bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial cell‐specific STIM1 deletion prevents lung vascular leak
Authors: DebRoy Auditi , Vogel Stephen M , Sundivakkam Premanand C , Zhao You‐Yang , Malik Asrar B , Tiruppathi Chinnaswamy 
Published: June 2021

BackgroundThe calcium‐sensor protein, Stromal Interaction Molecule 1 (STIM1), is critical for activation of store‐operated calcium entry (SOCE) through Orai1 and TRPC channels in endothelial cells (ECs). We showed that activation of ECs by thrombin caused increased cytosolic Ca2+ ([Ca2+]i) via SOCE, but STIM1's role in mediating thrombin‐induced Ca2+ entry and its effect on endothelial permeability is unknown. In this study, we compare lung edemagenesis in normal and endothelial cell‐specific STIM1 knockout (STIM1EC−/−) mice.ResultsTo determine the in vivo functional role of STIM1 in ECs, we generated STIM1EC−/− mice by crossing STIM1fl/fl mice with Tie2 promoter‐driven‐Cre transgenic mice. STIM1EC−/− mice developed normally. In lung tissue, mRNA and protein expression of STIM1 was drastically reduced in STIM1EC−/− mice compared to STIM1fl/fl (wild type [WT]) mice. Interestingly, protein expression of Orai1 and TRPC4 was also reduced in lungs of STIM1EC−/− mice. Next, we measured PAR‐1 agonist peptide (TFLLRNPNDK‐NH2) effects on lung microvessel filtration coefficient (Kf,c), a measure of vascular permeability, in isolated lung preparations. In WT mice, PAR‐1 agonist peptide produced a 3‐ to 4‐fold increase in Kf,c over basal in 15 min. PAR‐1 effects were completely blocked in STIM1EC−/− mice.ConclusionResults suggest that STIM1 signaling in ECs regulates lung vascular leak.
Antioxidant properties and their bioaccessibility of Blessed Thistle under different processed treatments
Authors: Sahan Yasemin , Dulger Dilek 
Published: June 2021

Blessed thistle (Cnicus benedictus L.) is a wild plant, native to the Mediterranean region of Europe, and has been naturalized throughout the United States and Europe. Leaves, stems and flowers of blessed thistle has been used as a “bitter” tonic to stimulate appetite, enhance bile secretion, strengthen the liver, diminish jaundice, decrease flatulence, aid digestion. This plant is also used as a flavoring agent in alcoholic beverages. In addition the roots of blessed thistle are eaten cooked in Turkey. Most research has focused only on the antioxidant properties of different alternative wild plants. However, it is necessary to know the bioaccessibility of antioxidative compounds to evaluate their biological activity in body. Bioaccessibility studies are affected several factors, especially food processing related factors. In this study, extractable and hydrolysable extract of blessed thistle was used to investigate the effect of processed treatment (frozen and boiled) on its antioxidant properties and their bioaccessibility. Antioxidant capacity was assessed by CUPRAC, ABTS, and DPPH methods. Antioxidant capacities of fresh samples were found high level in all tested methods. Although the total phenolic accessibility is too high level, the antioxidant bioaccessibility of samples were low level.This Project was supported by Uludag University Scientific Research Committee (Project No: 2011/26).
Sedentary behavior and mortality in older women
Authors: Seguin Rebecca , Buchner David , Liu Jingmin , Allison Matthew , Manini Todd , Manson JoAnn , Messina Catherine , Patel Mahesh , Moreland Larry , LaCroix Andrea 
Published: June 2021

CONTEXTSedentary behavior has been associated with poor health outcomes. Additional research with older women and ethnically diverse populations is needed.PURPOSETo determine the relationship between sedentary time and mortality in a prospective cohort of ethnically diverse women.METHODS92,234 women aged 50–79 years at baseline who participated in the Women's Health Initiative Observational Study were the subjects for this study. Self‐reported daily sedentary behavior was assessed by questionnaire and examined by time quartiles in hours: Q1<6; Q2=6–8; Q3>;8–11; Q4>;11. Mortality risk was examined using Cox proportional hazard models adjusting for potential confounders. Models were stratified by age, race/ethnicity, body mass index, physical activity, and physical function to examine possible effect modification.RESULTSThe follow‐up period was 12 years. In multivariate analysis, greater sedentary time (Q1 versus Q4) was associated with increased risk of all‐cause mortality (HR=1.12; 95% CI: 1.05– 1.19), and a linear trend for mortality due to cancer, CHD, and CVD (all p<0.05). Black women in Q4 had a 41% increased death risk compared to women in Q1 (HR=1.41, 95% CI: 1.16–1.71).CONCLUSIONThere was a modest dose‐response relationship between greater sedentary time and mortality risk after controlling for multiple confounders.Research support: T32AG027677; K01HL108807
The effect of short‐term frozen storage of human milk on the validity of Vitamin A assays using the iCHECKTM rapid analyzer
Authors: Whang Christine , Bermudez Odilia , Chomat Anne Marie , Solomons Noel W 
Published: June 2021

BackgroundBreast milk retinol concentration is an indicator of both infant nutrient intake and population vitamin A status. Milk is easily and non‐invasively collected and rapid field methods for vitamin A analysis now exist.ObjectiveTo confirm or refute the assertion of restricting fluorescent assaying of milk vitamin A to “unfrozen” samples (Schweigert et al, Sight & Life Magazine 2011 (2) 18–22).MethodsFull‐breast expression milk samples were collected in 21 women from Mam‐Mayan rural communities in the Western Highlands of Guatemala. A milk‐fat packing volume (creamatocrit), expressed in volume percent (vol%), was measured on a hematocrit microcentrifuge. Retinol concentration was assayed, both fresh and after 20–26 d at −20°C, on an iCHECKTM rapid field analyzer (Bioanalyt, Telbow, Germany).ResultsRespective retinol concentrations were 539±221 μg/L (fresh) and 528±205 μg/L (post‐freezing) (p=0.45), with a Pearson correlation coefficient (P) and Spearman coefficient (S) both of r=0.959 (p=0.001). The corresponding values for creamatocrit were 8.1±3.1 vol% vs 9.0±4.0 vol% (p=0.17), with r=0.774 (p=0.001)(P) and r=0.844 (p=0.001)(S).ConclusionsMilk samples can be stored for at least 3 wks without affecting the validity of iCHECKTMassays. Funded by Sight & Life of Basel and Tufts University School of Medicine
Targeted disruption of the nucleosomal binding protein HMGN5 results in altered glutathione metabolism and mild hepatic dysfunction
Authors: Ciappio Eric D , Rochman Mark , Horsch Marion , Beckers Johannes , Krausz Kristopher W , Bonzo Jessica A , Gonzalez Frank J , Bustin Michael 
Published: June 2021

High mobility group nucleosome‐binding protein 5 (HMGN5) is a chromatin architectural protein that regulates gene expression by decompacting higher‐order chromatin structure; however, the physiological role of this protein is unknown. To examine the function of HMGN5 in vivo, we generated mice lacking the chromatin binding domain of the protein. Compared to wild type littermates, male Hmgn5−/Y mice had elevated serum albumin (p=0.03), fasting non‐HDL cholesterol (p=0.03), fasting triglycierides (p=0.05), and alanine transaminase (p=0.08), suggesting a mild hepatic dysfunction. An UPLC‐QTOF‐MS‐based metabolomic study in Hmgn5−/Y mice identified a 41% increase in hepatic glutathione (p=0.02) and significantly (p<0.05) decreased urinary concentrations of compounds related to the glutathione precursor glycine, such as betaine (−62%), phenylacetylglycine (−50%), and creatine (−42%). Microarray analysis and validation by real‐time PCR revealed that the expression of two genes affecting glutathione function, Gpx6 and Hk1, was significantly (p<0.05) decreased in Hmgn5−/Y mouse liver tissue. In sum, these data suggest that functional loss of the chromatin remodeling protein HMGN5 leads to transcriptional changes that alter glutathione metabolism resulting in mild hepatic dysfunction.Grant Funding Source: NIH/NCI/CCR Intramural Program
Dairy snack reduces glycaemia in normal weight children
Authors: Gheller Brandon , McCormick Molly , Li Athena , Anini Younes , Bellissimo Nick , Hamilton Jill , Anderson G. Harvey , Luhovyy Bohdan L 
Published: June 2021

Increased snacking in children is associated with higher energy and sugar intake, known risk factors for obesity and diabetes. The objective of this study was to determine the effect of dairy and non‐dairy snacks on glycaemia in children.MethodsIn a repeatedmeasures crossover design, normal weight (5th–85th BMI percentile) children (n =11, 5 boys and 6 girls; age: 9–14 y), were randomly assigned to consume one of two treatments: Greek yogurt (171 kcal) and mini sandwich type cookies (175 kcal). Both treatments contained 25 g of available carbohydrates. After an overnight fast, children consumed a standardized breakfast in the morning, two hours before arriving at the lab. Venous blood samples were collected for glucose and insulin at 0 min (immediately before the treatment), and at 30, 60, 90 and 120 min.ResultsThere was an effect of treatment, time and a time by treatment interaction (P<0.0001) on blood glucose and insulin over 120 min. The yogurt treatment resulted in lower glycaemic and higher insulin responses compared to the cookies treatment (P<0.0001). This effect can be explained by the higher content of protein in the yogurt treatment (17 g) compared to the cookies treatment (1.3 g).ConclusionMacronutrient composition of a snack predetermines its glycaemic response and can affect postprandial hyperglycaemia in children.Grant Funding Source: Dairy Farmers of Canada
Effects of low‐fat dairy intake on blood pressure and endothelial function in subjects with pre‐hypertension or stage I hypertension
Authors: Maki Kevin , Rains Tia , Schild Arianne , Dicklin Mary , Lawless Andrea , Kelley Kathleen , Park Keigan 
Published: June 2021

This randomized crossover trial assessed the effects of 5 wk of consuming low‐fat dairy (1 serving/d each of 1% fluid milk, low‐fat cheese and low‐fat yogurt) vs. non‐dairy products (1 serving/d each of apple juice, pretzels and cereal bar) on vascular function (EndoPAT), systolic (SBP) and diastolic (DBP) blood pressures, and plasma lipids. Subjects were 62 men and women (mean age 54.5 yr, body mass index 29.2 kg/m2) with pre‐hypertension or stage I hypertension (mean resting SBP/DBP 129.8/80.8 mm Hg) while not receiving antihypertensive medications. A standard breakfast meal challenge including 2 servings of study products was administered at the end of each treatment period. Dairy and non‐dairy treatments did not produce significantly different mean SBP or DBP from pre‐meal to 3.5‐hr post‐meal (SBP, 126.3 vs. 124.9; DBP, 76.5 vs.75.7 mm Hg), pre‐meal (2.35 vs. 2.20) or 2‐hr post‐meal (2.33 vs. 2.30) EndoPAT reactive hyperemia index, and pre‐meal (22.5 vs. 23.8) or 2‐hr post‐meal (12.4 vs. 13.2) augmentation index. Fasting lipoprotein lipid (total, LDL, HDL and non‐HDL cholesterol and triglyceride) values also did not differ between treatments. In conclusion, no significant effects of consuming low‐fat dairy products, compared with low‐fat non‐dairy products, were observed for blood pressure, measures of vascular function or lipid variables.Funded by Dairy Research Institute
Baicalein inhibits lipid accumulation through regulation of MCE and cell cycle during 3T3‐L1 adipocyte differentiation.
Authors: Seo Min‐Jung , Choi Hyeon‐Son , Lee Ok‐Hwan , Lee Boo‐Yong 
Published: June 2021

Baicalein is a type of flavonoid originated from Scutellaria baicalensis. It has been reported to have inhibitory effects in inflammation, proliferation and adipogenesis. In this study, we examined how baicalein inhibits lipid accumulation in adipogenesis of 3T3‐L1 cell. Our data showed that baicalein inhibits lipid accumulation in adipogenesis in a dose dependent manner. The inhibition of baicalein was limited to early adipogenic stage (day0–2). Trypan blue assay showed that baicalein inhibits adipocyte proliferation during day0–2, when mitotic clonal expansion (MCE) process occurs. Baicalein‐induced inhibition on MCE was shown to be derived through cell cycle arrest in G0/G1 phase of 3T3‐L1. In addition, baicalein suppressed mRNA expressions of CCAAT/ enhancer binding protein‐β (C/EBPβ), CCAAT/ enhancer binding protein‐δ (C/EBPδ), early growth response 2 (Egr2 or Krox20), Krueppel‐like factor 4 (KLF4) and Krueppel‐like factor 5 (KLF5). This result resulted in the downregulation of late adipogenic factors such as peroxisome proliferator‐activated receptor‐γ (PPARγ), CCAAT/ enhancer binding protein‐α (C/EBPα) and adipocyte protein 2 (aP2). Our data suggest that bacalein inhibit lipid accumulation by regulating MCE through cell cycle arrest as well as early adipogenic genes.Grant Funding Source: Korea and National Research Foundation of Korea
Antidiabetic effects and antioxidant capacity of polyphenolenhanced Rutgers Scarlet Lettuce
Authors: Cheng Diana Meimei , Pogrebnyak Natasha , Poulev Alexander , Kuhn Peter , Krueger Christian G. , Waterman Carrie , Raskin Ilya 
Published: June 2021

Many health‐promoting properties of botanicals are associated with their high polyphenol content and their strong antioxidant activity. To produce a polyphenol‐enhanced botanical, anthocyanin‐rich leaves were selected by tissue culture to develop Rutgers Scarlet Lettuce (RSL). RSL contained greater levels of polyphenolic compounds (~94 mg/g dry weight of leaves), including anthocyanins and flavonols, compared to their parental varieties. RSL also showed greater antioxidant capacity compared to parental varieties as well as commercial lettuce and blueberries. Three major phytochemicals associated with antidiabetic and/or antiinflammatory activities accumulated in RSL: chlorogenic acid (~26 mg/g), cyanidin‐malonyl‐glucoside (~19 mg/g), and quercetin‐malonyl‐glucoside (~34 mg/g). RSL also demonstrated anti‐diabetic effects in vivo and in vitro. In high fat diet‐induced obese mice, daily oral administration of lyophilized RSL leaves (300 mg/kg) for 6–8 days significantly lowered fasting blood glucose levels compared to vehicle (water) and improved insulin mediated glucose metabolism. Aqueous extracts of RSL and purified chlorogenic acid showed dose‐dependent inhibition of glucose production in H4IIE rat hepatomas. These results suggest daily consumption of polyphenol‐rich RSL may provide beneficial health effects and have the potential to ameliorate diabetic conditions.Grant Funding Source: NIH/NCCAM/ODS P50AT002776–01. NIH training grant T32: 5T32AT004094–04
P2Y2 Receptor Deficiency Reduces Vascular Inflammation and Atherosclerosis in Mice
Authors: Seye Cheikh 
Published: June 2021

The P2Y2 receptor (P2Y2R) is a primary regulator of vascular cell adhesion molecule‐1 which plays a key role in recruitment of inflammatory cells in atherosclerosis. The objective of this study was to evaluate the consequence of P2Y2R ablation in the development of atherosclerosis.Methods and resultsApolipoprotein E‐deficient (ApoE−/−)mice with genetic ablation of P2Y2R developed significantly smaller atherosclerotic lesions in the aortic sinus as compared to Apoe−/− littermates when fed a chow diet. Strikingly, lesions of Apoe−/−/P2Y2R−/−mice displayed a sharp decrease in macrophage infiltration and VCAM‐1 immunostaining. ApoE−/−mice exhibited spontaneous high blood levels of soluble VCAM‐1 (sVCAM‐1) and knockout of P2Y2Rdrastically lowered sVCAM‐1. Basal levels of sVCAM‐1 were detected by Elisa in primary endothelial cells of ApoE−/−mice but not in those from Apoe−/−/P2Y2R−/−mice. The P2Y2R agonists induced a rapid release of sVCAM‐1 from cultured endothelial cells from wild type but not P2Y2R−/−mice, suggesting that VCAM‐1 is part of a specific shedding pathway mediated through P2Y2R activation. Notably, inhibition of the pro‐protein convertase furin or specific knockdown of the metalloproteinase ADAM10 inhibited basal and nucleotide‐stimulated sVCAM‐1 release.ConclusionInactivation of P2Y2R protects against atherosclerosis, suggesting that drugs targeting this receptor could prevent recruitment of inflammatory cells.
Role of HO‐1 in neuroblastoma resistance to Bortezomib
Authors: Furfaro AnnaLisa , Piras Sabrina , Passalacqua Mario , Domenicotti Cinzia , Pronzato Maria Adelaide , Marinari Umberto Maria , Moretta Lorenzo , Traverso Nicola , Nitti Mariapaola 
Published: June 2021

Neuroblastoma (NB) is the most common solid tumor in childhood and is characterized by a poor prognosis due to the gain of a chemoresistant phenotype. Among the most recent anticancer therapies Bortezomib (BTZ) has shown impressive clinical activity to overcome cancer cell resistance to conventional therapy. The availability of antioxidants is recognized as one of the critical mechanisms in the development of cancer cell resistance and the up‐regulation of heme oxygenase‐1 (HO‐1) seems to play a key role. We analyzed the effects of BTZ on two different NB cell lines, SHSY‐5Y and HTLA‐230, well known respectively as sensitive and resistant to therapy, pointing out the role of HO‐1. SHSY‐5Y exposure to 5–40nM BTZ was able to strongly reduce cell proliferation while the same treatment was less effective on HTLA. Moreover, BTZ treatment was able to strongly up‐regulate HO‐1 in HTLA, while only a slight induction was observed in SHSY‐5Y. However, HO‐1 silencing was able to further decrease the proliferation rate of HTLA cells exposed to BTZ. In conclusion, we believe that proteasome inhibition could be a useful therapeutic approach against NB but the inhibition of HO‐1 should be considered in order to improve the effectiveness and prevent chemoresistance.Grants: PRIN2009M8FKBB_002 and Genoa University
Comparison of micro‐bubble assisted p53, pRB, and p130 gene therapy in combination with radiation therapy in prostate cancer in vitro and in vivo
Authors: Nande Rounak Paramjeet , Gossman Michael S. , Lopez Jeffrey P. , Howard Candace M. , Denvir James , Claudio Pier Paolo 
Published: June 2021

We used a novel approach using adenoviral (Ad) delivery of cell cycle proteins encapsulated in microbubbles (MBs), in combination with radiation to target p53 & pRB mutant prostate cancer cells. MBs deliver therapeutic Ads, combined with ultrasound (US)‐targeted MB destruction (UTMD), allowing for a site‐specific gene transfer system.In vitro: DU145 radio‐resistant human prostate cancer cells were exposed to 10 & 20Gy of x‐ray radiation. Immediately after irradiation, cells were transduced with Ads carrying p53, pRb, or p130. In vivo: Tumors were grown to a volume of 200 mm3 in nude mice on their flanks. Mice were treated with intravenous (IV) injections of the Ads ± MB. IV treatments were compared to intratumoral (IT) injections of the Ads. Combinational therapy groups were irradiated at 8Gy, & injected intravenously with MB/Ads ± US, every week for 4 weeks.Higher percentage of cell death was observed in 20Gy vs. 10Gy irradiated cells. Cells transduced with adenoviruses carrying RB, p53, and p130 showed a decreasing order of cell death. Statistically significant reduction of the US‐targeted MB/p53 or RB Ad transduced tumors was observed when compared to IT treatments or radiation alone. US targeted MB/Ads in combination with x‐ray radiation therapy resulted in the most efficient treatment.Combination treatments of radiation and UTMD increase the treatment potential of therapy resistant prostate cancer.
Peripheral and central NK1 receptors in emesis control in Suncus murinus
Authors: Rudd John A , Cheng Frankie HM. , Moreaux Benoit 
Published: June 2021

Brain penetrant tachykinin NK1 receptor antagonists are known to reduce cisplatin‐induced emesis in ferrets. In the present studies, we investigate the role of central versus peripheral NK1 receptors in the mechanism of emesis in S. murinus. R116301 was selected as a reference brain penetrant NK1 receptor antagonist, and R115614 was used as a peripherally restricted antagonist; both have similar affinity for S. murinus NK1 receptors (PA2~8) and in vivo potency to reduce substance P‐induced plasma extravasation (ID50 ~2.9 μmol/kg). Drugs or vehicle were administered s.c, or i.c.v. 30 min prior to nicotine (30.7 μmol/kg, s.c.), copper sulphate.5H2O (480.6 μmol/kg, i.g.), or cisplatin (100 μmol/kg, i.p).Peripheral StudiesR116301 (23–53 mmol/kg, s.c) attenuated nicotine‐ and cisplatin‐induced emesis by 76 and 52 %, respectively (P<0.05). R115614 (30–70 mmol/kg, s.c) reduced copper sulphate‐ and cisplatin‐induced emesis by 75 and 50 %, respectively (P<0.05).Central StudiesR116301 (10–100 nmol, i.c.v.) antagonised nicotine‐induced emesis 89 % (P<0.05), while R115614 (100–500 nmol, i.c.v.) was incative (P>;0.05). In conclusion, centrally located tachykinin NK1 receptors play an important role in the emetic reflex but peripherally located NK1 receptors may also be involved in some causes of emesis.
Therapeutic efficacy of MJ33, a novel inhibitor of phospholipase A2 (PLA2) of peroxiredoxin 6 (Prdx6), in LPS‐induced acute lung injury (ALI)
Authors: Lee Intae , Dodia Chandra , Chatterjee Shampa , Feinstein Sheldon I , Fisher Aron B 
Published: June 2021

We have shown that peroxiredoxin 6 (Prdx6) on PLA2 activity is required for activation of NOX2 and subsequent generation of ROS in normal cells and have proposed a role for it in LPS‐induced acute lung injury (ALI). We evaluated MJ33, a novel inhibitor of PLA2 activity of Prdx6, for its therapeutic efficacy in ALI. Our recent studies of MJ33 displayed its avid lung uptake (67–86%), >;85% inhibition of phospholipase A2 (PLA2) activity, and high margin of safety in the intact mouse [toxic dose= >;25μmol/kg; PLA2 inhibitory dose= ~0.02μmol/kg]. ROS generation by endothelial cells in vitro was increased 16–24h post LPS treatment. This increase was significantly reduced by MJ33. LPS (0111:B4 from E. coli, 1–5mg/kg) was administered intratracheally. 4nmol MJ33 in unilamellar liposomes was administered intratracheally or intravenously either concurrently or 2 h post LPS. LPS significantly increased lung infiltration with increasing in inflammatory cells, lung permeability [protein levels, lung wet to dry ratio, leakage of FITC‐dextran into the lung lavage fluid], lipid peroxidation [TBARS and 8‐isoprostanes], and protein oxidation [protein carbonylation]. MJ33 dramatically reduced all of these measured parameters. These findings show that MJ33 can suppress the manifestation of oxidant stress associated with lung inflammation and the activation of NOX2.Supported by NHLBI‐R01‐HL105509.
Effects of aerobic exercise training on obese female mice: metabolic and autonomic evaluation
Authors: Sartori Michelle , de Souza Leandro Eziquiel , de Souza Pamella Ramona , Santos Fernando , De Angelis Kátia , Irigoyen Maria Claudia 
Published: June 2021

The aim of this study was to evaluate the metabolic and autonomic parameters in trained youth obese mice. Female ob/ob mice (4 weeks old) were randomized into sedentary (OS, n=11) or trained (OT, n=8) (treadmill,5 days/w, 60 min/d, during 8 wks) groups. Blood glucose was measured by reagent strips. Blood pressure signals were recorded using a data acquisition system. The OT group had higher exercise capacity compared to the OS group. OT group had reduced body weight, white adipose tissue and blood glucose (45±2g, 6.1±1g and 133±3g mg/dL) compared to OS group (50±2g, 6.1±1g and 169±8 mg/dL). Exercise training improved glucose tolerance in trained group (OS: 27961±6501 vs. OT: 18258±6283 mg/dL/min). Mean arterial pressure and heart rate were similar between groups. The trained group showed increase in heart rate variability compared with sedentary group (OT: 50±12 vs. OS: 33±8ms2). Blood pressure variability and low frequency band were higher in OS group (23 ± 3mmHg2 and 7 ± 1 mmHg2) compared to OT (15 ± 2 mmHg2 and 5 ± 1 mmHg2). Moreover, the spontaneous baroreflex sensitivity, represented by alpha index, was lower in sedentary group (1.2 ± 0.3 ms/mmHg) compared to trained group (1.9 ± 0.2 ms/mmHg). In conclusion, our results suggest that physical training during lifespan can be effective inattenuating the increase in weight and blood glucose and improving blood pressure variability in obese mice.FAPESP 2011/20859–0