bluuebunny/crossref_metadata_2025_split huggingface dataset:
Androgen Receptor Regulation by Microtubule‐targeting Chemotherapeutics in Prostate Cancer
Authors: Martin Sarah K. , Kyprianou Natasha 
Published: June 2021

Prostate cancer (PCa) is the 2nd leading cause of cancer related death in N. American males and progression to androgen independence is associated with patient mortality. Castration‐resistant prostate cancer (CRPC) is a consequence of lack of apoptotic response to androgen‐ablation therapy (ADT) and chemotherapy, and the most critical therapeutic endpoint for PCa patients is defying this resistance. The basis for therapeutic failure to ADT is androgen independent activation of AR driving uncontrolled tumor growth. Taxane‐based chemotherapy is the only clinically effective treatment for CRPC via stabilization of microtubules resulting in apoptosis. Recent evidence identified the contribution of microtubules to AR signaling and consequences of their inhibition by taxanes on AR activity in PCa. Human PCa tumors exhibited decreased nuclear AR localization after taxol treatment versus untreated. Impairing AR activity enables a targeting platform for taxane‐based chemotherapy during PCa progression and supports a combination strategy toward an improved therapeutic response. AR variants capable of ligand independent signal may be critical in dictating taxane response. Ongoing work pursues the mechanism of taxane resistance driven by distinct AR variant activity in CRPC.Department of Defense Synergistic Idea Development Award
Aurora B is regulated by dynamic acetylation/deacetylation in prostate cancer cells
Authors: Fadri-Moskwik Maria Theresa Morato , Weiderhold Kim , Chuang Carol , Deeraksa Arpaporn , Pan Jing , Lin Sue-Hwa , Yu-Lee Li-Yuan 
Published: June 2021

Protein acetylation has been implicated to play a role during mitosis, but the targets remain to be explored. Aurora B kinase plays a crucial role in mitosis and posttranslational modifications of Aurora B are known to regulate its kinase activity, localization and function. Whether acetylation also regulates Aurora B activity is not known. Using PC3 prostate cancer cells, we found that Aurora B is acetylated in mitosis and undergoes rapid acetylation/deacetylation, with peak deacetylation occurring in prometaphase. We found that HDAC3, a deacetylase that was previously shown by our laboratory to localize to the mitotic spindle and regulate spindle stability, is associated with Aurora B by co‐immunoprecipitation. Knockdown of HDAC3 or inhibiting HDAC3 activity with a small molecule inhibitor apicidin led to a higher level of Aurora B acetylation. Increased Aurora B acetylation is correlated with reduced Aurora B kinase activity that resulted in defects in Aurora B‐dependent mitotic processes, including kinetochore‐microtubule attachment and chromosome congression. Thus, our studies suggest that Aurora B kinase activity and function are regulated by dynamic acetylation/deacetylation in mitotic prostate cancer cells.Funded by NIH/NIGMS # K12 GM084897 (MFM), D.L. Duncan Cancer Center and Alkek Award for Experimental Therpeutics (Ly YL), PC080847, PC093132(SHL)
Green tea extract (GTE) decreases the lymphatic absorption of dioxin in rats
Authors: Noh Sang K , Kim Juyeon , Koo Sung I 
Published: June 2021

Previously, we have shown that GTE markedly lowers the intestinal absorption of cholesterol and fat soluble compounds. Doixin is a lipophilic food contaminant. This study was conducted to examine whether enteral infusion of GTE would affect the lymphatic absorption of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) in rats. Male rats with lymph cannulae were infused at 3.0 mL/h for 8 h via a duodenal catheter with a lipid emulsion containing TCDD labeled with 3H (3H‐TCDD), 10 pg TCDD, 452 μmol triolein, 20.7 μmol cholesterol, and 3.1 μmol α‐tocopherol, and 396.0 μmol Na‐taurocholate without (control) or with 76.0 mg GTE in PBS buffer (pH, 6.4). Lymph was collected hourly for 8 h. No significant difference was noted in lymph flow (19.1 ± 6.0 mL in GTE‐infused vs. 20.8 ± 4.7 mL in control rats). However, the infusion of GTE markedly lowered the lymphatic absorption of 3H‐TCDD (18.0 ± 2.9% dose/8 h) compared with controls infused with the lipid emulsion alone (23.0 ± 1.7%). The results indicate that GTE has a profound inhibitory effect on the intestinal absorption of dioxin in rats. The mechanism(s) by which GTE decreases dioxin absorption remains to be elucidated.Supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2011‐0003818).
Increased ketone body flux into GABA in ketotic rat brain
Authors: ZHANG YIFAN , Kuang Youzhi , LaManna Joseph C , Puchowicz Michelle A 
Published: June 2021

We had previously reported a decrease of glucose oxidation which was replaced by an increase of ketone body oxidation in ketotic rat brain. The metabolic effect of ketosis on the TCA cycle flux remains to be explored. GABA, a neurotransmitter in the brain, is balanced by the supply of carbons from the TCA cycle. We investigated the carbon flux of ketones and glucose into GABA with ketosis.MethodTracer infusions of [U‐13C]acetoacetate or [U‐13C]glucose were used to measure 13C‐label incorporation into GABA and related intermediates in cortex of diet‐induced ketotic rats. GC‐MS and stable isoptopomer analysis was applied.Results13C‐label percent enrichment from ketone bodies was increased in GABA, glutamate, glumatine, succinate and citrate (1.6 ±0.2, 4.1±0.5, 3.5±0.3, 4.4±1.0, and 3.3±1.5%, respectively; p<0.01) with ketosis compared to non‐ketotic rats. The data show ketosis increases ketone body flux towards GABA which is supplied by the TCA cycle, suggesting a possible mechanism of neuroprotection.
Clinical Trial of Dried Cranberry Consumption to Reduce Urinary Tract Infection Incidence in Susceptible Women
Authors: Burleigh Alexandra Elizabeth , Benck Susan M. , McAchran Sarah E , Reed Jess D , Krueger Christian G , Khoo Christina , Hopkins Walter J 
Published: June 2021

Recurrent urinary tract infections (UTIs) occur in up to ten percent of women and are a significant source of patient morbidity and health care costs. A variety of cranberry products have been used for UTI prevention, but no previous studies have examined whether consumption of dried cranberries will decrease the incidence of UTIs in susceptible patients. We conducted a clinical trial in which 20 women with a history of recurrent UTIs consumed one serving of sweetened, dried cranberries daily for two weeks. Patients reported the dates of UTIs in the six‐month periods pre‐and post‐treatment. The efficacy of dried cranberry consumption in reducing UTI occurrence was determined by comparing pre‐and post‐treatment infection rates. Of the 17 patients who completed the study, nine (53%) did not experience any UTIs within six months after treatment, and the UTI rate per six months decreased significantly from 2.8 to 1.2 (p=0.005). Kaplan‐Meier analysis compared the incidence of UTIs in study patients to patients receiving placebo in a previous UTI vaccine trial. Women in the two trials had equivalent UTI histories. This analysis showed a significant reduction in the number of UTIs in the six months post‐treatment (p=0.02). Based on these two clinical evaluations, there appears to be a beneficial effect to consuming dried cranberries in reducing recurrent UTIs in susceptible women.Supported by Ocean Spray Cranberries, Inc
Sound and vibration recordings during normal motion and spinal manipulation
Authors: Cramer Gregory D , Bora Preetam , Ross Kim , Selby Scott 
Published: June 2021

Novel methods assessed and localized zygapophyseal (Z) joint audible sounds (crepitus and cavitations) during normal lumbar motion and side‐posture spinal manipulation (SMT).MethodsFive healthy subjects ages 21–65 years had 9 accelerometers and one specialized directional microphone (with modifications) applied to their lumbar region in a previously developed pattern that allowed specific localization of joint sounds. Each subject underwent full lumbar ranges of motion (ROM), lumbar SMT (left side = up‐side), and repeated full ROM; all while recordings were made from the accelerometers and microphone. Accelerometer and microphone data were assessed for cavitations and crepitus.ResultsVibration and acoustic methods were successfully implemented and provided complementary information that identified cavitations, crepitus, and verified artifacts. Ten cavitations and 1 crepitus were recorded from 7 joints (all left side). Three instances of multiple joint cavitations were identified [2 from 2 joints (L L1/L2 and L L3/L4) and 3 from 1 joint (L L1/L2)]. Some recordings identified a cavitation when inaudible to subject and clinician.ConclusionsAccelerometers and microphone provided unique and complementary information. Assessing accelerometer and acoustic data could help deepen understanding of spinal mechanics and SMT. Funding: NIH/NCCAM Grant # 3R01AT000123‐06S2.
Patterns of hepatic Nrf2 and antioxidant enzyme alterations in rats subjected to autologous orthotopic liver transplantation
Authors: Guo Na , Wang Yanling , Hei Ziqing , Xia Zhengyuan 
Published: June 2021

Increases in reactive oxygen species and the subsequent oxidative stress play critical roles in the pathogenesis of hepatic ischemia‐reperfusion injury (IRI). Nrf2 is a transcription factor that induces the expression of various genes including those that encode antioxidant enzymes. Up‐regulation of Nrf2 has been shown to attenuate hepatic IRI. However, the patterns of changes of Nrf2 and antioxidant capacity during liver transplantation and their impact on post‐ischemic liver injury remain unknown. We found that autologous orthotopic liver transplantation (AOLT) resulted in severe liver injury in rats manifested as significant elevations in liver pathological scores as early as 4 hours after AOLT and peaked at 8 hours after AOLT that was coincident with 1.6 to 2‐fold increases of O2• and •OH production and lipid peroxidation product malondialdehyde (MDA) and significant decreases (~30%) in antioxidant enzyme superoxide dismutase and catalase and a dramatic (~70%) decrease in total oxidant scavenging capacity (all P<0.01 vs. baseline). The liver injury score was positively correlated to MDA content (P<0.01). Significant increase in liver Nrf2 expression was not seen until 8 hours after AOLT. It is concluded that delayed up‐regulation of Nrf2 during AOLT is not sufficient to withstand oxidative stress‐mediated liver injury.Supported by Guangzhou technological planning project (No. 2011J4300056).
Swimming training improves the vasodilator response in coronary arteries of ovariectomized rats
Authors: Abreu Glaucia Rodrigues , Claudio Erick , Endlich Patrick , Moyses Margareth , Santos Luciana , Bissoli Nazare , Bonates Paulo , Silva J F , Lemos Virginia 
Published: June 2021

ObjectiveTo investigate the participation of antioxidant and endothelial system on the coronary vasodilator response of trained and ovariectomized rats.MethodsWistar rats were divided in groups: Sham (SHAM), ovariectomized (OVX), ovariectomized training (OVXT). The response vasodilator was tested with BK and correlated with the expression of superoxide dismutase (SOD‐1,SOD‐2), catalase (CAT) and eNOS isoforms in coronary vessels.ResultsThe drop in coronary pressure after BK was higher in OVXT than SHAM and OVX (17,0±1,4; 8,9±1,4 and 7,2±1,4 mmHg, p <0.05). The expression of SOD‐1A also was higher in the OVXT when compared to SHAM and OVX (1,01; 0,6 and 0,4, p <0.05), whereas SOD‐2 concentrations did not showed differences.. The CAT was significantly higher only in OVXT when compared to SHAM and OVX (1,7; 1,3 and 1,08, p <0.05). The training increase the eNOS in OVXT when compared to SHAM and OVX (0,98; 0,72; and 0,87;p <0.05).ConclusionThe swimming training preserves the vasodilator response to BK in the coronary vascular bed ovariectomized rats probably to increase the bioavailability of nitric oxide and the local antioxidant system. Support: CNPq
Early cardiovascular remodeling in the offspring of rats exposed to undernutrition during pregnancy
Authors: Gonzalez M. Carmen , Condezo-Hoyos Luis , España-Caparros Gabriel , López de Pablo Angel L. , Prachaney Parichat , Velazquez-Gauna Sergio , Guzmán Santos , Elizondo-Omaña Rodrigo E. , Montero Pilar , Lopez M. Rosario , Arribas Silvia M. 
Published: June 2021

AIMTo assess if undernutrition during pregnancy induces early structural cardiovascular alterations in the offspring.METHODSRats were fed ad libitum with standard chow throughout gestation (control; C) or restricted to 50% the last 10 days of gestation (restricted; R) and offspring was weighted at birth. In 6‐day old rats, body and heart weights were measured. Hearts were frozen in liquid N2 to quantify collagen content (Sircol Kit) or fixed and paraffine‐embedded to assess collagen distribution (sirius red staining). Carotid arteries were mounted on a pressure myograph to measure geometrical parameters.RESULTSR pups had smaller birth weight (5.25±0.21g; n=24) compared to C (6.44±0.14 g, n=21; p<0.05). This difference was maintained in 6‐day old rats (R=10.6±0.25 g; C=12.23±0.28g, p<0.05) together with heart hypertrophy (R=0.007±0.0002; C=0.006±0.0001 heart weight/body weight; n=10; p<0.05) and increased heart collagen content located in the interstitium. Carotid arteries from R pups showed a significant reduction of internal and external diameters.CONCLUSIONMaternal undernutrition is associated with early cardiovascular remodeling which might predispose to increase blood pressure later in life.
In vivo MEMRI reveals persistent activation of the brain autonomic areas by an acute systemic angiotensin II injection
Authors: Zubcevic Jasenka , Perez Pablo D , Jun Joo Yun , Carvajal Jessica Marulanda , Raizada Mohan K , Febo Marcelo 
Published: June 2021

IntroductionAngiotensin II (ANGII) acts centrally to activate the sympathetic nervous system in hypertension. Here, we show that even a single systemic ANGII injection causes long‐lasting neuronal activation in the autonomic brain areas.MethodsIn vivo mapping of basal and ANGII‐evoked neuronal activity was carried out in the Wistar‐Kyoto (WKY) rat using manganese‐enhanced MRI (MEMRI) at 4.7Tesla. Rats were treated with manganese chloride (MnCl2 30 mM solution, i.p.;16–20 hrs prior to the MRI), and T1‐weighted images were obtained 16–20 hrs after a single ANGII injection (0.32μg/kg i.p.). Coronal slice scans (positioned caudally from end of the cerebellum/medulla rostrally towards the hypothalamus) were manually segmented using itkSNAP, and data analyzed for differences in normalized signal intensity.ResultsAcute ANGII injection caused an immediate pressor response (ÄSBP=~20mmHg) which normalized 2 hours following the injection. Despite this, ANGII evoked persistent neuronal activation in the central amygdala, hypothalamus (PVN, preoptic and lateral hypothalamic areas), and brainstem (NTS and RVLM).ConclusionEven a single systemic ANGII injection results in a lasting effect on the brain autonomic areas. Thus, repeated pro‐hypertensive stimuli in these brain areas may lead to pre‐sympathetic neuronal plasticity, resulting in heightened sympathetic drive and hypertension.
Vitamin D supplement use by adult Canadians: sociodemographic correlates
Authors: Barr Susan I. , Green Tim J. 
Published: June 2021

The 2011 Recommended Dietary Allowances (RDAs) for vitamin D intake in the absence of sunlight exposure are 15 μg/d (1–70 y) and 20 μg/d (70+ y). In Canada, these intakes are not feasible to obtain from food alone, and in winter months cutaneous vitamin D synthesis is very limited, suggesting the need for supplementation. To assess the prevalence and correlates of vitamin D supplement use subsequent to release of the 2011 RDAs, an on‐line survey was completed in September 2011 by a nationally‐representative sample of 2554 English‐ or French‐speaking adults aged ≥19 y. The survey assessed use of vitamin D supplements, health perceptions, and sociodemographic variables. Characteristics associated with supplement use in univariate analysis were used to determine multivariable‐adjusted odds ratios for supplement use. Overall, 47.9% reported use of a supplement with vitamin D; users’ median (interquartile range) supplemental intake was 10 (5, 25) μg/d. Significant adjusted odds ratios (95% CI >; 1.0) were detected for age group (19–30, 31–50, 51–70, 71+ y), female sex, speaking English (vs. French), having an osteoporosis diagnosis, perceived lactose intolerance, and university education. Adjusted odds ratio for marital status, ethnicity and income level were not significant. Certain population subgroups may benefit from targeted information about vitamin D supplementation.Supported by the UBC Vitamin Research Fund and the Canadian Agri‐Science Cluster Initiative.
Modulation of indoleamine 2,3‐dioxygenase pathway by a combination therapy strategy targeting myeloid derived suppressor cell function in lung cancer
Authors: Schafer Cara , Jin Tong Huan , Sawant Anandi , Roth Justin , Grant Stefan , Ponnazhagan Selvarangan , Deshane Jessy 
Published: June 2021

Immunosuppression in the tumor microenvironment (TME) has dampened the efficacy of current front line combination chemotherapies for lung cancer thus providing limited improvement in patient survival. Myeloid Derived Suppressor Cells (MDSCs) are the major contributors of immunosuppression by producing Reactive Oxygen Species (ROS) and by modulating amino acid metabolism in the TME. Indoleamine 2,3‐dioxygenase (IDO) is an intracellular enzyme that is a key regulator of tryptophan metabolism and is involved in immunosuppression.We have previously shown that a combination strategy using gemcitabine, a front line therapy for lung cancer and inhibitor of MDSC expansion, along with a Superoxide Dismutase (SOD) mimetic, which targets ROS in the TME, enhanced anti‐tumor immunity in mice and prolonged survival compared to controls. We hypothesized that this combination therapy will modulate IDO expression and activity and will diminish tumor burden. By flow cytometry and Western blot analyses, we demonstrate a significant reduction in IDO+ immunosuppressive cell types within tumor and in overall IDO expression in tumor and lung tissues, respectively, of tumor challenged mice treated with combination therapy compared to controls. Our preliminary studies suggest that this novel combination therapy may be effective in modulating the IDO pathway and in promoting long‐term immunity against lung cancer.NCI CA 13148–39 UAB CCC CDGP
Opioid‐mediated sustained ligand‐activated preconditioning induces cardiac protection in type II diabetes mellitus
Authors: Hoe Louise Elizabeth See , Zemljic‐Harpf Alice , Schilling Jan , Finley Cameron , Kellerhals Sarah , Roth David , Peart Jason , Patel Hemal , Headrick John 
Published: June 2021

Classic preconditioning is impaired in aged and diabetic hearts; however, opioid‐mediated sustained ligand‐activated preconditioning (SLP) is effective in aged myocardium. Here we test cardioprotective effects of SLP in a mouse model of type II diabetes (T2D) induced by streptozotocin with 2 months of high fat feeding. T2D mice exhibited markedly elevated body weight (30%) and fasting glucose, decreased ability to handle glucose loading, and myocardial dysfunction on echocardiography.Analysis of isolated perfused hearts revealed substantially greater contractile dysfunction and LDH efflux, following ischemia‐reperfusion in T2D vs. non‐diabetic hearts. SLP (5 days subcutaneous morphine pellets) reversed T2D contractile dysfunction in vivo and enhanced ex vivo I‐R tolerance to levels observed in non‐diabetic hearts (also protected by SLP), in association with significant improvements in Ca2+‐dependent mitochondrial swelling and respiratory function, with suppressed ROS generation. SLP also normalized blood glucose and induced a 20% fall in body weight.In summary, T2D‐dependent cardiac dysfunction and ischemic intolerance are reversed by SLP in association with mitochondrial preservation and shifts in glucose homeostasis and body weight. SLP may be a novel intervention in disease states refractory to conventional approaches.Research support provided by NIH, VA Merit and QLD Intl Fellowship.
Metabolic and Coronary Dysfunction in Obesity Resistant and Obesity Prone High Fat Fed Rats
Authors: Oltman Christine L , Dake Brian L. 
Published: June 2021

The purpose of this study was to compare physiologic, metabolic and microvascular complications in obesity resistant (OR) and obesity prone (OP) rats fed a high fat (HF) diet. 8 week old male rats were fed a diet containing 45% kcal saturated fat for 42 weeks. Blood pressure was measured by telemetry. Reactivity of small (75 – 150 μm intraluminal diameter) coronary arteries was evaluated. Body weights were 504±7, 669±25*, 685±8*, and 924±39* grams for OR control, OR HF, OP control OP HF rats, respectively. Blood pressure was increased in OP rats on control diet (121.5 ± 4.3mmHg*) and further increased with HF diet (129.7 ± 2.4mmHg*), compared to OR rats on control (98.3 ± 4.3mmHg) or HF diet (99.5 ± 3.1mmHg). Glucose clearance was impaired in high fat fed OR and OP rats. Acetylcholine (ACh)‐mediated relaxation of coronary arteries from HF fed rats was impaired (% relaxation to 10 μM Ach: OR control=67 ± 10, OR HF = 36±12*, OP control = 41±8*, and OP HF = 22±6*). Sodium nitroprusside (SNP) responses were not altered (% relaxation to 0.1 mM SNP: OR control = 72 ± 5, OR HF = 60 ± 7, OP control = 62 ± 8, and OP HF = 74 ± 6%). *p<0.05 vs OR control diet. These studies indicate that HF diet augments metabolic and microvascular complications in OP rats.Supported by VA Merit to Dr. Oltman.
In vitro antibacterial activity of the leucocyte and platelet‐rich fibrin clot exudate (L‐PRF)
Authors: Bozelli Ana Flavia , de Menezes Reiff Rodrigo Bezerra , Semeghini Dalmyr Osmar , Corbi Pedro Paulo , Lustri Wilton Rogério , Amaral André Capaldo 
Published: June 2021

The leucocyte and platelet‐rich fibrin (L‐PRF) is a potential tool to investigate the effects attributed to platelet concentrates. Although able to stimulate tissue repair, there are no reports regarding its antibacterial activity. To evaluate the action of the exudate extracted from the L‐PRF in vitro, blood samples of 10 male volunteers (ages 18–24) were centrifuged in clot activator tubes. The clots were shaken vigorously after 1 and 6 hours of activation for the extraction of exudate. Platelet (PLA), leucocyte (LEU) and erythrocyte (ERY) counting was performed in whole blood, platelet‐poor serum (PPS) and exudate. The antibacterial activity was investigated by disk diffusion technique in strains of Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (27853) and Staphylococcus aureus (25923), using specific antibiotics as positive controls. Cell counting in whole blood yielded a value of 6 ± 1 × 103 for LEU, 226 ± 28 × 103 for PLA and 5 ± 0.3×106 for ERY; 1‐hour PPS: 0.1 ± 0.1 to LEU and 0.5 ± 0.8 for PLA; 6‐hour PPS: 0.1 ± 0.2 to LEU and 0.4 ± 0.7 for PLA; exudate 1 hour: 5 ± 4 to LEU and 82 ± 56 for PLA; exudate 6 hours: 8 ± 7 to LEU and 211 ± 240 for PLA. The values of the ERY in the exudate and PPS were negligible. The exudates and PPS samples did not generate an inhibition zone and the positive controls exhibited halos with specific inhibition patterns. The L‐PRF exudate showed no antibacterial activity.Financial Support: CNPq Brazil