 40 (TOMM40) genotype, AD family history (FH), the vascular risk factor homocysteine, and vascular neuropathology.MethodsWe performed linear mixed model regression on longitudinal imaging and biomarker data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Among 210 healthy adults with 1 or 2 Apolipoprotein ɛ4 (APOE4) alleles (mean age 73.8), we stratified by TOMM40 genotypes S/L (n=84), L/L (n=49), L/VL (n=68). Main effects and interactions between TOMM40 and FH were conducted on neurovascular outcomes, including white matter hyperintensities (WMH), infarctions, as well as total intracranial volume. Vascular risk factors were similarly tested, including homocysteine and total cholesterol. Models were adjusted for age, gender, body mass index and hyperglycemia status.ResultsFH * TOMM40 interactions showed that L/L and L/VL genotypes respectively exercised “beneficial” effects for FH negative (FH−) and “detrimental” effects for FH positive (FH+) participants. In FH+, for example, risk alleles were associated with higher serum homocysteine (P=0.024), total cholesterol (P=0.005), infarction occurrence (P=0.045), and greater WMH burden (P = 0.032). Total intracranial volume was also smaller (P<0.001). Homocysteine levels mediated FH * TOMM40 associations with neurovascular measures.ConclusionsThese results suggest that FH modulates TOMM40's effects on vascular markers and neurovascular pathology of AD in APOE4 participants. These interactions between FH and TOMM40 influence on neuropathology may be mediated via homocysteine suggesting that TOMM40 genotype could serve as a novel predictor for AD and that homocysteine may be one potential mechanism.Support or Funding InformationThis study was supported in part by the National Institutes of Health award number K99AG047282, an Iowa State University Stewart Research Award and an Iowa State University University Honor's Program Research Award. Role of Funding: The funding sources had no role in the design or conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the abstract.
THE ROLE OF INSULIN RESISTANCE AND SIRT‐1 IN CARDIAC REMODELING INDUCED BY CIGARETTE SMOKE
Authors: Azevedo Paula Schmidt , Pires Vanessa , Santos Priscila , Gonçalves Andrea , Okoshi Marina , Fernandes Ana Angelica , Roscani Meliza , Polegato Bertha , Paiva Sergio , Zornoff Leonardo , Minicucci Marcos 
Published: November 2023

The aim of this study is to investigate if insulin resistance and SIRT‐1 participate of cardiac remodeling induced by TS.Methods20 animals were allocated into 2 groups: group exposed to cigarette smoke (CS) and group not exposed to cigarette smoke (C). After 2 months the animals were subjected to: a) echocardiographic study; b) energy metabolism enzymes evaluation; c) Western blot for Akt, AMPK, SIRT‐1 and GLUT‐4. Cotinine and insulin was measured by ELISA kit. The HOMA‐index was calculated. The CS group showed larger left atrium size and lower ejection fraction than those of group. Serum cotinine was positive in CS exposed group (P<0,001). HOMA‐index showed insulin resistance in CS group (P<0,05). As regards the analysis of energy metabolism enzymes, phosphofructokinase (PFK); P = 0.003), lactate dehydrogenases (LDH) (P = 0.017) were greater in the TS group and citrate synthase P <0.001), complex I ( P <0.001), complex II (P <0.001), ATP synthase (P <0.001) were lower in the TS group. Akt/Aktp was similar between the groups. AMPK was reduced in CS group (p<0,001), SIRT‐1 increased in CS group (P<0,001) and GLUT‐4 (P=0,47) was similar.ConclusionCigarette smoke induced insulin resistance, that may have reduced AMPK and probably compromised glucose metabolism and energy transformation. SIRT‐1 increases in oxidative stress set and may promote hypertrophy and apoptosis. Therefore, SIRT‐1 is also a possible metabolic pathway involved in CS induced remodeling.Support or Funding InformationSupported by FAPESP
Recommendations of the 2015–2020 Dietary Guidelines for Americans
Authors: Casavale Kellie O. , Stoody Eve Essery , Rihane Colette , Olson Richard 
Published: November 2023

ObjectiveThe US Departments of Health and Human Services and Agriculture released the 8th edition (2015–2020) of the Dietary Guidelines for Americans (DGA) in January 2016.MethodsThe DGA is required under the National Nutrition Monitoring and Related Research Act of 1990 and informs the development of federal food, nutrition, and health policies and programs.ResultsThe 2015–2020 DGA focuses on shifts in eating patterns to align current dietary intake with recommendations and highlight multiple strategies across all segments of society to promote healthy eating and physical activity behaviors. In abbreviation, the 5 overarching Guidelines are to follow a healthy eating pattern across the life span; focus on variety, nutrient density, and amount; limit calories from added sugars and saturated fats and reduce sodium intake; shift to healthier food and beverage choices; and support healthy eating patterns for all. Key Recommendations provide further guidance on how individuals can follow the five Guidelines and state that a healthy eating pattern accounts for all foods and beverages within an appropriate calorie level and includes a variety of vegetables from all of the subgroups (dark green, red and orange, legumes/beans and peas, starchy, and other); fruits (especially whole fruits); grains (at least half of which are whole grains); fat‐free or low‐fat dairy (including milk, yogurt, cheese, and fortified soy beverages); a variety of protein foods (including seafood, lean meats and poultry, eggs, legumes/beans and peas, and nuts, seeds, and soy products); and oils. A healthy eating pattern also limits saturated fats and trans fats, added sugars, and sodium. Key Recommendations that are quantitative are provided for several components of the diet of particular public health concern that should be limited: consume less than 10% of calories per day from added sugars; consume less than 10% of calories per day from saturated fats; consume less than 2,300mg/d of sodium; and if alcohol is consumed, it should be consumed in moderation(up to 1 drink per day for women and up to 2 drinks per day for men and only by adults of legal drinking age). The DGA also recommends to meet the Physical Activity Guidelines for Americans.ConclusionEveryone has a role in supporting healthy eating patterns. Concerted efforts among health care professionals, communities, businesses and industries, organizations, governments, and other segments of society are important to support individuals and families in making dietary and physical activity choices that align with the DGA. Health care professionals can help individuals identify how they can modify and improve their dietary patterns. Educational materials for both professionals and consumers will be available in 2016.Support or Funding InformationNone
Effect of Baking on the β‐carotene Content of Orange Flesh Sweetpotato (Ipomoea batatas) Puree Bread and OFSP Flour Bread
Authors: Muzhingi Tawanda , Mbogo Daniel , Low Jan , Magnaghi Antonio , Heck Simon , Gule Simon 
Published: November 2023

Orange Fleshed Sweetpotato (OFSP) is a biofortified crop rich in provitamin A carotenoids, and is being promoted a sustainable food‐based strategy to address vitamin A deficiency in sub Saharan Africa. This study was aimed at evaluating the provitamin A carotenoid retention in bread made using OFSP flour to substitute for 10% of wheat flour, and bread made using OFSP puree to substitute for 45% of wheat flour. Samples of OFSP flour, OFSP puree, bread and ingredients for baking were obtained from local bakers in Kenya. The OFSP flour, OFSP puree, dough and breads were extracted for carotenoid by KOH saponification and hexane extraction. The extracted carotenoids were analyzed in an HPLC system with C30 Carotenoid S column and eluted in methanol, water and methyl tert butyl ether gradient profiles. The major carotenoids of OFSP were all‐trans β‐carotene, and its isomers (9‐cis β‐carotene and 13‐cis β‐carotene). Bread made with OFSP puree had the highest all‐trans β‐carotene content of 3.14 mg/100g dry weigh (dw) compared to 0.08mg/100g dw of OFSP flour bread. Adjusting for moisture content the OFSP puree bread will provide about 507μg all‐trans β‐carotene/slice (39g) of bread. Therefore, two slices of OFSP puree bread will provide 42.25 Retinol Activity Equivalence (RAE), which meets almost 30% of the RDA for vitamin A in children aged 1–3 years old.Support or Funding InformationDFID (CIP SUSTAIN) and BMGF (CIP SASHA 2)
Routine, Automated RNA in situ Hybridization Profiling of Target Candidates and Safety Markers in Preclinical Animal Model Tissue Panels using RNAscope® LS Assay on Leica Biosystems’ BOND RX
Authors: Fang Li , He Ming‐Xiao , Kim Daniel , Franks Tania , Roy Marc , Bunker Chris , Luo Yuling , Ma Xiao‐Jun , Park Emily 
Published: November 2023

Determining tissue expression profiles of therapeutic target candidates is essential for safety assessment and the potential for adverse events. Immunohistochemistry is often not possible due to lack of reagents with the required specificity and sensitivity coupled with extensive time in attempts to validate IHC. RNAscope® in situ hybridization (ISH) technology is a universal assay able to detect and characterize tissue distribution of any target mRNA. RNAscope ISH has molecular sensitivity, high specificity and robust performance in FFPE tissue. Fully automated RNAscope ISH is performed on Ventana Discovery and Leica Biosystem Bond RX instrumentation; detection of marker RNAs is achieved in 8 hours and visualized via bright field microscopy. Marker RNAs can be quantified with cellular resolution using digital image analysis software.We present RNAscope methods for routine detection of very low copy RNAs, typical of most targets in normal tissues, as well as applications for detection of cell‐type, proliferation and apoptosis markers in animal tissues used in safety assessment and toxicity studies. We demonstrate robust performance in 25 tissues from rat, dog and cynomolgus monkey using probes to low‐, medium‐ and high‐expression housekeeping gene RNAs (POLR2A, PPIB and UBC). Specific signals and well‐maintained morphology was achieved efficiently for all 25 tissues. Based on optimized epitope retrieval conditions, tissues were grouped into two multi‐tissue microarrays for high‐throughput marker analysis. We examined and present tissue‐specific expression patterns of endothelial marker CD31, macrophage marker CD68, proliferation markers Ki‐67 and Cyclin E1, and apoptosis molecules, Puma, Fas/CD95 and DR5.The presentation demonstrates RNAscope as a method that can be replicated in any lab and suitable for efficient and reliable detection of any target candidate or safety/toxicity biomarker mRNA from any species for interrogation in any tissue.
Oxidative stress and diabetic wound healing
Authors: Tie Lu , Shi Yun‐Di , Li Xue‐Jun 
Published: November 2023

ObjectivesRefractory wounds in diabetic patients constitute a serious complication that often leads to amputation with limited treatment regimens. Oxidative stress has been proposed as an important pathogenic factor in diabetic wound complications. The present study was designed to determine the protective effect of the GTP cyclohydrolase I (GTPCH), the rate‐limiting enzyme of BH4 synthesis; soy isoflavone genistein and Ganoderma lucidum polysaccharide (Gl‐PS) on diabetic wound healing.MethodsStreptozotocin‐induced diabetic mice with full‐thickness excisional wounds were used.ResultsThe rate of wound closure in diabetic mice was delayed compared to normal wild‐type (WT) mice, which was rescued in GTPCH transgenic (Tg‐GCH) diabetic mice. In WT diabetic mice, cutaneous eNOS activity and nitrite levels were decreased compared to WT mice, paralleled by increased levels of superoxide anion (O2.−) level. In Tg‐GCH diabetic mice, nitrite levels were potentiated and O2.− level was suppressed. Genistein treatment dose‐dependently rescued the delay of wound closure in diabetic mice and increased the mean perfusion rate. Genistein significantly normalized the elevated O2− production and reversed the attenuated nitrite level by inhibition of forkhead box O transcription factor 1 (FoxO1) levels. Gl‐PS treatment could also rescue the delay of wound closure in diabetic mice. Gl‐PS normalized the increased mitochondrial O2.− production and nitrotyrosine formation by inhibition of MnSOD nitration and the redox enzyme p66Shc expression in diabetic wound tissues.ConclusionGTPCH, genistein and Gl‐PS rescued the delayed wound healing and improved wound angiogenesis in diabetic mice, at least in part, by suppression of oxidative stress.Support or Funding InformationThis work was supported by the National Natural Science Foundation of China No. 81373405 and 30901803, Beijing Higher Education Young Elite Teacher Project (No. YETP0053), Leading Academic Discipline Project of Beijing Education Bureau (No. BMU20110254) and the Fund of Janssen Research Council China (JRCC2011).
Inhibition of STAT3 phosphorylation by sulforaphane reduces the lipopolysaccharide‐induced adhesion molecule expression in vascular endothelial cell
Authors: Ahn Hee Y , Cho Young S 
Published: November 2023

Intercellular adhesion molecule 1 (ICAM‐1) and vascular cell adhesion molecule 1 (VCAM‐1) play key roles in the initiation of vascular inflammation. In this study, we explored whether sulforaphane, a dietary phytochemical, can inhibit the expression of ICAM‐1 and VCAM‐1 in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS), and the mechanisms involved. Sulforaphane prevented the LPS‐mediated increase in ICAM‐1 and VCAM‐1 expression, (P<0.01) in HUVEC. Sulforaphane also prevented the LPS‐mediated increase in the phosphorylation of signal transducer and activator of transcription 3 (STAT3) (P<0.01). Stattic, a STAT3 inhibitor, reduced the LPS‐induced expression of ICAM‐1 and VCAM‐1, and STAT3 phosphorylation (P<0.01). STAT3 small interfering RNA treatment reduced the LPS‐induced expression of ICAM‐1, VCAM‐1 and STAT3 (P<0.01). Sulforaphane reduced LPS‐mediated THP‐1 monocyte adhesion to HUVEC (P<0.01).These data provide insight into the mechanism through which sulforaphane partly reduces the expression of ICAM‐1 and VCAM‐1 on the vascular endothelial cell by inhibiting STAT3 phosphorylation.Support or Funding InformationThis research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning(2012010913).
Characterization and Functional Effects of Multi‐site Interactions between calmodulin and the angiotensin II receptor type 1A
Authors: Clements Robert , Ehlers Kevin , VerMeer Mark , Tran Kim 
Published: November 2023

The angiotensin II receptor type 1A (AT1AR) is responsible for many effects of angiotensin II (AngII). Calmodulin (CaM) is essential for many cell functions due to its interactions with many proteins. CaM has previously been demonstrated to interact with AT1AR at a.a. 305 – 327 in the fourth submembrane domain (SMD4) (Thomas WG et al., FEBS Lett. 1999;455:367–371) and a.a. 214 – 231 in the third submembrane domain (Zhang R et al., PLOS One 2013;8:e65266). The functional effects of CaM interaction with AT1AR, however, remains incompletely understood. Additionally, the interaction domains are not completely identified and characterized. We have observed that AT1R coimmunoprecipitates with CaM in vascular smooth muscle under resting conditions, association that is enhanced by stimulation with AngII or thapsigargin. Using novel FRET biosensors with EYFP‐ECFP pair flanking each of AT1AR's submembrane domains, we have identified a novel CaM‐binding domain in the submembrane domain 2 and found that full interaction between CaM and SMD3 requires a significantly longer sequence than previously reported. All three domains interact with CaM in a Ca2+‐dependent fashion, with drastically different affinities. Simultaneous determinations of biosensor responses and free Ca2+ concentrations showed that these interactions take place at significantly different Ca2+ sensitivities in the physiological range of intracellular Ca2+. Notably, SMD3 interacts with CaM with a Ca2+ sensitivity that falls in the range of resting intracellular Ca2+ concentration. Cells heterologously expressing full‐length AT1AR containing mutations that reduced CaM interactions at individual CaM binding domains on SMD2, SMD3 or SMD4, exhibit ~ 1.8‐, 2‐ or 3‐fold reductions in AngII‐stimulated ERK1/2 phosphorylation, respectively. These data demonstrate that CaM is involved in AngII signaling via direct interactions with multiple domains in AT1R and allow prediction of interactions between CaM and individual SMDs under distinct physiological scenarios.Support or Funding InformationIowa Osteopathic and Educational Research FundsNational Institutes of Health Grant HL‐112184
Statin Therapy Reduces Differentiation of Ventricular Fibroblast to Myofibroblasts in Human Failing Heart
Authors: ROSS GRACIOUS R , KRAFT KELSEY , EMELYANOVA LARISA , RIZVI FARHAN , HOLMUHAMEDOV EKHSON L , WERNER PAUL , TAJIK JAMIL , JAHANGIR ARSHAD 
Published: November 2023

BackgroundCardiac fibrosis (CF) is a major factor underlying the progression of heart failure (HF). Apart from the established lipid lowering effect, HMG‐CoA (3‐hydroxy‐3‐methylglutaryl‐CoenzymeA) reductase inhibition by statins reverses CF in various animal models of HF but its effect in human failing heart ventricular fibroblasts (hVF), responsible for fibrosis, is not known. Hence, we tested the differentiation phenotype of hVF isolated from HF patients under statin therapy (HF+Statin) for at least 1 year or not (HF‐No_Statin) and normal, as fibroblast to myofibroblast trans‐differentiation precedes fibrosis.MethodsPrimary hVF cultures obtained from HF patients undergoing left‐ventricle assist device implantation (n=4 each) and non‐diseased hVF from trauma victims (n=3) were used at passage 3 or 4. Confocal microscopy, immunohistochemistry, western blotting, Edu (5‐ethynyl‐2′‐deoxyuridine)‐incorporation assay data were obtained and analyzed by unpaired t test or one‐Way Analysis of Variance.ResultsImmunoblot (Fig. A) data showed significantly (P<0.05) higher expression of α‐smooth muscle actin (α‐SMA+) and immunohistochemistry (Fig. B) showed significantly high population of myofibroblasts (α‐SMA+) in the HF‐No_Statin group vs the control or HF+Statin groups, suggesting statin‐sensitive increased hVF differentiation in failing heart. In vitro treatment of simvastatin (0.3μM for 72 hrs) on HF‐No_Statin group hVFs significantly (P<0.05) reduced the high expression of α‐SMA, indicating a reversal effect of statins on myofibroblast to fibroblast. Edu‐incorporation data showed that the percentage of proliferating hVFs was not significantly different in failing heart without statins(82±3%) compared to control(82±4%) and HF+ Statin (69±5%), indicating that the DNA synthesis and proliferative capacity of hVFs remain unaltered in failing heart, irrespective of statin therapy, compared to normal.ConclusionThe failing heart ventricle has a large population of differentiated myofibroblasts. Statins prevent/reverse hVF differentiation decreasing the ratio of myofibroblast to fibroblasts, which is anti‐fibrotic. The significance of statins’ anti‐fibrotic effect for HF therapeutics may be in reducing the CF progression by inhibiting/reversing hVF differentiation to myofibroblasts, thereby improving the cardiovascular outcome in HF patientsSupport or Funding InformationAurora Health Care ‐ Cardiovascular Surgery Research Award (CVSRA 2015) to Gracious R Ross and NIH R01‐HL101240 to Arshad Jahangir.