bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combinatory mixture of Rubus coreanus and Astragalus membranaceus attenuates bone loss through RANK signal pathway in ovariectized mice (1034.9)
Authors: Koo Hyun Jung , Sohn Eun‐Hwa , Kang Se Chan 
Published: June 2021

Background: Estrogen deficiency after menopause accelerates excessive loss of trabecular bone, leading to osteoporosis. Aim: The present study investigated the effects of the optimal combination of R. coreanus and A. membranaceus in 7:3 mixture (RAM) in ovariectomized (OVX) mice. Methods: Female ICR mice were ovariectomized (OVX) or sham‐operated (Sham) and divided into six groups; (1) Sham received daily oral phosphate‐buffered‐saline (PBS) ; (2) OVX mice received a daily oral gavage of PBS; (3) OVX mice treated daily with 50 mg/kg b.w./day of RAM; (4) with 100 mg/kg b.w./day of RAM; (5) with 200 mg/kg b.w./day of RAM via oral gavage; (6) OVX mice received i.p. injections of 17β‐estradiol (E2) (0.1 mg/kg b.w./day) three times per week for 12 wk. Results: RAM administration prevented tibial bone loss and preserved trabecular bone microarchitecture. RAM also showed recovery effects on the levels of TNF‐α, OPG and RANKL in OVX mice. Moreover, the anti‐osteoporotic property of RAM is closely correlated with the inhibition of osteoclast‐specific genes including TRAF6, NFATc1, calcitonin receptors and cathepsin K. Conclusions: Our findings suggest that RAM can be clinically used in the prevention and treatment of postmenopausal osteoporosis.Grant Funding Source: This work was supported by a grant from the Next‐Generation BioGreen 21 Program (No. PJ009049), RDA.
Development and clinical trial of an eHealth program for pre‐diabetics (1035.12)
Authors: Block Gladys , Azar Kristen , Block Torin , Block Clifford , Palaniappan Latha 
Published: June 2021

One‐third of American adults have pre‐diabetes (PD), and each year 5‐10% progress to Type 2 diabetes. Our health care system needs strategies to reach those 79 million people with assistance in changing their health behaviors. Alive‐Pre‐Diabetes is a scalable one‐year multimedia email‐web‐smartphone program to help pre‐diabetics improve their physical activity, eating habits and weight. The objective of the clinical trial is to assess the effectiveness of Alive‐PD in changing glucose and A1c.To be effective, technology‐based behavior‐change programs need to move beyond simply using tailoring and health behavior‐change principles: they must overcome the common problem of low engagement and dropout. In creating Alive‐PD from NutritionQuest's previously‐proven Alive! wellness program, we focused on features to increase and sustain engagement. Different learning styles are engaged through infographics, quizzes, automated phone‐based coaching and printed newsletters. Sharing with social media is enabled, and other features facilitate active social support by friends and family. A team system promotes competition between and support within teams. A points system may be used for monetary rewards or contributions to charity. These engagement features support a program of long‐ and short‐term goal‐setting, a user‐defined activity plan, diabetes‐focused health information, and motivational messaging.The trial is assessing change in glucose/A1c in 300 persons, and change in lipids and weight. Participants are being randomized to the Alive‐PD program or delayed control, and are re‐assessed at 3 and 6 months.Grant Funding Source: NIH, National Institute for Nursing Research
Whole egg protein markedly increases blood vitamin D concentrations in male Sprague‐Dawley rats (1041.9)
Authors: Van Wyk Korey , Schalinske Kevin 
Published: June 2021

Diabetes is characterized by altered methyl group and vitamin D metabolism; aberrations that may play a role in cardiovascular disease and other co‐morbidities. Whole eggs are a rich source of nutrients such as choline, vitamin B6, vitamin B12, and sulfur amino acids that can optimize methyl group metabolism. Egg yolks also are a natural source of vitamin D, which may help to elevate circulating vitamin D (25‐OH‐vitamin D) concentrations. To date, the impact of whole egg consumption on methyl group metabolism and vitamin D balance has not been explored in a rat model. Eighteen male Sprague‐Dawley rats were fed three diets formulated to contain 20% protein from casein (control), egg white, or lyophilized whole egg for 6 wks. Blood, liver, kidney, and urine samples were obtained for analysis. Both the egg white protein and whole egg groups exhibited a trend (p= 0.07) for elevated activity of hepatic glycine N‐methyltransferase, a key regulatory enzyme in methyl group metabolism that is disrupted in a diabetic state. Although there was no difference in circulating 25‐OH‐vitamin D concentrations between the control and egg white protein diets, the whole egg diet resulted in a 4‐fold increase. This finding may be important in diabetes as urinary loss of 25‐OH‐vitamin D is elevated. These results suggest that whole egg consumption could be a viable approach to enhancing vitamin D status and optimizing methyl group metabolism.Grant Funding Source: Supported by Egg Nutrition Center
Effect of processed Atlantic horse mackerel (Trachurus trachurus) on some hematological indices and enzyme activities in selected rat tissues (1044.2)
Authors: Adeyemi Olaoluwa , Osilesi O. , Adebawo O. , Onajobi F. , Oyedemi S , Afolayan A 
Published: June 2021

Trachurus trachurus, also called kote is a table fish. It contains some nutrients & bioactive compounds that are beneficial to human health. Processing methods may interfere with it's nutrients & are sources of reactive dicarbonyl compounds (RDCs) & polyaromatic hydrocarbons (PAHs). Effect of processed kote fillet; skin, head & bones (SHB) on weaned male wistar rats (WMWR) were evaluated using standard methods. Five isocaloric/isonitrogenous diets were compounded containing soybean‐groundnut cake (positive control); 0% protein (negative control); poached, coal & wood smoked kote fillet & SHB. 40 WMWR (40.76±2.42g) were randomly divided to 8 groups & fed on one of the 5 diets for 14 days. Voluntary feed intake, weight gains & digestibility were recorded. Rats were sacrificed at end of the experiment. Individual blood samples were analyzed for full blood count, electrolytes, Cholesterol (Chol), triglycerides (TGs), urea, Creatinine (CRT) & total proteins (TPs). Activities of Alkaline phosphatase (ALP) & Lactate dehydrogenase (LDH) were determined in the brain, liver, kidney, heart, stomach, small intestine (S.I) & spleen; Alanine transaminase (ALT) & Aspatate transaminase (AST) in liver & heart; Glucose (Gluc), Chol & CRT in brain. All data were subjected to analysis of variance by Duncan's multiple range test & considered significant at minimum of p < 0.05. Levels of red blood count (RBC), hemoglobin (Hgb), Chol & TGs; AST, ALP, LDH & Gluc in liver, heart, kidney & brain were low (p<0.05) in rats fed test diets compared to the controls, but within accepted limit. Variations in serum electrolyte, TPs, CRT & urea were insignificant. Levels of ALT, LDH & CRT in kidney, stomach & S.I were high (p<0.05) compared to the controls, but within accepted limit. Overall coal smoked fillet & SHB aided growth in rats, followed by the wood smoked & poached diets at the expense of mild effects of high levels of RDC & PAHs on RBC & Hgb. Processed SHB could be a veritable source of valuable nutrients for human food & animal feed.Grant Funding Source: National Research Foundation (NRF) of South Africa
Altered expression of epigenetic modulators involved in cisplatin resistance of ovarian cancer (1047.12)
Authors: Lim Jin Yeong , Lee Ja Yeon , Park Yoon Jung 
Published: June 2021

Ovarian cancer is the most fatal gynecologic malignancy with its high risk of late diagnosis and recurrence. Cisplatin is a typical treatment effective for primary tumors, but even the responsive tumors become refractory in many cases of recurrence. The mechanism underlying the acquisition of the resistance is not clear, although it has been associated with genetic and epigenetic alterations. We analyzed genome‐wide patterns of DNA methylation and expression in 9 ovarian cancer cell lines, which have different sensitivity to cisplatin, and compared differences between sensitive (SC) and resistant cell lines (RC). The majority of differential methylation probes were hypomethylated ones in RC compared to SC, while relatively hypermethylated ones in RC were only 16%. In order to understand the drivers for such epigenomic changes, we analyzed expression patterns of epigenetic modulators including modifiers for DNA methylation and histone modifications as well as chromatin remodelers. Intriguingly, the unsupervised clustering of the expression patterns classified the cell lines according to the cisplatin sensitivity. Various histone demethylases (KDMs) were overrepresented in differentially expressed genes and mainly downregulated in RC. Also, Enzymes that relate to maintain DNA methylation were significantly lower in RC, which might explain broad hypomethylation occurred in RC. The results showed that cisplatin resistance was distinguished by differential epigenetic patterns mediated by altered expression of key epigenetic master regulators. The effects of combinational changes of the regulators need to be further elucidated.Grant Funding Source: Supported by Korean NRF (22A20130012143) & the Korean Health Tech R&D Project(HI12C0050)
Methods for rapid extraction of high‐quality RNA from FFPE cancer tissue (1048.14)
Authors: Hoover Malachia , Brown Mark , Maawy Ali , Hoffman Robert , Bouvet Michael , Doebler Robert , Kelber Jonathan 
Published: June 2021

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer‐related deaths. Because there are virtually no biomarkers to aid in early detection or predicting therapy response, newly diagnosed patients have a dismal prognosis. Substantial archives of formalin‐fixed, paraffin‐embedded (FFPE) samples from PDAC tissue have been established and linked to clinical data. However, identifying biomarkers from these tumors is severely hindered because extracting high‐quality nucleic acid material from FFPE samples is time‐consuming and inefficient. Thus, developing improved methods for extracting high‐quality RNA/DNA from FFPE samples represents an unmet need in the fields of cancer biology and Next‐Generation Sequencing (NGS). We have tested Claremont BioSolutions’ microhomogenization (mH) tools in combination with commercial FFPE RNA extraction kits for their ability to improve high‐quality RNA recovery from PDAC xenograft samples. Our results demonstrate that the addition of brief (< 5min) mH steps improves total RNA yield up to 3‐fold over current methods, as well as RNA purity and length, as characterized by 260/280 ratios (2.03 +/‐ 0.02 w/ mH step) and chip‐based electrophoresis (RNA Quality Index = 7.3 w/ mH step). These results have important implications for streamlining the FFPE‐RNA‐NGS workflow as a realistic approach for cancer biomarker identification.Grant Funding Source: n/a
Angiotensin receptor blockers are not carcinogenic in rodents (1049.4)
Authors: De Felice Albert , Link William , Gatti Philip 
Published: June 2021

A published meta‐analysis (Sipahi, 2010) of several clinical trials of three angiotensin receptor blockers (ARBs) showed an 8% excess (95% CI of 1‐15%) in new diagnosed cancer, and 25% excess in lung cancer (95% CI of 5‐49%). Despite numerous acknowledged shortcomings of that analysis, and no difference in cancer death, FDA's Division of Cardiovascular and Renal Products re‐visited all 19 FDA‐mandated rodent carcinogenicity trials of nine ARBs: 16 lifetime(2 year) trials in standard mice and rat strains, and 3 six mo. trials in transgenic mice(2 inTgrasH2 and 1 in p‐53 +/‐ ). Regression analysis of placebo‐controlled mouse lung tumor incidence collapsed across strains , gender, and ARBs vs. multiples of maximum human exposure revealed no tumor excess at dosages up to 20‐200X that in humans(R2=0.01). Regression analysis was confined to data from the mice since both control and treated rats were devoid of lung tumors in lifetime trials.Accordingly, and regardless of strain, ARBs neither promoted nor initiated lung tumors in mice or rats, respectively. This finding is consistent with prior formal survival‐adjusted statistical analyses of individual rodent carcinogenicity trials submitted to this Division over the last several decades. Such trials were uniformly judged to be negative for excess lung or any other site‐specific tumors by FDA's executive carcinogenicity assessment committee per p‐values selected to allow no more than a 10% false positive rate in a standard test battery( 2‐yr rat and mice), or the ICH battery(2 yr rat and 6‐mo.transgenic mouse).FDA's own comprehensive study‐level meta‐analysis of 31 clinical trials of 6 ARBs vs non‐ARBs also absolved them of excess lung or other site‐specific tumor and of excess cancer death (FDA safety announcement,2011)
FishPharm: zebrafish in pharmacology education and research (1058.5)
Authors: Chatti Kiranam 
Published: June 2021

We highlight the application and utility of zebrafish (Danio rerio) as effective model organisms in pharmacology education and propose the name “FishPharm” as a catchword. We have found that zebrafish are valuable tools in pharmacology education, especially in resource‐poor settings. We have focused on developing simple methods and experiments using zebrafish embryos to illustrate fundamental concepts in pharmacology and hypothesis‐driven experimental design. This work describes four case studies of experiments performed by undergraduate, graduate and medical students using zebrafish embryos: 1) The effect of caffeine on heart rate. 2) The basis for the utility of zebrafish in tyrosine kinase pharmacology. 3) Development of a colorimetry‐based protocol to measure cell proliferation in vivo. 4) Evaluation of the anti‐angiogenic effect of drugs in vivo. Two of the above student projects led to peer‐reviewed research manuscripts. In summary, we highlight zebrafish as animal models for pharmacology education, especially in integrative and systems pharmacology. Zebrafish are emerging alternative animal models in drug discovery as featured in recent literature, and training pharmacology students in their use is also relevant in the above context. A discussion forum is being created at www.fishpharm.org.Grant Funding Source: Ministry of Science and Technology, Govt. of India
A renal‐like organic anion transport system in the ciliary body epithelium of the eye (1064.16)
Authors: Lee Jonghwa , Pelis Ryan 
Published: June 2021

The ciliary body epithelium (CE) is a bilayer consisting of a pigmented cell layer and a non‐pigmented cell layer, which together act as a physical barrier between the circulation and the eye interior. Previous studies show that clearance of organic anions from the eye is slowed by the well‐established organic anion transport inhibitor, probenecid. The purpose of this study was to determine the direction of organic anion transport across the CE and the transport proteins that may contribute. Paired unidirectional fluxes (aqueous humor‐to‐blood and blood‐to‐aqueous humor) and net flux (the difference between the unidirectional fluxes) of the organic anion para‐aminohippurate (PAH) across the freshly dissected rabbit CE was determined using Ussing chambers. RT‐PCR, immunoblotting and immunohistochemistry were used to examine organic anion transporter expression in the human eye. Net active PAH transport across the rabbit CE was in the aqueous humor‐to‐blood direction, with flux ratios of ~5. Probenecid (0.1 mM) inhibited net active PAH transport by reducing the unidirectional aqueous humor‐to‐blood flux. The organic anion transporters OAT1, OAT3, NaDC3 and MRP4 were detected in extracts of human ciliary body by RT‐PCR. The efflux transporter MRP4 was also detected in human ciliary body extracts by immunoblotting, where it localized to the basolateral membrane (blood‐facing side) of pigmented cells (determined by immunohistochemistry). These data suggest that the CE contains an organic anion transport system similar to that found in the renal proximal tubule. We speculate that this system is functionally similar in that it is involved in clearing potentially harmful endobiotic and xenobiotic organic anions from the eye interior. Supported by NSERC, NSHRF and CIHR.Grant Funding Source: Supported by NSERC, NSHRF and CIHR
Identification of novel signaling regulators of the mu opioid receptor (1066.1)
Authors: Edwards Katie , LaVigne Justin , Moses‐Fynn Emmanuel , Mullen Nate , Streicher John 
Published: June 2021

Recent evidence has suggested that specific downstream signaling pathways of the mu opioid receptor (MOR) carry out specific aspects of the behavioral response, such as antinociception or side effects. These findings have led to a drug discovery effort to develop functionally selective MOR ligands which activate the desired cascades (G protein) and not the undesirable cascades (βarrestin2). However, the βarrestin pathway is the only such functionally selective target identified for MOR drug discovery. In order to discover additional novel MOR regulators, we have developed two unbiased screening approaches. First, we have used co‐immunoprecipitation of the drug activated MOR signaling complex in MOR‐expressing CHO cells, followed by proteomic analysis. In addition, we have developed a pooled small‐hairpin RNA screen to find regulators of MOR induced signaling (ERK MAPK readout) in MOR‐expressing HEK293 cells. We present here our current progress using these screens, the outcome of which are lists of candidate MOR signaling regulators. One possible MOR‐regulating scaffold protein has been knocked down in MOR‐expressing CHO cells using small‐interfering RNA and shows evidence of regulating ERK MAPK pathways induced by the MOR. By defining the MOR signaling complex in this way, we hope to identify future targets for functionally selective drug discovery in order to improve the treatment of chronic pain.Grant Funding Source: Supported by UNE COBRE Seed Grant P20GM103643
Effects of eicosapentaenoic acid and the GPR120 agonist TUG‐891 on lysophosphatidic acid signaling in human prostate cancer cells (1066.10)
Authors: Hopkins Mandi , Liu Ze , Meier Kathryn 
Published: June 2021

There is a high incidence of prostate cancer in the Western world, which may be partially attributed to Western diets that are generally deficient in omega‐3 fatty acids (n‐3 FAs). Dietary n‐3 FAs have been shown to inhibit proliferation of prostate cancer cells in culture. The G protein‐coupled receptor GPR120, which is expressed in normal prostate and prostate tumors, serves as a receptor for the n‐3 FA eicosapentaenoic acid (EPA). We therefore hypothesized that the inhibitory effects of n‐3 FAs on prostate cancer cell proliferation are mediated by GPR120. To test this hypothesis, we performed proliferation and signal transduction studies, comparing the effects of lysophosphatidic acid (LPA), EPA, the GPR120 agonist TUG‐891, and the GPR40 agonist GW9508 in DU145 and PC‐3 cells. We found that EPA and TUG‐891 inhibit proliferation of human prostate cancer cells in response to LPA. In addition, brief (15 minute) pre‐incubation of serum‐starved cells with EPA or TUG‐891 suppresses subsequent activation of ERK, p70S6K, and FAK in response to LPA. This rapid effect of EPA is consistent with mediation by a GPCR. Our data suggest that GPR120 shows promise as a therapeutic target in prostate cancer.Grant Funding Source: Washington State University College of Pharmacy
Brain tissue oxygenation in response to changes in arterial pressure in patients with mild cognitive impairment (1068.6)
Authors: Liu Jie , Tarumi Takashi , Tseng Benjamin , Hill Candace , Armstrong Kyle , Hynan Linda , Hodics Timea , Zhang Rong 
Published: June 2021

Purpose: To test the hypothesis that brain oxygenation responses to changes in arterial pressure are altered in patients with amnestic mild cognitive impairment (aMCI).Methods: Forty‐five aMCI patients (18 males, 65 ± 6 yr) and 30 age and education matched cognitively normal control subjects (NC, 15 males, 66 ± 6 yr) underwent stepwise changes in mean arterial blood pressure (MAP) induced by intravenous infusion of sodium nitroprusside and phenylephrine. Transcranial Doppler and near‐infrared spectroscopy were used to measure the cerebral blood flow velocity (CBFV) at the middle cerebral artery and cortical tissue oxygenation index (TOI) at the prefrontal lobe, simultaneously. All measurements were normalized as percentage changes from baseline (Δ, %). Random coefficient mixed model was used to estimate the regression slopes of ΔCBFV% and ΔTOI% to changes in ΔMAP%.Results: Drug induced changes in MAP were from ‐26% to 49% (65~143 mmHg) relative to the baseline. The mixed model regression slopes of ∆CBFV% to ∆MAP% showed no differences between aMCI and NC (0.313 ± 0.047 vs. 0.219 ± 0.065, P = 0.238), suggesting the presence of intact cerebral autoregulation in aMCI. However, the slope of ∆TOI% to ∆MAP% was steeper in aMCI than in NC (‐0.253 ± 0.024 vs. ‐0.147 ± 0.032, P = 0.007), indicating an enhanced cortical oxygenation response to changes in blood pressure in aMCI.Conclusion: The enhanced cortical oxygenation responses to changes in blood pressure in patients with aMCI suggest that abnormalities of the cerebral microvasculature in regulation of brain tissue oxygenation may occur early in Alzheimer disease.Grant Funding Source: NIH grant R01AG033106‐01 and R01HL102457
Effects of aging and high fat diet on endothelial function in middle cerebral arteries is not additive (1070.11)
Authors: Reihl Kelly , Walker Ashley , Henson Grant , Donato Anthony , Lesniewski Lisa 
Published: June 2021

Vascular dysfunction in cerebral arteries has been associated with cognitive impairments with advancing age and disease. It is not known, however, how aging and consumption of a high fat (HF) obesigenic diet interact to impact cerebrovascular function. We examined endothelium dependent dilation (EDD) to acetylcholine in the middle cerebral arteries of young (6‐8 mo) and old (29‐31 mo) normal chow (NC) and HF diet fed mice. Maximal EDD was reduced with aging (68 ± 6 vs. 40 ± 2%, P<0.01) in NC mice. HF reduced EDD in young (41 ± 3%, P<0.01) but was without effect in old (34 ± 5%, P=0.3) mice. Differences in maximal EDD with aging and after HF diet were eliminated after inhibition of nitric oxide (NO) synthase by L‐NAME, indicating that the impairments resulted from reduced NO bioavailability. There were no differences in endothelium independent dilation to sodium nitroprusside between groups (P’s>0.5). Advancing age and consumption of a HF diet independently reduce cerebrovascular endothelial function through reductions in NO, but there is no further decrement in old mice fed HF diet.Grant Funding Source: Supported by NIH grants: R21 AG033755, K01 AG033196, R01 AG040297